US20030060619A1

US20030060619A1 - Secreted protein HFEAF41

Info

Publication number: US20030060619A1
Application number: US09/983,966
Authority: US
Inventors: Paul Young; John Greene; Ann Ferrie; Steven Ruben; Craig Rosen; Roxanne Duan; Jing-Shan Hu; Kimberly Florence; Henrik Olsen; Reinhard Ebner; Laurie Brewer; Paul Moore; Yanggu Shi; David LaFleur; Jian Ni
Original assignee: Individual
Current assignee: Individual
Priority date: 1997-03-21
Filing date: 2001-10-26
Publication date: 2003-03-27
Also published as: US20030050461A1; WO1998042738A1; US20020165374A1; JP2005218453A; US7169565B2; US20030018180A1; JP2001522239A; US20030069406A1; US20050089911A1; US20070154912A1; CA2284550A1

Abstract

The present invention relates to 87 novel human secreted proteins and isolated nucleic acids containing the coding regions of the genes encoding such proteins. Also provided are vectors, host cells, antibodies, and recombinant methods for producing human secreted proteins. The invention further relates to diagnostic and therapeutic methods useful for diagnosing and treating disorders related to these novel human secreted proteins.

Description

This application is a continuation-in-part of, and claims benefit under 35 U.S.C. §120 of copending United States patent application Serial No: PCT/US98/053 11, filed Mar. 19, 1998, which is hereby incorporated by reference, which claims benefit under 35 U.S.C. §119(e) based on U.S. Provisional Applications:



	Filing Date	Appln No.

1.	Mar 21, 1997	60/041,277
2.	Mar 21, 1997	60/042,344
3.	Mar 21, 1997	60/041,276
4.	Mar 21, 1997	60/041,281
5.	May 30, 1997	60/048,094
6.	May 30, 1997	60/048,350
7.	May 30, 1997	60/048,188
8.	May 30, 1997	60/048,135
9.	May 30, 1997	60/050,937
10.	May 30, 1997	60/048,187
11.	May 30, 1997	60/048,099
12.	May 30, 1997	60/048,352
13.	May 30, 1997	60/048,186
14.	May 30, 1997	60/048,069
15.	May 30, 1997	60/048,095
16.	May 30, 1997	60/048,131
17.	May 30, 1997	60/048,096
18.	May 30, 1997	60/048,355
19.	May 30, 1997	60/048,160
20.	May 30, 1997	60/048,351
21.	May 30, 1997	60/048,154
22.	Aug 05, 1997	60/054,804
23.	Aug 19, 1997	60/056,370
24.	Oct 02, 1997	60/060,862

FIELD OF THE INVENTION

This invention relates to newly identified polynucleotides and the polypeptides encoded by these polynucleotides, uses of such polynucleotides and polypeptides, and their production.

BACKGROUND OF THE INVENTION

Unlike bacterium, which exist as a single compartment surrounded by a membrane, human cells and other eucaryotes are subdivided by membranes into many functionally distinct compartments. Each membrane-bounded compartment, or organelle, contains different proteins essential for the function of the organelle. The cell uses “sorting signals,” which are amino acid motifs located within the protein, to target proteins to particular cellular organelles.

One type of sorting signal, called a signal sequence, a signal peptide, or a leader sequence, directs a class of proteins to an organelle called the endoplasmic reticulum (ER). The ER separates the membrane-bounded proteins from all other types of proteins. Once localized to the ER, both groups of proteins can be further directed to another organelle called the Golgi apparatus. Here, the Golgi distributes the proteins to vesicles, including secretory vesicles, the cell membrane, lysosomes, and the other organelles.

Proteins targeted to the ER by a signal sequence can be released into the extracellular space as a secreted protein. For example, vesicles containing secreted proteins can fuse with the cell membrane and release their contents into the extracellular space-a process called exocytosis. Exocytosis can occur constitutively or after receipt of a triggering signal. In the latter case, the proteins are stored in secretory vesicles (or secretory granules) until exocytosis is triggered. Similarly, proteins residing on the cell membrane can also be secreted into the extracellular space by proteolytic cleavage of a “linker” holding the protein to the membrane.

Despite the great progress made in recent years, only a small number of genes encoding human secreted proteins have been identified. These secreted proteins include the commercially valuable human insulin, interferon, Factor VIII, human growth hormone, tissue plasminogen activator, and erythropoeitin. Thus, in light of the pervasive role of secreted proteins in human physiology, a need exists for identifying and characterizing novel human secreted proteins and the genes that encode them. This knowledge will allow one to detect, to treat, and to prevent medical disorders by using secreted proteins or the genes that encode them.

SUMMARY OF THE INVENTION

The present invention relates to novel polynucleotides and the encoded polypeptides. Moreover, the present invention relates to vectors, host cells, antibodies, and recombinant methods for producing the polypeptides and polynucleotides. Also provided are diagnostic methods for detecting disorders related to the polypeptides therapeutic methods for treating such disorders. The invention further relates to screening methods for identifying binding partners of the polypeptides.

DETAILED DESCRIPTION Definitions

The following definitions are provided to facilitate understanding of certain terms used throughout this specification.

In the present invention, “isolated” refers to material removed from its original environment (e.g., the natural environment if it is naturally occurring), and thus is altered “by the hand of man” from its natural state. For example, an isolated polynucleotide could be part of a vector or a composition of matter, or could be contained within a cell, and still be “isolated” because that vector, composition of matter, or particular cell is not the original environment of the polynucleotide.

In the present invention, a “secreted” protein refers to those proteins capable of being directed to the ER, secretory vesicles, or the extracellular space as a result of a signal sequence, as well as those proteins released into the extracellular space without necessarily containing a signal sequence. If the secreted protein is released into the extracellular space, the secreted protein can undergo extracellular processing to produce a “mature” protein. Release into the extracellular space can occur by many mechanisms, including exocytosis and proteolytic cleavage.

As used herein, a “polynucleotide” refers to a molecule having a nucleic acid sequence contained in SEQ ID NO:X or the cDNA contained within the clone deposited with the ATCC. For example, the polynucleotide can contain the nucleotide sequence of the full length cDNA sequence, including the 5′ and 3′ untranslated sequences, the coding region, with or without the signal sequence, the secreted protein coding region, as well as fragments, epitopes, domains, and variants of the nucleic acid sequence. Moreover, as used herein, a “polypeptide” refers to a molecule having the translated amino acid sequence generated from the polynucleotide as broadly defined.

In the present invention, the full length sequence identified as SEQ ID NO:X was often generated by overlapping sequences contained in multiple clones (contig analysis). A representative clone containing all or most of the sequence for SEQ ID NO:X was deposited with the American Type Culture Collection (“ATCC”). As shown in Table 1, each clone is identified by a cDNA Clone ID (Identifier) and the ATCC Deposit Number. The ATCC is located at 10801 University Boulevard, Manassas, Va. 20110-2209, USA. The ATCC deposit was made pursuant to the terms of the Budapest Treaty on the international recognition of the deposit of microorganisms for purposes of patent procedure.

A “polynucleotide” of the present invention also includes those polynucleotides capable of hybridizing, under stringent hybridization conditions, to sequences contained in SEQ ID NO:X, the complement thereof, or the cDNA within the clone deposited with the ATCC. “Stringent hybridization conditions” refers to an overnight incubation at 42° C. in a solution comprising 50% formamide, 5×SSC (750 mM NaCl, 75 mM sodium citrate), 50 mM sodium phosphate (pH 7.6), 5×Denhardt's solution, 10% dextran sulfate, and 20 μg/ml denatured, sheared salmon sperm DNA, followed by washing the filters in 0.1×SSC at about 65° C.

Also contemplated are nucleic acid molecules that hybridize to the polynucleotides of the present invention at lower stringency hybridization conditions. Changes in the stringency of hybridization and signal detection are primarily accomplished through the manipulation of formamide concentration (lower percentages of formamide result in lowered stringency); salt conditions, or temperature. For example, lower stringency conditions include an overnight incubation at 37° C. in a solution comprising 6×SSPE (20×SSPE 3M NaCl; 0.2M NaH ₂PO₄; 0.02M EDTA, pH 7.4), 0.5% SDS, 30% formamide, 100 μg/ml salmon sperm blocking DNA; followed by washes at 50° C. with 1×SSPE, 0.1% SDS. In addition, to achieve even lower stringency, washes performed following stringent hybridization can be done at higher salt concentrations (e.g. 5×SSC).

Note that variations in the above conditions may be accomplished through the inclusion and/or substitution of alternate blocking reagents used to suppress background in hybridization experiments. Typical blocking reagents include Denhardt's reagent, BLOTTO, heparin, denatured salmon sperm DNA, and commercially available proprietary formulations. The inclusion of specific blocking reagents may require modification of the hybridization conditions described above, due to problems with compatibility.

Of course, a polynucleotide which hybridizes only to polyA+sequences (such as any 3′ terminal polyA+tract of a cDNA shown in the sequence listing), or to a complementary stretch of T (or U) residues, would not be included in the definition of “polynucleotide,” since such a polynucleotide would hybridize to any nucleic acid molecule containing a poly (A) stretch or the complement thereof (e.g., practically any double-stranded cDNA clone).

The polynucleotide of the present invention can be composed of any polyribonucleotide or polydeoxribonucleotide, which may be unmodified RNA or DNA or modified RNA or DNA. For example, polynucleotides can be composed of single- and double-stranded DNA, DNA that is a mixture of single- and double-stranded regions, single- and double-stranded RNA, and RNA that is mixture of single- and double-stranded regions, hybrid molecules comprising DNA and RNA that may be single-stranded or, more typically, double-stranded or a mixture of single- and double-stranded regions. In addition, the polynucleotide can be composed of triple-stranded regions comprising RNA or DNA or both RNA and DNA. A polynucleotide may also contain one or more modified bases or DNA or RNA backbones modified for stability or for other reasons. “Modified” bases include, for example, tritylated bases and unusual bases such as inosine. A variety of modifications can be made to DNA and RNA; thus, “polynucleotide” embraces chemically, enzymatically, or metabolically modified forms.

The polypeptide of the present invention can be composed of amino acids joined to each other by peptide bonds or modified peptide bonds, i.e., peptide isosteres, and may contain amino acids other than the 20 gene-encoded amino acids. The polypeptides may be modified by either natural processes, such as posttranslational processing, or by chemical modification techniques which are well known in the art. Such modifications are well described in basic texts and in more detailed monographs, as well as in a voluminous research literature. Modifications can occur anywhere in a polypeptide, including the peptide backbone, the amino acid side-chains and the amino or carboxyl termini. It will be appreciated that the same type of modification may be present in the same or varying degrees at several sites in a given polypeptide. Also, a given polypeptide may contain many types of modifications. Polypeptides may be branched, for example, as a result of ubiquitination, and they may be cyclic, with or without branching. Cyclic, branched, and branched cyclic polypeptides may result from posttranslation natural processes or may be made by synthetic methods. Modifications include acetylation, acylation, ADP-ribosylation, amidation, covalent attachment of flavin, covalent attachment of a heme moiety, covalent attachment of a nucleotide or nucleotide derivative, covalent attachment of a lipid or lipid derivative, covalent attachment of phosphotidylinositol, cross-linking, cyclization, disulfide bond formation, demethylation, formation of covalent cross-links, formation of cysteine, formation of pyroglutamate, formylation, gamma-carboxylation, glycosylation, GPI anchor formation, hydroxylation, iodination, methylation, myristoylation, oxidation, pegylation, proteolytic processing, phosphorylation, prenylation, racemization, selenoylation, sulfation, transfer-RNA mediated addition of amino acids to proteins such as arginylation, and ubiquitination. (See, for instance, PROTEINS—STRUCTURE AND MOLECULAR PROPERTIES, 2nd Ed., T.E. Creighton, W.H. Freeman and Company, New York (1993); POSTTRANSLATIONAL COVALENT MODIFICATION OF PROTEINS, B.C. Johnson, Ed., Academic Press, New York, pgs. 1-12 (1983); Seifter et al., Meth Enzymol 182:626-646 (1990); Rattan et al., Ann NY Acad Sci 663:48-62 (1992).)

“SEQ ID NO:X” refers to a polynucleotide sequence while “SEQ ID NO:Y” refers to a polypeptide sequence, both sequences identified by an integer specified in Table 1.

“A polypeptide having biological activity” refers to polypeptides exhibiting activity similar, but not necessarily identical to, an activity of a polypeptide of the present invention, including mature forms, as measured in a particular biological assay, with or without dose dependency. In the case where dose dependency does exist, it need not be identical to that of the polypeptide, but rather substantially similar to the dose-dependence in a given activity as compared to the polypeptide of the present invention (i.e., the candidate polypeptide will exhibit greater activity or not more than about 25-fold less and, preferably, not more than about tenfold less activity, and most preferably, not more than about three-fold less activity relative to the polypeptide of the present invention.)

Polynucleotides and Polypeptides of the Invention Features of Protein Encoded by Gene No:1

The translation product of this gene shares sequence homology with nucleolin, which is thought to be important in macromolecule binding, as well as some membrane proteins. Preferred polypeptide fragments comprise the amino acid'sequence:

DPEAADSGEPQNKRTPDLPEEEYVKEEIQENEEAVKKMLVEATREFEEVVVDES (SEQ ID NO:23 1);

QKLKRKAEEDPEAADSGEPQNKRTPDLPEEEYVKEEIQENEEAVKKMLVEATREFEEVVVDES (SEQ ID NO:232);

KAMEKSSLTQHSWQSLKDRYLKHLRGQEHKYLLGDAPVSPSSQKLKRKAEEDPEAADSGEPQNKRTPDLPEEEYVKEEIQENEEAVKKMLVEATREFEEVVVDESPPDFEIHI(SEQ ID NO: 233)

Also preferred are the polynucleotide fragments encoding these polypeptide fragments. This gene maps to chromosome 16, and therefore can be used as a marker in linkage analysis for chromosome 16.

This gene is expressed primarily in brain and kidney and to a lesser extent in wide range of tissues.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cell-cell interaction or cell-matrix interaction. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the brain and kidney, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., brain and other tissue of the nervous system, and kidney, and cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.121 as residues: Met-1 to Trp-10.

The tissue distribution in brain and kidney combined with the homology to nucleolin indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment/diagnosis of diseases involving cell-cell interaction or cell-extracellular matrix interaction. Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker and/or immunotherapy target for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:11 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1665 of SEQ ID NO:11, b is an integer of 15 to 1679, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:11, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:2

The translation product of this gene shares sequence homology with a porcine zona pellucida protein ZPDS.1711. (See Accession No. R39356.) These two proteins have weak homology with Drosophila commissureless and metal homeostasis proteins which are thought to be important in controlling growth cone guidance across the CNS midline and protecting cells against reactive oxygen toxicity. Thus, based on homology, it is likely that this gene may also be involved in development. Preferred polypeptide fragments comprise the amino acid sequence: LPSYDEAERTKAEATIPLVPGRDEDF VGRDDFDDADQLRIGNDGIFMLTFFMAFLFNWIGFFLSFCLTTSAAGRTGAISG FGLSLIKWILIVRFSTYFPGYFDGQYWLWWVFLVLGFLLFLRGFINYAKVRKM PETFSNLPRTRVLFI (SEQ ID NO:234); and/or AGRYGAISGFGLSLIKWILIVRFS (SEQ ID NO:235). Also preferred are polynucleotide fragments encoding these polypeptide fragments. The gene that encodes the disclosed cDNA is thought to reside on Chromosome 5. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 5.

This gene is expressed primarily in kidney, adrenal gland, brain, fetal and reproductive tissues, and to a lesser extent in wide range of tissues.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, fertilization control or tissue damage by metabolites or other toxic agents. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive, urogenital or renal system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g. reproductive, kidney, adrenal gland, and brain and other tissue of the nervous system, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, amniotic fluid, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The tissue distribution in reproductive tissues combined with the homology to zona pellucida protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for fertility control such as contraceptive development. The homology with metal homeostasis and commissureless genes indicates the gene's function in spermatozoa guidance and protection. It would also be useful for the treatment/diagnosis of tissue damages caused by toxic metabolites and other agents since the gene product is also expressed in urosecretive tissues. Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker and/or immunotherapy target for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:12 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1949 of SEQ ID NO:12, b is an integer of 15 to 1963, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:12, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:3

This gene is expressed primarily in liver and to a lesser extent in placenta. Preferred polypeptide fragments comprise the amino acid sequence:

MKHLSAWNFTKLTFLQLWEIFEGSVENCQTLTSYSKLQIKYTFSRGSTFYI (SEQ ID NO:236).

Also preferred are polynucleotide fragments encoding these polypeptide fragments.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, digestive, metabolic, developmental, and nutrient transport/utilization disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the digestive and circulatory system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., liver, and placenta, and cancerous and wounded tissues) or bodily fluids (e.g., amniotic fluid, lymph, bile, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The tissue distribution in liver and placenta indicates that the protein product is either an extracellular enzyme or a molecule carrier. Therefore, polynucleotides and polypeptides corresponding to this gene are useful for diagnosis/treatment of digestive and nutrient transport/utilization disorders, including malabsorption and malnutrition. Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker and/or immunotherapy target for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:13 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1198 of SEQ ID NO:13, b is an integer of 15 to 1212, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:13, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:4

This gene shares homology with the sap47 gene of Drosophila melanogaster, a gene which codes for a conserved neuronal protein associated with synaptic terminals. (See Mol. Brain Res. 32:45-54 (1995); see also, Accession No. 929571.) Thus, based on homology, the gene of the present invention also should be associated with synaptic terminals. Preferred polypeptide fragments comprise the amino acid sequence:


FSSDFRTSPWESRRVESKATSARCGLWGSGPRRRPASGMFRGLSSWLGLQQP	(SEQ ID NO:237);
VAGGGQPNGDAPPEQPSETVAESAEEELQQAGDQELLHQAKDFGNYLFNFASA
ATKKITESVAETAQTIKKSVEEGKIDGIIDKTIIGDFQKEQKKFVEEQHTKKSEA
AVPPWVDTNDEETIQQQILALSADKRNFLRDPPAGVQFNFDFDQMYPVALVML

MRFALVPKLVKEEVFWRNYFYRVSLIKQSAQLTALAAQQQAAGKGGEEQ	(SEQ ID NO:238);

STSPGVSEFVSDAFDACNLNQEDLRKEMEQL	(SEQ ID NO:239);
VLDKKQEETAVLEEDSADWEKELQQELQEYEVVTESEKRDENWDK

SPWESRRVESKATSARCGLWGSGPRRRPASGMFRGLSSWLGLQQ	(SEQ ID NO:240);
PVAGGGQPNGDAPPEQPS

PVAGGGQPNGDAPPEQPSETV	(SEQ ID NO:241); and/or
ESAEEELQQAGDQELLHQAKDFGNYLFNFASAATKKITESVAE

FQKEQKKFVEEQHTKKSEAAVPPWVDTNDEETIQQQILALSADKR	(SEQ ID NO:242).
NFLRDPPAGVQFNFDFDQMYPVALVML

Also preferred are polynucleotide fragments encoding these polypeptide fragments. Contact of cells with supernatant expressing the product of this gene increases the permeability of the plasma membrane of aortic smooth muscle cells to calcium. Thus, it is likely that the product of this gene is involved in a signal transduction pathway that is initiated when the product binds a receptor on the surface of the aortic smooth muscle cells. Thus, polynucleotides and polypeptides have uses which include, but are not limited to, activating aortic smooth muscle cells.

This gene is expressed primarily in kidney pyramids and to a lesser extent in lung and other tissues of various types. This gene fluxes calcium in human aortic smooth muscle cells, and therefore is involved in signal transduction.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, renal, developmental, vascular, and nervous disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the kidney and/or system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., kidney, lung, brain and other tissue of the nervous system, developmental, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, amniotic fluid, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The tissue distribution in kidney and lung and homology with sap47 indicates that the protein product has regulatory or direct functions in molecular exchange with body fluids and nervous system signaling. Polynucleotides and polypeptides corresponding to this gene are useful for treatment of disorders in kidney and nervous system. The activity of the translation product of this gene in activating aortic smooth muscle cells supports the notion that this protein is involved in regulatory or direct functions in molecular exchange with body fluids. This clone would be useful for the dignosis and treatment of disorders in kidney and the nervous system. Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker and/or immunotherapy target for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:14 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2047 of SEQ ID NO:14, b is an integer of 15 to 2061, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:14, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:5

The translation product of this gene shares sequence homology with the mouse Ly-9.2 antigen which is thought to be an important cell surface marker in lymphoids, myeloids and hematopoietic progenitors. (See Accession No. gi|198932.) Preferred polypeptide fragments comprise the amino acid sequence:

PFICVARNPVSRNFSSPILARKLCEGAA (SEQ ID NO:243);

and/or

KEDPANTVYSTVEIPKKMENPHSLLTMPDTPRL (SEQ ID NO:244).

Also preferred are polynucleotide fragments encoding these polypeptide fragments. Based on homology, it is likely that this gene is also a cell surface marker, involved in hematopoiesis.

This gene is expressed primarily in activated macrophages, monocytes and T-cells and to a lesser extent in spleen and bone marrow.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune and hematopoietic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and hematopoietic systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g. immune, blood cells, and bone marrow, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.125 as residues: Lys-26 to Tyr-33, Arg-44 to Ile-49, Ser-53 to Lys-71, Lys-86 to Pro-91.

The tissue distribution in immune tissue combined with the homology to a protein within the Ly-9.2 surface immunoglobulin family indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis of immune and hematopoietic disorders. Polypeptides and polynucleotides corresponding to this gene are also be used as a marker for leukemia or a modulator of the functions of the cells of macrophage/monocyte or T-cell types. Expression of this gene product in immune cells suggests a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages,-including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:15 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1398 of SEQ ID NO:15, b is an integer of 15 to 1412, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:15, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:6

The translation product of this gene shares sequence homology with the Drosophila glutactin gene which is thought to be important in cell-cell interaction or cell-extracellular matrix contact. The gene encoding the disclosed cDNA is thought to reside on chromosome 16. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 16.

This gene is expressed primarily in colon tissue, aorta endothelial cells and to a lesser extent in skin, breast tissue and T-cells.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of these tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases of the gastrointestinal tract, vascular system or T-cell development. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of these tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the digestive system, cardiovascular system, and immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., colon, endothelial, cardiovascular tissue, skin, mammary tissue, and blood cells, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, breast milk, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The tissue distribution and homology to glutactin indicates that polynucleotides and polypeptides corresponding to this gene are useful for the development and maintenance of the integrity of the basal membrane in the gastrointestinal tract, or vasculature in the cardiovascular system. The expression in T-cells also indicates the protein may be involved in T-cell adhesion, cell-cell interaction and development. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:16 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1038 of SEQ ID NO:16, b is an integer of 15 to 1052, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:16, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:7

The translation product of this gene shares sequence homology with MURF4 protein, an ATPase homolog, which is thought to be important in ATP hydrolysis.

This gene is expressed primarily in breast tissue.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, breast cancer and non-neoplastic breast diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of these tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the breast tissue, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., mammary tissue, and cancerous and wounded tissues) or bodily fluids (e.g., breast milk, lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The tissue distribution in breast tissue combined with the homology to the MURF4 gene indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of neoplastic or non-neoplastic breast diseases because ATPase like protein may be involved in changed metabolic states of the breast. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:17 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 669 of SEQ ID NO:17, b is an integer of 15 to 683, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:17, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:8

This gene shares homology to the alcohol dehydrogenase gene. Preferred polypeptide fragments comprise comprise the amino acid sequence: ASAVLLDLPNSG


ASAVLLDLPNSG	(SEQ ID NO:245);
GEAQAKKLGNNCVFAPADVTSEKDVQTALALAKGKFGRVDVAVNCAGIAVAS
KTYNLKKGQTHTLEDFQRVLDVNLMGTFNVIRLVAGEMGQNEPDQGGQRGVI
INTASVAAFEGQVGQAAYSASKGGIVGMTLPIARDLAPIGIRVMTIAPGLFGTPL
LTSLPEKVCNFLASQVPFPSRLGDPAEYAHLVQAIIENPFLNGEVIRLDGAIRMQP

SVAAFEGQVGQAAYSASKGGIVGMTLPIA	(SEQ ID NO:246). and/or

SVAAFEGQVGQAAYSASKGGIVGMTLPIA	(SEQ ID NO:247).

Polynucleotides encoding these fragements are also encompassed by the invention. Other groups have also recently cloned this gene, recognizing its homology to alcohol dehydrogenase. (See Accession No. 1778355.) Moreover, a second group recently cloned the mouse homologue of this gene. (See Accession No. 2078284.) They found that the mouse homologue binds to amyloid beta-peptide and mediates neurotoxicity in Alzheimer's disease, calling the protein ERAB. This gene maps to chromosome X, and therefore can be used in linkage analysis as a marker for chromosome X. Therefore, mutations in the translated product of this gene may be involved in Alzheimer's disease in humans, as well as other sex linked diseases. This gene can be used as a diagnostic marker for these diseases.

It has been discovered that this gene is expressed primarily in breast cancer tissue, infant brain, and to a lesser extent in fetal liver tissue.

Therefore, nucleic acids of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of the following diseases and conditions: neurodegenerative diseases, breast cancer, non-neoplastic breast diseases, or developmental disorders. Similarly, polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of these tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the brain and CNS, and breast tissue, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. brain, breast, metabolic, developmental, immune, hematopoietic, cancerous and wounded tissues) or bodily fluids (e.g., lymph, amniotic fluid, serum, plasma, urine, synovial fluid or spinal fluid) taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.128 as residues: Arg-45 to Ser-53.

The tissue distribution in neural tissue combined with the homology to the ERAB mouse gene suggests that the protein product of this clone would be useful for the diagnosis and treatment of Alzheimers and related neurodegenerative diseases. Mutations in the translated product of this gene may be involved in Alzheimer's disease in humans, as well as other sex linked diseases. This gene can be used as a diagnostic marker for these diseases. Furthermore, the tissue distribution suggests that this gene may also be involved in neoplastic or non-neoplastic breast diseases in humans. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:18 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a-nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1040 of SEQ ID NO:18, b is an integer of 15 to 1054, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:18, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:9

The translation product of this gene shares week sequence homology with rat N-methyl-D-aspartate receptor subunit and other proline-rich proteins which are thought to be important in neurotransmission or protein-protein intereaction.

This gene is expressed primarily in synovial hypoxia and to a lesser extent in ovary, senescent cells and brain.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, synovial hypoxia, reproductive, or neural disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the synovia and brain, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., synovial tissue, ovary and other reproductive tissue, and brain and other tissue of the nervous system, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression-level in healthy tissue or bodily fluid from an individual not having the disorder.

The tissue distribution in synovial hypoxia and nerve tissues, and homology to N-methyl-D-aspartate receptor subunit and other proline-rich proteins indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of synovial hypoxia and other synovial disorders, particularly disorders involving nitric oxide signaling. Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker and/or immunotherapy target for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:19 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1379 of SEQ ID NO:19, b is an integer of 15 to 1393, whereboth a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:19, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:10

This gene is expressed primarily in prostate and keratinocytes, and to a lesser extent in placenta, ovary and primary dendritic cells.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, male and female infertility, cancer, skin disorders, and other hyperproliferative disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of these tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, skin, and neoplasia, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., prostate, skin, placenta, ovary and other reproductive tissue, and cancerous and wounded tissues) or bodily fluids (e.g., amniotic fluid, lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.130 as residues: Pro-17 to Met-23, Ala-30 to Trp-38, Ile-49 to Trp-54, Lys-68 to Gly-74, Thr-93 to Gly-99, Met-126 to Glu-132, Gly-173 to Ser-178, Lys-205 to Tyr-214.

The tissue distribution of this gene in the prostate, placenta and ovary indicates that this gene product is useful for treatment/diagnosis of male or female infertility, endocrine disorders, fetal deficiencies, ovarian failure, amenorrhea, ovarian cancer, benign prostate hyperplasia, prostate cancer, and other forms of cancer of the reproductive system. The tissue distribution also suggests that the protein product of this clone would be useful for the treatment, diagnosis, and/or prevention of various skin disorders including congenital disorders (i.e. nevi, moles, freckles, Mongolian spots, hemangiomas, port-wine syndrome), integumentary tumors (i.e. keratoses, Bowen's disease, basal cell carcinoma, squamous cell carcinoma, malignant melanoma, Paget's disease, mycosis fungoides, and Kaposi's sarcoma), injuries and inflammation of the skin (i.e. wounds, rashes, prickly heat disorder, psoriasis, dermatitis), atherosclerosis, uticaria, eczema, photosensitivity, autoimmune disorders (i.e. lupus erythematosus, vitiligo, dermatomyositis, morphea, scleroderma, pemphigoid, and pemphigus), keloids, striae, erythema, petechiae, purpura, and xanthelasma. Moreover, such disorders may predispose increased susceptibility to viral and bacterial infections of the skin (i.e. cold sores, warts, chickenpox, molluscum contagiosum, herpes zoster, boils, cellulitis, erysipelas, impetigo, tinea, athletes foot, and ringworm). Protein, as well as, antibodies directed against the protain may show utility as a tissue-specific marker and/or immuntherapy target for the above-listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:20 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1201 of SEQ ID NO:20, b is an integer of 15 to 1215, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:20, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:11

This gene is expressed primarily in the thyroid and to a lesser extent in the pineal gland. The gene encoding the disclosed cDNA is thought to reside on chromosome 10. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 10.Preferred polypeptide fragments comprise the amino acid sequence:


HPIEWAINAATLSQFY	(SEQ ID NO:248);

CWIKYCLTLMQN AQLSMQDNIG	(SEQ ID NO:249);

KVSYLRPLDFEEARELFLLGQHYVF	(SEQ ID NO:250);

MERRCKMHKRXIAMLEPLTVDLNPQ	(SEQ ID NO:251); and/or

SHIV KKINNLNKSALKYYQLFLD	(SEQ ID NO:252).

Also preferred are polynucleotides encoding these polypeptide fragments.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune, thyroid and pineal gland disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of these tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and endocrine systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g. immune, thyroid and pineal gland, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.131 as residues: Ser-2 to Ser-8, Thr-38 to Arg-44.

The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treating/detecting immune disorders such as arthritis, asthma, immune deficiency diseases (e.g., ADS), and leukemia, as well as treating/detecting thymus disorders (e.g., Graves Disease, lymphocytic thyroiditis, hyperthyroidism, and hypothyroidism), and treating/detecting pineal gland disorders (e.g., circadian rhythm disturbances associated with shift work, jet lag, blindness, insomnia and old age). Protein, as well as, antibodies directed against the protain may show utility as a tissue-specific marker and/or immuntherapy target for the above-listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:21 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2028 of SEQ ID NO:21, b is an integer of 15 to 2042, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:21, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:12

The gene encoding the disclosed EDNA is thought to reside on chromosome 9. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 9.

It has been discovered that this gene is expressed primarily in colon and brain tissue, and to a lesser extent in lung and tonsils.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, pulmonary or immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of these tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the pulmonary and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, brain, pulmonary tissue, and tonsils, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, pulmonary surfactant or sputum, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.132 as residues: Glu-28 to Gly-49.

The tissue distribution of this gene only in lung indicates that it could play a role in the treatment/detection of lung lymphoma or sarcoma formation, pulmonary edema and embolism, bronchitis and cystic fibrosis. Its expression in tonsils indicates a potential role in the treatment/detection of immune disorders such as arthritis, asthma, immune deficiency diseases (e.g., AIDS), and leukemia, in addition to the treatment/detection of tonsillitis. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:22 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1858 of SEQ ID NO:22, b is an integer of 15 to 1872, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:22, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:13

This gene is expressed primarily in progenitor cells (CD34 cells) of lymphoid, myeloid and erythroid cells.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, hematopoietic and immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of these tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hematopoietic and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, blood cells, myeloid cells, and bone marrow, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The predominant tissue distribution of this gene in hematopoietic cell types indicates that the gene could be important for the treatment or detection of immune or hematopoietic disorders including arthritis, asthma, immunodeficiency diseases and leukemia. Preferred embodiments of the present invention are polypeptide fragments comprising the amino acid sequence:


FTHLSTCLLSLLLVRMSGFLLLARASPSICALDSSCFVEYCSSYSSSCFLHQHFPSLLDKLCQ	(SEQ ID NO:253); or

FLLLARASPSICALDSSCFVQEY	(SEQ ID NO:254).

Also preferred are polynucleotide fragments encoding these polypeptide fragments. Protein, as well as, antibodies directed against the protain may show utility as a tissue-specific marker and/or immuntherapy target for the above-listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:23 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 275 of SEQ ID NO:23, b is an integer of 15 to 289, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:23, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:14

This gene is homologous to the Drosophila Regena (Rga) gene. (See Accession No. 1658504.) This Drosophila gene is thought to be a homolog of the global negative transcriptional regulator NOT2 (CDC36) from yeast, which modifies gene expression and suppresses position effect variegation. Preferred polypeptide fragments comprise the amino acid sequence:


PDGRVTNIPQGMVTDQFGMIGLLTFIRAAETDPGMVHL	(SEQ ID NO:255);
ALGSDLTTLGLNLNS

VHLALGSDLTTLGLNLNSPENLYP	(SEQ ID NO:257);

EDLLFYLYYMNGGDVLQLLAAVELFNRDWRYHKEERVWITR	(SEQ ID NO:256);

EDLLFYLYYMNGGDVLQLLAAVELFNRDWRYHKEERVWITR	(SEQ ID NO:258); and/or

HNEDFPALPGS	(SEQ ID NO:259).

This gene is expressed primarily in placenta and to a lesser extent in infant brain.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurodegenerative and developmental disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the neurological system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., placenta, and brain and other tissue of the nervous system, reproductive, developmental tissues, and cancerous and wounded tissues) or bodily fluids (e.g., amniotic fluid, lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.134 as residues: Leu-9 to Tyr-15, Asp-34 to Gln-46, Pro-51 to Asp-57, Gly-88 to Thr-104, Thr-123 to Ser-128.

The tissue distribution of this gene in neural tissue indicates that it could be used in the detection and/or treatment of neurological disorders such as such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, and panic disorder. Similarly, expression within fetal and other cellular sources marked by proliferating cells, combined with the homology to a transcriptional regulator suggests that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, embryonic development also involves decisions involving cell differentiation and/or apoptosis in patter formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:24 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 3519 of SEQ ID NO:24, b is an integer of 15 to 3533, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:24, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:15

This gene is expressed primarily in adrenal gland tumor and osteoclastoma.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, endocrine and bone disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine system and in bone, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., adrenal gland, and bone, skeletal tissues, and cancerous' and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.135 as residues: Ile-52 to Trp-57.

The tissue distribution of this gene in endocrine tissue indicates that it may be involved in the treatment and/or detection of adrenal gland tumors, osteosarcomas, endocrine disorders and bone disorders, particularly osteoporosis. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:25 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1134 of SEQ ID NO:25, b is an integer of 15 to 1148, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:25, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:16

The translation product of this gene shares sequence homology with the FK506 binding protein, a protein which plays an important role in immunosupression. (See Accession No. M75099.) Specifically, a 12-kDa FK506-binding protein (FKBP-12) is a cytosolic receptor for the immunosuppressants FK506 and rapamycin. (See, Proc. Natl. Acad. Sci. 88: 6677-6681 (1991).) Thus, based on homology, it is likely that this gene also has immunosuppression activity or may be involved in other activities related to calcium dependent regulation. Preferred polypeptides comprise the amino acid sequence:


GRIIDTSLTRDPLVIELGQKQVIPGLEQSLLDMCVGEKRRAIIPSH	(SEQ ID NO:260); and/or
LAYGKRGFPPSVPADAVVQYDVELIALIR

IHYTGSLVDGR IIDTS	(SEQ ID NO:261).

Also preferred are the polynucleotide fragments encoding these polypeptides.

This gene is expressed primarily in melanocytes. Furthermore, northern analysis demonstrated that this gene is also abundant in fetal liver and kidney. In adult tissues, it is expressed relatively highly in spleen, placenta, and thymus, and at a low level in other tissues.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, developmental conditions, or cancer and other hyperproliferative disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system and cancer, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g. immune, melanocytes, developmental, integumentary, hepatic, renal, and cancerous and wounded tissues) or bodily fluids (e.g., amniotic fluid, lymph, bile, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.136 as residues: Ala-118 to Phe-124, Arg-178 to Lys-201.

The tissue distribution in developing tissues combined with the homology to the FK506 binding proteins which are believed to a role in immunosupression mediated by the immunosupressant drugs rapamycin and cyclosporin, indicates that this gene could serve as a novel target for the identification of novel immunosupressant drugs. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:26 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 703 of SEQ ID NO:26, b is an integer of 15 to 717, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:26, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:17

The translation product of this gene shares sequence homology with the rat calcium-activated potassium channel rSK3, which is thought to be important in regulating vascular tone. (See Accession No. gi|2564072, gi|1575663, and gi|1575661.) Although homologous to these proteins, this gene contains an 18 amino acid insert, not previously identified in the homologs. Preferred polypeptide fragments comprise the amino acid sequence:

CESPESPAQPSGSSLPAWYH (SEQ ID NO:262).

Also preferred are the polynucleotide fragments encoding these polypeptides.

This gene is expressed primarily in B-cells, frontal cortex and endothelial cells.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune, cardiovascular (hyper/hypotension, asthma, pulmonary edema, pneumonia, heart disease, restenosis, atherosclerosis, stoke, angina and thrombosis) or neurological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the cardiovascular and nervous systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g. cardiac, blood cells, immune, brain and other-tissues of the nervous system, and endothelium, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.137 as residues: Glu-72 to Gly-82, His-90 to Val-95, Gln-168 to Lys-174, Val-202 to Ser-212.

The tissue distribution in endothelial cells combined with the homology to calcium-activated potassium channels indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of vascular disorders (hyper/hypotension, athesma, pulmonary edema, pneumonia, heart disease, restenosis, atherosclerosis, stoke, angina and thrombosis). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:27 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1085 of SEQ ID NO:27, b is an integer of 15 to 1099, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:27, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:18

This gene is expressed primarily in smooth muscle and hematopoietic cells and to a lesser extent in brain (amygdala, corpus colosum, hippocampus).

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cardiovascular (hypertension, heart disease, athesma, pulmonary edema, restenosis, atherosclerosis, stoke, angina, thrombosis, and wound healing), immune, or neurological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the cardiovascular and neurological systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, smooth muscle, vascular, and brain and other tissue of the nervous system, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.138 as residues: Lys-43 to Arg-49, Tyr-58 to Glu-65.

The tissue distribution in smooth muscle indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of cadiovascular disorders (hypertension, heart disease, athesma, pulmonary edema, restenosis, atherosclerosis, stoke, angina, thrombosis, and wound healing). Expression in brain indicates a role in the treatment and diagnosis of behavioral or neurological disorders, such as depression, schizophrenia, Alzheimer's disease, mania, dementia, paranoia, and addictive behavior. Expression of this gene product in hematopietic cells suggests a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:28 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b where a is any integer between 1 to 927 of SEQ ID NO:28, b is an integer of 15 to 941, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:28, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:19

This gene is expressed primarily in T-cells (Jurkats, resting, activated, and anergic T-cells), endothelial cells, pineal gland, and to a lesser extent in a variety of other tissues and cell types. Preferred polypeptide fragments comprise the amino acid sequence:


EEAGAGRRCSHGGARPAGLGNEGLGGDPDHTDTGSRSKQRINN	(SEQ ID NO:263); and/or
WKESKHKVIMASASARGNQDKDAHFPPPSKQSLLFCPKSKLHIHRAEISK

SKQRINNWKESKHKVIMASASAR	(SEQ ID NO:264).

Also preferred are the polynucleotide fragments encoding these polypepides.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to immune disorders, such as , inflammation, immunodeficiencies, or cardiovascular disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of these tissue(s) or cell type(s) For a number of disorders of the above tissues or cells, particularly of the immune, neurological and vascular systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., T-cells and other blood cells, endothelial cells, and pineal gland, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. . Preferred epitopes include those comprising a sequence shown in SEQ ID NO.139 as residues: Phe-71 to Arg-76, Pro-82 to His-87, Glu-103 to Ala-111.

The tissue distribution in T-cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of immune disorders including: leukemias, lymphomas, auto-immune, immuno-supressive (e.g. transplantation) and immunodeficiencies (e.g. AIDS) and hematopoietic disorders. In addition, expression in the pineal gland might suggest a role in the diagnosis of specific brain tumors and treatment of neurological disorders. Endothelial cell expression might suggest a role in cadiovascular or respiratory/pulmonary disorders or infections (athesma, pulmonary edema, pneumonia). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:29 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 742 of SEQ ID NO:29, b is an integer of 15 to 756, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:29, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:20

The gene encoding the disclosed cDNA-is thought to reside on chromosome 15. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis form chromosome 15.

This gene is expressed primarily in brain and embryo and to a lesser extent in leukocytes.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, developmental, immune, and neurological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., brain, immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph, amniotic fluid, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.140 as residues: Met-1 to Gly-8.

The tissue distribution in immune tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of immune disorders including: leukemias, lymphomas, auto-immune, immuno-supressive (e.g. transplantation) and immunodeficiencies- (e.g. AIDS) and hematopoietic disorders. The expression in the brain—and in particular the fetal brain—would suggest a possible role in the treatment and diagnosis of developmental and neurodegenerative diseases of the brain and nervous system (depression, schizophrenia, Alzheimer's disease, mania, dementia, paranoia, and addictive behavior). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:30 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2086 of SEQ ID NO:30, b is an integer of 15 to 2100, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:30, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:21

The gene encoding the disclosed cDNA is thought to reside on chromosome 17. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 17.

This gene is expressed primarily in brain, kidney, lung, liver, spleen, and a variety of leukocytes (especially T-cells) and to a lesser extent in a variety of other tissues and cell types.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, leukemias, lymphomas, autoimmune, immunosuppressive, and immunodeficiencies, hematopoietic disorders, as well as renal disorders, and neoplasms. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the renal, pulmonary, immune, and central nervous systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., brain and other tissue of the nervous system, renal, pulmonary tissue, liver, spleen, and blood cells, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, bile, pulmonary surfactant or sputum, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The tissue distribution in immune tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of renal conditions, such as acture renal failure, kidney fibrosis, and kidney tubule regeneration. The expression in leukocytes and other immune tissues indicates a role in immune disorders including: leukemias, lymphomas, auto-immune, immuno-supressive (e.g. transplantation) and immunodeficiencies (e.g. AIDS) and hematopoietic disorders. The expression in the brain—and in particular the fetal brain—indicates a possible role in the treatment and diagnosis of developmental and neurodegenerative diseases of the brain and nervous system (depression, schizophrenia, Alzheimer's disease, mania, dementia, paranoia, and addictive behavior). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:31 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1434 of SEQ ID NO:31, b is an integer of 15 to 1448, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:31, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:22

The gene encoding the disclosed cDNA is thought to reside on chromosome 19. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 19.

This gene is expressed primarily in skin (fetal epithelium, keratinocytes and skin).

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, skin cancers (e.g., melanomas), eczema, psoriasis or other disorders of the integumentary system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of these tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the skin, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., keratinocytes, epithelium, integumentary, endothelial and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.142 as residues: Pro-28 to Glu-35, Ser-39 to Phe-44, Ala-94 to Gln-99.

The tissue distribution in integumentary tissue, suggests that the protein product of this clone would be useful for the treatment, diagnosis, and/or prevention of various skin disorders including congenital disorders (i.e. nevi, moles, freckles, Mongolian spots, hemangiomas, port-wine syndrome), integumentary tumors (i.e. keratoses, Bowen's disease, basal cell carcinoma, squamous cell carcinoma, malignant melanoma, Paget's disease, mycosis fungoides, and Kaposi's sarcoma), injuries and inflammation of the skin (i.e. wounds, rashes, prickly heat disorder, psoriasis, dermatitis), atherosclerosis, uticaria, eczema, photosensitivity, autoimmune disorders (i.e. lupus erythematosus, vitiligo, dermatomyositis, morphea, scleroderma, pemphigoid, and pemphigus), keloids, striae, erythema, petechiae, purpura, and xanthelasma. Moreover, such disorders may predispose increased susceptibility to viral and bacterial infections of the skin (i.e. cold sores, warts, chickenpox, molluscum contagiosum, herpes zoster, boils, cellulitis, erysipelas, impetigo, tinea, athletes foot, and ringworm). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:32 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 442 of SEQ ID NO:32, b is an integer of 15 to 456, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:32, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:23

This gene maps to chromosome 11. Another group recently isolated this same gene, associating the sequence to the region thought to harbor the gene involved in Multiple Endocrine Neoplasia Type 1, or MEN 1. (See Accession No. 2529721 and Genome Res. 7(7), 725-735 (1997), incorporated herein by reference in its entirety.) Preferred polypeptide fragments comprise the amino acid sequence:

LFHWACLNERAAQLPRNTAXAGYQCPSCNGPS (SEQ ID NO:265).

This gene is expressed primarily in epididymus, pineal gland, T-cells, as well as fetal epithelium, lung and kidney.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune, metabolic mediated disorders, reproductive, endocrine, and MEN. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune, renal, neurological and pulmonary systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, epididymus and other reproductive tissue, pineal gland, T-cells and other blood cells, epithelium, lung, and kidney, and cancerous and wounded tissues) or bodily fluids (e.g., seminal fluid, lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The tissue distribution in fetal tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of developmental deficiencies or abnormalities as well as a host of different disorders which arise as a result of conditions in the indicated tissues or cell types. An area of particular interest is in the treatment and diagnosis of immune disorders including: leukemias, lymphomas, auto-immune, immuno-supressive (e.g. transplantation) and immunodeficiencies (e.g. AIDS) and hematopoietic disorders. The expression in the brain, and in particular the fetal brain, would suggest a possible role in the treatment and diagnosis of developmental and neurodegenerative diseases of the brain and nervous system (depression, schizophrenia, Alzheimer's disease, mania, dementia, paranoia, and addictive behavior). Respiratory/pulmonary disorders, such as athesma, pulmonary edema are also potential therapeutic areas, as well as renal conditions such as acute renal failure, kidney fibrosis and kidney tubule regeneration. Moreover, this gene can be used in the treatment and/or detection of MEN I. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:33 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1312 of SEQ ID NO:33, b is an integer of 15 to 1326, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:33, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:24

This gene is expressed primarily in fetal spleen.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to developmental, leukemia, lymphoma, AIDS, hematopoeitic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and hematopoietic systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g. immune, spleen, developmental, hepatic, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, amniotic fluid, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The tissue distribution in fetal spleen indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of immune disorders including: leukemias, lymphomas, auto-immune, immuno-supressive (e.g. transplantation) and immunodeficiencies (e.g. AIDS) and hematopoietic disorders. Expression of this gene product in fetal spleen suggests a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:34 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 696 of SEQ ID NO:34, b is an integer of 15 to 710, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:34, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:25

A closely related homolog of this gene was recently cloned by another group, calling the gene CDO, an oncogene-, serum-, and anchorage-regulated member of the Ig/fibronectin type III repeat family. (See Accession No. 2406628, and J. Cell Biol. 138(1): 203-213 (1997), herein incorporated by reference in its entirety.) Preferred polypeptide fragments comprise the amino acid sequence:


FYIYYRPTDSDNDSDYKK	(SEQ ID NO:266); or
DMVEGDKYWHSISHLQPETSYDIKMQCFNEGGESEFSNVMICETKARKSSGQP
GRLPPPTLAPPQPPLPETIERPVGTGAMVARSSDLPYLIVGVVLGSIVLIVTFIPF
CLWRAWSKQKHTTDLGFPRSALPPSCPYTMVPLGGLPGHQAVDSPTSVASVDGPVLM

YIYYRPTDSDNDSDYKKDMVEGDKYWHSISHLQ	(SEQ ID NO:267).
PETSYDIKMQCFNEGGESEFSNVMICETKARKS

This gene is expressed primarily in fetal lung and kidney, human embryo and osteoclastoma stromal cells and to a lesser extent in a variety of other tissues and cell types.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, developmental disorders and cancers, as well as pulmonary and renal disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the respiratory/pulmonary, skeletal and renal systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., lung, kidney, embryonic tissue, and bone cells, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, amniotic fluid, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.145 as residues: Thr-5 to Pro-18, Ala-76 to Tbr-84.

The tissue distribution in fetal tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of osteoperosis, fractures, osteosarcoma, ossification, and osteonecrosis, as well as respiratory/pulmonary disorders, such as athesma, pulmonary edema, and renal conditions such as acute renal failure, kidney fibrosis and kidney tubule regeneration. Alternatively, this gene may function in a tumor suppression capacity, and it may be down-regulated by tumor cells or proto-oncogenes. Expression of this gene may be important in the prevention of tumor growth or metastasis. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:35 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1174 of SEQ ID NO:35, b is an integer of 15 to 1188, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:35, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:26

This gene is homologous to the HIV envelope glycoprotein. (See Accession No. 2641463.) Preferred polypeptide fragments comprise the amino acid sequence:

NVRALLHRMPEPPKINTAKFNNNKRKNLSL (SEQ ID NO:268).

This gene is expressed primarily in pineal gland and skin, and to a lesser extent in lung.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurological and behavior disorders; respiratory/pulmonary disorders, such as athesma, pulmonary edema; skin conditions such as eczema, psoriasis, acne and skin cancer, as well as AIDS. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous and respiratory systems, as well as skin and AIDS, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., blood cells, pineal gland, integumentary, endocrine, epidermis, and pulmonary tissue, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.146 as residues: Gln-15 to Gln-20.

The tissue distribution in integumentary tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of conditions which affect the above tissues, such as skin cancer, eczema, psoriasis, acne, athesma, pulmonary edema, neuro-degenerative or developmental disorders such as Alzheimer's, depression, schizophrenia, dementia, and AIDS. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:36 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 942 of SEQ ID NO:36, b is an integer of 15 to 956, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:36, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:27

Preferred polypeptide encoded by this gene comprise the following amino acid sequence:

NTNQREALQYAKNFQPFALNHQKDIQVLMGSLVYLRQGIENSPYYHLLDA

NQWADICDIFTRDACALLGLSVESPLSVSFSAGCVALPALINIKAVIEQR

QCTGVWNQKDELPIEVDLGKKCWYHSIFACPILRQQTTDNNPPMKLVCGH

IISRDALNKMFNGSKLKCPYCPMEQSPGDAKQIFF (SEQ ID NO:

269).

Polynucleotides encoding such polypeptides are also provided as are complementary polynucleotides thereto. The gene encoding the disclosed cDNA is thought to reside on chromosome 2. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 2. Contact of cells with supernatant expressing the product of this gene increases the permeability of the plasma membranes of both astrocytes and monocytes to calcium. Thus, it is likely that the product of this gene is involved in signal transduction pathway(s) which are initiated when the product binds a receptor(s) on the surface of both astrocytes and monocytes. Thus, polynucleotides have uses which include, but are not limited to, activating astrocytes and monocytes.

This gene is expressed primarily in liver (adult and fetal) and spleen tissue, and to a lesser extent in placenta, T helper cells, kidney tumor, ovarian tumor, melanocytes and fetal heart.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune and developmental diseases and disorders and liver diseases such as liver cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune, circulatory and hematopoietic systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., liver, spleen, placenta, blood cells, developmental, kidney, ovary and other reproductive tissue, melanocytes, and heart, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, amniotic fluid, bile, serum-plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The tissue distribution in immune cells indicates that the protein products of this gene are useful for study, diagnosis and treatment of growth, hematopoietic and immune system disorders particularly related to the liver. Expression of this gene product in hematopoietic cells suggests a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:37 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1589 of SEQ ID NO:37, b is an integer of 15 to 1603, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:37, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:28

The translation product of this gene shares sequence homology with prostaglandin transporter which is thought to be important in metabolic and endocrine disorders. See, for example, Gastroenterology Oct: 109(4):1274-1282 (1995). Preferred polypeptides encoded by this gene comprise the following amino acid sequence:


SYLSACFAGCNSTNLTGCACLTTVPAENATVVPGKCPSPGCQEAFLTFLCVMCI	(SEQ ID NO:270); and/or
CSLIGAMARHP

PSVIILIRTVSPELKSYALGVLFLLLRL
LGFIPPPLIFGAGIDSTCLFWSTFCGEQGACVLYDNVVYRYLYVSIAIALKSFAFI	(SEQ ID NO:271).

This gene is expressed primarily in hematopoietic and brain tissues.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, metabolic, immune and endocrine diseases and disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the metabolic, immune and endocrine systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, endocrine tissue, hematopoietic tissue, and brain and other tissue of the nervous system, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The tissue distribution in hematopoietic cells combined with the homology to a prostaglandin (and anion) transporter indicates that polynucleotides and polypeptides corresponding to this gene are useful for study, diagnosis and treatment of endocrine, metabolic, immune and kidney disorders. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:38 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1075 of SEQ ID NO:38, b is an integer of 15 to 1089, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:38, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:29

This gene is expressed primarily in early stage human lung.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, growth and respiratory disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the developmental and respiratory systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., pulmonary tissue, developmental, and cancerous and wounded tissues) or bodily fluids (e.g., amniotic fluid, lymph, pulmonary, surfactant or sputum, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.149 as residues: Val-50 to Trp-55.

The tissue distribution in fetal lung indicates that the protein products of this gene are useful for study, diagnosis and treatment of respiratory and growth diseases and disorders. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some- of these sequences are related to SEQ ID NO:39 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 615 of SEQ ID NO:39, b is an integer of 15 to 629, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:39, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:30

The translation product of this gene shares sequence homology with human DNA helicase which is thought to be important in accurate and complete DNA replication in creation of new cells. Preferred polypeptides encoded by this gene comprise the following amino acid sequence:


QSLFTRFVRVGVPTVDLDAQGRARA	(SEQ ID NO:272); and/or

SLCXXYNWRYKNLGNLPHVQLLPEFSTANAGLLYDFQLINVEDFQGVGESEPN

PYFYQNLGEAEYVVALFMYMCLLGYPADKISILTTYNGQKHLIRDIINRRCGNN

PLIGRPNKVTTVDRFQGQQNDYILLSLVRTRAVGHLRDVRRLVVAMSRAR

LVKEAKIIAMTCTHAALKRHDLVKLGFKYDNILMEE	(SEQ ID NO:273)

AAQILEIETFIPLLLQNPQDGFSRLKRWIMIGDHHQLPPVI

The gene encoding the disclosed cDNA is thought to reside on chromosome 15. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 15.

This gene is expressed primarily testes tumor and to a lesser extent in adrenal gland tumor and placenta.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, reproductive disorders. cancers and endocrine/growth disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine, developmental, and reproductive systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., testes and other reproductive tissue, adrenal gland, and placenta, and cancerous and wounded tissues) or bodily fluids (e.g., seminal fluid, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The tissue distribution in testes combined with the homology to a DNA helicase indicates that the protein products of this gene are useful for study. treatment, and diagnosis of many cancer types, including testicular cancer; as well as disorders involving endocrine function and normal growth and development. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:40 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1950 of SEQ ID NO:40, b is an integer of 15 to 1964, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:40, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:31

The translation product of this gene shares sequence homology with BID-apoptotic death gene (mouse), Genbank accession no. PID g1669514, which is thought to be important in programmed cell death.

This gene is expressed primarily in jurkat membrane bound polysomes and activated neutrophils and to a lesser extent in endothelial cells and human cerebellum.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancers and other proliferative disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g. immune, blood cells, hematopoietic, endothelium, and brain and other tissue of the nervous system, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.151 as residues: Glu-4 to Leu-11, Cys-28 to Arg-35, Gln-50 to His-66, Glu-73 to Gln-79, Gly-94 to Ser-100, Arg-114 to Asp-126, Pro-139 to Lys-146.

The tissue distribution in immune cells combined with the homology to the BID-apoptotic death gene indicates that the protein products of this gene are useful for study of cell death, and treatment and diagnosis of proliferative disorders and cancers. Apoptosis—programmed cell death—is a physiological mechanism involved in the deletion of peripheral T lymphocytes of the immune system, and its dysregulation can lead to a number of different pathogenic processes. Diseases associated with increased cell survival, or the inhibition of apoptosis, include cancers (such as follicular lymphomas, carcinomas with p53 mutations, and hormone-dependent tumors, such as breast cancer, prostrate cancer, Kaposiís sarcoma and ovarian cancer); autoimmune disorders (such as systemic lupus erythematosus and immune-related glomerulonephritis rheumatoid arthritis) and viral infections (such as herpes viruses, pox viruses and adenoviruses), inflammation; graft vs. host disease, acute graft rejection, and chronic graft rejection. Diseases associated with increased apoptosis include AIDS; neurodegenerative disorders (such as Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Retinitis pigmentosa, Cerebellar degeneration); myelodysplastic syndromes (such as aplastic anemia), ischemic injury (such as that caused by myocardial infarction, stroke and reperfusion injury), toxin-induced liver disease (such as that caused by alcohol), septic shock, cachexia and anorexia. Thus, the invention provides a method of enhancing apoptosis in an individual by treating the individual with a polypeptide encoded by this gene. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:41 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1508 of SEQ ID NO:41, b is an integer of 1-5 to 1522, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:41, and where the b is greater than or equal to a +14.

Features of Protein Encoded by Gene No:32

The translation product of this gene shares sequence homology with human fructose transporter which is thought to be important in normal metabolic function and activity.

This gene is expressed primarily in T-cell lymphoma.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, leukemia and other cancers, and metabolic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hematopoietic, lymph and metabolic systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g. immune, brain, T-cells and other blood cells, metabolic tissues, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.152 as residues: Pro-22 to Gly-48, Ser-54 to Pro-61.

The tissue distribution in T-cell lymphoma indicates that the protein products of this gene are useful for study of mechanisms leading to cancer, treatment and diagnosis of cancerous and pre-cancerous conditions; as well as the study and treatment of various metabolic diseases and disorders. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:42 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 861 of SEQ ID NO:42, b is an integer of 15 to 875, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:42, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:33

This gene is expressed primarily in human meningima and placental tissues.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, inflammation and other disorders of the CNS. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the CNS and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g. immune, meningima, developmental, proliferating, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, amniotic fluid, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.153 as residues: Asn-23 to Pro-31.

The tissue distribution in neural tissue indicates that the protein products of this gene are useful for study, diagnosis and treatment of disorders of the CNS and inflammatory responses. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:43 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 829 of SEQ ID NO:43, b is an integer of 15 to 843, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:43, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:34

This gene is expressed primarily in activated monocytes and wound healing tissues and to a lesser extent in fetal epithelium.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune and inflammatory disorders and wound healing and tissue repair dysfunctions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune, epithelial and gastrointestinal systems, and healing wounds, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g. immune, keratinocytes, monocytes, integumentary, developmental, and other blood cells, and epithelium, and cancerous and wounded tissues) or bodily fluids (e.g., amniotic fluid, lymph, sem, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.154 as residues: Ala-28 to Ala-33, Gly-35 to Glu-45.

The tissue distribution in immune cells indicates that the protein products of this gene are useful for diagnosis, study and treatment of immune and inflammatory disorders and wound healing dysfunctions. Expression of this gene product in immune cells suggests a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above Listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:44 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 475 of SEQ ID NO:44, b is an integer of 15 to 489, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:44, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:35

This gene is expressed primarily in human osteosarcoma and prostate cancer.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, skeletal and neoplastic conditions such as bone and prostate cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and skeletal systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, bone, prostate, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.155 as residues: Ser-14 to Gly-22, Leu-37 to Gln-43.

The tissue distribution in skeletal cells indicates that the protein products of this gene are useful for diagnosis and treatment of skeletal disorders and cancer. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:45 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 520 of SEQ ID NO:45, b is an integer of 15 to 534, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:45, and where the b is greater than or equal to a +14.

Features of Protein Encoded by Gene No:36

This gene encodes a protein which is highly homologous to a protein called congenital heart disease protein 5, presumably implicated in congenital heart disease (see Genbank PID g2810996).

This gene is expressed primarily in Hodgkin's lymphoma, erythroleukemia cells, and TNF activated synovial fibroblasts, to a lesser extent in ovarian cancer, cerebellum, spleen, fetal liver and placenta and finally to a lesser extent in various other mesenchymal tissues.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancer, immune, hematopoietic and cardiovascular disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune, hematopoietic and cardiovascular systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., heart and other cardiovascular tissue, immune, lymphoid tissue, blood cells, bone marrow, ovary and other reproductive tissue, brain and other tissue of the nervous system, spleen, liver, and mesenchymal tissue, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, bile, amniotic fluid, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ED NO.156 as residues: Lys-41 to Met-49, Gln-54 to Glu-59, Glu-76 to Thr-88.

The homology of this gene and translation product to congenital heart disease protein 5 indicates a role for this protein in the diagnosis, prognosis and/or treatment of heart disease or other cardiovascular related disorders. In addition, predominant expression in cells associated with the immune and hematopoetic system indicates a role for this protein in the treatment, diagnosis and/or prognosis of immune and autoimmune diseases, such as lupus, transplant rejection, allergic reactions, arthritis, asthma, immunodeficiency diseases, leukemia, AIDS, thymus disorders such as Graves Disease, lymphocytic thyroiditis, hyperthyroidism and hypothyroidism, Craft versus host reaction, graft versus host disease, transplant rejection, myelogenous leukemia bone marrow fibrosis, and myeloproliferative disease. The protein could also be used to enhance or protect proliferation, differentiation and functional activation of hematopoietic progenitor cells such as bone marrow cells, which could be useful for cancer patients undergoing chemotherapy or patients undergoing bone marrow transplantation. The protein may also be useful to increase the proliferation of peripheral blood leukocytes, which could be useful in the combat of a range of hematopoietic disorders including immunodeficiency diseases, leukemia, and septicemia. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:46 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1360 of SEQ ID NO:46, b is an integer of 15 to 1374, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:46, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:37

This gene is expressed primarily in ovarian cancer.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, urogenital neoplasias, reproductive, or endocrine disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., ovary and other reproductive tissue, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.157 as residues: Asn-22 to Asn-27.

The tissue distribution in ovarian tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for study, diagnosis and treatment of ovarian and other tumors. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:47 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 582 of SEQ ID NO:47, b is an integer of 15 to 596, where both a and b correspond to the positions of nucleotide residues. shown in SEQ ID NO:47, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:38

The translation product of this gene shares sequence homology with zinc finger proteins, which are small DNA-binding molecules noted for their occurrence in a large number of eukaryotic transcription factors.

This gene is expressed primarily in fetal, cancer, and endothelial lines.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune and growth disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the cardiovascular system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g. immune, fetal tissue, and endothelial cells, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, bile, amniotic fluid, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The tissue distribution in fetal tissue indicates that the protein products of this gene are useful for study, diagnosis and treatment of immune and developmental conditions and cancer. The homology to zinc finger proteins suggests that this protein may play a role in the transcriptional regulation of certain cancer genes. Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker and/or immunotherapy target for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:48 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 837 of SEQ ID NO:48, b is an integer of 15 to 851, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:48, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:39

This gene is expressed primarily in fetal, infant, and adult brain and to a lesser extent in other brain and endocrine organs and blastomas.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, brain tumors and neurodegenerative conditions, in addition to developmental disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the nervous and endocrine systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., brain and other tissue of the nervous system, endocrine tissue, and cancerous and wounded tissues) or bodily fluids (e.g., amniotic fluid, lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The tissue distribution in neural tissue indicates that the protein products of this gene are useful for the study, diagnosis and treatment of brain cancer and other neurological disorders such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses, autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Protect as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:49 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2006 of SEQ ID NO:49, b is an integer of 15 to 2020, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:49, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:40

The translation product of this gene shares sequence homology with vesicular glycoproteins and lectins. Preferred polypeptides encoded by this gene comprise the following amino acid sequence:


DTYPNEEKQQERVFPXXSAMVNNGSLSYDHER	(SEQ ID NO:274); and/or

DGRPTELGGCXAIVRNLHYDTFLVIRYVKRHLTIMMDIDGKHEWRDCIEVPGV

RLPRGYYFGTSSITGDLSDNHDVISLKLFELTVERTPEEE

LKREHSLSKPYQGVGTGSSSLWNLMGNAMVMTQYIRLTPDMQSKQGA

LWNRVPCFLRDWELQVHFKIHGQGKKNLHGDGLAIWYT	(SEQ ID NO:275).

The gene encoding the disclosed cDNA is thought to reside on chromosome 2. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 2. When tested against U937 myeloid cell lines and Jurkat T-cell lines, supernatants removed from cells containing this gene activated the GAS pathway. Thus, it is likely that this gene activates myeloid cells and T-cells through the Jaks-STAT signal transduction pathway. The Gamma Activating Sequence (GAS) is a promoter element found upstream of many genes which are involved in the Jaks-STAT pathway. The Jaks-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jaks-STAT pathway, reflected by the binding of the GAS element, can be used to indicate proteins involved in the proliferation and differentiation of cells. When tested against sensory neuron cell lines, supernatants removed from cells containing this gene activated the EGR1 pathway. Thus, it is likely that this gene activates sensory neuron cells through a signal transduction pathway induced by the EGR1 promoter. The Early Growth Response Gene 1 (EGR1) is a separate signal transduction pathway in which the EGR1 promoter induces various tissues and cell types upon activation, leading the cells to undergo differentiation and proliferation.

This gene is expressed primarily in infant brain and to a lesser extent in various normal and transformed neural, endocrine, and immune organs.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurological and neurodevelopmental conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the nervous and hormonal systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., brain and other tissue of the nervous system, endocrine tissue, and tissue and cells of the immune system, developmental disorders, and cancerous and wounded tissues) or bodily fluids (e.g., amniotic fluid, lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. . Preferred epitopes include those comprising a sequence shown in SEQ ID NO.160 as residues: Pro-64 to Gly-71, Gly-94 to Leu-100, Thr-110 to Pro-116, Thr-135 to Arg-145, Glu-164 to Glu-171, Asp-204 to Asp-21 1, Arg-253 to His-261, Asn-312 to Tyr-323.

The tissue distribution in neural tissue indicates that the protein products of this gene are useful for the study, diagnosis and treatment of mental retardation and other neurological disorders and neoplasias. The activity of this gene seen in various biological assays indicates that this gene is involved in a number of signal transduction assays, which further suggests that this gene could be important in cell proliferation and differentiation. Protein, as well as, antibodies directed against the protain may show utility as a tissue-specific marker and/or immuntherapy target for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:50 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2418 of SEQ ID NO:50, b is an integer of 15 to 2432, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:50, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:41

This gene displays homology to the glycosyltransferase family, which catalyze the addition of sialic acids to carbohydrate groups which are present on glycoproteins and glycolipids.

This gene is expressed primarily in smooth muscle and to a lesser extent in pineal gland, fetal liver, and infant brain.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, gastrointestinal injury, inflamatory and neurodegenerative conditions, endocrine, hematopoietic, hepatic or developmental disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and nervous systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., smooth muscle, pineal gland, liver, and brain and other tissue of the nervous system, and cancerous and wounded tissues) or bodily fluids (e.g., amniotic fluid, lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.161 as residues: Ser-12 to Trp-21, Arg-24 to Pro-32, Asp-73 to Lys-82, Lys-90 to Ala-97.

The tissue distribution in neural and fetal tissue indicates that the protein products of this gene are useful for the study, diagnosis and treatment of neurodegenerative and growth disorders and gastrointestinal repair. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:51 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2326 of SEQ ID NO:51, b is an integer of 15 to 2340, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:51, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:42

The translation product of this gene shares sequence similarity with metallothionein polypeptides. See, for example, Proc. Natl. Acad. Sci. USA 1992 July 15:89(14):6333-6337. Metallothioneins are believed to inhibit neuronal survival among other biological functions. Based on the sequence similarity (especially the conserved cysteine motifs characteristic of the metallothionein family) the translation product of this gene is expected to share certain biological activities with other members of the metallothionein polypeptide family. Preferred polypeptides encoded by this gene comprise the following amino acid sequence:

PGTLQCSALHHDPGCANCSRFCRD CSPPACQC (SEQ ID NO:276).

This gene is expressed exclusively in placenta and fetal liver, and to a lesser extent in osteoblast and bone marrow cells.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, hematopoietic and immune disorders and hepatic or skeletal system conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, placenta, liver, brain and other tissue of the nervous system, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, amniotic fluid, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The tissue distribution in immune cells and homology to metallothionien indicates that the protein products of this gene are useful for diagnosis and treatment of immune and hematopoietic system disorders and neurological diseases, especially in fetal development. Expression of this gene product in hematopoietic cells suggests a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also-used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:52 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 587 of SEQ ID NO:52, b is an integer of 15 to 601, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:52, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:43

Preferred polypeptides encoded by this gene comprise the following amino acid sequence:

FLYDVLMXHEAVMRTHQIHLPDPEFPS (SEQ ID NO:277).

This gene is expressed primarily in T-cells and synovial tissue.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune system disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain issues or cell types (e.g., synovial tissue, and T-cells and other blood cells, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from and individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The tissue distribution in T-cells indicates that the protein products of this gene are useful for treatment and diagnosis of disorders of the immune system. Expression of this gene product in immune cells suggests a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:53 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 345 of SEQ ID NO:53, b is an integer of 15 to 359, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:53, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:44

The translation product of this gene shares sequence similarity with several methyltransferases (e.g., see Genbank gi|1065505) which suggests this protein would be important in normal developmental and cellular processes.

This gene is expressed primarily in ovary, thymus, infant adrenal gland, tissues of the nervous system and the hematopoietic tissue, and to a lesser extent in adipose tissue and other tissues.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, disorders of the reproductive system, the endocrine-system, the hematopoietic system and the CNS. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune, endocrine, CNS and reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., ovary and other reproductive tissue, thymus, adrenal gland, brain and other tissue of the nervous system, hematopoietic tissue, and adipose tissue, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.164 as residues: Ser-3 to Gly-12, Asp-19 to Arg-31, Tyr-70 to Tyr-77, Asn-130 to Lys-140, Pro-165 to Gln-170, Pro-192 to Lys-199, Leu-216 to Glu-227, Glu-254 to Phe-281.

The tissue distribution in hematopoietic cells and homology to methyltransferase indicates that the protein products of this gene are useful for diagnosis and treatment of disorders of the CNS, the hematopoietic system and reproductive organs and tissues. For example, the abundant expression in the ovary may indicate that the gene product can be used as a hormone with either systemic or reproductive functions; as growth factors for germ cell maintenance and in vitro culture; as a fertility control agent; remedy for sexual dysfunction or sex development disorders; diagnostics/treatment for ovarian tumors, such as serous adenocarcinoma, dysgerminoma, embryonal carcinoma, choriocarcinoma, teratoma, etc.; The expression in thymus may indicate its utility in T-cell development and thus its applications in immune related medical conditions, such as infection, allergy, immune deficiency, tissue/organ transplantation, etc. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:54 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more-polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1127 of SEQ ID NO:54, b is an integer of 15 to 1141, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:54, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:45

The translation product of this gene shares sequence homology with cytochrome C oxidase which is thought to be important in the metabolic function of cells. This gene has now recently been published as estrogen response gene. See Genbank accession no. AB007618 and Mol. Cell. Biol. 18 (1), 442-449 (1998). See also J Immunol. March 1:154(5): 2384-2392 (1995), where the mouse homologue was published and implicated in siliocis. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:


PADXKPVVSTEAPPIIFATPTKLTSDSTVY	(SEQ ID NO:278) or

DYAGKNKVPELQKFFQKADGVPVYLKRGLPDQMLYRTTMALTVGGTIYCLIAL

YMASQPKNK

SFSGAVALAADAGSRTLGVMYYKFSGFTQ

KLAGAWASEAYSPQIXSLWFPQKHHLSYLPHQLN	(SEQ ID NO:279).

Polynucleotides encoding these polypeptides are also encompassed by the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 2. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 2.

This gene is expressed primarily in -adipose tissue, kidney and fetal brain and to a lesser extent in other tissues and organs.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, metabolic diseases involving especially adipose tissue, brain and kidney. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the CNS and vascular system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., adipose tissue, kidney, brain and other tissue of the nervous system, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, amniotic fluid, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.165 as residues: Thr-8 to Ser-13, Ser-29 to Ala-34, Pro-64 to Lys-77.

The tissue distribution and homology to cytochrome C oxidase, estrogen response gene product and siliocis related gene product indicates that the protein products of this gene are useful for diagnosis and treatment of metabolic disorders in the CNS, adipose tissue and kidney, particularly siliocis. Expression within fetal suggests that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, embryonic development also involves decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:55 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1546 of SEQ ID NO:55, b is an integer of 15 to 1560, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:55, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:46

The translation product of this gene shares sequence homology with reticulocalbin. See, for example, J. Biochem. 117 (5), 1113-1119 (1995). Based on the sequence similarity, the translation product of this gene is expected to share certain biological activities with reticulocalbin, e.g., Ca++ binding activities. This gene product is sometimes hereinafter referred to as “Reticulocalbin-2”. When tested against Jurkat T-cell lines, supernatants removed from cells containing this gene activated the GAS pathway. Thus, it is likely that this gene activates T-cells through the Jaks-STAT signal transduction pathway. The Gamma Activating Sequence (GAS) is a promoter element found upstream of many genes which are involved in the Jaks-STAT pathway. The Jaks-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jas-STAT pathway, reflected by the binding of the GAS element, can be used to indicate proteins involved in the proliferation and differentiation of cells. When tested against K562 leukemia cell lines, supernatants removed from cells containing this gene activated the ISRE pathway. Thus, it is likely that this gene activates leukemia cells through a signal transduction pathway induced by the ISRE promoter. The Interferon-Sensitive Responsive Element (ISRE) is a promoter element found upstream in many genes which are involved in the Jaks-STAT pathway. The Jaks-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jaks-STAT pathway, reflected by the binding of the ISRE element, can be used to indicate proteins involved in the proliferation and differentiation of cells

This gene is expressed primarily in breast, endothelial cells, synovial, heart and smooth muscle cells.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases of the breast, vascular, skeletal/cardiac muscular system as well as the integumentary system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the breast, vascular and skeleto-muscular system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues and cell types (e.g., mammary tissue, endothelial cells, synovial tissue, heart and other cardiovascular tissue, smooth muscle, integumentary, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, breast milk, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having-such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.166 as residues:


SEQ ID NO. 166 as residues:

Gly-16 to Arg-32, Ala-42 to Asn-50, Glu-66 to Gln-76, Arg-85 to Gly-94, Thr-108 to

Asp-115, Trp-121 to Gly-130, Leu-137 to His-144, Glu-155 to Lys-161, Asp-175 to

Ser-180, Glu-209 to Gly-217, Glu-232 to Glu-237, Thr-243 to Asp-261, Glu-287 to

Arg-295.

The tissue distribution in smooth muscle cells indicates that the protein products of this gene are useful for diagnosis and treatment of diseases of the vascular and skeletal/cardiac muscular system. The homology of the gene with reticulocalbin indicates its biological function in regulating calcium store, a particularly important function in muscular cell types. The gene expression in the heart may indicate its utilities in diagnosis and remedy in heart failure, ischemic heart diseases, cardiomyopathy, hypertension, arrhythmia, etc. The abundant expression in the breast may indicate its applications in breast neoplasia and breast cancers, such as fibroadenoma, papillary carcinoma, ductal carcinoma, Pagetís disease, medullary carcinoma, mucinous carcinoma, tubular carcinoma, secretory carcinoma and apocrine carcinoma; juvenile hypertrophy and gynecomastia, mastitis and abscess, duct ectasia, fat necrosis and fibrocystic diseases, etc. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:56 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1493 of SEQ ID NO:56, b is an integer of 15 to 1507, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:56, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:47

The translation product of this gene shares weak sequence homology with H+-transporting ATP synthase which is thought to be important in cell metabolism or signal transduction.

This gene is expressed only in testis.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of some types of diseases and conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the brain and hematopoietic tissues, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues and cell types (e.g., testes and other reproductive tissue, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, seminal fluid, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

Since only one out of about a million expressed sequence tags are found in testes, it is reasonable to suggest that the expression of this gene is selective for testes. Since some of the genes only expressed in testes are usually expressed in brain or in certain induced hematopoietic cells/tissues, it is speculated that this gene will be expressed in brain or hematopoietic cells/tissues and is useful for diagnosis and treatment of disorders of these systems. Similarly, the secreted protein can also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions and as nutritional supplements. It may also have a very wide range of biological activities. Typical of these are cytokine, cell proliferation/differentiation modulating activity or induction of other cytokines; immunostimulating/immunosuppressant activities (e.g. for treating human immunodeficiency virus infection, cancer, autoimmune diseases and allergy); regulation of hematopoiesis (e.g. for treating anaemia or as adjunct to chemotherapy); stimulation or growth of bone, cartilage, tendons, ligaments and/or nerves (e.g. for treating wounds, stimulation of follicle stimulating hormone (for control of fertility); chemotactic and chemokinetic activities (e.g. for treating infections, tumors); hemostatic or thrombolytic activity (e.g. for treating haemophilia, cardiac infarction etc.); anti-inflammatory, activity (e.g. for treating septic shock, Crohn's disease); as antimicrobials; for treating psoriasis or other hyperproliferative diseases; for regulation of metabolism, and behaviour. Also contemplated is the use of the corresponding nucleic acid in gene therapy procedures. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed-tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:57 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one-or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 436 of SEQ ID NO:57, b is an integer of 15 to 450, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:57, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:48

The translation product of this gene shares sequence homology with human polymeric immunoglobulin receptor (accession No. X73079) which is thought to be important in antibody recognition and immune defenses. In one embodiment, polypeptides of the invention comprise the sequence

GWYWCG (SEQ ID NO:230).

Polynucleotides encoding these polypeptides are also encompassed by the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 1. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 1.

This gene is expressed primarily in placenta and to a lesser extent in corpus callosum and fetal liver and spleen.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, disorders of the immune system, e.g. autoimmune diseases and immunodeficiency, in addition to developmental disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues and cell types (e.g., placenta, liver, and spleen, developmental tissues, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, amniotic fluid, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 168 as residues: Tyr-37 to Cys-49, Gly-51 to Tyr-56, Lys-88 to Trp-93, Leu-130 to Glu-136.

The tissue distribution in fetal liver and spleen combined with the homology to human polymeric immunoglobulin receptor indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of immune disorders, e.g. autoimmune diseases and immunodeficiencies. Expression within fetal tissues and other cellular sources marked by proliferating cells suggests that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, embryonic development also involves decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:58 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1133 of SEQ ID NO:58, b is an integer of 15 to 1147, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:58, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:49

This gene is expressed in thymus.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune disorders, such as inflammation or immunodeficiencies. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly-higher or lower levels may be routinely detected in certain tissues (e.g. immune, hematopoietic, thymus and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The tissue distribution in thymus indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of immune disorders, such as autoimmunity and immunodeficiency disorders. Similarly, this gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:59 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 763 of SEQ ID NO:59, b is an integer of 15 to 777, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:59, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:50


MKVGARIRVKMSVNKAHPVVSTHWRWPAEWPQMFLHLAQEPRTE

VKSRPLGLAGFIRQDSKTRKPLEQETIMSAADTALWPYGHGNREHQENELQKY

LQYKDMHLLDSGQSLGHTHTLQGSHNLTALNI	(SEQ ID NO:281).

Polynucleotides encoding this polypeptide are also provided as are complementary polynucleotides thereto.

This gene is expressed primarily in adrenal gland, pituitary, T helper cells, and breast cells and to a lesser extent in a wide variety of tissues.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of the some diseases and conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and endocrine systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues and cell types (e.g., adrenal gland, pituitary, T-cells and other blood cells, and mammary tissue, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, breast milk, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.170 as residues: Gln-39 to Ser-47, Arg-57 to Glu-67, Tyr-82 to Gln-95.

The tissue distribution in immune tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of a wide range of disorders, such as immune and endocrine disorders. Similarly, the secreted protein can also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions and as nutritional supplements. It may also have a very wide range of biological acitivities. Typical of these are cytokine, cell proliferation/differentiation modulating activity or induction of other cytokines; immunostimulating/immunosuppressant activities (e.g.for treating human immunodeficiency virus infection, cancer, autoimmune diseases and allergy); regulation of hematopoiesis (e.g. for treating anaemia or as adjunct to chemotherapy); stimulation or growth of bone, cartilage, tendons, ligaments and/or nerves (e.g. for treating wounds, stimulation of follicle stimulating hormone (for control of fertility); chemotactic and chemokinetic activities (e.g. for treating infections, tumors); hemostatic or thrombolytic activity (e.g. for treating haemophilia, cardiac infarction etc.); anti-inflammatory activity (e.g. for treating septic shock, Crohn's disease); as antimicrobials; for treating psoriasis or other hyperproliferative diseases; for regulation of metabolism, and behaviour. Also contemplated is the use of the corresponding nucleic acid in gene therapy procedures. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:60 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1177 of SEQ-ID NO:60, b is an integer of 15 to 1191, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:60, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:51

The translation product of this gene shares sequence homology with human Sop2p-like protein which is important in cytoskeleton structure. In one embodiment, polypeptides of the invention comprise the sequence

SLHKNSVSQISVLSGGKAKCSQFCTTGMDGGMSIWDVKSLESALKDLKI (SEQ ID NO:282).

Polynucleotides encoding this polypeptide are also encompassed by the invention. This gene maps to chromosome 7. Therefore, polynucleotides of the invention can be used in linkage analysis as a marker for chromosome 7.

This gene is expressed primarily in immune and hematopoietic tissues/cells and to a lesser extent in other tissues.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immunological and hematopoietic disorders and inflammation. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and hematopoietic systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues and cell types (e.g., immune and hematopoietic tissue/cells, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in


SEQ ID NO. 171 as residues: Lys-49 to Gln-54, Ala-61 to Arg-66,

Lys-82 to Lys-87, Glu-126 to Val-133, His-136 to Ile-141, Glu-175 to Ser-137, Asp-286

to Leu-296, Ala-298 to Ser-310.

The tissue distribution in immune tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of immunological, hematopoietic, and inflammatory disorders, e.g., immunodeficiency, autoimmunity, inflammation. Protein, as well as, antibodies directed against the protain may show utility as a tissue-specific marker and/or immuntherapy target for the above-listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:61 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1566 of SEQ ID NO:61, b is an integer of 15 to 1580, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:61, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:52

The translation product of this gene shares sequence homology with Caenorhabditis elegans R53.5 gene encoding a putative secreted protein.

This gene is expressed primarily in endothelial cells, brain and several highly vascularized, and tumor tissues and to a lesser extent in other tissues.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, aberrant angiogensis and tumorigenesis. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the vascular and neural systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues and cell types (e.g., endothelial cells, brain and other tissue of the nervous system, and vascular tissue, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.172 as residues: Thr-43 to Asn-60, Thr-106 to Phe-115, Asp-122 to Arg-133, Arg-186 to Asp-192, Leu-211 to Lys-216.

The tissue distribution in vascular tissue combined with the homology to a C. elegans secreted protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis or treatment of disorders of the vascular or central nervous system, e.g. aberrant angiogenesis, ischemia, neurodegeneration, stroke, etc. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:62 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1103 of SEQ ID NO:62, b is an integer of 15 to 1117, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:62, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:53

In one embodiment, polypeptides of the invention comprise the sequence

EASKSSHAGLDLFSVAACHRF (SEQ ID NO:283).

Polynucleotides encoding this polypeptide are also encompassed by the invention. When tested against Jurkat T-cell lines, supernatants removed from cells containing this gene activated the GAS pathway. Thus, it is likely that this gene activates T-cells through the Jaks-STAT signal transduction pathway. The Gamma Activating Sequence (GAS) is a promoter element found upstream of many genes which are involved in the Jaks-STAT pathway. The Jaks-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jaks-STAT pathway, reflected by the binding of the GAS element, can be used to indicate proteins involved in the proliferation and differentiation of cells.

This gene is expressed primarily in T-cells and to a lesser extent in brain.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, lymphocytic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the lymphoid system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues and cell types (e.g. immune, T-cells, or other blood cells, brain and other tissue of the nervous system, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.173 as residues: Pro-3 to Thr-8, Arg-37 to Asp-46.

The tissue distribution in T-cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis, treatment, and cure of lymphocytic disorders. Alternatively, expression within neural tissue suggests that the protein product of this clone would be useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. . Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:63 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 347 of SEQ-ID NO:63, b is an integer of 15 to 361, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:63, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No:54

The translation product of this gene shares sequence homology with secreted cartilage matrix protein, a major component of the extracellular matrix of nonarticular cartilage which is thought to be important in cartilage structure. In specific embodiments, polypeptides of the invention comprise the sequence:


RCKKCTEGPI	(SEQ ID NO:292);

DLVFVIDGSKSLGEENFEVVKQF

VTGIIDSLTISPKAARVGL	(SEQ ID NO:285);

LQYSTQVH

TEFTLRNFNSAKDMKKAVAHMKYM	(SEQ ID NO:286);

GKGSMTGLALKHMFERSFTQGEGARPF	(SEQ ID NO:287);

STRVP	(SEQ ID NO:288)

RAAIVFTDGRAQDDVSEWASKAKANGITMYAVGVGKAIE

EELQEIASEPTNKHLFYAEDFSTMDEISEKLKKGICEALEDS	(SEQ ID NO:289);

TQRLEEMTQRM	(SEQ ID NO:290);

PQGCPEQPLH	(SEQ ID NO:291);

YMGKGSMTGLALKHMFERSFT	(SEQ ID NO:284),

GWETLPKKDVCKST	(SEQ ID NO:293), or

HHGCEHICVNNGNSYICKCSXGFVLAEDGRRCKKCTEGPIDLVFVIDGSKSLG

EENFEVVKQFVTGIIDSLTISPKAARVGLLQYSTQVHTEFTLRNFNSAKDMKKA

VAHMKYMGKGSMTGLALKHMFERSFTQGEGARPFPQGCPEQPLCSPTDGLR

MTSPSGPVKPRPMVSLCMLLG

KFYPRRRGQALSTRVP

RAAIVFTDGRAQDDVSEWASKAKANGITMYAVGVGKAIEEELQEIASEPTNKH

LFYAEDFSTMDEISEKLKKGICEALEDSDGRQDSPAGELPKTVQQPTVQHRYLF

EEDNLLRSTQKLSHSTKPSGSPLEEKHDQCKCENLIMFQNLANEEVRKLTQRLE

EMTQRMEALENRLRYR	(SEQ ID NO:294).

Polynucleotides encoding these polypeptides are also encompassed by the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 8. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 8.

This gene is expressed primarily in placenta, infant brain, prostate, fetal lung and to a lesser extent in endometrium and fetal tissues.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, abnormal placenta and pregnancy, disorder and injury in brain, prostate, and vasculature. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproduction, neuronal, and vascular systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g. developing, placenta, brain and other tissue of the nervous system, prostate, lung and endometrium, and cancerous and wounded tissues) or bodily fluids (e.g. amniotic fluid, seminal fluid, pulmonary surfactant, or sputum, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The tissue distribution in placental tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis, treatment, and cure of abnormalities in placenta and pregnancy, disorder and injury in brain, prostate, and vasculature. Similarly, the homology to the cartilage matrix protein suggests that the protein product of this clone would be useful for the treatment, diagnosis, and/or prevention of various skin disorders including congenital disorders (i.e. nevi, moles, freckles, Mongolian spots, hemangiomas, port-wine syndrome), integumentary tumors (i.e. keratoses, Bowen's disease, basal cell carcinoma, squamous cell carcinoma, malignant melanoma, Paget's disease, mycosis fungoides, and Kaposi's sarcoma), injuries and inflammation of the skin (i.e. wounds, rashes, prickly heat disorder, psoriasis, dermatitis), atherosclerosis, uticaria, eczema, photosensitivity, autoimmune disorders (i.e. lupus erythematosus, vitiligo, dermatomyositis, morphea, scleroderma, pemphigoid, and pemphigus), keloids, striae, erythema, petechiae, purpura, and xanthelasma. In addition, such disorders may predispose increased susceptibility to viral and bacterial infections of the skin (i.e. cold sores, warts, chickenpox, molluscum contagiosum, herpes zoster, boils, cellulitis, erysipelas, impetigo, tinea, althletes foot, and ringworm). Moreover, the protein product of this clone may also be useful for the treatment or diagnosis of various connective tissue disorders such as arthritis, trauma, tendonitis, chrondomalacia and inflamation, autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (i.e. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:64 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1654 of SEQ ID NO:64, b is an integer of 15 to 1668, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:64, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 55

The translation product of this gene is the human ortholog of bovine and hamster CII-3, a succinate-ubiquinone oxidoreductase complex II membrane-intrinsic subunit, which is thought to be important in mitochondrial electron transport chain during metabolism. In specific embodiments, the polypeptides of the invention comprise


MAALLLRHVGRHCLRAHFSPQLCIRNAVPLGTTAKEEMERFWNKNIGSNRPLSPHITIYS	(SEQ ID NO:295);

VFPLMYHTWNGIRHLMWDLGKGLKIPQLYQSG	(SEQ ID NO:296);

MAALLLRHVGRHCLRAH	(SEQ ID NO:297);

VKSLCLGPALIHTAKFAL	(SEQ ID NO:298);

VFPLMYHTWNGIRHLMWDLGKGL	(SEQ ID NO:299).

This gene is expressed in 8-week old early stage human.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, metabolic or developmental disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., developmental, metabolic, cancerous and wounded tissues) or bodily fluids (e.g., lymph, amniotic fluid, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The tissue distribution in fetal tissue combined with the homology to a metabolic protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis, treatment, and cure of metabolism disorders. Similarly, expression within embryonic tissue and other cellular sources marked by proliferating cells suggests that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, embryonic development also involves decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Protein, as well as, antibodies directed against the protain may show utility as a tissue-specific marker and/or immuntherapy target for the above-listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:65 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1339 of SEQ ID NO:65, b is an integer of 15 to 1353, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:65, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 56

This gene is expressed primarily in umbilical vein endothelial cells, human ovarian tumor cells, human meningima cells, and human Jurkat membrane bound polysomes. In specific embodiments, polypeptides of the invention comprise the amino acid sequence:


RVWDVRPFAPKERCVKIFQGNV	(SEQ ID NO:300);

HNFEKNLLRCSWSPDGSKIAAGSADRFVYV	(SEQ ID NO:301);

WDTTSRRILYKLPGHAGSINEVAFHPDEPI	(SEQ ID NO:302),

YQGLGLRQNKLTYTMRGHADSVTG	(SEQ ID NO:303), or

LSLSSEGSYLLSNAMDNTVRVWDVRPFAPKERCVKIFQGNVHNFEKNLLRCS

WSPDGSKIAAGSADRFVYVWDTTSRRILYKLPGHAGSINEVAFHPDEPIIISASS

DKRLYMGEIQ

RKKAAIQTFONTYQVLAVTFNDTSDQIISGGIDNDIKVWDCARTS	(SEQ ID NO:304).

Polynucleotides encoding these polypeptides are also encompassed by the invention.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, inflammation, immune and cardiovascular disorders and urogenital neoplasias, and developmental disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of these tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune, neurological, urogenital, reproductive system and vascular systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues and cell types (e.g., blood cells, cells, endothelial cells, ovary and other reproductive tissue, developmental, meningima, and cancerous and wounded tissues) or bodily fluids (e.g. amniotic fluid, seminal fluid, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 143 as residues: Phe-71 to Arg-76, Pro-82 to His-87, Glu-103 to Ala-111.

The tissue distribution in immune cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of immune disorders including: leukemias, lymphomas, auto-immune, immuno-supressive (e.g. transplantation) and immunodeficiencies (e.g. AIDS) and hematopoietic disorders. In addition, expression in ovarian tumor cells suggests that polynucleotides and polypeptides corresponding to this gene are useful for study, diagnosis, and treatment of ovarian tumors, and other tumors and neoplasias. Further, endothelial cell expression suggests a role in cadiovascular or respiratory/pulmonary disorders or infections (athsma, pulmonary edema, pneumonia). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:66 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 997 of SEQ ID NO:66, b is an integer of 15 to 1011, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:66, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 57

The translation product of this gene shares sequence homology with type I collagen. In specific embodiments, the polypeptides of the invention comprise the sequence:


GRIPAPAPSVPAGPDSR	(SEQ ID NO:308);

VRGRTVLRPGLDAEPELSPE	(SEQ ID NO:305);

EQRVLERKLKKERKKEERQ	(SEQ ID NO:306);

ARRSGAELAWDYLCRWAQKHKNWRFQKTRQTWLLLHMYDSDKVPDEHFSTLLAYLE	(SEQ ID NO:309); and/or

GLQGR

RLREAGLVAQHPP	(SEQ ID NO:307).

Polynucleotides encoding these polypeptides are also encompassed by the invention. Polynucleotides of the invention do not comprise the nucleic acid sequence shown as Genbank Accession No. gb|L07392|HUMRETPIGA, which is hereby incorporated herein by reference.

This gene is expressed primarily in epididymus, prostate cell line (LNCAP), and pituitary gland; and to a lesser extent in many other tissues.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, abnormalities of the epididymus, prostate (especially prostate cancer), pituitary gland, or other reproductive, urogenital, or endocrine disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the male reproductive system and neuroendocrine system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues and cell types (e.g., epididymus and other reproductive tissue, prostate, and pituitary gland, and cancerous and wounded tissues) or bodily fluids (e.g. seminal fluid, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The tissue distribution and homology to type I collagen, indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of abnormalities of the epididymus, prostate (especially prostate cancer), and pituitary gland. Similarly, the protein product of this clone may also be useful for the treatment or diagnosis of various connective tissue disorders such as arthritis, trauma, tendonitis, chrondomalacia and inflammation, autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (i.e. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:67 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1179 of SEQ ID NO:67, b is an integer of 15 to 1193, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:67, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 58

This gene is expressed primarily in the frontal cortex of the brain from a schizophrenic individual.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neural disorders, particularly neurodegenerative disorders such as schizophrenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues and cell types (e.g., brain and other tissue of the nervous system, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The tissue distribution in brain indicates that polynucleotides and polypeptides corresponding to this gene are useful for for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:68 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 546 of SEQ ID NO:68, b is an integer of 15 to 560, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:68, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 59

The polypeptide encoded by Gene 59 is homologous to human surface 4 integral membrane protein. In specific embodiments, the polypeptides of the invention comprise the sequence:


TGCVLVLSRNFVQYACFGLFGIIALQTIAYSILWDLKF LMRN	(SEQ ID NO:310);

SRSEGKSMFAGVPTMRESSPKQYMQLGGRVLLVLMFMTLLH	(SEQ ID NO:311);
FDASFFSIVQNIVG

GTAEDFADQFLRVTKQYLP HVARLCLIST	(SEQ ID NO:312);
FLEDGIRMFQWSEQRDYIDTTWNCGYLLAS

LMRNESRS	(SEQ ID NO:314);

ASFLLSRTSWGTA	(SEQ ID NO:315);

ASFLLSRTSW	(SEQ ID NO:313),
GTALMIL

ASFLLSRTSWGTALMIL	(SEQ ID NO:316),

PSFTL	(SEQ ID NO:317),
TPASFLLSRTSWGTALMILVAIGFKTKLAALTLVVWYLFAINVYFNAFWTIPVYK
PMHDFLKYDFFQT

RTEPPPGTSCGGRSGCGRRRARASE	(SEQ ID NO:318),
RASEPSRASRRRHGPERPDGHGRGLRRPVPPCHKAVPAPRGAPLSDQHLPGG
RHPYVVPVERAARLHRHHLELRLPAGLVLRLPQLAGTXTGCVLVLSRNFVQYA
CFGLFGIIALQTIAYSILWDLKFLMRNLALGGGLLLLLAESRSEGKSMFAGVPT
MRESSPKQYMQLGGRVLLVLMFMTLLHFDASFFSIVQNIVGHSSDDFSGHWF

GXSRRRALPVEAAAGAGADGREPASERASRAEPPAVAMGQ	(SEQ ID NO:319), or
NDLMGTAEDFADQFLRVTKQYLPHVARLCLISTFLEDGIRMWFQWSEQRDYIDT
TWNCGYLLASSFVFLNLLGX

WVFLFLLALGGLGP	(SEQ ID NO:320)
DSGRCLCREGRISGIYQLILAKQFLRFFCFMWETDLNLILCCILYLSCV

NO:320). Polynucleotides encoding these polypeptides are also encompassed by the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 9. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 9.

This gene is expressed primarily in Hodgkin's lymphoma and lung; and to a lesser extent in many other human tissues.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune discorders, particularly Hodgkin's lymphoma, tumors or other abnormalities of the lung. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and respiratory systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types(e.g. hematopoietic, lymphoid tissue, and pulmonary tissue, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, pulmonary surfactant or sputum, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.179 as residues: Met-20 to Trp-27.

The tissue distribution in immune tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of Hodgkin's lymphoma, tumors or other abnormalities of the lung. Similarly, expression of this clone within immune tissues, particularly Hodgkin's lymphoma, suggests a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:69 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1643 of SEQ ID NO:69, b is an integer of 15 to 1657, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:69, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 60

The gene encoding the disclosed cDNA is believed to reside on chromosome 17. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 17.

This gene is expressed primarily in bone cancer and stomach cancer, and to a lesser extent in many other tissues.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, bone cancer and stomach cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the bone, and the stomach, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., bone, and stomach, skeletal, gastrointestinal, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, chyme, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The tissue distribution in skeletal tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of skeletal or gastrointestinal disorders, particularly cancer. Similarly, the expression of this gene product in skeletal tissue would suggest a role in the detection and treatment of disorders and conditions affecting the skeletal system, in particular osteoporosis, bone cancer, as well as, disorders afflicting connective tissues (e.g. arthritis, trauma, tendonitis, chrondomalacia and inflammation), such as in the diagnosis or treatment of various autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (i.e. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as-EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:70 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 697 of SEQ ID NO:70, b is an integer of 15 to 711, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:70, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 61

The gene encoding the disclosed cDNA is believed to reside on the X chromosome. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for the X chromosome.

This gene is expressed primarily in epididymus, and lymph node of breast cancer, and to a lesser extent in many other tissues.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, abnormalities of the epididymus, and breast cancer or other reproductive conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the epididymus and breast, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues and cell types (e.g., epididymus and other reproductive tissue, lymphoid tissue, and mammary tissue, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, breast milk, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.181 as residues: Arg-57 to Ser-65.

The tissue distribution in reproductive tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of abnormalities of the epididymus, breast cancer, or other reproductive disorders. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:71 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 921 of SEQ ID NO:71, b is an integer of 15 to 935, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:71, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 62

The translation product of this gene appears to be the human homolog of bovine NADH dehydrogenase which is thought to be important in cellular metabolism. In specific embodiments, the polypeptides of the invention comprise the amino acid sequence:


SMSALTRLASFARVGGRLFRSGCARTAGDGGVRH	(SEQ ID NO:321),

AGGGVHIEPRYRQFPQLTRSQVFQSEFFSGLMWF

WILWRFWHDSEEVLGHFPYPDPSQWTDEELGIPP

DDED

or fragments thereof. Polynucleotides encoding this polypeptide are also encompassed by the invention.

This gene is expressed in larynx tumor, lymph node, brain amygdala, human cardiomyopathy, and retina.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases affecting cellular metabolism. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues and cell types (e.g., larynx, lymphoid tissue, endothelial, brain and other tissue of the nervous system, heart and cardiovascular tissue, and retina, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.182 as residues: Pro-42 to Thr-5 1, Pro-85 to Glu-95.

The tissue distribution and homology to NADH dehydrogenase indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of diseases involving cellular metabolism. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:72 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 490 of SEQ ID NO:72, b is an integer of 15 to 504, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:72, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 63

This gene is expressed primarily in amygdala, and to a lesser extent in many other tissues.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neural disorders, particularly neurodegenerative disorders or abnormalities of the amygdala. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the amygdala, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues and cell types (e.g. neural, amygdala, and lymphoid tissue, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.183 as residues: Gln-17 to Glu-29, Pro-41 to Phe-46, Ser-59 to Ile-70, Thr-97 to Leu-105.

The tissue distribution in neural tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of abnormalities of amygdala. Similarly, expression within neural tissues suggests that the protein product of this clone would be useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations's, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive

disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:73 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 606 of SEQ ID NO:73, b is an integer of 15 to 620, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:73, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 64

This gene is expressed primarily in female bladder, and to a lesser extent in chronic synovitis and hemangiopericytoma.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, urogenital or skeletal disorders, particularly bladder cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the urinary tract, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., bladder, synovial tissue, and vascular tissue, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.184 as residues: Pro-2 to Gln-7, Pro-27 to Phe-34.

The tissue distribution in urogenital tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatments of defects of the urinary tract, especially bladder cancer. Alternatively, expression within synovitis tissue suggests a role in the detection and treatment of disorders and conditions affecting the skeletal system, in particular osteoporosis, bone cancer, as well as, disorders afflicting connective tissues such as arthritis, trauma, tendonitis, chrondomalacia, autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (i.e. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:74 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 567 of SEQ ID NO:74, b is an integer of 15 to 581, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:74, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 65

This gene is expressed primarily in fetal spleen, and to a lesser extent in hemangiopericytoma, thymus, and synovial sarcoma.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, defects of immune of hematopoietic systems. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune of hematopoietic systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g. immune, hematopoietic, spleen, vascular tissue, thymus, blood cells, and synovial tissue, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, amniotic fluid, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The protein product of this gene is useful for treatment of defects of the immune or hematopoietic systems, because of the gene's expression in thymus and spleen. Similarly, the secreted protein can also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions and as nutritional supplements. It may also have a very wide range of biological acitivities. Typical of these are cytokine, cell proliferation/differentiation modulating activity or induction of other cytokines; immunostimulating/immunosuppressant activities (e.g. for treating human immunodeficiency virus infection, cancer, autoimmune diseases and allergy); regulation of hematopoiesis (e.g. for treating anaemia or as adjunct to chemotherapy); stimulation or growth of bone, cartilage, tendons, ligaments and/or nerves (e.g. for treating wounds, stimulation of follicle stimulating hormone (for control of fertility); chemotactic and chemokinetic activities (e.g. for treating infections, tumors); hemostatic or thrombolytic activity (e.g. for treating haemophilia, cardiac infarction etc.); anti-inflammatory activity (e.g. for treating septic shock, Crohn's disease); as antimicrobials; for treating psoriasis or other hyperproliferative diseases; for regulation of metabolism, and behaviour. Also contemplated is the use of the corresponding nucleic acid in gene therapy procedures. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:75 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1829 of SEQ ID NO:75, b is an integer of 15 to 1843, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:75, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 66

This gene is expressed primarily in human pituitary and to a lesser extent in placenta and fetal lung.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, endocrine growth disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification-of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., pituitary and other endocrine tissue, placenta, developmental and pulmonary tissue, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, amniotic fluid, pulmonary surfactant or sputum, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.186 as residues: Val-38 to Asn-44, Gly-53 to Ser-65.

The tissue distribution in fetal tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment of disorders related to endocrine or pituitary dysfunction, particularly growth disorders. Similarly, expression within fetal tissue and other cellular sources marked by proliferating cells suggests that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, embryonic development also involves decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:76 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1427 of SEQ ID NO:76, b is an integer of 15 to 1441, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:76, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 67

The translation product of this gene shares sequence homology with a Caenorhabditis elegans gene. In specific embodiments, the polypeptides of the invention comprise the sequence:


DPRRPNKVLRYKPPPSE CNPALDDPTP	(SEQ ID NO:323);

DYMNLLGMIFSMCGLMLKLKWCAWVA VYCS	(SEQ ID NO:324);

FISFANSRSSEDTKQMMSSF	(SEQ ID NO:322);
	and/or

MLSISAVVMSYLQNPQPMTPPW	(SEQ ID NO:325).

Polynucleotides encoding these polypeptides are also encompassed by the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 19. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 19.

This gene is expressed primarily in primary breast cancer and lymph node breast cancer and to a lesser extent in adult brain, lung cancer, colon cancer, epithelioid sarcoma, and Caco-2 cell line.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, reproductive, neural, or endothelial disorders, particularly cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the cancer and tumor tissues, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., mammary tissue, lymphoid tissue, brain and other tissue of the nervous system, lung, colon, and epithelium, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, pulmonary surfactant or sputum, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.187 as residues: Asn-34 to Lys-42.

The tissue distribution in a variety of cancer tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of a variety of cancer and tumor types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:77 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 896 of SEQ ID NO:77, b is an integer of 15 to 910, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:77, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 68

The translation product of this gene shares sequence homology with steroid membrane binding protein. The translation product of this gene has recently been published as progesterone binding protein. See Genbank AJ002030. Preferred polypeptides encoded by this gene comprise the following amino acid sequence:


AAGDGDVKLGTLGSGSESSNDGGSESPGDAGAAAXGGGWAAAALALLTGGGE	(SEQ ID NO:326), or

STHASGRAVMAAGDGDVKLGTLGSGSESSNDGG
SESPGDAGAAAXGGGWAAAALALLTGGGE	(SEQ ID NO:327).

The gene encoding the disclosed cDNA is believed to reside on chromosome 4. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 4.

This gene is expressed primarily in breast, and to a lesser extent in placenta and fetal tissue.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, breast cancer or developmental disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of breast or fetal tissues, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g. reproductive, mammary tissue, placenta, and fetal tissue, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, amniotic fluid, breast milk, , serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.188 as residues: Pro-43 to Asp-49, Gln-54 to Pro-64, Asp-110 to Asp-118, Lys-138 to Tyr-143, Pro-150 to Asp-170.

The tissue distribution in reproductive tissues combined with the homology to a steroid membrane binding protein and to progesterone binding protein indicates that the protein products of this gene are useful for treatment of breast cancers, especially those caused by estrogen and progesterone binding. Similarly, expression within fetal tissues and other cellular sources marked by proliferating cells suggests that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, embryonic development also involves decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:78 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2762 of SEQ ID NO:78, b is an integer of 15 to 2776, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:78, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 69

It is likely that the open reading frame containing the predicted signal peptide continues in the 5′ direction. Therefore, preferred polypeptides encoded by this gene comprise the following amino acid sequence:

AADNYGIPRACRNSARSYGAAWLLLXPAGSSRVEPTQDISISDQLGGQDV

PFRNLSLLVVGVGAVFSLLFHLGTRERRRPHAXEPGEHTPLLAPATAQPL

LLWKHWLREXAFYQVGILYMTTRLIVNLSQTYMAMYLTYSLHLPKKFIAT

IPLVMYLSGFLSSFLMKPINKCIGRN (SEQ ID NO:328).

This gene is expressed primarily in macrophage (GM-CSF treated), and to a lesser extent in monocytes and dendritic cells.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune or hematopoietic disorders, particularly inflammation and infection . Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues and cell types (e.g. immune, macrophages and other blood cells, and dendritic cells, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not -having the disorder.

The tissue distribution in immune tissue indicates that the protein products of this gene are useful for treatment of infection or inflammation or other events or defects involving the immune system. Similarly, the tissue distribution suggests a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:79 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1473 of SEQ ID NO:79, b is an integer of 15 to 1487, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:79, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 70

This gene was found to have homology to a conserved human 15 kDa selenoprotein (See Genbank Accession No. gi|3095111 (AF051894)) which may be involved in the regulation of important cellular functions such as metabolism or cell cycle regulation.

This gene is expressed primarily in adult brain and to a lesser extent in thyroid, 12 week old early stage human, and stromal cell TF274.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurological or neuro-endocrine diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous or endocrine systems, expression of tills gene at significantly higher or lower levels may be routinely detected in certain tissues and cell types (e.g., brain and other tissue of the nervous system, developmental, immune, thyroid, endocrine, and stromal cells, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, amniotic fluid, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.190 as residues: Pro-65 to Cys-71.

The tissue distribution in neural tissue indicates that the protein products of this gene are useful for treatment and diagnosis of neurological diseases or metabolic conditions involving the neuro-endocrine system. Similarly, the protein product of this clone would be useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:80 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1549 of SEQ ID NO:80, b is an integer of 15 to 1563, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:80, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 71

In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:

CTLAMWXLGHCDPRRCTGRKLARLGLVRCLRLGHRFGGLVLSPVGKQYAS

PADRQLVAQSGVAVIDCSWARLDETPFGK (SEQ ID NO:329).

This gene is expressed in helper T-cells and, to a lesser extent, in adult brain and adult testes.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune disorders, meningitis or reproductive problems. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune, neural and reproductive systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues and cell types (e.g., T-cells and other blood cells, brain and other tissue of the nervous system, testes and other reproductive tissue, and cancerous and wounded tissues) or bodily fluids (e.g. seminal fluid, lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.191 as residues: Val-18 to Tyr-24, Ala-89 to Asp-99, Asp-104 to Ala-117, Leu-121 to Pro-136.

The tissue distribution in immune cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of immune and reproductive disorders. Similarly, the secreted protein can also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions and as nutritional supplements. It may also have a very wide range of biological acitivities. Typical of these are cytokine, cell proliferation/differentiation modulating activity or induction of other cytokines; immunostimulating/immunosuppressant activities (e.g. for treating human immunodeficiency virus infection, cancer, autoimmune diseases and allergy); regulation of hematopoiesis (e.g. for treating anaemia or as adjunct to chemotherapy); stimulation or growth of bone, cartilage, tendons, ligaments and/or nerves (e.g. for treating wounds, stimulation of follicle stimulating hormone (for control of fertility); chemotactic and chemokinetic activities (e.g. for treating infections, tumors); hemostatic or thrombolytic activity (e.g. for treating haemophilia, cardiac infarction etc.); anti-inflammatory activity (e.g. for treating septic shock, Crohn's disease); as antimicrobials; for treating psoriasis or other hyperproliferative diseases; for regulation of metabolism, and behaviour. Also contemplated is the use of the corresponding nucleic acid in gene therapy procedures. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:81 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1006 of SEQ ID NO:81, b is an integer of 15 to 1020, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:8 1, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 72

The translated polypeptide of this contig has a high degree of identity with the Ob Receptor-Associated Protein deposited as GenBank Accession No. 2266638. No function has been determined for the Ob Receptor-Associated Protein, however it is expressed upon stimulation of the Ob Receptor by Leptin. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:

SGRGARSDVTAMAGIKALISLSFGGAIGLMFLMLGCALPIYNKVPLFVLFFYI LSPIPYCIARRLVDDTDA (SEQ ID NO:330).

This gene is expressed in T-cells and to a lesser extent in endothelial and bone marrow cells.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, acute lymphoblastic leukemia, hematapoetic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and hematapoetic systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues and cell types (e.g. immune, T-cells and other blood cells, endothelial cells, and bone marrow, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder Preferred epitopes include those comprising a sequence shown in SEQ ID NO.192 as residues: Ser-61 to Trp-70.

The tissue distribution in T-cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of leukemia and other disorders of the primary immune system. In addition, since this gene appears to be related to the Ob Receptor-Related Protein, it is likely that this polypeptide is also involved in the Ob/Leptin signal transduction cascade. As a result, this protein may be of use in the molecular diagnosis and therapeutic intervention of obesity and related disorders. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:82 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 756 of SEQ ID NO:82, b is an integer of 15 to 770, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:82, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 73

The translation product of this contig has homology with furin, a protein thought to be a key endopeptidase in the constitutive secretory pathway. The identification and initial characterization of Furin was reported by Takahasi and colleagues (BiochemBiophys Res Commun 1993 September 15;195(2):1019-1026).

This gene is expressed primarily in neutrophils.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases of the immune system such as allergies, wound healing and antigen recognition. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues and cell types (e.g. immune tissues, neutrophils and other blood cells, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment of allergies or other immune disorders since neutrophils are an important part of an allergic response. Further, since this protein appears to be related to furin, it can be used diagnostically and therapeutically to treat secretory protein processing disorders. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:83 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 467 of SEQ ID NO:83, b is an integer of 15 to 481, where both a and b correspond to the positions of nucleotide residues shown in SEQ D NO:83, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 74

This gene is expressed in the frontal cortex.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, of the motor activity and sensory functions that involve the central nervous system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., brain and other tissue of the nervous system, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The tissue distribution in neural tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of neural disorders that affect cognitive functions. Similarly, the protein product of this clone would be useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses, autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:84 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 630 of SEQ ID NO:84, b is an integer of 15 to 644, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 84, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 75

The translation product of this gene shares sequence homology with inorganic pyrophophatase which is thought to be important in the catalysis the hydrolysis of diphosphate bonds, chiefly in nucleoside di- and triphosphates and essential enzymes that are important for controlling the cellular levels of inorganic pyrophosphate (PPi). The bovine homolog of this gene has been identified by Yang and Wensel (J. Biol. Chem. 267:24641-24647 (1992)). In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:

ARVRXRGALSLSVGAACGLVALWQRRRQDSGT (SEQ ID NO:331).

This gene is expressed in osteoclastoma cells and to a lesser extent in epithelial cells.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, osteoporosis and other skeletal disorders. Similarly, polypeptides and antibodies-directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the skeletal system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues and cell types (e.g., bone, and epithelial cells, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.195 as residues: Lys-22 to Tyr-28, Asp-64 to Lys-77, Pro-86 to Ile-91, Gln-99 to Pro-119, Tyr-169 to Asp-174, Lys-176 to Gly-181, Trp-189 to Asn-202, Lys-233 to Gly-239, Ser-250 to Asp-257.

The tissue distribution in osteoclastoma cells and homology to inorganic pyrophophatase indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of osteoporosis through the removal of bone by demineralization. Similarly, the expression of this gene product in osteoclastoma cells would suggest a role in the detection and treatment of disorders and conditions affecting the skeletal system, in particular osteoporosis, bone cancer, as well as, disorders afflicting connective tissues such as arthritis, trauma, tendonitis, chrondomalacia, autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (i.e. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:85 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1337 of SEQ ID NO:85, b is an integer of 15 to 1351, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:85, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 76

The translation product of this gene shares exact sequence homology with ATP sulfurylase/APS kinase (GenBank Accession No. 2673862) which is thought to be important in biosynthesis of the activated sulfate donor, adenosine 3′-phosphate 5′-phosphosulfate, involves the sequential action of two enzyme activities: ATP sulfurylase, which catalyzes the formation of adenosine 5′-phosphosulfate (APS) from ATP and free sulfate, and APS kinase, which subsequently phosphorylates APS to produce adenosine 3′-phosphate 5′-phosphosulfate. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:


LSNNAQNWGMQRATNVTYQAHHVSRNKRGQVVGTRGGFRGCTVWL	(SEQ ID NO:332),

VSMALEEYLVCHGIPCYTLDGDNIRQGLNKNLGFSPED	(SEQ ID NO:333),

TQDRNNARQIHEGASLPFFEVFVDAPLHVCEQRDVKGLY	(SEQ ID NO:334),

FTGIDSEYEKPEAPELVLKTDSCDVNDCVQQVVELLQERD	(SEQ ID NO:335),

AETLPALKINKVDMQWVQVLAEGWATPLNGFMREREYLQCL	(SEQ ID NO:336),

VPIVLTATHEDKERLDGCTAFALMYEGRRV	(SEQ ID NO:337),

IGGDLQVLDRVYWVNDGLDQYRLTPTELKQKFKDMNADAV	(SEQ ID NO:338),

GHALLMQDTHKQLLERGYRRPVLLLHPLGGWTKDDDV	(SEQ ID NO:339),

MYAGPTEVQWHCRARMVAGANFYIVGRDPAGMPHPETGKDL	(SEQ ID NO:340),

LTMAPGLITLEIVPFRVAAYNKKKKRMDYYDSEH	(SEQ ID NO:341) or,

GFMAPKAWTVLTEYYKSLE	(SEQ ID NO:342).

This gene is expressed in osteoclastoma cells and to a lesser extent in developmental tissues.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, antibiotic resistant bacterial infections, osteoarthritis and other auto immune diseases, or skeletal disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune or skeletal structure expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., bone, and developmental tissues, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, amniotic fluid, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in


SEQ ID NO. 196 as residues: Asn-15 to Trp-20,

Ser-36 to Gly-41, Pro-103 to Val-110, Pro-134 to Arg-143, Leu-173 to Arg-178, Ser-

190 to Ala-197, His-314 to Arg-319, Arg-354 to Asn-362, Asp-391 to Arg-397, Glu-

402 to Asp-409, Asp-434 to Leu-439, GIu-441 to Arg-446, Gly-455 to Asp-462, Pro-

528 to His-541, Asn-566 to Arg-571, Tyr-574 to Glu-581, Thr-589 to Glu-603.

The tissue distribution and homology to ATP sulfurylase/APS kinase indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment or detection of autoimmune diseases. Similarly, the expression of this gene product in synovium would suggest a role in the detection and treatment of disorders and conditions affecting the skeletal system, in particular osteoporosis, bone cancer, as well as, disorders afflicting connective tissues such as arthritis, trauma, tendonitis, chrondomalacia, autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (i.e. spondyloepiphyseal dysplasia congenital familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:86 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2513 of SEQ ID NO:86, b is an integer of 15 to 2527, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:86, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 77

This polypeptide is identical to the SLP-76-associated protein reported by Musci and colleagues (J. Biol. Chem. 272 (18), 11674-11677 (1997)) and to the FYB protein reported by da Silva and coworkers (Proc. Natl. Acad. Sci. U.S.A. (1997) In press). These proteins have been reported to be novel T-cell Proteins which bind FYN and SLP-76 and regulate IL-2 production. Preferred polypeptides encoded by this gene comprise the following amino acid sequence:

RITDNPEGKWLGRTARGSYGYTKTTAVEIXYDSLKLKKDSLGAPSRPIED

DQEVYDDVAEQDDISSHSQSGSGGIFPPPPDDDIYDGIEEEDADDGFPAP

PKQLDMGDEVYDDVDTSDFPVSSAEMSQGTNVGKAKTEEKDLKKLKKQXK

EXKDFRKKFKYDGEIRVLYSTKVTTSITSKKWGTRDLQVKPGESLEVIQT

TDDTKVLCRNEEGKYGYVLRSYLADNDGEIYDDIADGCIYDND (SEQ

ID NO:343).

This gene is expressed in CD34 positive cells (hematopoietic progenitor cells) and to a lesser extent in adult spleen derived from a chronic lymphocytic leukemia patient.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, chronic lymphocytic leukemia; hematopoietic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and hematopoietic systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., T-cells and other blood cells, bone marrow, hematopoietic cells, and spleen, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Further, nucleic acids and polypeptides of the present invention are useful both diagnostically and therapeutically in the intervention of immune and other disorders in which the ability to alter IL-2 expression is desired. Preferred epitopes include those comprising a sequence shown in


SEQ ID NO. 197 as residues: Ala-17 to Lys-37, Val-39 to Ser-45, Lys-59 to His-70,

Arg-90 to Leu-95, Lys-97 to Lys-107, Ser-117 to Leu-124, Phe-133 to Ser-138, Trp-

146 to Leu-167, Pro-175 to Asn-185, Lys-190 to Ser-211, Pro-213 to Ser-222, His-

230 to Pro-235, Pro-240 to Pro-246, Pro-253 to Gly-261, Leu-271 to Leu-303, Leu-

305 to Leu-326, Lys-343 to Leu-349, Thr-363 to Leu-371, Arg-373 to Tyr-381, Tyr-

391 to Leu-401, Pro-404 to VaI-414, Ser-426 to Ser-432, IIe-448 to Ser-457, Gln-462

to Trp-468, Lys-477 to Ser-501, Asp-518 to Ser-523, Ala-541 to Gln-554.

The tissue distribution in immune cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment of a variety of hematopoietic disorders. The noted expression of this gene in hematopoietic progenitor cell—as determined by its expression on CD34 positive hematopoietic stem and progenitor cells—indicates that it plays a critical role in the expansion or proliferation of hematopoietic stem/progenitor cells, as well as in the differentiation of the various blood cell lineages. Thus it could be useful in the reconstitution of the hematopoietic system of patients with leukemias and other hematopoietic diseases. Protein, as well as, antibodies directed against the protain may show utility as a tissue-specific marker and/or immuntherapy target for the above-listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:87 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2552 of SEQ ID NO:87, b is an integer of 15 to 2566, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:87, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 78

This gene is homologous to heparin cofactor II (HCII) which is a 66-kDa plasma glycoprotein that inhibits thrombin rapidly in the presence of dermatan sulfate or heparin.

This gene is expressed in apoptotic and anergic T-cells.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, thrombopienia T-cell lymphomas; Hodgkin's lymphoma. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system—most notably the T-cell compartment, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues and cell types (e.g., T-cells and other blood cells, and lymphoid tissue, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The homology to heparin cofactor II (HCII) and the tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoietic disorders particularly in thrombopoesis, most notably of the T-cell compartment. This could include immune modulation, inflammation, immune surveillance, graft rejection, and autoimmunity. Protein, as well as, antibodies directed against the protain may show utility as a tissue-specific marker and/or immuntherapy target for the above-listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:88 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 526 of SEQ ID NO:88, b is an integer of 15 to 540, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:88, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 79

The translation product of this gene shares sequence homology with a mouse protein believed to represent an integral membrane protein.

This gene is expressed in fetal cochlea and epididymus and to a lesser extent in adult spleen and osteoclastoma.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, osteoclastoma; disorders of the inner ear; male fertility disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the inner ear; male reproductive tract; bone; and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., cochlea, epididymus and other reproductive tissue, spleen, immune tissue, and bone, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, seminal fluid, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.199 as residues: Lys-13 to Gly-23, Cys-38 to Asp-43, Gly-48 to Trp-53, Cys-223 to Ile-237, Ile-240 to Ser-246.

The tissue distribution in reproductive tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment of hearing and fertility disorders. Likewise, it may have a role in the modulation of immune function and in the treatment of osteoporosis. Protein, as well as, antibodies directed against the protain may show utility as a tissue-specific marker and/or immuntherapy target for the above-listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:89 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1849 of SEQ ID NO:89, b is an integer of 15 to 1863, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:89, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 80

The translation product of this gene shares sequence homology with reticulocalbin which is thought to be important in the binding of calcium, particularly within the endoplasmic reticulum.

This gene is expressed in endothelial cells and stromal cells and to a lesser extent in osteoblasts, osteoclasts, and T-cells.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, osteoperosis; osteoclastomas; T-cell lymphomas; Hodgkin's disease. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the vasculature, bone, and immune systems - particularly the T-cell compartments, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues and cell types (e.g., endothelial cells, stromal cells, bone, T-cells and other blood cells, and lymphoid tissue, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in

SEQ ID NO. 200 as residues: Lys-20 to Arg-27,

Pro-32 to Asp-48, Leu-64 to Arg-72, Asp-108 to

Lys-114, Glu-128 to Thr-133, Asp-139 to Phe-147,

Thr-196 to Ala-204, Tyr-218 to Glu-228, Val-230 to

Gln-236, Arg-241 to Lys-255, Glu-276 to Lys-287.

The tissue distribution and homology to reticulocalbin indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of bone disorders such as osteoporosis; the diagnosis and treatment of T-cell lymphomas and Hodgkin's lymphoma; and the treatment of diseases and defects of the vasculature, such as vascular leak syndrome and aberrant angiogenesis that accompanies tumor growth. Protein, as well as, antibodies directed against the protain may show utility as a tissue-specific marker and/or immuntherapy target for the above-listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:90 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2464 of SEQ ID NO:90, b is an integer of 15 to 2478, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:90, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 81

The translation product of this gene shares sequence homology with a family of peptide transport genes—particularly the AtPTR2-B gene from Arabidopsis—which are thought to be important in the uptake of small peptides.

This gene is expressed in a number of fetal tissues, most notably lung, brain, cochlea, and liver/spleen, and to a lesser extent in osteoclastoma and endometrial tumors.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, osteoclastoma; endometrial tumors; cancer; leukemias. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the bone and endometrium, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., fetal tissue, pulmonary tissue, bone, brain and other tissue of the nervous system, cochlea, liver, and spleen, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, pulmonary surfactant or sputum, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.201 as residues: Lys-186 to Asn-199, Pro-202 to Ala-207.

The tissue distribution in fetal tissues combined with the homology to peptide transport proteins indicates that polynucleotides and polypeptides corresponding to this gene are useful for the control of cell proliferation, owing to its strong expression in fetal tissues undergoing active cell division, as well as its expression in a variety of tumors or cancers of adult tissues. Potentially, it may regulate the uptake of peptides that stimulate cell proliferation. This gene product may also be useful in stimulating the uptake of a variety of peptide-based drug compounds. Protein, as well as, antibodies directed against the protain may show utility as a tissue-specific marker and/or immuntherapy target for the above-listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:91 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2044 of SEQ ID NO:91, b is an integer of 15 to 2058, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:91, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 82

This gene is expressed in fetal liver and spleen and to a lesser extent in endothelial cells.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancer and tumors of a hematopoietic and/or endothelial cell origin; leukemias. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system and/or vasculature, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues and cell types (e.g., liver, spleen, endothelial cells, vascular tissue, and tissue and cells of the immune system, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, amniotic fluid, bile, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder Preferred epitopes include those comprising a sequence shown in SEQ ID NO.202 as residues: Met-1 to Asp-9, Arg-66 to Gly-76, Asp-164 to Arg-171.

The tissue distribution in immune tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment of disorders of the immune system. Expression of this gene product in both fetal liver/spleen and endothelial cells indicates that it may be expressed in the hemangioblast, the progenitor cell for both the immune system and the vasculature. Thus, it is most likely expressed in hematopoietic stem cells, and may be useful for the expansion of hematopoietic stem and progenitor cells in conjunction with cancer treatment for a variety of leukemias. Protein, as well as, antibodies directed against the protain may show utility as a tissue-specific marker and/or immuntherapy target for the above-listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:92 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1397 of SEQ ID NO:92, b is an integer of 15 to 1411, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:92, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 84

The translation product of this gene shares sequence homology with NADH dehydrogenase which is thought to be important in cellular metabolism.

This gene is expressed in fetal dura mater and to a lesser extent in T-cells and hypothalamus.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases affecting cellular metabolism. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues and cell types (e.g., fetal tissue, T-cells and other blood cells, and brain and other tissue of the nervous system, and cancerous and wounded tissues) or bodily fluids (e.g., amniotic fluid, lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.204 as residues: Pro-27 to Gln-32, Arg-42 to Glu-51.

The tissue distribution and homology to NADH dehydrogenase indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of diseases involving cellular metabolism. Protein, as well as, antibodies directed against the protain may show utility as a tissue-specific marker and/or immuntherapy target for the above-listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:94 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 743 of SEQ ID NO:94, b is an integer of 15 to 757, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:94, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 85

The translation product of this gene shares sequence homology with I-TRAF, a novel TNF receptor associated factor (TRAF)-interacting protein that regulates TNF receptor-mediated signal transduction. This protein is thought to be important in regulating the cellular response to tumor necrosis factor (TNF), which is an important mediator of inflammation.

This gene is expressed in endothelial cells and to a lesser extent in glioblastoma and osteoblastoma.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, inflammation; glioblastoma and osteoblastoma. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues and cell types (e.g., endothelial cells, bone, and glial cells and tissue of the nervous system, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in

SEQ ID NO. 205 as residues: Glu-15 to Thr-22,

Glu-46 to Leu-62, Arg-103 to Glu-119, Gln-127 to

Glu-132, Asn-152 to Trp-158, Gln-191 to Gln-210,

Glu-264 to Thr-271, Tyr-282 to Leu-288, Trp-319 to

Thr-331, Glu-335 to Ser-348, Ser-353 to Ser-358,

Asp-382 to Asn-392.

The tissue distribution in endothelial cells combined with the homology to the I-TRAF protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of inflammatory diseases, including rheumatoid arthritis, sepsis, inflammatory bowel disease, and psoriasis, particularly where tumor necrosis factor is known to be involved. Protein, as well as, antibodies directed against the protain may show utility as a tissue-specific marker and/or immuntherapy target for the above-listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:95 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2380 of SEQ ID NO:95, b is an integer of 15 to 2394, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:95, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 86

This gene has homology with a candidate gene involved in X-linked Retinopathy reported by Wong and colleagues (Genomics 15:467-471 (1993)).

This gene is expressed in a T-cell line.

Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, inflammation and autoimmune diseases; T-cell lymphoma. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues and cell types (e.g., T-cells and other blood cells, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.

The tissue distribution in T-cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of inflammatory disorders such as sepsis, inflammatory bowel disease, psoriasis, and rheumatoid arthritis as well as autoimmune disease such as lupus. It could also be useful in immune modulation and in the process of immune surveillance. The present invention can be used diagnostically and therapeutically to treat X-linked Retinopathy. Protein, as well as, antibodies directed against the protain may show utility as a tissue-specific marker and/or immuntherapy target for the above-listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:96 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 658 of SEQ ID NO:96, b is an integer of 15 to 672, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:96, and where the b is greater than or equal to a+14.

Features of Protein Encoded by Gene No: 87

This gene is expressed in human brain tissue. Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, brain disorders; neurodegenerative disorders; tumors of a brain origin. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., brain and other tissue of the nervous system, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO:211 as residues: Cys-32 to Tyr-38. Preferred epitopes include those comprising a sequence shown in SEQ ID NO.207 as residues: Cys-32 to Tyr-38.

The tissue distribution in neural tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of CNS disorders such as epilepsy, paranoia, depression, Alzheimer's disease, and schizophrenia. It could be useful in the survival and/or proliferation of neurons and could effect neuronal regeneration. Protein, as well as, antibodies directed against the protain may show utility as a tissue-specific marker and/or immuntherapy target for the above-listed tissues. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:11 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1665 of SEQ ID NO:11, b is an integer of 15 to 1679, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:11, and where the b is greater than or equal to a+14. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:97 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1405 of SEQ ID NO:97, b is an integer of 15 to 1419, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:97, and where the b is greater than or equal to a+14.



	5' NT

NT

of

AA

First

Last

ATCC

SEQ

5' NT

3' NT

5' NT

First

SEQ

AA

First AA

Last

Deposit

ID

Total

of

AA of

ID

of

AA

Gene

cDNA

Nr and

NO:

NT

Clone

Start

Signal

NO:

Sig

Secreted

of

No.

Clone ID

Date

Vector

X

Seq.

Condon

Pep

Y

Pep

Portion

ORF

1	HAGEW82	97923	Uni-ZAP XR	11	1679	247	1607	353	353	121	1			31
		03/07/97
		209071
		05/22/97
2	HAGFY16	97923	Uni-ZAP XR	12	1963	209	1922	251	251	122	1	28	29	198
		03/07/97
		209071
		05/22/97
2	HAGFY16	97923	Uni-ZAPXR	98	1830	87	1786	128	128	208	1	26	27	45
		03/07/97
		209071
		05/22/97
3	HALAA60	97923	Uni-ZAP XR	13	1212	1	1212	99	99	123	1	24	25	39
		03/07/97
		209071
		05/22/97
4	HAPBL78	97923	Uni-ZAP XR	14	2061	882	2061	900	900	124	1	22	23	23
		03/07/97
		209071
		05/22/97
5	HASAV70	97923	Uni-ZAP XR	15	1412	10	733	103	103	125	1	20	21	110
		03/07/97
		209071
		05/22/97
6	HBNAF22	97923	Uni-ZAP XR	16	1052	276	880	538	538	126	1	23	24	63
		03/07/97
		209071
		05/22/97
7	HBNBL77	97923	Uni-ZAP XR	17	683	1	683	181	181	127	1			30
		03/07/97
		209071
		05/22/97
8	HCDDR90	97923	Uni-ZAP XR	18	1054	86	1007	86	86	128	1	23	24	53
		03/07/97
		209071
		05/22/97
9	HCEEF50	97923	Uni-ZAP XR	19	1393	132	1393	192	192	129	1	17	18	57
		03/07/97
		209071
		05/22/97
10	HCEMU42	97923	Uni-ZAP XR	20	1215	277	1070	401	401	130	1	18	19	216
		03/07/97
		209071
		05/22/97
11	HCENE16	97923	Uni-ZAP XR	21	2042	614	2011	793	793	131	1	26	27	49
		03/07/97
		209071
		05/22/97
12	HMSJJ74	97923	Uni-ZAP XR	22	1872	21	1872	69	69	132	1	23	24	68
		03/07/97
		209071
		05/22/97
13	HCUBF15	97923	ZAP Express	23	289	1	289	89	89	133	1	29	30	52
		03/07/97
		209071
		05/22/97
14	HE2DE47	97923	Uni-ZAP XR	24	3533	2821	3532	808	808	134	1	30	31	540
		03/07/97
		209071
		05/22/97
14	HE2DE47	97923	Uni-ZAP XR	99	1145	435	1115	515	515	209	1	22	23	81
		03/07/97
		209071
		05/22/97
15	HKMLH01	97923	pBluescript	25	1148	171	907	196	196	135	1	26	27	57
		03/07/97
15	HE6DG34	97923	Uni-ZAP XR	100	734	25	734	295	295	210	1	36	37	49
		03/07/97
		209071
		05/22/97
16	HE9DG49	97923	Uni-ZAP XR	26	717	1	717	70	70	136	1	27	28	201
		03/07/97
		209071
		05/22/97
16	HE9DG49	97923	Uni-ZAP XR	101	713	17	713	78	78	211	1	28	29	203
		03/07/97
		209071
		05/22/97
17	HELBA06	97923	Uni-ZAP XR	27	1099	1	1099	38	38	137	1	22	23	216
		03/07/97
		209071
		05/22/97
17	HELBA06	97923	Uni-ZAP XR	102	1080	1	1080	149	149	212	1	25	26	186
		03/07/97
		209071
		05/22/97
18	HSLFM29	97923	Uni-ZAP XR	28	941	171	941	128	128	138	1	42	43	102
		03/07/97
		209071
		05/22/97
19	HELBW38	97923	Uni-ZAP XR	29	756	62	756	294	294	139	1	30	31	112
		03/07/97
		209071
		05/22/97
20	HETHN28	97923	Uni-ZAP XR	30	2100	408	2093	496	496	140	1			20
		03/07/97
		209071
		05/22/97
21	HFCDK17	97923	Uni-ZAP XR	31	1448	475	1392	567	567	141	1			30
		03/07/97
		209071
		05/22/97
22	HFEAF41	97923	Uni-ZAP XR	32	456	1	409	21	21	142	1	28	29	99
		03/07/97
		209071
		05/22/97
23	HFKFL13	97923	Uni-ZAP XR	33	1326	1	1322	210	210	143	1			8
		03/07/97
		209071
		05/22/97
24	HFSBG13	97923	Uni-ZAP XR	34	710	1	710	242	242	144	1	16	17	39
		03/07/97
		209071
		05/22/97
25	HFTBE43	97923	Uni-ZAP XR	35	1188	110	1161	178	178	145	1	26	27	131
		03/07/97
		209071
		05/22/97
26	HFTDJ36	97923	Uni-ZAP XR	36	956	1	938	144	144	146	1	21	22	32
		03/07/97
		209071
		05/22/97
27	HKTAC77	97924	Uni-ZAP XR	37	1603	974	1581	1104	1104	147	1			14
		03/07/97
28	HLHSH36	97924	pBluescript	38	1089	55	1067		209	148	1			8
		03/07/97
29	HLHSV96	97924	pBluescript	39	629	1	629	119	119	149	1	32	33	68
		03/07/97
30	HLQBQ86	97924	Lambda ZAP	40	1964	408	1793	581	581	150	1			26
		03/07/97	II
31	HLTBX31	97924	Uni-ZAP XR	41	1522	13	1123	126	126	151	1	32	33	195
		03/07/97
32	HLTCJ63	97924	Uni-ZAP XR	42	875	1	875	43	43	152	1	18	19	91
		03/07/97
33	HMKAH44	97924	pSport1	43	843	1	843	171	171	153	1	30	31	31
		03/07/97
34	HMQAJ64	97924	Uni-ZAP XR	44	489	3	489	55	55	154	1	19	20	90
		03/07/97
34	HMQAJ64	97924	Uni-ZAP XR	103	489	6	489	58	58	213	1	22	23	90
		03/07/97
35	HOABG65	97924	Uni-ZAP XR	45	534	1	534	17	17	155	1	18	19	89
		03/07/97
36	HODCL36	97924	Uni-ZAP XR	46	1374	1	1374	15	15	156	1	20	21	174
		03/07/97
36	HODCL36	97924	Uni-ZAP XR	104	1529	40	1399	54	54	214	1	27	28	48
		03/07/97
37	HODCL50	97924	Uni-ZAP XR	47	596	1	596	269	269	157	1	27	28	45
		03/07/97
38	HODCV74	97924	Uni-ZAP XR	48	851	99	822	170	170	158	1			23
		03/07/97
39	HODCZ16	97924	Uni-ZAP XR	49	2020	569	2020	638	638	159	1	17	18	70
		03/07/97
40	HTOEU03	97924	Uni-ZAP XR	50	2432	848	2432	99	99	160	1	19	20	323
		03/07/97
40	HTOEU03	97924	Uni-ZAP XR	105	2435	849	2435	928	928	215	1	31	32	70
		03/07/97
41	HPBCJ74	97924	pBluescript	51	2340	1627	2340	150	150	161	1	60	61	320
		03/07/97	SK-
41	HPBCJ74	97924	pBluescript	106	805	92	791	239	239	216	1	21	22	83
		03/07/97	SK-
42	HPMBU33	97924	Uni-ZAP XR	52	601	188	601	432	432	162	1			31
		03/07/97
43	HSAUL66	97924	Uni-ZAP XR	53	359	1	337	142	142	163	1	18	19	72
		03/07/97
44	HSIDQ18	97924	Uni-ZAP XR	54	1141	1	1141	25	25	164	1	30	31	281
		03/07/97
44	HSIDQ18	97924	Uni-ZAP XR	107	1166	21	1166	433	433	217	1	30	31	43
		03/07/97
45	HSJBB37	97924	Uni-ZAP XR	55	1560	413	1498	714	714	165	1	31	32	81
		03/07/97
46	HSJBQ79	97924	Uni-ZAP XR	56	1507	164	608	57	57	166	1	19	20	327
		03/07/97
46	HSJBQ79	97924	Uni-ZAP XR	108	586	4	586	35	35	218	1	23	24	184
		03/07/97
47	HTEGA76	97958	Uni-ZAP XR	57	450	1	450	90	90	167	1	43	44	65
		03/13/97
		209072
		05/22/97
48	HTEJN13	97958	Uni-ZAP XR	58	1147	1	1147	163	163	168	1	15	16	159
		03/13/97
		209072
		05/22/97
48	HTEJN13	97958	Uni-ZAP XR	109	1134	1	1134	155	155	219	1	19	20	71
		03/13/97
		209072
		05/22/97
49	HTHBL86	97958	Uni-ZAP XR	59	777	1	777	115	115	169	1	18	19	123
		03/13/97
		209072
		05/22/97
50	HTSFO71	97958	pBluescript	60	1191	48	598	52	52	170	1	30	31	129
		03/13/97
		209072
		05/22/97
50	HTSFO71	97958	pBluescript	110	1333	594	1333	829	829	220	1			10
		03/13/97
		209072
		05/22/97
51	HAPNO80	209235	Uni-ZAP XR	61	1580	443	1554	114	114	171	1	1	2	372
		09/04/97
51	HAUCC47	97958	Uni-ZAP XR	111	1015	249	708	244	244	221	1	28	29	138
		03/13/97
52	HBMCL41	97958	pBluescript	62	1117	105	1034	182	182	172	1	28	29	216
		03/13/97
		209072
		05/22/97
53	HCFLD84	97958	pSport1	63	361	1	361	97	97	173	1	32	33	55
		03/13/97
		209072
		05/22/97
54	HE8EM69	97958	Uni-ZAP XR	64	1668	1	1638	150	150	174	1	20	21	23
		03/13/97
		209072
		05/22/97
55	HE8EZ48	97958	Uni-ZAP XR	65	1353	35	1303	231	231	175	1	33	34	103
		03/13/97
		209072
		05/22/97
56	HEBGF73	97958	Uni-ZAP XR	66	1011	655	1011	703	703	176	1	38	39	48
		03/13/97
		209072
		05/22/97
57	HFEBF41	97958	Uni-ZAP XR	67	1193	267	1090	459	459	177	1	35	36	96
		03/13/97
		209072
		05/22/97
58	HFRBU14	97958	Uni-ZAP XR	68	560	1	560	63	63	178	1	29	30	95
		03/13/97
		209072
		05/22/97
59	HFVGZ79	97958	pBluescript	69	1657	765	1581	839	839	179	1	21	22	27
		03/13/97
		209072
		05/22/97
60	HHGCM76	97958	Lambda ZAP	70	711	8	711	270	270	180	1	22	23	89
		03/13/97	II
		209072
		05/22/97
60	HHGCM76	97958	Lambda ZAP	112	711	8	711	270	270	222	1			11
		03/13/97	II
		209072
		05/22/97
61	HHGCO88	97958	Lambda ZAP	71	935	111	935	272	272	181	1	19	20	65
		03/13/97	II
		209072
		05/22/97
62	HHGCP52	97958	Lambda ZAP	72	504	113	484	45	45	182	1	15	16	105
		03/13/97	II
		209072
		05/22/97
63	HHGDB72	97958	Lambda ZAP	73	620	1	620	96	96	183	1	18	19	132
		03/13/97	II
		209072
		05/22/97
64	HHGDI71	97958	Lambda ZAP	74	581	156	581	248	248	184	1	32	33	69
		03/13/97	II
		209072
		05/22/97
65	HHSDI45	97958	Uni-ZAP XR	75	1843	537	1786	630	630	185	1	27	28	45
		03/13/97
		209072
		05/22/97
66	HHSEB66	97958	Uni-ZAP XR	76	1441	116	800	167	167	186	1	36	37	65
		03/13/97
		209072
		05/22/97
67	HAUAI83	97958	Uni-ZAP XR	77	910	1	886	253	253	187	1	37	38	49
		03/13/97
		209072
		05/22/97
67	HJPAZ83	97958	Uni-ZAP XR	113	1076	398	1076		575	223	1	11	12	23
		03/13/97
		209072
		05/22/97
68	HLDBO49	97958	pCMVSport	78	2776	18	1888	187	187	188	1	14	15	170
		03/13/97	3.0
		209072
		05/22/97
69	HLDBQ19	209226	pCMVSport	79	1487	401	1487	534	534	189	1	22	23	132
		08/28/97	3.0
69	HLDBQ19	97958	pCMVSport	114	1525	401	1480	534	534	224	1	22	23	66
		03/13/97	3.0
		209072
		05/22/97
70	HMSGT42	97958	Uni-ZAP XR	80	1563	33	1077	40	40	190	1	32	33	92
		03/13/97
		209072
		05/22/97
71	HMWIC78	97957	Uni-Zap XR	81	1020	18	780	238	238	191	1	23	24	176
		03/13/97
		209073
		05/22/97
72	HTTCT79	97957	Uni-ZAP XR	82	770	101	770	286	286	192	1	26	27	70
		03/13/97
		209073
		05/22/97
73	HNGJU84	97957	Uni-ZAP XR	83	481	1	481	58	58	193	1	20	21	25
		03/13/97
		209073
		05/22/97
74	HNTAC73	97957	pCMVSport	84	644	1	623	14	14	194	1	25	26	73
		03/13/97	3.0
		209073
		05/22/97
75	HOSEI45	97957	Uni-ZAP XR	85	1351	435	1284	98	98	195	1	12	13	289
		03/13/97
		209073
		05/22/97
75	HOSEI45	97957	Uni-ZAP XR	115	1350	428	1283		545	225	1			28
		03/13/97
		209073
		05/22/97
76	HOSFD58	97957	Uni-ZAP XR	86	2527	290	1747	56	56	196	1	30	31	624
		03/13/97
		209073
		05/22/97
76	HOSFD58	97957	Uni-ZAP XR	116	2527	288	1747	477	477	226	1	32	33	61
		03/13/97
		209073
		05/22/97
77	HSAUM95	97957	Uni-ZAP XR	87	2566	1843	2566	251	251	197	1	30	31	649
		03/13/97
		209073
		05/22/97
77	HSAUM95	97957	Uni-ZAP XR	117	1098	375	1098	677	677	227	1	21	22	29
		03/13/97
		209073
		05/22/97
78	HSAUR67	97957	Uni-ZAP XR	88	540	1	540	83	83	198	1	32	33	55
		03/13/97
		209073
		05/22/97
79	HSKDI81	97957	Uni-ZAP XR	89	1863	152	1165	188	188	199	1	11	12	266
		03/13/97
		209073
		05/22/97
79	HSKDI81	97957	Uni-ZAP XR	118	1679	152	1166	315	315	228	1			18
		03/13/97
		209073
		05/22/97
80	HSKDW91	97957	Uni-ZAP XR	90	2478	1149	2449	92	92	200	1	19	20	315
		03/13/97
		209073
		05/22/97
81	HTLEX50	97957	Uni-ZAP XR	91	2058	476	2058	414	414	201	1	20	21	207
		03/13/97
		209073
		05/22/97
82	HSKHL65	97957	pBluescript	92	1411	345	1411	157	157	202	1	69	70	195
		03/13/97
		209073
		05/22/97
82	HSKHL65	97957	pBluescript	119	1411	345	1411	526	526	229	1	37	38	72
		03/13/97
		209073
		05/22/97
83	HHFGA11	97957	Uni-ZAP XR	93	2187	147	2184	397	397	203	1	30	31	330
		03/13/97
		209073
		05/22/97
83	HOEBX83	97957	Uni-ZAP XR	120	2223	144	2136	198	198	230	1	20	21	142
		03/13/97
		209073
		05/22/97
84	HWTBL40	97957	Uni-ZAP XR	94	757	524	608	445	445	204	1	20	21	58
		03/13/97
		209073
		05/22/97
85	HBXFG80	97957	ZAP Express	95	2394	481	2394	523	523	205	1	1	2	392
		03/13/97
		209073
		05/22/97
86	HCACY32	97957	Uni-ZAP XR	96	672	1	672	117	117	206	1	21	22	26
		03/13/97
		209073
		05/22/97
87	HCEDO21	97957	Uni-ZAP XR	97	1419	1	1419	207	207	207	1	20	21	38
		03/13/97
		209073
		05/22/97

Table 1 summarizes the information corresponding to each “Gene No.” described above. The nucleotide sequence identified as “NT SEQ ID NO:X” was assembled from partially homologous (“overlapping”) sequences obtained from the “cDNA clone ID” identified in Table 1 and, in some cases, from additional related DNA clones. The overlapping sequences were assembled into a single contiguous sequence of high redundancy (usually three to five overlapping sequences at each nucleotide position), resulting in a final sequence identified as SEQ ID NO:X.

The cDNA Clone ID was deposited on the date and given the corresponding deposit number listed in “ATCC Deposit No:Z and Date.” Some of the deposits contain multiple different clones corresponding to the same gene. “Vector” refers to the type of vector contained in the cDNA Clone ID.

“Total NT Seq.” refers to the total number of nucleotides in the contig identified by “Gene No.” The deposited clone may contain all or most of these sequences, reflected by the nucleotide position indicated as “5′ NT of Clone Seq.” and the “3′ NT of Clone Seq.” of SEQ ID NO:X. The nucleotide position of SEQ ID NO:X of the putative start codon (methionine) is identified as “5′ NT of Start Codon.” Similarly, the nucleotide position of SEQ ID NO:X of the predicted signal sequence is identified as “5′ NT of First AA of Signal Pep.”

The translated amino acid sequence, beginning with the methionine, is identified as “AA SEQ ID NO:Y,” although other reading frames can also be easily translated using known molecular biology techniques. The polypeptides produced by these alternative open reading frames are specifically contemplated by the present invention.

The first and last amino acid position of SEQ ID NO:Y of the predicted signal peptide is identified as “First AA of Sig Pep” and “Last AA of Sig Pep.” The predicted first amino acid position of SEQ ID NO:Y of the secreted portion is identified as “Predicted First AA of Secreted Portion.” Finally, the amino acid position of SEQ ID NO:Y of the last amino acid in the open reading frame is identified as “Last AA of ORF.”

SEQ ID NO:X and the translated SEQ ID NO:Y are sufficiently accurate and otherwise suitable for a variety of uses well known in the art and described further below. For instance, SEQ ID NO:X is useful for designing nucleic acid hybridization probes that will detect nucleic acid sequences contained in SEQ ID NO:X or the cDNA contained in the deposited clone. These probes will also hybridize to nucleic acid molecules in biological samples, thereby enabling a variety of forensic and diagnostic methods of the invention. Similarly, polypeptides identified from SEQ ID NO:Y may be used to generate antibodies which bind specifically to the secreted proteins encoded by the cDNA clones identified in Table 1.

Nevertheless, DNA sequences generated by sequencing reactions can contain sequencing errors. The errors exist as misidentified nucleotides, or as insertions or deletions of nucleotides in the generated DNA sequence. The erroneously inserted or deleted nucleotides cause frame shifts in the reading frames of the predicted amino acid sequence. In these cases, the predicted amino acid sequence diverges from the actual amino acid sequence, even though the generated DNA sequence may be greater than 99.9% identical to the actual DNA sequence (for example, one base insertion or deletion in an open reading frame of over 1000 bases).

Accordingly, for those applications requiring precision in the nucleotide sequence or the amino acid sequence, the present invention provides not only the generated nucleotide sequence identified as SEQ ID NO:X and the predicted translated amino acid sequence identified as SEQ ID NO:Y, but also a sample of plasmid DNA containing a human cDNA of the invention deposited with the ATCC, as set forth in Table 1. The nucleotide sequence of each deposited clone can readily be determined by sequencing the deposited clone in accordance with known methods. The predicted amino acid sequence can then be verified from such deposits. Moreover, the amino acid sequence of the protein encoded by a particular clone can also be directly determined by peptide sequencing or by expressing the protein in a suitable host cell containing the deposited human cDNA, collecting the protein, and determining its sequence.

The present invention also relates to the genes corresponding to SEQ ID NO:X, SEQ ID NO:Y, or the deposited clone. The corresponding gene can be isolated in accordance with known methods using the sequence information disclosed herein. Such methods include preparing probes or primers from the disclosed sequence and identifying or amplifying the corresponding gene from appropriate sources of genomic material.

Also provided in the present invention are species homologs. Species homologs may be isolated and identified by making suitable probes or primers from the sequences provided herein and screening a suitable nucleic acid source for the desired homologue.

The polypeptides of the invention can be prepared in any suitable manner. Such polypeptides include isolated naturally occurring polypeptides, recombinantly produced polypeptides, synthetically produced polypeptides, or polypeptides produced by a combination of these methods. Means for preparing such polypeptides are well understood in the art.

The polypeptides may be in the form of the secreted protein, including the mature form, or may be a part of a larger protein, such as a fusion protein (see below). It is often advantageous to include an additional amino acid sequence which contains secretory or leader sequences, pro-sequences, sequences which aid in purification, such as multiple histidine residues, or an additional sequence for stability during recombinant production.

The polypeptides of the present invention are preferably provided in an isolated form, and preferably are substantially purified. A recombinantly produced version of a polypeptide, including the secreted polypeptide, can be substantially purified by the one-step method described in Smith and Johnson, Gene 67:31-40 (1988). Polypeptides of the invention also can be purified from natural or recombinant sources using antibodies of the invention raised against the secreted protein in methods which are well known in the art.

Signal Sequences

Methods for predicting whether a protein has a signal sequence, as well as the cleavage point for that sequence, are available. For instance, the method of McGeoch, Virus Res. 3:271-286 (1985), uses the information from a short N-terminal charged region and a subsequent uncharged region of the complete (uncleaved) protein. The method of von Heinje, Nucleic Acids Res. 14:4683-469O (1986) uses the information from the residues surrounding the cleavage site, typically residues −13 to +2, where +1 indicates the amino terminus of the secreted protein. The accuracy of predicting the cleavage points of known mammalian secretory proteins for each of these methods is in the range of 75-80%. (von Heinje, supra.) However, the two methods do not always produce the same predicted cleavage point(s) for a given protein.

In the present case, the deduced amino acid sequence of the secreted polypeptide was analyzed by a computer program called SignalP (Henrik Nielsen et al., Protein Engineering 10:1-6 (1997)), which predicts the cellular location of a protein based on the amino acid sequence. As part of this computational prediction of localization, the methods of McGeoch and von Heinje are incorporated. The analysis of the amino acid sequences of the secreted proteins described herein by this program provided the results shown in Table 1.

As one of ordinary skill would appreciate, however, cleavage sites sometimes vary from organism to organism and cannot be predicted with absolute certainty. Accordingly, the present invention provides secreted polypeptides having a sequence shown in SEQ ID NO:Y which have an N-terminus beginning within 5 residues (i.e., + or −5 residues) of the predicted cleavage point. Similarly, it is also recognized that in some cases, cleavage of the signal sequence from a secreted protein is not entirely uniform, resulting in more than one secreted species. These polypeptides, and the polynucleotides encoding such polypeptides, are contemplated by the present invention.

Moreover, the signal sequence identified by the above analysis may not necessarily predict the naturally occurring signal sequence. For example, the naturally occurring signal sequence may be further upstream from the predicted signal sequence. However, it is likely that the predicted signal sequence will be capable of directing the secreted protein to the ER. These polypeptides, and the polynucleotides encoding such polypeptides, are contemplated by the present invention.

Polynucleotide and Polypeptide Variants

“Variant” refers to a polynucleotide or polypeptide differing from the polynucleotide or polypeptide of the present invention, but retaining essential properties thereof. Generally, variants are overall closely similar, and, in many regions, identical to the polynucleotide or polypeptide of the present invention.

By a polynucleotide having a nucleotide sequence at least, for example, 95% “identical” to a reference nucleotide sequence of the present invention, it is intended that the nucleotide sequence of the polynucleotide is identical to the reference sequence except that the polynucleotide sequence may include up to five point mutations per each 100 nucleotides of the reference nucleotide sequence encoding the polypeptide. In other words, to obtain a polynucleotide having a nucleotide sequence at least 95% identical to a reference nucleotide sequence, up to 5% of the nucleotides in the reference sequence, may be deleted or substituted with another nucleotide, or a number of nucleotides up to 5% of the total nucleotides in the reference sequence may be inserted into the reference sequence. The query sequence may be an entire sequence shown in Table 1, the ORF (open reading frame), or any fragement specified as described herein.

As a practical matter, whether any particular nucleic acid molecule or polypeptide is at least 90%, 95%, 96%, 97%, 98% or 99% identical to a nucleotide sequence of the presence invention can be determined conventionally using known computer programs. A preferred method for determing the best overall match between a query sequence (a sequence of the present invention) and a subject sequence, also referred to as a global sequence alignment, can be determined using the FASTDB computer program based on the algorithm of Brutlag et al. (Comp. App. Biosci. (1990) 6:237-245). In a sequence alignment the query and subject sequences are both DNA sequences. An RNA sequence can be compared by converting U's to T's. The result of said global sequence alignment is in percent identity. Preferred parameters used in a FASTDB alignment of DNA sequences to calculate percent identiy are: Matrix=Unitary, k-tuple=4, Mismatch Penalty=1, Joining Penalty=30, Randomization Group Length=0, Cutoff Score=1, Gap Penalty=5, Gap Size Penalty 0.05, Window Size=500 or the lenght of the subject nucleotide sequence, whichever is shorter.

If the subject sequence is shorter than the query sequence because of 5′ or 3′ deletions, not because of internal deletions, a manual correction must be made to the results. This is becuase the FASTDB program does not account for 5′ and 3′ truncations of the subject sequence when calculating percent identity. For subject sequences truncated at the 5′ or 3′ ends, relative to the the query sequence, the percent identity is corrected by calculating the number of bases of the query sequence that are 5′ and 3′ of the subject sequence, which are not matched/aligned, as a percent of the total bases of the query sequence. Whether a nucleotide is matched/aligned is determined by results of the FASTDB sequence alignment. This percentage is then subtracted from the percent identity, calculated by the above FASTDB program using the specified parameters, to arrive at a final percent identity score. This corrected score is what is used for the purposes of the present invention. Only bases outside the 5′ and 3′ bases of the subject sequence, as displayed by the FASTDB alignment, which are not matched/aligned with the query sequence, are calculated for the purposes of manually adjusting the percent identity score.

For example, a 90 base subject sequence is aligned to a 100 base query sequence to determine percent identity. The deletions occur at the 5′ end of the subject sequence and therefore, the FASTDB alignment does not show a matched/alignement of the first 10 bases at 5′ end. The 10 unpaired bases represent 10% of the sequence (number of bases at the 5′ and 3′ ends not matched/total number of bases in the query sequence) so 10% is subtracted from the percent identity score calculated by the FASTDB program. If the remaining 90 bases were perfectly matched the final percent identity would be 90%. In another example, a 90 base subject sequence is compared with a 100 base query sequence. This time the deletions are internal deletions so that there are no bases on the 5′ or 3′ of the subject sequence which are not matched/aligned with the query. In this case the percent identity calculated by FASTDB is not manually corrected. Once again, only bases 5′ and 3′ of the subject sequence which are not matched/aligned with the query sequnce are manually corrected for. No other manual corrections are to made for the purposes of the present invention.

By a polypeptide having an amino acid sequence at least, for example, 95% “identical” to a query amino acid sequence of the present invention, it is intended that the amino acid sequence of the subject polypeptide is identical to the query sequence except that the subject polypeptide sequence may include up to five amino acid alterations per each 100 amino acids of the query amino acid sequence. In other words, to obtain a polypeptide having an amino acid sequence at least 95% identical to a query amino acid sequence, up to 5% of the amino acid residues in the subject sequence may be inserted, deleted, (indels) or substituted with another amino acid. These alterations of the reference sequence may occur at the amino or carboxy terminal positions of the reference amino acid sequence or anywhere between those terminal positions, interspersed either individually among residues in the reference sequence or in one or more contiguous groups within the reference sequence.

As a practical matter, whether any particular polypeptide is at least 90%, 95%, 96%, 97%, 98% or 99% identical to, for instance, the amino acid sequences shown in Table 1 or to the amino acid sequence encoded by deposited DNA clone can be determined conventionally using known computer programs. A preferred method for determing the best overall match between a query sequence (a sequence of the present invention) and a subject sequence, also referred to as a global sequence alignment, can be determined using the FASTDB computer program based on the algorithm of Brutlag et al. (Comp. App. Biosci. (1990) 6:237-245). In a sequence alignment the query and subject sequences are either both nucleotide sequences or both amino acid sequences. The result of said global sequence alignment is in percent identity. Preferred parameters used in a FASTDB amino acid alignment are: Matrix=PAM 0, k-tuple=2, Mismatch Penalty=1, Joining Penalty=20, Randomization Group Length=0, Cutoff Score=1, Window Size=sequence length, Gap Penalty=5, Gap Size Penalty=0.05, Window Size=500 or the length of the subject amino acid sequence, whichever is shorter.

If the subject sequence is shorter than the query sequence due to N- or C-terminal deletions, not because of internal deletions, a manual correction must be made to the results. This is becuase the FASTDB program does not account for N- and C-terminal truncations of the subject sequence when calculating global percent identity. For subject sequences truncated at the N- and C-termini, relative to the the query sequence, the percent identity is corrected by calculating the number of residues of the query sequence that are N- and C-terminal of the subject sequence, which are not matched/aligned with a corresponding subject residue, as a percent of the total bases of the query sequence. Whether a residue is matched/aligned is determined by results of the FASTDB sequence alignment. This percentage is then subtracted from the percent identity, calculated by the above FASTDB program using the specified parameters, to arrive at a final percent identity score. This final percent identity score is what is used for the purposes of the present invention. Only residues to the N- and C-termini of the subject sequence, which are not matched/aligned with the query sequence, are considered for the purposes of manually adjusting the percent identity score. That is, only query residue positions outside the farthest N- and C-terminal residues of the subject sequence.

For example, a 90 amino acid residue subject sequence is aligned with a 100 residue query sequence to determine percent identity. The deletion occurs at the N-terminus of the subject sequence and therefore, the FASTDB alignment does not show a matching/alignment of the first 10 residues at the N-terminus. The 10 unpaired residues represent 10% of the sequence (number of residues at the N- and C-termini not matched/total number of residues in the query sequence) so 10% is subtracted from the percent identity score calculated by the FASTDB program. If the remaining 90 residues were perfectly matched the final percent identity would be 90%. In another example, a 90 residue subject sequence is compared with a 100 residue query sequence. This time the deletions are internal deletions so there are no residues at the N- or C-termini of the subject sequence which are not matched/aligned with the query. In this case the percent identity calculated by FASTDB is not manually corrected. Once again, only residue positions outside the N- and C-terminal ends of the subject sequence, as displayed in the FASTDB alignment, which are not matched/aligned with the query sequnce are manually corrected for. No other manual corrections are to made for the purposes of the present invention.

The variants may contain alterations in the coding regions, non-coding regions, or both. Especially preferred are polynucleotide variants containing alterations which produce silent substitutions, additions, or deletions, but do not alter the properties or activities of the encoded polypeptide. Nucleotide variants produced by silent substitutions due to the degeneracy of the genetic code are preferred. Moreover, variants in which 5-10, 1-5, or 1-2 amino acids are substituted, deleted, or added in any combination are also preferred. Polynucleotide variants can be produced for a variety of reasons, e.g., to optimize codon expression for a particular host (change codons in the human mRNA to those preferred by a bacterial host such as E. coli).

Naturally occurring variants are called “allelic variants,” and refer to one of several alternate forms of a gene occupying a given locus on a chromosome of an organism. (Genes II, Lewin, B., ed., John Wiley & Sons, New York (1985).) These allelic variants can vary at either the polynucleotide and/or polypeptide level. Alternatively, non-naturally occurring variants may be produced by mutagenesis techniques or by direct synthesis.

Using known methods of protein engineering and recombinant DNA technology, variants may be generated to improve or alter the characteristics of the polypeptides of the present invention. For instance, one or more amino acids can be deleted from the N-terminus or C-terminus of the secreted protein without substantial loss of biological function. The authors of Ron et al., J. Biol. Chem. 268: 2984-2988 (1993), reported variant KGF proteins having heparin binding activity even after deleting 3, 8, or 27 amino-terminal amino acid residues. Similarly, Interferon gamma exhibited up to ten times higher activity after deleting 8-10 amino acid residues from the carboxy terminus of this protein. (Dobeli et al., J. Biotechnology 7:199-216 (1988).)

Moreover, ample evidence demonstrates that variants often retain a biological activity similar to that of the naturally occurring protein. For example, Gayle and coworkers (J. Biol. Chem 268:22105-22111 (1993)) conducted extensive mutational analysis of human cytokine IL-1a. They used random mutagenesis to generate over 3,500 individual IL-1a mutants that averaged 2.5 amino acid changes per variant over the entire length of the molecule. Multiple mutations were examined at every possible amino acid position. The investigators found that “[m]ost of the molecule could be altered with little effect on either [binding or biological activity].” (See, Abstract.) In fact, only 23 unique amino acid sequences, out of more than 3,500 nucleotide sequences examined, produced a protein that significantly differed in activity from wild-type.

Furthermore, even if deleting one or more amino acids from the N-terminus or C-terminus of a polypeptide results in modification or loss of one or more biological functions, other biological activities may still be retained. For example, the ability of a deletion variant to induce and/or to bind antibodies which recognize the secreted form will likely be retained when less than the majority of the residues of the secreted form are removed from the N-terminus or C-terminus. Whether a particular polypeptide lacking N- or C-terminal residues of a protein retains such immunogenic activities can readily be determined by routine methods described herein and otherwise known in the art.

Thus, the invention further includes polypeptide variants which show substantial biological activity. Such variants include deletions, insertions, inversions, repeats, and substitutions selected according to general rules known in the art so as have little effect on activity. For example, guidance concerning how to make phenotypically silent amino acid substitutions is provided in Bowie, J. U. et al., Science 247:1306-1310 (1990), wherein the authors indicate that there are two main strategies for studying the tolerance of an amino acid sequence to change.

The first strategy exploits the tolerance of amino acid substitutions by natural selection during the process of evolution. By comparing amino acid sequences in different species, conserved amino acids can be identified. These conserved amino acids are likely important for protein function. In contrast, the amino acid positions where substitutions have been tolerated by natural selection indicates that these positions are not critical for protein function. Thus, positions tolerating amino acid substitution could be modified while still maintaining biological activity of the protein.

The second strategy uses genetic engineering to introduce amino acid changes at specific positions of a cloned gene to identify regions critical for protein function. For example, site directed mutagenesis or alanine-scanning mutagenesis (introduction of single alanine mutations at every residue in the molecule) can be used. (Cunningham and Wells, Science 244:1081-1085 (1989).) The resulting mutant molecules can then be tested for biological activity.

As the authors state, these two strategies have revealed that proteins are surprisingly tolerant of amino acid substitutions. The authors further indicate which amino acid changes are likely to be permissive at certain amino acid positions in the protein. For example, most buried (within the tertiary structure of the protein) amino acid residues require nonpolar side chains, whereas few features of surface side chains are generally conserved. Moreover, tolerated conservative amino acid substitutions involve replacement of the aliphatic or hydrophobic amino acids Ala, Val, Leu and Ile; replacement of the hydroxyl residues Ser and Thr; replacement of the acidic residues Asp and Glu; replacement of the amide residues Asn and Gln, replacement of the basic residues Lys, Arg, and His; replacement of the aromatic residues Phe, Tyr, and Trp, and replacement of the small-sized amino acids Ala, Ser, Thr, Met, and Gly.

Besides conservative amino acid substitution, variants of the present invention include (i) substitutions with one or more of the non-conserved amino acid residues, where the substituted amino acid residues may or may not be one encoded by the genetic code, or (ii) substitution with one or more of amino acid residues having a substituent group, or (iii) fusion of the mature polypeptide with another compound, such as a compound to increase the stability and/or solubility of the polypeptide (for example, polyethylene glycol), or (iv) fusion of the polypeptide with additional amino acids, such as an IgG Fc fusion region peptide, or leader or secretory sequence, or a sequence facilitating purification. Such variant polypeptides are deemed to be within the scope of those skilled in the art from the teachings herein.

For example, polypeptide variants containing amino acid substitutions of charged amino acids with other charged or neutral amino acids may produce proteins with improved characteristics, such as less aggregation. Aggregation of pharmaceutical formulations both reduces activity and increases clearance due to the aggregate's immunogenic activity. (Pinckard et al., Clin. Exp. Immunol. 2:331-340 (1967); Robbins et al., Diabetes 36: 838-845 (1987); Cleland et al., Crit. Rev. Therapeutic Drug Carrier Systems 10:307-377 (1993).)

Polynucleotide and Polypeptide Fragments

In the present invention, a “polynucleotide fragment” refers to a short polynucleotide having a nucleic acid sequence contained in the deposited clone or shown in SEQ ID NO:X. The short nucleotide fragments are preferably at least about 15 nt, and more preferably at least about 20 nt, still more preferably at least about 30 nt, and even more preferably, at least about 40 nt in length. A fragment “at least 20 nt in length,” for example, is intended to include 20 or more contiguous bases from the cDNA sequence contained in the deposited clone or the nucleotide sequence shown in SEQ ID NO:X. These nucleotide fragments are useful as diagnostic probes and primers as discussed herein. Of course, larger fragments (e.g., 50, 150, 500, 600, 2000 nucleotides) are preferred.

Moreover, representative examples of polynucleotide fragments of the invention, include, for example, fragments having a sequence from about nucleotide number 1-50, 51-100, 101-150, 151-200, 201-250, 251-300, 301-350, 351-400, 401-450, 451-500, 501-550, 551-600, 651-700, 701-750, 751-800, 800-850, 851-900, 901-950, 951-1000, 1001-1050, 1051-1100, 1101-1150, 1151-1200, 1201-1250, 1251-1300, 1301-1350, 1351-1400, 1401-1450, 1451-1500, 1501-1550, 1551-1600, 1601-1650, 1651-1700, 1701-1750, 1751-1800, 1801-1850, 1851-1900, 1901-1950, 1951-2000, or 2001 to the end of SEQ ID NO:X or the cDNA contained in the deposited clone. In this context “about” includes the particularly recited ranges, larger or smaller by several (5, 4, 3, 2, or 1) nucleotides, at either terminus or at both termini. Preferably, these fragments encode a polypeptide which has biological activity. More preferably, these polynucleotides can be used as probes or primers as discussed herein.

In the present invention, a “polypeptide fragment” refers to a short amino acid sequence contained in SEQ ID NO:Y or encoded by the cDNA contained in the deposited clone. Protein fragments may be “free-standing,” or comprised within a larger polypeptide of which the fragment forms a part or region, most preferably as a single continuous region. Representative examples of polypeptide fragments of the invention, include, for example, fragments from about amino acid number 1-20, 21-40, 41-60, 61-80, 81-100, 102-120, 121-140, 141-160, or 161 to the end of the coding region. Moreover, polypeptide fragments can be about 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, or 150 amino acids in length. In this context “about” includes the particularly recited ranges, larger or smaller by several (5, 4, 3, 2, or 1) amino acids, at either extreme or at both extremes.

Preferred polypeptide fragments include the secreted protein as well as the mature form. Further preferred polypeptide fragments include the secreted protein or the mature form having a continuous series of deleted residues from the amino or the carboxy terminus, or both. For example, any number of amino acids, ranging from 1-60, can be deleted from the amino terminus of either the secreted polypeptide or the mature form. Similarly, any number of amino acids, ranging from 1-30, can be deleted from the carboxy terminus of the secreted protein or mature form. Furthermore, any combination of the above amino and carboxy terminus deletions are preferred. Similarly, polynucleotide fragments encoding these polypeptide fragments are also preferred.

Also preferred are polypeptide and polynucleotide fragments characterized by structural or functional domains, such as fragments that comprise alpha-helix and alpha-helix forming regions, beta-sheet and beta-sheet-forming regions, turn and turn-forming regions, coil and coil-forming regions, hydrophilic regions, hydrophobic regions, alpha amphipathic regions, beta amphipathic regions, flexible regions, surface-forming regions, substrate binding region, and high antigenic index regions. Polypeptide fragments of SEQ ID NO:Y falling within conserved domains are specifically contemplated by the present invention. Moreover, polynucleotide fragments encoding these domains are also contemplated.

Other preferred fragments are biologically active fragments. Biologically active fragments are those exhibiting activity similar, but not necessarily identical, to an activity of the polypeptide of the present invention. The biological activity of the fragments may include an improved desired activity, or a decreased undesirable activity.

Epitopes & Antibodies

In the present invention, “epitopes” refer to polypeptide fragments having antigenic or immunogenic activity in an animal, especially in a human. A preferred embodiment of the present invention relates to a polypeptide fragment comprising an epitope, as well as the polynucleotide encoding this fragment. A region of a protein molecule to which an antibody can bind is defined as an “antigenic epitope.” In contrast, an “immunogenic epitope” is defined as a part of a protein that elicits an antibody response. (See, for instance, Geysen et al., Proc. Natl. Acad. Sci. USA 81:3998-4002 (1983).)

Fragments which function as epitopes may be produced by any conventional means. (See, e.g., Houghten, R. A., Proc. Natl. Acad. Sci. USA 82:5131-5135 (1985) further described in U.S. Pat. No. 4,631,211.)

In the present invention, antigenic epitopes preferably contain a sequence of at least seven, more preferably at least nine, and most preferably between about 15 to about 30 amino acids. Antigenic epitopes are useful to raise antibodies, including monoclonal antibodies, that specifically bind the epitope. (See, for instance, Wilson et al., Cell 37:767-778 (1984); Sutcliffe, J. G. et al., Science 219:660-666 (1983).)

Similarly, immunogenic epitopes can be used to induce antibodies according to methods well known in the art. (See, for instance, Sutcliffe et al., supra; Wilson et al., supra; Chow, M. et al., Proc. Natl. Acad. Sci. USA 82:910-914; and Bittle, F. J. et al., J. Gen. Virol. 66:2347-2354 (1985).) A preferred immunogenic epitope includes the secreted protein. The immunogenic epitopes may be presented together with a carrier protein, such as an albumin, to an animal system (such as rabbit or mouse) or, if it is long enough (at least about 25 amino acids), without a carrier. However, immunogenic epitopes comprising as few as 8 to 10 amino acids have been shown to be sufficient to raise antibodies capable of binding to, at the very least, linear epitopes in a denatured polypeptide (e.g., in Western blotting.) As used herein, the term “antibody” (Ab) or “monoclonal antibody” (Mab) is meant to include intact molecules as well as antibody fragments (such as, for example, Fab and F(ab′)2 fragments) which are capable of specifically binding to protein. Fab and F(ab′)2 fragments lack the Fc fragment of intact antibody, clear more rapidly from the circulation, and may have less non-specific tissue binding than an intact antibody. (Wahl et al., 3. Nucl. Med. 24:316-325 (1983).) Thus, these fragments are preferred, as well as the products of a FAB or other immunoglobulin expression library. Moreover, antibodies of the present invention include chimeric, single chain, and humanized antibodies.

Fusion Proteins

Any polypeptide of the present invention can be used to generate fusion proteins. For example, the polypeptide of the present invention, when fused to a second protein, can be used as an antigenic tag. Antibodies raised against the polypeptide of the present invention can be used to indirectly detect the second protein by binding to the polypeptide. Moreover, because secreted proteins target cellular locations based on trafficking signals, the polypeptides of the present invention can be used as targeting molecules once fused to other proteins.

Examples of domains that can be fused to polypeptides of the present invention include not only heterologous signal sequences, but also other heterologous functional regions. The fusion does not necessarily need to be direct, but may occur through linker sequences.

Moreover, fusion proteins may also be engineered to improve characteristics of the polypeptide of the present invention. For instance, a region of additional amino acids, particularly charged amino acids, may be added to the N-terminus of the polypeptide to improve stability and persistence during purification from the host cell or subsequent handling and storage. Also, peptide moieties may be added to the polypeptide to facilitate purification. Such regions may be removed prior to final preparation of the polypeptide. The addition of peptide moieties to facilitate handling of polypeptides are familiar and routine techniques in the art.

Moreover, polypeptides of the present invention, including fragments, and specifically epitopes, can be combined with parts of the constant domain of immunoglobulins (IgG), resulting in chimeric polypeptides. These fusion proteins facilitate purification and show an increased half-life in vivo. One reported example describes chimeric proteins consisting of the first two domains of the human CD4-polypeptide and various domains of the constant regions of the heavy or light chains of mammalian immunoglobulins. (EP A 394,827; Traunecker et al., Nature 331:84-86 (1988).) Fusion proteins having disulfide-linked dimeric structures (due to the IgG) can also be more efficient in binding and neutralizing other molecules, than the monomeric secreted protein or protein fragment alone. (Fountoulakis et al., J. Biochem. 270:3958-3964 (1995).)

Similarly, EP-A-O 464 533 (Canadian counterpart 2045869) discloses fusion proteins comprising various portions of constant region of immunoglobulin molecules together with another human protein or part thereof. In many cases, the Fc part in a fusion protein is beneficial in therapy and diagnosis, and thus can result in, for example, improved pharmacokinetic properties. (EP-A 0232 262.) Alternatively, deleting the Fc part after the fusion protein has been expressed, detected, and purified, would be desired. For example, the Fc portion may hinder therapy and diagnosis if the fusion protein is used as an antigen for immunizations. In drug discovery, for example, human proteins, such as hIL-5, have been fused with Fc portions for the purpose of high-throughput screening assays to identify antagonists of hIL-5. (See, D. Bennett et al., J. Molecular Recognition 8:52-58 (1995); K. Johanson et al., J. Biol. Chem. 270:9459-9471 (1995).)

Moreover, the polypeptides of the present invention can be fused to marker sequences, such as a peptide which facilitates purification of the fused polypeptide. In preferred embodiments, the marker amino acid sequence is a hexa-histidine peptide, such as the tag provided in a pQE vector (QIAGEN, Inc., 9259 Eton Avenue, Chatsworth, Calif., 91311), among others, many of which are commercially available. As described in Gentz et al., Proc. Natl. Acad. Sci. USA 86:821-824 (1989), for instance, hexa-histidine provides for convenient purification of the fusion protein. Another peptide tag useful for purification, the “HA” tag, corresponds to an epitope derived from the influenza hemagglutinin protein. (Wilson et al., Cell 37:767 (1984).)

Thus, any of these above fusions can be engineered using the polynucleotides or the polypeptides of the present invention.

Vectors. Host Cells. and Protein Production

The present invention also relates to vectors containing the polynucleotide of the present invention, host cells, and the production of polypeptides by recombinant techniques. The vector may be, for example, a phage, plasmid, viral, or retroviral vector. Retroviral vectors may be replication competent or replication defective. In the latter case, viral propagation generally will occur only in complementing host cells.

The polynucleotides may be joined to a vector containing a selectable marker for propagation in a-host. Generally, a plasmid vector is introduced in a precipitate, such as a calcium phosphate precipitate, or in a complex with a charged lipid. If the vector is a virus, it may be packaged in vitro using an appropriate packaging cell line and then transduced into host cells.

The polynucleotide insert should be operatively linked to an appropriate promoter, such as the phage lambda PL promoter, the E. coli lac, trp, phoA and tac promoters, the SV40 early and late promoters and promoters of retroviral LTRs, to name a few. Other suitable promoters will be known to the skilled artisan. The expression constructs will further contain sites for transcription initiation, termination, and, in the transcribed region, a ribosome binding site for translation. The coding portion of the transcripts expressed by the constructs will preferably include a translation initiating codon at the beginning and a termination codon (UAA, UGA or UAG) appropriately positioned at the end of the polypeptide to be translated.

As indicated, the expression vectors will preferably include at least one selectable marker. Such markers include dihydrofolate reductase, G418 or neomycin resistance for eukaryotic cell culture and tetracycline, kanamycin or ampicillin resistance genes for culturing in E. coli and other bacteria. Representative examples of appropriate hosts include, but are not limited to, bacterial cells, such as E. coli, Streptomyces and Salmonella typhimurium cells; fungal cells, such as yeast cells; insect cells such as Drosophila S2 and Spodoptera Sf9 cells; animal cells such as CHO, COS, 293, and Bowes melanoma cells; and plant cells. Appropriate culture mediums and conditions for the above-described host cells are known in the art.

Among vectors preferred for use in bacteria include pQE70, pQE60 and pQE-9, available from QIAGEN, Inc.; pBluescript vectors, Phagescript vectors, pNH8A, pNH16a, pNH18A, pNH46A, available from Stratagene Cloning, Systems, Inc.; and ptrc99a, pKK223-3, pKK233-3, pDR540, pRIT5 available from Pharmacia Biotech, Inc. Among preferred eukaryotic vectors are pWLNEO, pSV2CAT, pOG44, pXT1 and pSG available from Stratagene; and pSVK3, pBPV, pMSG and pSVL available from Pharmacia. Other suitable vectors will be readily apparent to the skilled artisan.

Introduction of the construct into the host cell can be effected by calcium phosphate transfection, DEAE-dextran mediated transfection, cationic lipid-mediated transfection, electroporation, transduction, infection, or other methods. Such methods are described in many standard laboratory manuals, such as Davis et al., Basic Methods In Molecular Biology (1986). It is specifically contemplated that the polypeptides of the present invention may in fact be expressed by a host cell lacking a recombinant vector.

A polypeptide of this invention can be recovered and purified from recombinant cell cultures by well-known methods including ammonium sulfate or ethanol precipitation, acid extraction, anion or cation exchange chromatography, phosphocellulose chromatography, hydrophobic interaction chromatography, affinity chromatography, hydroxylapatite chromatography and lectin chromatography. Most preferably, high performance liquid chromatography (“HPLC”) is employed for purification.

Polypeptides of the present invention, and preferably the secreted form, can also be recovered from: products purified from natural sources, including bodily fluids, tissues and cells, whether directly isolated or cultured; products of chemical synthetic procedures; and products produced by recombinant techniques from a prokaryotic or eukaryotic host, including, for example, bacterial, yeast, higher plant, insect, and mammalian cells. Depending upon the host employed in a recombinant production procedure, the polypeptides of the present invention may be glycosylated or may be non-glycosylated. In addition, polypeptides of the invention may also include an initial modified methionine residue, in some cases as a result of host-mediated processes. Thus, it is well known in the art that the N-terminal methionine encoded by the translation initiation codon generally is removed with high efficiency from any protein after translation in all eukaryotic cells. While the N-terminal methionine on most proteins also is efficiently removed in most prokaryotes, for some proteins, this prokaryotic removal process is inefficient, depending on the nature of the amino acid to which the N-terminal methionine is covalently linked.

Uses of the Polynucleotides

Each of the polynucleotides identified herein can be used in numerous ways as reagents. The following description should be considered exemplary and utilizes known techniques.

The polynucleotides of the present invention are useful for chromosome identification. There exists an ongoing need to identify new chromosome markers, since few chromosome marking reagents, based on actual sequence data (repeat polymorphisms), are presently available. Each polynucleotide of the present invention can be used as a chromosome marker.

Briefly, sequences can be mapped to chromosomes by preparing PCR primers (preferably 15-25 bp) from the sequences shown in SEQ D NO:X. Primers can be selected using computer analysis so that primers do not span more than one predicted exon in the genomic DNA. These primers are then used for PCR screening of somatic cell hybrids containing individual human chromosomes. Only those hybrids containing the human gene corresponding to the SEQ ID NO:X will yield an amplified fragment.

Similarly, somatic hybrids provide a rapid method of PCR mapping the polynucleotides to particular chromosomes. Three or more clones can be assigned per day using a single thermal cycler. Moreover, sublocalization of the polynucleotides can be achieved with panels of specific chromosome fragments. Other gene mapping strategies that can be used include in situ hybridization, prescreening with labeled flow-sorted chromosomes, and preselection by hybridization to construct chromosome specific-cDNA libraries.

Precise chromosomal location of the polynucleotides can also be achieved using fluorescence in situ hybridization (FISH) of a metaphase chromosomal spread. This technique uses polynucleotides as short as 500 or 600 bases; however, polynucleotides 2,000-4,000 bp are preferred. For a review of this technique, see Verna et al., “Human Chromosomes: a Manual of Basic Techniques,” Pergamon Press, New York (1988).

For chromosome mapping, the polynucleotides can be used individually (to mark a single chromosome or a single site on that chromosome) or in panels (for marking multiple sites and/or multiple chromosomes). Preferred polynucleotides correspond to the noncoding regions of the cDNAs because the coding sequences are more likely conserved within gene families, thus increasing the chance of cross hybridization during chromosomal mapping.

Once a polynucleotide has been mapped to a precise chromosomal location, the physical position of the polynucleotide can be used in linkaae analysis. Linkage analysis establishes coinheritance between a chromosomal location and presentation of a particular disease. (Disease mapping data are found, for example, in V. McKusick, Mendelian Inheritance in Man (available on line through Johns Hopkins University Welch Medical Library) Assuming 1 megabase mapping resolution and one gene per 20 kb, a cDNA precisely localized to a chromosomal region associated with the disease could be one of 50-500 potential causative genes.

Thus, once coinheritance is established, differences in the polynucleotide and the corresponding gene between affected and unaffected individuals can be examined. First, visible structural alterations in the chromosomes, such as deletions or translocations, are examined in chromosome spreads or by PCR. If no structural alterations exist, the presence of point mutations are ascertained. Mutations observed in some or all affected individuals, but not in normal individuals, indicates that the mutation may cause the disease. However, complete sequencing of the polypeptide and the corresponding gene from several normal individuals is required to distinguish the mutation from a polymorphism. If a new polymorphism is identified, this polymorphic polypeptide can be used for farther linkage analysis.

Furthermore, increased or decreased expression of the gene in affected individuals as compared to unaffected individuals can be assessed using polynucleotides of the present invention. Any of these alterations (altered expression, chromosomal rearrangement, or mutation) can be used as a diagnostic or prognostic marker.

In addition to the foregoing, a polynucleotide can be used to control gene expression through triple helix formation or antisense DNA or RNA. Both methods rely on binding of the polynucleotide to DNA or RNA. For these techniques, preferred polynucleotides are usually 20 to 40 bases in length and complementary to either the region of the gene involved in transcription (triple helix—see Lee et al., Nucl. Acids Res. 6:3073 (1979); Cooney et al., Science 241:456 (1988); and Dervan et al., Science 251:1360 (1991) ) or to the mRNA itself (antisense—Okano, J. Neurochem. 56:560 (1991); Oligodeoxy-nucleotides as Antisense Inhibitors of Gene Expression, CRC Press, Boca Raton, Fla. (1988).) Triple helix formation optimally results in a shut-off of RNA transcription from DNA, while antisense RNA hybridization blocks translation of an mRNA molecule into polypeptide. Both techniques are effective in model systems, and the information disclosed herein can be used to design antisense or triple helix polynucleotides in an effort to treat disease.

Polynucleotides of the present invention are also useful in gene therapy. One goal of gene therapy is to insert a normal gene into an organism having a defective gene, in an effort to correct the genetic defect. The polynucleotides disclosed in the present invention offer a means of targeting such genetic defects in a highly accurate manner. Another goal is to insert a new gene that was not present in the host genome, thereby producing a new trait in the host cell.

The polynucleotides are also useful for identifying individuals from minute biological samples. The United States military, for example, is considering the use of restriction fragment length polymorphism (RFLP) for identification of its personnel. In this technique, an individual's genomic DNA is digested with one or more restriction enzymes, and probed on a Southern blot to yield unique bands for identifying personnel. This method does not suffer from the current limitations of “Dog Tags” which can be lost, switched, or stolen, making positive identification difficult. The polynucleotides of the present invention can be used as additional DNA markers for RFLP.

The polynucleotides of the present invention can also be used as an alternative to RFLP, by determining the actual base-by-base DNA sequence of selected portions of an individual's genome. These sequences can be used to prepare PCR primers for amplifying and isolating such selected DNA, which can then be sequenced. Using this technique, individuals can be identified because each individual will have a unique set of DNA sequences. Once an unique ID database is established for an individual, positive identification of that individual, living or dead, can be made from extremely small tissue samples.

Forensic biology also benefits from using DNA-based identification techniques as disclosed herein. DNA sequences taken from very small biological samples such as tissues, e.g., hair or skin, or body fluids, e.g., blood, saliva, semen, etc., can be amplified using PCR. In one prior art technique, gene sequences amplified from polymorphic loci, such as DQa class II HLA gene, are used in forensic biology to identify individuals. (Erlich, H., PCR Technology, Freeman and Co. (1992).) Once these specific polymorphic loci are amplified, they are digested with one or more restriction enzymes, yielding an identifying set of bands on a Southern blot probed with DNA corresponding to the DQa class II HLA gene. Similarly, polynucleotides of the present invention can be used as polymorphic markers for forensic purposes.

There is also a need for reagents capable of identifying the source of a particular tissue. Such need arises, for example, in forensics when presented with tissue of unknown origin. Appropriate reagents can comprise, for example, DNA probes or primers specific to particular tissue prepared from the sequences of the present invention. Panels of such reagents can identify tissue by species and/or by organ type. In a similar fashion, these reagents can be used to screen tissue cultures for contamination.

In the very least, the polynucleotides of the present invention can be used as molecular weight markers on Southern gels, as diagnostic probes for the presence of a specific mRNA in a particular cell type, as a probe to “subtract-out” known sequences in the process of discovering novel polynucleotides, for selecting and making oligomers for attachment to a “gene chip” or other support, to raise anti-DNA antibodies using DNA immunization techniques, and as an antigen to elicit an immune response.

Uses of the Polypeptides

Each of the polypeptides identified herein can be used in numerous ways. The following description should be considered exemplary and utilizes known techniques.

A polypeptide of the present invention can be used to assay protein levels in a biological sample using antibody-based techniques. For example, protein expression in tissues can be studied with classical immunohistological methods. (Jalkanen, M., et al., J. Cell. Biol. 101:976-985 (1985); Jalkanen, M., et al., J. Cell . Biol. 105:3087-3096 (1987).) Other antibody-based methods useful for detecting protein gene expression include immunoassays, such as the enzyme linked immunosorbent assay (ELISA) and the radioimmunoassay (RIA). Suitable antibody assay labels are known in the art and include enzyme labels, such as, glucose oxidase, and radioisotopes, such as iodine (125I, 121I), carbon (14C), sulfur (35S), tritium (3H), indium (112In), and technetium (99mTc), and fluorescent labels, such as fluorescein and rhodamine, and biotin.

In addition to assaying secreted protein levels in a biological sample, proteins can also be detected in vivo by imaging. Antibody labels or markers for in vivo imaging of protein include those detectable by X-radiography, NMR or ESR. For X-radiography, suitable labels include radioisotopes such as barium or cesium, which emit detectable radiation but are not overtly harmful to the subject. Suitable markers for NMR and ESR include those with a detectable characteristic spin, such as deuterium, which may be incorporated into the antibody by labeling of nutrients for the relevant hybridoma.

A protein-specific antibody or antibody fragment which has been labeled with an appropriate detectable imaging moiety, such as a radioisotope (for example, 131I, 112In, 99mTc), a radio-opaque substance, or a material detectable by nuclear magnetic resonance, is introduced (for example, parenterally, subcutaneously, or intraperitoneally) into the mammal. It will be understood in the art that the size of the subject and the imaging system used will determine the quantity of imaging moiety needed to produce diagnostic images. In the case of a radioisotope moiety, for a human subject, the quantity of radioactivity injected will normally range from about 5 to 20 millicuries of 99mTc. The labeled antibody or antibody fragment will then preferentially accumulate at the location of cells which contain the specific protein. In vivo tumor imaging is described in S. W. Burchiel et al., “Inmunopharmacokinetics of Radiolabeled Antibodies and Their Fragments.” (Chapter 13 in Tumor Imaging: The Radiochemical Detection of Cancer, S. W. Burchiel and B. A. Rhodes, eds., Masson Publishing Inc. (1982).)

Thus, the invention provides a diagnostic method of a disorder, which involves (a) assaying the expression of a polypeptide of the present invention in cells or body fluid of an individual; (b) comparing the level of gene expression with a standard gene expression level, whereby an increase or decrease in the assayed polypeptide gene expression level compared to the standard expression level is indicative of a disorder.

Moreover, polypeptides of the present invention can be used to treat disease. For example, patients can be administered a polypeptide of the present invention in an effort to replace absent or decreased levels of the polypeptide (e.g., insulin), to supplement absent or decreased levels of a different polypeptide (e.g., hemoglobin S for hemoglobin B), to inhibit the activity of a polypeptide (e.g., an oncogene), to activate the activity of a polypeptide (e.g., by binding to a receptor), to reduce the activity of a membrane bound receptor by competing with it for free ligand (e.g., soluble TNF receptors used in reducing inflammation), or to bring about a desired response (e.g., blood vessel growth).

Similarly, antibodies directed to a polypeptide of the present invention can also be used to treat disease. For example, administration of an antibody directed to a polypeptide of the present invention can bind and reduce overproduction of the polypeptide. Similarly, administration of an antibody can activate the polypeptide, such as by binding to a polypeptide bound to a membrane (receptor).

At the very least, the polypeptides of the present invention can be used as molecular weight markers on SDS-PAGE gels or on molecular sieve gel filtration columns using methods well known to those of skill in the art. Polypeptides can also be used to raise antibodies, which in turn are used to measure protein expression from a recombinant cell, as a way of assessing transformation of the host cell. Moreover, the polypeptides of the present invention can be used to test the following biological activities.

Biological Activities

The polynucleotides and polypeptides of the present invention can be used in assays to test for one or more biological activities. If these polynucleotides and polypeptides do exhibit activity in a particular assay, it is likely that these molecules may be involved in the diseases associated with the biological activity. Thus, the polynucleotides and polypeptides could be used to treat the associated disease.

Immune Activity

A polypeptide or polynucleotide of the present invention may be useful in treating deficiencies or disorders of the immune system, by activating or inhibiting the proliferation, differentiation, or mobilization (chemotaxis) of immune cells. Immune cells develop through a process called hematopoiesis, producing myeloid (platelets, red blood cells, neutrophils, and macrophages) and lymphoid (B and T lymphocytes) cells from pluripotent stem cells. The etiology of these immune deficiencies or disorders may be genetic, somatic, such as cancer or some autoimmune disorders, acquired (e.g., by chemotherapy or toxins), or infectious. Moreover, a polynucleotide or polypeptide of the present invention can be used as a marker or detector of a particular immune system disease or disorder.

A polynucleotide or polypeptide of the present invention may be useful in treating or detecting deficiencies or disorders of hematopoietic cells. A polypeptide or polynucleotide of the present invention could be used to increase differentiation and proliferation of hematopoietic cells, including the pluripotent stem cells, in an effort to treat those disorders associated with a decrease in certain (or many) types hematopoietic cells. Examples of immunologic deficiency syndromes include, but are not limited to: blood protein disorders (e.g. agammaglobulinemia, dysgammaglobulinemia), ataxia telangiectasia, common variable immunodeficiency, Digeorge Syndrome, HIV infection, HTLV-BLV infection, leukocyte adhesion deficiency syndrome, lymphopenia, phagocyte bactericidal dysfunction, severe combined immunodeficiency (SCIDs), Wiskott-Aldrich Disorder, anemia, thrombocytopenia, or hemoglobinuria.

Moreover, a polypeptide or polynucleotide of the present invention could also be used to modulate hemostatic (the stopping of bleeding) or thrombolytic activity (clot formation). For example, by increasing hemostatic or thrombolytic activity, a polynucleotide or polypeptide of the present invention could be used to treat blood coagulation disorders (e.g., afibrinogenemia, factor deficiencies), blood platelet disorders (e.g. thrombocytopenia), or wounds resulting from trauma, surgery, or other causes. Alternatively, a polynucleotide or polypeptide of the present invention that can decrease hemostatic or thrombolytic activity could be used to inhibit or dissolve clotting. These molecules could be important in the treatment of heart attacks (infarction), strokes, or scarring.

A polynucleotide or polypeptide of the present invention may also be useful in treating or detecting autoimmune disorders. Many autoimmune disorders result from inappropriate recognition of self as foreign material by immune cells. This inappropriate recognition results in an immune response leading to the destruction of the host tissue. Therefore, the administration of a polypeptide or polynucleotide of the present invention that inhibits an immune response, particularly the proliferation, differentiation, or chemotaxis of T-cells, may be an effective therapy in preventing autoimmune disorders.

Examples of autoimmune disorders that can be treated or detected by the present invention include, but are not limited to: Addison's Disease, hemolytic anemia, antiphospholipid syndrome, rheumatoid arthritis, dermatitis, allergic encephalomyelitis, glomerulonephritis, Goodpasture's Syndrome, Graves'Disease, Multiple Sclerosis, Myasthenia Gravis, Neuritis, Ophthalmia, Bullous Pemphigoid, Pemphigus, Polyendocrinopathies, Purpura, Reiter's Disease, Stiff-Man Syndrome, Autoimmune Thyroiditis, Systemic Lupus Erythematosus, Autoimmune Pulmonary Inflammation, Guillain-Barre Syndrome, insulin dependent diabetes mellitis, and autoimmune inflammatory eye disease.

Similarly, allergic reactions and conditions, such as asthma (particularly allergic asthma) or other respiratory problems, may also be treated by a polypeptide or polynucleotide of the present invention. Moreover, these molecules can be used to treat anaphylaxis, hypersensitivity to an antigenic molecule, or blood group incompatibility.

A polynucleotide or polypeptide of the present invention may also be used to treat and/or prevent organ rejection or graft-versus-host disease (GVHD). Organ rejection occurs by host immune cell destruction of the transplanted tissue through an immune response. Similarly, an immune response is also involved in GVHD, but, in this case, the foreign transplanted immune cells destroy the host tissues. The administration of a polypeptide or polynucleotide of the present invention that inhibits an immune response, particularly the proliferation, differentiation, or chemotaxis of T-cells, may be an effective therapy in preventing organ rejection or GVHD.

Similarly, a polypeptide or polynucleotide of the present invention may also be used to modulate inflammation. For example, the polypeptide or polynucleotide may inhibit the proliferation and differentiation of cells involved in an inflammatory response. These molecules can be used to treat inflammatory conditions, both chronic and acute conditions, including inflammation associated with infection (e.g., septic shock, sepsis, or systemic inflammatory response syndrome (SIRS)), ischemia-reperfusion injury, endotoxin lethality, arthritis, complement-mediated hyperacute rejection, nephritis, cytokine or chemokine induced lung injury, inflammatory bowel disease, Crohn's disease, or resulting from over production of cytokines (e.g., TNF or

Hyperproliferative Disorders

A polypeptide or polynucleotide can be used to treat or detect hyperproliferative disorders, including neoplasms. A polypeptide or polynucleotide of the present invention may inhibit the proliferation of the disorder through direct or indirect interactions. Alternatively, a polypeptide or polynucleotide of the present invention may proliferate other cells which can inhibit the hyperproliferative disorder.

For example, by increasing an immune response, particularly increasing antigenic qualities of the hyperproliferative disorder or by proliferating, differentiating, or mobilizing T-cells, hyperproliferative disorders can be treated. This immune response may be increased by either enhancing an existing immune response, or by initiating a new immune response. Alternatively, decreasing an immune response may also be a method of treating hyperproliferative disorders, such as a chemotherapeutic agent.

Examples of hyperproliferative disorders that can be treated or detected by a polynucleotide or polypeptide of the present invention include, but are not limited to neoplasms located in the: abdomen, bone, breast, digestive system, liver, pancreas, peritoneum, endocrine glands (adrenal, parathyroid, pituitary, testicles, ovary, thymus, thyroid), eye, head and neck, nervous (central and peripheral), lymphatic system, pelvic, skin, soft tissue, spleen, thoracic, and urogenital.

Similarly, other hyperproliferative disorders can also be treated or detected by a polynucleotide or polypeptide of the present invention. Examples of such hyperproliferative disorders include, but are not limited to: hypergammaglobulinemia, lymphoproliferative disorders, paraproteinemias, purpura, sarcoidosis, Sezary Syndrome, Waldenstron's Macroglobulinemia, Gaucher's Disease, histiocytosis, and any other hyperproliferative disease, besides neoplasia, located in an organ system listed above.

Infectious Disease

A polypeptide or polynucleotide of the present invention can be used to treat or detect infectious agents. For example, by increasing the immune response, particularly increasing the proliferation and differentiation of B and/or T cells, infectious diseases may be treated. The immune response may be increased by either enhancing an existing immune response, or by initiating a new immune response. Alternatively, the polypeptide or polynucleotide of the present invention may also directly inhibit the infectious agent, without necessarily eliciting an immune response.

Viruses are one example of an infectious agent that can cause disease or symptoms that can be treated or detected by a polynucleotide or polypeptide of the present invention. Examples of viruses, include, but are not limited to the following DNA and RNA viral families: Arbovirus, Adenoviridae, Arenaviridae, Arterivirus, Birnaviridae, Bunyaviridae, Caliciviridae, Circoviridae, Coronaviridae, Flaviviridae, Hepadnaviridae (Hepatitis), Herpesviridae. (such as, Cytomegalovirus, Herpes Simplex, Herpes Zoster), Mononegavirus (e.g. Paramyxoviridae, Morbillivirus, Rhabdoviridae), Orthomyxoviridae (e.g., Influenza), Papovaviridae, Parvoviridae, Picornaviridae, Poxviridae (such as Smallpox or Vaccinia), Reoviridae (e.g., Rotavirus), Retroviridae (HTLV-I, HTLV-II, Lentivirus), and Togaviridae (e.g., Rubivirus). Viruses falling within these families can cause a variety of diseases or symptoms, including, but not limited to: arthritis, bronchiollitis, encephalitis, eye infections (e.g., conjunctivitis, keratitis), chronic fatigue syndrome, hepatitis (A, B, C, E, Chronic Active, Delta), meningitis, opportunistic infections (e.g., AIDS), pneumonia, Burkitt's Lymphoma, chickenpox, hemorrhagic fever, Measles, Mumps, Parainfluenza, Rabies, the common cold, Polio, leukemia, Rubella, sexually transmitted diseases, skin diseases (e.g., Kaposi's. warts), and viremia. A polypeptide or polynucleotide of the present invention can be used to treat or detect any of these symptoms or diseases.

Similarly, bacterial or fungal agents that can cause disease or symptoms and that can be treated or detected by a polynucleotide or polypeptide of the present invention include, but not limited to, the following Gram-Negative and Gram-positive bacterial families and fungi: Actinomycetales (e.g., Corynebacterium, Mycobacterium, Norcardia), Aspergillosis, Bacillaceae (e.g., Anthrax, Clostridium), Bacteroidaceae, Blastomycosis, Bordetella, Borrelia, Brucellosis, Candidiasis, Campylobacter, Coccidioidomycosis, Cryptococcosis, Dermatocycoses, Enterobacteriaceae (Klebsiella, Salmonella, Serratia, Yersinia), Erysipelothrix, Helicobacter, Legionellosis, Leptospirosis, Listeria, Mycoplasmatales, Neisseriaceae (e.g., Acinetobacter, Gonorrhea, Menicococcall, Pasteurellacea Infections (e.g., Actinobacillus, Heamophilus, Pasteurella), Pseudomonas, Rickettsiaceae, Chlamydiaceae, Syphilis, and Staphylococcal. These bacterial or fungal families can cause the following diseases or symptoms, including, but not limited to: bacteremia, endocarditis, eye infections (conjunctivitis, tuberculosis, uveitis), gingivitis, opportunistic infections (e.g., AIDS related infections), paronychia, prosthesis-related infections, Reiter's Disease, respiratory tract infections, such as Whooping Cough or Empyema, sepsis, Lyme Disease, Cat-Scratch Disease, Dysentery, Paratyphoid Fever, food poisoning, Typhoid, pneumonia, Gonorrhea, meningitis, Chlamydia, Syphilis, Diphtheria, Leprosy, Paratuberculosis, Tuberculosis, Lupus, Botulism, gangrene, tetanus, impetigo, Rheumatic Fever, Scarlet Fever, sexually transmitted diseases, skin diseases (e.g., cellulitis, dermatocycoses), toxemia, urinary tract infections, wound infections. A polypeptide or polynucleotide of the present invention can be used to treat or detect any of these symptoms or diseases.

Moreover, parasitic agents causing disease or symptoms that can be treated or detected by a polynucleotide or polypeptide of the present invention include, but not limited to, the following families: Amebiasis, Babesiosis, Coccidiosis, Cryptosporidiosis, Dientamoebiasis, Dourine, Ectoparasitic, Giardiasis, Helminthiasis, Leishmaniasis, Theileriasis, Toxoplasmosis, Trypanosomiasis, and Trichomonas. These parasites can cause a variety of diseases or symptoms, including, but not limited to: Scabies, Trombiculiasis, eye infections, intestinal disease (e.g., dysentery, giardiasis), liver disease, lung disease, opportunistic infections (e.g., AIDS related), Malaria, pregnancy complications, and toxoplasmosis. A polypeptide or polynucleotide of the present invention can be used to treat or detect any of these symptoms or diseases.

Preferably, treatment using a polypeptide or polynucleotide of the present invention could either be by administering an effective amount of a polypeptide to the patient, or by removing cells from the patient, supplying the cells with a polynucleotide of the present invention, and returning the engineered cells to the patient (ex vivo therapy). Moreover, the polypeptide or polynucleotide of the present invention can be used as an antigen in a vaccine to raise an immune response against infectious disease.

Regeneration

A polynucleotide or polypeptide of the present invention can be used to differentiate, proliferate, and attract cells, leading to the regeneration of tissues. (See, Science 276:59-87 (1997).) The regeneration of tissues could be used to repair, replace, or protect tissue damaged by congenital defects, trauma (wounds, burns, incisions, or ulcers), age, disease (e.g. osteoporosis, osteocarthritis, periodontal disease, liver failure), surgery, including cosmetic plastic surgery, fibrosis, reperfusion injury, or systemic cytokine damage.

Tissues that could be regenerated using the present invention include organs (e.g., pancreas, liver, intestine, kidney, skin, endothelium), muscle (smooth, skeletal or cardiac), vascular (including vascular endothelium), nervous, hematopoietic, and skeletal (bone, cartilage, tendon, and ligament) tissue. Preferably, regeneration occurs without or decreased scarring. Regeneration also may include angiogenesis.

Moreover, a polynucleotide or polypeptide of the present invention may increase regeneration of tissues difficult to heal. For example, increased tendon/ligament regeneration would quicken recovery time after damage. A polynucleotide or polypeptide of the present invention could also be used prophylactically in an effort to avoid damage. Specific diseases that could be treated include of tendinitis, carpal tunnel syndrome, and other tendon or ligament defects. A further example of tissue regeneration of non-healing wounds includes pressure ulcers, ulcers associated with vascular insufficiency, surgical, and traumatic wounds.

Similarly, nerve and brain tissue could also be regenerated by using a polynucleotide or polypeptide of the present invention to proliferate and differentiate nerve cells. Diseases that could be treated using this method include central and peripheral nervous system diseases, neuropathies, or mechanical and traumatic disorders (e.g., spinal cord disorders, head trauma, cerebrovascular disease, and stoke). Specifically, diseases associated with peripheral nerve injuries, peripheral neuropathy (e.g., resulting from chemotherapy or other medical therapies), localized neuropathies, and central nervous system diseases (e.g., Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and Shy-Drager syndrome), could all be treated using the polynucleotide or polypeptide of the present invention.

Chemotaxis

A polynucleotide or polypeptide of the present invention may have chemotaxis activity. A chemotaxic molecule attracts or mobilizes cells (e.g., monocytes, fibroblasts, neutrophils, T-cells, mast cells, eosinophils, epithelial and/or endothelial cells) to a particular site in the body, such as inflammation, infection, or site of hyperproliferation. The mobilized cells can then fight off and/or heal the particular trauma or abnormality.

A polynucleotide or polypeptide of the present invention may increase chemotaxic activity of particular cells. These chemotactic molecules can then be used to treat inflammation, infection, hyperproliferative disorders, or any immune system disorder by increasing the number of cells targeted to a particular location in the body. For example, chemotaxic molecules can be used to treat wounds and other trauma to tissues by attracting immune cells to the injured location. Chemotactic molecules of the present invention can also attract fibroblasts, which can be used to treat wounds.

It is also contemplated that a polynucleotide or polypeptide of the present invention may inhibit chemotactic activity. These molecules could also be used to treat disorders. Thus, a polynucleotide or polypeptide of the present invention could be used as an inhibitor of chemotaxis.

Binding Activity

A polypeptide of the present invention may be used to screen for molecules that bind to the polypeptide or for molecules to which the polypeptide binds. The binding of the polypeptide and the molecule may activate (agonist), increase, inhibit (antagonist), or decrease activity of the polypeptide or the molecule bound. Examples of such molecules include antibodies, oligonucleotides, proteins (e.g., receptors),or small molecules.

Preferably, the molecule is closely related to the natural ligand of the polypeptide, e.g., a fragment of the ligand, or a natural substrate, a ligand, a structural or functional mimetic. (See, Coligan et al., Current Protocols in Immunology 1(2):Chapter 5 (1991).) Similarly, the molecule can be closely related to the natural receptor to which the polypeptide binds, or at least, a fragment of the receptor capable of being bound by the polypeptide (e.g., active site). In either case, the molecule can be rationally designed using known techniques.

Preferably, the screening for these molecules involves producing appropriate cells which express the polypeptide, either as a secreted protein or on the cell membrane. Preferred cells include cells from mammals, yeast, Drosophila, or E. coli. Cells expressing the polypeptide (or cell membrane containing the expressed polypeptide) are then preferably contacted with a test compound potentially containing the molecule to observe binding, stimulation, or inhibition of activity of either the polypeptide or the molecule.

The assay may simply test binding of a candidate compound to the polypeptide, wherein binding is detected by a label, or in an assay involving competition with a labeled competitor. Further, the assay may test whether the candidate compound results in a signal generated by binding to the polypeptide.

Alternatively, the assay can be carried out using cell-free preparations, polypeptide/molecule affixed to a solid support, chemical libraries, or natural product mixtures. The assay may also simply comprise the steps of mixing a candidate compound with a solution containing a polypeptide, measuring polypeptide/molecule activity or binding, and comparing the polypeptide/molecule activity or binding to a standard.

Preferably, an ELISA assay can measure polypeptide level or activity in a sample (e.g., biological sample) using a monoclonal or polyclonal antibody. The antibody can measure polypeptide level or activity by either binding, directly or indirectly, to the polypeptide or by competing with the polypeptide for a substrate.

All of these above assays can be used as diagnostic or prognostic markers. The molecules discovered using these assays can be used to treat disease or to bring about a particular result in a patient (e.g., blood vessel growth) by activating or inhibiting the polypeptide/molecule. Moreover, the assays can discover agents which may inhibit or enhance the production of the polypeptide from suitably manipulated cells or tissues.

Therefore, the invention includes a method of identifying compounds which bind to a polypeptide of the invention comprising the steps of: (a) incubating a candidate binding compound with a polypeptide of the invention; and (b) determining if binding has occurred. Moreover, the invention includes a method of identifying agonists/antagonists comprising the steps of: (a) incubating a candidate compound with a polypeptide of the invention, (b) assaying a biological activity , and (b) determining if a biological activity of the polypeptide has been altered.

Other Activities

A polypeptide or polynucleotide of the present invention may also increase or decrease the differentiation or proliferation of embryonic stem cells, besides, as discussed above, hematopoietic lineage.

A polypeptide or polynucleotide of the present invention may also be used to modulate mammalian characteristics, such as body height, weight, hair color, eye color, skin, percentage of adipose tissue, pigmentation, size, and shape (e.g., cosmetic surgery). Similarly, a polypeptide or polynucleotide of the present invention may be used to modulate mammalian metabolism affecting catabolism, anabolism, processing, utilization, and storage of energy.

A polypeptide or polynucleotide of the present invention may be used to change a mammal's mental state or physical state by influencing biorhythms, caricadic rhythms, depression (including depressive disorders), tendency for violence, tolerance for pain, reproductive capabilities (preferably by Activin or Inhibin-like activity), hormonal or endocrine levels, appetite, libido, memory, stress, or other cognitive qualities.

A polypeptide or polynucleotide of the present invention may also be used as a food additive or preservative, such as to increase or decrease storage capabilities, fat content, lipid, protein, carbohydrate, vitamins, minerals, cofactors or other nutritional components.

Other Preferred Embodiments

Other preferred embodiments of the claimed invention include an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to a sequence of at least about 50 contiguous nucleotides in the nucleotide sequence of SEQ ID NO:X wherein X is any integer as defined in Table 1.

Also preferred is a nucleic acid molecule wherein said sequence of contiguous nucleotides is included in the nucleotide sequence of SEQ ID NO:X in the range of positions beginning with the nucleotide at about the position of the 5′ Nucleotide of the Clone Sequence and ending with the nucleotide at about the position of the 3′ Nucleotide of the Clone Sequence as defined for SEQ ID NO:X in Table 1.

Also preferred is a nucleic acid molecule wherein said sequence of contiguous nucleotides is included in the nucleotide sequence of SEQ ID NO:X in the range of positions beginning with the nucleotide at about the position of the 5′ Nucleotide of the Start Codon and ending with the nucleotide at about the position of the 3′ Nucleotide of the Clone Sequence as defined for SEQ ID NO:X in Table 1.

Similarly preferred is a nucleic acid molecule wherein said sequence of contiguous nucleotides is included in the nucleotide sequence of SEQ ID NO:X in the range of positions beginning with the nucleotide at about the position of the 5′ Nucleotide of the First Amino Acid of the Signal Peptide and ending with the nucleotide at about the position of the 3′ Nucleotide of the Clone Sequence as defined for SEQ ID NO:X in Table 1.

Also preferred is an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to a sequence of at least about 150 contiguous nucleotides in the nucleotide sequence of SEQ ID NO:X.

Further preferred is an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to a sequence of at least about 500 contiguous nucleotides in the nucleotide sequence of SEQ ID NO:X.

A further preferred embodiment is a nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to the nucleotide sequence of SEQ ID NO:X beginning with the nucleotide at about the position of the 5′ Nucleotide of the First Amino Acid of the Signal Peptide and ending with the nucleotide at about the position of the 3′ Nucleotide of the Clone Sequence as defined for SEQ ID NO:X in Table 1.

A further preferred embodiment is an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to the complete nucleotide sequence of SEQ ID NO:X.

Also preferred is an isolated nucleic acid molecule which hybridizes under stringent hybridization conditions to a nucleic acid molecule, wherein said nucleic acid molecule which hybridizes does not hybridize under stringent hybridization conditions to a nucleic acid molecule having a nucleotide sequence consisting of only A residues or of only T residues.

Also preferred is a composition of matter comprising a DNA molecule which comprises a human cDNA clone identified by a cDNA Clone Identifier in Table 1, which DNA molecule is contained in the material deposited with the American Type Culture Collection and given the ATCC Deposit Number shown in Table 1 for said cDNA Clone Identifier.

Also preferred is an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to a sequence of at least 50 contiguous nucleotides in the nucleotide sequence of a human cDNA clone identified by a cDNA Clone Identifier in Table 1, which DNA molecule is contained in the deposit given the ATCC Deposit Number shown in Table 1.

Also preferred is an isolated nucleic acid molecule, wherein said sequence of at least 50 contiguous nucleotides is included in the nucleotide sequence of the complete open reading frame sequence encoded by said human cDNA clone.

Also preferred is an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to sequence of at least 150 contiguous nucleotides in the nucleotide sequence encoded by said human cDNA clone.

A further preferred embodiment is an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to sequence of at least 500 contiguous nucleotides in the nucleotide sequence encoded by said human cDNA clone.

A further preferred embodiment is an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to the complete nucleotide sequence encoded by said human cDNA clone.

A further preferred embodiment is a method for detecting in a biological sample a nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to a sequence of at least 50 contiguous nucleotides in a sequence selected from the group consisting of: a nucleotide sequence of SEQ ID NO:X wherein X is any integer as defined in Table 1; and a nucleotide sequence encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1; which method comprises a step of comparing a nucleotide sequence of at least one nucleic acid molecule in said sample with a sequence selected from said group and determining whether the sequence of said nucleic acid molecule in said sample is at least 95% identical to said selected sequence.

Also preferred is the above method wherein said step of comparing sequences comprises determining the extent of nucleic acid hybridization between nucleic acid molecules in said sample and a nucleic acid molecule comprising said sequence selected from said group. Similarly, also preferred is the above method wherein said step of comparing sequences is performed by comparing the nucleotide sequence determined from a nucleic acid molecule in said sample with said sequence selected from said group. The nucleic acid molecules can comprise DNA molecules or RNA molecules.

A further preferred embodiment is a method for identifying the species, tissue or cell type of a biological sample which method comprises a step of detecting nucleic acid molecules in said sample, if any, comprising a nucleotide sequence that is at least 95% identical to a sequence of at least 50 contiguous nucleotides in a sequence selected from the group consisting of: a nucleotide sequence of SEQ ID NO:X wherein X is any integer as defined in Table 1; and a nucleotide sequence encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1.

The method for identifying the species, tissue or cell type of a biological sample can comprise a step of detecting nucleic acid molecules comprising a nucleotide sequence in a panel of at least two nucleotide sequences, wherein at least one sequence in said panel is at least 95% identical to a sequence of at least 50 contiguous nucleotides in a sequence selected from said group.

Also preferred is a method for diagnosing in a subject a pathological condition associated with abnormal structure or expression of a gene encoding a secreted protein identified in Table 1, which method comprises a step of detecting in a biological sample obtained from said subject nucleic acid molecules, if any, comprising a nucleotide sequence that is at least 95% identical to a sequence of at least 50 contiguous nucleotides in a sequence selected from the group consisting of: a nucleotide sequence of SEQ ID NO:X wherein X is any integer as defined in Table 1; and a nucleotide sequence encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1.

The method for diagnosing a pathological condition can comprise a step of detecting nucleic acid molecules comprising a nucleotide sequence in a panel of at least two nucleotide sequences, wherein at least one sequence in said panel is at least 95% identical to a sequence of at least 50 contiguous nucleotides in a sequence selected from said group.

Also preferred is a composition of matter comprising isolated nucleic acid molecules wherein the nucleotide sequences of said nucleic acid molecules comprise a panel of at least two nucleotide sequences, wherein at least one sequence in said panel is at least 95% identical to a sequence of at least 50 contiguous nucleotides in a sequence selected from the group consisting of: a nucleotide sequence of SEQ ID NO:X wherein X is any integer as defined in Table 1; and a nucleotide sequence encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1. The nucleic acid molecules can comprise DNA molecules or RNA molecules.

Also preferred is an isolated polypeptide comprising an amino acid sequence at least 90% identical to a sequence of at least about 10 contiguous amino acids in the amino acid sequence of SEQ ID NO:Y wherein Y is any integer as defined in Table 1.

Also preferred is a polypeptide, wherein said sequence of contiguous amino acids is included in the amino acid sequence of SEQ ID NO:Y in the range of positions beginning with the residue at about the position of the First Amino Acid of the Secreted Portion and ending with the residue at about the Last Amino Acid of the Open Reading Frame as set forth for SEQ ID NO:Y in Table 1.

Also preferred is an isolated polypeptide comprising an amino acid sequence at least 95% identical to a sequence of at least about 30 contiguous amino acids in the amino acid sequence of SEQ ID NO:Y.

Further preferred is an isolated polypeptide comprising an amino acid sequence at least 95% identical to a sequence of at least about 100 contiguous amino acids in the amino acid sequence of SEQ ID NO:Y.

Further preferred is an isolated polypeptide comprising an amino acid sequence at least 95% identical to the complete amino acid sequence of SEQ ID NO:Y.

Further preferred is an isolated polypeptide comprising an amino acid sequence at least 90% identical to a sequence of at least about 10 contiguous amino acids in the complete amino acid sequence of a secreted protein encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1.

Also preferred is a polypeptide wherein said sequence of contiguous amino acids is included in the amino acid sequence of a secreted portion of the secreted protein encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1.

Also preferred is an isolated polypeptide comprising, an amino acid sequence at least 95% identical to a sequence of at least about 30 contiguous amino acids in the amino acid sequence of the secreted portion of the protein encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1.

Also preferred is an isolated polypeptide comprising an amino acid sequence at least 95% identical to a sequence of at least about 100 contiguous amino acids in the amino acid sequence of the secreted portion of the protein encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1.

Also preferred is an isolated polypeptide comprising an amino acid sequence at least 95% identical to the amino acid sequence of the secreted portion of the protein encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1.

Further preferred is an isolated antibody which binds specifically to a polypeptide comprising an amino acid sequence that is at least 90% identical to a sequence of at least 10 contiguous amino acids in a sequence selected from the group consisting of: an amino acid sequence of SEQ ID NO:Y wherein Y is any integer as defined in Table 1; and a complete amino acid sequence of a protein encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1.

Further preferred is a method for detecting in a biological sample a polypeptide comprising an amino acid sequence which is at least 90% identical to a sequence of at least 10 contiguous amino acids in a sequence selected from the group consisting of: an amino acid sequence of SEQ ID NO:Y wherein Y is any integer as defined in Table 1; and a complete amino acid sequence of a protein encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1; which method comprises a step of comparing an amino acid sequence of at least one polypeptide molecule in said sample with a sequence selected from said group and determining whether the sequence of said polypeptide molecule in said sample is at least 90% identical to said sequence of at least 10 contiguous amino acids.

Also preferred is the above method wherein said step of comparing an amino acid sequence of at least one polypeptide molecule in said sample with a sequence selected from said group comprises determining the extent of specific binding of polypeptides in said sample to an antibody which binds specifically to a polypeptide comprising an amino acid sequence that is at least 90% identical to a sequence of at least 10 contiguous amino acids in a sequence selected from the group consisting of: an amino acid sequence of SEQ ID NO:Y wherein Y is any integer as defined in Table 1; and a complete amino acid sequence of a protein encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1.

Also preferred is the above method wherein said step of comparing sequences is performed by comparing the amino acid sequence determined from a polypeptide molecule in said sample with said sequence selected from said group.

Also preferred is a method for identifying the species, tissue or cell type of a biological sample which method comprises a step of detecting polypeptide molecules in said sample, if any, comprising an amino acid sequence that is at least 90% identical to a sequence of at least 10 contiguous amino acids in a sequence selected from the group consisting of: an amino acid sequence of SEQ ID NO:Y wherein Y is any integer as defined in Table 1; and a complete amino acid sequence of a secreted protein encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1.

Also preferred is the above method for identifying the species, tissue or cell type of a biological sample, which method comprises a step of detecting polypeptide molecules comprising an amino acid sequence in a panel of at least two amino acid sequences, wherein at least one sequence in said panel is at least 90% identical to a sequence of at least 10 contiguous amino acids in a sequence selected from the above group.

Also preferred is a method for diagnosing in a subject a pathological condition associated with abnormal structure or expression of a gene encoding a secreted protein identified in Table 1, which method comprises a step of detecting in a biological sample obtained from said subject polypeptide molecules comprising an amino acid sequence in a panel of at least two amino acid sequences, wherein at least one sequence in said panel is at least 90% identical to a sequence of at least 10 contiguous amino acids in a sequence selected from the group consisting of: an amino acid sequence of SEQ ID NO:Y wherein Y is any integer as defined in Table 1; and a complete amino acid sequence of a secreted protein encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1.

In any of these methods, the step of detecting said polypeptide molecules includes using an antibody.

Also preferred is an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to a nucleotide sequence encoding a polypeptide wherein said polypeptide comprises an amino acid sequence that is at least 90% identical to a sequence of at least 10 contiguous amino acids in a sequence selected from the group consisting of: an amino acid sequence of SEQ ID NO:Y wherein Y is any integer as defined in Table 1; and a complete amino acid sequence of a secreted protein encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1.

Also preferred is an isolated nucleic acid molecule, wherein said nucleotide sequence encoding a polypeptide has been optimized for expression of said polypeptide in a prokaryotic host.

Also preferred is an isolated nucleic acid molecule, wherein said polypeptide comprises an amino acid sequence selected from the group consisting of: an amino acid sequence of SEQ ID NO:Y wherein Y is any integer as defined in Table 1; and a complete amino acid sequence of a secreted protein encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1.

Further preferred is a method of making a recombinant vector comprising inserting any of the above isolated nucleic acid molecule into a vector. Also preferred is the recombinant vector produced by this method. Also preferred is a method of making a recombinant host cell comprising introducing the vector into a host cell, as well as the recombinant host cell produced by this method.

Also preferred is a method of making an isolated polypeptide comprising culturing this recombinant host cell under conditions such that said polypeptide is expressed and recovering said polypeptide. Also preferred is this method of making an isolated polypeptide, wherein said recombinant host cell is a eukaryotic cell and said polypeptide is a secreted portion of a human secreted protein comprising an amino acid sequence selected from the group consisting of: an amino acid sequence of SEQ ID NO:Y beginning with the residue at the position of the First Amino Acid of the Secreted Portion of SEQ ID NO:Y wherein Y is an integer set forth in Table 1 and said position of the First Amino Acid of the Secreted Portion of SEQ ID NO:Y is defined in Table 1; and an amino acid sequence of a secreted portion of a protein encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1. The isolated polypeptide produced by this method is also preferred.

Also preferred is a method of treatment of an individual in need of an increased level of a secreted protein activity, which method comprises administering to such an individual a pharmaceutical composition comprising an amount of an isolated polypeptide, polynucleotide, or antibody of the claimed invention effective to increase the level of said protein activity in said individual.

Having generally described the invention, the same will be more readily understood by reference to the following examples, which are provided by way of illustration and are not intended as limiting.

EXAMPLES

Example 1

Isolation of a Selected cDNA Clone From the Deposited Sample

Each cDNA clone in a cited ATCC deposit is contained in a plasmid vector. Table 1 identifies the vectors used to construct the cDNA library from which each clone was isolated. In many cases, the vector used to construct the library is a phage vector from which a plasmid has been excised. The table immediately below correlates the related plasmid for each phage vector used in constructing the cDNA library. For example, where a particular clone is identified in Table 1 as being is isolated in the vector “Lambda Zap,” the corresponding deposited clone is in “pBluescript.”



Vector Used to Construct Library	Corresponding Deposited Plasmid

Lambda Zap	pBluescript (pBS)
Uni-Zap XR	pBluescript (pBS)
Zap Express	pBK
lafmid BA	plafmid BA
pSport1	pSport1
pCMVSport 2.0	pCMVSport 2.0
pCMVSport 3.0	pCMVSport 3.0
pCR ® 2.1	pCR ® 2.1

Vectors Lambda Zap (U.S. Pat. Nos. 5,128,256 and 5,286,636), Uni-Zap XR (U.S. Pat. Nos. 5,128, 256 and 5,286,636), Zap Express (U.S. Pat. Nos. 5,128,256 and 5,286,636), pBluescript (pBS) (Short, J. M. et al., Nucleic Acids Res. 16:7583-7600 (1988); Alting-Mees, M. A. and Short, J. M., Nucleic Acids Res. 17:9494 (1989)) and pBK (Alting-Mees, M. A. et al., Strategies 5:58-61 (1992)) are commercially available from Stratagene Cloning Systems, Inc., 11011 N. Torrey Pines Road, La Jolla, Calif., 92037. pBS contains an ampicillin resistance gene and pBK contains a neomycin resistance gene. Both can be transformed into [0542] E. coli strain XL-1 Blue, also available from Stratagene. pBS comes in 4 forms SK+, SK−, KS+ and KS. The S and K refers to the orientation of the polylinker to the T7 and T3 primer sequences which flank the polylinker region (“S” is for SacI and “K” is for KpnI which are the first sites on each respective end of the linker). “+” or “−” refer to the orientation of the f1 origin of replication (“ori”), such that in one orientation, single stranded rescue initiated from the f1 ori generates sense strand DNA and in the other, antisense.
Vectors pSport1, pCMVSport 2.0 and pCMVSport 3.0, were obtained from Life Technologies, Inc., P. O. Box 6009, Gaithersburg, Md. 20897. All Sport vectors contain an ampicillin resistance gene and may be transformed into [0543] E. coli strain DH10B, also available from Life Technologies. (See, for instance, Gruber, C. E., et al., Focus 15:59 (1993).) Vector lafmid BA (Bento Soares, Columbia University, NY) contains an ampicillin resistance gene and can be transformed into E. coli strain XL-1 Blue. Vector pCR®2.I, which is available from Invitrogen, 1600 Faraday Avenue, Carlsbad, Calif. 92008, contains an ampicillin resistance gene and may be transformed into E. coli strain DH10B, available from Life Technologies. (See, for instance, Clark, J. M., Nuc. Acids Res. 16:9677-9686 (1988) and Mead, D. et al., Bio/Technology 9: (1991).) Preferably, a polynucleotide of the present invention does not comprise the phage vector sequences identified for the particular clone in Table 1, as well as the corresponding plasmid vector sequences designated above.
The deposited material in the sample assigned the ATCC Deposit Number cited in Table 1 for any given cDNA clone also may contain one or more additional plasmids, each comprising a cDNA clone different from that given clone. Thus, deposits sharing the same ATCC Deposit Number contain at least a plasmid for each cDNA clone identified in Table 1. Typically, each ATCC deposit sample cited in Table 1 comprises a mixture of approximately equal amounts (by weight) of about 50 plasmid DNAs, each containing a different cDNA clone; but such a deposit sample may include plasmids for more or less than 50 cDNA clones, up to about 500 cDNA clones. [0544]
Two approaches can be used to isolate a particular clone from the deposited sample of plasmid DNAs cited for that clone in Table 1. First, a plasmid is directly isolated by screening the clones using a polynucleotide probe corresponding to SEQ ID NO:X. [0545]
Particularly, a specific polynucleotide with 30-40 nucleotides is synthesized using an Applied Biosystems DNA synthesizer according to the sequence reported. The oligonucleotide is labeled, for instance, with [0546] ³²P-γ-ATP using T4 polynucleotide kinase and purified according to routine methods. (E.g., Maniatis et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Press, Cold Spring, N.Y. (1982).) The plasmid mixture is transformed into a suitable host, as indicated above (such as XL-1 Blue (Stratagene)) using techniques known to those of skill in the art, such as those provided by the vector supplier or in related publications or patents cited above. The transformants are plated on 1.5% agar plates (containing the appropriate selection agent, e.g., ampicillin) to a density of about 150 transformants (colonies) per plate. These plates are screened using Nylon membranes according to routine methods for bacterial colony screening (e.g., Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd Edit., (1989), Cold Spring Harbor Laboratory Press, pages 1.93 to 1.104), or other techniques known to those of skill in the art.
Alternatively, two primers of 17-20 nucleotides derived from both ends of the SEQ ID NO:X (i.e., within the region of SEQ ID NO:X bounded by the 5′ NT and the 3′ NT of the clone defined in Table 1) are synthesized and used to amplify the desired cDNA using the deposited cDNA plasmid as a template. The polymerase chain reaction is carried out under routine conditions, for instance, in 25 μl of reaction mixture with 0.5 ug of the above cDNA template. A convenient reaction mixture is 1.5-5 mM MgCl[0547] ₂, 0.01% (w/v) gelatin, 20 μM each of dATP, dCTP, dGTP, dTTP, 25 pmol of each primer and 0.25 Unit of Taq polymerase. Thirty five cycles of PCR (denaturation at 94° C. for 1 min; annealing at 55° C. for 1 min; elongation at 72° C. for 1 min) are performed with a Perkin-Elmer Cetus automated thermal cycler. The amplified product is analyzed by agarose gel electrophoresis and the DNA band with expected molecular weight is excised and purified. The PCR product is verified to be the selected sequence by subcloning and sequencing the DNA product.
Several methods are available for the identification of the 5′ or 3′ non-coding portions of a gene which may not be present in the deposited clone. These methods include but are not limited to, filter probing, clone enrichment using specific probes, and protocols similar or identical to 5′ and 3′ “RACE” protocols which are well known in the art. For instance, a method similar to 5′ RACE is available for generating the missing 5′ end of a desired full-length transcript. (Fromont-Racine et al., Nucleic Acids Res. 21(7):1683-1684 (1993).) [0548]
Briefly, a specific RNA oligonucleotide is ligated to the 5′ ends of a population of RNA presumably containing full-length gene RNA transcripts. A primer set containing a primer specific to the ligated RNA oligonucleotide and a primer specific to a known sequence of the gene of interest is used to PCR amplify the 5′ portion of the desired full-length gene. This amplified product may then be sequenced and used to generate the full length gene. [0549]
This above method starts with total RNA isolated from the desired source, although poly-A+RNA can be used. The RNA preparation can then be treated with phosphatase if necessary to eliminate 5′ phosphate groups on degraded or damaged RNA which may interfere with the later RNA ligase step. The phosphatase should then be inactivated and the RNA treated with tobacco acid pyrophosphatase in order to remove the cap structure present at the 5′ ends of messenger RNAs. This reaction leaves a 5′ phosphate group at the 5′ end of the cap cleaved RNA which can then be ligated to an RNA oligonucleotide using T4 RNA ligase. [0550]
This modified RNA preparation is used as a template for first strand cDNA synthesis using a gene specific oligonucleotide. The first strand synthesis reaction is used as a template for PCR amplification of the desired 5′ end using a primer specific to the ligated RNA oligonucleotide and a primer specific to the known sequence of the gene of interest. The resultant product is then sequenced and analyzed to confirm that the 5′ end sequence belongs to the desired gene. [0551]

Example 2

Isolation of Genomic Clones Corresponding to a Polynucleotide

A human genomic P1 library (Genomic Systems, Inc.) is screened by PCR using primers selected for the cDNA sequence corresponding to SEQ ID NO:X., according to the method described in Example 1. (See also, Sambrook.) [0552]

Example 3

Tissue Distribution of Polypeptide

Tissue distribution of mRNA expression of polynucleotides of the present invention is determined using protocols for Northern blot analysis, described by, among others, Sambrook et al. For example, a cDNA probe produced by the method described in Example 1 is labeled with P[0553] ³²using the rediprime™ DNA labeling system (Amershan Life Science), according to manufacturer's instructions. After labeling, the probe is purified using CHROMA SPIN-100™ column (Clontech Laboratories, Inc.), according to manufacturer's protocol number PT1200-1. The purified labeled probe is then used to examine various human tissues for mRNA expression.
Multiple Tissue Northern (MTN) blots containing various human tissues (H) or human immune system tissues (IM) (Clontech) are examined with the labeled probe using ExpressHyb™ hybridization solution (Clontech) according to manufacturer's protocol number PT1190-1. Following hybridization a nd washing, the blots are mounted and exposed to film at −70° C. overnight, and the films developed according to standard procedures. [0554]

Example 4

Chromosomal Mapping of the Polynucleotides

An oligonucleotide primer set is designed according to the sequence at the 5′ and of SEQ ID NO:X. This primer preferably spans about 100 nucleotides. This primer set is then used in a polymerase chain reaction under the following set of conditions: 30 seconds, 95° C.; 1 minute, 56° C.; 1 minute, 70° C. This cycle is repeated 32 times followed by one 5 minute cycle at 70° C. Human, mouse, and hamster DNA is used as template in addition to a somatic cell hybrid panel containing individual chromosomes or chromosome fragments (Bios, Inc). The reactions is analyzed on either 8% polyacrylamide gels or 3.5% agarose gels. Chromosome mapping is determined by the presence of an approximately 100 bp PCR fragment in the particular somatic cell hybrid. [0555]

Example 5

Bacterial Expression of a Polypeptide

A polynucleotide encoding a polypeptide of the present invention is amplified using PCR oligonucleotide primers corresponding to the 5′ and 3′ ends of the DNA sequence, as outlined in Example 1, to synthesize insertion fragments. The primers used to amplify the cDNA insert should preferably contain restriction sites, such as BamHI and XbaI, at the 5′ end of the primers in order to clone the amplified product into the expression vector. For example, BamHI and XbaI correspond to the restriction enzyme sites on the bacterial expression vector pQE-9. (Qiagen, Inc., Chatsworth, Calif.). This plasmid vector encodes antibiotic resistance (Amp[0556] ^r), a bacterial origin of replication (ori), an IPTG-regulatable promoter/operator (P/O), a ribosome binding site (RBS), a 6-histidine tag (6-His), and restriction enzyme cloning sites.
The pQE-9 vector is digested with BamHI and XbaI and the amplified fragment is ligated into the pQE-9 vector maintaining the reading frame initiated at the bacterial RBS. The ligation mixture is then used to transform the [0557] E. coli strain M15/rep4 (Qiagen, Inc.) which contains multiple copies of the plasmid pREP4, which expresses the lacI repressor and also confers kanamycin resistance (Kan^r). Transformants are identified by their ability to grow on LB plates and ampicillin/kanamycin resistant colonies are selected. Plasmid DNA is isolated and confirmed by restriction analysis.
Clones containing the desired constructs are grown overnight (O/N) in liquid culture in LB media supplemented with both Amp (100 ug/ml) and Kan (25 ug/ml). The O/N culture is used to inoculate a large culture at a ratio of 1:100 to 1:250. The cells are grown to an optical density 600 (O.D.[0558] ⁶⁰⁰) of between 0.4 and 0.6. IPTG (Isopropyl-B-D-thiogalacto pyranoside) is then added to a final concentration of 1 mM. IPTG induces by inactivating the lacI repressor, clearing the P/O leading to increased gene expression.
Cells are grown for an extra 3 to 4 hours. Cells are then harvested by centrifugation (20 mins at 6000×g). The cell pellet is solubilized in the chaotropic agent 6 Molar Guanidine HCl by stirring for 3-4 hours at 4° C. The cell debris is removed by centrifugation, and the supernatant containing the polypeptide is loaded onto a nickel-nitrilo-tri-acetic acid (“Ni-NTA”) affinity resin column (available from QIAGEN, Inc., supra). Proteins with a 6×His tag bind to the Ni-NTA resin with high affinity and can be purified in a simple one-step procedure (for details see: The QIAexpressionist (1995) QIAGEN, Inc., supra). [0559]
Briefly, the supernatant is loaded onto the column in 6 M guanidine-HCl, pH 8, the column is first washed with 10 volumes of 6 M guanidine-HCl, pH 8, then washed with 10 volumes of 6 M guanidine-HCl pH 6, and finally the polypeptide is eluted with 6 M guanidine-HCl, pH 5. [0560]
The purified protein is then renatured by dialyzing it against phosphate-buffered saline (PBS) or 50 mM Na-acetate, pH 6 buffer plus 200 mM NaCl. Alternatively, the protein can be successfully refolded while immobilized on the Ni-NTA column. The recommended conditions are as follows: renature using a linear 6M-1M urea gradient in 500 mM NaCl, 20% glycerol, 20 mM Tris/HCl pH 7.4, containing protease inhibitors. The renaturation should be performed over a period of 1.5 hours or more. After renaturation the proteins are eluted by the addition of 250 mM imidazole. Immidazole is removed by a final dialyzing step against PBS or 50 mM sodium acetate pH 6 buffer plus 200 mM NaCl. The purified protein is stored at 4° C. or frozen at −80° C. [0561]
In addition to the above expression vector, the present invention further includes an expression vector comprising phage operator and promoter elements operatively linked to a polynucleotide of the present invention, called pHE4a. (ATCC Accession Number 209645, deposited on Feb. 25, 1998.) This vector contains: 1) a neomycinphosphotransferase gene as a selection marker, 2) an [0562] E. coli origin of replication, 3) a T5 phage promoter sequence, 4) two lac operator sequences, 5) a Shine-Delgarno sequence, and 6) the lactose operon repressor gene (lacIq). The origin of replication (oriC) is derived from pUC19 (LTI, Gaithersburg, Md.). The promoter sequence and operator sequences are made synthetically.
DNA can be inserted into the pHEa by restricting the vector with NdeI and XbaI, BamHI, XhoI, or Asp718, running the restricted product on a gel, and isolating the larger fragment (the stuffer fragment should be about 310 base pairs). The DNA insert is generated according to the PCR protocol described in Example 1, using PCR primers having restriction sites for NdeI (5′ primer) and XbaI, BamHI, XhoI, or Asp718 (3′ primer). The PCR insert is gel purified and restricted with compatible enzymes. The insert and vector are ligated according to standard protocols. [0563]
The engineered vector could easily be substituted in the above protocol to express protein in a bacterial system. [0564]

Example 6

Purification of a Polypeptide from an Inclusion Body

The following alternative method can be used to purify a polypeptide expressed in [0565] E. coli when it is present in the form of inclusion bodies. Unless otherwise specified, all of the following steps are conducted at 4-10° C.
Upon completion of the production phase of the [0566] E. coli fermentation, the cell culture is cooled to 4-10° C. and the cells harvested by continuous centrifugation at 15,000 rpm (Heraeus Sepatech). On the basis of the expected yield of protein per unit weight of cell paste and the amount of purified protein required, an appropriate amount of cell paste, by weight, is suspended in a buffer solution containing 100 mM Tris, 50 mM EDTA, pH 7.4. The cells are dispersed to a homogeneous suspension using a high shear mixer.
The cells are then lysed by passing the solution through a microfluidizer (Microfuidics, Corp. or APV Gaulin, Inc.) twice at 4000-6000 psi. The homogenate is then mixed with NaCl solution to a final concentration of 0.5 M NaCl, followed by centrifugation at 7000×g for 15 min. The resultant pellet is washed again using 0.5M NaCl, 100 mM Tris, 50 mM EDTA, pH 7.4. [0567]
The resulting washed inclusion bodies are solubilized with 1.5 M guanidine hydrochloride (GuHCl) for 2-4 hours. After 7000×g centrifugation for 15 min., the pellet is discarded and the polypeptide containing supernatant is incubated at 4° C. overnight to allow further GuHCl extraction. [0568]
Following high speed centrifugation (30,000×g) to remove insoluble particles, the GuHCl solubilized protein is refolded by quickly mixing the GuHCl extract with 20 volumes of buffer containing 50 mM sodium, pH 4.5, 150 mM NaCl, 2 mM EDTA by vigorous stirring. The refolded diluted protein solution is kept at 4° C. without mixing for 12 hours prior to further purification steps. [0569]
To clarify the refolded polypeptide solution, a previously prepared tangential filtration unit equipped with 0.16 μm membrane filter with appropriate surface area (e.g., Filtron), equilibrated with 40 mM sodium acetate, pH 6.0 is employed. The filtered sample is loaded onto a cation exchange resin (e.g., Poros HS-50, Perseptive Biosystems). The column is washed with 40 mM sodium acetate, pH 6.0 and eluted with 250 mM, 500 mM, 1000 mM, and 1500 mM NaCl in the same buffer, in a stepwise manner. The absorbance at 280 nm of the effluent is continuously monitored. Fractions are collected and further analyzed by SDS-PAGE. [0570]
Fractions containing the polypeptide are then pooled and mixed with 4 volumes of water. The diluted sample is then loaded onto a previously prepared set of tandem columns of strong anion (Poros HQ-50, Perseptive Biosystems) and weak anion (Poros CM-20, Perseptive Biosystems) exchange resins. The columns are equilibrated with 40 mM sodium acetate, pH 6.0. Both columns are washed with 40 mM sodium acetate, pH 6.0, 200 mM NaCl. The CM-20 column is then eluted using a 10 column volume linear gradient ranging from 0.2 M NaCl, 50 mM sodium acetate, pH 6.0 to 1.0 M NaCl, 50 mM sodium acetate, pH 6.5. Fractions are collected under constant A[0571] ₂₈₀monitoring of the effluent. Fractions containing the polypeptide (determined, for instance, by 16% SDS-PAGE) are then pooled.
The resultant polypeptide should exhibit greater than 95% purity after the above refolding and purification steps. No major contaminant bands should be observed from Commassie blue stained 16% SDS-PAGE gel when 5 μg of purified protein is loaded. The purified protein can also be tested for endotoxin/LPS contamination, and typically the LPS content is less than 0.1 ng/ml according to LAL assays. [0572]

Example 7

Cloning and Expression of a Polypeptide in a Baculovirus Expression System

In this example, the plasmid shuttle vector pA2 is used to insert a polynucleotide into a baculovirus to express a polypeptide. This expression vector contains the strong polyhedrin promoter of the [0573] Autographa californica nuclear polyhedrosis virus (AcMNPV) followed by convenient restriction sites such as BamHI, Xba I and Asp718. The polyadenylation site of the simian virus 40 (“SV40”) is used for efficient polyadenylation. For easy selection of recombinant virus, the plasmid contains the beta-galactosidase gene from E. coli under control of a weak Drosophila promoter in the same orientation, followed by the polyadenylation signal of the polyhedrin gene. The inserted genes are flanked on both sides by viral sequences for cell-mediated homologous recombination with wild-type viral DNA to generate a viable virus that express the cloned polynucleotide.
Many other baculovirus vectors can be used in place of the vector above, such as pAc373, pVL941, and pAcIM1, as one skilled in the art would readily appreciate, as long as the construct provides appropriately located signals for transcription, translation, secretion and the like, including a signal peptide and an in-frame AUG as required. Such vectors are described, for instance, in Luckow et al., Virology 170:31-39 (1989). [0574]
Specifically, the cDNA sequence contained in the deposited clone, including the AUG initiation codon and the naturally associated leader sequence identified in Table 1, is amplified using the PCR protocol described in Example 1. If the naturally occurring signal sequence is used to produce the secreted protein, the pA2 vector does not need a second signal peptide. Alternatively, the vector can be modified (pA2 GP) to include a baculovirus leader sequence, using the standard methods described in Summers et al., “A Manual of Methods for Baculovirus Vectors and Insect Cell Culture Procedures,” Texas Agricultural Experimental Station Bulletin No. 1555 (1987). [0575]
The amplified fragment is isolated from a 1% agarose gel using a commercially available kit (“Geneclean,” BIO 101 Inc., La Jolla, Calif.). The fragment then is digested with appropriate restriction enzymes and again purified on a 1% agarose gel. [0576]
The plasmid is digested with the corresponding restriction enzymes and optionally, can be dephosphorylated using calf intestinal phosphatase, using routine procedures known in the art. The DNA is then isolated from a 1% agarose gel using a commercially available kit (“Geneclean” BIO 101 Inc., La Jolla, Calif.). [0577]
The fragment and the dephosphorylated plasmid are ligated together with T4 DNA ligase. [0578] E. coli HB101 or other suitable E. coli hosts such as XL-1 Blue (Stratagene Cloning Systems, La Jolla, Calif.) cells are transformed with the ligation mixture and spread on culture plates. Bacteria containing the plasmid are identified by digesting DNA from individual colonies and analyzing the digestion product by gel electrophoresis. The sequence of the cloned fragment is confirmed by DNA sequencing.
Five μg of a plasmid containing the polynucleotide is co-transfected with 1.0 μg of a commercially available linearized baculovirus DNA (“BaculoGold™ baculovirus DNA”, Pharmingen, San Diego, Calif.), using the lipofection method described by Felgner et al., Proc. Natl. Acad. Sci. USA 84:7413-7417 (1987). One μg of BaculoGold™ virus DNA and 5 μg of the plasmid are mixed in a sterile well of a microtiter plate containing 50 μl of serum-free Grace's medium (Life Technologies Inc., Gaithersburg, Md.). Afterwards, 10 μl Lipofectin plus 90 μl Grace's medium are added, mixed and incubated for 15 minutes at room temperature. Then the transfection mixture is added drop-wise to Sf9 insect cells (ATCC CRL 1711) seeded in a 35 mm tissue culture plate with 1 mil Grace's medium without serum. The plate is then incubated for 5 hours at 27° C. The transfection solution is then removed from the plate and 1 ml of Grace's insect medium supplemented with 10% fetal calf serum is added. Cultivation is then continued at 27° C. for four days. [0579]
After four days the supernatant is collected and a plaque assay is performed, as described by Summers and Smith, supra. An agarose gel with “Blue Gal” (Life Technologies Inc., Gaithersburg) is used to allow easy identification and isolation of gal-expressing clones, which produce blue-stained plaques. (A detailed description of a “plaque assay” of this type can also be found in the user's guide for insect cell culture and baculovirology distributed by Life Technologies Inc., Gaithersburg, page 9-10.) After appropriate incubation, blue stained plaques are picked with the tip of a micropipettor (e.g., Eppendorf). The agar containing the recombinant viruses is then resuspended in a microcentrifuge tube containing 200 μl of Grace's medium and the suspension containing the recombinant baculovirus is used to infect Sf9 cells seeded in 35 mm dishes. Four days later the supernatants of these culture dishes are harvested and then they are stored at 4° C. [0580]
To verify the expression of the polypeptide, Sf9 cells are grown in Grace's medium supplemented with 10% heat-inactivated FBS. The cells are infected with the recombinant baculovirus containing the polynucleotide at a multiplicity of infection (“MOI”) of about 2. If radiolabeled proteins are desired, 6 hours later the medium is removed and is replaced with SF900II medium minus methionine and cysteine (available from Life Technologies Inc., Rockville, Md.). After 42 hours, 5 μCi of [0581] ³⁵S-methionine and 5 μCi ³⁵S-cysteine (available from Amersham) are added. The cells are further incubated for 16 hours and then are harvested by centrifugation. The proteins in the supernatant as well as the intracellular proteins are analyzed by SDS-PAGE followed by autoradiography (if radiolabeled).
Microsequencing of the amino acid sequence of the amino terminus of purified protein may be used to determine the amino terminal sequence of the produced protein. [0582]

Example 8

Expression of a Polypeptide in Mammalian Cells

The polypeptide of the present invention can be expressed in a mammalian cell. A typical mammalian expression vector contains a promoter element, which mediates the initiation of transcription of mRNA, a protein coding sequence, and signals required for the termination of transcription and polyadenylation of the transcript. Additional elements include enhancers, Kozak sequences and intervening sequences flanked by donor and acceptor sites for RNA splicing. Highly efficient transcription is achieved with the early and late promoters from SV40, the long terminal repeats (LTRs) from Retroviruses, e.g., RSV, HTLVI, HIVI and the early promoter of the cytomegalovirus (CMV). However, cellular elements can also be used (e.g., the human actin promoter). [0583]
Suitable expression vectors for use in practicing the present invention include, for example, vectors such as pSVL and pMSG (Pharmacia, Uppsala, Sweden), pRSVcat (ATCC 37152), pSV2dhfr (ATCC 37146), pBC12MI (ATCC 67109), pCMVSport 2.0, and pCMVSport 3.0. Mammalian host cells that could be used include, human Hela, 293, H9 and Jurkat cells, mouse NIH3T3 and C127 cells, Cos 1, Cos 7 and CV1, quail QC1-3 cells, mouse L cells and Chinese hamster ovary (CHO) cells. [0584]
Alternatively, the polypeptide can be expressed in stable cell lines containing the polynucleotide integrated into a chromosome. The co-transfection with a selectable marker such as dhfr, gpt, neomycin, hygromycin allows the identification and isolation of the transfected cells. [0585]
The transfected gene can also be amplified to express large amounts of the encoded protein. The DHFR (dihydrofolate reductase) marker is useful in developing cell lines that carry several hundred or even several thousand copies of the gene of interest. (See, e.g., Alt, F. W., et al., J. Biol. Chem. 253:1357-1370 (1978); Hamlin, J. L. and Ma, C., Biochem. et Biophys. Acta, 1097:107-143 (1990); Page, M. J. and Sydenham, M. A., Biotechnology 9:64-68 (1991).) Another useful selection marker is the enzyme glutamine synthase (GS) (Murphy et al., Biochem J. 227:277-279 (1991), Bebbington et al., Bio/Technology 10:169-175 (1992). Using these markers, the mammalian cells are grown in selective medium and the cells with the highest resistance are selected. These cell lines contain the amplified gene(s) integrated into a chromosome. Chinese hamster ovary (CHO) and NSO cells are often used for the production of proteins. [0586]
Derivatives of the plasmid pSV2-dhfr (ATCC Accession No. 37146), the expression vectors pC4 (ATCC Accession No. 209646) and pC6 (ATCC Accession No.209647) contain the strong promoter (LTR) of the Rous Sarcoma Virus (Cullen et al., Molecular and Cellular Biology, 438-447 (March, 1985)) plus a fragment of the CMV-enhancer (Boshart et al., Cell 41:521-530 (1985).) Multiple cloning sites, e.g., with the restriction enzyme cleavage sites BamHI, XbaI and Asp718, facilitate the cloning of the gene of interest. The vectors also contain the 3′ intron, the polyadenylation and termination signal of the rat preproinsulin gene, and the mouse DHFR gene under control of the SV40 early promoter. [0587]
Specifically, the plasmid pC6, for example, is digested with appropriate restriction enzymes and then dephosphorylated using calf intestinal phosphates by procedures known in the art. The vector is then isolated from a 1% agarose gel. [0588]
A polynucleotide of the present invention is amplified according to the protocol outlined in Example 1. If the naturally occurring signal sequence is used to produce the secreted protein, the vector does not need a second signal peptide. Alternatively, if the naturally occurring signal sequence is not used, the vector can be modified to include a heterologous signal sequence. (See, e.g., WO 96/34891.) [0589]
The amplified fragment is isolated from a 1% agarose gel using a commercially available kit (“Geneclean,” BIO 101 Inc., La Jolla, Calif.). The fragment then is digested with appropriate restriction enzymes and again purified on a 1% agarose gel. [0590]
The amplified fragment is then digested with the same restriction enzyme and purified on a 1% agarose gel. The isolated fragment and the dephosphorylated vector are then ligated with T4 DNA ligase. [0591] E. coli HB-101 or XL-1 Blue cells are then transformed and bacteria are identified that contain the fragment inserted into plasmid pC6 using, for instance, restriction enzyme analysis.
Chinese hamster ovary cells lacking an active DHFR gene is used for transfection. Five μg of the expression plasmid pC6 is cotransfected with 0.5 μg of the plasmid pSVneo using lipofectin (Felgner et al., supra). The plasmid pSV2-neo contains a dominant selectable marker, the neo gene from Tn5 encoding an enzyme that confers resistance to a group of antibiotics including G418. The cells are seeded in alpha minus MEM supplemented with 1 mg/ml G418. After 2 days, the cells are trypsinized and seeded in hybridoma cloning plates (Greiner, Germany) in alpha minus MEM supplemented with 10, 25, or 50 ng/ml of metothrexate plus 1 mg/ml G418. After about 10-14 days single clones are trypsinized and then seeded in 6-well petri dishes or 10 ml flasks using different concentrations of methotrexate (50 nM, 100 nM, 200 nM, 400 nM,. 800 nM). Clones growing at the highest concentrations of methotrexate are then transferred to new 6-well plates containing even higher concentrations of methotrexate (1 μM, 2 μM, 5 μM, 10 mM, 20 mM). The same procedure is repeated until clones are obtained which grow at a concentration of 100-200 μM. Expression of the desired gene product is analyzed, for instance, by SDS-PAGE and Western blot or by reversed phase HPLC analysis. [0592]

Example 9

Protein Fusions

The polypeptides of the present invention are preferably fused to other proteins. These fusion proteins can be used for a variety of applications. For example, fusion of the present polypeptides to His-tag, HA-tag, protein A, IgG domains, and maltose binding protein facilitates purification. (See Example 5; see also EP A 394,827; Traunecker, et al., Nature 331:84-86 (1988).) Similarly, fusion to IgG-1, IgG-3, and albumin increases the halflife time in vivo. Nuclear localization signals fused to the polypeptides of the present invention can target the protein to a specific subcellular localization, while covalent heterodimer or homodimers can increase or decrease the activity of a fusion protein. Fusion proteins can also create chimeric molecules having more than one function. Finally, fusion proteins can increase solubility and/or stability of the fused protein compared to the non-fused protein. All of the types of fusion proteins described above can be made by modifying the following protocol, which outlines the fusion of a polypeptide to an IgG molecule, or the protocol described in Example 5. [0593]
Briefly, the human Fc portion of the IgG molecule can be PCR amplified, using primers that span the 5′ and 3′ ends of the sequence described below. These primers also should have convenient restriction enzyme sites that will facilitate cloning into an expression vector, preferably a mammalian expression vector. [0594]
For example, if pC4 (Accession No. 209646) is used, the human Fc portion can be ligated into the BamHI cloning site. Note that the 3′ BamHI site should be destroyed. Next, the vector containing the human Fc portion is re-restricted with BamHI, linearizing the vector, and a polynucleotide of the present invention, isolated by the PCR protocol described in Example 1, is ligated into this BamHI site. Note that the polynucleotide is cloned without a stop codon, otherwise a fusion protein will not be produced. [0595]
If the naturally occurring signal sequence is used to produce the secreted protein, pC4 does not need a second signal peptide. Alternatively, if the naturally occurring signal sequence is not used, the vector can be modified to include a heterologous signal sequence. (See, e.g., WO 96/34891.) [0596]

Human IgG Fc region:

(SEQ ID NO:1)

GGGATCCGGAGCCCAAATCTTCTGACAAAACTCACACATGCCCACCGTGC

CCAGCACCTGAATTCGAGGGTGCACCGTCAGTCTTCCTCTTCCCCCCAAA

ACCCAAGGACACCCTCATGATCTCCCGGACTCCTGAGGTCACATGCGTGG

TGGTGGACGTAAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTG

GACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTA

CAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACT

GGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCA

ACCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACC

ACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGG

TCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCAAGCGACATCGCCGTG

GAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCC

CGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGG

ACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCAT

GAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGG

TAAATGAGTGCGACGGCCGCGACTCTAGAGGAT

Example 10

Production of an Antibody from a Polypeptide

The antibodies of the present invention can be prepared by a variety of methods. (See, Current Protocols, Chapter 2.) For example, cells expressing a polypeptide of the present invention is administered to an animal to induce the production of sera containing polyclonal antibodies. In a preferred method, a preparation of the secreted protein is prepared and purified to render it substantially free of natural contaminants. Such a preparation is then introduced into an animal in order to produce polyclonal antisera of greater specific activity. [0598]
In the most preferred method, the antibodies of the present invention are monoclonal antibodies (or protein binding fragments thereof). Such monoclonal antibodies can be prepared using hybridoma technology. (Köhler et al., Nature 256:495 (1975); Köhler et al., Eur. J. Immunol. 6:511 (1976); Köhler et al., Eur. J. Immunol. 6:292 (1976); Hammerling et al., in: Monoclonal Antibodies and T-Cell Hybridomas, Elsevier, N.Y., pp. 563-681 (1981).) In general, such procedures involve immunizing an animal (preferably a mouse) with polypeptide or, more preferably, with a secreted polypeptide-expressing cell. Such cells may be cultured in any suitable tissue culture medium; however, it is preferable to culture cells in Earle's modified Eagle's medium supplemented with 10% fetal bovine serum (inactivated at about 56° C.), and supplemented with about 10 g/l of nonessential amino acids, about 1,000 U/ml of penicillin, and about 100 μg/ml of streptomycin. [0599]
The splenocytes of such mice are extracted and fused with a suitable myeloma cell line. Any suitable myeloma cell line may be employed in accordance with the present invention; however, it is preferable to employ the parent myeloma cell line (SP2O), available from the ATCC. After fusion, the resulting hybridoma cells are selectively maintained in HAT medium, and then cloned by limiting dilution as described by Wands et al. (Gastroenterology 80:225-232 (1981).) The hybridoma cells obtained through such a selection are then assayed to identify clones which secrete antibodies capable of binding the polypeptide. [0600]
Alternatively, additional antibodies capable of binding to the polypeptide can be produced in a two-step procedure using anti-idiotypic antibodies. Such a method makes use of the fact that antibodies are themselves antigens, and therefore, it is possible to obtain an antibody which binds to a second antibody. In accordance with this method, protein specific antibodies are used to immunize an animal, preferably a mouse. The splenocytes of such an animal are then used to produce hybridoma cells, and the hybridoma cells are screened to identify clones which produce an antibody whose ability to bind to the protein-specific antibody can be blocked by the polypeptide. Such antibodies comprise anti-idiotypic antibodies to the protein-specific antibody and can be used to immunize an animal to induce formation of further protein-specific antibodies. [0601]
It will be appreciated that Fab and F(ab′)2 and other fragments of the antibodies of the present invention may be used according to the methods disclosed herein. Such fragments are typically produced by proteolytic cleavage, using enzymes such as papain (to produce Fab fragments) or pepsin (to produce F(ab′)2 fragments). Alternatively, secreted protein-binding fragments can be produced through the application of recombinant DNA technology or through synthetic chemistry. [0602]
For in vivo use of antibodies in humans, it may be preferable to use “humanized” chimeric monoclonal antibodies. Such antibodies can be produced using genetic constructs derived from hybridoma cells producing the monoclonal antibodies described above. Methods for producing chimeric antibodies are known in the art. (See, for review, Morrison, Science 229:1202 (1985); Oi et al., BioTechniques 4:214 (1986); Cabilly et al., U.S. Pat. No. 4,816,567; Taniguchi et al., EP 171496; Morrison et al., EP 173494; Neuberger et al., WO 8601533; Robinson et al., WO 8702671; Boulianne et al., Nature 312:643 (1984); Neuberger et al., Nature 314:268 (1985).) [0603]

Example 11

Production Of Secreted Protein For High-Throughput Screening Assays

The following protocol produces a supernatant containing a polypeptide to be tested. This supernatant can then be used in the Screening Assays described in Examples 13-20. [0604]
First, dilute Poly-D-Lysine (644 587 Boehringer-Mannheim) stock solution (1 mg/ml in PBS) 1:20 in PBS (w/o calcium or magnesium 17-516F Biowhittaker) for a working solution of 50 ug/ml. Add 200 ul of this solution to each well (24 well plates) and incubate at RT for 20 minutes. Be sure to distribute the solution over each well (note: a 12-channel pipetter may be used with tips on every other channel). Aspirate off the Poly-D-Lysine solution and rinse with 1 ml PBS (Phosphate Buffered Saline). The PBS should remain in the well until just prior to plating the cells and plates may be poly-lysine coated in advance for up to two weeks. [0605]
Plate 293T cells (do not carry cells past P+20) at 2×10[0606] ⁵cells/well in 0.5 ml DMEM(Dulbecco's Modified Eagle Medium)(with 4.5 G/L glucose and L-glutamine (12-604F Biowhittaker))/10% heat inactivated FBS(14-503F Biowhittaker)/1×Penstrep(17-602E Biowhittaker). Let the cells grow overnight.
The next day, mix together in a sterile solution basin: 300 ul Lipofectamine (18324-012 Gibco/BRL) and 5 ml Optimem I (31985070 Gibco/BRL)/96-well plate. With a small volume multi-channel pipetter, aliquot approximately 2 ug of an expression vector containing a polynucleotide insert, produced by the methods described in Examples 8 or 9, into an appropriately labeled 96-well round bottom plate. With a multi-channel pipetter, add 50 ul of the Lipofectamine/Optimem I mixture to each well. Pipette up and down gently to mix. Incubate at RT 15-45 minutes. After about 20 minutes, use a multi-channel pipetter to add 150 ul Optimem I to each well. As a control, one plate of vector DNA lacking an insert should be transfected with each set of transfections. [0607]
Preferably, the transfection should be performed by tag-teaming the following tasks. By tag-teaming, hands on time is cut in half, and the cells do not spend too much time on PBS. First, person A aspirates off the media from four 24-well plates of cells, and then person B rinses each well with 0.5-1 ml PBS. Person A then aspirates off PBS rinse, and person B, using a12-channel pipetter with tips on every other channel, adds the 200 ul of DNA/Lipofectamine/Optimem I complex to the odd wells first, then to the even wells, to each row on the 24-well plates. Incubate at 37° C. for 6 hours. [0608]
While cells are incubating, prepare appropriate media, either 1% BSA in DMEM with 1× penstrep, or CHO-5 media (0.116.6 mg/L of CaCl2 (anhyd); 0.00130 mg/L CuSO[0609] ₄-5H₂O; 0.050 mg/L of Fe(NO₃)₃-9H₂O; 0.417 mg/L of FeSO₄-7H₂O; 311.80 mg/L of Kcl; 28.64 mg/L of MgCl₂; 48.84 mg/L of MgSO₄; 6995.50 mg/L of NaCl; 2400.0 mg/L of NaHCO₃; 62.50 mg/L of NaH₂PO₄-H₂O; 71.02 mg/L of Na₂HPO4; 0.4320 mg/L of ZnSO₄-7H₂O; 0.002 mg/L of Arachidonic Acid; 1.022 mg/L of Cholesterol; 0.070 mg/L of DL-alpha-Tocopherol-Acetate; 0.0520 mg/L of Linoleic Acid; 0.010 mg/L of Linolenic Acid; 0.010 mg/L of Myristic Acid; 0.010 mg/L of Oleic Acid; 0.010 mg/L of Palmitric Acid; 0.010 mg/L of Palmitic Acid; 100 mg/L of Pluronic F-68; 0.010 mg/L of Stearic Acid; 2.20 mg/L of Tween 80; 4551 mg/L of D-Glucose; 130.85 mg/ml of L-Alanine; 147.50 mg/ml of L-Arginine-HCL; 7.50 mg/ml of L-Asparagine-H₂O; 6.65 mg/ml of L-Aspartic Acid; 29.56 mg/ml of L-Cystine-2HCL-H₂O; 31.29 mg/ml of L-Cystine-2HCL; 7.35 mg/ml of L-Glutamic Acid; 365.0 mg/ml of L-Glutamine; 18.75 mg/ml of Glycine; 52.48 mg/ml of L-Histidine-HCL-H₂O; 106.97 mg/ml of L-Isoleucine; 111.45 mg/ml of L-Leucine; 163.75 mg/ml of L-Lysine HCL; 32.34 mg/ml of L-Methionine; 68.48 mg/ml of L-Phenylalainine; 40.0 mg/ml of L-Proline; 26.25 mg/ml of L-Serine; 101.05 mg/ml of L-Threonine; 19.22 mg/ml of L-Tryptophan; 91.79 mg/ml of L-Tryrosine-2Na-2H₂O; 99.65 mg/ml of L-Valine; 0.0035 mg/L of Biotin; 3.24 mg/L of D-Ca Pantothenate; 11.78 mg/L of Choline Chloride; 4.65 mg/L of Folic Acid; 15.60 mg/L of i-Inositol; 3.02 mg/L of Niacinamide; 3.00 mg/L of Pyridoxal HCL; 0.031 mg/L of Pyridoxine HCL; 0.319 mg/L of Riboflavin; 3.17 mg/L of Thiamine HCL; 0.365 mg/L of Thymidine; and 0.680 mg/L of Vitamin B₁₂; 25 mM of HEPES Buffer; 2.39 mg/L of Na Hypoxanthine; 0.105 mg/L of Lipoic Acid; 0.081 mg/L of Sodium Putrescine-2HCL; 55.0 mg/L of Sodium Pyruvate; 0.0067 mg/L of Sodium Selenite; 20 uM of Ethanolamine; 0.122 mg/L of Ferric Citrate; 41.70 mg/L of Methyl-B-Cyclodextrin complexed with Linoleic Acid; 33.33 mg/L of Methyl-B-Cyclodextrin complexed with Oleic Acid; and 10 mg/L of Methyl-B-Cyclodextrin complexed with Retinal) with 2 mm glutamine and 1×penstrep. (BSA (81-068-3 Bayer) 100 gm dissolved in IL DMEM for a 10% BSA stock solution). Filter the media and collect 50 ul for endotoxin assay in 15 ml polystyrene conical.
The transfection reaction is terminated, preferably by tag-teaming, at the end of the incubation period. Person A aspirates off the transfection media, while person B adds 1.5 ml appropriate media to each well. Incubate at 37° C. for 45 or 72 hours depending on the media used: 1%BSA for 45 hours or CHO-5 for 72 hours. [0610]
On day four, using a 300 ul multichannel pipetter, aliquot 600 ul in one 1 ml deep well plate and the remaining supernatant into a 2 ml deep well. The supernatants from each well can then be used in the assays described in Examples 13-20. [0611]
It is specifically understood that when activity is obtained in any of the assays described below using a supernatant, the activity originates from either the polypeptide directly (e.g., as a secreted protein) or by the polypeptide inducing expression of other proteins, which are then secreted into the supernatant. Thus, the invention further provides a method of identifying the protein in the supernatant characterized by an activity in a particular assay. [0612]

Example 12

Construction of GAS Reporter Construct

One signal transduction pathway involved in the differentiation and proliferation of cells is called the Jaks-STATs pathway. Activated proteins in the Jaks-STATs pathway bind to gamma activation site “GAS” elements or interferon-sensitive responsive element (“ISRE”), located in the promoter of many genes. The binding of a protein to these elements alter the expression of the associated gene. [0613]
GAS and ISRE elements are recognized by a class of transcription factors called Signal Transducers and Activators of Transcription, or “STATs.” There are six members of the STATs farily. Stat1 and Stat3 are present in many cell types, as is Stat2 (as response to IFN-alpha is widespread). Stat4 is more restricted and is not in many cell types though it has been found in T helper class I, cells after treatment with IL-12. Stat5 was originally called mammary growth factor, but has been found at higher concentrations in other cells including myeloid cells. It can be activated in tissue culture cells by many cytokines. [0614]
The STATs are activated to translocate from the cytoplasm to the nucleus upon tyrosine phosphorylation by a set of kinases known as the Janus Kinase (“Jaks”) family. Jaks represent a distinct family of soluble tyrosine kinases and include Tyk2, Jak1, Jak2, and Jak3. These kinases display significant sequence similarity and are generally catalytically inactive in resting cells. [0615]
The Jaks are activated by a wide range of receptors summarized in the Table below. (Adapted from review by Schidler and Darnell, Ann. Rev. Biochem. 64:621-51 (1995).) A cytokine receptor family, capable of activating Jaks, is divided into two groups: (a) Class 1 includes receptors for IL-2, IL-3, IL-4, IL-6, IL-7, IL-9, IL-11, IL-12, IL-15, Epo, PRL, GH, G-CSF, GM-CSF, LIF, CNTF, and thrombopoietin; and (b) Class 2 includes IFN-a, IFN-g, and IL-10. The Class 1 receptors share a conserved cysteine motif (a set of four conserved cysteines and one tryptophan) and a WSXWS motif (a membrane proxial region encoding Trp-Ser-Xxx-Trp-Ser (SEQ ID NO:2)). [0616]
Thus, on binding of a ligand to a receptor, Jaks are activated, which in turn activate STATs, which then translocate and bind to GAS elements. This entire process is encompassed in the Jaks-STATs signal transduction pathway. [0617]

Therefore, activation of the Jaks-STATs pathway, reflected by the binding of the GAS or the ISRE element, can be used to indicate proteins involved in the proliferation and differentiation of cells. For example, growth factors and cytokines are known to activate the Jaks-STATs pathway. (See Table below.) Thus, by using GAS elements linked to reporter molecules, activators of the Jaks-STATs pathway can be identified.



	JAKs

Ligand	tyk2	Jak1	Jak2	Jak3	STATS	GAS (elements) or ISRE

IFN family
IFN-a/B	+	+	−	−	1,2,3	ISRE
IFN-g		+	+	−	1	GAS (IRF1 > Lys6 > IFP)
Il-10	+	?	?	−	1,3
gp130 family
IL-6 (Pleiotrohic)	+	+	+	?	1,3	GAS (IRF1 > Lys6 > IFP)
Il-11 (Pleiotrohic)	?	+	?	?	1,3
OnM (Pleiotrohic)	?	+	+	?	1,3
LIF (Pleiotrohic)	?	+	+	?	1,3
CNTF (Pleiotrohic)	−/+	+	+	?	1,3
G-CSF (Pleiotrohic)	?	+	?	?	1,3
IL-12 (Pleiotrohic)	+	−	+	+	1,3
g-C family
IL-2 (lymphocytes)	−	+	−	+	1,3,5	GAS
IL-4 (lymph/myeloid)	−	+	−	+	6	GAS (IRF1 = IFP >> Ly6)(IgH)
IL-7 (lymphocytes)	−	+	−	+	5	GAS
IL-9 (lymphocytes)	−	+	−	+	5	GAS
IL-13 (lymphocyte)	−	+	?	?	6	GAS
IL-15	?	+	?	+	5	GAS
gp140 family
IL-3 (myeloid)	−	−	+	−	5	GAS (IRF1 > IFP >> Ly6)
IL-5 (myeloid)	−	−	+	−	5	GAS
GM-CSF (myeloid)	−	−	+	−	5	GAS
Growth hormone family
GH	?	−	+	−	5
PRL	?	+/−	+	−	1,3,5
EPO	?	−	+	−	5	GAS (B-CAS > IRF1 = IFP >> Ly6)
Receptor Tyrosine Kinases
EGF	?	+	+	−	1,3	GAS (IRF1)
PDGF	?	+	+	−	1,3
CSF-1	?	+	+	−	1,3	GAS (not IRF1)

To construct a synthetic GAS containing promoter element, which is used in the Biological Assays described in Examples 13-14, a PCR based strategy is employed to generate a GAS-SV40 promoter sequence. The 5′ primer contains four tandem copies of the GAS binding site found in the IRFI promoter and previously demonstrated to bind STATs upon induction with a range of cytokines (Rothman et al., Immunity 1:457-468 (1994).), although other GAS or ISRE elements can be used instead. The 5′ primer also contains 18 bp of sequence complementary to the SV40 early promoter sequence and is flanked with an XhoI site. The sequence of the 5′ primer is: [0619]

(SEQ ID NO:3)

5′:GCGCCTCGAGATTTCCCCGAAATCTAGATTTCCCCGAAATGATTTCC

CCGAAATGATTTCCCCGAAATATCTGCCATCTCAATTAG:3′
The downstream primer is complementary to the SV40 promoter and is flanked with a Hind III site:[0620]
5′:GCGGCAAGCTTTTTGCAAAGCCTAGGC:3′ (SEQ ID NO:4)

PCR amplification is performed using the SV40 promoter template present in the B-gal:promoter plasmid obtained from Clontech. The resulting PCR fragment is digested with XhoI/Hind III and subcloned into BLSK2-. (Stratagene.) Sequencing with forward and reverse primers confirms that the insert contains the following sequence:

(SEQ ID NO:5)

5′:CTCGAGATTTCCCCGAAATCTAGATTTCCCCGAAATGATTTCCCCGA

AATGATTTCCCCGAAATATCTGCCATCTCAATTAGTCAGCAACCATAGTC

CCGCCCCTAACTCCGCCCATCCCGCCCCTAACTCCGCCCAGTTCCGCCCA

TTCTCCGCCCCATGGCTGACTAATTTTTTTTATTTATGCAGAGGCCGAGG

CCGCCTCGGCCTCTGAGCTATTCCAGAAGTAGTGAGGAGGCTTTTTTGGA

GGCCTAGGCTTTTGCAAAAAGCTT:3′

With this GAS promoter element linked to the SV40 promoter, a GAS:SEAP2 reporter construct is next engineered. Here, the reporter molecule is a secreted alkaline phosphatase, or “SEAP.” Clearly, however, any reporter molecule can be instead of SEAP, in this or in any of the other Examples. Well known reporter molecules that can be used instead of SEAP include chloramphenicol acetyltransferase (CAT), luciferase, alkaline phosphatase, B-galactosidase, green fluorescent protein (GFP), or any protein detectable by an antibody. [0622]
The above sequence confirmed synthetic GAS-SV40 promoter element is subcloned into the pSEAP-Promoter vector obtained from Clontech using HindIII and XhoI, effectively replacing the SV40 promoter with the amplified GAS:SV40 promoter element, to create the GAS-SEAP vector. However, this vector does not contain a neomycin resistance gene, and therefore, is not preferred for mammalian expression systems. [0623]
Thus, in order to generate mammalian stable cell lines expressing the GAS-SEAP reporter, the GAS-SEAP cassette is removed from the GAS-SEAP vector using SalI and NotI, and inserted into a backbone vector containing the neomycin resistance gene, such as pGFP-1 (Clontech), using these restriction sites in the multiple cloning site, to create the GAS-SEAP/Neo vector. Once this vector is transfected into mammalian cells, this vector can then be used as a reporter molecule for GAS binding as described in Examples 13-14. [0624]
Other constructs can be made using the above description and replacing GAS with a different promoter sequence. For example, construction of reporter molecules containing NFK-B and EGR promoter sequences are described in Examples 15 and 16. However, many other promoters can be substituted using the protocols described in these Examples. For instance, SRE, IL-2, NFAT, or Osteocalcin promoters can be substituted, alone or in combination (e.g., GAS/NF-KB/EGR, GAS/NF-KB, Il-2/NFAT, or NF-KB/GAS). Similarly, other cell lines can be used to test reporter construct activity, such as HELA (epithelial), HUVEC (endothelial), Reh (B-cell), Saos-2 (osteoblast), HUVAC (aortic), or Cardiomyocyte. [0625]

Example 13

High-Throughput Screening Assay for T-cell Activity.

The following protocol is used to assess T-cell activity by identifying factors, such as growth factors and cytokines, that may proliferate or differentiate T-cells. T-cell activity is assessed using the GAS/SEAP/Neo construct produced in Example 12. Thus, factors that increase SEAP activity indicate the ability to activate the Jaks-STATS signal transduction pathway. The T-cell used in this assay is Jurkat T-cells (ATCC Accession No. TIB-152), although Molt-3 cells (ATCC Accession No. CRL-1552) and Molt-4 cells (ATCC Accession No. CRL-1582) cells can also be used. [0626]
Jurkat T-cells are lymphoblastic CD4+Th1 helper cells. In order to generate stable cell lines, approximately 2 million Jurkat cells are transfected with the GAS-SEAP/neo vector using DMRIE-C (Life Technologies)(transfection procedure described below). The transfected cells are seeded to a density of approximately 20,000 cells per well and transfectants resistant to 1 mg/ml genticin selected. Resistant colonies are expanded and then tested for their response to increasing concentrations of interferon gamma. The dose response of a selected clone is demonstrated. [0627]
Specifically, the following protocol will yield sufficient cells for 75 wells containing 200 ul of cells. Thus, it is either scaled up, or performed in multiple to generate sufficient cells for multiple 96 well plates. Jurkat cells are maintained in RPMI +10% serum with 1% Pen-Strep. Combine 2.5 mls of OPTI-MEM (Life Technologies) with 10 ug of plasmid DNA in a T25 flask. Add 2.5 ml OPTI-MEM containing 50 ul of DMRIE-C and incubate at room temperature for 15-45 mins. [0628]
During the incubation period, count cell concentration, spin down the required number of cells (10[0629] ⁷per transfection), and resuspend in OPTI-MEM to a final concentration of 10⁷cells/ml. Then add 1 ml of 1×10⁷cells in OPTI-MEM to T25 flask and incubate at 37° C. for 6 hrs. After the incubation, add 10 ml of RPMI+15% serum.
The Jurkat:GAS-SEAP stable reporter lines are maintained in RPMI+10% serum, 1 mg/ml Genticin, and 1% Pen-Strep. These cells are treated with supernatants containing a polypeptide as produced by the protocol described in Example 11. [0630]
On the day of treatment with the supernatant, the cells should be washed and resuspended in fresh RPMI+10% serum to a density of 500,000 cells per ml. The exact number of cells required will depend on the number of supernatants being screened. For one 96 well plate, approximately 10 million cells (for 10 plates, 100 million cells) are required. [0631]
Transfer the cells to a triangular reservoir boat, in order to dispense the cells into a 96 well dish, using a 12 channel pipette. Using a 12 channel pipette, transfer 200 ul of cells into each well (therefore adding 100,000 cells per well). [0632]
After all the plates have been seeded, 50 ul of the supernatants are transferred directly from the 96 well plate containing the supernatants into each well using a 12 channel pipette. In addition, a dose of exogenous interferon gamma (0.1, 1.0, 10 ng) is added to wells H9, H10, and H11 to serve as additional positive controls for the assay. [0633]
The 96 well dishes containing Jurkat cells treated with supernatants are placed in an incubator for 48 hrs (note: this time is variable between 48-72 hrs). 35 ul samples from each well are then transferred to an opaque 96 well plate using a 12 channel pipette. The opaque plates should be covered (using sellophene covers) and stored at −20° C. until SEAP assays are performed according to Example 17. The plates containing the remaining treated cells are placed at 4° C. and serve as a source of material for repeating the assay on a specific well if desired. [0634]
As a positive control, 100 Unit/ml interferon gamma can be used which is known to activate Jurkat T cells. Over 30 fold induction is typically observed in the positive control wells. [0635]

Example 14

High-Throughput Screening Assay Identifying Myeloid Activity

The following protocol is used to assess myeloid activity by identifying factors, such as growth factors and cytokines, that may proliferate or differentiate myeloid cells. Myeloid cell activity is assessed using the GAS/SEAP/Neo construct produced in Example 12. Thus, factors that increase SEAP activity indicate the ability to activate the Jaks-STATS signal transduction pathway. The myeloid cell used in this assay is U937, a pre-monocyte cell line, although TF-1, HL60, or KG1 can be used. [0636]
To transiently transfect U937 cells with the GAS/SEAP/Neo construct produced in Example 12, a DEAE-Dextran method (Kharbanda et. al., 1994, Cell Growth & Differentiation, 5:259-265) is used. First, harvest 2×10e[0637] ⁷U937 cells and wash with PBS. The U937 cells are usually grown in RPMI 1640 medium containing 10% heat-inactivated fetal bovine serum (FBS) supplemented with 100 units/ml penicillin and 100 mg/ml streptomycin.
Next, suspend the cells in 1 ml of 20 mM Tris-HCl (pH 7.4) buffer containing 0.5 mg/ml DEAE-Dextran, 8 ug GAS-SEAP2 plasmid DNA, 140 mM NaCl, 5 mM KCl, 375 uM Na[0638] ₂HPO₄.7H₂O, 1 mM MgCl₂, and 675 uM CaCl₂. Incubate at 37° C. for 45 min.
Wash the cells with RPMI 1640 medium containing 10% FBS and then resuspend in 10 ml complete medium and incubate at 37° C. for 36 hr. [0639]
The GAS-SEAP/U937 stable cells are obtained by growing the cells in 400 ug/ml G418. The G418-free medium is used for routine growth but every one to two months, the cells should be re-grown in 400 ug/ml G418 for couple of passages. [0640]
These cells are tested by harvesting 1×10[0641] ⁸cells (this is enough for ten 96-well plates assay) and wash with PBS. Suspend the cells in 200 ml above described growth medium, with a final density of 5×10⁵cells/ml. Plate 200 ul cells per well in the 96-well plate (or 1×10⁵cells/well).
Add 50 ul of the supernatant prepared by the protocol described in Example 11. Incubate at 37° C. for 48 to 72 hr. As a positive control, 100 Unit/ml interferon gamma can be used which is known to activate U937 cells. Over 30 fold induction is typically observed in the positive control wells. SEAP assay the supernatant according to the protocol described in Example 17. [0642]

Example 15

High-Throughput Screening Assay Identifying Neuronal Activity.

When cells undergo differentiation and proliferation, a group of genes are activated through many different signal transduction pathways. One of these genes, EGR1 (early growth response gene 1), is induced in various tissues and cell types upon activation. The promoter of EGR1 is responsible for such induction. Using the EGR1 promoter linked to reporter molecules, activation of cells can be assessed. [0643]
Particularly, the following protocol is used to assess neuronal activity in PC12 cell lines. PC12 cells (rat phenochromocytoma cells) are known to proliferate and/or differentiate by activation with a number of mitogens, such as TPA (tetradecanoyl phorbol acetate), NGF (nerve growth factor), and EGF (epidermal growth factor). The EGR1 gene expression is activated during this treatment. Thus, by stably transfecting PC12 cells with a construct containing an EGR promoter linked to SEAP reporter, activation of PC12 cells can be assessed. [0644]
The EGR/SEAP reporter construct can be assembled by the following protocol. The EGR-1 promoter sequence (−633 to +1)(Sakamoto K et al., Oncogene 6:867-871 (1991)) can be PCR amplified from human genomic DNA using the following primers: [0645]

5′ GCGCTCGAGGGATGACAGCGATAGAACCC (SEQ ID NO:6)

CGG-3′

5′ GCGAAGCTTCGCGACTCCCCGGATCCGCCTC-3′ (SEQ ID NO:7)
Using the GAS:SEAP/Neo vector produced in Example 12, EGR1 amplified product can then be inserted into this vector. Linearize the GAS:SEAP/Neo vector using restriction enzymes XhoI/HindIII, removing the GAS/SV40 stuffer. Restrict the EGR1 amplified product with these same enzymes. Ligate the vector and the EGR1 promoter. [0646]
To prepare 96 well-plates for cell culture, two mls of a coating solution (1:30 dilution of collagen type I (Upstate Biotech Inc. Cat#08-115) in 30% ethanol (filter sterilized)) is added per one 10 cm plate or 50 ml per well of the 96-well plate, and allowed to air dry for 2 hr. [0647]
PC12 cells are routinely grown in RPMI-1640 medium (Bio Whittaker) containing 10% horse serum (JRH BIOSCIENCES, Cat. # 12449-78P), 5% heat-inactivated fetal bovine serum (FBS) supplemented with 100 units/ml penicillin and 100 ug/ml streptomycin on a precoated 10 cm tissue culture dish. One to four split is done every three to four days. Cells are removed from the plates by scraping and resuspended with pipetting up and down for more than 15 times. [0648]
Transfect the EGR/SEAP/Neo construct into PC12 using the Lipofectamine protocol described in Example 11. EGR-SEAP/PC 12 stable cells are obtained by growing the cells in 300 ug/ml G418. The G418-free medium is used for routine growth but every one to two months, the cells should be re-grown in 300 ug/ml G418 for couple of passages. [0649]
To assay for neuronal activity, a 10 cm plate with cells around 70 to 80% confluent is screened by removing the old medium. Wash the cells once with PBS (Phosphate buffered saline). Then starve the cells in low serum medium (RPMI-1640 containing 1% horse serum and 0.5% FBS with antibiotics) overnight. [0650]
The next morning, remove the medium and wash the cells with PBS. Scrape off the cells from the plate, suspend the cells well in 2 ml low serum medium. Count the cell number and add more low serum medium to reach final cell density as 5×10[0651] ⁵cells/ml.
Add 200 ul of the cell suspension to each well of 96-well plate (equivalent to 1×10[0652] ⁵cells/well). Add 50 ul supernatant produced by Example 11, 37° C. for 48 to 72 hr. As a positive control, a growth factor known to activate PC12 cells through EGR can be used, such as 50 ng/ul of Neuronal Growth Factor (NGF). Over fifty-fold induction of SEAP is typically seen in the positive control wells. SEAP assay the supernatant according to Example 17.

Example 16

High-Throughput Screening Assay for T-cell Activity

NF-κB (Nuclear Factor κB) is a transcription factor activated by a wide variety of agents including the inflammatory cytokines IL-1 and TNF, CD30 and CD40, lymphotoxin-alpha and lymphotoxin-beta, by exposure to LPS or thrombin, and by expression of certain viral gene products. As a transcription factor, NF-κB regulates the expression of genes involved in immune cell activation, control of apoptosis (NF-κB appears to shield cells from apoptosis), B and T-cell development, anti-viral and antimicrobial responses, and multiple stress responses. [0653]
In non-stimulated conditions, NF-κB is retained in the cytoplasm with I-κB (Inhibitor κB). However, upon stimulation, I-κB is phosphorylated and degraded, causing NF-κB to shuttle to the nucleus, thereby activating transcription of target genes. Target genes activated by NF-κB include IL-2, IL-6, GM-CSF, ICAM-1 and class 1 MHC. [0654]
Due to its central role and ability to respond to a range of stimuli, reporter constructs utilizing the NF-κB promoter element are used to screen the supernatants produced in Example 11. Activators or inhibitors of NF-κB would be useful in treating diseases. For example, inhibitors of NF-κB could be used to treat those diseases related to the acute or chronic activation of NF-κB, such as rheumatoid arthritis. [0655]
To construct a vector containing the NF-κB promoter element, a PCR based strategy is employed. The upstream primer contains four tandem copies of the NF-κB binding site[0656]
(GGGGACTTTCCC) (SEQ ID NO:8),
18 bp of sequence complementary to the 5′ end of the SV40 early promoter sequence, and is flanked with an XhoI site: [0657]

(SEQ ID NO:9)

5′:GCGGCCTCGAGGGGACTTTCCCGGGGACTTTCCGGGGACTTTCC

GGGACTTTCCATCCTGCCATCTCAATTAG:3′
The downstream primer is complementary to the 3′ end of the SV40 promoter and is flanked with a Hind m site:[0658]
5′:GCGGCAAGCTTTTTGCAAAGCCTAGGC:3′ (SEQ ID NO:4)

PCR amplification is performed using the SV40 promoter template present in the pB-gal:promoter plasmid obtained from Clontech. The resulting PCR fragment is digested with XhoI and Hind III and subcloned into BLSK2-. (Stratagene) Sequencing with the T7 and T3 primers confirms the insert contains the following sequence:

(SEQ ID NO:10)

5′:CTCGAGGGGACTTTCCCGGGGACTTTCCGGGGACTTTCCGGGACTTT

CCATCTGCCATCTCAATTAGTCAGCAACCATAGTCCCGCCCCTAACTCCG

CCCATCCCGCCCCTAACTCCGCCCAGTTCCGCCCATTCTCCGCCCCATGG

CTGACTAATTTTTTTTATTTATGCAGAGGCCGAGGCCGCCTCGGCCTCTG

AGCTATTCCAGAAGTAGTGAGGAGGCTTTTTTGGAGGCCTAGGCTTTTGC

AAAAAGCTT:3′

Next, replace the SV40 minimal promoter element present in the pSEAP2-promoter plasmid (Clontech) with this NF-κB/SV40 fragment using XhoI and HindIII. However, this vector does not contain a neomycin resistance gene, and therefore, is not preferred for mammalian expression systems. [0660]
In order to generate stable mammalian cell lines, the NF-κB/SV40/SEAP cassette is removed from the above NF-κB/SEAP vector using restriction enzymes SalI and NotI, and inserted into a vector containing neomycin resistance. Particularly, the NF-κB/SV40/SEAP cassette was inserted into pGFP-1 (Clontech), replacing the GFP gene, after restricting pGFP-1 with SalI and NotI. [0661]
Once NF-κB/SV40/SEAP/Neo vector is created, stable Jurkat T-cells are created and maintained according to the protocol described in Example 13. Similarly, the method for assaying supernatants with these stable Jurkat T-cells is also described in Example 13. As a positive control, exogenous TNF alpha (0.1,1, 10 ng) is added to wells H9, H10, and H11, with a 5-10 fold activation typically observed. [0662]

Example 17

Assay for SEAP Activity

As a reporter molecule for the assays described in Examples 13-16, SEAP activity is assayed using the Tropix Phospho-light Kit (Cat. BP400) according to the following general procedure. The Tropix Phospho-light Kit supplies the Dilution, Assay, and Reaction Buffers used below. [0663]
Prime a dispenser with the 2.5×Dilution Buffer and dispense 15 μl of 2.5×dilution buffer into Optiplates containing 35 μl of a supernatant. Seal the plates with a plastic sealer and incubate at 65° C. for 30 min. Separate the Optiplates to avoid uneven heating. [0664]
Cool the samples to room temperature for 15 minutes. Empty the dispenser and prime with the Assay Buffer. Add 50 μl Assay Buffer and incubate at room temperature 5 min. Empty the dispenser and prime with the Reaction Buffer (see the table below). Add 50 μl Reaction Buffer and incubate at room temperature for 20 minutes. Since the intensity of the chemiluminescent signal is time dependent, and it takes about 10 minutes to read 5 plates on luminometer, one should treat 5 plates at each time and start the second set 10 minutes later. [0665]

Read the relative light unit in the luminometer. Set H12 as blank, and print the results. An increase in chemiluminescence indicates reporter activity.

Reaction Buffer Formulation:

# of plates	Rxn buffer diluent (ml)	CSPD (ml)

10	60	3
11	65	3.25
12	70	3.5
13	75	3.75
14	80	4
15	85	4.25
16	90	4.5
17	95	4.75
18	100	5
19	105	5.25
20	110	5.5
21	115	5.75
22	120	6
23	125	6.25
24	130	6.5
25	135	6.75
26	140	7
27	145	7.25
28	150	7.5
29	155	7.75
30	160	8
31	165	8.25
32	170	8.5
33	175	8.75
34	180	9
35	185	9.25
36	190	9.5
37	195	9.75
38	200	10
39	205	10.25
40	210	10.5
41	215	10.75
42	220	11
43	225	11.25
44	230	11.5
45	235	11.75
46	240	12
47	245	12.25
48	250	12.5
49	255	12.75
50	260	13

Example 18

High-Throughput Screening Assay Identifying Changes in Small Molecule Concentration and Membrane Permeability

Binding of a ligand to a receptor is known to alter intracellular levels of small molecules, such as calcium, potassium, sodium, and pH, as well as alter membrane potential. These alterations can be measured in an assay to identify supernatants which bind to receptors of a particular cell. Although the following protocol describes an assay for calcium, this protocol can easily be modified to detect changes in potassium, sodium, pH, membrane potential, or any other small molecule which is detectable by a fluorescent probe. [0667]
The following assay uses Fluorometric Imaging Plate Reader (“FLIPR”) to measure changes in fluorescent molecules (Molecular Probes) that bind small molecules. Clearly, any fluorescent molecule detecting a small molecule can be used instead of the calcium fluorescent molecule, fluo-3, used here. [0668]
For adherent cells, seed the cells at 10,000-20,000 cells/well in a Co-star black 96-well plate with clear bottom. The plate is incubated in a CO[0669] ₂incubator for 20 hours. The adherent cells are washed two times in Biotek washer with 200 ul of HBSS (Hank's Balanced Salt Solution) leaving 100 ul of buffer after the final wash.
A stock solution of 1 mg/ml fluo-3 is made in 10% pluronic acid DMSO. To load the cells with fluo-3, 50 ul of 12 ug/ml fluo-3 is added to each well. The plate is incubated at 37° C. in a CO[0670] ₂incubator for 60 min. The plate is washed four times in the Biotek washer with HBSS leaving 100 ul of buffer.
For non-adherent cells, the cells are spun down from culture media. Cells are re-suspended to 2-5×10[0671] ⁶cells/ml with HBSS in a 50-ml conical tube. 4 ul of 1 mg/ml fluo-3 solution in 10% pluronic acid DMSO is added to each ml of cell suspension. The tube is then placed in a 37° C. water bath for 30-60 min. The cells are washed twice with HBSS, resuspended to 1×10⁶cells/ml, and dispensed into a microplate, 100 ul/well. The plate is centrifuged at 1000 rpm for 5 min. The plate is then washed once in Denley CellWash with 200 ul, followed by an aspiration step to 100 ul final volume.
For a non-cell based assay, each well contains a fluorescent molecule, such as fluo-3. The supernatant is added to the well, and a change in fluorescence is detected. [0672]
To measure the fluorescence of intracellular calcium, the FLIPR is set for the following parameters: (1) System gain is 300-800 mW; (2) Exposure time is 0.4 second; (3) Camera F/stop is F/2; (4) Excitation is 488 nm; (5) Emission is 530 nm; and (6) Sample addition is 50 ul. Increased emission at 530 nm indicates an extracellular signaling event which has resulted in an increase in the intracellular Ca[0673] ⁺⁺ concentration.

Example 19

High-Throughput Screening Assay Identifying Tyrosine Kinase Activity

The Protein Tyrosine Kinases (PTK) represent a diverse group of transmembrane and cytoplasmic kinases. Within the Receptor Protein Tyrosine Kinase RPTK) group are receptors for a range of mitogenic and metabolic growth factors including the PDGF, FGF, EGF, NGF, HGF and Insulin receptor subfamilies. In addition there are a large family of RPTKs for which the corresponding ligand is unknown. Ligands for RPTKs include mainly secreted small proteins, but also membrane-bound and extracellular matrix proteins. [0674]
Activation of RPTK by ligands involves ligand-mediated receptor dimerization, resulting in transphosphorylation of the receptor subunits and activation of the cytoplasmic tyrosine kinases. The cytoplasmic tyrosine kinases include receptor associated tyrosine kinases of the src-family (e.g., src, yes, Ick, lyn, fyn) and non-receptor linked and cytosolic protein tyrosine kinases, such as the Jak family, members of which mediate signal transduction triggered by the cytokine superfamily of receptors (e.g., the Interleukins, Interferons, GM-CSF, and Leptin). [0675]
Because of the wide range of known factors capable of stimulating tyrosine kinase activity, the identification of novel human secreted proteins capable of activating tyrosine kinase signal transduction pathways are of interest. Therefore, the following protocol is designed to identify those novel human secreted proteins capable of activating the tyrosine kinase signal transduction pathways. [0676]
Seed target cells (e.g., primary keratinocytes) at a density of approximately 25,000 cells per well in a 96 well Loprodyne Silent Screen Plates purchased from Nalge Nunc (Naperville, Ill.). The plates are sterilized with two 30 minute rinses with 100% ethanol, rinsed with water and dried overnight. Some plates are coated for 2 hr with 100 ml of cell culture grade type I collagen (50 mg/ml), gelatin (2%) or polylysine (50 mg/ml), all of which can be purchased from Sigma Chemicals (St. Louis, Mo.) or 10% Matrigel purchased from Becton Dickinson (Bedford, Mass.), or calf serum, rinsed with PBS and stored at 4° C. Cell growth on these plates is assayed by seeding 5,000 cells/well in growth medium and indirect quantitation of cell number through use of alamarBlue as described by the manufacturer Alamar Biosciences, Inc. (Sacramento, Calif.) after 48 hr. Falcon plate covers #3071 from Becton Dickinson (Bedford, Mass.) are used to cover the Loprodyne Silent Screen Plates. Falcon Microtest III cell culture plates can also be used in some proliferation experiments. [0677]
To prepare extracts, A431 cells are seeded onto the nylon membranes of Loprodyne plates (20,000/200 ml/well) and cultured overnight in complete medium. Cells are quiesced by incubation in serum-free basal medium for 24 hr. After 5-20 minutes treatment with EGF (60 ng/ml) or 50 ul of the supernatant produced in Example 11, the medium was removed and 100 ml of extraction buffer ((20 mM HEPES pH 7.5, 0.15 M NaCl, 1% Triton X-100, 0.1% SDS, 2 mM Na3VO4, 2 mM Na4P2O7 and a cocktail of protease inhibitors (# 1836170) obtained from Boehringer Mannheim (Indianapolis, Ind.) is added to each well and the plate is shaken on a rotating shaker for 5 minutes at 4° C. The plate is then placed in a vacuum transfer manifold and the extract filtered through the 0.45 mm membrane bottoms of each well using house vacuum. Extracts are collected in a 96-well catch/assay plate in the bottom of the vacuum manifold and immediately placed on ice. To obtain extracts clarified by centrifugation, the content of each well, after detergent solubilization for 5 minutes, is removed and centrifuged for 15 minutes at 4° C. at 16,000×g. [0678]
Test the filtered extracts for levels of tyrosine kinase activity. Although many methods of detecting tyrosine kinase activity are known, one method is described here. [0679]
Generally, the tyrosine kinase activity of a supernatant is evaluated by determining its ability to phosphorylate a tyrosine residue on a specific substrate (a biotinylated peptide). Biotinylated peptides that can be used for this purpose include PSK1 (corresponding to amino acids 6-20 of the cell division kinase cdc2-p34) and PSK2 (corresponding to amino acids 1-17 of gastrin). Both peptides are substrates for a range of tyrosine kinases and are available from Boehringer Mannheim. [0680]
The tyrosine kinase reaction is set up by adding the following components in order. First, add 10 ul of 5 uM Biotinylated Peptide, then 10 ul ATP/Mg[0681] ₂₊ (5 mM ATP/50 mM MgCl₂), then 10 ul of 5x Assay, Buffer (40 mM imidazole hydrochloride, pH7.3, 40 mM beta-glycerophosphate, 1 mM EGTA, 100 nM MgCl₂, 5 mM MnCl₂, 0.5 mg/ml BSA), then 5 ul of Sodium Vanadate(1 mM), and then 5 ul of water. Mix the components gently and preincubate the reaction mix at 30° C. for 2 min. Initial the reaction by adding 10 ul of the control enzyme or the filtered supernatant.
The tyrosine kinase assay reaction is then terminated by adding 10 ul of 120 mm EDTA and place the reactions on ice. [0682]
Tyrosine kinase activity is determined by transferring 50 ul aliquot of reaction mixture to a microtiter plate (MTP) module and incubating at 37° C. for 20 min. This allows the streptavadin coated 96 well plate to associate with the biotinylated peptide. Wash the MTP module with 300 ul/well of PBS four times. Next add 75 ul of anti-phospotyrosine antibody conjugated to horse radish peroxidase(anti-P-Tyr-POD (0.5 u/ml)) to each well and incubate at 37° C. for one hour. Wash the well as above. [0683]
Next add 100 ul of peroxidase substrate solution (Boehringer Mannheim) and incubate at room temperature for at least 5 mins (up to 30 min). Measure the absorbance of the sample at 405 nm by using ELISA reader. The level of bound peroxidase activity is quantitated using an ELISA reader and reflects the level of tyrosine kinase activity. [0684]

Example 20

High-Throughput Screening Assay Identifying Phosphorylation Activity

As a potential alternative and/or compliment to the assay of protein tyrosine kinase activity described in Example 19, an assay which detects activation (phosphorylation) of major intracellular signal transduction intermediates can also be used. For example, as described below one particular assay can detect tyrosine phosphorylation of the Erk-1 and Erk-2 kinases. However, phosphorylation of other molecules, such as Raf, JNK, p38 MAP, Map kinase kinase (MEK), MEK kinase, Src, Muscle specific kinase (MuSK), IRAK, Tec, and Janus, as well as any other phosphoserine, phosphotyrosine, or phosphothreonine molecule, can be detected by substituting these molecules for Erk-1 or Erk-2 in the following assay. [0685]
Specifically, assay plates are made by coating the wells of a 96-well ELISA plate with 0.1 ml of protein G (1 ug/ml) for 2 hr at room temp, (RT). The plates are then rinsed with PBS and blocked with 3% BSA/PBS for 1 hr at RT. The protein G plates are then treated with 2 commercial monoclonal antibodies (100 ng/well) against Erk-1 and Erk-2 (1 hr at RT) (Santa Cruz Biotechnology). (To detect other molecules, this step can easily be modified by substituting a monoclonal antibody detecting any of the above described molecules.) After 3-5 rinses with PBS, the plates are stored at 4° C. until use. [0686]
A431 cells are seeded at 20,000/well in a 96-well Loprodyne filterplate and cultured overnight in growth medium. The cells are then starved for 48 hr in basal medium (DMEM) and then treated with EGF (6 ng/well) or 50 ul of the supernatants obtained in Example 11 for 5-20 minutes. The cells are then solubilized and extracts filtered directly into the assay plate. [0687]
After incubation with the extract for 1 hr at RT, the wells are again rinsed. As a positive control, a commercial preparation of MAP kinase (10 ng/well) is used in place of A431 extract. Plates are then treated with a commercial polyclonal (rabbit) antibody (1 ug/ml) which specifically recognizes the phosphorylated epitope of the Erk-1 and Erk-2 kinases (1 hr at RT). This antibody is biotinylated by standard procedures. The bound polyclonal antibody is then quantitated by successive incubations with Europium-streptavidin and Europium fluorescence enhancing reagent in the Wallac DELFIA instrument (time-resolved fluorescence). An increased fluorescent signal over background indicates a phosphorylation. [0688]

Example 21

Method of Determining Alterations in a Gene Corresponding to a Polynucleotide

RNA isolated from entire families or individual patients presenting with a phenotype of interest (such as a disease) is be isolated. cDNA is then generated from these RNA samples using protocols known in the art. (See, Sambrook.) The cDNA is then used as a template for PCR, employing primers surrounding regions of interest in SEQ ID NO:X. Suggested PCR conditions consist of 35 cycles at 95° C. for 30 seconds; 60-120 seconds at 52-58° C.; and 60-120 seconds at 70° C., using buffer solutions described in Sidransky, D., et al., Science 252:706 (1991). [0689]
PCR products are then sequenced using primers labeled at their 5′ end with T4 polynucleotide kinase, employing SequiTherm Polymerase. (Epicentre Technologies). The intron-exon borders of selected exons is also determined and genomic PCR products analyzed to confirm the results. PCR products harboring suspected mutations is then cloned and sequenced to validate the results of the direct sequencing. [0690]
PCR products is cloned into T-tailed vectors as described in Holton, T. A. and Graham, M. W., Nucleic Acids Research, 19:1156 (1991) and sequenced with T7 polymerase (United States Biochemical). Affected individuals are identified by mutations not present in unaffected individuals. [0691]
Genomic rearrangements are also observed as a method of determining alterations in a gene corresponding to a polynucleotide. Genomic clones isolated according to Example 2 are nick-translated with digoxigenindeoxy-uridine 5′-triphosphate (Boehringer Mannheim), and FISH performed as described in Johnson, Cg. et al., Methods Cell Biol. 35:73-99 (1991). Hybridization with the labeled probe is carried out using a vast excess of human cot-1 DNA for specific hybridization to the corresponding genomic locus. [0692]
Chromosomes are counterstained with 4,6-diamino-2-phenylidole and propidium iodide, producing a combination of C- and R-bands. Aligned images for precise mapping are obtained using a triple-band filter set (Chroma Technology, Brattleboro, Vt.) in combination with a cooled charge-coupled device camera (Photometrics, Tucson, Ariz.) and variable excitation wavelength filters. (Johnson, Cv. et al., Genet. Anal. Tech. Appl., 8:75 (1991).) Image collection, analysis and chromosomal fractional length measurements are performed using the ISee Graphical Program System. (Inovision Corporation, Durham, N.C.) Chromosome alterations of the genomic region hybridized by the probe are identified as insertions, deletions, and translocations. These alterations are used as a diagnostic marker for an associated disease. [0693]

Example 22

Method of Detecting Abnormal Levels of a Polypeptide in a Biological Sample

A polypeptide of the present invention can be detected in a biological sample, and if an increased or decreased level of the polypeptide is detected, this polypeptide is a marker for a particular phenotype. Methods of detection are numerous, and thus, it is understood that one skilled in the art can modify the following assay to fit their particular needs. [0694]
For example, antibody-sandwich ELISAs are used to detect polypeptides in a sample, preferably a biological sample. Wells of a microtiter plate are coated with specific antibodies, at a final concentration of 0.2 to 10 ug/ml. The antibodies are either monoclonal or polyclonal and are produced by the method described in Example 10. The wells are blocked so that non-specific binding of the polypeptide to the well is reduced. [0695]
The coated wells are then incubated for >2 hours at RT with a sample containing the polypeptide. Preferably, serial dilutions of the sample should be used to validate results. The plates are then washed three times with deionized or distilled water to remove unbounded polypeptide. [0696]
Next, 50 ul of specific antibody-alkaline phosphatase conjugate, at a concentration of 25-400 ng, is added and incubated for 2 hours at room temperature. The plates are again washed three times with deionized or distilled water to remove unbounded conjugate. [0697]
Add 75 ul of 4-methylumbelliferyl phosphate (MUP) or p-nitrophenyl phosphate (NPP) substrate solution to each well and incubate 1 hour at room temperature. Measure the reaction by a microtiter plate reader. Prepare a standard curve, using serial dilutions of a control sample, and plot polypeptide concentration on the X-axis (log scale) and fluorescence or absorbance of the Y-axis (linear scale). Interpolate the concentration of the polypeptide in the sample using the standard curve. [0698]

Example 23

Formulating a Polypeptide

The secreted polypeptide composition will be formulated and dosed in a fashion consistent with good medical practice, taking into account the clinical condition of the individual patient (especially the side effects of treatment with the secreted polypeptide alone), the site of delivery, the method of administration, the scheduling of administration, and other factors known to practitioners. The “effective amount” for purposes herein is thus determined by such considerations. [0699]
As a general proposition, the total pharmaceutically effective amount of secreted polypeptide administered parenterally per dose will be in the range of about 1 ug/kg/day to 10 mg/kg/day of patient body weight, although, as noted above, this will be subject to therapeutic discretion. More preferably, this dose is at least 0.01 mg/kg/day, and most preferably for humans between about 0.01 and 1 mg/kg/day for the hormone. If given continuously, the secreted polypeptide is typically administered at a dose rate of about 1 μg/kg/hour to about 50 μg/kg/hour, either by 1-4 injections per day or by continuous subcutaneous infusions, for example, using a mini-pump. An intravenous bag solution may also be employed. The length of treatment needed to observe chances and the interval following treatment for responses to occur appears to vary depending on the desired effect. [0700]
Pharmaceutical compositions containing the secreted protein of the invention are administered orally, rectally, parenterally, intracistemally, intravaginally, intraperitoneally, topically (as by powders, ointments, gels, drops or transdermal patch), bucally, or as an oral or nasal spray. “Pharmaceutically acceptable carrier” refers to a non-toxic solid, semisolid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type. The term “parenteral” as used herein refers to modes of administration which include intravenous, intramuscular, intraperitoneal, intrastemal, subcutaneous and intraarticular injection and infusion. [0701]
The secreted polypeptide is also suitably administered by sustained-release systems. Suitable examples of sustained-release compositions include semi-permeable polymer matrices in the form of shaped articles, e.g., films, or mirocapsules. Sustained-release matrices include polylactides (U.S. Pat. No. 3,773,919, EP 58,481), copolymers of L-glutamic acid and gamma-ethyl-L-glutamate (Sidman, U. et al., Biopolymers 22:547-556 (1983)), poly (2-hydroxyethyl methacrylate) (R. Langer et al., J. Biomed. Mater. Res. 15:167-277 (1981), and R. Langer, Chem. Tech. 12:98-105 (1982)), ethylene vinyl acetate (R. Langer et al.) or poly-D-(-)-3-hydroxybutyric acid (EP 133,988). Sustained-release compositions also include liposomally entrapped polypeptides. Liposomes containing the secreted polypeptide are prepared by methods known per se: DE 3,218,121; Epstein et al., Proc. Natl. Acad. Sci. USA 82:3688-3692 (1985); Hwang et al., Proc. Natl. Acad. Sci. USA 77:4030-4034 (1980); EP 52,322; EP 36,676; EP 88,046; EP 143,949; EP 142,641; Japanese Pat. Appl. 83-118008; U.S. Pat. Nos. 4,485,045 and 4,544,545; and EP 102,324. Ordinarily, the liposomes are of the small (about 200-800 Angstroms) unilamellar type in which the lipid content is greater than about 30 mol. percent cholesterol, the selected proportion being adjusted for the optimal secreted polypeptide therapy. [0702]
For parenteral administration, in one embodiment, the secreted polypeptide is formulated generally by mixing it at the desired degree of purity, in a unit dosage injectable form (solution, suspension, or emulsion), with a pharmaceutically acceptable carrier, i.e., one that is non-toxic to recipients at the dosages and concentrations employed and is compatible with other ingredients of the formulation. For example, the formulation preferably does not include oxidizing agents and other compounds that are known to be deleterious to polypeptides. [0703]
Generally, the formulations are prepared by contacting the polypeptide uniformly and intimately with liquid carriers or finely divided solid carriers or both. Then, if necessary, the product is shaped into the desired formulation. Preferably the carrier is a parenteral carrier, more preferably a solution that is isotonic with the blood of the recipient. Examples of such carrier vehicles include water, saline, Ringer's solution, and dextrose solution. Non-aqueous vehicles such as fixed oils and ethyl oleate are also useful herein, as well as liposomes. [0704]
The carrier suitably contains minor amounts of additives such as substances that enhance isotonicity and chemical stability. Such materials are non-toxic to recipients at the dosages and concentrations employed, and include buffers such as phosphate, citrate, succinate, acetic acid, and other organic acids or their salts; antioxidants such as ascorbic acid; low molecular weight (less than about ten residues) polypeptides, e.g., polyarginine or tripeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids, such as glycine, glutamic acid, aspartic acid, or arginine; monosaccharides, disaccharides, and other carbohydrates including cellulose or its derivatives, glucose, manose, or dextrins; chelating agents such as EDTA; sugar alcohols such as mannitol or sorbitol; counterions such as sodium; and/or nonionic surfactants such as polysorbates, poloxamers, or PEG. [0705]
The secreted polypeptide is typically formulated in such vehicles at a concentration of about 0.1 mg/ml to 100 mg/ml, preferably 1-10 mg/ml, at a pH of about 3 to 8. It will be understood that the use of certain of the foregoing excipients, carriers, or stabilizers will result in the formation of polypeptide salts. [0706]
Any polypeptide to be used for therapeutic administration can be sterile. Sterility is readily accomplished by filtration through sterile filtration membranes (e.g., 0.2 micron membranes). Therapeutic polypeptide compositions generally are placed into a container having a sterile access port, for example, an intravenous solution bag or vial having a stopper pierceable by a hypodermic injection needle. [0707]
Polypeptides ordinarily will be stored in unit or multi-dose containers, for example, sealed ampoules or vials, as an aqueous solution or as a lyophilized formulation for reconstitution. As an example of a lyophilized formulation, 10-ml vials are filled with 5 ml of sterile-filtered 1% (w/v) aqueous polypeptide solution, and the resulting mixture is lyophilized. The infusion solution is prepared by reconstituting the lyophilized polypeptide using bacteriostatic Water-for-Injection. [0708]
The invention also provides a pharmaceutical pack or kit comprising one or more containers filled with one or more of the ingredients of the pharmaceutical compositions of the invention. Associated with such container(s) can be a notice in the form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals or biological products, which notice reflects approval by the agency of manufacture, use or sale for human administration. In addition, the polypeptides of the present invention may be employed in conjunction with other therapeutic compounds. [0709]

Example 24

Method of Treating Decreased Levels of the Polypeptide

It will be appreciated that conditions caused by a decrease in the standard or normal expression level of a secreted protein in an individual can be treated by administering the polypeptide of the present invention, preferably in the secreted form. Thus, the invention also provides a method of treatment of an individual in need of an increased level of the polypeptide comprising administering to such an individual a pharmaceutical composition comprising an amount of the polypeptide to increase the activity level of the polypeptide in such an individual. [0710]
For example, a patient with decreased levels of a polypeptide receives a daily dose 0.1-100 ug/kg of the polypeptide for six consecutive days. Preferably, the polypeptide is in the secreted form. The exact details of the dosing scheme, based on administration and formulation, are provided in Example 23. [0711]

Example 25

Method of Treating Increased Levels of the Polypeptide

Antisense technology is used to inhibit production of a polypeptide of the present invention. This technology is one example of a method of decreasing levels of a polypeptide, preferably a secreted form, due to a variety of etiologies, such as cancer. [0712]
For example, a patient diagnosed with abnormally increased levels of a polypeptide is administered intravenously antisense polynucleotides at 0.5, 1.0, 1.5, 2.0 and 3.0 mg/kg day for 21 days. This treatment is repeated after a 7-day rest period if the treatment was well tolerated. The formulation of the antisense polynucleotide is provided in Example 23. [0713]

Example 26

Method of Treatment Using Gene Therapy

One method of gene therapy transplants fibroblasts, which are capable of expressing a polypeptide, onto a patient. Generally, fibroblasts are obtained from a subject by skin biopsy. The resulting tissue is placed in tissue-culture medium and separated into small pieces. Small chunks of the tissue are placed on a wet surface of a tissue culture flask, approximately ten pieces are placed in each flask. The flask is turned upside down, closed tight and left at room temperature over night. After 24 hours at room temperature, the flask is inverted and the chunks of tissue remain fixed to the bottom of the flask and fresh media (e.g., Ham's F12 media, with 10% FBS, penicillin and streptomycin) is added. The flasks are then incubated at 37° C. for approximately one week. [0714]
At this time, fresh media is added and subsequently changed every several days. After an additional two weeks in culture, a monolayer of fibroblasts emerge. The monolayer is trypsinized and scaled into larger flasks. [0715]
pMV-7 (Kirschmeier, P. T. et al., DNA, 7:219-25 (1988)), flanked by the long terminal repeats of the Moloney murine sarcoma virus, is digested with EcoRI and HindIII and subsequently treated with calf intestinal phosphatase. The linear vector is fractionated on agarose gel and purified, using glass beads. [0716]
The cDNA encoding a polypeptide of the present invention can be amplified using PCR primers which correspond to the 5′ and 3′ end sequences respectively as set forth in Example 1. Preferably, the 5′ primer contains an EcoRI site and the 3′ primer includes a HindIII site. Equal quantities of the Moloney murine sarcoma virus linear backbone and the amplified EcoRI and HindIII fragment are added together, in the presence of T4 DNA ligase. The resulting mixture is maintained under conditions appropriate for ligation of the two fragments. The ligation mixture is then used to transform bacteria HB101, which are then plated onto agar containing kanamycin for the purpose of confirming that the vector has the gene of interest properly inserted. [0717]
The amphotropic pA317 or GP+am12 packaging cells are grown in tissue culture to confluent density in Dulbecco's Modified Eagles Medium (DMEM) with 10% calf serum (CS), penicillin and streptomycin. The MSV vector containing the gene is then added to the media and the packaging cells transduced with the vector. The packaging cells now produce infectious viral particles containing the gene (the packaging cells are now referred to as producer cells). [0718]
Fresh media is added to the transduced producer cells, and subsequently, the media is harvested from a 10 cm plate of confluent producer cells. The spent media, containing the infectious viral particles, is filtered through a millipore filter to remove detached producer cells and this media is then used to infect fibroblast cells. Media is removed from a sub-confluent plate of fibroblasts and quickly replaced with the media from the producer cells. This media is removed and replaced with fresh media. If the titer of virus is high, then virtually all fibroblasts will be infected and no selection is required. If the titer is very low, then it is necessary to use a retroviral vector that has a selectable marker, such as neo or his. Once the fibroblasts have been efficiently infected, the fibroblasts are analyzed to determine whether protein is produced. [0719]
The engineered fibroblasts are then transplanted onto the host, either alone or after having been grown to confluence on cytodex 3 microcarrier beads. [0720]
It will be clear that the invention may be practiced otherwise than as particularly described in the foregoing description and examples. Numerous modifications and variations of the present invention are possible in light of the above teachings and, therefore, are within the scope of the appended claims. [0721]
The entire disclosure of each document cited (including patents, patent applications, journal articles, abstracts, laboratory manuals, books, or other disclosures) in the Background of the Invention, Detailed Description, and Examples is hereby incorporated herein by reference. Further, the hard copy of the sequence listing submitted herewith and the corresponding computer readable form are both incorporated herein by reference in their entireties. [0722]
1 343 1 733 DNA Homo sapiens 1 gggatccgga gcccaaatct tctgacaaaa ctcacacatg cccaccgtgc ccagcacctg 60 aattcgaggg tgcaccgtca gtcttcctct tccccccaaa acccaaggac accctcatga 120 tctcccggac tcctgaggtc acatgcgtgg tggtggacgt aagccacgaa gaccctgagg 180 tcaagttcaa ctggtacgtg gacggcgtgg aggtgcataa tgccaagaca aagccgcggg 240 aggagcagta caacagcacg taccgtgtgg tcagcgtcct caccgtcctg caccaggact 300 ggctgaatgg caaggagtac aagtgcaagg tctccaacaa agccctccca acccccatcg 360 agaaaaccat ctccaaagcc aaagggcagc cccgagaacc acaggtgtac accctgcccc 420 catcccggga tgagctgacc aagaaccagg tcagcctgac ctgcctggtc aaaggcttct 480 atccaagcga catcgccgtg gagtgggaga gcaatgggca gccggagaac aactacaaga 540 ccacgcctcc cgtgctggac tccgacggct ccttcttcct ctacagcaag ctcaccgtgg 600 acaagagcag gtggcagcag gggaacgtct tctcatgctc cgtgatgcat gaggctctgc 660 acaaccacta cacgcagaag agcctctccc tgtctccggg taaatgagtg cgacggccgc 720 gactctagag gat 733 2 5 PRT Homo sapiens MISC_FEATURE (3) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 2 Trp Ser Xaa Trp Ser 1 5 3 86 DNA Homo sapiens 3 gcgcctcgag atttccccga aatctagatt tccccgaaat gatttccccg aaatgatttc 60 cccgaaatat ctgccatctc aattag 86 4 27 DNA Homo sapiens 4 gcggcaagct ttttgcaaag cctaggc 27 5 271 DNA Homo sapiens 5 ctcgagattt ccccgaaatc tagatttccc cgaaatgatt tccccgaaat gatttccccg 60 aaatatctgc catctcaatt agtcagcaac catagtcccg cccctaactc cgcccatccc 120 gcccctaact ccgcccagtt ccgcccattc tccgccccat ggctgactaa ttttttttat 180 ttatgcagag gccgaggccg cctcggcctc tgagctattc cagaagtagt gaggaggctt 240 ttttggaggc ctaggctttt gcaaaaagct t 271 6 32 DNA Homo sapiens 6 gcgctcgagg gatgacagcg atagaacccc gg 32 7 31 DNA Homo sapiens 7 gcgaagcttc gcgactcccc ggatccgcct c 31 8 12 DNA Homo sapiens 8 ggggactttc cc 12 9 73 DNA Homo sapiens 9 gcggcctcga ggggactttc ccggggactt tccggggact ttccgggact ttccatcctg 60 ccatctcaat tag 73 10 256 DNA Homo sapiens 10 ctcgagggga ctttcccggg gactttccgg ggactttccg ggactttcca tctgccatct 60 caattagtca gcaaccatag tcccgcccct aactccgccc atcccgcccc taactccgcc 120 cagttccgcc cattctccgc cccatggctg actaattttt tttatttatg cagaggccga 180 ggccgcctcg gcctctgagc tattccagaa gtagtgagga ggcttttttg gaggcctagg 240 cttttgcaaa aagctt 256 11 1679 DNA Homo sapiens misc_feature (1656) n equals a,t,g, or c 11 gcagcgcacc cgggcgatcg cttcacggat gcggacgacg tagccatcct tacctacgtg 60 aaggaaaatg cccgctcgcc cagctccgtc accggtaacg ccttgtggaa agcgatggag 120 aagagctcgc tcacgcagca ctcgtggcag tccctgaagg accgctacct caagcacctg 180 cggggccagg agcataagta cctgctgggg gacgcgccgg tgagcccctc ctcccagaag 240 ctcaagcgga aggcggagga ggacccggag gccgcggata gcggggaacc acagaataag 300 agaactccag atttgcctga agaagagtat gtgaaggaag aaatccagga gaatgaagaa 360 gcagtcaaaa agatgcttgt ggaagccacc cgggagtttg aggaggttgt ggtggatgag 420 agccctcctg attttgaaat acatataact atgtgtgatg atgatccacc cacacctgag 480 gaagactcag aaacacagcc tgatgaggag gaagaagaag aagaagaaaa agtttctcaa 540 ccagaggtgg gagctgccat taagatcatt cggcagttaa tggagaagtt taacttggat 600 ctatcaacag ttacacaggc cttcctaaaa aatagtggtg agctggaggc tacttccgcc 660 ttcttagcgt ctggtcagag agctgatgga tatcccattt ggtcccgaca agatgacata 720 gatttgcaaa aagatgatga ggataccaga gaggcattgg tcaaaaaatt tggtgctcag 780 aatgtagctc ggaggattga atttcgaaag aaataattgg caagataatg agaaaagaaa 840 aaagtcatgg taggtgaggt ggttaaaaaa aattgtgacc aatgaacttt agagagttct 900 tgcattggaa ctggcactta ttttctgacc atcgctgctg ttgctctgtg agtcctagat 960 ttttgtagcc aagcagagtt gtagaggggg ataaaaagaa aagaaattgg atgtatttac 1020 agctgtcctt gaacaagtat caatgtgttt atgaaaggaa gatctaaatc agacaggagt 1080 tggtctacat agtagtaatc cattgttgga atggaaccct tgctatagta gtgacaaagt 1140 gaaaggaaat ttaggaggca taggccattt caggcagcat aagtaatctc ctgtcctttg 1200 gcagaagctc ctttagattg ggatagattc caaataaaga atctagaaat aggagaagat 1260 ttaattatga ggccttgaac acggattatc cccaaaccct tgtcatttcc cccagtgagc 1320 tctgatttct agactgcttt gaaaatgctg tattcatttt gctaacttag tatttgggta 1380 ccctgctctt tggctgttct ttttttggag cccttctcag tcaagtctgc cggatgtctt 1440 tctttaccta cccctcagtt ttccttaaaa cgcgcacaca actctagaga gtgttaagaa 1500 taatgttact tggttaatgt gttatttatt gagtattgtt tgtgctaagc attgtgttag 1560 atttaaaaaa ttagtggatt gactccactt tgttgtgttg ttttcattgt tgaaaataaa 1620 tataactttg tattcgaaaa aaaaaaaaaa aaaatnrctg cggnccgaca agggaattc 1679 12 1963 DNA Homo sapiens misc_feature (335) n equals a,t,g, or c 12 ggatcctcgc ggcggcggcg gtgcttacag cctgagaaga gcgtctcgcc cgggagcggc 60 ggcggccatc gagacccacc caaggcgcgt ccccctcggc ctcccagcgc tcccaagccg 120 cagcggccgc gccccttcag ctagctcgct cgctcgctct gcttccctgc tgccggctgc 180 gcatggcktt ggcgttggcg gcgctggcgg cggtcgagcc gcctgcgcag ccggtaccag 240 cagttgcaga atgaagaaga gtctggagaa cctgaacagg ctgcaggtga tgctcctcca 300 ccttacagca gcatttctgc agagagcgca gcatnatttt gactacaagg atgagtctgg 360 gtttccaaag cccccatctt acaatgtagc tacaacactg cccagttatg atgaagcgga 420 gaggaccaag gctgaagcta ctatcccttt ggttcctggg agagatgagg attttgtggg 480 tcgggatgat tttgatgatg ctgaccagct gaggatagga aatgatggga ttttcatgtt 540 aacttttttc atggcattcc tctttaactg gattgggttt ttcctgtctt tttgcctgac 600 cacttcagct gcaggaaggt atggggccat ttcaggattt ggtctctctc taattaaatg 660 gatcctgatt gtcaggtttt ccacctattt ccctggatat tttgatggtc agtactggct 720 ctggtgggtg ttccttgttt taggctttct cctgtttctc agaggattta tcaattatgc 780 aaaagttcgg aagatgccag aaactttctc aaatctcccc aggaccagag ttctctttat 840 ttattaaaga tgttttctgg caaaggcctt cctgcattta tgaattctct ctcaagaagc 900 aagagaacac ctgcaggaag tgaatcaaga tgcagaacac agaggaataa tcacctgctt 960 taaaaaaata aagtactgtt gaaaagatca tttctctcta tttgttccta ggtgtaaaat 1020 tttaatagtt aatgcagaat tctgtaatca ttgaatcatt agtggttaat gtttgaaaaa 1080 gctcttgcaa tcaagtctgt gatgtattaa taatgcctta tatattgttt gtagtcattt 1140 taagtagcat gagccatgtc cctgtagtcg gtagggggca gtcttgcttt attcatcctc 1200 catctcaaaa tgaacttgga attaaatatt gtaagatatg tataatgctg gccattttaa 1260 aggggttttc tcaaaagtta aacttttgtt atgactgtgt ttttgcacat aatccatatt 1320 tgctgttcaa gttaatctag aaatttattc aattctgtat gaacacctgg aagcaaaatc 1380 atagtgcaaa aatacattta aggtgtggtc aaaaataagt ctttaattgg taaataataa 1440 gcattaattt tttatagcct gtattcacaa ttctgcggta ccttattgta cctaagggat 1500 tctaaaggtg ttgtcactgt ataaaacaga aagcactagg atacaaatga agcttaatta 1560 ctaaaatgta attcttgaca ctctttctat aattagcgtt cttcaccccc acccccaccc 1620 ccacccccct tattttcctt ttgtctcctg gtgattaggc caaagtctgg gagtaaggag 1680 aggattaggt acttaggagc aaagaaagaa gtagcttgga acttttgaga tgatccctaa 1740 catactgtac tacttgcttt tacaatgtgt tagcagaaac cagtgggtta taatgtagaa 1800 tgatgtgctt tctgcccaag tggtaattca tcttggtttg ctatgttaaa actgtaaata 1860 caacagaaca ttaataaata tctcttgtgt agcaccttta aaaaaaaaaa aaaaaaaaaa 1920 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaana aaa 1963 13 1212 DNA Homo sapiens 13 tgtttgaagt tgttactttt gtttacagca aagtttgatg tagtgtgcag tagtgagctc 60 tagactgatc tttttctaaa tcagaaagtg attaaagtat gcacaaccaa aggcaggttt 120 ttctttttca tttattcagc aactatttat taagcatcaa ctctgtgcca ggcacgttac 180 tagctgctac atactgtctg aacatgacat acggttaagt aactttacaa ttattatcaa 240 atacttcaat gtagatattt cttaagttga aatagcatta actaggataa tgctttcatg 300 ttattttatt tgtcttgtga tagaaattca actttgtacc atcttaaaac taggttgcta 360 taaaaatagg aggatgaagt caataaagtt tatgccagtt taaaaactgg aaggaaaagg 420 taagagctct ccattataaa atagttgcat tcggttaatt tttacacatt agtgcattgc 480 gtatatcaac tggccctcaa tgaagcattt aagtgcttgg aattttacta aactgacttt 540 tttgcaactt tgggagattt ttgaggggag tgttgaaaat tgccaaacac tcacctctta 600 ctcaaaactt caaataaaat acacattttc aagagggagc accttttata tttgataagt 660 tttcattata aaccttataa taccagtcac aaagaggttg tctgtctatg gtttagcaaa 720 catttgcttt tctttttgga agtgtgattg caattgcaga acagaaagtg agaaaacact 780 gccagcggtg attgctactt gaggtagttt tttacaacta ccatttcccc tccatgaaat 840 tatgtgaaat ttattttatc tttgggaaaa gttgagaaga tagtaaaaga attaggaatt 900 taaaattaca gggaaaaata tgtaagtgaa aagcaataaa tattttgttc actttgctat 960 caagatgttc actatcagat atttattata tggcagcaat ttatattttt aatcattgcc 1020 cattaataga cgcagtaaaa tatttttgaa tcagacattt ggggtttgta tgtgcattaa 1080 aattgtcttt tgtactgtaa gttactgtta atttgaatat tttattgaac tgtctccctg 1140 tgcctttata atataaagtt gtttctacaa cttttaatga tcttaataaa gaatacttta 1200 agaaaaaaaa aa 1212 14 2061 DNA Homo sapiens misc_feature (1703) n equals a,t,g, or c 14 ggttttcctc cgacttccgg acatctccct gggagtcgcg cagagtggag tcaaaggcaa 60 ccagtgctcg ctgcggtctc tggggatcgg gaccgcggcg gcggcccgcg agcgggatgt 120 tccggggctt gagcagttgg ttgggcttgc agcagccggt ggcaggcggt gggcagccca 180 atggagatgc tccacccgag cagccgtccg agacggtggc tgagtctgcg gaggaggagc 240 tgcagcaagc gggagaccag gagctcctcc accaggccaa agacttcggc aactatttat 300 ttaactttgc atctgctgcc acaaaaaaga taactgaatc agttgctgaa acagcacaaa 360 caataaagaa atccgtagaa gaaggaaaaa tagatggcat cattgacaag acaattatag 420 gagattttca gaaggaacag aaaaaatttg ttgaagagca acatacaaag aagtcagaag 480 cagctgtgcc cccatgggtt gacactaacg atgaagaaac aattcaacaa caaattttgg 540 ccttatcagc tgacaagagg aatttccttc gtgaccctcc ggctggcgtg caatttaatt 600 tcgactttga tcagatgtac cccgtggccc tggtcatgct ccaggaggat gagctgctar 660 caagatgaga tttgccctcg ttcctaaact tgtgaaggaa gaagtgttct ggaggaacta 720 cttttaccgc gtctccctga ttaagcagtc agcccagctc acggccctgg ctgcccaaca 780 gcaggccgca gggaagggag gagaagagca atggcagaga gcaagatttg ccgctggaga 840 ggcagtacgg cccaaaacgc cacccgttgt aatcaaatct cagcttaaaa ctcaagagga 900 tgaggaagaa atttctacta gcccaggtgt ttctgagttt gtcagtgatg ccttcgatgc 960 ctgtaaccta aatcaggaag atctaaggaa agaaatggag caactagtgc ttgacaaaaa 1020 gcaagaggag acagccgtac tggaagagga ttctgcagat tgggaaaaag aactgcagca 1080 ggaacttcaa gaatatgaag tggtgacaga atctgaaaaa cgagatgaaa actgggataa 1140 ggaaatagag aaaatgcttc aagaggaaaa ttagctgttc ctgaaataga agaataatcc 1200 ttaacagtct gcaaactgac attaaattct agatgttgac aattactgaa tcagaaggca 1260 tgaaagagta taattttatg aaattcaaaa ttattctttt ttcaagttga aacttgcctc 1320 ttctacttta aaaaagtata tagaacagtt acttctaata atcagaaaga gatgttttat 1380 agaacatttc tttaatataa agttagagat gtcttcatag gcagtatggc tatctttgcc 1440 acagaaacat aagtaaaatt ttagagttct gttttccatg aggtcaaaaa tataatttat 1500 tcctcagtca tggttttcta aatatctgta ctccacattc cattttaatt gatatgaggg 1560 tgttaaagta cctacttaat gggttgatta ctatcaaaat gaccaaatta taccaaagaa 1620 cttaagagga agcactttca gaactattca cttgccaggt attttctaaa attccacctg 1680 aaagccaaaa gataaaatac atnagttgga ttttaatgat ataagcatca cacaatttta 1740 cattaagaaa tactgtgcag cccatgcgtg gtggctcagg cctgtaatcc cagcantttg 1800 ggaggccgag gtgggcagat caccggaggt caggagttcg agaccagcct tgccaacata 1860 gtgaaaccct gtctttacta aaaatacaaa aattagccgg gcatggtggc aggcacctgt 1920 aatcccagct actagggagg cttttgaacc caggaggcag aggttgcagc gagctgagat 1980 cgcgccactg cactccagcc tgggtgatag agtgagattc agtctcaaaa aaaaaaaaaa 2040 aaaaaaaaaa aatgacctcg a 2061 15 1412 DNA Homo sapiens misc_feature (1362) n equals a,t,g, or c 15 cccttcatct gcgttgccag gaaccctgtc agcagaaact tctcaagccc catccttgcc 60 aggaagctct gtgaaggtgc tgctgatgac ccagattcct ccatggtcct cctgtgtctc 120 ctgttggtgc ccctcctgct cagtctcttt gtactggggc tatttctttg gtttctgaag 180 agagagagac aagaagagta cattgaagag aagaagagag tggacatttg tcgggaaact 240 cctaacatat gcccccattc tggagagaac acagagtacg acacaatccc tcacactaat 300 agaacaatcc taaaggaaga tccagcaaat acggtttact ccactgtgga aataccgaaa 360 aagatggaaa atccccactc actgctcacg atgccagaca caccaaggct atttgcctat 420 gagaatgtta tctagacagc agtgcactcc cctaagtctc tgctcaaaaa aaaaacaatt 480 ctcggcccaa agaaaacaat cagaagaatt cactgatttg actagaaaca tcaaggaaga 540 atgaagaacg ttgacttttt tccaggataa attatctctg atgcttcttt agatttaaga 600 gttcataatt ccatccactg ctgagaaatc tcctcaaacc cagaaggttt aatcacttca 660 tcccaaaaat gggattgtga atgtcagcaa accataaaaa aagtgcttag aagtattcct 720 ataaaaatgt aaatgcaagg tcacacatat taatgacagc ctgttgtatt aatgatggct 780 ccaggtcagt gtctggagtt tcattccatc ccagggcttg gatgtcagga ttataccaag 840 agtcttgcta ccaggagggc aagaagacca aaacagacag acaagtccag cagaagcaga 900 tgcacctgac aaaaatggat gtattaattg gctctataaa ctatgtgccc agcaytatgc 960 tgagcttaca ctaattggtc agacatgctg tctgccctca tgaaattggc tccaaatgaw 1020 tgaactactt tcatgagcag ttgtagcagg cctgaccaca gattcccaga gggccaggtg 1080 tggatccaca ggacttgaag gtcaaagttc acaaagatga agaatcaggg tagctgacca 1140 tgtttggcag atactataat ggagacacag aagtgtgcat ggcccaagga caaggacctc 1200 cagccaggct tcatttatgc acttgtctgc aaaagaaaag tctaggtttt aaggctgtgc 1260 cagaacccat cccaataaag agaccgagtc tgaagtcaca ttgtaaatct agtgtaggag 1320 acttggagtc aggcagtgag actggtgggg cacggggggc antgggtant gtaaaccttt 1380 taaagatggt taattcntca ttagtgtttt tt 1412 16 1052 DNA Homo sapiens 16 ttcctctcct ctctctaccc ctcctgtctc tcctcccctc ctctctcttc ctctcctctc 60 tctcttcctc tcctctctct tcccttcctg tctctcttcc cctcctctct ctcttcctgt 120 cctctatctc ttcccctcct ctatctcttc ctctcctctc tctcttcctc tcctctctct 180 ctcttscttt cttctctctc tcctgtctcg gctgttgtgg gttgcaggtt gggtgctgct 240 gttgtggtcc ttcccagaaa ctgccagtag agggcagcct gggcatccta atgcttactc 300 tggttgttac acaaagaaaa tattggggtc actggcgagc ccacccacac tcaccagaat 360 ctccactgta gtccccctaa caaacagccc ttcacttcct ctcccacttc agcaatttgt 420 attttgatgc cattggcctc agatcagagt gttttaaatc atcacgccct ggcttatccc 480 tggtcgagcc aggacacggg gtgcttcagt gggtctgtca ccctctctcc ttgaagcatg 540 ttgcttttat ttatttactt ttactctcac cctgctcctg taccagcagg ggccacttca 600 aagccaaggt acagggtgat aacttgtggt ccagcatcag ttttctccac ttctttctcc 660 cactcacccc cagcaaggtg cctggggaga cttgagcaga tgtttcattt tggcctggcc 720 agtggctgaa agcaggcctc caatgcactg tgacctctgg cttccccagc agctttccca 780 gagaggcaga ggggccttcc acagcccggg ttctcctgct gcctcctgcc tgctgcagct 840 gcaggcattc tgaggggcaa cgtggaggaa gggccaggga tgcatgggat tttaattgtt 900 tcatcacacc ttccccgtgg caaagaaaca gtcagtcctc ttcaggtgtc ttctggattt 960 ctggtgatgg acagagaaat ctttttacag tttcaaatta tgttcaacaa ataaaaattg 1020 cattttttat tttggaaaaa aaaaaaaaaa aa 1052 17 683 DNA Homo sapiens 17 aattcggcag aggcacttat catgtacata tagcctgttt tttagcattg ttagacaaag 60 taggcatatt cctttccatc caagaactca taacctagta attgtagttg gctgatagct 120 cattgcccat acacaaggat ctaacacaac ctcttgaata aacatccccc ttattcagaa 180 atgccttttc ctatttccat attgcaactt tgcttacaaa tttccaatct gtctttctgt 240 ttacagaaga tatacaaaat tccttttgta tgatctcttt atatctcttg attttctttt 300 gtgtttgcta ccaaagggcc tgcacatagt gagaagattg tgcatgatct gtgagctcta 360 ccacacctgg aattagggat caccaatatg agaaaaaaaa ttggaggtac aaataacatt 420 atcatatgtw attggcatat aaattacaga tgtwtctatg actaaaaacc ctgtggatat 480 waaccmaatg cagataawtw taataaaatw twtaaaaatw twatcmaata atgatagtgc 540 tattcaaata cttcaaattt gcacagtgat ttatttctta aaatatgtta acacatgtga 600 gccaatacac tgaggtcact ggataaataa acagattctt gcaaaaaaaa aaaaaaaaaa 660 actcgagggg ggcccgtacc ctt 683 18 1054 DNA Homo sapiens misc_feature (74) n equals a,t,g, or c 18 aaactcattt aggtgacact atagaaggta cgcctgcagg taccggtccg gaattcccgg 60 gtcgacccac gmgnccggcg acaagatggc agcagcgtgt cggagcgtga agggcctggt 120 ggcggtaata accggaggag cctcgggcct gggcctggcc acggcggacg acttgtgggg 180 cagggagcct ctgctgtgct tctggacctg cccaactcgg gtggggaggc ccaagccaag 240 aagttaggaa acaactgcgt tttcgcccca gccgacgtga cctctgagaa ggatgtgcaa 300 acagctctgg ctctagcaaa aggaaagttt ggccgtgtgg atgtagctgt caactgtgca 360 ggcatcgcgg tggctagcaa gacgtacaac ttaaagaagg gccagaccca taccttggaa 420 gacttccagc gagttcttga tgtgaatctc atgggcacct tcaatgtgat ccgcctggtg 480 gctggtgaga tgggccagaa tgaaccagac cagggaggcc aacgtggggt catcatcaac 540 actgccagtg tggctgcctt cgagggtcag gttggacaag ctgcatactc tgcttccaag 600 gggggaatag tgggcatgac actgcccatt gctcgggatc tggctcccat aggtatccgg 660 gtgatgacca ttgccccagg tctgtttggc accccactgc tgaccagcct cccagagaaa 720 gtgtgcaact tcttggccag ccaagtgccc ttccctagcc gactgggtga ccctgctgag 780 tatgctcacc tcgtacaggc catcatcgag aacccattcc tcaatggaga ggtcatccgg 840 ctggatgggg ccattcgtat gcagccttga agggagaagg cagagaaaac acacgctcct 900 ctgcccttcc tttccctggg gtactactct ccagcttggg aggaagccca gtagccattt 960 tgtaactgcc taccagtcgc cctctgtgcc taataaagtc tctttttctc acanaaaaaa 1020 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaa 1054 19 1393 DNA Homo sapiens misc_feature (127) n equals a,t,g, or c 19 ggaacaagct gggatatgtg agcgttaagc tactcacatc cttcaaaaag gtgaaacatc 60 ttacacggga ctggagaacc acagcacatg ctttgaagta ttcagtggtc cttgagttga 120 atgaggncca ccggaaggtg aggaggacca cccccgtccc actgttcccc aacgagaacc 180 tccccagcaa gatgctcctg gtctatgatc tctacttgty tcctaagctg tgggctctgg 240 ccacccccca gaagaatggg aagggtgcaa garaaggtga tggaacacct gctcaagctt 300 tttgggactt ttggagtcat ctcatcagtg cggatcctca aacctgggag agagctgccc 360 cctgacatcc ggaggntcca gcagccgcta cagctcctct gaccccgaga gcaaccccac 420 atcccctatg gcgggccgac ggcacgngkc caccaacaag ctcagcccgt ctggccacca 480 gaatctcttt ctgagtccaa atgcctcccc gtgcacaagt ccttggagca gccccttggc 540 ccaacgcaaa ggcgtttcca gaaagtcccc actggcggag gaaggtagac tgaactgcag 600 caccagccct gagatcttcc gcaagtgtat ggattattcc tctgacagca gcgtcactcc 660 ctctggcagc ccctgggtcc ggaggcgtcg ccaagccgag atggggaccc aggagaaaag 720 ccccggtacg agtcccctgc tctcccggaa gatgcagact gcagatgggs tacccgtagg 780 tngcttgagg ttgcccaggg gtcctgacaa caccagagga tttcatggcc atgagaggag 840 cagggcctgt gtataaatac cttctatttt taatacaagc tccactgaaa accaccttcg 900 ttttcaaggt tctgacaaac acctggcatg acagaatgga attcgttccc ctttgagaga 960 ttttttattc atgtagacct cttaatttat ctatctgtaa tatacataaa tcggtacgcc 1020 atggtttgaa gaccaccttc tagttcagga ctcctgttct tcccagcatg gccactattt 1080 tgatgatggc tgatgtgtgt gagtgtgatg gccctgaagg gctgtaggac ggaggttccc 1140 tgggggaagt ctgttctttg gtatggaatt tttctctctt ctttggtatg gaatttttcc 1200 cttcagtgac tgagctgtcc tcgataggcc atgcaagggc ttcctgagag ttcaggaaag 1260 ttctcttgtg caacagcaag tagctaagcc tatagcatgg tgtcttgtag gaccaaatcg 1320 atgttacctg tcaagtaaat aaataataaa acacccaact gggagtgctg aaaaaaaana 1380 annaaaaaac tcg 1393 20 1215 DNA Homo sapiens misc_feature (15) n equals a,t,g, or c 20 aggaaaagtt ttccnaattg gaaagcgggc agtgagcgca acgcaattaa tgtgagttag 60 ntcantcatt aggcacccca ggctttacac tttatgcttc cggntcgtat gttgtgtgga 120 attgtgagcg gataacaatt tcacacagga aacagctatg accatgatta cgccaagctn 180 taatacgact cactataggg aaagctggta cgcctgcagg taccggtccg gaattcccgg 240 gtcgacccac gcgtccgccc acgcgtccgt gaaaatccga agtgccgcgg aaagtggagg 300 tgagggccgc ccgccctaga ggtgcccgtc cgagaggcag agctgacaag gaaggtttcg 360 agcgttttgc tggcaaaggg atttcttaca acctccaggc atgcgtcttt ctgccctgct 420 ggccttggca tccaaggtca ctctgccccc ccattaccgc tatgggatga gccccccagg 480 ctctgttgca gacaagagga agaacccccc atggatcagg cggcgcccag tggttgtgga 540 acccatctct gatgaagact ggtatctgtt ctgtggggac acggtggaga tcctagaagg 600 caaggatgcc gggaagcagg gcaaagtggt tcaagttatc cggcagcgaa actgggtggt 660 cgtgggaggg ctgaacacac attaccgcta cattggcaag accatggatt accggggaac 720 catgatccct agtgaagccc ccttgctcca ccgccaggtc aaacttgtgg atcctatgga 780 caggaaaccc actgagatcg agtggagatt tactgaagca ggagagcggg tacgagtctc 840 cacacgatca gggagaatta tccctaaacc cgaatttccc agagctgatg gcatcgtccc 900 tgaaacgtgg attgatggcc ccaaagacac atcagtggaa gatgctttag aaagaaccta 960 tgtgccctgt ctaaagacac tgcaggagga ggtgatggag gccatgggga tcaaggagac 1020 ccggaaatac aagaaggtct attggtattg agcctggggc agagcagctc ctccccaact 1080 tctgtcccag ccttgaaggc tgaggcactt ctttttcaga tgccaataaa gagcacttta 1140 tgagtcctcc aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1200 aaaaggggcg gccgc 1215 21 2042 DNA Homo sapiens 21 ctgcatccag gcgcagaata acctgggtat cttgtggtct gaaagagaga aattgaaact 60 gcacaggctt acctagagtc atcagaagca ctatataatc agtatatgaa agaggttggg 120 agtcctcctc ttgatcctac tgagcgtttt cttctgaaga agagaaactt actgaacaag 180 agagatcaaa aagatttgaa aaggtttata ctcataacct atattaccta gctcaagtct 240 accagcatct ggaaatgttt gagaaggctg ctcactattg ccatagtaca ctaaaacgcc 300 agcttgagca caatgcctac catcctatag agtgggctat caatgctgct accttgtcac 360 agttttacat caataagcta tgctttatgg aggccaggca ctgtttatca gctgctaatg 420 tcatttttgg tcaaactgga aagatctcag ccacagaaga cactcctgaa gctgaaggag 480 aagtgccaga gctttatcat caaagaaagg gggaaatagc aaggtgctgg atcaaatact 540 gtttgactct catgcagaat gcccaactct ccatgcagga caacatagga gagcttgatc 600 ttgataaaca gtctgaactt agagctttaa ggaaaaaaga actagatgag gaggaaagca 660 ttcggaaaaa agctgtgcag tttggaaccg gtgaactgtg tgatgccatc tctgcagtag 720 aagagaaagt gagctacttg agacctttag attttgaaga agccagagaa cttttcttat 780 tgggtcagca ctatgtcttt gaggcaaaag agttctttca gattgatggt tatgtcactg 840 accatattga agttgtccaa gaccacagtg ctctgtttaa ggtgcttgca ttctttgaaa 900 ctgacatgga gagacggtgc aagatgcata aacgcrgaat agccatgcta gagcccctaa 960 ctgtagacct gaatccacag tattatctgt tggtcaacag acagatccag tttgaaattg 1020 cacatgctta ctatgatatg atggatttga aggttgccat tgctgacagg ctaagggatc 1080 ctgattcaca cattgtaaaa aaaataaata atcttaataa gtcagcactg aagtactacc 1140 agctcttctt agactccctg agagacccaa ataaagtatt ccctgagcat ataggggaag 1200 atgttcttcg ccctgccatg ttagctaagt ttcgagttgc ccgtctctat ggcaaaatca 1260 ttactgcaga tcccaagaaa gagctggaaa atttggcaac atcattggga acattacaaa 1320 tttattgttg attactgtga aaagcatcct gaggccgccc aggaaataga agttgagcta 1380 gaacttagta aagagatggt tagtcttctc ccaacaaaaa tggagagatt cagaaccaag 1440 atggccctga cttaatcctt gtttttaaag aaaggaaatg tgcaatattg aagtgatctt 1500 tttccctagt cagacaggcc caattccatt gtgatgttta cctttatagc caggtgagtg 1560 cagtttgaac ttgagataca gtcaactgag tgtttgctag gatcctaagg aacataaagt 1620 taattaaaaa cttacaccta attatgtaaa ttgccttgtt aaagacatgt gatttgtatt 1680 ttagatgctt gtttcctatt aaaatacaga catttctacc ctcagtttct aaatgtagac 1740 tatttgttgg ctagtacttg atagattcct tgtaagaaaa aatgctgggt aatgtacctg 1800 gtaacaagcc tgttaatata ttaagattga aaaagtaact tctatagtta ctccttctaa 1860 aatatttgac ttcctacatt ccccccaccc aaaatctttc ccttttgaaa atactaaaaa 1920 ctaagttatg ttattataaa gtgtaaaatg gtttgtctta attataggag aaaaaggcct 1980 tgttagaaat aaaataaact gacttatttc actaatgaaa aaaaaaaaaa aaaaaaaaaa 2040 tt 2042 22 1872 DNA Homo sapiens misc_feature (1871) n equals a,t,g, or c 22 gggtcgaccc acgcgtccga ttggcctaga gctcctgtga ccgagagcgc cacggaagcc 60 tggggatgat gtcgggcagc tttattcttt gcttggcttt ggtaactagg tggtcccctc 120 aagcatcctc agttcctctt gctgtttatg aatctaagac aaggaagtcc tatagaagcc 180 aaagggacag ggacggaaag gacaggtccc aagggatggg gctgtcttta cttgtggaaa 240 ccaggaaatt gctcctctca gccaaccaag gttgaccaca caccaccctt ccggagcagc 300 tcagtcagcc ctcggggacg rgaaaccaca agcgcagaga cgctgaggcc caggcaggtg 360 aagaggaagt ggctttgggt ttttaaagta ggtgagcgtg acctctctga ctgcttcttc 420 cccggggggg actgcaaacc gctcagggtt gcggcagagc catggacttc cggtccctgc 480 aacgggtgac ctaagcgtgg tgcacccatc agtcacgcag gaggactgac ttgacagacg 540 aaagacaagc ccggatgaca cagggtgaga agagtcaggg ccgcacctct gtccctgcaa 600 accaacaggt gcatggtgag tgtggcagtc cccacagctc cacaatgggc tcccccgcca 660 acggggacga cagggatctt caggaacttc tgacctcacc aagtcaagtg gaccactctc 720 cactccacga ggatgtgaaa cggttcttta aaatgggatt ttagagcctc gggaatgcat 780 gtgcgtcgca tctttcatat tatgggtcag gatagattca tttcttgcaa catagtggaa 840 aagatataag ctgcagtaat ttgctctttg aatgaccgtc acccccagta taggatatgc 900 ttgtatcccc ccgtcactcc tccgcctgtt ttttaaactt ttccaccacc tgcgtccaaa 960 aagaatgtta tagcgagtgc tcttaaatgt tgaacctggg tgttgcttcc gggccagtct 1020 gcgtggctcc atgaaaagct cactgctgcc ccagccgggc ttcttagagg aggtcagttg 1080 tcctatgtat catcatttac tctgggaatc ctactgtgaa atcatgtctg tatttttctg 1140 gagcagttca catagagtag aatgtggaat ttcccgtgaa cgtctccttc ctcccccgta 1200 tctgccgcct gtcacttcgc caccgtgcta gaatactgtt gtgttgtaag atgactaatt 1260 ttaaaagaac ctgccctgaa aagttcttag aaacgcaatg aaagggagga acttgtcctt 1320 tacccagttt ttcctttgta ggatgggaaa gtataaaaag gcacagaagg ttgtcatggg 1380 ctgttccttg ggggttttta tcctgctcac cgtggagata agcctgcggc ttgtctaacc 1440 agcgcagcgm aaaggtctca atgccttttg gtaacatccg tcattgcaga agaaagttta 1500 cacgacgtca aaaagtgacg ttcatgctaa gtgtttttcc agaaatattg gtttcatgtt 1560 tcttattkgc tctgcctcct gtgcttatat catccaaaaa ctttttaaaa aggtccagaa 1620 ttctatttta acctgatgtt gagcaccttt aaaacgttcg tatgtgtgtt gcactaattc 1680 taaactttgg aggcattttg ctgtgtgagg ccgatcgcca ctgtaaaggt cctagagttg 1740 cctgtttgtc tctggagatg gaattaaacc aaataaagag cttccactgg aggcttgtat 1800 tgaccttgta actatatgtt aatctcgtgt taaaataaaa tataacttgt gaaaaaaaaa 1860 aaaaaaaaac nt 1872 23 289 DNA Homo sapiens misc_feature (284) n equals a,t,g, or c 23 catttaccca cctatcaaca tgtttgcttt ctcttttgtt ggtgagaatg agtggcttct 60 tgctcctagc tagagccagt ccttccatat gtgctttaga ttcttcctgt tttgttcaag 120 aatattgctc aagctattct tcctcctgtt tcctgcatca gcatttcccc tctctactag 180 atcatctctg tcagtaaatg aacatgttgt tgtttctcct agaagtactg tttctatatc 240 tagatagtac tctagctaga gttaaaaaaa aaaaaaaaaa cctnggggg 289 24 3533 DNA Homo sapiens misc_feature (44) n equals a,t,g, or c 24 ttttatttac ttcaaattaa ctgtacttta ctcaaataga aaangaataa ttttcacatt 60 atgaagctac acaattccaa aatacacatg ctgaggctct ttttaagtcc gaattgtcta 120 gtaattacaa aaaagtgaag agtttacaga tatacaagga aataaaggcg aattattgca 180 aagaaaacaa gtttaatttc actttgaatg acaacgattt ttctggaaag cagatacttc 240 actcctttaa gtttccaccc aagccacaat aatttcaaac ggtcttgcgg atgacccagc 300 tggtcactct tgtttatgtg gggactggag gtaatgagag ccaaaaaaag tgctataaac 360 ctaatttggc tagagcaagt tcacacgaca cgaccgtgct ttaaaaactt gctctccatt 420 atgtacttcc ttccatcagg ttggggaaaa aaaaatggtg gggatggtga gtaaacacac 480 cagtggtttc atcagagggg aactcactac tcaggaggtg acggtgacgt ggtgccggtc 540 cctgaagtac gcgcacaagc tccggaggtt gcgggagctt ccgctgccgc ctggagggaa 600 gccggagcga cgggggtcac ggcggcggtc agagggtaaa ggtcttgctc ccagcagcct 660 ccgcggtgga tacgtcgcca tcttggatcc gcgggacaag aaaattcatg cgagggagac 720 gtggtgggcg gtccttcctg tgacacgacc cttgagtgac agttctattt gattgcctcc 780 ggtactgtga ggaaaggaca cgactctatg gtgaggactg atggacatac attatctgag 840 aaaagaaact accaggtgac aaacagcatg tttggtgctt caagaaagaa gtttgtagag 900 ggggtcgaca gtgactacca tgacgaaaac atgtactaca gccagtcttc tatgtttcca 960 catcggtcag aaaaagatat gctggcatca ccatctacat caggtcagct gtctcagttt 1020 ggggcaagtt tatacgggca acaaagtgca ctaggccttc caatgagggg gatgagcaac 1080 aatacccctc agttaaatcg cagcttatca caaggcactc agttaccgag ccacgtcacg 1140 ccaacaacag gggtaccaac aatgtcactt cacacgcctc catctccaag caggggtatt 1200 ttgcctatga atcctargaa tatgatgaac cactcccagg ttggtcaggg cattggaatt 1260 cctagcagga caaatagcat gagcagttca gggttaggta gccccaacag aagctcgcca 1320 agcataatat gtatgccaaa gcagcagcct tctcgacagc cttttactgt gaacagtatg 1380 tctggatttg gaatgaacag gaatcaggca tttggaatga ataactcctt atcaagtaac 1440 atttttaatg gaacagacgg aagtgaaaat gtgacaggat tggacctttc agatttccca 1500 gcattagcag accgaaacag gagggaagga agtggtaacc caactccatt aataaacccc 1560 ttggctggaa gagctcctta tgttggaatg gtaacaaaac cagcaaatga acaatcccag 1620 gacttctcaa tacacaatga agattttcca gcattaccag gctccagcta taaagatcca 1680 acatcaagta atgatgacag taaatctaat ttgaatacat ctggcaagac aacttcaagt 1740 acagatggac ccaaattccc tggagataaa agttcaacaa cacaaaataa taaccagcag 1800 aaaaaaggga tccaggtgtt acctgatggt cgggttacta acattcctca agggatggtg 1860 acggaccaat ttggaatgat tggcctgtta acatttatca gggcagcaga gacagaccca 1920 ggaatggtac atcttgcatt aggaagtgac ttaacaacat taggcctcaa tctgaactct 1980 cctgaaaatc tctaccccaa atttgcgtca ccctgggcat cttcaccttg tcgacctcaa 2040 gacatagact tccatgttcc atctgagtac ttaacgaaca ttcacattag ggataagctg 2100 gctgcaataa aacttggccg atatggtgaa gaccttctct tctatctcta ttacatgaat 2160 ggaggagacg tattacaact tttagctgca gtggagcttt ttaaccgtga ttggagatac 2220 cacaaagaag aacgagtatg gattaccagg gcaccaggca tggagccaac aatgaaaacc 2280 aatacctatg agaggggaac atattacttc tttgactgtc ttaactggag gaaagtagct 2340 aaggagttcc atctggaata tgacaaatta gaagaacggc ctcacctgcc atccaccttc 2400 aactacaacc ctgctcagca agccttctaa aaaaaaaaaa aaaaaaaaaa aaaaagactt 2460 cccttttctt ggggtatggc tgtctcagca caatactcaa cataactgca gaactgatgt 2520 ggctcaggca ccctggtttt aattccttga ggatctggca attggcttac gcaaaaggtc 2580 accatttgag gtcctgcctt actaattatg tgctgcccaa caactaaatt tgtaatttgt 2640 ttttctctag tttgagcagg gtctgaattt tttcatttat ttcctttttt gccagcagac 2700 agacttgagt ctgtaaagac aagcaaatac actgacagaa gtttaccata gtttctaaaa 2760 tgtaaaaaag aaaaccccca aaagactcaa gaaaattaga ccacaaattt tgcattgttc 2820 attgtagcac tattggtaat aaaataacaa atgtttgtgc atttttatgt gaagatcctt 2880 ctcgtatttc atttggaaag atgagcaaga ggtctgcttc cttcatttta cttccccttc 2940 tgtttttgaa aggcagtttc gccaagctta atgcaagaat atctgactgt ttagaagaaa 3000 gatattgcca caatctctgg atggttttcc agggttgtgt tattactgag cttcatcttt 3060 ccagaatgag caaaacactg tccagtcttt gttacgattt tgtaataaat gtgtacattt 3120 tttttaaatt tttggacatc acatgaataa aggtatgtat gtacgaatgt gtatatatta 3180 tatatatgac atctattttg gaaaatgttt gccctgctgt acctcatttt taggaggtgt 3240 gcatggatgc aatatatgaa aatgggacat tctggaactg ctggtcaggg gactttgtcg 3300 ccctgtgcac taaaagggcc agattttcag cagccaagga catccatacc caagtgaatg 3360 tgatgggact taaaagaagt gaactgagac aattcactct ggctgtttga acagcagcgt 3420 ttcataggaa gagaaaaaaa gatcaatctt gtattttctg accacataaa ggcttcttct 3480 ctttgtaata aagtagaaaa gctctcctca aaaaaaaaaa aaaaaaactc gag 3533 25 1148 DNA Homo sapiens 25 acccacgcgt ccgcaaatta tacttcctca ttcatattat gttgatacaa aagaccttgg 60 cagccatttc tcccagcagt tttaaaggat gaacattgga tttcatgcca tcccatagaa 120 aacctgtttt aaaattttag ggatctttac ttggtcatac atgaaaagta cactgcttag 180 aaattataga ctattatgat ctgtccacag tgcccattgt cacttctttg tctcatttct 240 tccctttgtt ccttagtcat ccaaataagc ctgaaaacca taagagatat tactttattg 300 aatatggttg gcattaaatt tagcatttca ttatctaaca aaattaatat aaattccagg 360 acatggtaaa atgtgtttta ataaccccca gacccaaatg aaaatttcaa agtcaatacc 420 agcagattca tgaaagtaaa tttagtccta taattttcag cttaattata aacaaaggaa 480 caaataagtg gaagggcagc tattaccatt cgcttagtca aaacattcgg ttactgccct 540 ttaatacact cctatcatca gcacttccac catgtattac aagtcttgac ccatccctgt 600 cgtaactcca gtaaaagtta ctgttactag aaaattttta tcaattaact gacaaatagt 660 ttctttttaa agtagtttct tccatcttta ttctgactag cttccaaaat gtgttccctt 720 tttgaatcga ggtttttttg ttttgttttg ttttctgaaa aaatcataca actttgtgct 780 tctattgctt ttttgtgttt tgttaagcat gtcccttggc ccaaatggaa gaggaaatgt 840 ttaattaatg ctttttagtt taaataaatt gaatcattta taataatcag tgttaacaat 900 ttagtgaccc ttggtaggtt aaaggttgca ttatttatac ttgagatttt tttcccctaa 960 ctattctgtt ttttgtactt taaaactatg ggggaaatat cactggtctg tcaagaaaca 1020 gcagtaatta ttactgagtt aaattgaaaa gtccagtgga ccaggcattt cttatataaa 1080 taaaattggt ggtactaatg tgaaaaaaaa aaaaaaaaaa aactcgaggg gggcccggta 1140 ccctatta 1148 26 717 DNA Homo sapiens 26 ggcacgagct agctgccgcc acccgaacag cctgtcctgg tgccccggct ccctgccccg 60 cgcccagtca tgaccctgcg cccctcactc ctcccgctcc atctgctgct gctgctgctg 120 ctcagtgcgg cggtgtgccg ggctgaggct gggctcgaaa ccgaaagtcc cgtccggacc 180 ctccaagtgg agaccctggt ggagccccca gaaccatgtg ccgagcccgc tgcttttgga 240 gacacgcttc acatacacta cacgggaagc ttggtagatg gacgtattat tgacacctcc 300 ctgaccagag accctctggt tatagaactt ggccaaaagc aggtgattcc aggtctggag 360 cagagtcttc tcgacatgtg tgtgggagag aagcgaaggg caatcattcc ttctcacttg 420 gcctatggaa aacggggatt tccaccatct gtcccagcgg atgcagtggt gcagtatgac 480 gtggagctga ttgcactaat ccgagccaac tactggctaa agctggtgaa gggcattttg 540 cctctggtag ggatggccat ggtgccagcc ctcctgggcc tcattgggta tcacctatac 600 agaaaggcca atagacccaa agtctccaaa aagaagctca aggaagagaa acgaaacaag 660 agcaaaaaga aataataaat aataaatttt aaaaaaaaaa aaaaaaaaaa aaaaaaa 717 27 1099 DNA Homo sapiens misc_feature (1030) n equals a,t,g, or c 27 ggcacgagcc gatgtggaca tcatcctgtc tatccccatg ttcctgcgcc tgtacctgat 60 cgcccgagtc atgctgctgc acagcaagct cttcaccgat gcctcgtccc gcagcatcgg 120 ggccctcaac aagatcaact tcaacacccg ctttgtcatg aagacgctca tgaccatctg 180 ccctggcact gtgctgctcg tgttcagcat ctctctgtgg atcattgctg cctggaccgt 240 ccgtgtctgt gaaagtcctg aatcaccagc ccagccttct ggctcatcac ttcctgcttg 300 gtaccatgac cagcaggacg taactagtaa ctttctgggt gccatgtggc tcatctccat 360 cacattcctt tccattggtt atggggacat ggtgccccac acatactgtg ggaaaggtgt 420 ctgtctcctc actggcatca tgggtgcagg ctgcactgcc cttgtggtgg ccgtggtggc 480 ccgaaagctg gaactcacca aagcggagaa gcacgttcat aacttcatga tggacactca 540 gctcaccaag cggatcaaga atgctgcagc caatgtcctt cgggaaacat ggttaatcta 600 taaacacaca aagctgctaa agaagattga ccatgccaaa gtgaggaaac accagaggaa 660 gttcctccca agctatccac cagtttgagg agcgtcccag atggaacaga ggaaagctga 720 gtgaccaagc caacactctg gtggaccttt ccaagatgca gaatgtcatg tatgacttaa 780 tcacagaact caatgaccgg agcgaagacc tggagaagca gattggcagc ctggagtcga 840 agctggagca tctcaccgcc agcttcaact ccctgccgct gctcatcgcc gacaccctgc 900 gccagcagca gcagcagctc ctgtctgcca tcatcgaggc ccggggtgtc agcgtggcag 960 tgggcaccac ccacacccca atctccgata gccccattgg ggtcagctcc acctccttcc 1020 cgaccccgtn cacaagttca agcagttgct aaataaatct ccccactcca gaagcattaa 1080 aaaaaaaaaa aaaaaaaaa 1099 28 941 DNA Homo sapiens misc_feature (864) n equals a,t,g, or c 28 aattcggcag agagccaacc gagggcgttc ctgtcggggc tgcagcggcg ggagggagcc 60 cagtggaggc gccctcccga agcgccactg cccatgctga ccacccagcc ctccggctgc 120 tgatgtcatg agtaacacca ctgtgcccaa tgccccccag gccaacagcg actccatggt 180 gggctatgtg ttggggccct tcttcctcat caccctggtc ggggtggtgg tggctgtggt 240 aatgtatgta cagaagaaaa agcgggtgga ccggctgcgc catcacctgc tccccatgta 300 cagctatgac ccagctgagg aactgcatga ggctgagcag gagctgctct ctgacatggg 360 agaccccaag gtggtacatg gctggcagag tggctaccag cacaagcgga tgccactgct 420 ggatgtcaag acgtgacctg acccccttgc cccacccttc agagcctggg gtyctggact 480 gcctggggcc ctgccatctg cttcccctgc tgtcacctgg stccccctgc tgggtgctgg 540 gtctccattt ctccctccac ccaccctcag cagcatctgc ttcccatgcc ctcaccatca 600 cctcactgcc cccaggcctt ctgccctttg tgggtgttga gctcaccgcc cacccacagg 660 cactcatggg aagaggcttt ccttctggga tggcggcggc tggtagacac ctttgctttc 720 tctagccctc ctgggctggg cttgggcaca aatccccagg caggctttgg agttgtttcc 780 atggtgatgg ggccagatgt atagtattca gtatatattt tgtaaataaa atgttttgtg 840 gctaaaaaaa aaaaaaaaaa atcnaagggg gggccggtac ccaaattccc cctatantga 900 attcgtatta acaattcact tggggccgtc cttttaanaa c 941 29 756 DNA Homo sapiens 29 ggcacgagga agctggagcg ggccggcggt gcagtcacgg gggagcgagg cctgctgggc 60 ttggcaacga gggactcggc ctcggaggcg acccagacca cacagacact gggtcaagga 120 gtaagcagag gataaacaac tggaaggaga gcaagcacaa agtcatcatg gcttcagcgt 180 ctgctcgtgg aaaccaagat aaagatgccc attttccacc accaagcaag cagagcctgt 240 tgttttgtcc aaaatcaaaa ctgcacatcc acagagcaga gatctcaaag attatgcgag 300 aatgtcagga agaaagtttc tggaagagag ctctgccttt ttctcttgta agcatgcttg 360 tcacccaggg actagtctac caaggttatt tggcagctaa ttctagattt ggatcattgc 420 ccaaagttgc acttgctggt ctcttgggat ttggccttgg aaaggtatca tacataggag 480 tatgccagag taaattccat ttttttgaag atcagctccg tggggctggt tttggtccac 540 agcataacag gcactgcctc cttacctgtg aggaatgcaa aataaagcat ggattaagtg 600 agaagggaga ctctcagcct tcagcttcct aaattctgtg tctgtgactt tcgaagtttt 660 ttaaacctct gaatttgtac acatttaaaa tttcaagtgt actttaaaat aaaatacttc 720 taatggaaaa aaaaaaaaaa aaaaaaaaaa actcga 756 30 2100 DNA Homo sapiens misc_feature (1) n equals a,t,g, or c 30 nccagaggca gaaagtcctg cttctggggc gtaacctaca ggatatcctt ggaacagaag 60 atcttattgt ggaagtract tccaatgatg ctgtgagatt ttatccctgg accattgata 120 ataaatacta ttcagcagac atcaatctat gtgtggtgcc aaacaaattt cttgttactg 180 cagagattgc agaatctgtc caagcatttg tggtttactt tgacagcaca caaaaatcgg 240 gccttgatag tgtctcctca tggcttccac tggcaaaagc atggttaccy gaggtgatga 300 tcttggtctg cgatagagtg tctgaagatg gtataaaccg acaaaaagct caagaatggt 360 gcatccaaac atggctttga attggtagaa cttagtccag aggagttgcc tgaggaggat 420 gatgacttcc cagaatctac aggagtaaag cgaattgtcc aagccctgaa tgccaatgtg 480 tggtccaatg tagtgatgaa gaatgatagg aaccaaggct ttagcttgct gcaactcatt 540 gactggaaca aaccatagca ttgggtcagc agatccctgt cacccagagc aaccccattt 600 gccagcagca gatagtactg aatccctctc tgatcatcgg ggtggtgcat ctaacacaac 660 agatgcccag gttgatagca ttgtggatcc catgttagat ctggatattc aagaattagc 720 cagtcttacc actggaggag gagatgtgga gaattttgaa agactctttt caaagttaaa 780 ggaaatgaaa gacaaggctg cgacgcttcc tcatgagcaa agaaaagtgc atgcagaaaa 840 ggtggccaaa gcattctgga tggcaatcgg gggagacaga gatgaaattg aaggcctttc 900 atctgatgaa gagcactgaa ttattcatac tagggtttga ccaacaaaga tgctagctgt 960 ctctgagata cctctctact cagcccagtc atattttgcc aaaattgccc ttatcatgtt 1020 ggctgcctga cttgtttata gggtcccctt aattttagtt tttagtagga ggttaaggag 1080 aaatcttttt tttcctcagt atattgtaag agagtgagga atacagtgat agtaatgagt 1140 gaggatttct taaatrtact ttttttttgt tctaggaatg agggtaggat aaatctcaga 1200 ggtctgtgtg atttactcaa gttgaagaca acctccaggc cattcctggt caacctttta 1260 agtagcattt ccagcattca cacttgatac tgcacatcag gagttgtgtc acctttcctg 1320 ggtgatttgg gttttctcca ttcaaggagc ttgtagctct gaagctatga tgcttttatt 1380 gggaggaaag gaggcagctg cagaattgat gtgagctatg tggggccgaa gtctcagccc 1440 gcagctaagt ctctacctaa gaaaatgcct ctgggcattc ttttgaagta tagtgtctga 1500 gctcatgcta gaaagaatca aaaagccagt gtggattttt agactgtaat aaatgaggca 1560 aaggatttct attccagtgg gaagraaacc tctctactga gttgtggggg atatgttgta 1620 tgttagagag aaccttaagg agtccttgta tgggccatgg agacagtatg tgataacata 1680 ccgtgatttt catgaagaaa ttcttctgtc ttagagttct cccctgctgc ttgagatgcc 1740 agagctgtgt tgttgcacac ctgcaaaaca aggcacattt ccccctttct ctttaaagcc 1800 aaagagagat cactgccaaa gtgggagcac taaggggtgg gtggggaagt gaaatgttag 1860 gcgatgaatt cctgagcacc ttgtttttct tccaaggttc gtagctcctc tctgcccttc 1920 caagcctgta acctcggagg actatctttt gttctttatc ctttgtcttg tttgagtggg 1980 tcagccccag aggaactgat aagcaaatgg caagttttta aaggaagagt ggaaagtact 2040 gcaaataaaa atccttattt gtttttgtag aaaaaaaaaa aaaaaaaaaa aaaaaaaaag 2100 31 1448 DNA Homo sapiens 31 aaaaaaaaaa aaagcccacc tgaaagcctg tctctttcca ctttgttggc ccttccagtg 60 ggattatcga gcatgttgtt ttttcatagt gcctttttcc ttatttcaag ggttgcttct 120 gagtggtgtt tttttttttt ttaatttgtt ttgttttaaa ataagttaaa gacagtccag 180 agcttttcag ccaatttgtc tcctactctg tgtaaatatt tttccctccg ggcaggggag 240 ccagggtaga gcaaaggaga caagcaggag tggaaggtga ggcgttctcc tgcttgtact 300 aagccaggag stttaagctc cagctttaag ggttgtgagc cccttggggt tcagggaact 360 gcttgcccag ggtgcagtgt gagtgtgatg ggccaccggg gcaagaggga aggtgaccgc 420 ccagctctcc cacatcccac tggatctggc ttacaggggg gtcggaagcc tgtcctcacc 480 gtctcggggg ttgtggcccc cgccccctcc ctatatgcac ccctggaacc agcaagtccc 540 agacaaggag agcggaggag gaagtcatgg gaacgcagcc tccagttgta gcaggtttca 600 ctattcctat gctggggtac acagtgagag tactcacttt tcacttgtct tgctcttaga 660 ttgggccatg gctttcatcc tgtgtcccct gacctgtcca ggtgagtgtg agggcagcac 720 tgggaagctg gagtgctgct tgtgcctccc ttcccagtgg gctgtgttga ctgctgctcc 780 ccacccctac cgatggtccc aggaagcagg gagagttggg gaaggcaaga ttggaaagac 840 aggaagacca aggcctcggc agaactctct gtcttctctc cacttctggt cccctgtggt 900 gatgtgcctg taatcttttt ctccacccaa accccttccc acgacaaaaa caagactgcc 960 tccctctctt ccgggagctg gtgacagcct tgggcctttc agtcccaaag cggccgatgg 1020 gagtctccct ccgactccag atatgaacag ggcccaggcc tggagcgttt gctgtgccag 1080 gaggcggcag ctcttctggg cagagcctgt ccccgccttc cctcactctt cctcatcctg 1140 cttctctttt cctcgcagat gataaaagga atctggcatt ctacacctgg accatttgat 1200 tgttttattt tggaattggt gtatatcatg aagccttgct gaactaagtt ttgtgtgtat 1260 atatttaaaa aaaaaatcag tgtttaaata aagacctatg tacttaatcc tttaactctg 1320 cggatagcat ttggtaggta gtgattaact gtgaataata aatacacaat gaattcttma 1380 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaccccggg gggggccccg ggccccaatt 1440 ccccccaa 1448 32 456 DNA Homo sapiens misc_feature (444) n equals a,t,g, or c 32 ggcacagcaa acttgacgcc atgaagatcc cggtccttcc tgccgtggtg ctcctctccc 60 tcctggtgct ccactctgcc cagggagcca ccctgggtgg tcctgaggaa gaaagcacca 120 ttgagaatta tgcgtcacga cccgaggcct ttaacacccc gttcctgaac atcgacaaat 180 tgcgatctgc gtttaaggct gatgagttcc tgaactggca cgccctcttt gagtctatca 240 aaaggaaact tcctttcctc aactgggatg cctttcctaa gctgaaagga ctgaggagcg 300 caactcctga tgcccagtga ccatgacctc cactggaaga gggggctagc gtgagcgctg 360 attctcaacc taccataact ctttcctgcc tcaggaactc caataaaaca ttttccatcc 420 aaaaaaaaaa aaaaaaaaac cccngggggg gcccgg 456 33 1326 DNA Homo sapiens misc_feature (352) n equals a,t,g, or c 33 ggcacgagtg caggcccaga gaggactcat tgaaaggact gaaaggggag gtggcgtttt 60 cttcctaccc aaacttaccc ctgtgagctg gacagcttgg tagcacctgc ctggacttag 120 atggtggtag ccaagaagac tgacatttta gggaacagga cggggaggag aaggctctgg 180 cacacacaca tgtgtccata tgtcctgcaa tggtctgggg actattgcta ggctaggagc 240 cctaagtgtc ttcttcctca tgtctmttct cccctgtstc atgggcccta agrtctcttt 300 cactgggcct gcctcaatga acgtgctgcc cagctacccc gaaacacggc anctgccggc 360 tatcaatgcc ccagctgcaa tggcccatct tcccccaacc aacctggctg ggcccgtggg 420 ctccgcactg agararaaas ttggcacart caactgggcc cgggcaggac tgggccyccc 480 tctgatcgat gaagktggtg arcccagagc ccgagcccct caacacgtct gacttctctg 540 actggtctag ttttaatgcc agcagtaccc ctggaccaga ggaggtagac agcgcctctg 600 ctgccccagc cttctacagc cgagcccccc ggcccccagc ttccccaggc cggcccgagc 660 agcacacagt gatccacatg ggcaatcctg agcccttgac tcacgcccct aggaaggtgt 720 atgatacgcg ggatgatgac cggacaccag gcctccatgg agactgtgac gatgacaagt 780 accgacgtcg gccggccttg ggttggctgg cccggctgct aaggagccgg gctgggtctc 840 ggaagcgrcc gctgaccctg ctccagcggg cggggctgct gctactcttg ggactgctgg 900 gcttcctggc cctccttgcc ctcatgtctc gcctaggccg ggccgcagct gacagcgatc 960 ccaacctgga cccactcatg aaccctcaca tccgcgtggg cccctcctga gcccccttgc 1020 ttgtggctag gccagcctag gatgtgggtt ctgtggagga gaggcggggt aatggggagg 1080 ctgagggcac ctcttcactg cccctctccc tcaagcctaa gacactaaga ccccagaccc 1140 aaagccaagt ccaccagagt ggctgcaggc caggcctgga gtccccgtgg gtcaagcatt 1200 tgtcttgact tgctttcctc ccgggtytcc agcctccgac ccctcgcccc atgaaggagc 1260 tggcaggtgg aaataaacaa caactttatt aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1320 aaanaa 1326 34 710 DNA Homo sapiens 34 gcgaaagaga aaaaggctgg agctcccgcc cccggggctg tcagatggct tgggtttctg 60 cgacgcgatt ggctcgcgga gggcagaaat tactcagcaa acatgactat tattagctgc 120 ttagcaacag ctcaccaaag tagagagacc acccaggtag gcaacccagt gtgtgcatcc 180 tcggcttcgg ggcagcctct gagagcgcca accttctcgc atgcaatact tccattaagg 240 aatgctcccc ctcctttctc tcttattcct tttcttttca acagtgtctt ctttttgtgg 300 gatgcctttg cgcgcacaca cgcgcgcgca sgcacacaca cgaacatttg cctcgcggta 360 gacacggggg gaaatgtwat atttttttaa gcgcttaaac aatttctgaa attcctcaaa 420 gaaaagcctt tcagargcac cttggcctca agctgcaaca aatactggga rgtccggctc 480 gcattcccag gcctgcacca ataatgacag cgtgctggat artgcgccag tgtgtgccag 540 attttttttt cctcttctct tttcttttat aactaaaggg aagacttagg ctcttgcagg 600 gaacaacgcc tcgcattaag ataaacagaa tggaaagtta aagaggaaag caaggacgtt 660 gggaaaagcc atctttctta aaatccgtct gccccccagc cgctttctcc 710 35 1188 DNA Homo sapiens 35 gatggctttt atatctatta tcgacccaca gacagtgaca atgatagtga ctacaagaag 60 gatatggtgg aaggggacaa gtactggcac tccatcagcc acctgcagcc agagacctcc 120 tacgacatta agatgcagtg cttcaatgaa ggaggggaga gcgagttcag caacgtgatg 180 atctgtgaga ccaaagctcg gaagtcttct ggccagcctg gtcgactgcc acccccaact 240 ctggccccac cacagccgcc ccttcctgaa accatagagc ggccggtggg cactggggcc 300 atggtggctc gctccagcga cctgccctat ctgattgtcg gggtcgtcct gggctccatc 360 gttctcatca tcgtcacctt catccccttc tgcttgtgga gggcctggtc taagcaaaaa 420 catacaacag acctgggttt tcctcgaagt gcccttccac cctcctgccc gtatactatg 480 gtgccattgg gaggactccc aggccaccag gcagtggaca gccctacctc agtggcatca 540 gtggacgggc ctgtgctaat gggatccaca tgaatagggg ctgcccctcg gctgcagtgg 600 gctacccggg catgaagccc cagcagcact gcccaggcga gcttcagcag cagagtgaca 660 ccagcagcct gctgaggcag acccatcttg gcaatggata tgacccccaa agtcaccaga 720 tcacgagggg tcccaagtct agcccggacg agggctcttt cttatacaca ctgcccgacg 780 actccactca ccagctgctg cagccccatc acgactgctg ccaacgccag gagcagcctg 840 ctgstgtggg ccagtcaggg gtgaggagag cccccgacag tcctgtcctg gaagcagtgt 900 gggaccctcc atttcactca gggcccccat gctgcttggg ccttgtgcca gttgaagagg 960 tggacagtcc tgactcctgc caagtgagtg gaggagactg gtgtccccag caccccgtag 1020 gggcctacgt aggacaggaa cctggaatgc agctctcccc ggggccactg gtgcgtgtgt 1080 cttttgaaac accacctctc acaatttagg cagaagctga tatcccagaa agactatata 1140 ttgttttttt tttaaaaaaa aaaaaaaaaa awcycggggg ggggcccc 1188 36 956 DNA Homo sapiens misc_feature (404) n equals a,t,g, or c 36 ggcagagcag tgaaaatgca tcctaaaaat tcaatgttta taccaggctc atgacactaa 60 gatgtgacat ctggacacga ggggtcagcc acgtggatac atccctccca gattgcatct 120 ccaggaatca ctctgctagc agaatgggcg ccccatccct tactatgctg ctcctcctca 180 aagtgcagcc cagaaggacc caggcctttg atgcacattg ggtgggtctc ccactacttt 240 agttgaaatg ggagcatgct ggagtcggcg ttctgttgct tctggtgaga aggacatccc 300 attgacccct ggccaccagg tccagtattc catccttcct tctgtcccag cctatcgccc 360 tccccacyag gcccaccccc acaacttctc ctcaagggag gttntcccgc agctggaggg 420 cttgcacaga ccagcagtca cagaaatcat tcttcctgct gtactgggcc ttaactgcct 480 gcaaatgtcc gagcactact gcataggatg ccagagccac cgaagataaa cacagccaag 540 tttaataata ataaaaggaa aaatctcagc ctgcagaact ctggttttga cccaccatcg 600 gccagatgca catcttcagg gcctgttgag caccttctga aaagcagggc tcgtaataga 660 ctccagcaca ttccatcaga gtcaggaaaa ctgcggtgag tcccagagaa tctagggtgc 720 agggcaggga gcaggagtca taaggagtga taacctaaac tgtgtgtagt cagcggggag 780 ggtcttatgt tatcaggtga aatgagagcc agtaagttag ttgatcctgt cacagatata 840 accctgataa caccccatag atacgcgaca cgtgtgtcct gcccctgctt tccccatcca 900 acatggttct tctgttccac agacattaaa ggggctttct gcaattactt aaaaaa 956 37 1603 DNA Homo sapiens 37 tcgacccacg cgtccgctct gccaggaatc tggtctttct gtagacccaa gtcagaaaga 60 accatttgtg gagttaaatc gaatattaga rgcattaaar gtcagagttc tgagacctgc 120 tctggaatgg gcagtttcaa accgagagat gcttatagcc caaaacagct ccttggaatt 180 taaactacac agactgtatt ttattagctt rttaatgggt ggaacacaaa tcagcgagar 240 gcattacaat atgctaaaaa ttttcagcca tttgccctaa atcatcaaaa agacattcag 300 gttttgatgg gaagccttgt gtacctgaga caagggattg agaactcacc atatgttcac 360 ctacttgatg caaaccagtg ggctgatatc tgtgacatct ttacacggga tgcttgtgcc 420 ctcctggggc tctccgtgga gtcccctctc agtgtcagtt tctcagcagg ttgtgtggcg 480 ctgccagctt taattaacat caaagccgtg attgaacaga ggcagtgtac tggagtttgg 540 aaccagaaag atgaattacc tattgaagtg gaccttggta aaaagtgctg gtatcactct 600 atatttgcct gccccattct tcgtcagcaa acaacagata acaatccacc catgaaattg 660 gtctgtggtc atattatatc aagagatgcc ctgaataaaa tgtttaatgg tagcaaatta 720 aaatgtccct actgtccaat ggaacaaagt ccaggagatg ccaaacagat atttttctga 780 agagataact ttagtttgca atttgtaagt gaaactgaat cgtgggtgca tttcagaaga 840 gaacgttcca tataatgcag ctaaccaagg actcctgtgt ttctataagc taatgctcca 900 gaaactttgc caacctgtta gtgtacacac actgagggga gtgctcccgg tgaatattat 960 catagggctt tattatattc ttggtcttca tttctgatca agtaaataca ccagcagttg 1020 tcattcaatg caggtttttg tacttaatta tatggtgatt tttttacttt ttaagagcag 1080 aaacggaaat tgacctcccc gccatgtgtt taatattcct cctgctttta cttttgtcat 1140 tttcttgata atcgtaagcc ttgagagtgt ttgtgaaaaa gttttatttc ctgttatgta 1200 tacataatta aatgaaaatt cttcagaaaa agtttgataa attgaattgt ggttatgaaa 1260 ctaatttgca tttttatttg cttaagaaag aaagctgtga tagattccag atatgctttt 1320 tgatgttttc ctctgctcca gctccaagaa gtcagcacac ctgcatttta gctctgcatg 1380 cagccccagc aggctgcgtg tttaagaatt tcattgttta actggctggt gtgagaagtc 1440 ttccgttagc atagagtgga aggagtacta ttgtttggtt gggtttttgt ttgtttgttt 1500 tttgtttttg cttttattgc caagaggtgc ttgttttaaa agtatgttta ataaaatgaa 1560 attctaaagt taaraagtgt tcttaaagtt gatatttaac tct 1603 38 1089 DNA Homo sapiens 38 ggcacgagct acctttctgc ctgctttgct ggctgcaaca gcacgaatct cacgggctgt 60 gcgtgcctca ccaccgtccc tgctgagaac gcaaccgtgg ttcctggaaa atgccccagt 120 cctgggtgcc aagaggcctt cctcactttc ctctgtgtga tgtgtatctg cagcctgatc 180 ggtgccatgg caagacaccc tcagtcatca tcctcatcag gacagtcagc cctgaactca 240 agtcttacgc tttgggagtt ctttttctcc tccttcgttt gttgggcttc atccctccac 300 ccctcatctt cggggctggc atcgactcca cctgcctgtt ctggagcacg ttctgtgggg 360 agcaaggcgc ctgcgtcctc tacgacaatg tggtctaccg atacctgtat gtcagcatcg 420 ccatcgcgct caaatccttc gccttcatcc tgtacaccac cacgtggcag tgctgaggaa 480 aaactataaa cgctacatca aaaaccacga gggcgggctg agcaccagtg agttctttgc 540 ctctactctg accctagaca acctggggag ggaccctgtg cccgcaaacc agacacatag 600 gacaaagttt atctataacc tggaagacca tgagtggtgt gaaaacatgg agtccgtttt 660 atagtgacta aaggagggct gaactctgta ttagtaatcc aagggtcatt tttttcttaa 720 aaaaagaaaa aaaggttcca aaaaaaacca aaactcagta cacacacaca ggcacagatg 780 cacacacacg cagacagaca caccgacttt gtcctttttc tcagcatcag agccagacag 840 gattcagaat aaggagagaa tgacatcgtg cggcagggtc ctggaggcca ctcgcgcggc 900 tgggccacag agtctacttt gaaggcacct catggttttc aggatgctga cagctgcaag 960 caacaggcac tgccaaattc agggaacagt ggtggccagc ttggaggatg gacatttctg 1020 gatacacata cacatacaaa acagaaaaca ttttttaaaa gaagtttcct aaaataaaaa 1080 aaaaaaaaa 1089 39 629 DNA Homo sapiens 39 agctcagttc ccttagaaat gaaattttaa atgacactac caggtaagcc actgagacca 60 gtggaggtga tagctaagaa cataaggaat taagaatttt taatggagaa aggaggtaat 120 gaataccagt tacatcctaa gactcactgt agtggtgagt gttgtaattt atctcgctat 180 ccatcctctt ttaagttttt ccttagaaag tcctctattg gtaccttgga gggactgctg 240 tcaaaatata tggaaaagtg ggtctgtgtg gtacaagagg tggactttgc cacacatgga 300 agtttgctgc caagatcttc actaatgaaa gaaatcacca gtgagctgca cagattagcc 360 aaatactgag ctcattagaa ctactaaggc ctggacattt ctgcctaatc caggactcct 420 gtaattatca gtctttgctt tggagcttcc cattgtgtag ctgaraattt gtcatatctg 480 cattataatc taaggctcca catacttaat cctgcttctc cccctttttc tttccctttc 540 ccagcggtca gctctgctgc atagtctgaa gactttccct gcccaatcct gataaaattc 600 ttgcactcgt aaccccatct cagtgtctg 629 40 1964 DNA Homo sapiens misc_feature (353) n equals a,t,g, or c 40 aagaagacat ggaaattgct gaaggatgtt tcaggcatat taagaaaatc tttacgcagc 60 ttgaggaatt cagagcctct gaattgcttc gaagtggact ggacagatct aaataccttt 120 tagtgaaaga agccaaaatt attgctatga cctgtactca tgctgcctta aaacgacatg 180 acttggtcaa gctaggtttc aagtatgaca acattttgat ggaagaggct gctcagattc 240 tggagataga aacttttatc cctcttcttc tacagaatcc tcaggatgga tttagccgac 300 taaaacgatg gattatgatt ggcgatcatc accagttacc tccagttatt aangaacatg 360 gcctttcaaa agtactcaaa catggagcag tctctcttca ctcgctttgt tcgcgttgga 420 gttccgactg ttgaccttga tgctcaaggg agagccagag caagcttgtg camctnctac 480 aactggcgat acaagaatct aggaaactta ccccatgtgc agctcttgcc agagtttagt 540 acagcaaatg ctggcttact gtatgacttc cagctcatta atgttgaaga ttttcaagga 600 gtgggagaat ctgaacctaa tccttacttc tatcagaatc ttggagaggc agaatatgta 660 gtagcacttt ttatgtacat gtgtttactt ggttaccctg ctgacaaaat cagtattcta 720 acaacatata atggccaaaa gcatcttatt cgcgacatca tcaatagacg atgtggaaac 780 aatccattga ttggaagacc aaacaaggtg acaactgttg atagatttca aggtcaacag 840 aatgactata ttcttctttc tctggtacga accagggcag tgggccatct gagggatgtc 900 cgtcgcttgg tagtggccat gtctagagcc agacttggac tttatatctt cgccagagta 960 tccctcttcc aaaactgttt tgaactgact ccagctttca gtcagctcac agctcgcccc 1020 cttcatttgc atataattcc aacagaacct ttcccaacta ctagaaagaa tggagagaga 1080 ccatctcatg aagtacaaat aataaaaaat atgccccaga tggcaaactt tgtatacaac 1140 atgtacatgc atttgataca gactacacat cattatcatc agactttatt acaactacca 1200 cctgctatgg tagaagaggg tgaggaagtt caaaatcaag aaacagaatt ggaaacagaa 1260 gaagaggcca tgactgttca agctgacatc atacccagtc caacagacac cagctgccgt 1320 caagaaactc cagcctttca aactgacacc acccccagtg agacaggagc cacttccact 1380 ccagaagcca tccctgcttt atctgagacc acccctactg tggtaggagc tgtatctgca 1440 ccggcagaag ctaacacacc tcaggatgcc acatctgccc cagaagagac caagtagcca 1500 aactgtagtc cttctaaagg aggacatggc agtcaaaaag tctgagtaaa gctgtttttt 1560 gtattttata tttgcttctg ccattttact gtcactaatt aatgtttagt tcttatattt 1620 gttaactgat ttcggtgtct tgaatatatt tttttaaatt atgtgtatga acaattctag 1680 tttcatttgt tcaatcagaa gagcaaataa ccattccttt catgttttga tcactgagtg 1740 tgtctgtaat catacctaca ttaaaatcat tttctatgaa tatataatat atacttcaca 1800 tttttagtga acttctctaa agaagaggac agaatatact ggacttaacc acgaataccc 1860 ttgagtgtcc aaattgggaa ggaactkgtt tcttcygtta tactaycaaa tgcttaaatt 1920 ckgtttcctt ttttcttacc tttgtttgct gtctttatgt aaag 1964 41 1522 DNA Homo sapiens misc_feature (1282) n equals a,t,g, or c 41 cgtgtccgcg cgcctgggag acgctgcctc ggcccggacg cgcccgcgcc cccgcggctg 60 gagggtggtc gccactggga cactgtgaac caggagtrag tcggagctgc cgcgctgccc 120 aggccatgga ctgtgaggtc aacaacggtt ccagcctcag ggatgagtgc atcacaaacc 180 tactggtgtt tggcttcctc caaagctgtt ctgacaacag cttccgcaga gagctggacg 240 cactgggcca cgagctgcca gtgctggctc cccagtggga gggctacgat gagctgcaga 300 ctgatggcaa ccgcagcagc cactcccgct tgggaagaat agaggcagat tctgaaagtc 360 aagaagacat catccggaat attgccaggc acctcgccca ggtcggggac agcatggacc 420 gtagcatccc tccgggcctg gtgaacggcc tggccctgca gctcaggaac accagccggt 480 cggaggagga ccggaacagg gacctggcca ctgccctgga gcagctgctg caggcctacc 540 ctagagacat ggagaaggag aagaccatgc tggtgctggc cctgctgctg gccaagaagg 600 tggccagtca cacgccgtcc ttgctccgtg atgtctttca cacaacagtg aattttatta 660 accagaacct acgcacctac gtgaggagct tagccagaaa tgggatggac tgaacggaca 720 gttccagaag tgtgactggc taaagctcga tgtggtcaca gctgtatagc tgcttccagt 780 gtagacggag ccctggcatg tcaacagcgt tcctagagaa gacaggctgg aagatagctg 840 tgacttctat tttaaagaca atgttaaact tataacccac tttaaaatat ctacattaat 900 atacttgaat gaaaatgtcc atttacacgt atttgaatgg ccttcatatc atccacacat 960 gaatctgcac atctgtaaat ctacacacgg tgcctttatt tccactgtgc aggttcccac 1020 ttaaaaatta aattggaaag caggtttcaa ggaagtagaa acaaaataca atttttttgg 1080 taaaaaaaaa ttactgttta ttaaagtaca accatagagg atggtcttac agcaggcagt 1140 atcctgtttg aggaaagcaa gaatcagaga aggaacatac cccttacaaa tgaaaaattc 1200 cactcaaaat agggactatc yatcttaata ctaaggaacc aacaatcttc ctgtttaaaa 1260 aaccacatgg cacagagatt cngaactaaa gtgctgcact caaatgatgg gaagtcccgg 1320 ccccagtaca ccaggggctt tggacttttt tcaacttcgt ttccttttgt ttggantcca 1380 aaagaaccac tttgtggttc ttaaaagggt gtgaaggtga tttaaggggc ccaggtcagc 1440 cactggttgg tttacaaaat cngggtaact aactgcatac aactttttcc cntttccatg 1500 ncatcaggac tttgctaaag ac 1522 42 875 DNA Homo sapiens 42 tgggatttcc ctttatcatg gaggccttgt cccacttcct ctatgtccct ttccttggtg 60 tctgtgtctg tggggccatc tacactggcc tgttccttcc tgagaccaaa ggcaagacct 120 tccaagagat ctccgaggaa ttacacagac tcaacttccc caggcgggcc cagggcccca 180 cgtggaggag cctggaggtt atccagtcaa cagaactcta gtcccaaagg ggtggccgta 240 gccaaagcca gctaccgtcc tgtcctctgc ttcctgccag ggccctggtc ctcamtycct 300 yctgcattcc tcatttaagg agtgtttatt gagcaccctt tgtgtgcaga catggctcca 360 ggtgcttagc aatcawtggt gagcgtggta tccaggctaa aggtaattaa ctgacagraa 420 atcagtaaca acataattac aggytggttg tggcagytca tgactgtaat cccagcactt 480 ttgggagcca aggtgggarg atcaattgag gccagagttt gaaamcagct aggtaacata 540 gtgagacccc ctatctctac aaaaaatttt aaacattagc tgggcatggt ggtatgtgct 600 aacagctcta gctactcagg aggctgaggc agcaggatca cttgagtcca agagttcaag 660 gtagcagtaa gctacaatca caccactgca tgccagactg ggtgacagag ggagacttca 720 tctctttaaa acataataat aataattaca gactcaggaa atgcagtgaa agaaaaatac 780 aggttggcca ggtgaggtgg ctgatgcctg taatcccagc actttgggag gccaagatgg 840 gaagattgct ttgagaccag aagtttgaga ccagc 875 43 843 DNA Homo sapiens misc_feature (14) n equals a,t,g, or c 43 cccacgcggt ccgnatcgtc cttccctcac ttcagagggt ggccagagct gaatacccag 60 agagggacaa gtaagggtcc agttccaaaa catcatgagg atgtatcatc ccacgtgtct 120 cacctgacag ttacagagga aacccgcacc cagaatgcac gtgctgtctt atgggaacac 180 tcagcgcaga gtgctcaggt ccggccacac tcgggctgtg cttggtcgtg ccatggaatt 240 cctcaggact ttctcagcct ccctaatggc agaagcccct ttacagcaag acatttaccg 300 tttgtctgaa aatagccgaa ctgagctttt cttcaggcta tatgagaagt ctctagacag 360 tgggcaccgt cagaaagccc agagccttgt gatagctccc accctgcctg gctcagatct 420 tcccattttt tttcctctgg cactaacctc accttttgtt tttttgtgtt tgtgtttgtt 480 tttgtttttg cagagttgga ttacagaaac tcctatgaaa ttgaatatat ggagaaaatt 540 ggctcctcct tacctgtaag ttcgtctgcc tcgggccact taggggactc gctttcctgc 600 cttcaggggc ctcctcccct gtgcagagtg tctctgggag ctcagacccc aaatcgagtg 660 ttttctgtgt acacagcttc ccgggtgcac agcaatgatg gactggggct ggggggttga 720 ggtttgtact caatccactt cgtttgacat tttcagggag aaaatgatag aatacaatta 780 gacgtcctgc agaattactt tcctagactg agaaagagct agagatttct ttaaaaaaaa 840 aaa 843 44 489 DNA Homo sapiens 44 ctcttaggct ttgaagcatt tttgtctgtg ctccctgatc ttcaggtcac caccatgaag 60 ttcttagcag tcctggtact cttgggagtt tccatctttc tggtctctgc ccagaatccg 120 acaacagctg ctccagctga cacgtatcca gctactggtc ctgctgatga tgaagcccct 180 gatgctgaaa ccactgctgc tgcaaccact gcgaccactg ctgctcctac cactgcaacc 240 accgctgctt ctaccactgc tcgtaaagac attccagttt tacccaaatg ggttggggat 300 ctcccgaatg gtagagtgtg tccctgagat ggaatcagct tgagtcttct gcaattggtc 360 acaactattc atgcttcctg tgatttcatc caactactta ccttgcctac gatatcccct 420 ttatctctaa tcagtttatt ttctttcaaa taaaaaataa ctatgagcaa caaaaaaaaa 480 aaaaaaaaa 489 45 534 DNA Homo sapiens misc_feature (470) n equals a,t,g, or c 45 gaagcagtgt gtatctatga ttatatctct gttcatctat atatttttga catgtagcaa 60 cacctctcca tcttatcaag gaactcaact cggtctgggt ctccccagtg cccagtggtg 120 gcctttgaca ggtaggagga tgcagtgctg caggctattt tgttttttgt tacaaaactg 180 tcttttccct tttcccctcc acctgattca gcatgatccc tgtgagctgg ttctcacaat 240 ctcctgggac tgggctgagg caggggcttc gctctattct ccctaaccat actgtcttcc 300 tttccccttg ccacttagca gttatccccc cagctatgcc ttctccctcc ctcccttgcc 360 ctggcatata ttgtgcctta tttatgctgc aaatataaca ttaaactatc aagtgaaaaa 420 aaaaaaaaaa aaaactccaa gggggggccg gtacccaatt ccccctatan tgagtcntat 480 tacaattcac tgggccgtcg ttttacaacg tcgtgaatgg gaaaacctgg gcgt 534 46 1374 DNA Homo sapiens 46 ggcacgagtc cgggatgagc tcagccgcgg ccgaccactg ggcgtggttg ctggtgctca 60 gcttcgtgtt tggatgcaat gttcttagga tcctcctccc gtccttctca tccttcatgt 120 ccagggtgct gcagaaggac gcggagcagg agtcacagat gagagcggag atccaggaca 180 tgaagcagga gctctccaca gtcaacatga tggacgagtt tgccagatat gccaggctgg 240 aaagaaagat caacaagatg acggataagc tcaaaaccca tgtgaaagct cggacagctc 300 aattagccaa gataaaatgg gtgataagtg tcgctttcta cgtattgcag gctgccctga 360 tgatctcact catttggaag tattattctg tccctgtggc tgtcgtgccg agtaaatgga 420 taacccctct agaccgcctg gtagcctttc ctactagagt agcaggtggt gttggaatta 480 cctgttggat tttagtctgt aacaaagttg tcgctattgt gcttcatccg ttcagctgaa 540 caggaggatg gatacagccg cgaggctaaa aaacggattt cctcttccta gcttaaaatc 600 tgatttacac tgttttgttt tttaagaaac aaaagtgcat agtttagatt tttttttttg 660 ttgaatatgt ttgttcttgg actttatgag agagtcttat aagaatcacg attttctaca 720 cctgtcattg agccaagaaa gtccagttta tgacacgtat gtactagtga acaccgtcct 780 cgatctgtac gaaatgtgaa atgtttaggg acatctccat gctgtcactt gtgatttgcc 840 ctcttatgta ttttggtcat attgccaact ggaaagtcaa aattttctaa caactttaag 900 taagttcttt gaagacttag tgctgttttt aatccagttt agaaagtaac ttaattttaa 960 taccactact aaaaattcga aaatttcttc tttaatcaca ttcaatatgg ttaaaagaac 1020 aacactaatt gacattgcgt gggctttttc tccctttgtt taaaatgtca tttgttgagc 1080 aagagttgta tagtattatc tacttacttg aggctgttaa tttttcatta cagtgttttg 1140 taaatgtatc cacgagacca tgatgcattg ttttgtgctc aacttgtgtt ttgtatttaa 1200 agcattttga atgaagtgta ttttataagc atttaatatt tatgctcttt agaatggaac 1260 acagaaaaca aaccttataa gtcctgatta atctgaacca ataacctgtg tggcctacaa 1320 agtataattc tattaaatgt tccttaaaac aaaaaaaaaa aaaaaaaaaa aaaa 1374 47 596 DNA Homo sapiens misc_feature (8) n equals a,t,g, or c 47 gaattcgnca cgagattact tggacatgaa agaactcagg ttcaagttta ttcatttact 60 aagttagtta aatcatgtgc cttccatgag ccttcatttg gtaacttgga aaatggaaat 120 aataacacta gtcatatata ttctacactg ctaccatatg gaccaaaggg attatagatt 180 acaatcacca tcattcctgc tgacaggtat atagaaaaca atttcattga agaaaagtcc 240 ttacatttat ccttttccta atatctgcat gggtaaacta ataaatatag tcattagaaa 300 acccttatta ttattattag ttcaatgtga gaactgctgc agaaaaaata tgctttataa 360 tattttcttg aatatacata atattcataa attttcaaat cattgaaaat taccttaaaa 420 ttggaaaaaa tgtgcatttc tactcatata acagtataaa attcctatgt caatctcttt 480 tttttttttt tgttttgagt tggagtctcg ctctgtcgcc caggctgggc aacagagcag 540 gaccctgtct taattaaaaa aaaaaaaaaa aaactcgagg ggggcccggt acccta 596 48 851 DNA Homo sapiens 48 cacatgaaga cacacagtgg tgagaagccc ttccgctgcg cccgctgtcc ttatgcctct 60 cctcatctgg ataacctgaa acggcaccag cgcgtccata caggagagaa gccctacaag 120 tgccccctct gcccttatgc ctgtggcaat ctggccaacc tcaagcgtca tggtcgcatc 180 cactctggtg acaaaccttt tcggtgtagc ctttgcaact acagctgcaa ccagagcatg 240 aacctcaaac gtcacatgct gcggcacaca ggcgagaagc cttccgctgt gccacctgcg 300 cctataccac gggccactgg gacaactaca agcgccacca gaaggtgcat ggccacggtg 360 gggcaggagg gcctggtctc tctgcctctg agggctgggc cccacctcat agcccaccct 420 ctgttttgag ctctcggggc ccaccagccc tggggactgc tggcagccgg gctgtccaca 480 cagactcatc ctgaactagg tccttcttcc ccatgtttta tacagacgga ccagaagcca 540 cctttttctc ccccgctggc caggggctcc acacagacta acgtaggcac tataaggacc 600 agcccaaccc catgggcggg ggggcccata tggaccaggg gaccttgcct tgactgaggc 660 acttcacgag ctcagtgaga agggccctgt attcacctcc actgccccca ggggctgtgg 720 acaaaccggc tgggggactg cccagcctcc cacctgttta tttaacttat ttcagtgctt 780 tataataaag gaaacactaa caaagccatg tctatgctga attggcaatg gcaggcaatt 840 tggccttacc c 851 49 2020 DNA Homo sapiens misc_feature (1239) n equals a,t,g, or c 49 gtgaaatgaa aacagtcttt ttatagcctt tagcttgtga gtttggaagt ttggggggtc 60 ttatgtttgt tttgcctctt ctgtttcttg gaggagagtt gaggcttttc ttaggtgcat 120 acacagaccc aggtgaacac gctgactgtg aacctgccct gtatccggag ctgtgctggg 180 cactgagggg atgcaacaaa attaggagag gwtccttgct cccaacgtct acttctccta 240 cctcaacagg ggtccagggt gcagtgaact cagttcttgg cccttgggtg aggattcatg 300 gatgaatgaa agctagacct gatggggagg cattatgact aaataggccc agcctccttc 360 ccttccagct ctgtcctagg agcataggcg ggaaatctga gtagagtctg actgcagttt 420 ttgcttatga tttgtaaaag ccgtcatggg gtcaataaga aaataggggt gatggagggg 480 gagaagccca ggactgggag aatcgcacgt gccccagggg ttttcaccaa ggattttcaa 540 gacaaactgg agtaagaatt aaagccccag aggatttaat tatcctggtt tgcaaaagag 600 cctcccatgc cagtaccgcc cagccttgga ggccggaatg ctcatggccc ctgtggtctg 660 cttgtccttc agcccatgcc cagcagatac ctctctgact ggagacgggc tcaaagctgg 720 attagaaagg ggagmggcac ttgtgacttt gtttgactct gtgactcact tcctcgctca 780 caccttgttt gaactactgg actttcaact ggctttcctt aggtcaggca agcagacagc 840 tccccactga agaggtctgt acagtgacaa cccgggccgg cagcaaggac acagatgcag 900 ccacagtaag gctccatcag gactgggtca gtgatggcaa caggatggcc aaggatggct 960 ctagaacayt ctgtccatgc gtcactcccc ccagttttrt ttttagcttt ggcttcaggg 1020 agtgacagcc atcacaaata gccacattct gctctactct ccaacatacc agattstaca 1080 ctgttgttat ttcatgagac gtgaatgttg cagagagtgg ggggattctg gttgttaagg 1140 aacttacact ggggagcttt actcttccgt gtcaacaatg tgactacatg ttctccagat 1200 tagccacaca tgcaaacatc agtgtccttc tagctttanc cgagaaagaa accagtccca 1260 gggaatgaat ggtggtctcc ccactcccgg cagcacttta ggcagcccat aagctatgcg 1320 agaatgtgaa cgctcacctt gctccgtcac ggttctgacc taccacataa acaggaagaa 1380 gccagtgacc ggaacagctc taggaataac aagtcagaat agaagtgtcc tttatattac 1440 cagaaaatat gggcttggcc taagtcgctg tctcctaacc tgccggggtc attccccacc 1500 aaacacccca tactaaggag ccatgagcca cctggacatt caccttttct ttgaccatct 1560 ggagtctggg gcaacttaag gaaggcncca cacagtggtg caggcacatt tccaagcgta 1620 ggtgtccctg gcttttgtgg ccaaagctag tgttatggtc aacaacaggc cagggtctgt 1680 ggggcactga ccttgaaagt ggcaaaatgg aggtttcaca ggctgtgcgg gagcaggacg 1740 gcttgcttca tctaacaatc tcagtttcct ttaaaaaaag aaagaaagga aaagatttca 1800 taagcaggtg tcagtggaca gtttaagyac ttaaccattt ctctttcttc ttatggatgt 1860 gaactgtgct gtggataaat catttgtatt tcttgaatgt tctctatgac taacagttat 1920 taagtcggtt gtgtatatgt gtaactaatg taactgcctt ttaaaatttc attacaataa 1980 aaatgacttt gctctgaama aaaaaaaaaa aaaaactcga 2020 50 2432 DNA Homo sapiens 50 atgaagggtc gttggtggga aagatggcgg cgactctggg accccttggg tcgtggcagc 60 agtggcggcg atgtttgtcg gctcgggatg ggtccaggat gttactcctt cttcttttgt 120 tggggtctgg gcaggggcca cagcaagtcg gggcgggtca aacgttcgag tacttgaaac 180 gggagcactc gctgtcgaag ccctaccagg gtgtgggcac aggcagttcc tcactgtgga 240 atctgatggg caatgccatg gtgatgaccc agtatatccg ccttacccca gatatgcaaa 300 gtaaacaggg tgccttgtgg aaccgggtgc catgtttcct gagagactgg gagttgcagg 360 tgcacttcaa aatccatgga caaggaaaga agaatctgca tggggatggc ttggcaatct 420 ggtacacaag gaatcggatg cagccagggc ctgtgtttgg aaacatggac aaatttgtgg 480 ggctgggagt atttgtagac acctacccca atgaggagaa gcagcaagag cgggtattcc 540 cctacatctc agccatggtg aacaacggct ccctcagcta tgatcatgag cgggatgggc 600 ggcctacaga gctgggaggc tgcacagcca ttgtccgcaa tcttcattac gacaccttcc 660 tggtgattcg ctacgtcaag aggcatttga cgataatgat ggatattgat ggcaagcatg 720 agtggaggga ctgcattgaa gtgcccggag tccgcctgcc ccgcggctac tacttcggca 780 cctcctccat cactggggat ctctcagata atcatgatgt catttccttg aagttgtttg 840 aactgacagt ggagagaacc ccagaagagg aaaagctcca tcgagatgtg ttcttgccct 900 cagtggacaa tatgaagctg cctgagatga cagctccact gccgcccctg agtggcctgg 960 ccctcttcct catcgtcttt ttctccctgg tgttttctgt atttgccata gtcattggta 1020 tcatactcta caacaaatgg caggaacaga gccgaaagcg cttctactga gccctcctgc 1080 tgccaccact tttgtgactg tcacccatga ggtatggaag gagcaggcac tggcctgagc 1140 atgcagcctg gagagtgttc ttgtctctag cagctggttg gggactatat tctgtcactg 1200 gagttttgaa tgcagggacc ccgcattccc atggttgtgc atggggacat ctaactctgg 1260 tctgggaagc cacccacccc agggcaatgc tgctgtgatg tgcctttccc tgcagtcctt 1320 ccatgtggga gcagaggtgt gaagagaatt tacgtggttg tgatgccaaa atcacagaac 1380 agaatttcat agcccaggct gccgtgttgt ttgactcaga aggcccttct acttcagttt 1440 tgaatccaca aagaattaaa aactggtaac accacaggct ttctgaccat ccattcgttg 1500 ggttttgcat ttgacccaac cctctgccta cctgaggagc tttctttgga aaccaggatg 1560 gaaacttctt ccctgcctta ccttcctttc actccattca ttgtcctctc tgtgtgcaac 1620 ctgagctggg aaaggcattt ggatgcctct ctgttggggc ctggggctgc agaacacacc 1680 tgcgtttcac tggccttcat taggtggccc tagggagatg gctttctgct ttggatcact 1740 gttccctagc atgggtcttg ggtctattgg catgtccatg gccttcccaa tcaagtctct 1800 tcaggccctc agtgaagttt ggctaaaggt tggtgtaaaa atcaagagaa gcctggaaga 1860 catcatggat gccatggatt agctgtgcaa ctgaccagct ccaggtttga tcaaaccaaa 1920 agcaacattt gtcatgtggt ctgaccatgt ggagatgttt ctggacttgc tagagcctgc 1980 ttagctgcat gttttgtagt tacgattttt ggaatcccac tttgagtgct gaaagtgtaa 2040 ggaagctttc ttcttacacc ttgggcttgg atattgccca gagaagaaat ttggcttttt 2100 ttttcttaat ggacaagaga cagttgctgt tctcatgttc caagtctgag agcaacagac 2160 cctcatcatc tgtgcctgga agagttcact gtcattgagc agcacagcct gagtgctggc 2220 ctctgtcaac ccttattcca ctgccttatt tgacaagggg ttacatgctg ctcaccttac 2280 tgccctggga ttaaatcagt tacaggccag agtctccttg gagggcctgg aactctgagt 2340 cctcctatga acctctgtag cctaaatgaa attcttaaaa tcaccgatgg aaccaaaaaa 2400 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aa 2432 51 2340 DNA Homo sapiens misc_feature (96) n equals a,t,g, or c 51 gacgctgggg gcgggtgggg gcgcggggta ccgggctgga cggccggccg gcgccccctc 60 attagtatgc ggacgaagcg gcgggctgcg cggagngacg tcccctgcag ccgcggaccg 120 aggcagcggc ggcacctgcc ggccgagcaa tgccaagtga gtacacctat gtraaactga 180 gaagtgattg ctcgaggcct tccctgcaat ggtacacccg agctcaaagc aagatgagaa 240 ggcccagctt gttattaaaa gacatcctca aatgtacatt gcttgtgttt ggagtgtgga 300 tcctttatat cctcaagtta aattatacta ctgaagaatg tgacatgaaa aaaatgcatt 360 atgtggaccc tgaccatgta aagagagctc agaaatatgc tcagcaagtc ttgcagaagg 420 aatgtcgtcc caagtttgcc aagacatcaa tggcgctgtt atttgagcac aggtatagcg 480 tggacttact cccttttgtg cagaaggscc ccaaagacag tgaagctgag tccaagtacg 540 atcctccttt tgggttccgg aagttctcca gtaaagtcca gaccctcttg gaactcttgc 600 cagagcacga cctccctgaa cacttgaaag ccaagacctg tcggcgctgt gtggttattg 660 gaagcggagg aatactgcac ggattagaac tgggccacac cctgaaccag ttcgatgttg 720 tgataaggtt aaacagtgca ccagttgagg gatattcaga acatgttgga aataaaacta 780 ctataaggat gacttatcca gagggcgcac cactgtctga ccttgaatat tattccaatg 840 acttatttgt tgctgtttta tttaagagtg ttgatttcaa ctggcttcaa gcaatggtaa 900 aaaaggaaac cctgccattc tgggtacgac tcttcttttg gaagcaggtg gcagaaaaaa 960 tcccactgca gccaaaacat ttcaggattt tgaatccagt tatcatcaaa gagactgcct 1020 ttgracatcc ttcagtactc agagcctcag tcaaggttct gggggccgag ataagaacgt 1080 ccccacaatc ggtgtcattg ccgttgtctt agccacacat ctgtgcgatg aagtcagttt 1140 ggcgggtttt ggatatgacc tcaatcaacc cagaacacct ttgcactact tcgacagtca 1200 atgcatggct gctatgaact ttcagaccat gcataatgtg acaacggaaa ccaagttcct 1260 cttaaagctg gtcaaagagg gagtggtgaa agatctcagt ggaggcattg atcgtgaatt 1320 ttgaacacag aaaacctcag ttgaaaatgc aactctaact ctgagagctg tttttgacag 1380 ccttcttgat gtatttctcc atcctgcaga tactttgaag tgcagctcat gtttttaact 1440 tttaatttaa aaacacaaaa aaaattttag ctcttcccac tttttttttc ctatttattt 1500 gaggtcagtg tttgtttttg cacaccattt tgtaaatgaa acttaagaat tgaattggaa 1560 agacttctca aagagaattg tatgtaacga tgttgtwttg atttttaaga aagtaattta 1620 atttgtaaaa cttctgctcg tttacactgc acattgaata caggtaacta attggaagga 1680 gaggggaggt cactcttttg atggtggccc tgaacctcat tctggttccc tgctgcgctg 1740 cttggtgtga cccacggagg atccactccc aggatgacgt gctccgtagc tctgctgctg 1800 atactgggtc tgcgatgcag cggcgtgagg cctgggctgg ttggagaagg tcacaaccct 1860 tctctgttgg tctgccttct gctgaaagac tcgagaacca accagggaag ctgtcctgga 1920 ggtccctggt cggagaggga catagaatct gtgacctctg acaactgtga agccaccctg 1980 ggctacagaa accacagtct tcccagcaat tattacaatt cttgaattcc ttggggattt 2040 tttactgccc tttcaaagca cttaagtgtt agatctaacg tgttccagtg tctgtctgag 2100 gtgacttaaa aaatcagaac aaaacttcta ttatccagag tcatgggaga gtacaccctt 2160 tccaggaata atgttttggg aaacactgaa atgaaatctt cccagtatta taaattgtgt 2220 atttaaaaaa aagaaacttt tctgaatgcc tactggcggt gtataccagg cagtgtgcca 2280 gtttaaaaag atgaaaaaga ataaaaactt ttgaggaama aaaaaaaaaa aaaaactcga 2340 52 601 DNA Homo sapiens misc_feature (115) n equals a,t,g, or c 52 agtaggggag actgagactg accggtagcc aggcaggcgg acgacgcacg cccggacaga 60 ctgagcaggc gccggagaac cactcacagg ttccccccgc ctttcccttt gaaanctagg 120 cttttgcctt tcccgtggcg cccgagagag aatgctggac tctgccgact tcagcgcaac 180 taangatttc tcaagctagg ggacaaacga tcagcccaat cctgagaagg ggggaaccaa 240 gcaccccgtc cccatccccc tcccctcccc cgactaaact cgggcgccaa acccagccct 300 tctctaacca ccctacttcc tcctctcctt tctagcatgg tggctgtatg gacagtctga 360 cagaacagag actgacatct cccaatctgc cggcccccca cctggaacac tacagtgttc 420 tgcattgcac catgaccctg gatgtgcaaa ctgtagtcgt ttttgccgtg attgtagtcc 480 tcctgcttgt caatgtcata ctcatgtttt tcctgggaac gcgctgaatg gagtccagnc 540 acctgagctg tcgcgaactc tcgctttgat ttcatcccga gagccaccga gaagaaaaaa 600 a 601 53 359 DNA Homo sapiens misc_feature (343) n equals a,t,g, or c 53 ctcgtgccga attcggcacg agagatggta cttttaagag gtaattaggt tgctaagatg 60 gattaacatc tttctcttga cactgagact gggttctcct gggaatggtt agttcccaag 120 agagtgagtt gttataaaac aatgctgcct cttctatttt gcgctttttg tttgcacaaa 180 ctcggtcccc ttctgtttct ctacgatgtt ttgatgcrgc atgaggcagt catgagaacc 240 caccagatac agctgcctga tcctgaattt cccagccaac agaaccaagt gctaaataaa 300 actcttttta ataagttaaa aaaaaaaaaa aaaaaaaaaa aanaaanana aaaaaaaaa 359 54 1141 DNA Homo sapiens 54 ggcacgagct gctgaggcgt gagaatggcg tcccgcggcc ggcgtccgga gcatggcgga 60 cccccagagc tgttttatga cgagacagaa gcccggaaat acgttcgcaa ctcacggatg 120 attgatatcc agaccaggat ggctgggcga gcattggagc ttctttatct gccagagaat 180 aagccctgtt acctgctgga tattggctgt ggcactgggc tgagtggaag ttatctgtca 240 gatgaagggc actattgggt gggcctggat atcagccctg ccatgctgga tgaggctgtg 300 gaccgagaga tagagggaga cctgctgctg ggggatatgg gccagggcat cccattcaag 360 ccaggcacat ttgatggttg catcagcatt tctgctgtgc agtggctctg taatgctaac 420 aagaagtctg aaaaccctgc caagcgcctg tactgctttt ttgcttctct tttttctgtt 480 ctcgtccggg gatcccgagc tgtcctgcag ctgtaccctg agaactcaga gcagttggag 540 ctgatcacaa cccaggccac aaaggcaggc ttctccggtg gcatggtggt agactaccct 600 aacagtgcca aagcaaagaa attctacctc tgcttgtttt ctgggccttc gacctttata 660 ccagaggggc tgagtgaaaa tcaggatgaa gttgaaccca gggagtctgt gttcaccaat 720 gagaggttcc cattaaggat gtcgaggcgg ggaatggtga ggaagagtcg ggcatgggtg 780 ctggagaaga aggagcggca caggcgccag ggcagggaag tcagacctga cacccagtac 840 accggccgca agcgcaagcc ccgcttctaa gtcaccacgc ggttctggaa aggcacttgc 900 ctctgcactt ttctatattg ttcagctgac aaagtagtat tttagaaaag ttctaaagtt 960 ataaaaatgt tttctgcagt aaaaaaaaag ttctctgggc cgggcgtggt ggctcacacc 1020 tgtaatccca gcaccttggg aggctgaggt gggaggatca tttgaggcca ggagtttgag 1080 acctgcctgg gcaacataat gaaacttcct ttccagggag aaaaaaaaaa aaaaaaaaaa 1140 a 1141 55 1560 DNA Homo sapiens misc_feature (8) n equals a,t,g, or c 55 gagagagnga gagaggtatc actgcaaggc tactatgagt attttcaaat caccacatct 60 tatcctgagc aagaggtcac tgttctgtgc tatggtaaga tacaaactat tccttcatat 120 ataataaaat tccacctttt ttcaaaatta atatagggta agtgaagtct mccaatcatg 180 acrgcaragg aaattagtgt ctaaatgrac tgtgrgttac aggtaccttt cactwagggg 240 caggcaggtt tttataaaaa accmtgtggt aatcatcmat tgccattaag ctcctattac 300 tagcttttaa gaccatttta taaagattat ctggtgccta attaacaaga aagaaattag 360 actcaggttt aagatgctgc tggtgttctg aaattactct gaaaggtcat tcaaagaact 420 tcaaacttaa aatttttcat tcatgtattt attccacagt caaaataaat caaaatttaa 480 agctataaca tttttaaaag ataaaggaga atttgtggca cagctgcatt aacaaaacag 540 acaccagtct aaagtgcaac actaaacagg tattctctgt tcccacggtg gaataaatac 600 acacaattac acataagatt tcactaaaga taggagatga ggcaaataac cctttgaaat 660 tacctgccca acaaatagag gcaggctaca ttaatttaac attttactgc aaaatggaaa 720 aaatccccga ggtgactaac tcaaactcct catttcatgc acatgacctt ggcttctgtg 780 ttctttccat agccacatcc aaatccagaa aggctcctgc accccatgct caaaaatgca 840 acctcaagtc cctgaggtcc tcagcacaga ctgacattaa caagcctgtg ttcagccttc 900 atccagaacc tccagggaaa tcaggagcac aaacacagag caaagcaccg tttctttaaa 960 caatggcttt aactgtcgaa tgagctctga caagccatat gcatttcata aacaaaccaa 1020 aacatcatct tcatatcttc ctatttttct tgcaaaaatg ttaagccatc caagtaaaaa 1080 aaaaaatttt aatttaacaa tgaaaaagga acttcaaagg gtttatgcca aaaaacaaac 1140 cagtcctctg cagcctaact catttgtttt tgggctgcga agccatgtag agggcgatca 1200 ggcagtagat ggtccctccc acagtcagcg ccatggtggt ccggtaaagc atttggtcag 1260 gcaggcctcg tttcaggtag acgggcacac catcagcttt ctggaaaaac ttttgtagct 1320 ctggaacttt gtttttccca gcataatcat acactgtgga atcggaggtc agtttagttg 1380 gtgtggcaaa tatgataggt ggtgcttctg tggaaaccac aggctttnaa tctgcgggct 1440 ataggcctcc gaagcccatg ctcctgccaa cttctgcgtg aagccactaa acttgtagta 1500 catgacgccc agagtccggc ttcccgcatc cgctgccaac gcgaccgccc cagagaagga 1560 56 1507 DNA Homo sapiens misc_feature (1047) n equals a,t,g, or c 56 ggaacgcaga gcggagcgtg gagagcggag cgaagctgga taacagggga ccgatgatgt 60 ggcgaccatc agttctgctg cttctgttgc tactgaggca cggggcccag gggaagccat 120 ccccagacgc aggccctcat ggccagggga gggtgcacca ggcggccccc ctgagcgacg 180 ctccccatga tgacgcccac gggaacttcc agtacgacca tgaggctttc ctgggacggg 240 aagtggccaa ggaattcgac caactcaccc cagaggaaag ccaggcccgt ctggggcgga 300 tcgtggaccg catggaccgc gcgggggacg gcgacggctg ggtgtcgctg gccgagcttc 360 gcgcgtggat cgcgcacacg cagcagcggc acatacggga ctcggtgagc gcggcctggg 420 acacgtacga cacggaccgc gacgggcgtg tgggttggga ggagctgcgc aacgccacct 480 atggccacta cgcgcccggt gaagaatttc atgacgtgga ggatgcagag acctacaaaa 540 agatgctggc tcgggacgag cggcgtttcc gggtggccga ccaggatggg gactcgatgg 600 ccactcgaga ggagctgaca gccttcctgc accccgagga gttccctcac atgcgggaca 660 tcgtgattgc tgaaaccctg gaggacctgg acagaaacaa agatggctat gtccaggtgg 720 aggagtacat cgcggatctg tactcagccg agcctgggga ggaggagccg gcgtgggtgc 780 agacggagag gcagcagttc cgggacttcc gggatctgaa caaggatggg cacctggatg 840 ggagtgaggt gggccactgg gtgctgcccc ctgcccagga ccagcccctg gtggaagcca 900 accacctgct gcacgaragc gacacggaca aggaygggcg gctgagcaaa gcgsaaatcc 960 tgggtaattg gaacatgttt gtgggcagtc aggccaccaa ctatggygag gacctgaccc 1020 ggcaccacga tgagctgtga gcmccgngca cctgccacag cctcagaggc ccgcacaatg 1080 accggaggag gggccgctgt ggtctggccc cctccctgtc caggccccgc aggaggcaga 1140 tgcagtccca ggcatcctcc tkcccctggg ctctcaggga ccccctgggt cggcttctgt 1200 ccctgtcaca cccccaaccc cagggagggg ctgtcatagt cccagaggat aagcaatacc 1260 tatttctgac tgagtctccc agcccagacc cagggaccct nggccccaag ctcagctcta 1320 agaaccgccc caacccctcc agctccaaat ctgagcctcc accacataga ctgaaactcc 1380 cctggcccca gccctctcct gcctggcctg gcctgggaca cctcctctct gccaggaggc 1440 aataaaagcc agcgccggga aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1500 aaaaaan 1507 57 450 DNA Homo sapiens 57 tttttttact cgaaaaaatg tttaatagaa tttaaaattt taacttcagg gaatttggaa 60 gttcaatcat tctcaaagag gctgtaagga tgattaaaat cctgaaggaa gccattgaag 120 aaacttcctt ctgctctttc tggaggatct cttttcaatt atctattcat catatatttc 180 ttatcttctg tgcacaattg acaactcttc tttacagcac attcctctty attcccatct 240 cttggtttct gattgttcct ggggctgtgg ataaaaccat tctctgagaa gctgataagc 300 aattggatga gaaagargga gargaaaact ggcaggarga tctggsccca tgcccgcagc 360 cagcacatct ctcttcagac ctggtgaccc cagccactgg gaacctggca ggcaccagct 420 acagtgttgg acactgctcg tgccgaattc 450 58 1147 DNA Homo sapiens 58 ggcacgagac ccattgagca gaaggaggcc aggtgggaaa gctcctggga agagcagcca 60 gactggacac tgggctgctt gagtcctgag tcacaattca gaattcctgg gctccctggg 120 tgcattctat cattccagtt gaaagtttgc ttccttccag tcatgtggct cttcattcta 180 ctctccttgg ctctcatttc agatgccatg gtcatggatg aaaaggtcaa gagaagcttt 240 gtgctggaca cggcttctgc catctgcaac tacaatgccc actacaagaa tcaccccaaa 300 tactggtgcc gaggctattt ccgtgactac tgcaacatca tcgccttctc ccctaacagc 360 accaatcatg tggccctgaa ggacacaggg aaccagctca ttgtcactat gtcctgcctg 420 aacaaagaag acacgggctg gtactggtgt ggcatccagc gggactttgc cagggatgac 480 atggatttta cagagctgat tgtaactgac gacaaaggaa cctggccaat gactttggtc 540 tgggaaagac tatcaggcac aaaaccagaa gctgcaaggc tcccaaagtt gtccgcaagg 600 ctgaccgctc caggacgtcc attctcatca tttgcatact gatcacgggt ttgggaatca 660 tctctgtaat cagtcatttg accaaaagga ggagaagtca aaggaataga agggtaggca 720 acactttgaa gcccttctcg cgtgtcctga ctccaaagga aatggctcct actgaacaga 780 tgtgactgaa gattttttta atttagttca taaagtgatg ctacaacaga ataatcacca 840 tgacaactgg ccccacacct cagagactga ttctgatctc ccaggaattc tgaaggtccc 900 tctatccttg acaacaatca tttgcagcca ggtagcaacg gcagtagtca gaggagctat 960 gatagaccac acccaagcaa ggctgccctc aaataacatc tcaagatctt agttcttatg 1020 cattccatca gtcagaagtg aagaagaggt ggagaatctg gattggggac caggaaatca 1080 cttgtatttt gttagccaat aaattcctag ccagtgttga atgaaaaaaa aaaaaaaaaa 1140 aaaaaaa 1147 59 777 DNA Homo sapiens 59 ggcagaggct cctcagaagg gcgtgggctc tccagtcttc cacagtcccc accatgccct 60 gttgccttac cgctgacgta gctcacccat cttttacttg cctggctaag atgcatggca 120 tywcatttcc tccttgttgc actgcagtca gtccctcact gcccccatct cctggaagag 180 gagcataagc tttgcaaggt cagccacttc tctggggtca cactagttac atcaagacag 240 gactccagct catatgtgcc agtgcagaca ctcttcatcc acctggggcc ctgggcttgg 300 gacctggytc cttgcacagc agargacccg gaggctgaga ggagcttgcg gttgtgtcat 360 agtcacctgg ccagarggaa cgtgagcccc tcccaagctg cagarggarg garcargcgt 420 ggctgtcagc accgaggtag cagagaatta acattcttgt cagcagagaa tgaagcagga 480 atataattaa aactttgccc ttggaatagc tgattcattt gaattttatt ccacacgttt 540 gaaagaggaa agaaaatgtg aagacttgca gcctggttct cgcctggcct gggctggccc 600 agctgtcagg cccggttcct ttctgagcat tcagtccact gatgttgact gagggccagg 660 agagaccctc agcagggtat taccatatca gcctcctatc gctgctggga gaaattacca 720 tgaattcagt ggcttaaaac aacacacgag cctctctgag cctaccctgg ctcagga 777 60 1191 DNA Homo sapiens misc_feature (5) n equals a,t,g, or c 60 aagantgatt ttccttactc tccaaagcgt cagcattttg aagtttcttt tatgaaagtg 60 ggggcaagaa tcagggtgaa aatgagtgta aacaaagccc atcctgtggt cagcacccac 120 tggaggtggc cagcagagtg gcctcagatg ttcctgcacc tggcccagga gcccaggaca 180 gaggtcaaat ctaggcccct tggtctggct ggattcatca ggcaagattc gaaaacaaga 240 aaacctctag aacaagaaac aatcatgtct gcagcagata cggcactgtg gccctatggc 300 catggcaatc gtgagcacca agagaatgag ttacagaaat atctccaata caaagacatg 360 catctcctgg acagtggaca gtcgctggga cacacacaca cacttcaagg ctcacacaac 420 ctaacagcct taaatatctg aagaaacaga atcacgacat taagtcagca gagggagagg 480 taggctgaag cagcaggagg ccaattttat atcccacaga tttttttaaa aatgactccc 540 cagcaagggg tggggagaaa gccactgatt taggagagtt cttggctcag ccaaccactg 600 cggttatcta cacgttttac aaaggcacrg aagtagagag gggctgcact cacgaccctc 660 cccagggccc gcacagccag acacggtggg ttcttccttt ttcccttctg gccttggtgg 720 aattcctacc acggtggcct ctgcctttgg gacaatgcct tcatgctcat ccccgggtca 780 aggatggagt ctgttaccat tttccagggg aaattccaag gaccagcccc gcctcattac 840 gttcacccca caggaaggtg atctggaaag cctgtaaaca cgtactctgg gtggctgagt 900 ggtgtcacca agctgctttt gtgcagggct gaagcacaga caagagggca ggcagctgcc 960 ggaggcctga agtggggaga gatccccgca ggcctgcagg agccagggag aacctccaac 1020 tggatctaaa ctgtgggaca gcccaggcgt gcccctcttc acatggctcc caggctccct 1080 caaagccctt cccaggccct gcaggaagag agggagggtg aggagaggca gggagggcag 1140 aggtcgcctg aaagcctggg ctccgaactc cctcagcaga gctttaaagt g 1191 61 1580 DNA Homo sapiens misc_feature (1567) n equals a,t,g, or c 61 ccccgccccc cgcccacgaa ggaagtggct gctgctccgg cgcggaccca gagccggttc 60 ggcgcgtcga ctgcccagag tccgcggccg ggcgcgggag gagccaagcc gccatggcct 120 accacagctt cctggtggag cccatcagct gccacgcctg gaacaaggac cgcacccaga 180 ttgccatctg ccccaacaac catgaggtgc atatctatga aaagagcggt gccaaatgga 240 ccaaggtgca cgagctcaag gagcacaacg ggcaggtgac aggcatcgac tgggcccccg 300 agagtaaccg tattgtgacc tgcggcacag accgcaacgc ctacgtgtgg acgctgaagg 360 gccgcacatg gaagcccacg ctggtcatcc tgcggatcaa ccgggctgcc cgctgcgtgc 420 gctgggcccc caacgagaac aagtttgctg tgggcagcgg ctctcgtgtg atctccatct 480 gttatttcga gcaggagaat gactggtggg tttgcaagca catcaagaag cccatccgct 540 ccaccgtcct cagcctggac tggcacccca acaatgtgct gctggctgcc ggctcctgtg 600 acttcaagtg tcggatcttt tcagcctaca tcaaggaggt ggaggaacgg ccggcaccca 660 ccccgtgggg ctccaagatg ccctttgggg aactgatgtt cgaatccagc agtagctgcg 720 gctgggtaca tggcgtctgt ttctcagcca gcgggagccg cgtggcctgg gtaagccacg 780 acagcaccgt ctgcctggct gatgccgaca agaagatggc cgtcgcgact ctggcctctg 840 aaacactacc actgctggcg ctgaccttca tcacagacaa cagcctggtg gcagcgggcc 900 acgactgctt cccggtgctg ttcacctatg acgccgccgc ggggatgctg agcttcggcg 960 ggcggctgga cgttcctaag cagagctcgc agcgtggctt gacggcccgc gagcgcttcc 1020 agaacctgga caagaaggcg agctccgagg gtggcacggc tgcgggcgcg ggcctagact 1080 cgctgcacaa gaacagcgtc agccagatct cggtgctcag cggcggcaag gccaagtgct 1140 cgcagttctg caccactggc atggatggcg gcatgagtat ctgggatgtg aagagcttgg 1200 agtcagcctt gaaggacctc aagatcaaat gacctgtgag gaatatgttg ccttcatcct 1260 agctgctggg gaagcgggga gaggggtcag ggaggctaat ggttgctttg ctgaatgttt 1320 ctggggtacc aatacgagtt cccatagggg ctgctccctc aaaaagggag gggacagatg 1380 gggagctttt cttacctatt caaggaatac gtgccttttt cttaaatgct ttcatttatt 1440 gaaaaaaaaa aaaaatgccc ccaaagcact atgctggtca tgaactgctt caaaatgtgg 1500 aggtaataaa atgcaactgt gtaaaaaaaa aaaaaaaaaa aaatgaccct cgcgatctag 1560 aactagncgg acgcntgggt 1580 62 1117 DNA Homo sapiens 62 ggcacgaggc gcgatgcagc acaggctaga ggctgcgcaa sgcgggggcc cgcccctggg 60 accctccggg ccgggcggtt tggcccctta gcgcccgggc gtcggggcgg taaaaggccg 120 gcagaaggga ggcacttgag aaatgtcttt cctccaggac ccaagtttct tcaccatggg 180 gatgtggtcc attggtgcag gagccctggg ggctgctgcc ttggcattgc tgcttgccaa 240 cacagacgtg tttctgtcca agccccagaa agcggccctg gagtacctgg aggatataga 300 cctgaaaaca ctggagaagg aaccaaggac tttcaaagca aaggagctat gggaaaaaaa 360 tggagctgtg attatggccg tgcggaggcc aggctgtttc ctctgtcgag aggaagctgc 420 ggatctgtcc tccctgaaaa gcatgttgga ccagctgggc gtccccctct atgcagtggt 480 aaaggagcac atcaggactg aagtgaagga tttccagcct tatttcaaag gagaaatctt 540 cctggatgaa aagaaaaagt tctatggtcc acaaaggcgg aagatgatgt ttatgggatt 600 tatccgtctg ggagtgtggt acaacttctt ccgagcctgg aacggaggct tctctggaaa 660 cctggaagga gaaggcttca tccttggggg agttttcgtg gtgggatcag gaaagcaggg 720 cattcttctt gagcaccgag aaaaagaatt tggagacaaa gtaaacctac tttctgttct 780 ggaagctgct aagatgatca aaccacagac tttggcctca gagaaaaaat gattgtgtga 840 aactgcccag ctcagggata accagggaca ttcacctgtg ttcatgggat gtattgtttc 900 cactcgtgtc cctaaggagt gagaaaccca tttatactct actctcagta tggattatta 960 atgtatttta atattctgtt taggcccact aaggcaaaat agccccaaaa caagactgac 1020 aaaaatctga aaaactaatg aggattatta agctaaaacc tgggaaatag gaggcttwaa 1080 atgactgccm gctggtgcrt gctcacactt ggcccac 1117 63 361 DNA Homo sapiens 63 cccacgcgtg ckggcgcctg gcagccaccg cctgggaggt tactgtaagg cccgcagctc 60 ccgccagctc ccgcggacts ctgccgcctc cttaccatga agccagtaag tcgtcgcacg 120 ctggactgga tttattcagt gttgctgctt gccatcgttt taatctcctg gggctgcatc 180 atctatgctt cgatggtgtc tgcaagacga cagctaagga agaaataccc agacaaaatc 240 tttgggacga atgaaaattt gtaactcttc tggatttaat tatctgaaaa tacagttctt 300 tccctcatgc ttatgtagat ataaaaataa aattcataat gcaaaaaaaa aaaaaaaaaa 360 g 361 64 1668 DNA Homo sapiens misc_feature (1664) n equals a,t,g, or c 64 ggcacgaggt ctgccaagct atagaccatg gctgtgaaca catttgtgtg aacagtgacg 60 actcatacac gtgcgagtgc ttggagggat tccggctcgc tgaggatggg aaacgctgcc 120 gaagaaggat gtctgcaaat caacccacca tggctgcgaa cacatttgtg ttaataatgg 180 gaattcctac atctgcaaat gctcakaggg atttgttcta gctgaggacg gaagacggtg 240 caagaaatgc actgaaggcc caattgacct ggtctttgtg atcgatggat ccaagagtct 300 tggagaagag aattttgagg tcgtgaagca gtttgtcact ggaattatag attccttgac 360 aatttccccc aaagccgctc gagtggggct gctccagtat tccacacagg tccacacaga 420 gttcactctg agaaacttca actcagccaa agacatgaaa aaagccgtgg cccacatgaa 480 atacatggga aagggctcta tgactgggct ggccctgaaa cacatgtttg agagaagttt 540 tacccaagga gaaggggcca ggccctttcc acaagggtgc ccagagcagc cattgtgttc 600 accgacggac gggctcagga tgacgtctcc gagtgggcca gtaaagccaa ggccaatggt 660 atcactatgt atgctgttgg ggtaggaaaa gccattgagg aggaactaca agagattgcc 720 tctgagccca caaacaagca tctcttctat gccgaagact tcagcacaat ggatgagata 780 agtgaaaaac tcaagaaagg catctgtgaa gctctagaag actccgatgg aagacaggac 840 tctccagcag gggaactgcc aaaaacggtc caacagccaa cagtgcaaca cagatatctg 900 tttgaagaag acaatctttt acggtctaca caaaagcttt cccattcaac aaaaccttca 960 ggaagccctt tggaagaaaa acacgatcaa tgcaaatgtg aaaaccttat aatgttccag 1020 aaccttgcaa acgaagaagt aagaaaatta acacagcgct tagaagaaat gacacagaga 1080 atggaagccc tggaaaatcg cctgagatac agatgaagat tagaaatcgc gacacatttg 1140 tagtcattgt atcacggatt acaatgaacg cagtgcagag ccccaaagct caggctattg 1200 ttaaatcaat aatgttgtga agtaaaacaa tcagtactga gaaacctggt ttgccacaga 1260 acaaagacaa gaagtataca ctaacttgta taaatttatc taggaaaaaa atccttcaga 1320 attctaagat gaatttacca ggtgagaatg aataagctat gcaaggtatt ttgtaatata 1380 ctgtggacac aacttgcttc tgcctcatcc tgccttagtg tgcaatctca tttgactata 1440 cgataaagtt tgcacagtct tacttctgta gaacactggc cataggaaat gctgtttttt 1500 tgtaytggac tttaccttga tatatgtata tggatgtatg cataaaatca taggacatat 1560 gtacttgtgg aacaagttgg attttttata caatattaaa attcaccact tcagagraaa 1620 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaanaaaa 1668 65 1353 DNA Homo sapiens misc_feature (1322) n equals a,t,g, or c 65 gggtcgaccc acgcgtccgc ccacgcgtcc ggatggctgc gctgttgctg agacacgttg 60 gtcgtcattg cctccgagcc cactttagcc ctcagctctg tatcagaaat gctgttcctt 120 tgggaaccac ggccaaagaa gagatggagc ggttctggaa taagaatata ggttcaaacc 180 gtcctctgtc tccccacatt actatctaca gttggtctct tcccatggcg atgtccatct 240 gccaccgtgg cactggtatt gctttgagtg caggggtctc tctttttggc atgtcggccc 300 tgttactccc tgggaacttt gagtcttatt tggaacttgt gaagtccctg tgtctggggc 360 cagcactgat ccacacagct aagtttgcac ttgtcttccc tctcatgtat catacctgga 420 atgggatccg acacttgatg tgggacctag gaaaaggcct gaagattccc cagctatacc 480 agtctggagt ggttgtcctg gttcttactg tgttgtcctc tatggggctg gcagccatgt 540 gaagaaagga ggctcccagc atcatcttcc tacacattat tacattcacc catctttctg 600 tttgtcattc ttatctccag cctgggaaaa gttctcctta tttgtttaga tccttttgta 660 ttttcagatc tccttggagc agtagagtac ctggtagacc ataatagtgg aaaagggtct 720 agttttcccc ttgtttctaa agatgaggtg gctgcaaaaa ctcccctttt ttgcccacag 780 cttgcctact ctcggcctag aagcagttat tctctctcca tattgggctt tgatttgtgc 840 tgagggtcag cttttggctc cttcttcctg agacagtgga aacaatgcca gctctgtggc 900 ttctgccctg gggatgggcc gggttggggg gtgggttggt gaggctttgg gtgccactgc 960 ctgtgggttg ctggcttaaa ggacaattct cttcattggt gagagcccag gccattaaca 1020 cctacacagt gttattgaaa gaagagaggt gggggtggag gggaattagt ctgtcccagc 1080 tagagggaga taaagagggc tagttagttc ttggagcagc tgcttttgag gagaaaatat 1140 atagctttgg acacgaggaa gatctagaaa attatcattg aacatattaa tggttatttc 1200 tttttcttgg atttccagaa aagcctctta attttatgct ttctcatcga agtaatgtac 1260 cctttttttc tgaaactgaa ttaaatactc attttatctt tgaaaaaaaa aaaaaaaacc 1320 tngggggggg ccccggaccc naattggccc tat 1353 66 1011 DNA Homo sapiens misc_feature (951) n equals a,t,g, or c 66 cggaagaaag cagccatcca gacatttcag aacacgtacc aggtgttagc tgtgaccttc 60 aatgacacaa gtgatcagat tatttctggt ggaatagaca atgatatcaa ggtctgggac 120 tgcgccagaa caagctaacc tacaccatga gaggccatgc agattcagtg actggcctga 180 gtttaagttc tgaaggctct tatcttttgt ccaatgcaat ggacaataca gttcgtgtct 240 gggatgtccg gccatttgcc cccaaagaga gatgtgtaaa gatatttcaa ggaaatgtgc 300 acaactttga aaagaacctt ctgagatgtt cttggtcacc tgatggaagc aaaatagcag 360 ctggctcagc cgacaggttt gtttatgtgt gggataccac aagcaggaga atattgtata 420 agctgcccgg ccatgctggc tccatcaatg aagtggcttt ccaccctgat gagcccatca 480 ttatctcagc atcgagtgac aagagactgt atatgggaga gattcagtga agatatggac 540 tggaagactc caaggccgct tgtctttgag acctcagact gcataagtga tgccaaatgt 600 tggatgtcca ggytagcacc ctcccttcag atgaccattg ctagcaagaa acaggaggcg 660 gtggccatat tccaaaaacc acttctgtcc catttcacca ggatgactaa ggcaagctcc 720 ctgtggcctc taaaaaccac ctgccagatt tcagggactg tttttttttt tctttttctt 780 ttttcctgtt ttctaatgca ggcccaatgt gacaaatttg ttggttggga tttttttttt 840 tttttgtaac tggcttgtat gatattttct ttctgtattt ctctatatca ttttgtatta 900 aaagccaaat agatgccttt ttacaagarm aaaaaaaaaa aaaaaaaaaa nnaaaaaaaa 960 ctgggagggg gggcccggta cccaaatcgc cggatatgat cgtaaacaat c 1011 67 1193 DNA Homo sapiens misc_feature (512) n equals a,t,g, or c 67 ggccgggcgg tgcgcactgc gggcgcatcc ctgccccggc gccgtccgtg cccgcgggac 60 ctgacagccg ggtcagaggg cgaactgtgc tcaggcccgg gctggacgca gagccagagc 120 tgtccccaga ggagcagagg gtcctggaaa ggaagctgaa aaaggaacgg aagaaagagg 180 agaggcagcg tctgcgggag gcaggccttg tggcccagca cccgcctgcc aggcgctcgg 240 gggccgaact ggcctgggac tacctctgca gatgggccca aaagcacaag aactggaggt 300 ttcagaagac gaggcagacg tggctcctgc tgcacatgta tgacagtgac aaggttcccg 360 atgagcactt ctccaccctg ctggcctacc tggaggggct gcagggccgg gcccgagagc 420 tgacggtgca gaaggcggaa gcctgatgcg ggagctggat gaggagggct ctgatccccc 480 cctgccgggg agggcccagc gcatccgaca gntgctgcag ctgctctcct agtgggttca 540 gcgcggggcg gggccgctgc ccagtgcagg gctgcctcag accacacagg gtgcagctcc 600 tccggcggtg ggggccgggt tcaccagcag ggcagcggct gagcaagggc tttcagctcc 660 tccggtggtg ggggccggga tcaccagcac cagagcctcg caagggcccc ttccctcctc 720 cagaccctcc ttggccggtg acgctgtgac agtgatggca ggttcagtgc cttcagcgca 780 gagcgtggat gctctggaat cacccggacc cctggccttg gagggaccct ccagccccag 840 gaatctgctt tggagggaaa tgtctatttt tctaccggga atattttaga gattggggca 900 tgctggctcc tcccgccagc tgcaaacctg caccttccgc ctgattcccg atccccctgc 960 gtgggccgca ttcctggtcc cctgcctgcg tccatcgagg ggcctggctg tggcctgttt 1020 tcctttgacc ccacacagcg tcattgcggg tcatggggag cccctggtgg gagcttgtgg 1080 agtcggatca cgtacctgtg cagaaaccgc ctctgtggct gcatttgaaa taaaacccga 1140 cccagcagca aaaaaaaaaa aaaaaancnc nagggggggc ccggnaccca att 1193 68 560 DNA Homo sapiens 68 gaattcggca cgagttggca catgatgcaa aatgcatttc tcagagtaga ttgcagtcaa 60 aaatgttgga aactactaag catgtgcara tagcatgcat gctgctgctg acctgccaga 120 tatttctccc ttcctccctt tctccctcat ttattcattc attaactgat tcattcatcc 180 cattaaaaaa attatatgta tgttttgtgc aaagcaccct actcaaggct gcggggtaca 240 aaagtatatc agaagccttg ggctttgacm wacttctctg tagtagtgct agatttgtgt 300 ggatctgcca cacttactcc aggcctcttg tgacctgtgc tttgcattaa tctcttaggc 360 taagccacat accttttcat tatacaatct ttgctgatgc taaggacaga ttccaaagtg 420 ccctccttat aatttttgta tttaatgcaa agtgtaatca agaataggcc attgttaggt 480 caattgcttt tctgtattta tcttttcaaa caataaataa tcagtgggat gaaaaagggc 540 cggaaaaaaa aaaaaaaaaa 560 69 1657 DNA Homo sapiens misc_feature (6) n equals a,t,g, or c 69 cggacngagc cgccgccggg cacttcctgt ggaggccgca gcgggtgcgg gcgccgacgg 60 gcgagagcca gcgagcgagc gagcgagccg agccgagcct cccgccgtcg ccatgggcca 120 gaacgacctg atgggcacgg ccgaggactt cgccgaccag ttcctccgtg tcacaaagca 180 gtacctgccc cacgtggcgc gcctctgtct gatcagcacc ttcctggagg acggcatccg 240 tatgtggttc cagtggagcg agcagcgcga ctacatcgac accacctgga actgcggcta 300 cctgctggcc tcgtccttcg tcttcctcaa cttgctggga cantgactgg ctgcgtcctg 360 gtgttgagca ggaacttcgt gcagtacgcc tgcttcgggc tctttggaat catagctctg 420 cagacgattg cctacagcat tttatgggac ttgaagtttt tgatgaggaa cctggccctg 480 ggaggaggcc tgttgctgct cctagcagaa tcccgttctg aagggaagag catgtttgcg 540 ggcgtcccca ccatgcgtga gagctccccc aaacagtaca tgcagctcgg aggcagggtc 600 ttgctggttc tgatgttcat gaccctcctt cactttgacg ccagcttctt ttctattgtc 660 cagaacatcg tggggcacag ctctgatgat tttagtggcc attggtttta aaaccaagct 720 ggctgctttg actcttgttg tgtggctctt tgccatcaac gtatatttca acgccttctg 780 gaccattcca gtctacaagc ccatgcatga cttcctgaaa tacgacttct tccagaccat 840 gtcggtgatt gggggcttgc tcctggtggt ggccctgggc cctgggggtg tctccatgga 900 tgagaagaag aaggagtggt aacagtcaca gatccctacc tgcctggcta agacccgtgg 960 ccgtcaagga ctggttcggg gtggattcaa caaaactgcc agcttttatg tatcctcttc 1020 ccttcccctc ccttggtaaa ggcacagatg ttttgagaac tttatttgca gagacacctg 1080 agaatcaatg gcttcaggac atgggttctc ttctcctgtg atcattcaag tgctcactgc 1140 atgaagactg gcttgtctca gtgtttcaac ctcaccaggg ctgtctcttg gtccacacct 1200 cgctccctgt tagtgccgta tgacagcccc catcaaatga ccttggccaa gtcacggttt 1260 ctctgtggtc aaggttggtt ggctgattgg tggaaagtag ggtggaccaa aggaggccac 1320 gtgagcagtc agcaccagtt ctgcaccagc agcgcctccg tcctagtggg tgttcctgtt 1380 tctcctggcc ctgggtgggc tagggcctga ttcgggaaga tgcctttgca gggaggggag 1440 gataagtggg atctaccaat tgattctggc aaaacaattt ctaagatttt tttgctttat 1500 gtgggaaaca gatctaaatc tcattttatg ctgtatttta tatcttagtt gtgtttgaaa 1560 acgttttgat ttttggaaac acatcaaaat aaataatggc gtttgttgta aaaaaaaaaa 1620 aaaaaaactc grgggggggc ccggtaccca aatcgcc 1657 70 711 DNA Homo sapiens 70 ggcacgagcg aagaccctgt tcggaccctg ccccgattcc agactcaggt agatcgtcgg 60 cataccctct accgtggaca ccaggcagcc ctggggctga tggagagaga tcaggtatcc 120 cccagggagt aggggctacc ttgaggggat gatagacctc ccccactccc agtgkkactc 180 tggaaatatg aaggaactag ggagtggaag agatttcaga gctggggaga ggagttcctc 240 ccttcaaagc cagcaactgc ctttggggaa tgtcgggggg tctctccttt ctcctgcttg 300 tgtkargtgg tacacagtcc ccccttcacc tggcgggaag ctgtcccgga cagactcatc 360 tcagctttcc cttggggcag gatcgggggc agcagctcca gcagaaacag caggatctgg 420 agcaggaagg cctcgaggcc acacaggggc tgctggccgg cgagtgggcc ccacccctct 480 ggragctggg cagcctcttc caggccttcg tgaagaggga gagccaggct tatgcgtaag 540 cttcatagct tctgctggcc tggggtggac ccaggacccc tggggcctgg gtgccctgag 600 tggtggtaaa gtggagcaat cccttcacgc tccttggcca tgttctgagc ggccagcttg 660 gcctttgcct taataaatgt gctttatttt caaaaaaaaa aaaaaaaaac t 711 71 935 DNA Homo sapiens misc_feature (510) n equals a,t,g, or c 71 ggcacagggt gaaagccagc taaaccccaa gtggagaagt gaaagacatg gttgttccca 60 taagtttatt gctcacatta tgaaagaagc catagtcatg agtgaaccac tccctaggtt 120 gataaggaaa ccaacacgga agatctcttt ctggaagaag cagccagcct cgtgaaggag 180 cggcccagcc gccgggcccg agggtcgcct tttgttcgga gtggcacgat tgtccgttcc 240 cagacattct cgcctggagc acgaagccag tatgtttgca gactttatcg tagtgacagc 300 gacagttcaa cgctgccccg gaagtccccc tttgtccgaa atactttgga aagacgaacc 360 cttcgctata agcagtcatg caggtcttcc ctggctgagc tcatggcccg cacctccctg 420 gacttggagc tggatctcca ggcgtcgaga acacggcaga ggcagctgaa tgaggagctc 480 tgcgccctcc gtgagctgcg gcagcggttn ggaggacgcc cagctccgtg gccagactga 540 cctcccaccc tgggtgcttc gggacgagcg gctccgtggc ctgctgcggg agccgagcgg 600 cagacaagac agaccaaact tgactaccgt catgagcagg cggctgagaa gatgctgaag 660 aaggcctcca aggagatcta ccagctgcgt ggcagagcca caaagagccc atccaagtgc 720 agacctttag ggagaagata gcattcttca caaggccaag gatcaacata cctcctctcc 780 cagccgacga cgtctgatgg agtgcattgt gcacatgaag tatttatcca cctgttttat 840 tttcatgaag ttcttagact agctgaattt gtctttaaaa tatttgtgca aagctattaa 900 tatacacatt ttgtaaaaaa aaaaaaaaaa aaact 935 72 504 DNA Homo sapiens misc_feature (504) n equals a,t,g, or c 72 gcaggggcga ggggytgggg accgcggggc ggacgggagc gagtatgtcc gctctgactc 60 ggctggcgtc tttcgctcgc gttggaggcc gccttttcag aagcggctgc gcacggactg 120 ctggagatgg tggagtccgt catgccggtg gtggtgtgca cattgagccc cggtatagac 180 agttccccca gctgaccaga tcccaggtgt tccagagcga gttcttcagc ggactcatgt 240 ggttctggat tctctggcgc ttttggcatg actcagaaga ggtgctgggt cactttccgt 300 atcctgatcc ttcccagtgg acagatgaag aattaggtat ccctcctgat gatgaagact 360 gaaggtgtag actcagcctc actctgtaca agagccaggt gagaatttca aggattatcg 420 acttcatatt gcacattaaa gttacaaatt aaagtggctt ggtcaagaat garaaaaaaa 480 aaaaaaaatt gggggggggc cccn 504 73 620 DNA Homo sapiens 73 gaattcggca cgaggaggag gggaggcggg gtaagtttgg tgggaaactc tgtaatttcc 60 wtttttactt tcacagcaat agtgcagaat ccagaatgga tgtcctcttt gtagccatct 120 ttgctgtgcc acttatcctg ggacaagaat atgaggatga agaaagactg ggagaggatg 180 aatattatca ggtggtctat tattatacag tcacccccag ttatgatgac tttagtgcag 240 atttcaccat tgattactcc atatttgagt cagaggacag gctgaacagg ttggataagg 300 acataacaga agcaatagag actaccatta gtcttgaaac agcacgtgca gaccatccga 360 agcctgtaac tgtgaaacca gtaacaacgg aacctcagag tccagatctg aacgatgccg 420 tgtccagttt gcgaagtcct attcccctcc tcctgtcgtg tgcctttgtt caggtgggga 480 tgtatttcat gtagaaggtg gaagaaggct gctatgactc tttggatggg agtctggcaa 540 gaggaaattg gaagataaaa taaataataa gtgaaataaa aaaaaaaaaa aaaaactcga 600 gggggggccc ggtacccaat 620 74 581 DNA Homo sapiens 74 acaaggtgtg tgtaaagttt atgtttgtaa actgaattct atcttaaatc caaaaagaac 60 tcgggagtaa ttcatttttg tagcataaag atccctaagt tttattttga aatatctgat 120 ttttacacgt taaaaaataa cagggcatcg agaggattcc taggtgacat ccagactcct 180 ttagctttgt gtgtgtggca ccggttagtc tgcttctctc tcctttcttg cactgcttca 240 cacagccatg ccctgccagc ccgggcaggt gccttcctgt caatgtacat ttgggcttct 300 gctcatgctg ccctccctcc cctcccctgc ctcccaaccc cgcccctttt gttcctccat 360 ggagtacttc catgggtgtg cctcccccag ccaagccata ataggtggtt tccccttcgc 420 ttctgtagcc cttgcagaca tcctctgttt acagtaggtg ttgacttact tcccctctcc 480 ccgstaaagc cataaactcc ttaaggacag gtagcattct tagtatcttc gttcttctca 540 atgaccagta gaccattaaa catgtagcaa acaaatgtga a 581 75 1843 DNA Homo sapiens misc_feature (10) n equals a,t,g, or c 75 aaacccaacn ccctccggtc cccnaaagaa agcccagccc aaatcccaag ccggcagtga 60 gcccgcgaac aaggccctca agacgcccag ncgaacaagc agcccccagg aggccccgca 120 agagaactcc ctggcggccc aagcgggcag cttctgtgcg gcagaactca gccaccgaga 180 gcgcagacag catcgagatt tatgtcccgg agncccagac caggctctga gaccatgcag 240 gaggaaagaa acgattttaa atcattaaaa acacaaaaac taagtgcgaa cggaacagag 300 ttttctcaac ctttgctatg gttattctgt ctagagaccc tgagccaact ttcaaattga 360 cgcatacaag ggctcacaat ttggcttttt tgggtccctc ccagctttag gttatgaaga 420 ttttactcac aaaaaaaatc aacaaaaatc acgaaactag aaaacttttt ttttcctctt 480 gctggccgtg gtggactaga tagatggacg tcggcaactc ccggcccagc ctccatactg 540 cggtcttttt actcgttcta tctgatgaga actcacacta gcttgtttac aagatgacga 600 cagtccaagg gcagccttgg gcacctgcca tgtccctcct ttccccagct atccccgctc 660 tgaccttgat tttcattctt atgtttttct cttttccctt cagagctcac acagtggtca 720 ccattgtggc aagcggcttt ctgggtctca gccctctctg cggttgaggg cccagaggac 780 agagagatgg acatgcgtcc cctccctccc cccgccaagt gctcacacac aacctcacgc 840 gcacacacac acacgcagat ggaggcgcct cactgggagg tgccccgcca gccctgggca 900 gtgtcaggca ggactcactc accgctgagc agatgagaga agttttagtc ttggcgggtg 960 gaaatgagac gaagccacag ttatcacact ccagactcct gcccttttat tttctccagc 1020 cccttcttcc ttcagcaaaa tctaggactc ccgagtggct tccagggggc cgtcagtcct 1080 cagccgcgcc tgtgtccggt gcccgagggg cgggcggcgg tgtctgtatg tatgtgtaca 1140 tatgcacata gaccttagag tgtatagtta acaaacgccc atctgctcac ccatgcccac 1200 ccagcgccgc cgccgctggc tctcggggca cctggcagga ggcgggtgtg tgaatagcat 1260 atatttttac atgtactata tctaggtgtg tgtacaagtg tgtgtaaaaa tatatacctt 1320 gtgtgtaagc agcccttttt ttttttggtc tccacccccc tccccccgcc ccgcactcct 1380 aagggcccat ctgcccagcc tctgagtttt ctgttctatt ttttttttaa ccccaattat 1440 ccttctctct ctcctgcccc cgcatcccac tcccagggtg tcacgagccc tgagctgcaa 1500 tggcccgggc ctgcagggcg gggtagggga gggcarggct sagccccgaa gccagctcag 1560 tacctgaggg gctgctctat gctgtgtatg cgcctctctg gcatccgaga catcctcttg 1620 gtggcgcttg ctngcagggg accccccccc cgtccccagg tgaaccaagg gtctgctccg 1680 gggcccattt ccagcttggc cgccgtctgt gaccttgggc aagtcacttg acctctgtgt 1740 gcctcaactt cctcctctgt aaaacgggga cagtccctgc ccctccctac ctcacaggca 1800 tgttgtgaga ataaatgagg taacgtgtaa aaaaaaaaaa aat 1843 76 1441 DNA Homo sapiens misc_feature (1056) n equals a,t,g, or c 76 tcgacccacg cgtccggctc cccgagccct gccaaccatg gtgaacttgg gtctgtcccg 60 ggtggacgac gccgtggctg ccaagcaccc gggactcggg gagtatgccg catgccagtc 120 acacgccttc atgaagggcg ttttcacctt cgtcacaggc accggcatgg cctttggctt 180 gcagatgttc attcagagga agtttccata ccctttgcag tggagcctcc tagtggccgt 240 ggttgcaggc tctgtggtca gctacggggt gacgagagtg gagtcggaga aatgcaacaa 300 cctctggctc ttcctggaga ccgggcagct ccccaaagac aggagcacag atcagagaag 360 ctaggagagc tccagcaggg gcacagagga ttgggggcag gaggagtctg gaacacagcc 420 ttcatgcccc ctgaccccag gccgaccctc cccacaccct agggtacccc agtcgtatcc 480 tctgtccgca tgtktggcca ggcctgacaa acacctgcag atggctgctg ccccaacctg 540 ggacctgccc agraggttgg agcagaaagg gctctccctg gggtggtgtt tctcctctag 600 ggtattggga tgcatgttct gcactgccag cagagagggt gtgtctgggg gccaccacct 660 atgggacacg gggtcgaagg ggcctgtaca ctctgtcatt tcctttctag cccctgcatc 720 tccaacaagt ccaaggtgac agctggtgct aggggcgtgg ggttaataaa tggcttatcc 780 ttctctccac ccaagtttcc acctgaccag gtgaaaaaca aatcagaagg gtaagatgat 840 gacaggtcac atgaaacctt tattacccta cagttgatat atgaggatca catgcaagtt 900 acatactgag gatgtacagg gaagttccca gcgctgaacc ccagaattag acgttcgcat 960 cagccccgta ggccacgtgg acaccaccac agcctctctg tatgggggtc tgcctctgta 1020 gcacttggca tgtaggggca gagcaaaagg ggccangctg gccagagcct ggctgctggg 1080 nagargaggg acttgtgggs cacgccacnt gcctatcatt ccccaytcat ctattagcca 1140 aagtcactcc ccagaggcag agctagcccg ttgtagccgt gtctgtgtgg agggaaagct 1200 tctgagtggg caagcctaca cacagccccg agccccaaga ggaggaagag gtggagacca 1260 gacggaacct ccacaagtcc atcatggtta cagctggctt ccccgcagca ccgaagaccc 1320 acagcatngg ccctgctgcc cccgacccag ctcagctgcc angcctcacc ttgccaggaa 1380 ttgaaagaaa gttattgagt actaattggc ctcagagtna caggaagctc aagttaaagt 1440 g 1441 77 910 DNA Homo sapiens 77 ggcagagctg gccttcgact cgctatgtcc actaacaata tgtcggaccc acggaggccg 60 aacaaagtgc tgaggtgagg accccagcgt cgtgggcacg ggttcgggtt gtgggtgtgg 120 atcggggccc tgggaagcgc ctgtctatcc cgggggcagg acctgagcgc ccctgaccct 180 cgagcctgtc gcaggtacaa gcccccgccg agcgaatgta acccggcctt ggacgacccg 240 acgccggact acatgaacct gctgggcatg atcttcagca tgtgcggcct catgcttaag 300 ctgaagtggt gtgcttgggt cgctgtctac tgctccttca tcagctttgc caactctcgg 360 agctcggagg acacgaagca aatgatgagt agcttcatgt gagacttgcc ctacagaaca 420 agtgactctt gagtaagggg tggggggacc ccagcctggc catcctagac tgacacctct 480 ctcctgtctt catgctgtcc atctctgccg tggtgatgtc ctatctgcag aatcctcagc 540 ccatgacgcc cccatggtga taccagccta gaagggtcac attttggacc ctgtctatcc 600 actaggcctg ggctttggct gctaaacctg ctgccttcag ctgccatcct ggacttccct 660 gaatgaggcc gtctcggtgc ccccagctgg atagagggaa cctggccctt tcctagggaa 720 caccctaggc ttacccctcc tgcctccctt cccctgcctg ctgctggggg agatgctgtc 780 catgtttcta ggggtattca tttgctttct cgttgaaacc tgttgttaat aaagtttttc 840 actctgaaaa aaaaaaaaaa aaaaaaaaac tygrgggggg gcccggaacc caattcsccg 900 gatagtgagt 910 78 2776 DNA Homo sapiens 78 tcgacccacg cgtccgggcg ggcagtgatg gcggctggtg atggggacgt gaagctaggc 60 accctgggga gtggcagcga gagcagcaac gacggcggca gcgagagtcc aggcgacgcg 120 ggagcggcag cgraaggggg aggctgggcg gcggcggcgt tggcgcttct gacggggggc 180 ggggaaatgc tgctgaacgt ggcgctggtg gctctggtgc tgctgggggc ctaccggctg 240 tgggtgcgct gggggcggcg gggtctgggg gccggggccg gggcgggcga ggagagcccc 300 gccacctctc tgcctcgcat gaagaagcgg gacttcagct tggagcagct gcgccagtac 360 gacggctccc gcaacccgcg catcctgctc gcggtcaatg ggaaagtctt cgacgtgacc 420 aaaggcagca agttctacgg cccggcgggt ccatatggaa tatttgctgg tagggatgcc 480 tccagaggac tggccacatt ttgcctagat aaagatgcac ttagagatga atatgatgat 540 ctctcagatt tgaatgcagt acaaatggag agtgttcgag aatgggaaat gcagtttaaa 600 gaaaaatatg attatgtagg cagactccta aaaccaggag aagaaccatc agaatataca 660 gatgaagaag ataccaagga tcacaataaa caggattgaa ctttgtaaac aaccaaagtc 720 aggggccttc agaactgcaa ttcttactcc ctttcacaga ctgtccggag tctttgggtt 780 tgattcacct gctgcgaaaa acattcaaca aattgtgtac aagataaatt aatctcacta 840 tgaagatttg aataactaga cattatttat gctgccaaac tcatttgttg cagttgtttg 900 taatgtctag tggggcttca tcatcctgaa aagaaggaga cagggatttt tttaaagagc 960 aagaaagtca caatattact tctttccttc cttttttcct tctttccttt cttctttctc 1020 tttctttctt tttaaaatat attgaagaca accagatatg tatttgctac tcaagtgtac 1080 agatctcctc aagaaacatc aagggactcc tgtgtcacat actgtgtttt tattttaaca 1140 tgggtgaggg aggcgacctg atcaggggag gtgggggtac acatcaattt gagttgttca 1200 ggctactgaa acattaaaat gtgaattccc aaacttttct ttttggcttt gtcagggaaa 1260 agaaaaatat ctttataaag aaatctttgg aaattaggag aaggaatttc aggtgggttt 1320 aagtcagagc tagttcccca acagaaagat catttgaaac cagtttttat cccttctctt 1380 tccttccctt tccctaaatc aaatcaatat taattgtgcc ttatttcact taacatagac 1440 ttgaattatt tttagggaaa gcccctataa tgaattcaga aatcactaca agcagcatta 1500 agactgaagt tggaatattc tgttgaccat aaaaccttga tatcattctg tgtatataga 1560 atgtaaaagg aatattacag tgttaactgc catatatgta atatacacaa actcaattag 1620 cattgtaatg gccaaatgca ttcccccatg cttttctgtt ttcaaaaaaa ttgaaaaaca 1680 aatcaactct tatccccaac agctgcctaa ttttaggagt ctgaccctcc acatctcact 1740 ggtgtgggtg catggggctg tggagtgggt gtcagtatgg atgtgtctga atgtgtgagg 1800 ccttggaagg gactctttct gcagatactg taaatacaag taccatttta ataaagcatg 1860 tacaataaac caaaataagc ttgagttgga ctttatatac agaactgtaa gccagtgcat 1920 tatgatacag ttgtaagatt gtgcatttga ttcaagataa ggaaaaatct tggaaatgaa 1980 aagcaggcac kggttaacca agttgtacac attgtaccac attcagcata actttaggaa 2040 gaaattccac tttgtgaaca ttctccagaa atccaagatt attcaggtaa gaattggtat 2100 attaaatgta catcttttta ctttctattt tgatgccaac tgattatact agacaattag 2160 cactccaggt ggttattgaa cacaaaacag taaaagaata ttgcactgat agatactaaa 2220 ttattatttt attaggttga aaaagccctt actaaaagcc cctcatatat caattacttt 2280 atttcattat gactacttag gttccgggct ggggacaagt tcacttaaaa aggcaatgtt 2340 atttaacagg tcaccagtta agacttctgc tttgtagata catgcagaag ccatcaaaca 2400 agggggrgct tttaactgca acaataagct aaagtatgta aaatactaca ttctattcag 2460 tcttggagtg ttttgtagaa agttatcttc agccaaatct ttgctgaaga ctggttgtgg 2520 agtgttggta aatgctttgt gtttttatgt aaaatatttt ctaaacaaaa aatgttaaaa 2580 gtacatgtcc tctgtagtaa actgatatct atatatatga atcattcaag cctaaagtct 2640 agtaataaac tgtacttgtg aatagagaaa ccctaaatat tcatgcagwa aaaattatgc 2700 ggtctgttaa gaaaaatgag taatttgtgt tttggacttg aaataaacag tgttctgtag 2760 ataattcctc aacttc 2776 79 1487 DNA Homo sapiens misc_feature (78) n equals a,t,g, or c 79 ccgctgctga taactatggc atcccccggg cctgcaggaa ttcggcacgg agctacggcg 60 ccgcctggct cctgctgnca cctgcaggct cgtcgcgggt ggagcccacc caagacatca 120 gcatcagcga ccagctgggg ggccaggacg tgcccgtgtt ccggaacctg tccctgctgg 180 tggtgggtgt cggcgccgtg ttctcactgc tattccacct gggcacccgg gagaggcgcc 240 ggccgcatgc ggasgagcca ggcgagcaca cccccctgtt ggcccctgcc acggcccagc 300 ccctgctgct ctggaagcac tggctccggg agcsggcttt ctaccaggtg ggcatactgt 360 acatgaccac caggctcatc gtgaacctgt cccagaccta catggccatg tacctcacct 420 actcgctcca cctgcccaag aagttcatcg cgaccattcc cctggtgatg tacctcagcg 480 gcttcttgtc ctccttcctc atgaagccca tcaacaagtg cattgggagg aacatgacct 540 acttctcagg cctcctggtg atcctggcct ttgccgcctg ggtggcgctg gcggagggac 600 tgggtgtggc cgtgtacgca gcggctgtgc tgctgggtgc tggctgtgcc accatcctcg 660 tcacctcgct ggccatgacg gccgacctca tcggtcccca cacgaacagc ggagckttcg 720 tgtacggctc catgagcttc ttggataagg tggccaatgg gctggcagtc atggccatcc 780 agagcctgca cccttgcccc tcagagctct gctgcagggc ctgcgtgagc ttttaccact 840 gggcgatggt ggctgtgacg ggcggcgtgg gcgtggccgc tgccctgtgt ctctgtagcc 900 tcctgctgtg gccgacccgc ctgcgacgct gatgagacct gcacgcantg gctcacagca 960 gcacgatttg tgacagcccg aggcggagaa caccgaacac ccagtgaagg tgaggggatc 1020 agcacggcgc ggccacccac gcacccacgc gctggaatga gactcagcca caaggaggtg 1080 cgaagctctg acccaggcca cagtgcggat gcaccttgag gatgtcacgc tcagtgagag 1140 acaccagaca cagaagggta cgctgtgatc ccacttctat gaaatgtcca ggacagacca 1200 atccacagaa tcagggagag gattcgtggg tgccgggact ggggaggggg acctgggggt 1260 gactaggtga cataatgggg acagggctgc cttctgggtg atgagaatgt tctggaatca 1320 gatgggatgg ctgcacggcg tggtgaaggt actgaacgcc acctcactgt aagacggtag 1380 attttgtatt ttaccacaat aaacaaaaca aaacaaaacc aaaaaaaaaa aaaaaaaaaa 1440 aaaaaaaagg aattcgatat caagcttatc gataccgtcg acctcga 1487 80 1563 DNA Homo sapiens misc_feature (14) n equals a,t,g, or c 80 aattcggcac gagncagaaa cctgcggaaa atggtagcga tggcggctgg gccgagtggg 60 tgtctggtgc cggcgtttgg gctacggttg ttgttggcga ctgtgcttca agcggtgtct 120 gcttttgggg cagagttttc atcggaggca tgcagagagt taggcttttc tagcaacttg 180 ctttgcagct cttgtgatct tctcggacag ttcaacctgc ttcagctgga tcctgattgc 240 agaggatgct gtcaggagga agcacaattt gaaaccaaaa agctgtatgc aggagctatt 300 cttgaagttt gtggatgaaa attgggaagg ttccctcaag tccaagcttt tgttaggagt 360 gataaaccca aactgttcag aggactgcaa atcaagtatg tccgtggttc agaccctgta 420 ttaaagcttt tggacgacaa tgggaacatt gctgaagaac tgagcattct caaatggaac 480 acagacagtg tagaagaatt cctgagtgaa aagttggaac gcatataaat cttgcttaaa 540 ttttgtccta tccttttgtt accttatcaa atgaaatatt acagcaccta gaaaataatt 600 tagttttgct tgcttccatt gatcagtctt ttacttgagg cattaaatat ctaattaaat 660 cgtgaaatgg cagtatagtc catgatatct aaggagttgg caagcttaac aaaacccatt 720 ttttataaat gtccatcctc ctgcatttgt tgataccact aacaaaatgc tttgtaacag 780 acttgcggtt aattatgcaa atgatagttt gtgataattg gtccagtttt acgaacaaca 840 gatttctaaa ttagagaggt taacaagaca gatgattact atgcctcatg tgctgtgtgc 900 tctttgaaag gaatgacagc agactacaaa gcaaataaga tatactgagc ctcaacagat 960 tgcctgctcc tcagagtctc tcctattttt gtattaccca gctttctttt taatacaaat 1020 gttatttata gtttacaatg aatgcactgc ataaaaactt tgtagcttca ttattgtaaa 1080 acatattcaa gatcctacag taagagtgaa acattcacaa agatttgcgt taatgaagac 1140 tacacagaaa acctttctag ggatttgtgt ggatcagata catacttggc aaatttttga 1200 gttttacatt cttacagaaa agtccattta aaagtgatca tttgtaagac caaaatataa 1260 ataaaaagtt tcaaaaatct atctgaattt ggaattcttc tggtttgttc tttcatgttt 1320 aaaaatgatg tttttcaatg catttttttc atgtaagccc tttttttagc caaaatgtaa 1380 aaatggctgt aatatttaaa acttataaca tcttattgtt ggtaatagtg ctttatattt 1440 gtctgatttt atttttcaaa gttttttcat ttatgaacac attttcattg gtatattatt 1500 taaggaatat ctcttgatat agaattttta tattaaaaat gatttttctt tgcttaaaaa 1560 aaa 1563 81 1020 DNA Homo sapiens misc_feature (20) n equals a,t,g, or c 81 tgcacgctgg ccatgtgggn gttgggccac tgcgaccccc ggcgctgcac gggccgcaag 60 ctggcccgcc tggggctggt gcgctgcctg cgcctgggcc acagattcgg cggtctggtg 120 ctgagccccg tgggcaagca gtacgcgtcc cccgcagaca gacagctggt ggcgcagtct 180 ggggtcgccg tcatcgactg ctcctgggcc aggctggacg agacaccgtt tgggaagatg 240 cgagggagcc acttgcgcct gttgccctac ctggtggccg ccaaccccgt gaactatggc 300 cggccctaca gactttcctg cgtggaagcg tttgctgcca ccttctgcat cgtaggcttt 360 ccagaccttg ctgtcatttt gctgcggaag tttaaatggg gcaagggctt cttggacctg 420 aaccgccagc tcctggacaa gtacgcggcc tgcggcagcc cggaggaggt gctgcaggcg 480 gagcaggagt tcttggccaa tgccaaggag agcccccagg aggaggagat cgatcccttc 540 gatgtggatt cagggagaga gtttggaaac cccaacaggc ctgtggccag cacccggctg 600 ccctcggaca ctgatgacag tgatgcgtct gaggacccag ggcctkgcgc cgagcgcgga 660 ggagccagca gcagctgctg tgaagaggag cagacgcagg gacggggggc tgaggccagg 720 gccccggctg aggtttggaa aggaatcaag aaacggcaga gagactgagg gttgcagaca 780 catatatttt tgaggctggg tgacgagaaa atctagagac atgagggaca taaatgggcc 840 tggcagcctc ggctctttgc ggctgctggc aggactgagc tgtccgggtt ctccccacac 900 ttccagcaca gctgtgctct gtgtcctgcc tcggcgctct cgcaaatgaa gctgcaggcc 960 aagaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaag gggggggggc 1020 82 770 DNA Homo sapiens misc_feature (757) n equals a,t,g, or c 82 tcgacccacg cgtccgggcc gccgtagcgc gtcttgggtc tcccggctgc cgctgctgcc 60 gccgccgcct cgggtcgtgg agccaggagc gacgtcaccg ccatggcagg catcaaagct 120 ttgattagtt tgtcctttgg aggagcaatc ggactgatgt ttttratgct tggatgtgcc 180 cttccaatat acaacaaata ctggcccctc tttgttctat ttttttacat cctttcacct 240 attccatact gcatagcaag aagattagtg gatgatacag atgctatgag taacgcttgt 300 aaggaacttg ccatctttct tacaacgggc attgtcgtgt cagcttttgg actccctatt 360 gtatttgcca gagcacatct gattgagtgg ggagcttgtg cacttgttct cacaggaaac 420 acagtcatct ttgcaactat actaggcttt ttcttggtct ttggaagcaa tgacgacttc 480 agctggcagc agtggtgaaa agaaattact gaactattgt caaatggact tcctgtcatt 540 tgttggccat tcacgcacac aggagatggg gcagttaatg ctgaatggta tagcaagcct 600 cttgggggta ttttaggtgc tcccttctca cttttattgt aagcatacta ttttcacaga 660 gacttgctga aggattaaaa ggattttctc ttttggaaaa aaaaaaaaaa aaaaacycga 720 gggggggccc gtwcccattc scccyatatg aattccnttt ttacaatccc 770 83 481 DNA Homo sapiens misc_feature (322) n equals a,t,g, or c 83 gaattcggca cgagcatagt gttaaccact agaattcact gcccttccta tccaaaaatg 60 acactactga tcatttttct tccttttsct tttacaacat tmacaaattc aggtggctct 120 ttcccagtac ggtaggctga ttcgtatgga tgcaccacgg ttggtgactc cccccacccc 180 acagagtttc tggcgttcat tcggttgaac ccaaggccag caagggctga ctgggaacaa 240 accgaacact aggccgtgaa ccaatcgtct ctccgtgccc gggagcgamc ccgggggcct 300 ttcactctcc caaggactcc angggggggc cgggtaccca attccgcccc tatagtgaat 360 ccgtnattac aattccacnt gggccgtccn tttttacaaa cgttccgttg aactgggaaa 420 aaccccttgg cggtttaccc caactttaat ccgcctttgc aagcacatcc cccccctttt 480 c 481 84 644 DNA Homo sapiens 84 gctgggatag agcatgaaag gagaactgct cccttttctg tttctcacag tttggttatg 60 gctttataaa cttktatttg gtgaaagccc cagataccca aatgtcattg gcaaaactta 120 tttttttttc tggacagatc agatttctag agagagcaga tttctagaga gattagcatt 180 catagtaagt gaaaattgtc taattttttt aatccatgct attactgggc agtaggtcta 240 attttttttg acaaaaaata gatctatttt ccttatatat tgatttagaa tcttaagtta 300 gaattttata gaagaaatgt ctgagcagtt ctatgtatgg aggagcaatt cagcttttca 360 gcagcaactt tatcttttgc cactagaggg agatctgtgg ttgctttctc ctttggagaa 420 tagctgcttt gcttttattt ttaatttcta aggttggaat agaacttatt ctcaaaattc 480 ctttagtgtt attaaatatt ttcatttatt agtcaaaggt aagttaatta agcttgttta 540 atgatgccaa tcttatgctt ttctgtaatc ttcaattttt aataaatgtg agttagatac 600 taagtgaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaa 644 85 1351 DNA Homo sapiens misc_feature (133) n equals a,t,g, or c 85 ggcacgagtg cgcasgcgtg gggctctctc cttgtcagtc ggcgccgcgt gcgggctggt 60 ggctctgtgg cagcggcggc ggcaggactc cggcactatg agcggcttca gcaccgagga 120 gcgcgccgcg ccnttctccc tggagtaccg agtcttcctc aaaaatgaga aaggacaata 180 tatatctcca tttcatgata ttccaattta tgcagataag gatgtgtttc acatggtagt 240 tgaagtacca cgctggtcta atgcaaaaat ggagattgct acaaaggacc ctttaaaccc 300 tattaaacaa gatgtgaaaa aaggaaaact tcgctatgtt gcgaatttgt tcccgtataa 360 aggatatatc tggaactatg gtgccatccc tcagacttgg gaagacccag ggcacaatga 420 taaacatact ggctgttgtg gtgacaatga cccaattgat gtgtgtgaaa ttggaagcaa 480 ggtatgtgca agaggtgaaa taattggcgt gaaagttcta ggcatattgg ctatgattga 540 cgaaggggaa accgactgga aagtcattgc cattaatgtg gatgatcctg atgcagccaa 600 ttataatgat atcaatgatg tcaaacggct gaaacctggc tacttagaag ctactgtgga 660 ctggtttaga aggtataagg ttcctgatgg aaaaccagaa aatgagtttg cgtttaatgc 720 agaatttaaa gataaggact ttgccattga tattattaaa agcactcatg accattggaa 780 agcattagtg actaagaaaa cgaatggaaa aggaatcagt tgcatgaata caactttgtc 840 tgagagcccc ttcaagtgtg atcctgatgc tgccagagcc attgtggatg ctttaccacc 900 accctgtgaa tctgcctgca cagtaccaac agacgtggat aagtggttcc atcaccagaa 960 aaactaatga gatttctctg gaatacaagc tgatattgct acatcgtgtt catctggatg 1020 tattagaagt aaaagtagta gcttttcaaa gctttaaatt tgtagaactc atctaactaa 1080 agtaaattct gctgtgacta atccaatata ctcagaatgt tatccatcta aagcattttt 1140 catatctcaa ctaagataac ttttagcaca tgcttaaata tcaaagcagt tgtcatttgg 1200 aagtcacttg tgaatagatg tgcaagggga gcacatattg gatgtatatg ttaccatatg 1260 ttaggaaata aaattatttt gctgaaaaaa aaaaaaaaaa aaccncgggg ggggccccgg 1320 tccccatttg gccctttggg gggnggtttt a 1351 86 2527 DNA Homo sapiens 86 ctcttgctac cttcccggcg cagagaaccc cggctgctca gcgcgctccg gggtcatgga 60 gatccccggg agcctgtgca agaaagtcaa gctgagcaat aacgcgcaga actggggaat 120 gcagagagca accaatgtca cctaccaagc ccatcatgtc agcaggaaca agagaggtca 180 ggtggtgggg accagaggtg gctttcgtgg ttgcacagtt tggctaacag gcttgtctgg 240 agcgggaaag actactgtga gcatggcctt ggaggagtac ctggtttgtc atggtattcc 300 atgctacact ctggatggtg acaatattcg tcaaggtctc aataaaaatc ttggctttag 360 tcctgaagac agagaagaga atgttcgacg catcgcagaa gttgctaaac tgtttgcaga 420 tgctggctta gtgtgcatca caagtttcat atcaccttac actcaggatc gcaacaatgc 480 aaggcaaatt catgaaggtg caagtttacc gttttttgaa gtatttgttg atgctcctct 540 gcatgtttgt gaacagaggg atgtcaaagg actctacaaa aaagcccggg caggagaaat 600 taaaggtttc actgggatcg attctgaata tgaaaagcca gaggcccctg agttggtgct 660 gaaaacagac tcctgtgatg taaatgactg tgtccagcaa gttgtggaac ttctacagga 720 acgggatatt gtacctgtgg atgcatctta tgaagtaaaa gaactatatg tgccagaaaa 780 taaacttcat ttggcaaaaa cagatgcgga aacattacca gcactgaaaa ttaataaagt 840 ggatatgcag tgggtgcagg ttttggcaga aggttgggca accccattga atggctttat 900 gagagagagg gagtacttgc agtgccttca ttttgattgt cttctggatg gaggtgtcat 960 taacttgtca gtacctatag ttctgactgc gactcatgaa gataaagaga ggctggacgg 1020 ctgtacagca tttgctctga tgtatgaggg ccgccgtgtg gccattcttc gcaatccaga 1080 gttttttgag cacaggaaag aggagcgctg tgccagacag tggggaacga catgcaagaa 1140 ccacccctat attaagatgg tgatggaaca aggagattgg ctgattggag gagatcttca 1200 agtcttggat cgagtttatt ggaatgatgg tcttgatcag tatcgtctta ctcctactga 1260 gctaaagcag aaatttaaag atatgaatgc tgatgctgtc tttgcatttc aactacgcaa 1320 cccagtgcac aatggacatg ccctgttaat gcaggatacc cataagcaac ttctagagag 1380 gggctaccgg cgccctgtcc tcctcctcca ccctctgggt ggctggacaa aggatgacga 1440 tgttcctttg atgtggcgta tgaagcagca tgctgcagtg ttggaggaag gagttctgaa 1500 tcctgagacg acagtggtgg ccatcttccc atctcccatg atgtatgctg gaccaactga 1560 ggtccagtgg cattgcagag cacggatggt tgcaggagcc aacttttaca ttgttggacg 1620 agaccctgct ggcatgcctc atccagaaac agggaaggat ctttatgagc caagtcatgg 1680 tgccaaagtg ctgacgatgg cccctggttt aatcactttg gaaatagttc cctttcgagt 1740 tgcagcttac aacaagaaaa agaagcgtat ggactactat gactctgaac accatgaaga 1800 ctttgaattt atttcaggaa cacgaatgcg caaacttgct cgagaaggcc agaaaccacc 1860 tgaaggtttc atggctccca aggcttggac cgtgctgaca gaatactaca aatccttgga 1920 gaaagcttag gctgttaacc cagtcactcc acctttgaca cattactagt aacaagaggg 1980 gaccacatag tctctgttgg catttctttg tggtgtctgt ctggacatgc ttcctaaaaa 2040 cagaccattt tccttaactt gcatcagttt tggtctgcct tatgagttct gttttgaaca 2100 agtgtaacac actgatggtt ttaatgtatc ttttccactt attatagtta tattcctaca 2160 atacaatttt aaaattgtct ttttatatta tatttatgct tctgtgtcat gattttttca 2220 agctgttata ttagttgtaa ccagtagtat tcacattaaa tcttgctttt tttcccctta 2280 aaaaaagaaa aaaattacca aacaataaac ttggctagac cttgttttga ggattttaca 2340 agacctttgt agcgattaga ttttttttct acattgaaaa tagaaactgc ttcctttctt 2400 ctttccagtc agctattggt ctttccagct gttataatct aaagtattct tatgatctgt 2460 gtaagctctg aatgaacttc tttactcaat aaaattaatt ttttggcttc ttaaaaaaaa 2520 aaaaaaa 2527 87 2566 DNA Homo sapiens misc_feature (22) n equals a,t,g, or c 87 cccaagaatt cggcacgagc gnggcawaak tgggatttct gaaacctgta ggccccaagc 60 ccatcaactt gcccaaagaa gattccaaac ctacatttcc ctggcctsct ggaaacaagc 120 catctcttca cagtgtaaac caagaccatg acttaaagcc actaggccga aatctgggcc 180 tactcctcca acctcagaaa atgaacagaa gcaagckttt cccaaattga ctggggttaa 240 agggaaattt atgtcagcat cacaagatct tgaacccaag cccctcttcc ccaaacccgc 300 ctttggccag aagccgcccc taagtaccga gaactcccat gaagacgaaa gccccatgaa 360 gaatgtgtct tcatcaaaag ggtccccagc tcccctggga gtcaggtcca aaagcggccc 420 tttaaaacca gcaagggaag actcagaaaa taaagaccat gcaggggaga tttcaagttt 480 gccctttcct ggagtggttt tgaaacctgc tgcgagcagg ggaggcccag gtctctccaa 540 aaatggtgaa gaaaaaaagg aagataggaa gatagatgct gctaagaaca ccttccagag 600 caaaataaat caggaagagt tggcctcagg gactcctcct gccaggttcc ctaaggcccc 660 ttctaagctg acagtggggg ggccatgggg ccaaagtcag gaaaaggaaa agggagacaa 720 gaattcagcc accccgaaac agaagccatt gcctcccttg tttaccttgg gtccacctcc 780 accaaaaccc aacagaccac caaatgttga cctgacgaaa ttccacaaaa cctcttctgg 840 aaacagtact agcaaaggcc agacgtctta ctcaacaact tccctgccac cacctccacc 900 atcccatccg gccagccaac caccattgcc agcatctcac ccatcacaac caccagtccc 960 aagcctacct cccagaaaca ttaaacctcc gtttgaccta aaaagccctg tcaatgaaga 1020 caatcaagat ggtgtcacgc actctgatgg tgctggaaat ctagatgagg aacaagacag 1080 tgaaggagaa acatatgaag acatagaagc atccaaagaa agagagaaga aaagggaaaa 1140 ggaagaaaag aagaggttag agctggagaa aaaggaacag aaagagaaag aaaagaaaga 1200 acaagaaata aagaagaaat ttaaactaac aggccctatt caagtcatcc atcttgcaaa 1260 agcttgttgt gatgtcaaag gaggaaagaa tgaactgagc ttcaagcaag gagagcaaat 1320 tgaaatcatc cgcatcacag acaacccaga aggaaaatgg ttgggcagaa cagcaagggg 1380 ttcatatggc tatattaaaa caactgctgt agagattgac tatgattctt tgaaactgaa 1440 aaaagactct cttggtgccc cttcaagacc tattgaagat gaccaagaag tatatgatga 1500 tgttgcagag caggatgata ttagcagcca cagtcagagt ggaagtggag ggatattccc 1560 tccaccacca gatgatgaca tttatgatgg gattgaagag gaagatgctg atgatggctc 1620 cacactacag gttcaagaga agagtaatac gtggtcctgg gggattttga agatgttaaa 1680 gggaaaagat gacagaaaga aaagtatacg agagaaacct aaagtctctg actcagacaa 1740 taatgaaggt tcatctttcc ctgctcctcc taaacaattg gacatgggag atgaagttta 1800 cgatgatgtg gatacctctg atttccctgt ttcatcagca gagatgagtc aaggaactaa 1860 tgttggaaaa gctaagacag aagaaaagga ccttaagaag ctaaaaaagc agraaaaara 1920 araaaaagac ttcaggaaaa aatttaaata tgatggtgaa attagagtcc tatattcaac 1980 taaagttaca acttccataa cttctaaaaa gtggggaacc agagatctac aggtaaaacc 2040 tggtgaatct ctagaagtta tacaaaccac agatgacaca aaagttctct gcagaaatga 2100 agaagggaaa tatggttatg tccttcggag ttacctagcg gacaatgatg gagagatcta 2160 tgatgatatt gctgatggct gcatctatga caatgactag cactcaactt tggtcattct 2220 gctgtgttca ttaggtgcca atgtgaagtc tggattttaa ttggcatgtt attgggtatc 2280 aagaaaatta atgcacaaaa ccacttatta tcatttgtta tgaaatccca attatcttta 2340 caaagtgttt aaagtttgaa catagaaaat aatctctctg cttaattgtt atctcagaag 2400 actacattag tgagatgtaa gaattattaa atattccatt tccgctttgg ctacaattat 2460 gaagaagttg aaggtacttc ttttagacca ccagtaaata atcctccttc aaaaaataaa 2520 aataaaaaaa aaaaaaaaaa actcgagggg gggcccggta cccaat 2566 88 540 DNA Homo sapiens 88 gaattcggca cgaggctttc tgtgtcctct gtggctgctt tagtgtgcca ccaggggcag 60 acttgggtgg gttgcagcag agatggcatg gccctcaagg tccaagatgt ttactctctt 120 gccggtcctc tgttatctct ggtctttgtg gttgccacag ttttcttgga tccaggagtt 180 aaaggcagtc ctgagggatg atggcctcat ctccgcagtt gcytggaatg ctgaatttca 240 gacgtgctaa aggagggttg cagacattgt gtggwatgca ttcagacccc agatgtgggt 300 gcaggaaggc aggcatggca cagccaggta gagactggtt tccaggccca agcagccttc 360 agcagctgtg cgccttgttt ctgatgttgt ttgggagtaa gaataatgta gacatggggg 420 gtcatgargc tcaataaaaa cttcaaggaa acctcccatg gcatggttgg gcgcagtgac 480 tcatgcctgt aaccccagca ctgtggaatg ccaaggtgga aggatcgctt gaggccaaga 540 89 1863 DNA Homo sapiens misc_feature (1836) n equals a,t,g, or c 89 tcgacccacg cgtccggcga gatccctacc gcagtagccg cctctgccgc cgcggagctt 60 cccgaacctc ttcagccgcc cggagccgct cccggagccc ggccgtagag gctgcaatcg 120 cagccgggag cccgcagccc gcgccccgag cccgccgccg cccttcgagg gcgccccagg 180 ccgcgccatg gtgaaggtga cgttcaactc cgctctggcc cagaaggagg ccaagaagga 240 cgagcccaag agcggcgagg aggcgctcat catccccccc gacgccgtcg cggtggactg 300 caaggaccca gatgatgtgg taccagttgg ccaaagaaga gcctggtgtt ggtgcatgtg 360 ctttggacta gcatttatgc ttgcaggtgt tattctagga ggagcatact tgtacaaata 420 ttttgcactt caaccagatg acgtgtacta ctgtggaata aagtacatca aagatgatgt 480 catcttaaat gagccctctg cagatgcccc agctgctctc taccagacaa ttgaagaaaa 540 tattaaaatc tttgaagaag aagaagttga atttatcagt gtgcctgtcc cagagtttgc 600 agatagtgat cctgccaaca ttgttcatga ctttaacaag aaacttacag cctatttaga 660 tcttaacctg gataagtgct atgtgatccc tctgaacact tccattgtta tgccacccag 720 aaacctactg gagttactta ttaacatcaa ggctggaacc tatttgcctc agtcctatct 780 gattcatgag cacatggtta ttactgatcg cattgaaaac attgatcacc tgggtttctt 840 tatttatcga ctgtgtcatg acaaggaaac ttacaaactg caacgcagag aaactattaa 900 aggtattcag aaacgtgaag ccagcaattg tttcgcaatt cggcattttg aaaacaaatt 960 tgccgtggaa actttaattt gttcttgaac agtcaagaaa aacattattg aggaaaatta 1020 atatcacagc ataaccccac cctttacatt ttgtgcagtg attatttttt aaagtcttct 1080 ttcatgtaag tagcaaacag ggctttacta tcttttcatc tcattaattc aattaaaacc 1140 attaccttaa aatttttttc tttcgaagtg tggtgtcttt tatatttgaa ttagtaactg 1200 tatgaagtca tagataatag tacatgtcac cttaggtagt aggaagaatt acaatttctt 1260 taaatcattt atctggattt ttatgtttta ttagcatttt caagaagacg gattatctag 1320 agaataatca tatatatgca tacgtaaaaa tggaccacag tgacttattt gtagttgtta 1380 gttgccctgc tacctagttt gttagtgcat ttgagcacac attttaattt tcctctaatt 1440 aaaatgtgca gtattttcag tgtcaaatat atttaactat ttagagaatg atttccacct 1500 ttatgtttta atatcctagg catctgctgt aataatattt tagaaaatgt ttggaattta 1560 agaaataact tgtgttacta atttgtataa cccatatctg tgcaatggaa tataaatatc 1620 acaaagttgt ttaactagac tgcgtgttgt ttttcccgta taataaaacc aaagaatagt 1680 ttggttcttc aaatcttaag agaatccaca taaaagaaga aactattttt taaaaattca 1740 cttctatata tacaatgagt aaaatcacag attttttctt taaataaaaa taagtcattt 1800 taataactaa accagattct ttgtgatact attaangtaa catttagccc caaaaaaaaa 1860 aaa 1863 90 2478 DNA Homo sapiens 90 ggcacagcgg cacgaggtga gctgagccgg tgggtgagcg gcggccacgg catcctgtgc 60 tgtgggggct acgaggaaag atctaattat catggacctg cgacagtttc ttatgtgcct 120 gtccctgtgc acagcctttg ccttgagcaa acccacagaa aagaaggacc gtgtacatca 180 tgagcctcag ctcagtgaca aggttcacaa tgatgctcag agttttgatt atgaccatga 240 tgccttcttg ggtgctgaag aagcaaagac ctttgatcag ctgacaccag aagagagcaa 300 ggaaaggctt ggaaagattg taagtaaaat agatggcgac aaggacgggt ttgtcactgt 360 ggatgagctc aaagactgga ttaaatttgc acaaaagcgc tggatttacg aggatgtaga 420 gcgacagtgg aaggggcatg acctcaatga ggacggcctc gtttcctggg aggagtataa 480 aaatgccacc tacggctacg ttttagatga tccagatcct gatgatggat ttaactataa 540 acagatgatg gttagagatg agcggaggtt taaaatggca gacaaggatg gagacctcat 600 tgccaccaag gaggagttca cagctttcct gcaccctgag gagtatgact acatgaaaga 660 tatagtagta caggaaacaa tggaagatat agataagaat gctgatggtt tcattgatct 720 agaagagtat attggtgaca tgtacagcca tgatgggaat actgatgagc cagaatgggt 780 aaagacagag cgagagcagt ttgttgagtt tcgggataag aaccgtgatg ggaagatgga 840 caaggaagag accaaagact ggatccttcc ctcagactat gatcatgcag aggcagaagc 900 caggcacctg gtctatgaat cagaccaaaa caaggatggc aagcttacca aggaggagat 960 cgttgacaag tatgacttat ttgttggcag ccaggccaca gattttgggg aggccttagt 1020 acggcatgat gagttctgag ctrcggagga accctcattt cctcaaaagt aatttatttt 1080 tacagcttct ggtttcacat gaaattgttt gcgctactga gactgttact acaaactttt 1140 taagacatga aaaggcgtaa tgaaaaccat cccgtcccca ttcctcctcc tctctgaggg 1200 actggaggga agccgtgctt ctgaggaaca actctaatta gtacacttgt gtttgtagat 1260 ttacactttg tattatgtat taacatggcg tgtttatttt tgtatttttc tctggttggg 1320 agtatgatat gaaggatcaa gatcctcaac tcacacatgt agacaaacat tagctcttta 1380 ctctttctca acccctttta tgattttaat aattctcact taactaattt tgtaagcctg 1440 agatcaataa gaaatgttca ggagagagga aagaaaaaaa atatatgctc cacaatttat 1500 atttagagag agaacactta gtcttgcctg tcaaaaagtc caacatttca taggtagtag 1560 gggccacata ttacattcag ttgctatagg tccagcaact gaacctgcca ttacctgggc 1620 aaggaaagat ccctttgctc taggaaagct tggcccaaat tgattttctt ctttttcccc 1680 ctgtaggact gactgttggc taattttgtc aagcacagct gtggtgggaa gagttagggc 1740 cagtgtcttg aaaatcaatc aagtagtgaa tgtgatctct ttgcagagct atagatagaa 1800 acagctggaa aactaaagga aaaatacaag tgttttcggg gcatacattt tttttctggg 1860 tgtgcatctg ttgaaatgct caagacttaa ttatttgcct tttgaaatca ctgtaaatgc 1920 ccccatccgg ttcctcttct tcccaggtgt gccaaggaat taatcttggt ttcactacaa 1980 ttaaaattca ctcctttcca atcatgtcat tgaaagtgcc tttaacgaaa gaaatggtca 2040 ctgaatggga attctcttaa gaaaccctga gattaaaaaa agactatttg gataacttat 2100 aggaaagcct agaacctccc agtagagtgg ggattttttt cttcttccct ttctcttttg 2160 gacaatagtt aaattagcag tattagttat gagtttggtt gcagtgttct tatcttgtgg 2220 gctgatttcc aaaaaccaca tgctgctgaa tttaccaggg atcctcatac ctcacaatgc 2280 aaaccactta ctaccaggcc tttttctgtg tccactggag agcttgagct cacactcaaa 2340 gatcagagga cctacagaga gggctctttg gtttgaggac catggcttac ctttcctgcc 2400 tttgacccat cacaccccat ttcctcctct ttccctctcc ccgctgccaa ttcctgcagc 2460 ccgggggaac cactagtt 2478 91 2058 DNA Homo sapiens misc_feature (69) n equals a,t,g, or c 91 tcggccttgc ttttgtggyc ttcctctgtg gccagagcgt tttcatcacc aagcctcctg 60 atggcagtnc cttcaccgat atgttcaaga tactgacgta ttcctgctgt tcccagaagc 120 gaagtggaga gcgccagagt aatggtgaag gcattggagt ntttcagcaa tcttctaaac 180 aaagtctgtt tgattcatgt aagatgtctc atggtgggcc atttacagaa gagaaagtgg 240 aagatgtgaa agctctggtc aagattgtcc ctgttttctt ggctttgata ccttactgga 300 cagtgtattt ccaaatgcag acaacatatg ttttacagag tcttcatttg aggattccag 360 aaatttcaaa tattacaacc actcctcaca cgctccctgc agcctggctg accatgtttg 420 atgctgtgct catcctcctg ctcatccctc tgaaggacaa actggtcgat cccattttga 480 gaagacatgg cctgctccca tcctccctga agaggatcgc cgtgggcatg ttctttgtca 540 tgtgctcrgc ctttgctgca ggaattttgg agagtaaaag gctgaacctt gttaaagaga 600 aaaccattaa tcagaccatc ggcaacgtcg tctaccatgc tgccgatctg tcgctgtggt 660 ggcaggtgcc gcagtacttg ctgattggga tcagcgagat ctttgcaagt atcgcaggcc 720 tggaatttgc atactcagct gcccccaagt ccatgcagag tgccataatg ggcttgttct 780 ttttcttctc tggcgtcggg tcgttcgtgg gttctggact gctggcactg gtgtctatca 840 aagccatcgg atggatgagc agtcacacag actttggtaa tattaacggc tgctatttga 900 actattactt tttccttctg gctgctattc aaggagctac cctcctgctt ttcctcatta 960 tttctgtgaa atatgaccat catcgagacc atcagcgatc aagagccaat ggcgtgccca 1020 ccagcaggag ggcctgacct tcctgaggcc atgtgcggtt tctgaggctg acatgtcagt 1080 aactgactgg ggtgcactga gaacaggcaa gactttaaat tcccataaaa tgtctgactt 1140 cactgaaact tgcatgttgc ctggattgat ttcttctttc cctctatcca aaggagcttg 1200 gtaagtgcct tactgcagcg tgtctcctgg cacgctgggc cctccgggag gagagctgca 1260 gatttcgagt atgtcgcttg tcattcaagg tctctgtgaa tcctctagct gggttccctt 1320 ttttacagaa actcacaaat ggagattgca aagtcttggg gaactccacg tgttagttgg 1380 catcccagtt tcttaaacaa atagtatcac ctgcttccca tagccatatc tcactgtaaa 1440 aaaaaaaatt aataaactgt tacttatatt taagaaagtg aggatttttt ttttttaaag 1500 ataaaagcat ggtcagatgc tgcaaggatt ttacataaat gccatattta tggtttcctt 1560 cctgagaaca atcttgctct tgccatgttc tttgatttag gctggtagta aacacatttc 1620 atctgctgct tcaaaaagta cttacttttt aaaccatcaa cattactttt ctttcttaag 1680 gcaaggcatg cataagagtc atttgagacc atgtgtccca tctcaagcca cagagcaact 1740 cacggggtac ttcacacctt acctagtcag agtgcttata tatagcttta ttttggtacg 1800 attgagacta aagactgatc atggttgtat gtaaggaaaa cattcttttg aacagaaata 1860 gtgtaattaa aaataattga aagtgttaaa tgtgaacttg agctgtttga ccagtcacat 1920 ttttgtattg ttactgtacg tgtatctggg gcttctccgt ttgttaatac tttttctgta 1980 tttgttgctg tatttttggc ataactttat tataaaaagc atctcaaatg cgaaawaaaa 2040 aaaaaaaaaa aaaaaaac 2058 92 1411 DNA Homo sapiens misc_feature (1391) n equals a,t,g, or c 92 ggcacaggag cgacccggga gaaggagggc camgakgcgg aagcggagga gtctccagga 60 gacccgggga cagcatcgcc caggcccctg tttgcaggcc tttcagatat atccatctca 120 caagacatcc ccgtagaagg agaaatcacc attcctatga gatctcgcat ccgggagttt 180 gacagctcca cattaaatga atctgttcgc aataccatca tgcgtgatct aaaagctgtt 240 gggaaaaaat tcatgcatgt tttgtaccca aggaaaagta atactctttt gagagattgg 300 gatttgtggg gccctttgat cctttgtgtg acactcgcat taatgctgca aagagactct 360 gcagatagtg aaaaagatgg agggccccaa tttgcagagg tgtttgtcat tgtctggttt 420 ggtgcagtta ccatcaccct caactcaaaa cttcttggag ggaacatatc tttttttcag 480 agcctctgtg tgctgggtta ctgtatactt cccttgacag tagcaatgct gatttgccgg 540 ctggtacttt tggctgatcc aggacctgta aacttcatgg ttcggctttt tgtggtgatt 600 gtgatgtttg cctggtctat agttgcctcc acagctttcc ttgctgatag ccagcctcca 660 aaccgcagag ccctagctgt ttatcctgtt ttcctgtttt actttgtcat cagttggatg 720 attctcacct ttactcctca gtaaatcagg aatgggaaat taaaaaccag tgaattgaaa 780 gcacatctga aagatgcaat tcaccatgga gctttgtctc tggcccttat ttgtctaatt 840 ttggaggtat ttgataactg agtaggtgag gagattaaaa gggagccata tagcactgtc 900 accccttatt tgaggaactg atgtttgaaa ggctgttctt ttctctctta atgtcatttc 960 tttaaaaata catgtgcata ctacacacag tatataatgc ctccttaagg catgatggag 1020 tcaccgtggt ccatttgggt gacaaccagt gacttgggaa gcacatagat acatcttaca 1080 agttgaatag agttgataac tattttcagt tttgagaata ccagttcagg tgcagctctt 1140 aaacacattg ccttatgact attagaatat gcctctcttt tcataaataa aaatacatgg 1200 tctatatcca ttttctttta tttctctctc ttaagcttaa aaaggcaatg agagaggtta 1260 ggagtgggtt catacacgga gaatgagaaa acatgcatta accaatattc agattttgat 1320 caggggaaat tctayacttg ttgcaaaaaa aaaaaaaaaa aaactcgagg ggggcccggt 1380 acccaatcgc ngtatatgat cgnaaacaat c 1411 93 2187 DNA Homo sapiens 93 gctttggctt tttttggcgg actggggcgc cctccggaag cgtttccaac tttccagaag 60 tttctcggga cgggcaggag ggggtgggga ctgccatata tagatcccgg gagcagggga 120 gcgggctaag agtagaatcg tgtcgcgctc gagagcgaga gtcacgtccc ggcgctagcc 180 cagcccgacc caggcccacc gtggtgcacg caaaccactt cctggccatg cgctccctcc 240 tgcttctcag cgccttctgc ctcctggagg cggccctggc cgccgaggtg aagaaacctg 300 cagccgcagc agctcctggc actgcggaga agttgagccc caaggcggcc acgcttgccg 360 agcgcagccg gcctggcctt cagcttgtac caggccatgg ccaaggacca ggcagtggag 420 aacatcctgg tgtcacccgt ggtggtggcc tcgtcgctgg ggctcgtgtc gctgggcggc 480 aaggcgacca cggcgtcgca ggccaaggca gtgctgagcg ccgagcagct gcgcgacgag 540 gaggtgcacg ccggcctggg cgagctgctg cgctcactca gcaactccac ggcgcgcaac 600 gtgacctgga agctgggcag ccgactgtac ggacccagct cagtgagctt cgctgatgac 660 ttcgtgcgca gcagcaagca gcactacaac tgcgagcact ccaagatcaa cttccgcgac 720 aagcgcagcg cgctgcagtc catcaacgag tgggccgcgc agaccaccga cggcaagctg 780 cccgaggtca ccaaggacgt ggagcgcacg gacggcgccc tgttagtcaa cgccatgttc 840 ttcaagccac actgggatga gaaattccac cacaagatgg tggacaaccg tggcttcatg 900 gtgactcggt cctataccgt gggtgtcatg atgatgcacc ggacaggcct ctacaactac 960 tacgacgacg agaaggaaaa gctgcaaatc gtggagatgc ccctggccca caagctctcc 1020 agcctcatca tcctcatgcc ccatcacgtg gagcctctcg agcgccttga aaagctgcta 1080 accaaagagc agctgaagat ctggatgggg aagatgcaga agaaggctgt tgccatctcc 1140 ttgcccaagg gtgtggtgga ggtgacccat gacctgcaga aacacctggc tgggctgggc 1200 ctgactgagg ccattgacaa gaacaaggcc gacttgtcac gcatgtcagg caagaaggac 1260 ctgtacctgg ccagcgtgtt ccacgccacc gcctttgagt tggacacaga tggcaaccct 1320 ttgaccagaa ttacgggcgg aggagtgcgc acccaagtgt tctacgccga ccaccccttc 1380 atttcctagt gcgggacacc caaagcggtc cctgctattc attgggcgcc tggtccggcc 1440 taagggtgac aagatgcgag acgagttata ggcctcaggg tgcacacagg atggcaggag 1500 gcatccaaag gctcctgaga cacatgggtg ctattggggt tgggggggag gtgaggtacc 1560 agccttggat actccatggg gtggggtgga aaagcagacc ggggttcccg tgtgcctgag 1620 cggacttccc agctagaatt cactccactt ggacatgggc cccagatacc atgatgctga 1680 gcccggaaac tccacatcct gtgggacctg ggccatagtc attctgcctg ccctgaaagt 1740 cccagatcaa gcctgcctca atcagtattc atatttatag ccaggtacct tctcacctgt 1800 gagaccaaat tgagctaggg gggtcagcca gccctcttct gacactaaaa cacctcagct 1860 gcctccccag ctctatccca acctctccca actataaaac taggtgctgc agcccctggg 1920 accaggcacc cccagaatga cctggccgca gtgaggcgga ttgagaagga gctcccagga 1980 ggggcttctg ggcagactct ggtcaagaag catcgtgtct ggcgttgtgg ggatgaactt 2040 tttgttttgt ttcttccttt tttagttctt caaagatagg gagggaaggg ggaacatgag 2100 cctttgttgc tatcaatcca agaacttatt tgtacatttt ttttttcaat aaaacttttc 2160 caatgacaaa aaaaaaaaaa aaaaaaa 2187 94 757 DNA Homo sapiens misc_feature (756) n equals a,t,g, or c 94 gacagtacgg tcggattccc gggtcgaccc acgcgtccgc ggacggtgaa gaaggtgaag 60 atggcggtgg ccagggccgg ggtcttggga gtccagtggc tgcaaagggc atcccggaac 120 gtgatgccgc tgggcgcacg gacagcctcc cacatgacca aggacatgtt cccggggccc 180 tatcctagga ccccagaaga acgggccgcc gccgccaaga agtataatat gcgtgtggaa 240 gactacgaac cttacccgga tgatggcatg gggtatggcg actacccgaa gctccctgac 300 cgctcacagc atgagagaga tccatggtat agctgggacc agccgggcct gaggttgaac 360 tggggtgaac cgatgcactg gcacctagac atgtacaaca ggaaccgtgt ggatacatcc 420 cccacacctg tttcttggca tgtcatgtgt atgcagctct tcggtttcct ggctttcatg 480 atattcatgt gctgggtggg ggacgtgtac cctgtctacc agcctgtggg accaaagcag 540 tatccttaca ataatctgta cctggaacga ggcggtgatc cctccaaaga accagagcgg 600 gtggttcact atgagatctg aggaggcttc gtgggctttt gggtcctcta actaggactc 660 cctcattcct agaaatttaa ccttaatgaa atccctaata aaactcagtg ctgtgttaaa 720 aaaaaaaaaa aaaaaaaaaa aaaaaggggg gccccnn 757 95 2394 DNA Homo sapiens misc_feature (1783) n equals a,t,g, or c 95 ggcacgagca ctcctgcact tccccacccc cacgaccgaa cctggcttcg ctaacgccct 60 cccagctccc tcgggcctga cttccggttt cctcgcgcgt ccctggcgcc gagccgcgga 120 cagcagcccc ttttccggct gagagctcat ccacacttcc aatcactttc cggagtgctt 180 cccctccctc cggcccgtgc tggtcccgac ggcgggcctg ggtctcgcgc gcgtattgct 240 gggtaacggg ccttctcycg cgtcggcccg gcccctcctg cctcggctcg tccctccttc 300 cagaacgtcc cgggctcctg ccgagtcaga agaaatggga ctccctccgc gacgtgcccg 360 gagcagctcc cttcgctgtg gaagcggcgg tgtcttcgaa gaaaccggaa gcccgtggtg 420 acccctggcg acccggtttg ttttcggtcc gtttccaaac actaaggaat cgaaactcgg 480 cggccttggg ggcggcccta cgtagcctgg cttctggttg tcatggatgc actggtagaa 540 gatgatatct gtattctgaa tcatgaaaaa gcccataaga gagatacagt gactccagtt 600 tcaatatatt caggagatga atctgttgct tcccattttg ctcttgtcac tgcatatgaa 660 gacatcaaaa aacgacttaa ggattcagag aaagagaact ctttgttaaa gaagagaata 720 agatttttgg aagaaaagct aatagctcga tttgaagaag aaacaagttc cgtgggacga 780 gaacaagtaa ataaggccta tcatgcatat cgagaggttt gcattgatag agataatttg 840 aagagcaaac tggacaaaat gaataaagac aactctgaat ctttgaaagt attgaatgag 900 cagctacaat ctaaagaagt agaactcctc cagctgagga cagaggtgga aactcagcag 960 gtgatgagga atttaaatcc accttcatca aactgggagg tggaaaagtt gagctgtgac 1020 ctgaagatcc atggtttgga acaagagctg gaactgatga ggaaagaatg tagcgatctc 1080 aaaatagaac tacagaaagc caaacaaacg gatccatatc aggaagacaa tctgaagagc 1140 agagatctcc aaaaactaag catttcaagt gataatatgc agcatgcata ctgggaactg 1200 aagagagaaa tgtctaattt acatctggtg actcaagtac aagctgaact actaagaaaa 1260 ctgaaaacct caactgcaat caagaaagcc tgtgcccctg taggatgcag tgaagacctt 1320 ggaagagaca gcacaaaact gcacttgatg aattttactg caacatacac aagacatccc 1380 cctctcttac caaatggcaa agctctttgt cataccacat cttccccttt accaggagat 1440 gtaaaggttt tatcagagaa agcaatcctc caatcatgga cagacaatga gagatccatt 1500 cctaatgatg gtacatgctt tcaggaacac agttcttatg gcagaaattc tctggaagac 1560 aattcctggg tatttccaag tcctcctaaa tcaagtgaga cagcatttgg ggaaactaaa 1620 actaaaactt tgcctttacc caaccttcca ccactgcatt acttggatca acataatcag 1680 aactgccttt ataagaatta atttggaaga gattcacgat ttcaccatga ggacacttat 1740 ctctttcagt ggtcctccca agaaattatt taacaaactg aanggagatt ttgattaaaa 1800 ttttgcagag gtcttcagta tctatatttg aacacactgt acaatagtac aaaaaccaac 1860 atagttggtt ttctagtatg aaagagcacc ctctagctcc atattctaag aatctgaaat 1920 atgctactat actaattaat aagtaaactt aaggtgttta aaaaactctg ccttctatat 1980 taattgtaaa attttgcctc tcagaagaat ggaattggag attgtagacg tggttttaca 2040 aaatgtgaaa tgtctaaata tctgttcata aaaataaaag gaaaacatgt ttcttcaaat 2100 tgcataatgg aacaaatggc aatgtgagta ggttacattt ctgttgttat aatgcgtaaa 2160 gatattgaaa atataatgaa ataaaagcat cttaggttat accatcttta tatgctattg 2220 cgtttcaata tttaagattt aaagtgattt tttggtcaca gtgttttgtt gataaaattt 2280 ttttagaatt gaagtttgaa ttctaagact tgaaacaacc tgatcactga agccaacttt 2340 gtcccagcac attccttaag tcctaattgg ggaaaaaaaa aaaaaaaaac tcga 2394 96 672 DNA Homo sapiens 96 agtgctctgt tgcccaggct ggagtgcgtt agtgtaatgt cagtccactg caacctccac 60 ccccaggttc aagcaattct catgcctcag cctcccaagt agctgaaatt actggcatgc 120 accaccacac ccagctgatg tttatttatt tatttatata tttatttatt ttaggtgttt 180 tttttttttt tttttgagac ggagtcttgc tctgttgccc tgggtgtggt tacgtggrat 240 taccatyctg ggtgactcac tgaaatgtac tcmcagtgag tcatgccttc maatgacatc 300 tcaagttctg cctgcttgga gatacatctg gggatcttaa ggggtgaggg actactcaac 360 aagaaggaat ttagcctgtc tttttaaata aacggcattt ctttttccta kaaaaatggg 420 aaattcttca attctctaat acagggacac tgagataaca aagaggaaag tgtctggttg 480 gaggttggga rgccaccctg gggtctctcc tacaaaaatg gaaaagaaaa gaacggtgar 540 aaatcmagca aagcacaara aaktttccct ttgctaaaag ggaaaagatg ccccmcaatg 600 cccataaaca tgaactgggg ataaggagga raatgtctct ycttggcacc cccaaacaaa 660 cgttaattac cc 672 97 1419 DNA Homo sapiens misc_feature (517) n equals a,t,g, or c 97 taagaacaga acagcaagta tgaaccacat ggaacttaaa acatatgggt gtgaagtcca 60 cttatgtaga caaaacttat aatttccaaa ctgttgtcta gtatacagtg atcagttgct 120 ctctgttcaa gtcattccac acatttccct attttaggct attataatat agaaagaaaa 180 tgggaagcat tagttggagc tagaaaatga actgtatatt attgctatat ttgctaatac 240 caactatttc aataagtgtt gtaccatatg tagcattaaa tataaaatac ataaaagaat 300 gtacagaaaa tagcttttat tgagtaatat tacatttcat ttatactgta gcaatatatt 360 tgtaggtata ctctgtaagg gctttaaata aaagaggtcc attaatactt ccttataaaa 420 attctagtct gtttcattac tgcccagatg ttttagagat aaatatttat gcagaaggta 480 ttttkgaaag tcyccytttg tctgatagag tttaacnaga tatttaaatt tagtgcycna 540 gaaatcccac aagtcacggt ctaaacacac ttagaatact acagcataaa tctgttagca 600 ttanttgcca aataagacag ttgggatccc aaaccccaag tccttgagca atgtttttcc 660 tcaaaaagct gctatnccaa tgatatagga aaawacattg tgttttccta aacacacttt 720 tctttttaaa tgtgcttcat tgtttgattt ggtcctgcct aaatttcaca agctaggcca 780 atgaaggctg aatcaaagac atttcatcca ccaatatcat gtgtagatat tatgtataga 840 aaataaaata aattatggct ctaacttctg tgttgctgtt tatcttgtta tttttcggcg 900 ttatactaat gngtttattg agagcatttt accttccaga cttctcatgg ctaacttttg 960 gtctgwattt tgstccttag atgkgaatat ttcttattag tytgctycct gcwacgcaat 1020 gactgcattt ctatcatttc tcagtttgtt agwatatgtg gatagtattc tactgtataa 1080 atgattgcaa agtttatcaa aaacaaatta ttatatgtag cttttctaca gtgctttgct 1140 aaaccatgta gtactagtta agtsttcctt gaaaataaag atacactctt ataggggaca 1200 gttcctgttc actcccagga aactttttta aaagatgaca ctgaatgttt attgcacttt 1260 agtgcagtga agtggcaata aaacctaaca tgaatcaagg ttgtttatgg cagatgcatg 1320 tgttgcttta cagagtttag caaaagctct taattttatg tcatactgta ttctactgaa 1380 taataaagct aacattattc aataataaaa tggaaaaaa 1419 98 1830 DNA Homo sapiens misc_feature (67) n equals a,t,g, or c 98 gcgaccgcgc ccttcagcta gctcgctcgc tcgctctgct tccctgctgc cggctgcgca 60 tggcttnggc gttggcggcg ctggcggcgg tcgagcngcc tgcgsagccg gtaccagcag 120 ttgcagaatg aagaagagtc tggagaacct gaacaggctg caggtgatgc tcctccacct 180 tacagcagca tttctgcaga gagcgcacat nattttgact acaaggatga gtctgggttt 240 ccaaagcccc catcttacaa tgtagctaca acactgccca gttatgatga agcggagagg 300 accaaggctg aagctactat ccctttggtt cctgggagag atgaggattt tgtgggtcgg 360 gatgattttg atgatgctga ccagctgagg ataggaaatg atgggatttt catgttaact 420 tttttcatgg cattcctctt taactggatt gggtttttcc tgtctttttg cctgaccact 480 tcagctgcag gaaggtatgg ggccatttca ggatttggtc tctctctaat taaatggatc 540 ctgattgtca ggttttccac ctatttccct ggatattttg atggtcagta ctggctctgg 600 tgggtgttcc ttgttttagg ctttctcctg tttctcagag gatttatcaa ttatgcaaaa 660 gttcggaaga tgccagaaac tttctcaaat ctccccagga ccagagttct ctttatttat 720 taaagatgtt ttctggcaaa ggccttcctg catttatgaa ttctctctca agaagcaaga 780 gaacacctgc aggaagtgaa tcaagatgca gaacacagag gaataatcac ctgctttaaa 840 aaaataaagt actgttgaaa agatcatttc tctctatttg ttcctaggtg taaaatttta 900 atagttaatg cagaattctg taatcattga atcattagtg gttaatgttt gaaaaagctc 960 ttgcaatcaa gtctgtgatg tattaataat gccttatata ttgtttgtag tcattttaag 1020 tagcatgagc catgtccctg tagtcggtag ggggcagtct tgctttattc atcctccatc 1080 tcaaaatgaa cttggaatta aatattgtaa gatatgtata atgctggcca ttttaaaggg 1140 gttttctcaa aagttaaact tttgttatga ctgtgttttt gcacataatc catatttgct 1200 gttcaagtta atctagaaat ttattcaatt ctgtatgaac acctggaagc aaaatcatag 1260 tgcaaaaata catttaaggt gtggtcaaaa ataagtcttt aattggtaaa taataagcat 1320 taatttttta tagcctgtat tcacaattct gcggtacctt attgtaccta agggattcta 1380 aaggtgttgt cactgtataa aacagaaagc actaggatac aaatgaagct taattactaa 1440 aatgtaattc ttgacactct ttctataatt agcgttcttc acccccaccc ccacccccac 1500 cccccttatt ttccttttgt ctcctggtga ttaggccaaa gtctgggagt aaggagagga 1560 ttaggtactt aggagcaaag aaagaagtag cttggaactt ttgagatgat ccctaacata 1620 ctgtactact tgcttttaca atgtgttagc agaaaccagt gggttataat gtagaatgat 1680 gtgctttctg cccaagtggt aattcatctt ggtttgctat gttaaaactg taaatacaac 1740 agaacattaa taaatatctc ttgtgtagca ccttttaaaa aaaaaaaaaa aaaaaaaaaa 1800 aaaaaaaaaa aancccgggg gggggccccn 1830 99 1145 DNA Homo sapiens 99 tttttttttt tttttttttt ttgactgaac taagtggctt ttttattaga gaaagccaga 60 attacaaaag acttcccttt tcttggggta tggctgtctc agcacaatac tcaacataac 120 tgcagaactg atgtggctca ggcaccctgg ttttaattcc ttgaggatct ggcaattggc 180 ttacgcaaaa ggtcaccatt tgaggtcctg ccttactaat tatgtgctgc ccaacaacta 240 aatttgtaat ttgtttttct ctagtttgag cagggtctga attttttcat ttatttcctt 300 ttttgccagc agacagactt gagtctgtaa agacaagcaa atacactgac agaagtttac 360 catagtttct aaaatgtaaa aaagaaaacc cccaaaagac tcaagaaaat tagaccacaa 420 attttgcatt gttcattgta gcactattgg taataaaata acaaatgttt gtgcattttt 480 atgtgaagat ccttctcgta tttcatttgg aaagatgagc aagaggtctg cttccttcat 540 tttacttccc cttctgtttt tgaaaggcag tttcgccaag cttaatgcaa gaatatctga 600 ctgtttagaa gaaagatatt gccacaatct ctggatggtt ttccagggtt gtgttattac 660 tgagcttcat ctttccagaa tgagcaaaac actgtccagt ctttgttacg attttgtaat 720 aaatgtgtac atttttttta aatttttgga catcacatga ataaaggtat gtatgtacga 780 atgtgtatat attatatata tgacatctat tttggaaaat gtttgccctg ctgtacctca 840 tttttaggag gtgtgcatgg atgcaatata tgaaaatggg acattctgga actgctggtc 900 aggggacttt gtcgccctgt gcactaaaag ggccagattt tcagcagcca aggacatcca 960 tacccaagtg aatgtgatgg gacttaaaag aagtgaactg agacaattca ctctggctgt 1020 ttgaacagca gcgtttcata ggaagagaaa aaaagatcaa tcttgtattt tctgaccaca 1080 taaaggcttc ttctctttgt aataaagtag aaaagctctc ctcaaaaaaa aaaaaaaaaa 1140 aaaaa 1145 100 734 DNA Homo sapiens 100 tacccggcgg attccaggaa ggtaaattta gtcctataat tttcagctta attataaaca 60 aaggaacaaa taagtggaag ggcagctatt accattcgct tagtcaaaac attcggttac 120 tgccctttaa tacactccta tcatcagcac ttccaccatg tattacaagt cttgacccat 180 ccctgtcgta actccagtaa aagttactgt tactagaaaa tttttatcaa ttaactgaca 240 aatagtttct ttttaaagta gtttcttcca tctttattct gactagcttc caaaatgtgt 300 tccctttttg aatcgaggtt tttttgtttt gttttgtttt ctgaaaaaat catacaactt 360 tgtgcttcta ttgctttttt gtgttttgtt aagcatgtcc cttggcccaa atggaagagg 420 aaatgtttaa ttaatgcttt ttagtttaaa taaattgaat catttataat aatcagtgtt 480 aacaatttag tgacccttgg taggttaaag gttgcattat ttatacttga gatttttttc 540 ccctaactat tctgtttttt gtactttaaa actatggggg aaatatcact ggtctgtcaa 600 gaaacagcag taattattac tgagttaaat tgaaaagtcc agtggaccag gcatttctta 660 tataaataaa attggtggta ctaatgtgaa aaaaaaaaaa aaaaaaaact cgaggggggc 720 ccggtaccct atta 734 101 713 DNA Homo sapiens misc_feature (27) n equals a,t,g, or c 101 ccgcgggaac gctgtcctgg ctgccgncac ccgaacagcc tgtcctggtg ccccggctcc 60 ctgccccgcg cccagtcatg accctgcgcc cctcactcct cccgctccat ctgctgctgc 120 tgctgctgct cagtgcggcg gtgtgccggg ctgaggctgg gctcgaaacc gaaagtcccg 180 tccggaccct ccaagtggag accctggtgg agcccccaga accatgtgcc gagcccgctg 240 cttttggaga cacgcttcac atacactaca cgggaagctt ggtagatgga cgtattattg 300 acacctccct gaccagagac cctctggtta tagaacttgg ccaaaagcag gtgattccag 360 gtctggagca gagtcttctc gacatgtgtg tgggagagaa gcgaagggca atcattcctt 420 ctcacttggc ctatggaaaa cggggatttc caccatctgt cccagcggat gcagtggtgc 480 agtatgacgt ggagctgatt gcactaatcc gagccaacta ctggctaaag ctggtgaagg 540 gcattttgcc tctggtaggg atggccatgg tgccaccctc ctgggcctca ttgggtatca 600 cctatacaga aaggccaata gacccaaagt ctccaaaaag aagctcaagg aagagaaacg 660 aaacaagagc aaaaagaaat aataaataat aaattttaaa aaacttaaaa aaa 713 102 1080 DNA Homo sapiens misc_feature (514) n equals a,t,g, or c 102 ccgatgtgga catcatcctg tctatcccca tgttcctgcg cctgtacctg atcgcccgag 60 tcatgctgct gcacagaagc tcttcaccga tgcctcgtcc cgcagcatcg gggccctcaa 120 caagatcaac ttcaacaccc gctttgtcat gaagacgctc atgaccatct gccctggcac 180 tgtgctgctc gtgttcagca tctctctgtg gatcattgct gcctggaccg tccgtgtctg 240 tgaaagtcct gaatcaccag cccagccttc tggctcatca cttcctgctt ggtaccatga 300 ccagcaggac gtaactagta actttctggg tgccatgtgg ctcatctcca tcacattcct 360 ttccattggt tatggggaca tggtgcccca cacatactgt gggaaaggtg tctgtctcct 420 cactggcatc atgggtgcag gctgcactgc ccttgtggtg gccgtggtgg cccgaaagct 480 ggaactcacc aaagcggaga agcacgttca taanttcatg atggacactc agctcaccaa 540 gcggatcaag aatgytgcag ccaatgtcct tsgggaaaca tggttaatct ataaacacac 600 aaagytgyta aagaagattg accatgccaa agtgaggaac accagaggaa gttcytccaa 660 gtatccacca gttgaggagc gtcaagatgg aacagaggaa gctgagtgac caagccaaca 720 ntctggtgga cctttccaag atgcagaatg tcmtgtatga cttaatcaca gaactcaatg 780 accggagcga agacctggag aagcagattg gcagcctgga gtcgaagctg gagcatctca 840 ccgccagctt caactccctg ccgctgctca tcgccgacac cctgcgccag cagcagcagc 900 agctcctgtc tgccatcatc gaggcccggg gtgtcagcgt ggcagtgggc accacccaca 960 ccccaatctc cgatagcccc attggggtca gctccacctc cttcccgacc ccgtacacaa 1020 gttcaagcag ttgctaaata aatctcccca ctccagaagc attaaaaaaa aaaaaaaaaa 1080 103 489 DNA Homo sapiens 103 ggcacgagag gctttgaagc atttttgtct gtgctccctg atcttcaggt caccaccatg 60 aagttcttag cagtcctggt actcttggga gtttccatct ttctggtctc tgcccagaat 120 ccgacaacag ctgctccagc tgacacgtat ccagctactg gtcctgctga tgatgaagcc 180 cctgatgctg aaaccactgc tgctgcaacc actgcgacca ctgctgctcc taccactgca 240 accaccgctg cttctaccac tgctcgtaaa gacattccag ttttacccaa atgggttggg 300 gatctcccga atggtagagt gtgtccctga gatggaatca gcttgagtct tctgcaattg 360 gtcacaacta ttcatgcttc ctgtgatttc atccaactac ttaccttgcc tacgatatcc 420 cctttatctc taatcagttt attttctttc aaataaaaaa taactatgag caacaaaaaa 480 aaaaaaaaa 489 104 1529 DNA Homo sapiens misc_feature (7) n equals a,t,g, or c 104 gggcacnaga tggagctgcc gtagcggacc cagcacagcc aggagcgtcc gggatgagct 60 cagccgcggc cgaccactgg gcgtggttgc tggtgctcag cttcgtgttt ggatgcaatg 120 ttcttaggat cctcctcccg tccttctcat ccttcatgtc cagggtgctg cagaaggacg 180 cggacaggag tcacagatga gagcggagat ccaggacatg aagcaggagc tctccacagt 240 caacatgatg gacgagtttg ccagatatgc caggctggaa agaaagatca acaagatgac 300 ggataagctc aaaacccatg tgaaagctcg gacagctcaa ttagccaaga taaaatgggt 360 gataagtgtc gctttctacg tattgcaggc tgccctgatg atctcactca tttggaagta 420 ttattctgtc cctgtggctg tcgtgccgag taaatggata acccctctag accgcctggt 480 agcctttcct actagagtag caggtggtgt tggaattacc tgttggattt tagtctgtaa 540 caaagttgtc gctattgtgc ttcatccgtt cagctgaaca ggaggatgga tacagccgcg 600 agtaaaaaaa cggatttcct cttcctagct taaaatctga tttacactgt tttgtttttt 660 aagaaacaaa agtgcatagt ttagattttt tttttgttga atatgtttgt tcttggactt 720 tatgagatag tcttataaga atcacgattt tctacacctg tcattgagcc aagaaagtcc 780 agtttatgac acgtatgtac tagtgaacac cgtcctcgat ctgtacgaaa tgtgaaatgt 840 ttagggacat ctccatgctg tcacttgtga tttgccctct tatgtatttt ggtcatattg 900 ccaactggaa agtcaaaatt ttctaacaac tttaagtaag ttctttgaag acttagtgct 960 gtttttaatc cagtttagaa agtaacttaa ttttaatacc rctactaaaa attcgaaaat 1020 ttcttcttta atcacattca atatggttaa aagaacaaca ctaattgaca ttgcgtgggc 1080 tttttctccc tttgtttaaa atgtcatttg ttgagcaaga gttgtatagt attatctact 1140 tacttgaggc tgttaatttt tcattacagt gttttgtaaa tgtatccacg agaccatgat 1200 gcattgtttt gtgctcaact tgtgttttgt atttaaagca ttttgaatga agtgtatttt 1260 ataagcattt aatatttatg ctctttagaa tggaacacag aaaacaaacc ttataagtcc 1320 tgattaatct gaaccaataa cctgtgtggc ctacaaagta taattctatt aaatgttcct 1380 taaaacactt ttttctaatt aaaatctttg caaatgcttg tgtaacttcc tgccttacag 1440 ctacttgttt gctgtgagcc acccgcaact gacaagtggc tgttaactga gtcaccatat 1500 cccagtaaag ctgaattttc tcactaaaa 1529 105 2435 DNA Homo sapiens misc_feature (455) n equals a,t,g, or c 105 atgaagggtc gttggtggga aagatggcgg cgactctggg accccttggt cgtggcagca 60 gtggcgrcga tgtttgtcgg ctcgggatgg gtccaggatg ttactccttc ttcttttgtt 120 ggggtctggg caggggccac agcaagtcgg ggcgggtcaa acgttcgagt acttgaaacg 180 ggagcactcg ctgtcgaagc cctaccaggg tgtgggcaca ggcagttcct cactgtggaa 240 tctgatgggc aatgccatgg tgatgaccca gtatatccgc cttaccccag atatgcaaag 300 taaacagggt gccttgtgga accgggtgcc atgtttcctg agagactggg agttgcaggt 360 gcacttcaaa atccatggac aaggaaagaa gaatctgcat ggggatggct tggcaatctg 420 gtacacaaag grwtcggatg cagccagggc ctgtntttgg gaaacatgga caaatttgtg 480 gggctgggag tatttgtaga cacctacccc aatgaggaga agcagcaaga gcgggtattc 540 ccctrcmtct cagccatggt gaacaacggc tccctcagct atgatcatga gcgggatggg 600 cggcctacag agctgggagg ctgcasagcc attgtccgca atcttcatta cgacaccttc 660 ctggtgattc gctacgtcaa gaggcatttr acgataatga tggatattga tggcaagcat 720 gagtggaggg actgcattga agtgcccgga gtccgcctgc cccgcggcta ctacttcggc 780 acctcctcca tcactgggga tctctcagat aatcatgatg tcatttcctt gaagttgttt 840 gaactgacag tggagagaac cccagaagag gaaaagctcc atcgagatgt gttcttgccc 900 tcagtggaca atatgaagct gcctgagatg acagctccac tgccgcccct gagtggcctg 960 gccctcttcc tcatcgtctt tttctccctg ggtgttttct gtatttgcca tagtcattgg 1020 tatcatactc tacaacaaat ggcaggaaca gagccgaaag cgcttctact gagccctcct 1080 gctgccacca cttttgtgac tgtcacccat gaggtatgga aggagcaggc actggcctga 1140 gcatgcagcc tggagagtgt tcttgtctct agcagctggt tggggactat attctgtcac 1200 tggagttttg aatgcaggga ccccgcattc ccatggttgt gcatggggac atctaactct 1260 ggtctgggaa gccacccacc ccagggcaat gctgctgtga tgtgcctttc cctgcagtcc 1320 ttccatgtgg gagcagaggt gtgaagagaa tttacgtggt tgtgatgcca aaatcacaga 1380 acagaatttc atagcccagg ctgccgtgtt gtttgactca gaaggccctt ctacttcagt 1440 tttgaatcca caaagaatta aaaactggta acaccacagg ctttctgacc atccattcgt 1500 tgggttttgc atttgaccca accctctgcc tacctgagga gctttctttg gaaaccagga 1560 tggaaacttc ttccctgcct taccttcctt tcactccatt cattgtcctc tctgtgtgca 1620 acctgagctg ggaaaggcat ttggatgcct ctctgttggg gcctggggct gcagaacaca 1680 cctgcgtttc actggccttc attaggtggc cctagggaga tggctttctg ctttggatca 1740 ctgttcccta gcatgggtct tgggtctatt ggcatgtcca tggccttccc aatcaagtct 1800 cttcaggccc tcagtgaagt ttggctaaag gttggtgtaa aaatcaagag aagcctggaa 1860 gacatcatgg atgccatgga ttagctgtgc aactgaccag ctccaggttt gatcaaacca 1920 aaagcaacat ttgtcatgtg gtctgaccat gtggagatgt ttctggactt gctagagcct 1980 gcttagctgc atgttttgta gttacgattt ttggaatccc actttgagtg ctgaaagtgt 2040 aaggaagctt tcttcttaca ccttgggctt ggatattgcc cagagaagaa atttggcttt 2100 ttttttnctt aatggacaag agacagttgc tgttctcatg ttccaagtct gagagcaaca 2160 gaccctcatc atctgtgcct ggaagagttc actgtcattg agcagcacag cctgagtgct 2220 ggcctctgtc aacccttatt ccactgcctt atttgacaag gggttacatg ctgctcacct 2280 tactgccctg ggattaaatc agttacaggc cagagtctcc ttggagggcc tggaactctg 2340 agtcctccta tgaacctctg tagcctaaat gaaattctta aaatcaccga tggaaccaaa 2400 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaan 2435 106 805 DNA Homo sapiens 106 atgaaactta agaattgaat tggaaagact tctcaaagag aattgtatgt aacgatgttg 60 tattgatttt taagaaagta atttaatttg taaaacttct gctcgtttac actgcacatt 120 gaatacaggt aactaattgg aaggagaggg gaggtcactc ttttgatggt ggccctgaac 180 ctcattctgg ttccctgctg cgctgcttgg tgtgacccac ggaggatcca ctcccaggat 240 gacgtgctcc gtagctctgc tgctgatact gggtctgcga tgcagcggcg tgaggcctgg 300 gctggttgga gaaggtcaca acccttctct gttggtctgc cttctgctga aagactcgag 360 aaccaaccag ggaagctgtc ctggaggtcc ctggtcggag agggacatag aatctgtgac 420 ctctgacaac tgtgaagcca ccctgggcta cagaaaccac agtcttccca gcaattatta 480 caattcttga attccttggg gattttttac tgccctttca aagcacttaa gtgttagatc 540 taacgtgttc cagtgtctgt ctgaggtgac ttaaaaaatc agaacaaaac ttctattatc 600 cagagtcatg ggagagtaca ccctttccag gaataatgtt ttgggaaaca ctgaaatgaa 660 atcttcccag tattataaat tgtgtattta aaaaaaagaa acttttctga atgcctactg 720 gcggtgtata ccaggcagtg tgccagttta aaaagatgaa aaagaataaa aacttttgag 780 gaacaaaaaa aaaaaaaaaa aaatt 805 107 1166 DNA Homo sapiens misc_feature (1039) n equals a,t,g, or c 107 ggcacgagag gcgccagtcg caggtgtgct gctgaggcgt gagaatggcg tcccgcggcc 60 ggcgtccgga gcatggcgga cccccagagc tgttttatga cgagacagaa gcccggaaat 120 acgttcgcaa ctcacggatg attgatatcc agaccaggat ggctgggcga gcattggagc 180 ttctttatct gccagagaat aagccctgtt acctgctgga tattggctgt ggcactgggc 240 tgagtggaag ttatctgtca gatgaagggc actattgggt gggcctggat atcagccctg 300 ccatgctgga tgaggctgtg gaccgagaga tagagggaga cctgctgctg ggggatatgg 360 gccagggcat cccattcaag ccaggcacat ttgatggttg catcagcatt tctgctgtgc 420 agtggctctg taatgctaac aagaagtctg aaaaccctgc caagcgcctg tactgctttt 480 ttgcttctct tttttctgtt ctcgtccggg gatcccgagc tgtcctgcag ctgtaccctg 540 agaactcaga gcagttggag ctgatcacaa cccaggccac aaaggcaggc ttctccggtg 600 gcatggtggt agactaccct aacagtgcca aagcaaagaa attctacctc tgcttgtttt 660 ctgggccttc gacctttata ccagaggggc tgagtgaaaa tcaggatgaa gttgaaccca 720 gggagtctgt gttcaccaat gagaggttcc cattaaggat gtcgaggcgg ggaatggtga 780 ggaagagtcg ggcatgggtg ctggagaaga aggagcggca caggcgccag ggcagggaag 840 tcagacctga cacccagtac accggccgca agcgcaagcc ccgcttctaa gtcaccacgc 900 ggttctggaa aggcacttgc ctctgcactt ttctatattg ttcagctgac aaagtagtat 960 tttagaaaag ttctaaagtt ataaaaatgt tttctgcagt aaaaaaaaag ttctctgggc 1020 cgggcgtggt ggctcacanc tgtaatccca gcaccttggg aggctgaggt gggaggatca 1080 tttgaggcca ggagtttgag acctgcctgg gcaacataat gaaacttcct ttccagggag 1140 aaaaaaaaaa aaaaaaaaaa actcga 1166 108 586 DNA Homo sapiens 108 agagcggacg aagctggata acaggggacc gatgatgtgg cgaccatcag ttctgctgct 60 tctgttgcta ctgaggcacg gggcccaggg gaagccatcc ccagacgcag gccctcatgg 120 ccaggggagg gtgcaccagg cggcccccct gagcgacgct ccccatgatg acgcccacgg 180 gaacttccag tacgaccatg aggctttcct gggacgggaa gtggccaagg aattcgacca 240 actcacccca gaggaaagcc aggcccgtct ggggcggatc gtggaccgca tggaccgcgc 300 gggggacggc gacggctggg tgtcgctggc cgagcttcgc gcgtggatcg cgcacacgca 360 gcagcggcac atacgggact cggtgagcgc ggcctgggac acgtacgaca cggaccgcga 420 cgggcgtgtg ggttgggagg agctgcgcaa cgycacctat ggccactasg sgcccgktga 480 agaatttcat gacgtggagg atgcagagac ytacaaaaag atgctggytc gggacgagcg 540 gcgtttccgg gtggccgacc aggatgggga ctcgatggcc actcga 586 109 1134 DNA Homo sapiens misc_feature (418) n equals a,t,g, or c 109 acccattgag cagaaggagg ccaggtggga aagctcctgg gaagagcagc cagactggac 60 actgggctgc ttgagtcctg agtcacaatt cagaattcct gggctccctg ggtgcattct 120 atcattccag ttgaaagttt gcttccttcc agtcatgtgg ctcttcattc tactctcctt 180 ggctctcatt tcagatgcca tggtcatgga tgaaaaggtc aagagaagtt tgtgctggac 240 acggcttctg ccatctgcaa ctacaatgcc caytacaaga atcaccccaa atactggtgc 300 cgaggytatt tccgtgayta ctgcaacatc atcgccttct cccctaacag caccaatcat 360 gtggccctga aggacacagg gaaccagctc attgtcacta tgtcctgcct gaacaaanaa 420 gacacgggct ggtactggtg tggcatccar cgggactttg cmagggatga catggatttt 480 acagagctga ttgtaactga cgacaaagga accctggcca atgacttttg gtctgggaaa 540 gacctatcag gcaacaaaac cagaagctgc aaggctccca aagttgtccg caagctgacc 600 gctccaggac gtccattctc atcatttgca tactgatcac gggtttggga atcatctctg 660 taatcagtca tttgaccaaa aggaggagaa gtcaaaggaa tagaagggta ggcaacactt 720 tgaagccctt ctcgcgtgtc ctgactccaa aggaaatggc tcctactgaa cagatgtgac 780 tgaagwtttt tttaatttag ttncataaag tgatgnctac aacagawtaa tcacccatga 840 caactggccc cacacctcag agactgattc tgatctccca ggaattctga aggaccctct 900 atccttgaca acaatcattt gcagccaggt agcaacggcr gtagtcagag gagctatgat 960 agaccacacc caagcaaggc tgccctcaaa taacatctca agatcttagt tcttatgcat 1020 tccatcagtc agaagtgaag aagaggtgga gaatctkgat tggggaccag gaaatcactt 1080 gtattttgtt agccaataaa ttcctagcca gtgttgaatg aaaaaaaaaa aaaa 1134 110 1333 DNA Homo sapiens 110 cactttaaag ctctgctgag ggagttcgga gcccaggctt tcaggcgacc tctgccctcc 60 ctgcctctcc tcaccctccc tctcttcctg cagggcctgg gaagggcttt gagggagcct 120 gggagccatg tgaagagggg cacgcctggg ctgtcccaca gtttagatcc agttggaggt 180 tctccctggc tcctgcaggc ctgcggggat ctctccccac ttcaggcctc cggcagctgc 240 ctgccctctt gtctgtgctt cagccctgca caaaagcagc ttggtgacac cactcagcca 300 cccagagtac gtgtttacag gctttccaga tcaccttcct gtggggtgaa cgtaatgagg 360 cggggctggt ccttggaatt tcccctggaa aatggtaaca gactccatcc ttgacccggg 420 gatgagcatg aaggcattgt cccaaaggca gaggccaccg tggtaggaat tccaccaagg 480 ccagaaggga aaaaggaaga acccaccgtg tctggctgtg cgggccctgg ggagggtcgt 540 gagtgcagcc cctctctact tcygtgcctt tgtaaaacgt gtagataacc gcagtggttg 600 gctgagccaa gaactctcct aaatcagtgg ctttctcccc accccttgct ggggagtcat 660 ttttaaaaaa atctgtggga tataaaattg gcctcctgct gcttcagcct acctctccct 720 ctgctgactt aatgtcgtga ttctgtttct tcagatattt aaggctgtta ggttgtgtga 780 gccttgaagt gtgtgtgtgt gtcccagcga ctgtccactg tccaggagat gcatgtcttt 840 gtattggaga tatttctgta actcattctc ttggtgctca cgattgccat ggccataggg 900 ccacagtgcc gtatctgctg cagacatgat tgtttcttgt tctagaggtt ttcttgtttt 960 cgaatcttgc ctgatgaatc cagccagacc aaggggccta gatttgacct ctgtcctggg 1020 ctcctgggcc aggtgcagga acatctgagg ccactctgct ggccacctcc agtgggtgct 1080 gaccacagga tgggctttgt ttacactcat tttcaccctg attcttgccc ccactttcat 1140 aaaagaaact tcaaaatgct gacgctttgg agagtaagaa aatcaatctt ggctgggcac 1200 ggtggctcct gcctgtgatc ctagcacttt gggaggctga agctgaagga tcacttgagc 1260 tcaggagttg gagaccaacc ctggcaacat aacaagaccc tgtctctaca aaaaaaaaaa 1320 aaaaaaaact cga 1333 111 1015 DNA Homo sapiens misc_feature (1014) n equals a,t,g, or c 111 ggcacgagcg gcacgagcgg cacgaggtga cttcaagtgt cggatctttt cagcctacat 60 caaggaggtg gaggaacggc cggcacccac cccgtgggct ccaagatgcc ctttggggaa 120 ctgatgttcg aatccagcag tagctgcggc tgggtacatg gcgtctgttt ctcagccagc 180 gggagccgcg tggcctgggt aagccacgac agcaccgtct gcctggctga tgccgacaag 240 aagatggccg tcgcgactct ggcctctgaa acactaccac tgctggcgct gaccttcatc 300 acagacaaca gcctggtggc agcgggccac gactgcttcc cggtgctgtt cacctatgac 360 gccgccgcgg ggatgctgag cttcggcggg cggctggacg ttcctaagca gagctcgcag 420 cgtggcttga cggcccgcga gcgcttccag aacctggaca agaaggcgag ctccgagggt 480 ggcacggctg cgggcgcggg cctagactcg ctgcacaaga acagcgtcag ccagatctcg 540 gtgctcagcg gcggcaaggc caagtgctcg cagttctgca ccactggcat ggatggcggc 600 atgagtatct gggatgtgaa gagcttggag tcagccttga aggacctcaa gatcaaatga 660 cctgtgagga atatgttgcc ttcatcctag ctgctgggga agcggggaga ggggtcaggg 720 aggctaatgg ttgctttgct gaatgtttct ggggtaccaa tacgagttcc cataggggct 780 gctccctcaa aaagggaggg gacagatggg gagcttttct tacctattca aggaatacgt 840 gcctttttct taaatgcttt catttattga aaaaaaaaaa aaatgccccc aaagcactat 900 gctggtcatg aactgcttca aaatgtggag gtaataaaat gcaactgtgt aaaaaaaaaa 960 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aacnc 1015 112 711 DNA Homo sapiens misc_feature (345) n equals a,t,g, or c 112 ggcacgagcg aagaccctgt tcggaccctg ccccgattcc agactcaggt agatcgtcgg 60 cataccctct accgtggaca ccaggcagcc ctggggctga tggagagaga tcaggtatcc 120 cccagggagt aggggctacc ttgaggggat gatagacctc ccccactccc agtgkkactc 180 tggaaatatg aaggaactag ggagtggaag agatttcaga gctggggaga ggagttcctc 240 ccttcaaagc cagcaactgc ctttggggaa tgtcgggggg tctctccttt ctcctgcttg 300 tttraggtgg tacacagtcc ccccttcamc tggsgggaag ctgtnccgga caractcatc 360 tcagctttcc cttggggcag gatcgggggc agcagctcca gcagaaacag caggatctgg 420 agcaggaagg cctcgaggcc acacaggggc tgctggccgg cgagtgggcc ccacccctct 480 ggragctggg cagcctcttc caggccttcg tgaagaggga gagccaggct tatgcgtaag 540 cttcatagct tctgctggcc tggggtggac ccaggacccc tggggcctgg gtgccctgag 600 tggtggtaaa gtggagcaat cccttcacgc tccttggcca tgttctgagc ggccagcttg 660 gcctttgcct taataaatgt gctttatttt caaaaaaaaa aaaaaaaaac t 711 113 1076 DNA Homo sapiens misc_feature (1029) n equals a,t,g, or c 113 ggcacgaggg gaaagccatg ctcccaggac tccttccttg cagccttaaa tcggtctgta 60 cggaaaattc cgcgccttag aaacccacgc ttgggtgtaa cttattattg ttcttcctga 120 cctacttcct gtttatcact tccgggttca tcattttggc atttcggtga tcgggttgga 180 actattgaag cccgctttca ggttcttttc cccattttcc ctttgaaagg aagacttctg 240 gcttctccta aatctccgtt ctctgggtaa ggggagtcca agcctctgtc atgaggaacg 300 gaaatgcgag ggcctcgggt gttactctaa aatccgccct cagcttgcac gccggaagct 360 gcgattcctg cagcggaaga ggcgtgatct ggccttcgac tcgctatgtc cactaacaat 420 atgtcggacc cacggaggcc gaacaaagtg ctgaggtaca agcccccgcc gagcgaatgt 480 aacccggcct tggacgaccc gacgccggac tacatgaacc tgctgggcat gatcttcagc 540 atgtgcggcc tcatgcttaa gctgaagtgg tgtgcttggg tcgctgtcta ctgctccttc 600 atcagctttg ccaactctcg gagctcggag gacacgaagc aaatgatgag tagcttcatg 660 ctgtccatct ctgccgtggt gatgtcctat ctgcagaatc ctcagcccat gacgccccca 720 tggtgatacc agcctagaag ggtcacattt tggaccctgt ctatccacta ggcctgggct 780 ttggctgcta aacctgctgc cttcagctgc catcctggac ttccctgaat gaggccgtct 840 cggtgccccc agctggatag agggaacctg gccctttcct agggaacacc ctaggcttac 900 ccctcctgcc tcccttcccc tgcctgctgc tgggggagat gctgtccatg tttctagggg 960 tattcatttg ctttctcgtt gaaacctgtt gttaataaag tttttcactc tgaaaaaaaa 1020 aaaaaaaana raaaacncgn gggggggccc ggaacccaat tcsccggata gtgagt 1076 114 1525 DNA Homo sapiens misc_feature (78) n equals a,t,g, or c 114 ccgctgctga taactatggc atcccccggg cctgcaggaa ttcggcacgg agctacggcg 60 ccgcctggct cctgctgnca cctgcaggct cgtcgcgggt ggagcccacc caagacatca 120 gcatcagcga ccagctgggg ggccaggacg tgcccgtgtt ccggaacctg tccctgctgg 180 tggtgggtgt cggcgccgtg ttctcactgc tattccacct gggcacccgg gagaggcgcc 240 ggccgcatgc ggasgagcca ggcgagcaca cccccctgtt ggcccctgcc acggcccagc 300 ccctgctgct ctggaagcac tggctccggg agcsggcttt ctaccaggtg ggcatactgt 360 acatgaccac caggctcatc gtgaacctgt cccagaccta catggccatg tacctcacct 420 actcgctcca cctgcccaag aagttcatcg cgaccattcc cctggtgatg tacctcagcg 480 gcttcttgtc ctccttcctc atgaagccca tcaacaagtg cattgggagg aacatgacct 540 acttctcagg cctcctggtg atcctggcct ttgccgcctg ggtggcgctg gcggagggac 600 tgggtgtggc cgtgtacgca gcggctgtgc tgctgggtgc tggctgtgcc accatcctcg 660 tcacctcgct ggccatgacg gccgacctca tcggtcccca cacgaacagc ggactktcgt 720 gtacggctcc atgagcttct tggataaggt ggccaatggg ctggcagtca tggccatcca 780 gagcctgcac ccttgcccct cagagctctg ctgcagggcc tgcgtgagct tttaccactg 840 ggcgatggtg gctgtgacgg gcggcgtggg cgtggccgct gccctgtgtc tctgtagcct 900 cctgctgtgg ccgacccgcc tgcgacgctg ggaccgtgat gcccggccct gactcctgac 960 agcctcctgc acctgtgcaa gggaactgtg gggacgcacg aggatgcccc ccarggcctt 1020 ggggaaaagc ccccactgcc cctcactctt ctctggaccc ccaccctcca tcctcaccca 1080 gctcccgggg gtggggtcgg gtgagggcag cagggatgcc cgccagggac ttgcaaggac 1140 cccctgggtt ttgagggtgt cccattctca actctaatcc atcccagccc tctggaggat 1200 ttggggtgcc cctctcggca gggaacagga agtaggaatc ccagaagggt ctgggggaac 1260 cctaaccctg agctcagtcc agttcacccc tcacctccag cctgggggtc tccagacact 1320 gccagggccc cctcaggacg gctggagcct ggaggagaca gccacggggt ggtgggctgg 1380 gcctggaccc caccgtggtg ggcagcaggg ctgcccggca ggcttggtgg actctgctgg 1440 cagcaaataa agagatgacg gcaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1500 aaaaaaaaaa aaacccaccg tccgc 1525 115 1350 DNA Homo sapiens misc_feature (15) n equals a,t,g, or c 115 ggcacgagtg cgcangcgtg gggctctctc cttgtcagtc ggcgccgcgt gcgggctggt 60 ggctctgtgg cagcggcggc ggcaggactc cggcactatg agcggcttca gcaccgagga 120 gcgcgccgcg ccttctccct ggagtaccga gtcttcctca aaaatgagaa aggacaatat 180 atatctccat ttcatgatat tccaatttat gcagataagg atgtgtttca catggtagtt 240 gaagtaccac gctggtctaa tgcaaaaatg gagattgcta caaaggaccc tttaaaccct 300 attaaacaag atgtgaaaaa aggaaaactt cgctatgttg cgaatttgtt cccgtataaa 360 ggatatatct ggaactatgg tgccatccct cagacttggg aagacccagg gcacaatgat 420 aaacatactg gctgttgtgg tgacaatgac ccaattgatg tgtgtgaaat tggaagcaag 480 gtatgtgcaa gaggtgaaat aattggcgtg aaagttctag gcatattggc tatgattgac 540 gaaggggaaa ccgactggaa agtcattgcc attaatgtgg atgatcctga tgcagccaat 600 tataatgata tcaatgatgt caaacggctg aaacctggct acttagaagc tactgtggac 660 tggtttagaa ggtataaggt tcctgatgga aaaccagaaa atgagtttgc gtttaatgca 720 gaatttaaag ataaggactt tgccattgat attattaaaa gcactcatga ccattggaaa 780 gcattagtga ctaagaaaac gaatggaaaa ggaatcagtt gcatgaatac aactttgtct 840 gagagcccct tcaagtgtga tcctgatgct gccagagcca ttgtggatgc tttaccacca 900 ccctgtgaat ctgcctgcac agtaccaaca gacgtggata agtggttcca tcaccagaaa 960 aactaatgag atttctctgg aatacaagct gatattgcta catcgtgttc atctggatgt 1020 attagaagta aaagtagtag cttttcaaag ctttaaattt gtagaactca tctaactaaa 1080 gtaaattctg ctgtgactaa tccaatatac tcagaatgtt atccatctaa agcatttttc 1140 atatctcaac taagataact tttagcacat gcttaaatat caaagcagtt gtcatttgga 1200 agtcacttgt gaatagatgt gcaaggggag cacatattgg atgtatatgt taccatatgt 1260 taggaaataa aattattttg ctgaaaaaaa aaaaaaaaaa acctsggggg gggscccggt 1320 ccccatttgg ccctttgggg ggnggtttta 1350 116 2527 DNA Homo sapiens 116 ctcttgctac cttcccggcg cagagaaccc cggctgctca gcgcgctccg gggtcatgga 60 gatccccggg agcctgtgca agaaagtcaa gctgagcaat aacgcgcaga actggggaat 120 gcagagagca accaatgtca cctaccaagc ccatcatgtc agcaggaaca agagaggtca 180 ggtggtgggg accagaggtg gctttcgtgg ttgcacagtt tggctaacag gcttgtctgg 240 agcgggaaag actactgtga gcatggcctt ggaggagtac ctggtttgtc atggtattcc 300 atgctacact ctggatggtg acaatattcg tcaaggtctc aataaaaatc ttggctttag 360 tcctgaagac agagaagaga atgttcgacg catcgcagaa gttgctaaac tgtttgcaga 420 tgctggctta gtgtgcatca caagtttcat atcaccttac actcaggatc gcaacaatgc 480 aaggcaaatt catgaaggtg caagtttacc gttttttgaa gtatttgttg atgctcctct 540 gcatgtttgt gaacagaggg atgtcaaagg actctacaaa aaagcccggg caggagaaat 600 taaaggtttc actgggatcg attctgaata tgaaaagcca gaggcccctg agttggtgct 660 gaaaacagac tcctgtgatg taaatgactg tgtccagcaa gttgtggaac ttctacagga 720 acgggatatt gtacctgtgg atgcatctta tgaagtaaaa gaactatatg tgccagaaaa 780 taaacttcat ttggcaaaaa cagatgcgga aacattacca gcactgaaaa ttaataaagt 840 ggatatgcag tgggtgcagg ttttggcaga aggttgggca accccattga atggctttat 900 gagagagagg gagtacttgc agtgccttca ttttgattgt cttctggatg gaggtgtcat 960 taacttgtca gtacctatag ttctgactgc gactcatgaa gataaagaga ggctggacgg 1020 ctgtacagca tttgctctga tgtatgaggg ccgccgtgtg gccattcttc gcaatccaga 1080 gttttttgag cacaggaaag aggagcgctg tgccagacag tggggaacga catgcaagaa 1140 ccacccctat attaagatgg tgatggaaca aggagattgg ctgattggag gagatcttca 1200 agtcttggat cgagtttatt ggaatgatgg tcttgatcag tatcgtctta ctcctactga 1260 gctaaagcag aaatttaaag atatgaatgc tgatgctgtc tttgcatttc aactacgcaa 1320 cccagtgcac aatggacatg ccctgttaat gcaggatacc cataagcaac ttctagagag 1380 gggctaccgg cgccctgtcc tcctcctcca ccctctgggt ggctggacaa aggatgacga 1440 tgttcctttg atgtggcgta tgaagcagca tgctgcagtg ttggaggaag gagttctgaa 1500 tcctgagacg acagtggtgg ccatcttccc atctcccatg atgtatgctg gaccaactga 1560 ggtccagtgg cattgcagag cacggatggt tgcaggagcc aacttttaca ttgttggacg 1620 agaccctgct ggcatgcctc atccagaaac agggaaggat ctttatgagc caagtcatgg 1680 tgccaaagtg ctgacgatgg cccctggttt aatcactttg gaaatagttc cctttcgagt 1740 tgcagcttac aacaagaaaa agaagcgtat ggactactat gactctgaac accatgaaga 1800 ctttgaattt atttcaggaa cacgaatgcg caaacttgct cgagaaggcc agaaaccacc 1860 tgaaggtttc atggctccca aggcttggac cgtgctgaca gaatactaca aatccttgga 1920 gaaagcttag gctgttaacc cagtcactcc acctttgaca cattactagt aacaagaggg 1980 gaccacatag tctctgttgg catttctttg tggtgtctgt ctggacatgc ttcctaaaaa 2040 cagaccattt tccttaactt gcatcagttt tggtctgcct tatgagttct gttttgaaca 2100 agtgtaacac actgatggtt ttaatgtatc ttttccactt attatagtta tattcctaca 2160 atacaatttt aaaattgtct ttttatatta tatttatgct tctgtgtcat gattttttca 2220 agctgttata ttagttgtaa ccagtagtat tcacattaaa tcttgctttt tttcccctta 2280 aaaaaagaaa aaaattacca aacaataaac ttggctagac cttgttttga ggattttaca 2340 agacctttgt agcgattaga ttttttttct acattgaaaa tagaaactgc ttcctttctt 2400 ctttccagtc agctattggt ctttccagct gttataatct aaagtattct tatgatctgt 2460 gtaagctctg aatgaacttc tttactcaat aaaattaatt ttttggcttc ttaaaaaaaa 2520 aaaaaaa 2527 117 1098 DNA Homo sapiens misc_feature (88) n equals a,t,g, or c 117 cgcatcacag acaacccaga aggaaaatgg ttgggcagaa cagcaagggg ttcatatggc 60 tatattaaaa caactgctgt agagattnnc tatgattctt tgaaactgaa aaaagactct 120 cttggtgccc cttcaagacc tattgaagat gaccaagaag tatatgatga tgttgcagag 180 caggatgata ttagcagcca cagtcagagt ggaagtggag ggatattccc tccaccacca 240 gatgatgaca tttatgatgg gattgaagag gaagatgctg atgatggttt ccctgctcct 300 cctaaacaat tggacatggg agatgaagtt tacgatgatg tggatacctc tgatttccct 360 gtttcatcag cagagatgag tcaaggaact aatgttggaa aagctaagac agaagaaaag 420 gaccttaaga agctaaaaaa gcagraaaaa gaaraaaaag acttcaggaa aaaatttaaa 480 tatgatggtg aaattagagt cctatattca actaaagtta caacttccat aacttctaaa 540 aagtggggaa ccagagatct acaggtaaaa cctggtgaat ctctagaagt tatacaaacc 600 acagatgaca caaaagttct ctgcagaaat gaagaaggga aatatggtta tgtccttcgg 660 agttacctag cggacaatga tggagagatc tatgatgata ttgctgatgg ctgcatctat 720 gacaatgact agcactcaac tttggtcatt ctgctgtgtt cattaggtgc caatgtgaag 780 tctggatttt aattggcatg ttattgggta tcmagaaaat taatgcacar aaccacttat 840 tatcatttgt tatgaaatcc caattatctt tacaaagtgt ttaaagtttg aacatagaaa 900 ataatctctc tgcttaattg ttatctcaga agactacatt agtgagatgt aagaattatt 960 aaatattcca tttccgcttt ggctacaatt atgaagaagt tgaaggtact tcttttagac 1020 caccagtaaa taatcctcct tcaaaaaata aaaataaaaa aaaaaaaaaa aaactcgagg 1080 gggggcccgg tacccaat 1098 118 1679 DNA Homo sapiens misc_feature (1679) n equals a,t,g, or c 118 tcgacccacg cgtccggcga gatccctacc gcagtagccg cctctgccgc cgcggagctt 60 cccgaacctc ttcagccgcc cggagccgct cccggagccc ggccgtagag gctgcaatcg 120 cagccgggag cccgcagccc gcgccccgag cccgccgccg cccttcgagg gcgccccagg 180 ccgcgccatg gtgaaggtga cgttcaactc cgctctggcc cagaaggagg ccaagaagga 240 cgagcccaag agcggcgagg aggcgctcat catccccccc gacgccgtcg cggtggactg 300 caaggaccca gatgatgtgg taccagttgg ccaaagaaga gcctggtgtt ggtgcatgtg 360 ctttggacta gcatttatgc ttgcaggtgt tattctagga ggagcatact tgtacaaata 420 ttttgcactt caaccagatg acgtgtacta ctgtggaata aagtacatca aagatgatgt 480 catcttaaat gagccctctg cagatgcccc agctgctctc taccagacaa ttgaagaaaa 540 tattaaaatc tttgaagaag aagaagttga atttatcagt gtgcctgtcc cagagtttgc 600 agatagtgat cctgccaaca ttgttcatga ctttaacaag aaacttacag cctatttaga 660 tcttaacctg gataagtgct atgtgatccc tctgaacact tccattgtta tgccacccag 720 aaacctactg gagttactta ttaacatcaa ggctggaacc tatttgcctc agtcctatct 780 gattcatgag cacatggtta ttactgatcg cattgaaaac attgatcacc tgggtttctt 840 tatttatcga ctgtgtcatg acaaggaaac ttacaaactg caacgcagag aaactattaa 900 aggtattcag aaacgtgaag ccagcaattg tttcgcaatt cggcattttg aaaacaaatt 960 tgccgtggaa actttaattt gttcttgaac agtcaagaaa aacattattg aggaaaatta 1020 atatcacagc ataaccccac cctttacatt ttgtgcagtg attatttttt aaagtcttct 1080 ttcatgtaag tagcaaacag ggctttacta tcttttcatc tcattaattc aattaaaacc 1140 attaccttaa aatttttttc tttcgaagtg tggtgtcttt tatatttgaa ttagtaactg 1200 tatgaagtca tagataatag tacatgtcac cttaggtagt aggaagaatt acaatttctt 1260 taaatcattt atctggattt ttatgtttta ttagcatttt caagaagacg gattatctag 1320 agaataatca tatatatgca tacgtaaaaa tggaccacag tgacttattt gtagttgtta 1380 gttgccctgc tacctagttt gttagtgcat ttgagcacac attttaattt tcctctaatt 1440 aaaatgtgca gtattttcag tgtcaaatat atttaactat ttagagaatg atttccacct 1500 ttatgtttta atatcctagg catctgctgt aataatattt tagaaaatgt ttggaattta 1560 agaaataact tgtgttacta atttgtataa cccatatctg tgcaatggaa tataaatatc 1620 acaaagttgt ttaamwaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaan 1679 119 1411 DNA Homo sapiens misc_feature (1391) n equals a,t,g, or c 119 ggcacaggag cgacccggga gaaggagggc camgakgcgg aagcggagga gtctccagga 60 gacccgggga cagcatcgcc caggcccctg tttgcaggcc tttcagatat atccatctca 120 caagacatcc ccgtagaagg agaaatcacc attcctatga gatctcgcat ccgggagttt 180 gacagctcca cattaaatga atctgttcgc aataccatca tgcgtgatct aaaagctgtt 240 gggaaaaaat tcatgcatgt tttgtaccca aggaaaagta atactctttt gagagattgg 300 gatttgtggg gccctttgat cctttgtgtg acactcgcat taatgctgca aagagactct 360 gcagatagtg aaaaagatgg agggccccaa tttgcagagg tgtttgtcat tgtctggttt 420 ggtgcagtta ccatcaccct caactcaaaa cttcttggag ggaacatatc tttttttcag 480 agcctctgtg tgctgggtta ctgtatactt cccttgacag tagcaatgct gatttgccgg 540 ctggtacttt tggctgatcc aggacctgta aacttcatgg ttcggctttt tgtggtgatt 600 gtgatgtttg cctggtctat agttgcctcc acagctttcc ttgctgatag ccagcctcca 660 aaccgcagag ccctagctgt ttatcctgtt ttcctgtttt actttgtcat cagttggatg 720 attctcacct ttactcctca gtaaatcagg aatgggaaat taaaaaccag tgaattgaaa 780 gcacatctga aagatgcaat tcaccatgga gctttgtctc tggcccttat ttgtctaatt 840 ttggaggtat ttgataactg agtaggtgag gagattaaaa gggagccata tagcactgtc 900 accccttatt tgaggaactg atgtttgaaa ggctgttctt ttctctctta atgtcatttc 960 tttaaaaata catgtgcata ctacacacag tatataatgc ctccttaagg catgatggag 1020 tcaccgtggt ccatttgggt gacaaccagt gacttgggaa gcacatagat acatcttaca 1080 agttgaatag agttgataac tattttcagt tttgagaata ccagttcagg tgcagctctt 1140 aaacacattg ccttatgact attagaatat gcctctcttt tcataaataa aaatacatgg 1200 tctatatcca ttttctttta tttctctctc ttaagcttaa aaaggcaatg agagaggtta 1260 ggagtgggtt catacacgga gaatgagaaa acatgcatta accaatattc agattttgat 1320 caggggaaat tctayacttg ttgcaaaaaa aaaaaaaaaa aaactcgagg ggggcccggt 1380 acccaatcgc ngtatatgat cgnaaacaat c 1411 120 2223 DNA Homo sapiens misc_feature (338) n equals a,t,g, or c 120 cctccggaag cgtttccaac tttccagaag tttctcggga cgggcaggag ggggtgggga 60 ctgccatata tagatcccgg gagcagggga gcgggctaag agtagaatcg tgtcgcggct 120 cgagagcgag agtcacgtcc cggcgctagc cagcccgacc caggcccacc gtggtgcacg 180 caaaccactt cctggccatg cgctccctcc tgcttctcag cgccttctgc ctcctggagg 240 cggccctggc cgccgaggtg aagaaacctg cagccgcagc agctcctggc actgcggaga 300 agttgagccc caaggcggcc acgcttgccg agcgcagncg gcctggcctt cagcttgtac 360 caggccatgg ccaaggacca ggcagtggag aacatcctgg tgtcacccgt ggtggtggcc 420 tcgtcgctgg ggctcgtgtc gctgggcggc aaggcgacca cggcgtcgca ggccaaggca 480 gtgctgagcg ccgagcagct gcgcgacgag gaggtgcacg ccggcctggg cgagctgctg 540 cgctcactca gcaactcsac ggcgcgcaac gtgacctgga agctgggcag ccgactgtac 600 ggacccagct cagtgagctt cgctgatgac ttcgtgcgca cagcaagcag cactacaact 660 gcgagcactc caagatcaac ttccgcgaca agcgcacgcg ctgcagtcca tcaacgagtg 720 ggccgcgcag accaccgacg gcaagctgcc cgaggtcacc aaggacgtgg agcgcacgga 780 cggcgccctg ytagtcaacg ccatgttctt caagccacac tgggatgaga aattccacca 840 caagatggtg gacaaccgtg gcttcatggt gactcggtcc tatacygtgg gtgtcatgat 900 gatgcaccgg acaggcctct acaactacta cgacgacgag aaggaaaagc tgcaaatcgt 960 ggagatgccc ctggcccaca agctctccag cctcatcatc ctcatgcccc atcacgtgga 1020 gcctctcgag cgccttgaaa agctgctaac caaagagcag ctgaagatct ggatggggaa 1080 gatgcagaag aaggctgttg ccatctcctt gcccaagggt gtggtggagg tgacccatga 1140 cctgcagaaa cacctggctg ggctgggcct gactgaggcc attgacaaga acaaggccga 1200 cttrtcacgc atgtcaggca agaaggacct gtacctggcc agcgtgttcc acgccaccgc 1260 ctttgagttg gacacagatg gcaacccctt tgaccaggac atctacgggc gcgaggagct 1320 gcgcasccca agctgttcta cgccgaccac cccttcatct tcctagtgcg ggacacccaa 1380 agcggctccc tgctattcat tgggcgcctg gtccggccta agggtgacaa gatgcgagac 1440 gagttatagg gcctcagggt gcacacagga tggcaggagg catccaaagg ctcctgagac 1500 acatgggtgc tattggggtt gggggggagg tgaggtacca gccttggata ctccatgggg 1560 tgggggtgga aaarcagacc ggggttcccg tgtgcctgag cggaccttcc cagctagaat 1620 tcactccact tggacatggg ccccagatac catgatgctg agcccggaaa ctccacatcc 1680 tgtgggacct gggccatagt cattctgcct gccctgaaag tcccagatca agcctgcctc 1740 aatcagtatt catatttata gccaggtacc ttctcacctg tgagaccaaa ttgagctagg 1800 ggggtcagcc agccctcttc tgacactaaa acacctcagc tgcctcccca gctctatccc 1860 aacctctccc aactataaaa ctaggtgctg cagcccctgg gaccaggcac ccccagaatg 1920 acctggccgc agtgaggcgg attgagaagg agctcccagg aggggcttct gggcagactc 1980 tggtcaagaa gcatcgtgtc tggcgttgtg gggatgaact ttttgttttg tttcttcctt 2040 ttttagttct tcaaagatag ggagggaagg gggaacatga gcctttgttg ctatcaatcc 2100 aagaacttat ttgtacattt tttttttcaa taaaactttt ccaatgacaa aaaaaaaaaa 2160 aaaaaaaaaa mwmggggsgg gccgctccta gagggatccc tccganggng cccaatcgaa 2220 aat 2223 121 31 PRT Homo sapiens 121 Met Lys Lys Gln Ser Lys Arg Cys Leu Trp Lys Pro Pro Gly Ser Leu 1 5 10 15 Arg Arg Leu Trp Trp Met Arg Ala Leu Leu Ile Leu Lys Tyr Ile 20 25 30 122 198 PRT Homo sapiens MISC_FEATURE (29) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 122 Met Lys Lys Ser Leu Glu Asn Leu Asn Arg Leu Gln Val Met Leu Leu 1 5 10 15 His Leu Thr Ala Ala Phe Leu Gln Arg Ala Gln His Xaa Phe Asp Tyr 20 25 30 Lys Asp Glu Ser Gly Phe Pro Lys Pro Pro Ser Tyr Asn Val Ala Thr 35 40 45 Thr Leu Pro Ser Tyr Asp Glu Ala Glu Arg Thr Lys Ala Glu Ala Thr 50 55 60 Ile Pro Leu Val Pro Gly Arg Asp Glu Asp Phe Val Gly Arg Asp Asp 65 70 75 80 Phe Asp Asp Ala Asp Gln Leu Arg Ile Gly Asn Asp Gly Ile Phe Met 85 90 95 Leu Thr Phe Phe Met Ala Phe Leu Phe Asn Trp Ile Gly Phe Phe Leu 100 105 110 Ser Phe Cys Leu Thr Thr Ser Ala Ala Gly Arg Tyr Gly Ala Ile Ser 115 120 125 Gly Phe Gly Leu Ser Leu Ile Lys Trp Ile Leu Ile Val Arg Phe Ser 130 135 140 Thr Tyr Phe Pro Gly Tyr Phe Asp Gly Gln Tyr Trp Leu Trp Trp Val 145 150 155 160 Phe Leu Val Leu Gly Phe Leu Leu Phe Leu Arg Gly Phe Ile Asn Tyr 165 170 175 Ala Lys Val Arg Lys Met Pro Glu Thr Phe Ser Asn Leu Pro Arg Thr 180 185 190 Arg Val Leu Phe Ile Tyr 195 123 39 PRT Homo sapiens 123 Met His Asn Gln Arg Gln Val Phe Leu Phe His Leu Phe Ser Asn Tyr 1 5 10 15 Leu Leu Ser Ile Asn Ser Val Pro Gly Thr Leu Leu Ala Ala Thr Tyr 20 25 30 Cys Leu Asn Met Thr Tyr Gly 35 124 23 PRT Homo sapiens 124 Met Arg Lys Lys Phe Leu Leu Ala Gln Val Phe Leu Ser Leu Ser Val 1 5 10 15 Met Pro Ser Met Pro Val Thr 20 125 110 PRT Homo sapiens 125 Met Val Leu Leu Cys Leu Leu Leu Val Pro Leu Leu Leu Ser Leu Phe 1 5 10 15 Val Leu Gly Leu Phe Leu Trp Phe Leu Lys Arg Glu Arg Gln Glu Glu 20 25 30 Tyr Ile Glu Glu Lys Lys Arg Val Asp Ile Cys Arg Glu Thr Pro Asn 35 40 45 Ile Cys Pro His Ser Gly Glu Asn Thr Glu Tyr Asp Thr Ile Pro His 50 55 60 Thr Asn Arg Thr Ile Leu Lys Glu Asp Pro Ala Asn Thr Val Tyr Ser 65 70 75 80 Thr Val Glu Ile Pro Lys Lys Met Glu Asn Pro His Ser Leu Leu Thr 85 90 95 Met Pro Asp Thr Pro Arg Leu Phe Ala Tyr Glu Asn Val Ile 100 105 110 126 63 PRT Homo sapiens 126 Met Leu Leu Leu Phe Ile Tyr Phe Tyr Ser His Pro Ala Pro Val Pro 1 5 10 15 Ala Gly Ala Thr Ser Lys Pro Arg Tyr Arg Val Ile Thr Cys Gly Pro 20 25 30 Ala Ser Val Phe Ser Thr Ser Phe Ser His Ser Pro Pro Ala Arg Cys 35 40 45 Leu Gly Arg Leu Glu Gln Met Phe His Phe Gly Leu Ala Ser Gly 50 55 60 127 30 PRT Homo sapiens 127 Met Pro Phe Pro Ile Ser Ile Leu Gln Leu Cys Leu Gln Ile Ser Asn 1 5 10 15 Leu Ser Phe Cys Leu Gln Lys Ile Tyr Lys Ile Pro Phe Val 20 25 30 128 53 PRT Homo sapiens 128 Met Ala Ala Ala Cys Arg Ser Val Lys Gly Leu Val Ala Val Ile Thr 1 5 10 15 Gly Gly Ala Ser Gly Leu Gly Leu Ala Thr Ala Asp Asp Leu Trp Gly 20 25 30 Arg Glu Pro Leu Leu Cys Phe Trp Thr Cys Pro Thr Arg Val Gly Arg 35 40 45 Pro Lys Pro Arg Ser 50 129 57 PRT Homo sapiens MISC_FEATURE (10) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 129 Met Leu Leu Val Tyr Asp Leu Tyr Leu Xaa Pro Lys Leu Trp Ala Leu 1 5 10 15 Ala Thr Pro Gln Lys Asn Gly Lys Gly Ala Arg Xaa Gly Asp Gly Thr 20 25 30 Pro Ala Gln Ala Phe Trp Asp Phe Trp Ser His Leu Ile Ser Ala Asp 35 40 45 Pro Gln Thr Trp Glu Arg Ala Ala Pro 50 55 130 216 PRT Homo sapiens 130 Met Arg Leu Ser Ala Leu Leu Ala Leu Ala Ser Lys Val Thr Leu Pro 1 5 10 15 Pro His Tyr Arg Tyr Gly Met Ser Pro Pro Gly Ser Val Ala Asp Lys 20 25 30 Arg Lys Asn Pro Pro Trp Ile Arg Arg Arg Pro Val Val Val Glu Pro 35 40 45 Ile Ser Asp Glu Asp Trp Tyr Leu Phe Cys Gly Asp Thr Val Glu Ile 50 55 60 Leu Glu Gly Lys Asp Ala Gly Lys Gln Gly Lys Val Val Gln Val Ile 65 70 75 80 Arg Gln Arg Asn Trp Val Val Val Gly Gly Leu Asn Thr His Tyr Arg 85 90 95 Tyr Ile Gly Lys Thr Met Asp Tyr Arg Gly Thr Met Ile Pro Ser Glu 100 105 110 Ala Pro Leu Leu His Arg Gln Val Lys Leu Val Asp Pro Met Asp Arg 115 120 125 Lys Pro Thr Glu Ile Glu Trp Arg Phe Thr Glu Ala Gly Glu Arg Val 130 135 140 Arg Val Ser Thr Arg Ser Gly Arg Ile Ile Pro Lys Pro Glu Phe Pro 145 150 155 160 Arg Ala Asp Gly Ile Val Pro Glu Thr Trp Ile Asp Gly Pro Lys Asp 165 170 175 Thr Ser Val Glu Asp Ala Leu Glu Arg Thr Tyr Val Pro Cys Leu Lys 180 185 190 Thr Leu Gln Glu Glu Val Met Glu Ala Met Gly Ile Lys Glu Thr Arg 195 200 205 Lys Tyr Lys Lys Val Tyr Trp Tyr 210 215 131 49 PRT Homo sapiens 131 Met Ser Leu Arg Gln Lys Ser Ser Phe Arg Leu Met Val Met Ser Leu 1 5 10 15 Thr Ile Leu Lys Leu Ser Lys Thr Thr Val Leu Cys Leu Arg Cys Leu 20 25 30 His Ser Leu Lys Leu Thr Trp Arg Asp Gly Ala Arg Cys Ile Asn Ala 35 40 45 Glu 132 68 PRT Homo sapiens 132 Met Ser Gly Ser Phe Ile Leu Cys Leu Ala Leu Val Thr Arg Trp Ser 1 5 10 15 Pro Gln Ala Ser Ser Val Pro Leu Ala Val Tyr Glu Ser Lys Thr Arg 20 25 30 Lys Ser Tyr Arg Ser Gln Arg Asp Arg Asp Gly Lys Asp Arg Ser Gln 35 40 45 Gly Met Gly Leu Ser Leu Leu Val Glu Thr Arg Lys Leu Leu Leu Ser 50 55 60 Ala Asn Gln Gly 65 133 52 PRT Homo sapiens 133 Met Cys Phe Arg Phe Phe Leu Phe Cys Ser Arg Ile Leu Leu Lys Leu 1 5 10 15 Phe Phe Leu Leu Phe Pro Ala Ser Ala Phe Pro Leu Ser Thr Arg Ser 20 25 30 Ser Leu Ser Val Asn Glu His Val Val Val Ser Pro Arg Ser Thr Val 35 40 45 Ser Ile Ser Arg 50 134 540 PRT Homo sapiens MISC_FEATURE (137) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 134 Met Val Arg Thr Asp Gly His Thr Leu Ser Glu Lys Arg Asn Tyr Gln 1 5 10 15 Val Thr Asn Ser Met Phe Gly Ala Ser Arg Lys Lys Phe Val Glu Gly 20 25 30 Val Asp Ser Asp Tyr His Asp Glu Asn Met Tyr Tyr Ser Gln Ser Ser 35 40 45 Met Phe Pro His Arg Ser Glu Lys Asp Met Leu Ala Ser Pro Ser Thr 50 55 60 Ser Gly Gln Leu Ser Gln Phe Gly Ala Ser Leu Tyr Gly Gln Gln Ser 65 70 75 80 Ala Leu Gly Leu Pro Met Arg Gly Met Ser Asn Asn Thr Pro Gln Leu 85 90 95 Asn Arg Ser Leu Ser Gln Gly Thr Gln Leu Pro Ser His Val Thr Pro 100 105 110 Thr Thr Gly Val Pro Thr Met Ser Leu His Thr Pro Pro Ser Pro Ser 115 120 125 Arg Gly Ile Leu Pro Met Asn Pro Xaa Asn Met Met Asn His Ser Gln 130 135 140 Val Gly Gln Gly Ile Gly Ile Pro Ser Arg Thr Asn Ser Met Ser Ser 145 150 155 160 Ser Gly Leu Gly Ser Pro Asn Arg Ser Ser Pro Ser Ile Ile Cys Met 165 170 175 Pro Lys Gln Gln Pro Ser Arg Gln Pro Phe Thr Val Asn Ser Met Ser 180 185 190 Gly Phe Gly Met Asn Arg Asn Gln Ala Phe Gly Met Asn Asn Ser Leu 195 200 205 Ser Ser Asn Ile Phe Asn Gly Thr Asp Gly Ser Glu Asn Val Thr Gly 210 215 220 Leu Asp Leu Ser Asp Phe Pro Ala Leu Ala Asp Arg Asn Arg Arg Glu 225 230 235 240 Gly Ser Gly Asn Pro Thr Pro Leu Ile Asn Pro Leu Ala Gly Arg Ala 245 250 255 Pro Tyr Val Gly Met Val Thr Lys Pro Ala Asn Glu Gln Ser Gln Asp 260 265 270 Phe Ser Ile His Asn Glu Asp Phe Pro Ala Leu Pro Gly Ser Ser Tyr 275 280 285 Lys Asp Pro Thr Ser Ser Asn Asp Asp Ser Lys Ser Asn Leu Asn Thr 290 295 300 Ser Gly Lys Thr Thr Ser Ser Thr Asp Gly Pro Lys Phe Pro Gly Asp 305 310 315 320 Lys Ser Ser Thr Thr Gln Asn Asn Asn Gln Gln Lys Lys Gly Ile Gln 325 330 335 Val Leu Pro Asp Gly Arg Val Thr Asn Ile Pro Gln Gly Met Val Thr 340 345 350 Asp Gln Phe Gly Met Ile Gly Leu Leu Thr Phe Ile Arg Ala Ala Glu 355 360 365 Thr Asp Pro Gly Met Val His Leu Ala Leu Gly Ser Asp Leu Thr Thr 370 375 380 Leu Gly Leu Asn Leu Asn Ser Pro Glu Asn Leu Tyr Pro Lys Phe Ala 385 390 395 400 Ser Pro Trp Ala Ser Ser Pro Cys Arg Pro Gln Asp Ile Asp Phe His 405 410 415 Val Pro Ser Glu Tyr Leu Thr Asn Ile His Ile Arg Asp Lys Leu Ala 420 425 430 Ala Ile Lys Leu Gly Arg Tyr Gly Glu Asp Leu Leu Phe Tyr Leu Tyr 435 440 445 Tyr Met Asn Gly Gly Asp Val Leu Gln Leu Leu Ala Ala Val Glu Leu 450 455 460 Phe Asn Arg Asp Trp Arg Tyr His Lys Glu Glu Arg Val Trp Ile Thr 465 470 475 480 Arg Ala Pro Gly Met Glu Pro Thr Met Lys Thr Asn Thr Tyr Glu Arg 485 490 495 Gly Thr Tyr Tyr Phe Phe Asp Cys Leu Asn Trp Arg Lys Val Ala Lys 500 505 510 Glu Phe His Leu Glu Tyr Asp Lys Leu Glu Glu Arg Pro His Leu Pro 515 520 525 Ser Thr Phe Asn Tyr Asn Pro Ala Gln Gln Ala Phe 530 535 540 135 57 PRT Homo sapiens 135 Met Ile Cys Pro Gln Cys Pro Leu Ser Leu Leu Cys Leu Ile Ser Ser 1 5 10 15 Leu Cys Ser Leu Val Ile Gln Ile Ser Leu Lys Thr Ile Arg Asp Ile 20 25 30 Thr Leu Leu Asn Met Val Gly Ile Lys Phe Ser Ile Ser Leu Ser Asn 35 40 45 Lys Ile Asn Ile Asn Ser Arg Thr Trp 50 55 136 201 PRT Homo sapiens 136 Met Thr Leu Arg Pro Ser Leu Leu Pro Leu His Leu Leu Leu Leu Leu 1 5 10 15 Leu Leu Ser Ala Ala Val Cys Arg Ala Glu Ala Gly Leu Glu Thr Glu 20 25 30 Ser Pro Val Arg Thr Leu Gln Val Glu Thr Leu Val Glu Pro Pro Glu 35 40 45 Pro Cys Ala Glu Pro Ala Ala Phe Gly Asp Thr Leu His Ile His Tyr 50 55 60 Thr Gly Ser Leu Val Asp Gly Arg Ile Ile Asp Thr Ser Leu Thr Arg 65 70 75 80 Asp Pro Leu Val Ile Glu Leu Gly Gln Lys Gln Val Ile Pro Gly Leu 85 90 95 Glu Gln Ser Leu Leu Asp Met Cys Val Gly Glu Lys Arg Arg Ala Ile 100 105 110 Ile Pro Ser His Leu Ala Tyr Gly Lys Arg Gly Phe Pro Pro Ser Val 115 120 125 Pro Ala Asp Ala Val Val Gln Tyr Asp Val Glu Leu Ile Ala Leu Ile 130 135 140 Arg Ala Asn Tyr Trp Leu Lys Leu Val Lys Gly Ile Leu Pro Leu Val 145 150 155 160 Gly Met Ala Met Val Pro Ala Leu Leu Gly Leu Ile Gly Tyr His Leu 165 170 175 Tyr Arg Lys Ala Asn Arg Pro Lys Val Ser Lys Lys Lys Leu Lys Glu 180 185 190 Glu Lys Arg Asn Lys Ser Lys Lys Lys 195 200 137 216 PRT Homo sapiens 137 Met Phe Leu Arg Leu Tyr Leu Ile Ala Arg Val Met Leu Leu His Ser 1 5 10 15 Lys Leu Phe Thr Asp Ala Ser Ser Arg Ser Ile Gly Ala Leu Asn Lys 20 25 30 Ile Asn Phe Asn Thr Arg Phe Val Met Lys Thr Leu Met Thr Ile Cys 35 40 45 Pro Gly Thr Val Leu Leu Val Phe Ser Ile Ser Leu Trp Ile Ile Ala 50 55 60 Ala Trp Thr Val Arg Val Cys Glu Ser Pro Glu Ser Pro Ala Gln Pro 65 70 75 80 Ser Gly Ser Ser Leu Pro Ala Trp Tyr His Asp Gln Gln Asp Val Thr 85 90 95 Ser Asn Phe Leu Gly Ala Met Trp Leu Ile Ser Ile Thr Phe Leu Ser 100 105 110 Ile Gly Tyr Gly Asp Met Val Pro His Thr Tyr Cys Gly Lys Gly Val 115 120 125 Cys Leu Leu Thr Gly Ile Met Gly Ala Gly Cys Thr Ala Leu Val Val 130 135 140 Ala Val Val Ala Arg Lys Leu Glu Leu Thr Lys Ala Glu Lys His Val 145 150 155 160 His Asn Phe Met Met Asp Thr Gln Leu Thr Lys Arg Ile Lys Asn Ala 165 170 175 Ala Ala Asn Val Leu Arg Glu Thr Trp Leu Ile Tyr Lys His Thr Lys 180 185 190 Leu Leu Lys Lys Ile Asp His Ala Lys Val Arg Lys His Gln Arg Lys 195 200 205 Phe Leu Pro Ser Tyr Pro Pro Val 210 215 138 102 PRT Homo sapiens 138 Met Ser Asn Thr Thr Val Pro Asn Ala Pro Gln Ala Asn Ser Asp Ser 1 5 10 15 Met Val Gly Tyr Val Leu Gly Pro Phe Phe Leu Ile Thr Leu Val Gly 20 25 30 Val Val Val Ala Val Val Met Tyr Val Gln Lys Lys Lys Arg Val Asp 35 40 45 Arg Leu Arg His His Leu Leu Pro Met Tyr Ser Tyr Asp Pro Ala Glu 50 55 60 Glu Leu His Glu Ala Glu Gln Glu Leu Leu Ser Asp Met Gly Asp Pro 65 70 75 80 Lys Val Val His Gly Trp Gln Ser Gly Tyr Gln His Lys Arg Met Pro 85 90 95 Leu Leu Asp Val Lys Thr 100 139 112 PRT Homo sapiens 139 Met Arg Glu Cys Gln Glu Glu Ser Phe Trp Lys Arg Ala Leu Pro Phe 1 5 10 15 Ser Leu Val Ser Met Leu Val Thr Gln Gly Leu Val Tyr Gln Gly Tyr 20 25 30 Leu Ala Ala Asn Ser Arg Phe Gly Ser Leu Pro Lys Val Ala Leu Ala 35 40 45 Gly Leu Leu Gly Phe Gly Leu Gly Lys Val Ser Tyr Ile Gly Val Cys 50 55 60 Gln Ser Lys Phe His Phe Phe Glu Asp Gln Leu Arg Gly Ala Gly Phe 65 70 75 80 Gly Pro Gln His Asn Arg His Cys Leu Leu Thr Cys Glu Glu Cys Lys 85 90 95 Ile Lys His Gly Leu Ser Glu Lys Gly Asp Ser Gln Pro Ser Ala Ser 100 105 110 140 20 PRT Homo sapiens 140 Met Lys Asn Asp Arg Asn Gln Gly Phe Ser Leu Leu Gln Leu Ile Asp 1 5 10 15 Trp Asn Lys Pro 20 141 30 PRT Homo sapiens 141 Met Gly Thr Gln Pro Pro Val Val Ala Gly Phe Thr Ile Pro Met Leu 1 5 10 15 Gly Tyr Thr Val Arg Val Leu Thr Phe His Leu Ser Cys Ser 20 25 30 142 99 PRT Homo sapiens 142 Met Lys Ile Pro Val Leu Pro Ala Val Val Leu Leu Ser Leu Leu Val 1 5 10 15 Leu His Ser Ala Gln Gly Ala Thr Leu Gly Gly Pro Glu Glu Glu Ser 20 25 30 Thr Ile Glu Asn Tyr Ala Ser Arg Pro Glu Ala Phe Asn Thr Pro Phe 35 40 45 Leu Asn Ile Asp Lys Leu Arg Ser Ala Phe Lys Ala Asp Glu Phe Leu 50 55 60 Asn Trp His Ala Leu Phe Glu Ser Ile Lys Arg Lys Leu Pro Phe Leu 65 70 75 80 Asn Trp Asp Ala Phe Pro Lys Leu Lys Gly Leu Arg Ser Ala Thr Pro 85 90 95 Asp Ala Gln 143 8 PRT Homo sapiens 143 Met Val Trp Gly Leu Leu Leu Gly 1 5 144 39 PRT Homo sapiens MISC_FEATURE (30) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 144 Met Leu Pro Leu Leu Ser Leu Leu Phe Leu Phe Phe Ser Thr Val Ser 1 5 10 15 Ser Phe Cys Gly Met Pro Leu Arg Ala His Thr Arg Ala Xaa Ala His 20 25 30 Thr Arg Thr Phe Ala Ser Arg 35 145 131 PRT Homo sapiens 145 Met Ile Cys Glu Thr Lys Ala Arg Lys Ser Ser Gly Gln Pro Gly Arg 1 5 10 15 Leu Pro Pro Pro Thr Leu Ala Pro Pro Gln Pro Pro Leu Pro Glu Thr 20 25 30 Ile Glu Arg Pro Val Gly Thr Gly Ala Met Val Ala Arg Ser Ser Asp 35 40 45 Leu Pro Tyr Leu Ile Val Gly Val Val Leu Gly Ser Ile Val Leu Ile 50 55 60 Ile Val Thr Phe Ile Pro Phe Cys Leu Trp Arg Ala Trp Ser Lys Gln 65 70 75 80 Lys His Thr Thr Asp Leu Gly Phe Pro Arg Ser Ala Leu Pro Pro Ser 85 90 95 Cys Pro Tyr Thr Met Val Pro Leu Gly Gly Leu Pro Gly His Gln Ala 100 105 110 Val Asp Ser Pro Thr Ser Val Ala Ser Val Asp Gly Pro Val Leu Met 115 120 125 Gly Ser Thr 130 146 32 PRT Homo sapiens 146 Met Gly Ala Pro Ser Leu Thr Met Leu Leu Leu Leu Lys Val Gln Pro 1 5 10 15 Arg Arg Thr Gln Ala Phe Asp Ala His Trp Val Gly Leu Pro Leu Leu 20 25 30 147 14 PRT Homo sapiens 147 Met Cys Leu Ile Phe Leu Leu Leu Leu Leu Leu Ser Phe Ser 1 5 10 148 8 PRT Homo sapiens 148 His Pro His Gln Asp Ser Gln Pro 1 5 149 68 PRT Homo sapiens 149 Met Asn Thr Ser Tyr Ile Leu Arg Leu Thr Val Val Val Ser Val Val 1 5 10 15 Ile Tyr Leu Ala Ile His Pro Leu Leu Ser Phe Ser Leu Glu Ser Pro 20 25 30 Leu Leu Val Pro Trp Arg Asp Cys Cys Gln Asn Ile Trp Lys Ser Gly 35 40 45 Ser Val Trp Tyr Lys Arg Trp Thr Leu Pro His Met Glu Val Cys Cys 50 55 60 Gln Asp Leu His 65 150 26 PRT Homo sapiens 150 Met Leu Lys Ile Phe Lys Glu Trp Glu Asn Leu Asn Leu Ile Leu Thr 1 5 10 15 Ser Ile Arg Ile Leu Glu Arg Gln Asn Met 20 25 151 195 PRT Homo sapiens 151 Met Asp Cys Glu Val Asn Asn Gly Ser Ser Leu Arg Asp Glu Cys Ile 1 5 10 15 Thr Asn Leu Leu Val Phe Gly Phe Leu Gln Ser Cys Ser Asp Asn Ser 20 25 30 Phe Arg Arg Glu Leu Asp Ala Leu Gly His Glu Leu Pro Val Leu Ala 35 40 45 Pro Gln Trp Glu Gly Tyr Asp Glu Leu Gln Thr Asp Gly Asn Arg Ser 50 55 60 Ser His Ser Arg Leu Gly Arg Ile Glu Ala Asp Ser Glu Ser Gln Glu 65 70 75 80 Asp Ile Ile Arg Asn Ile Ala Arg His Leu Ala Gln Val Gly Asp Ser 85 90 95 Met Asp Arg Ser Ile Pro Pro Gly Leu Val Asn Gly Leu Ala Leu Gln 100 105 110 Leu Arg Asn Thr Ser Arg Ser Glu Glu Asp Arg Asn Arg Asp Leu Ala 115 120 125 Thr Ala Leu Glu Gln Leu Leu Gln Ala Tyr Pro Arg Asp Met Glu Lys 130 135 140 Glu Lys Thr Met Leu Val Leu Ala Leu Leu Leu Ala Lys Lys Val Ala 145 150 155 160 Ser His Thr Pro Ser Leu Leu Arg Asp Val Phe His Thr Thr Val Asn 165 170 175 Phe Ile Asn Gln Asn Leu Arg Thr Tyr Val Arg Ser Leu Ala Arg Asn 180 185 190 Gly Met Asp 195 152 91 PRT Homo sapiens MISC_FEATURE (85) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 152 Met Ser Leu Ser Leu Val Ser Val Ser Val Gly Pro Ser Thr Leu Ala 1 5 10 15 Cys Ser Phe Leu Arg Pro Lys Ala Arg Pro Ser Lys Arg Ser Pro Arg 20 25 30 Asn Tyr Thr Asp Ser Thr Ser Pro Gly Gly Pro Arg Ala Pro Arg Gly 35 40 45 Gly Ala Trp Arg Leu Ser Ser Gln Gln Asn Ser Ser Pro Lys Gly Val 50 55 60 Ala Val Ala Lys Ala Ser Tyr Arg Pro Val Leu Cys Phe Leu Pro Gly 65 70 75 80 Pro Trp Ser Ser Xaa Pro Xaa Ala Phe Leu Ile 85 90 153 31 PRT Homo sapiens 153 Met Gly Thr Leu Ser Ala Glu Cys Ser Gly Pro Ala Thr Leu Gly Leu 1 5 10 15 Cys Leu Val Val Pro Trp Asn Ser Ser Gly Leu Ser Gln Pro Pro 20 25 30 154 90 PRT Homo sapiens 154 Met Lys Phe Leu Ala Val Leu Val Leu Leu Gly Val Ser Ile Phe Leu 1 5 10 15 Val Ser Ala Gln Asn Pro Thr Thr Ala Ala Pro Ala Asp Thr Tyr Pro 20 25 30 Ala Thr Gly Pro Ala Asp Asp Glu Ala Pro Asp Ala Glu Thr Thr Ala 35 40 45 Ala Ala Thr Thr Ala Thr Thr Ala Ala Pro Thr Thr Ala Thr Thr Ala 50 55 60 Ala Ser Thr Thr Ala Arg Lys Asp Ile Pro Val Leu Pro Lys Trp Val 65 70 75 80 Gly Asp Leu Pro Asn Gly Arg Val Cys Pro 85 90 155 89 PRT Homo sapiens 155 Met Ile Ile Ser Leu Phe Ile Tyr Ile Phe Leu Thr Cys Ser Asn Thr 1 5 10 15 Ser Pro Ser Tyr Gln Gly Thr Gln Leu Gly Leu Gly Leu Pro Ser Ala 20 25 30 Gln Trp Trp Pro Leu Thr Gly Arg Arg Met Gln Cys Cys Arg Leu Phe 35 40 45 Cys Phe Leu Leu Gln Asn Cys Leu Phe Pro Phe Pro Leu His Leu Ile 50 55 60 Gln His Asp Pro Cys Glu Leu Val Leu Thr Ile Ser Trp Asp Trp Ala 65 70 75 80 Glu Ala Gly Ala Ser Leu Tyr Ser Pro 85 156 174 PRT Homo sapiens 156 Met Ser Ser Ala Ala Ala Asp His Trp Ala Trp Leu Leu Val Leu Ser 1 5 10 15 Phe Val Phe Gly Cys Asn Val Leu Arg Ile Leu Leu Pro Ser Phe Ser 20 25 30 Ser Phe Met Ser Arg Val Leu Gln Lys Asp Ala Glu Gln Glu Ser Gln 35 40 45 Met Arg Ala Glu Ile Gln Asp Met Lys Gln Glu Leu Ser Thr Val Asn 50 55 60 Met Met Asp Glu Phe Ala Arg Tyr Ala Arg Leu Glu Arg Lys Ile Asn 65 70 75 80 Lys Met Thr Asp Lys Leu Lys Thr His Val Lys Ala Arg Thr Ala Gln 85 90 95 Leu Ala Lys Ile Lys Trp Val Ile Ser Val Ala Phe Tyr Val Leu Gln 100 105 110 Ala Ala Leu Met Ile Ser Leu Ile Trp Lys Tyr Tyr Ser Val Pro Val 115 120 125 Ala Val Val Pro Ser Lys Trp Ile Thr Pro Leu Asp Arg Leu Val Ala 130 135 140 Phe Pro Thr Arg Val Ala Gly Gly Val Gly Ile Thr Cys Trp Ile Leu 145 150 155 160 Val Cys Asn Lys Val Val Ala Ile Val Leu His Pro Phe Ser 165 170 157 45 PRT Homo sapiens 157 Met Gly Lys Leu Ile Asn Ile Val Ile Arg Lys Pro Leu Leu Leu Leu 1 5 10 15 Leu Val Gln Cys Glu Asn Cys Cys Arg Lys Asn Met Leu Tyr Asn Ile 20 25 30 Phe Leu Asn Ile His Asn Ile His Lys Phe Ser Asn His 35 40 45 158 23 PRT Homo sapiens 158 Met Val Ala Ser Thr Leu Val Thr Asn Leu Phe Gly Val Ala Phe Ala 1 5 10 15 Thr Thr Ala Ala Thr Arg Ala 20 159 70 PRT Homo sapiens MISC_FEATURE (33) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 159 Met Leu Met Ala Pro Val Val Cys Leu Ser Phe Ser Pro Cys Pro Ala 1 5 10 15 Asp Thr Ser Leu Thr Gly Asp Gly Leu Lys Ala Gly Leu Glu Arg Gly 20 25 30 Xaa Ala Leu Val Thr Leu Phe Asp Ser Val Thr His Phe Leu Ala His 35 40 45 Thr Leu Phe Glu Leu Leu Asp Phe Gln Leu Ala Phe Leu Arg Ser Gly 50 55 60 Lys Gln Thr Ala Pro His 65 70 160 323 PRT Homo sapiens 160 Met Leu Leu Leu Leu Leu Leu Leu Gly Ser Gly Gln Gly Pro Gln Gln 1 5 10 15 Val Gly Ala Gly Gln Thr Phe Glu Tyr Leu Lys Arg Glu His Ser Leu 20 25 30 Ser Lys Pro Tyr Gln Gly Val Gly Thr Gly Ser Ser Ser Leu Trp Asn 35 40 45 Leu Met Gly Asn Ala Met Val Met Thr Gln Tyr Ile Arg Leu Thr Pro 50 55 60 Asp Met Gln Ser Lys Gln Gly Ala Leu Trp Asn Arg Val Pro Cys Phe 65 70 75 80 Leu Arg Asp Trp Glu Leu Gln Val His Phe Lys Ile His Gly Gln Gly 85 90 95 Lys Lys Asn Leu His Gly Asp Gly Leu Ala Ile Trp Tyr Thr Arg Asn 100 105 110 Arg Met Gln Pro Gly Pro Val Phe Gly Asn Met Asp Lys Phe Val Gly 115 120 125 Leu Gly Val Phe Val Asp Thr Tyr Pro Asn Glu Glu Lys Gln Gln Glu 130 135 140 Arg Val Phe Pro Tyr Ile Ser Ala Met Val Asn Asn Gly Ser Leu Ser 145 150 155 160 Tyr Asp His Glu Arg Asp Gly Arg Pro Thr Glu Leu Gly Gly Cys Thr 165 170 175 Ala Ile Val Arg Asn Leu His Tyr Asp Thr Phe Leu Val Ile Arg Tyr 180 185 190 Val Lys Arg His Leu Thr Ile Met Met Asp Ile Asp Gly Lys His Glu 195 200 205 Trp Arg Asp Cys Ile Glu Val Pro Gly Val Arg Leu Pro Arg Gly Tyr 210 215 220 Tyr Phe Gly Thr Ser Ser Ile Thr Gly Asp Leu Ser Asp Asn His Asp 225 230 235 240 Val Ile Ser Leu Lys Leu Phe Glu Leu Thr Val Glu Arg Thr Pro Glu 245 250 255 Glu Glu Lys Leu His Arg Asp Val Phe Leu Pro Ser Val Asp Asn Met 260 265 270 Lys Leu Pro Glu Met Thr Ala Pro Leu Pro Pro Leu Ser Gly Leu Ala 275 280 285 Leu Phe Leu Ile Val Phe Phe Ser Leu Val Phe Ser Val Phe Ala Ile 290 295 300 Val Ile Gly Ile Ile Leu Tyr Asn Lys Trp Gln Glu Gln Ser Arg Lys 305 310 315 320 Arg Phe Tyr 161 320 PRT Homo sapiens MISC_FEATURE (120) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 161 Met Pro Ser Glu Tyr Thr Tyr Val Lys Leu Arg Ser Asp Cys Ser Arg 1 5 10 15 Pro Ser Leu Gln Trp Tyr Thr Arg Ala Gln Ser Lys Met Arg Arg Pro 20 25 30 Ser Leu Leu Leu Lys Asp Ile Leu Lys Cys Thr Leu Leu Val Phe Gly 35 40 45 Val Trp Ile Leu Tyr Ile Leu Lys Leu Asn Tyr Thr Thr Glu Glu Cys 50 55 60 Asp Met Lys Lys Met His Tyr Val Asp Pro Asp His Val Lys Arg Ala 65 70 75 80 Gln Lys Tyr Ala Gln Gln Val Leu Gln Lys Glu Cys Arg Pro Lys Phe 85 90 95 Ala Lys Thr Ser Met Ala Leu Leu Phe Glu His Arg Tyr Ser Val Asp 100 105 110 Leu Leu Pro Phe Val Gln Lys Xaa Pro Lys Asp Ser Glu Ala Glu Ser 115 120 125 Lys Tyr Asp Pro Pro Phe Gly Phe Arg Lys Phe Ser Ser Lys Val Gln 130 135 140 Thr Leu Leu Glu Leu Leu Pro Glu His Asp Leu Pro Glu His Leu Lys 145 150 155 160 Ala Lys Thr Cys Arg Arg Cys Val Val Ile Gly Ser Gly Gly Ile Leu 165 170 175 His Gly Leu Glu Leu Gly His Thr Leu Asn Gln Phe Asp Val Val Ile 180 185 190 Arg Leu Asn Ser Ala Pro Val Glu Gly Tyr Ser Glu His Val Gly Asn 195 200 205 Lys Thr Thr Ile Arg Met Thr Tyr Pro Glu Gly Ala Pro Leu Ser Asp 210 215 220 Leu Glu Tyr Tyr Ser Asn Asp Leu Phe Val Ala Val Leu Phe Lys Ser 225 230 235 240 Val Asp Phe Asn Trp Leu Gln Ala Met Val Lys Lys Glu Thr Leu Pro 245 250 255 Phe Trp Val Arg Leu Phe Phe Trp Lys Gln Val Ala Glu Lys Ile Pro 260 265 270 Leu Gln Pro Lys His Phe Arg Ile Leu Asn Pro Val Ile Ile Lys Glu 275 280 285 Thr Ala Phe Xaa His Pro Ser Val Leu Arg Ala Ser Val Lys Val Leu 290 295 300 Gly Ala Glu Ile Arg Thr Ser Pro Gln Ser Val Ser Leu Pro Leu Ser 305 310 315 320 162 31 PRT Homo sapiens 162 Met Thr Leu Asp Val Gln Thr Val Val Val Phe Ala Val Ile Val Val 1 5 10 15 Leu Leu Leu Val Asn Val Ile Leu Met Phe Phe Leu Gly Thr Arg 20 25 30 163 72 PRT Homo sapiens MISC_FEATURE (26) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 163 Met Leu Pro Leu Leu Phe Cys Ala Phe Cys Leu His Lys Leu Gly Pro 1 5 10 15 Leu Leu Phe Leu Tyr Asp Val Leu Met Xaa His Glu Ala Val Met Arg 20 25 30 Thr His Gln Ile Gln Leu Pro Asp Pro Glu Phe Pro Ser Gln Gln Asn 35 40 45 Gln Val Leu Asn Lys Thr Leu Phe Asn Lys Leu Lys Lys Lys Lys Lys 50 55 60 Lys Lys Lys Xaa Xaa Xaa Lys Lys 65 70 164 281 PRT Homo sapiens 164 Met Ala Ser Arg Gly Arg Arg Pro Glu His Gly Gly Pro Pro Glu Leu 1 5 10 15 Phe Tyr Asp Glu Thr Glu Ala Arg Lys Tyr Val Arg Asn Ser Arg Met 20 25 30 Ile Asp Ile Gln Thr Arg Met Ala Gly Arg Ala Leu Glu Leu Leu Tyr 35 40 45 Leu Pro Glu Asn Lys Pro Cys Tyr Leu Leu Asp Ile Gly Cys Gly Thr 50 55 60 Gly Leu Ser Gly Ser Tyr Leu Ser Asp Glu Gly His Tyr Trp Val Gly 65 70 75 80 Leu Asp Ile Ser Pro Ala Met Leu Asp Glu Ala Val Asp Arg Glu Ile 85 90 95 Glu Gly Asp Leu Leu Leu Gly Asp Met Gly Gln Gly Ile Pro Phe Lys 100 105 110 Pro Gly Thr Phe Asp Gly Cys Ile Ser Ile Ser Ala Val Gln Trp Leu 115 120 125 Cys Asn Ala Asn Lys Lys Ser Glu Asn Pro Ala Lys Arg Leu Tyr Cys 130 135 140 Phe Phe Ala Ser Leu Phe Ser Val Leu Val Arg Gly Ser Arg Ala Val 145 150 155 160 Leu Gln Leu Tyr Pro Glu Asn Ser Glu Gln Leu Glu Leu Ile Thr Thr 165 170 175 Gln Ala Thr Lys Ala Gly Phe Ser Gly Gly Met Val Val Asp Tyr Pro 180 185 190 Asn Ser Ala Lys Ala Lys Lys Phe Tyr Leu Cys Leu Phe Ser Gly Pro 195 200 205 Ser Thr Phe Ile Pro Glu Gly Leu Ser Glu Asn Gln Asp Glu Val Glu 210 215 220 Pro Arg Glu Ser Val Phe Thr Asn Glu Arg Phe Pro Leu Arg Met Ser 225 230 235 240 Arg Arg Gly Met Val Arg Lys Ser Arg Ala Trp Val Leu Glu Lys Lys 245 250 255 Glu Arg His Arg Arg Gln Gly Arg Glu Val Arg Pro Asp Thr Gln Tyr 260 265 270 Thr Gly Arg Lys Arg Lys Pro Arg Phe 275 280 165 81 PRT Homo sapiens 165 Met Glu Lys Ile Pro Glu Val Thr Asn Ser Asn Ser Ser Phe His Ala 1 5 10 15 His Asp Leu Gly Phe Cys Val Leu Ser Ile Ala Thr Ser Lys Ser Arg 20 25 30 Lys Ala Pro Ala Pro His Ala Gln Lys Cys Asn Leu Lys Ser Leu Arg 35 40 45 Ser Ser Ala Gln Thr Asp Ile Asn Lys Pro Val Phe Ser Leu His Pro 50 55 60 Glu Pro Pro Gly Lys Ser Gly Ala Gln Thr Gln Ser Lys Ala Pro Phe 65 70 75 80 Leu 166 327 PRT Homo sapiens MISC_FEATURE (300) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 166 Met Trp Arg Pro Ser Val Leu Leu Leu Leu Leu Leu Leu Arg His Gly 1 5 10 15 Ala Gln Gly Lys Pro Ser Pro Asp Ala Gly Pro His Gly Gln Gly Arg 20 25 30 Val His Gln Ala Ala Pro Leu Ser Asp Ala Pro His Asp Asp Ala His 35 40 45 Gly Asn Phe Gln Tyr Asp His Glu Ala Phe Leu Gly Arg Glu Val Ala 50 55 60 Lys Glu Phe Asp Gln Leu Thr Pro Glu Glu Ser Gln Ala Arg Leu Gly 65 70 75 80 Arg Ile Val Asp Arg Met Asp Arg Ala Gly Asp Gly Asp Gly Trp Val 85 90 95 Ser Leu Ala Glu Leu Arg Ala Trp Ile Ala His Thr Gln Gln Arg His 100 105 110 Ile Arg Asp Ser Val Ser Ala Ala Trp Asp Thr Tyr Asp Thr Asp Arg 115 120 125 Asp Gly Arg Val Gly Trp Glu Glu Leu Arg Asn Ala Thr Tyr Gly His 130 135 140 Tyr Ala Pro Gly Glu Glu Phe His Asp Val Glu Asp Ala Glu Thr Tyr 145 150 155 160 Lys Lys Met Leu Ala Arg Asp Glu Arg Arg Phe Arg Val Ala Asp Gln 165 170 175 Asp Gly Asp Ser Met Ala Thr Arg Glu Glu Leu Thr Ala Phe Leu His 180 185 190 Pro Glu Glu Phe Pro His Met Arg Asp Ile Val Ile Ala Glu Thr Leu 195 200 205 Glu Asp Leu Asp Arg Asn Lys Asp Gly Tyr Val Gln Val Glu Glu Tyr 210 215 220 Ile Ala Asp Leu Tyr Ser Ala Glu Pro Gly Glu Glu Glu Pro Ala Trp 225 230 235 240 Val Gln Thr Glu Arg Gln Gln Phe Arg Asp Phe Arg Asp Leu Asn Lys 245 250 255 Asp Gly His Leu Asp Gly Ser Glu Val Gly His Trp Val Leu Pro Pro 260 265 270 Ala Gln Asp Gln Pro Leu Val Glu Ala Asn His Leu Leu His Glu Ser 275 280 285 Asp Thr Asp Lys Asp Gly Arg Leu Ser Lys Ala Xaa Ile Leu Gly Asn 290 295 300 Trp Asn Met Phe Val Gly Ser Gln Ala Thr Asn Tyr Gly Glu Asp Leu 305 310 315 320 Thr Arg His His Asp Glu Leu 325 167 65 PRT Homo sapiens 167 Met Ile Lys Ile Leu Lys Glu Ala Ile Glu Glu Thr Ser Phe Cys Ser 1 5 10 15 Phe Trp Arg Ile Ser Phe Gln Leu Ser Ile His His Ile Phe Leu Ile 20 25 30 Phe Cys Ala Gln Leu Thr Thr Leu Leu Tyr Ser Thr Phe Leu Phe Ile 35 40 45 Pro Ile Ser Trp Phe Leu Ile Val Pro Gly Ala Val Asp Lys Thr Ile 50 55 60 Leu 65 168 159 PRT Homo sapiens 168 Met Trp Leu Phe Ile Leu Leu Ser Leu Ala Leu Ile Ser Asp Ala Met 1 5 10 15 Val Met Asp Glu Lys Val Lys Arg Ser Phe Val Leu Asp Thr Ala Ser 20 25 30 Ala Ile Cys Asn Tyr Asn Ala His Tyr Lys Asn His Pro Lys Tyr Trp 35 40 45 Cys Arg Gly Tyr Phe Arg Asp Tyr Cys Asn Ile Ile Ala Phe Ser Pro 50 55 60 Asn Ser Thr Asn His Val Ala Leu Lys Asp Thr Gly Asn Gln Leu Ile 65 70 75 80 Val Thr Met Ser Cys Leu Asn Lys Glu Asp Thr Gly Trp Tyr Trp Cys 85 90 95 Gly Ile Gln Arg Asp Phe Ala Arg Asp Asp Met Asp Phe Thr Glu Leu 100 105 110 Ile Val Thr Asp Asp Lys Gly Thr Trp Pro Met Thr Leu Val Trp Glu 115 120 125 Arg Leu Ser Gly Thr Lys Pro Glu Ala Ala Arg Leu Pro Lys Leu Ser 130 135 140 Ala Arg Leu Thr Ala Pro Gly Arg Pro Phe Ser Ser Phe Ala Tyr 145 150 155 169 123 PRT Homo sapiens MISC_FEATURE (3) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 169 Met Ala Xaa His Phe Leu Leu Val Ala Leu Gln Ser Val Pro His Cys 1 5 10 15 Pro His Leu Leu Glu Glu Glu His Lys Leu Cys Lys Val Ser His Phe 20 25 30 Ser Gly Val Thr Leu Val Thr Ser Arg Gln Asp Ser Ser Ser Tyr Val 35 40 45 Pro Val Gln Thr Leu Phe Ile His Leu Gly Pro Trp Ala Trp Asp Leu 50 55 60 Xaa Pro Cys Thr Ala Glu Asp Pro Glu Ala Glu Arg Ser Leu Arg Leu 65 70 75 80 Cys His Ser His Leu Ala Arg Xaa Asn Val Ser Pro Ser Gln Ala Ala 85 90 95 Glu Gly Xaa Xaa Xaa Arg Gly Cys Gln His Arg Gly Ser Arg Glu Leu 100 105 110 Thr Phe Leu Ser Ala Glu Asn Glu Ala Gly Ile 115 120 170 129 PRT Homo sapiens 170 Met Lys Val Gly Ala Arg Ile Arg Val Lys Met Ser Val Asn Lys Ala 1 5 10 15 His Pro Val Val Ser Thr His Trp Arg Trp Pro Ala Glu Trp Pro Gln 20 25 30 Met Phe Leu His Leu Ala Gln Glu Pro Arg Thr Glu Val Lys Ser Arg 35 40 45 Pro Leu Gly Leu Ala Gly Phe Ile Arg Gln Asp Ser Lys Thr Arg Lys 50 55 60 Pro Leu Glu Gln Glu Thr Ile Met Ser Ala Ala Asp Thr Ala Leu Trp 65 70 75 80 Pro Tyr Gly His Gly Asn Arg Glu His Gln Glu Asn Glu Leu Gln Lys 85 90 95 Tyr Leu Gln Tyr Lys Asp Met His Leu Leu Asp Ser Gly Gln Ser Leu 100 105 110 Gly His Thr His Thr Leu Gln Gly Ser His Asn Leu Thr Ala Leu Asn 115 120 125 Ile 171 372 PRT Homo sapiens 171 Met Ala Tyr His Ser Phe Leu Val Glu Pro Ile Ser Cys His Ala Trp 1 5 10 15 Asn Lys Asp Arg Thr Gln Ile Ala Ile Cys Pro Asn Asn His Glu Val 20 25 30 His Ile Tyr Glu Lys Ser Gly Ala Lys Trp Thr Lys Val His Glu Leu 35 40 45 Lys Glu His Asn Gly Gln Val Thr Gly Ile Asp Trp Ala Pro Glu Ser 50 55 60 Asn Arg Ile Val Thr Cys Gly Thr Asp Arg Asn Ala Tyr Val Trp Thr 65 70 75 80 Leu Lys Gly Arg Thr Trp Lys Pro Thr Leu Val Ile Leu Arg Ile Asn 85 90 95 Arg Ala Ala Arg Cys Val Arg Trp Ala Pro Asn Glu Asn Lys Phe Ala 100 105 110 Val Gly Ser Gly Ser Arg Val Ile Ser Ile Cys Tyr Phe Glu Gln Glu 115 120 125 Asn Asp Trp Trp Val Cys Lys His Ile Lys Lys Pro Ile Arg Ser Thr 130 135 140 Val Leu Ser Leu Asp Trp His Pro Asn Asn Val Leu Leu Ala Ala Gly 145 150 155 160 Ser Cys Asp Phe Lys Cys Arg Ile Phe Ser Ala Tyr Ile Lys Glu Val 165 170 175 Glu Glu Arg Pro Ala Pro Thr Pro Trp Gly Ser Lys Met Pro Phe Gly 180 185 190 Glu Leu Met Phe Glu Ser Ser Ser Ser Cys Gly Trp Val His Gly Val 195 200 205 Cys Phe Ser Ala Ser Gly Ser Arg Val Ala Trp Val Ser His Asp Ser 210 215 220 Thr Val Cys Leu Ala Asp Ala Asp Lys Lys Met Ala Val Ala Thr Leu 225 230 235 240 Ala Ser Glu Thr Leu Pro Leu Leu Ala Leu Thr Phe Ile Thr Asp Asn 245 250 255 Ser Leu Val Ala Ala Gly His Asp Cys Phe Pro Val Leu Phe Thr Tyr 260 265 270 Asp Ala Ala Ala Gly Met Leu Ser Phe Gly Gly Arg Leu Asp Val Pro 275 280 285 Lys Gln Ser Ser Gln Arg Gly Leu Thr Ala Arg Glu Arg Phe Gln Asn 290 295 300 Leu Asp Lys Lys Ala Ser Ser Glu Gly Gly Thr Ala Ala Gly Ala Gly 305 310 315 320 Leu Asp Ser Leu His Lys Asn Ser Val Ser Gln Ile Ser Val Leu Ser 325 330 335 Gly Gly Lys Ala Lys Cys Ser Gln Phe Cys Thr Thr Gly Met Asp Gly 340 345 350 Gly Met Ser Ile Trp Asp Val Lys Ser Leu Glu Ser Ala Leu Lys Asp 355 360 365 Leu Lys Ile Lys 370 172 216 PRT Homo sapiens 172 Met Trp Ser Ile Gly Ala Gly Ala Leu Gly Ala Ala Ala Leu Ala Leu 1 5 10 15 Leu Leu Ala Asn Thr Asp Val Phe Leu Ser Lys Pro Gln Lys Ala Ala 20 25 30 Leu Glu Tyr Leu Glu Asp Ile Asp Leu Lys Thr Leu Glu Lys Glu Pro 35 40 45 Arg Thr Phe Lys Ala Lys Glu Leu Trp Glu Lys Asn Gly Ala Val Ile 50 55 60 Met Ala Val Arg Arg Pro Gly Cys Phe Leu Cys Arg Glu Glu Ala Ala 65 70 75 80 Asp Leu Ser Ser Leu Lys Ser Met Leu Asp Gln Leu Gly Val Pro Leu 85 90 95 Tyr Ala Val Val Lys Glu His Ile Arg Thr Glu Val Lys Asp Phe Gln 100 105 110 Pro Tyr Phe Lys Gly Glu Ile Phe Leu Asp Glu Lys Lys Lys Phe Tyr 115 120 125 Gly Pro Gln Arg Arg Lys Met Met Phe Met Gly Phe Ile Arg Leu Gly 130 135 140 Val Trp Tyr Asn Phe Phe Arg Ala Trp Asn Gly Gly Phe Ser Gly Asn 145 150 155 160 Leu Glu Gly Glu Gly Phe Ile Leu Gly Gly Val Phe Val Val Gly Ser 165 170 175 Gly Lys Gln Gly Ile Leu Leu Glu His Arg Glu Lys Glu Phe Gly Asp 180 185 190 Lys Val Asn Leu Leu Ser Val Leu Glu Ala Ala Lys Met Ile Lys Pro 195 200 205 Gln Thr Leu Ala Ser Glu Lys Lys 210 215 173 55 PRT Homo sapiens 173 Met Lys Pro Val Ser Arg Arg Thr Leu Asp Trp Ile Tyr Ser Val Leu 1 5 10 15 Leu Leu Ala Ile Val Leu Ile Ser Trp Gly Cys Ile Ile Tyr Ala Ser 20 25 30 Met Val Ser Ala Arg Arg Gln Leu Arg Lys Lys Tyr Pro Asp Lys Ile 35 40 45 Phe Gly Thr Asn Glu Asn Leu 50 55 174 23 PRT Homo sapiens MISC_FEATURE (19) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 174 Met Ala Ala Asn Thr Phe Val Leu Ile Met Gly Ile Pro Thr Ser Ala 1 5 10 15 Asn Ala Xaa Arg Asp Leu Phe 20 175 103 PRT Homo sapiens 175 Met Ser Ile Cys His Arg Gly Thr Gly Ile Ala Leu Ser Ala Gly Val 1 5 10 15 Ser Leu Phe Gly Met Ser Ala Leu Leu Leu Pro Gly Asn Phe Glu Ser 20 25 30 Tyr Leu Glu Leu Val Lys Ser Leu Cys Leu Gly Pro Ala Leu Ile His 35 40 45 Thr Ala Lys Phe Ala Leu Val Phe Pro Leu Met Tyr His Thr Trp Asn 50 55 60 Gly Ile Arg His Leu Met Trp Asp Leu Gly Lys Gly Leu Lys Ile Pro 65 70 75 80 Gln Leu Tyr Gln Ser Gly Val Val Val Leu Val Leu Thr Val Leu Ser 85 90 95 Ser Met Gly Leu Ala Ala Met 100 176 48 PRT Homo sapiens 176 Met Thr Lys Ala Ser Ser Leu Trp Pro Leu Lys Thr Thr Cys Gln Ile 1 5 10 15 Ser Gly Thr Val Phe Phe Phe Leu Phe Leu Phe Ser Cys Phe Leu Met 20 25 30 Gln Ala Gln Cys Asp Lys Phe Val Gly Trp Asp Phe Phe Phe Phe Leu 35 40 45 177 96 PRT Homo sapiens MISC_FEATURE (18) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 177 Met Arg Arg Ala Leu Ile Pro Pro Cys Arg Gly Gly Pro Ser Ala Ser 1 5 10 15 Asp Xaa Cys Cys Ser Cys Ser Pro Ser Gly Phe Ser Ala Gly Arg Gly 20 25 30 Arg Cys Pro Val Gln Gly Cys Leu Arg Pro His Arg Val Gln Leu Leu 35 40 45 Arg Arg Trp Gly Pro Gly Ser Pro Ala Gly Gln Arg Leu Ser Lys Gly 50 55 60 Phe Gln Leu Leu Arg Trp Trp Gly Pro Gly Ser Pro Ala Pro Glu Pro 65 70 75 80 Arg Lys Gly Pro Phe Pro Pro Pro Asp Pro Pro Trp Pro Val Thr Leu 85 90 95 178 95 PRT Homo sapiens MISC_FEATURE (70) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 178 Met Leu Glu Thr Thr Lys His Val Gln Ile Ala Cys Met Leu Leu Leu 1 5 10 15 Thr Cys Gln Ile Phe Leu Pro Ser Ser Leu Ser Pro Ser Phe Ile His 20 25 30 Ser Leu Thr Asp Ser Phe Ile Pro Leu Lys Lys Leu Tyr Val Cys Phe 35 40 45 Val Gln Ser Thr Leu Leu Lys Ala Ala Gly Tyr Lys Ser Ile Ser Glu 50 55 60 Ala Leu Gly Phe Asp Xaa Leu Leu Cys Ser Ser Ala Arg Phe Val Trp 65 70 75 80 Ile Cys His Thr Tyr Ser Arg Pro Leu Val Thr Cys Ala Leu His 85 90 95 179 27 PRT Homo sapiens 179 Met Ser Val Ile Gly Gly Leu Leu Leu Val Val Ala Leu Gly Pro Gly 1 5 10 15 Gly Val Ser Met Asp Glu Lys Lys Lys Glu Trp 20 25 180 89 PRT Homo sapiens MISC_FEATURE (12) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 180 Met Ser Gly Gly Leu Ser Phe Leu Leu Leu Val Xaa Xaa Gly Thr Gln 1 5 10 15 Ser Pro Leu His Leu Ala Gly Ser Cys Pro Gly Gln Thr His Leu Ser 20 25 30 Phe Pro Leu Gly Gln Asp Arg Gly Gln Gln Leu Gln Gln Lys Gln Gln 35 40 45 Asp Leu Glu Gln Glu Gly Leu Glu Ala Thr Gln Gly Leu Leu Ala Gly 50 55 60 Glu Trp Ala Pro Pro Leu Trp Xaa Leu Gly Ser Leu Phe Gln Ala Phe 65 70 75 80 Val Lys Arg Glu Ser Gln Ala Tyr Ala 85 181 65 PRT Homo sapiens 181 Met Phe Ala Asp Phe Ile Val Val Thr Ala Thr Val Gln Arg Cys Pro 1 5 10 15 Gly Ser Pro Pro Leu Ser Glu Ile Leu Trp Lys Asp Glu Pro Phe Ala 20 25 30 Ile Ser Ser His Ala Gly Leu Pro Trp Leu Ser Ser Trp Pro Ala Pro 35 40 45 Pro Trp Thr Trp Ser Trp Ile Ser Arg Arg Arg Glu His Gly Arg Gly 50 55 60 Ser 65 182 105 PRT Homo sapiens 182 Met Ser Ala Leu Thr Arg Leu Ala Ser Phe Ala Arg Val Gly Gly Arg 1 5 10 15 Leu Phe Arg Ser Gly Cys Ala Arg Thr Ala Gly Asp Gly Gly Val Arg 20 25 30 His Ala Gly Gly Gly Val His Ile Glu Pro Arg Tyr Arg Gln Phe Pro 35 40 45 Gln Leu Thr Arg Ser Gln Val Phe Gln Ser Glu Phe Phe Ser Gly Leu 50 55 60 Met Trp Phe Trp Ile Leu Trp Arg Phe Trp His Asp Ser Glu Glu Val 65 70 75 80 Leu Gly His Phe Pro Tyr Pro Asp Pro Ser Gln Trp Thr Asp Glu Glu 85 90 95 Leu Gly Ile Pro Pro Asp Asp Glu Asp 100 105 183 132 PRT Homo sapiens 183 Met Asp Val Leu Phe Val Ala Ile Phe Ala Val Pro Leu Ile Leu Gly 1 5 10 15 Gln Glu Tyr Glu Asp Glu Glu Arg Leu Gly Glu Asp Glu Tyr Tyr Gln 20 25 30 Val Val Tyr Tyr Tyr Thr Val Thr Pro Ser Tyr Asp Asp Phe Ser Ala 35 40 45 Asp Phe Thr Ile Asp Tyr Ser Ile Phe Glu Ser Glu Asp Arg Leu Asn 50 55 60 Arg Leu Asp Lys Asp Ile Thr Glu Ala Ile Glu Thr Thr Ile Ser Leu 65 70 75 80 Glu Thr Ala Arg Ala Asp His Pro Lys Pro Val Thr Val Lys Pro Val 85 90 95 Thr Thr Glu Pro Gln Ser Pro Asp Leu Asn Asp Ala Val Ser Ser Leu 100 105 110 Arg Ser Pro Ile Pro Leu Leu Leu Ser Cys Ala Phe Val Gln Val Gly 115 120 125 Met Tyr Phe Met 130 184 69 PRT Homo sapiens 184 Met Pro Cys Gln Pro Gly Gln Val Pro Ser Cys Gln Cys Thr Phe Gly 1 5 10 15 Leu Leu Leu Met Leu Pro Ser Leu Pro Ser Pro Ala Ser Gln Pro Arg 20 25 30 Pro Phe Cys Ser Ser Met Glu Tyr Phe His Gly Cys Ala Ser Pro Ser 35 40 45 Gln Ala Ile Ile Gly Gly Phe Pro Phe Ala Ser Val Ala Leu Ala Asp 50 55 60 Ile Leu Cys Leu Gln 65 185 45 PRT Homo sapiens 185 Met Ser Leu Leu Ser Pro Ala Ile Pro Ala Leu Thr Leu Ile Phe Ile 1 5 10 15 Leu Met Phe Phe Ser Phe Pro Phe Arg Ala His Thr Val Val Thr Ile 20 25 30 Val Ala Ser Gly Phe Leu Gly Leu Ser Pro Leu Cys Gly 35 40 45 186 65 PRT Homo sapiens 186 Met Ala Phe Gly Leu Gln Met Phe Ile Gln Arg Lys Phe Pro Tyr Pro 1 5 10 15 Leu Gln Trp Ser Leu Leu Val Ala Val Val Ala Gly Ser Val Val Ser 20 25 30 Tyr Gly Val Thr Arg Val Glu Ser Glu Lys Cys Asn Asn Leu Trp Leu 35 40 45 Phe Leu Glu Thr Gly Gln Leu Pro Lys Asp Arg Ser Thr Asp Gln Arg 50 55 60 Ser 65 187 49 PRT Homo sapiens 187 Met Asn Leu Leu Gly Met Ile Phe Ser Met Cys Gly Leu Met Leu Lys 1 5 10 15 Leu Lys Trp Cys Ala Trp Val Ala Val Tyr Cys Ser Phe Ile Ser Phe 20 25 30 Ala Asn Ser Arg Ser Ser Glu Asp Thr Lys Gln Met Met Ser Ser Phe 35 40 45 Met 188 170 PRT Homo sapiens 188 Met Leu Leu Asn Val Ala Leu Val Ala Leu Val Leu Leu Gly Ala Tyr 1 5 10 15 Arg Leu Trp Val Arg Trp Gly Arg Arg Gly Leu Gly Ala Gly Ala Gly 20 25 30 Ala Gly Glu Glu Ser Pro Ala Thr Ser Leu Pro Arg Met Lys Lys Arg 35 40 45 Asp Phe Ser Leu Glu Gln Leu Arg Gln Tyr Asp Gly Ser Arg Asn Pro 50 55 60 Arg Ile Leu Leu Ala Val Asn Gly Lys Val Phe Asp Val Thr Lys Gly 65 70 75 80 Ser Lys Phe Tyr Gly Pro Ala Gly Pro Tyr Gly Ile Phe Ala Gly Arg 85 90 95 Asp Ala Ser Arg Gly Leu Ala Thr Phe Cys Leu Asp Lys Asp Ala Leu 100 105 110 Arg Asp Glu Tyr Asp Asp Leu Ser Asp Leu Asn Ala Val Gln Met Glu 115 120 125 Ser Val Arg Glu Trp Glu Met Gln Phe Lys Glu Lys Tyr Asp Tyr Val 130 135 140 Gly Arg Leu Leu Lys Pro Gly Glu Glu Pro Ser Glu Tyr Thr Asp Glu 145 150 155 160 Glu Asp Thr Lys Asp His Asn Lys Gln Asp 165 170 189 132 PRT Homo sapiens 189 Met Thr Tyr Phe Ser Gly Leu Leu Val Ile Leu Ala Phe Ala Ala Trp 1 5 10 15 Val Ala Leu Ala Glu Gly Leu Gly Val Ala Val Tyr Ala Ala Ala Val 20 25 30 Leu Leu Gly Ala Gly Cys Ala Thr Ile Leu Val Thr Ser Leu Ala Met 35 40 45 Thr Ala Asp Leu Ile Gly Pro His Thr Asn Ser Gly Ala Phe Val Tyr 50 55 60 Gly Ser Met Ser Phe Leu Asp Lys Val Ala Asn Gly Leu Ala Val Met 65 70 75 80 Ala Ile Gln Ser Leu His Pro Cys Pro Ser Glu Leu Cys Cys Arg Ala 85 90 95 Cys Val Ser Phe Tyr His Trp Ala Met Val Ala Val Thr Gly Gly Val 100 105 110 Gly Val Ala Ala Ala Leu Cys Leu Cys Ser Leu Leu Leu Trp Pro Thr 115 120 125 Arg Leu Arg Arg 130 190 92 PRT Homo sapiens 190 Met Ala Ala Gly Pro Ser Gly Cys Leu Val Pro Ala Phe Gly Leu Arg 1 5 10 15 Leu Leu Leu Ala Thr Val Leu Gln Ala Val Ser Ala Phe Gly Ala Glu 20 25 30 Phe Ser Ser Glu Ala Cys Arg Glu Leu Gly Phe Ser Ser Asn Leu Leu 35 40 45 Cys Ser Ser Cys Asp Leu Leu Gly Gln Phe Asn Leu Leu Gln Leu Asp 50 55 60 Pro Asp Cys Arg Gly Cys Cys Gln Glu Glu Ala Gln Phe Glu Thr Lys 65 70 75 80 Lys Leu Tyr Ala Gly Ala Ile Leu Glu Val Cys Gly 85 90 191 176 PRT Homo sapiens MISC_FEATURE (137) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 191 Met Arg Gly Ser His Leu Arg Leu Leu Pro Tyr Leu Val Ala Ala Asn 1 5 10 15 Pro Val Asn Tyr Gly Arg Pro Tyr Arg Leu Ser Cys Val Glu Ala Phe 20 25 30 Ala Ala Thr Phe Cys Ile Val Gly Phe Pro Asp Leu Ala Val Ile Leu 35 40 45 Leu Arg Lys Phe Lys Trp Gly Lys Gly Phe Leu Asp Leu Asn Arg Gln 50 55 60 Leu Leu Asp Lys Tyr Ala Ala Cys Gly Ser Pro Glu Glu Val Leu Gln 65 70 75 80 Ala Glu Gln Glu Phe Leu Ala Asn Ala Lys Glu Ser Pro Gln Glu Glu 85 90 95 Glu Ile Asp Pro Phe Asp Val Asp Ser Gly Arg Glu Phe Gly Asn Pro 100 105 110 Asn Arg Pro Val Ala Ser Thr Arg Leu Pro Ser Asp Thr Asp Asp Ser 115 120 125 Asp Ala Ser Glu Asp Pro Gly Pro Xaa Ala Glu Arg Gly Gly Ala Ser 130 135 140 Ser Ser Cys Cys Glu Glu Glu Gln Thr Gln Gly Arg Gly Ala Glu Ala 145 150 155 160 Arg Ala Pro Ala Glu Val Trp Lys Gly Ile Lys Lys Arg Gln Arg Asp 165 170 175 192 70 PRT Homo sapiens 192 Met Ser Asn Ala Cys Lys Glu Leu Ala Ile Phe Leu Thr Thr Gly Ile 1 5 10 15 Val Val Ser Ala Phe Gly Leu Pro Ile Val Phe Ala Arg Ala His Leu 20 25 30 Ile Glu Trp Gly Ala Cys Ala Leu Val Leu Thr Gly Asn Thr Val Ile 35 40 45 Phe Ala Thr Ile Leu Gly Phe Phe Leu Val Phe Gly Ser Asn Asp Asp 50 55 60 Phe Ser Trp Gln Gln Trp 65 70 193 25 PRT Homo sapiens MISC_FEATURE (11) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 193 Met Thr Leu Leu Ile Ile Phe Leu Pro Phe Xaa Phe Thr Thr Xaa Thr 1 5 10 15 Asn Ser Gly Gly Ser Phe Pro Val Arg 20 25 194 73 PRT Homo sapiens MISC_FEATURE (21) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 194 Met Lys Gly Glu Leu Leu Pro Phe Leu Phe Leu Thr Val Trp Leu Trp 1 5 10 15 Leu Tyr Lys Leu Xaa Phe Gly Glu Ser Pro Arg Tyr Pro Asn Val Ile 20 25 30 Gly Lys Thr Tyr Phe Phe Phe Trp Thr Asp Gln Ile Ser Arg Glu Ser 35 40 45 Arg Phe Leu Glu Arg Leu Ala Phe Ile Val Ser Glu Asn Cys Leu Ile 50 55 60 Phe Leu Ile His Ala Ile Thr Gly Gln 65 70 195 289 PRT Homo sapiens 195 Met Ser Gly Phe Ser Thr Glu Glu Arg Ala Ala Pro Phe Ser Leu Glu 1 5 10 15 Tyr Arg Val Phe Leu Lys Asn Glu Lys Gly Gln Tyr Ile Ser Pro Phe 20 25 30 His Asp Ile Pro Ile Tyr Ala Asp Lys Asp Val Phe His Met Val Val 35 40 45 Glu Val Pro Arg Trp Ser Asn Ala Lys Met Glu Ile Ala Thr Lys Asp 50 55 60 Pro Leu Asn Pro Ile Lys Gln Asp Val Lys Lys Gly Lys Leu Arg Tyr 65 70 75 80 Val Ala Asn Leu Phe Pro Tyr Lys Gly Tyr Ile Trp Asn Tyr Gly Ala 85 90 95 Ile Pro Gln Thr Trp Glu Asp Pro Gly His Asn Asp Lys His Thr Gly 100 105 110 Cys Cys Gly Asp Asn Asp Pro Ile Asp Val Cys Glu Ile Gly Ser Lys 115 120 125 Val Cys Ala Arg Gly Glu Ile Ile Gly Val Lys Val Leu Gly Ile Leu 130 135 140 Ala Met Ile Asp Glu Gly Glu Thr Asp Trp Lys Val Ile Ala Ile Asn 145 150 155 160 Val Asp Asp Pro Asp Ala Ala Asn Tyr Asn Asp Ile Asn Asp Val Lys 165 170 175 Arg Leu Lys Pro Gly Tyr Leu Glu Ala Thr Val Asp Trp Phe Arg Arg 180 185 190 Tyr Lys Val Pro Asp Gly Lys Pro Glu Asn Glu Phe Ala Phe Asn Ala 195 200 205 Glu Phe Lys Asp Lys Asp Phe Ala Ile Asp Ile Ile Lys Ser Thr His 210 215 220 Asp His Trp Lys Ala Leu Val Thr Lys Lys Thr Asn Gly Lys Gly Ile 225 230 235 240 Ser Cys Met Asn Thr Thr Leu Ser Glu Ser Pro Phe Lys Cys Asp Pro 245 250 255 Asp Ala Ala Arg Ala Ile Val Asp Ala Leu Pro Pro Pro Cys Glu Ser 260 265 270 Ala Cys Thr Val Pro Thr Asp Val Asp Lys Trp Phe His His Gln Lys 275 280 285 Asn 196 624 PRT Homo sapiens 196 Met Glu Ile Pro Gly Ser Leu Cys Lys Lys Val Lys Leu Ser Asn Asn 1 5 10 15 Ala Gln Asn Trp Gly Met Gln Arg Ala Thr Asn Val Thr Tyr Gln Ala 20 25 30 His His Val Ser Arg Asn Lys Arg Gly Gln Val Val Gly Thr Arg Gly 35 40 45 Gly Phe Arg Gly Cys Thr Val Trp Leu Thr Gly Leu Ser Gly Ala Gly 50 55 60 Lys Thr Thr Val Ser Met Ala Leu Glu Glu Tyr Leu Val Cys His Gly 65 70 75 80 Ile Pro Cys Tyr Thr Leu Asp Gly Asp Asn Ile Arg Gln Gly Leu Asn 85 90 95 Lys Asn Leu Gly Phe Ser Pro Glu Asp Arg Glu Glu Asn Val Arg Arg 100 105 110 Ile Ala Glu Val Ala Lys Leu Phe Ala Asp Ala Gly Leu Val Cys Ile 115 120 125 Thr Ser Phe Ile Ser Pro Tyr Thr Gln Asp Arg Asn Asn Ala Arg Gln 130 135 140 Ile His Glu Gly Ala Ser Leu Pro Phe Phe Glu Val Phe Val Asp Ala 145 150 155 160 Pro Leu His Val Cys Glu Gln Arg Asp Val Lys Gly Leu Tyr Lys Lys 165 170 175 Ala Arg Ala Gly Glu Ile Lys Gly Phe Thr Gly Ile Asp Ser Glu Tyr 180 185 190 Glu Lys Pro Glu Ala Pro Glu Leu Val Leu Lys Thr Asp Ser Cys Asp 195 200 205 Val Asn Asp Cys Val Gln Gln Val Val Glu Leu Leu Gln Glu Arg Asp 210 215 220 Ile Val Pro Val Asp Ala Ser Tyr Glu Val Lys Glu Leu Tyr Val Pro 225 230 235 240 Glu Asn Lys Leu His Leu Ala Lys Thr Asp Ala Glu Thr Leu Pro Ala 245 250 255 Leu Lys Ile Asn Lys Val Asp Met Gln Trp Val Gln Val Leu Ala Glu 260 265 270 Gly Trp Ala Thr Pro Leu Asn Gly Phe Met Arg Glu Arg Glu Tyr Leu 275 280 285 Gln Cys Leu His Phe Asp Cys Leu Leu Asp Gly Gly Val Ile Asn Leu 290 295 300 Ser Val Pro Ile Val Leu Thr Ala Thr His Glu Asp Lys Glu Arg Leu 305 310 315 320 Asp Gly Cys Thr Ala Phe Ala Leu Met Tyr Glu Gly Arg Arg Val Ala 325 330 335 Ile Leu Arg Asn Pro Glu Phe Phe Glu His Arg Lys Glu Glu Arg Cys 340 345 350 Ala Arg Gln Trp Gly Thr Thr Cys Lys Asn His Pro Tyr Ile Lys Met 355 360 365 Val Met Glu Gln Gly Asp Trp Leu Ile Gly Gly Asp Leu Gln Val Leu 370 375 380 Asp Arg Val Tyr Trp Asn Asp Gly Leu Asp Gln Tyr Arg Leu Thr Pro 385 390 395 400 Thr Glu Leu Lys Gln Lys Phe Lys Asp Met Asn Ala Asp Ala Val Phe 405 410 415 Ala Phe Gln Leu Arg Asn Pro Val His Asn Gly His Ala Leu Leu Met 420 425 430 Gln Asp Thr His Lys Gln Leu Leu Glu Arg Gly Tyr Arg Arg Pro Val 435 440 445 Leu Leu Leu His Pro Leu Gly Gly Trp Thr Lys Asp Asp Asp Val Pro 450 455 460 Leu Met Trp Arg Met Lys Gln His Ala Ala Val Leu Glu Glu Gly Val 465 470 475 480 Leu Asn Pro Glu Thr Thr Val Val Ala Ile Phe Pro Ser Pro Met Met 485 490 495 Tyr Ala Gly Pro Thr Glu Val Gln Trp His Cys Arg Ala Arg Met Val 500 505 510 Ala Gly Ala Asn Phe Tyr Ile Val Gly Arg Asp Pro Ala Gly Met Pro 515 520 525 His Pro Glu Thr Gly Lys Asp Leu Tyr Glu Pro Ser His Gly Ala Lys 530 535 540 Val Leu Thr Met Ala Pro Gly Leu Ile Thr Leu Glu Ile Val Pro Phe 545 550 555 560 Arg Val Ala Ala Tyr Asn Lys Lys Lys Lys Arg Met Asp Tyr Tyr Asp 565 570 575 Ser Glu His His Glu Asp Phe Glu Phe Ile Ser Gly Thr Arg Met Arg 580 585 590 Lys Leu Ala Arg Glu Gly Gln Lys Pro Pro Glu Gly Phe Met Ala Pro 595 600 605 Lys Ala Trp Thr Val Leu Thr Glu Tyr Tyr Lys Ser Leu Glu Lys Ala 610 615 620 197 649 PRT Homo sapiens MISC_FEATURE (555) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 197 Met Ser Ala Ser Gln Asp Leu Glu Pro Lys Pro Leu Phe Pro Lys Pro 1 5 10 15 Ala Phe Gly Gln Lys Pro Pro Leu Ser Thr Glu Asn Ser His Glu Asp 20 25 30 Glu Ser Pro Met Lys Asn Val Ser Ser Ser Lys Gly Ser Pro Ala Pro 35 40 45 Leu Gly Val Arg Ser Lys Ser Gly Pro Leu Lys Pro Ala Arg Glu Asp 50 55 60 Ser Glu Asn Lys Asp His Ala Gly Glu Ile Ser Ser Leu Pro Phe Pro 65 70 75 80 Gly Val Val Leu Lys Pro Ala Ala Ser Arg Gly Gly Pro Gly Leu Ser 85 90 95 Lys Asn Gly Glu Glu Lys Lys Glu Asp Arg Lys Ile Asp Ala Ala Lys 100 105 110 Asn Thr Phe Gln Ser Lys Ile Asn Gln Glu Glu Leu Ala Ser Gly Thr 115 120 125 Pro Pro Ala Arg Phe Pro Lys Ala Pro Ser Lys Leu Thr Val Gly Gly 130 135 140 Pro Trp Gly Gln Ser Gln Glu Lys Glu Lys Gly Asp Lys Asn Ser Ala 145 150 155 160 Thr Pro Lys Gln Lys Pro Leu Pro Pro Leu Phe Thr Leu Gly Pro Pro 165 170 175 Pro Pro Lys Pro Asn Arg Pro Pro Asn Val Asp Leu Thr Lys Phe His 180 185 190 Lys Thr Ser Ser Gly Asn Ser Thr Ser Lys Gly Gln Thr Ser Tyr Ser 195 200 205 Thr Thr Ser Leu Pro Pro Pro Pro Pro Ser His Pro Ala Ser Gln Pro 210 215 220 Pro Leu Pro Ala Ser His Pro Ser Gln Pro Pro Val Pro Ser Leu Pro 225 230 235 240 Pro Arg Asn Ile Lys Pro Pro Phe Asp Leu Lys Ser Pro Val Asn Glu 245 250 255 Asp Asn Gln Asp Gly Val Thr His Ser Asp Gly Ala Gly Asn Leu Asp 260 265 270 Glu Glu Gln Asp Ser Glu Gly Glu Thr Tyr Glu Asp Ile Glu Ala Ser 275 280 285 Lys Glu Arg Glu Lys Lys Arg Glu Lys Glu Glu Lys Lys Arg Leu Glu 290 295 300 Leu Glu Lys Lys Glu Gln Lys Glu Lys Glu Lys Lys Glu Gln Glu Ile 305 310 315 320 Lys Lys Lys Phe Lys Leu Thr Gly Pro Ile Gln Val Ile His Leu Ala 325 330 335 Lys Ala Cys Cys Asp Val Lys Gly Gly Lys Asn Glu Leu Ser Phe Lys 340 345 350 Gln Gly Glu Gln Ile Glu Ile Ile Arg Ile Thr Asp Asn Pro Glu Gly 355 360 365 Lys Trp Leu Gly Arg Thr Ala Arg Gly Ser Tyr Gly Tyr Ile Lys Thr 370 375 380 Thr Ala Val Glu Ile Asp Tyr Asp Ser Leu Lys Leu Lys Lys Asp Ser 385 390 395 400 Leu Gly Ala Pro Ser Arg Pro Ile Glu Asp Asp Gln Glu Val Tyr Asp 405 410 415 Asp Val Ala Glu Gln Asp Asp Ile Ser Ser His Ser Gln Ser Gly Ser 420 425 430 Gly Gly Ile Phe Pro Pro Pro Pro Asp Asp Asp Ile Tyr Asp Gly Ile 435 440 445 Glu Glu Glu Asp Ala Asp Asp Gly Ser Thr Leu Gln Val Gln Glu Lys 450 455 460 Ser Asn Thr Trp Ser Trp Gly Ile Leu Lys Met Leu Lys Gly Lys Asp 465 470 475 480 Asp Arg Lys Lys Ser Ile Arg Glu Lys Pro Lys Val Ser Asp Ser Asp 485 490 495 Asn Asn Glu Gly Ser Ser Phe Pro Ala Pro Pro Lys Gln Leu Asp Met 500 505 510 Gly Asp Glu Val Tyr Asp Asp Val Asp Thr Ser Asp Phe Pro Val Ser 515 520 525 Ser Ala Glu Met Ser Gln Gly Thr Asn Val Gly Lys Ala Lys Thr Glu 530 535 540 Glu Lys Asp Leu Lys Lys Leu Lys Lys Gln Xaa Lys Xaa Xaa Lys Asp 545 550 555 560 Phe Arg Lys Lys Phe Lys Tyr Asp Gly Glu Ile Arg Val Leu Tyr Ser 565 570 575 Thr Lys Val Thr Thr Ser Ile Thr Ser Lys Lys Trp Gly Thr Arg Asp 580 585 590 Leu Gln Val Lys Pro Gly Glu Ser Leu Glu Val Ile Gln Thr Thr Asp 595 600 605 Asp Thr Lys Val Leu Cys Arg Asn Glu Glu Gly Lys Tyr Gly Tyr Val 610 615 620 Leu Arg Ser Tyr Leu Ala Asp Asn Asp Gly Glu Ile Tyr Asp Asp Ile 625 630 635 640 Ala Asp Gly Cys Ile Tyr Asp Asn Asp 645 198 55 PRT Homo sapiens 198 Met Ala Trp Pro Ser Arg Ser Lys Met Phe Thr Leu Leu Pro Val Leu 1 5 10 15 Cys Tyr Leu Trp Ser Leu Trp Leu Pro Gln Phe Ser Trp Ile Gln Glu 20 25 30 Leu Lys Ala Val Leu Arg Asp Asp Gly Leu Ile Ser Ala Val Ala Trp 35 40 45 Asn Ala Glu Phe Gln Thr Cys 50 55 199 266 PRT Homo sapiens 199 Met Val Lys Val Thr Phe Asn Ser Ala Leu Ala Gln Lys Glu Ala Lys 1 5 10 15 Lys Asp Glu Pro Lys Ser Gly Glu Glu Ala Leu Ile Ile Pro Pro Asp 20 25 30 Ala Val Ala Val Asp Cys Lys Asp Pro Asp Asp Val Val Pro Val Gly 35 40 45 Gln Arg Arg Ala Trp Cys Trp Cys Met Cys Phe Gly Leu Ala Phe Met 50 55 60 Leu Ala Gly Val Ile Leu Gly Gly Ala Tyr Leu Tyr Lys Tyr Phe Ala 65 70 75 80 Leu Gln Pro Asp Asp Val Tyr Tyr Cys Gly Ile Lys Tyr Ile Lys Asp 85 90 95 Asp Val Ile Leu Asn Glu Pro Ser Ala Asp Ala Pro Ala Ala Leu Tyr 100 105 110 Gln Thr Ile Glu Glu Asn Ile Lys Ile Phe Glu Glu Glu Glu Val Glu 115 120 125 Phe Ile Ser Val Pro Val Pro Glu Phe Ala Asp Ser Asp Pro Ala Asn 130 135 140 Ile Val His Asp Phe Asn Lys Lys Leu Thr Ala Tyr Leu Asp Leu Asn 145 150 155 160 Leu Asp Lys Cys Tyr Val Ile Pro Leu Asn Thr Ser Ile Val Met Pro 165 170 175 Pro Arg Asn Leu Leu Glu Leu Leu Ile Asn Ile Lys Ala Gly Thr Tyr 180 185 190 Leu Pro Gln Ser Tyr Leu Ile His Glu His Met Val Ile Thr Asp Arg 195 200 205 Ile Glu Asn Ile Asp His Leu Gly Phe Phe Ile Tyr Arg Leu Cys His 210 215 220 Asp Lys Glu Thr Tyr Lys Leu Gln Arg Arg Glu Thr Ile Lys Gly Ile 225 230 235 240 Gln Lys Arg Glu Ala Ser Asn Cys Phe Ala Ile Arg His Phe Glu Asn 245 250 255 Lys Phe Ala Val Glu Thr Leu Ile Cys Ser 260 265 200 315 PRT Homo sapiens 200 Met Asp Leu Arg Gln Phe Leu Met Cys Leu Ser Leu Cys Thr Ala Phe 1 5 10 15 Ala Leu Ser Lys Pro Thr Glu Lys Lys Asp Arg Val His His Glu Pro 20 25 30 Gln Leu Ser Asp Lys Val His Asn Asp Ala Gln Ser Phe Asp Tyr Asp 35 40 45 His Asp Ala Phe Leu Gly Ala Glu Glu Ala Lys Thr Phe Asp Gln Leu 50 55 60 Thr Pro Glu Glu Ser Lys Glu Arg Leu Gly Lys Ile Val Ser Lys Ile 65 70 75 80 Asp Gly Asp Lys Asp Gly Phe Val Thr Val Asp Glu Leu Lys Asp Trp 85 90 95 Ile Lys Phe Ala Gln Lys Arg Trp Ile Tyr Glu Asp Val Glu Arg Gln 100 105 110 Trp Lys Gly His Asp Leu Asn Glu Asp Gly Leu Val Ser Trp Glu Glu 115 120 125 Tyr Lys Asn Ala Thr Tyr Gly Tyr Val Leu Asp Asp Pro Asp Pro Asp 130 135 140 Asp Gly Phe Asn Tyr Lys Gln Met Met Val Arg Asp Glu Arg Arg Phe 145 150 155 160 Lys Met Ala Asp Lys Asp Gly Asp Leu Ile Ala Thr Lys Glu Glu Phe 165 170 175 Thr Ala Phe Leu His Pro Glu Glu Tyr Asp Tyr Met Lys Asp Ile Val 180 185 190 Val Gln Glu Thr Met Glu Asp Ile Asp Lys Asn Ala Asp Gly Phe Ile 195 200 205 Asp Leu Glu Glu Tyr Ile Gly Asp Met Tyr Ser His Asp Gly Asn Thr 210 215 220 Asp Glu Pro Glu Trp Val Lys Thr Glu Arg Glu Gln Phe Val Glu Phe 225 230 235 240 Arg Asp Lys Asn Arg Asp Gly Lys Met Asp Lys Glu Glu Thr Lys Asp 245 250 255 Trp Ile Leu Pro Ser Asp Tyr Asp His Ala Glu Ala Glu Ala Arg His 260 265 270 Leu Val Tyr Glu Ser Asp Gln Asn Lys Asp Gly Lys Leu Thr Lys Glu 275 280 285 Glu Ile Val Asp Lys Tyr Asp Leu Phe Val Gly Ser Gln Ala Thr Asp 290 295 300 Phe Gly Glu Ala Leu Val Arg His Asp Glu Phe 305 310 315 201 207 PRT Homo sapiens 201 Met Phe Asp Ala Val Leu Ile Leu Leu Leu Ile Pro Leu Lys Asp Lys 1 5 10 15 Leu Val Asp Pro Ile Leu Arg Arg His Gly Leu Leu Pro Ser Ser Leu 20 25 30 Lys Arg Ile Ala Val Gly Met Phe Phe Val Met Cys Ser Ala Phe Ala 35 40 45 Ala Gly Ile Leu Glu Ser Lys Arg Leu Asn Leu Val Lys Glu Lys Thr 50 55 60 Ile Asn Gln Thr Ile Gly Asn Val Val Tyr His Ala Ala Asp Leu Ser 65 70 75 80 Leu Trp Trp Gln Val Pro Gln Tyr Leu Leu Ile Gly Ile Ser Glu Ile 85 90 95 Phe Ala Ser Ile Ala Gly Leu Glu Phe Ala Tyr Ser Ala Ala Pro Lys 100 105 110 Ser Met Gln Ser Ala Ile Met Gly Leu Phe Phe Phe Phe Ser Gly Val 115 120 125 Gly Ser Phe Val Gly Ser Gly Leu Leu Ala Leu Val Ser Ile Lys Ala 130 135 140 Ile Gly Trp Met Ser Ser His Thr Asp Phe Gly Asn Ile Asn Gly Cys 145 150 155 160 Tyr Leu Asn Tyr Tyr Phe Phe Leu Leu Ala Ala Ile Gln Gly Ala Thr 165 170 175 Leu Leu Leu Phe Leu Ile Ile Ser Val Lys Tyr Asp His His Arg Asp 180 185 190 His Gln Arg Ser Arg Ala Asn Gly Val Pro Thr Ser Arg Arg Ala 195 200 205 202 195 PRT Homo sapiens 202 Met Arg Ser Arg Ile Arg Glu Phe Asp Ser Ser Thr Leu Asn Glu Ser 1 5 10 15 Val Arg Asn Thr Ile Met Arg Asp Leu Lys Ala Val Gly Lys Lys Phe 20 25 30 Met His Val Leu Tyr Pro Arg Lys Ser Asn Thr Leu Leu Arg Asp Trp 35 40 45 Asp Leu Trp Gly Pro Leu Ile Leu Cys Val Thr Leu Ala Leu Met Leu 50 55 60 Gln Arg Asp Ser Ala Asp Ser Glu Lys Asp Gly Gly Pro Gln Phe Ala 65 70 75 80 Glu Val Phe Val Ile Val Trp Phe Gly Ala Val Thr Ile Thr Leu Asn 85 90 95 Ser Lys Leu Leu Gly Gly Asn Ile Ser Phe Phe Gln Ser Leu Cys Val 100 105 110 Leu Gly Tyr Cys Ile Leu Pro Leu Thr Val Ala Met Leu Ile Cys Arg 115 120 125 Leu Val Leu Leu Ala Asp Pro Gly Pro Val Asn Phe Met Val Arg Leu 130 135 140 Phe Val Val Ile Val Met Phe Ala Trp Ser Ile Val Ala Ser Thr Ala 145 150 155 160 Phe Leu Ala Asp Ser Gln Pro Pro Asn Arg Arg Ala Leu Ala Val Tyr 165 170 175 Pro Val Phe Leu Phe Tyr Phe Val Ile Ser Trp Met Ile Leu Thr Phe 180 185 190 Thr Pro Gln 195 203 330 PRT Homo sapiens 203 Met Ala Lys Asp Gln Ala Val Glu Asn Ile Leu Val Ser Pro Val Val 1 5 10 15 Val Ala Ser Ser Leu Gly Leu Val Ser Leu Gly Gly Lys Ala Thr Thr 20 25 30 Ala Ser Gln Ala Lys Ala Val Leu Ser Ala Glu Gln Leu Arg Asp Glu 35 40 45 Glu Val His Ala Gly Leu Gly Glu Leu Leu Arg Ser Leu Ser Asn Ser 50 55 60 Thr Ala Arg Asn Val Thr Trp Lys Leu Gly Ser Arg Leu Tyr Gly Pro 65 70 75 80 Ser Ser Val Ser Phe Ala Asp Asp Phe Val Arg Ser Ser Lys Gln His 85 90 95 Tyr Asn Cys Glu His Ser Lys Ile Asn Phe Arg Asp Lys Arg Ser Ala 100 105 110 Leu Gln Ser Ile Asn Glu Trp Ala Ala Gln Thr Thr Asp Gly Lys Leu 115 120 125 Pro Glu Val Thr Lys Asp Val Glu Arg Thr Asp Gly Ala Leu Leu Val 130 135 140 Asn Ala Met Phe Phe Lys Pro His Trp Asp Glu Lys Phe His His Lys 145 150 155 160 Met Val Asp Asn Arg Gly Phe Met Val Thr Arg Ser Tyr Thr Val Gly 165 170 175 Val Met Met Met His Arg Thr Gly Leu Tyr Asn Tyr Tyr Asp Asp Glu 180 185 190 Lys Glu Lys Leu Gln Ile Val Glu Met Pro Leu Ala His Lys Leu Ser 195 200 205 Ser Leu Ile Ile Leu Met Pro His His Val Glu Pro Leu Glu Arg Leu 210 215 220 Glu Lys Leu Leu Thr Lys Glu Gln Leu Lys Ile Trp Met Gly Lys Met 225 230 235 240 Gln Lys Lys Ala Val Ala Ile Ser Leu Pro Lys Gly Val Val Glu Val 245 250 255 Thr His Asp Leu Gln Lys His Leu Ala Gly Leu Gly Leu Thr Glu Ala 260 265 270 Ile Asp Lys Asn Lys Ala Asp Leu Ser Arg Met Ser Gly Lys Lys Asp 275 280 285 Leu Tyr Leu Ala Ser Val Phe His Ala Thr Ala Phe Glu Leu Asp Thr 290 295 300 Asp Gly Asn Pro Leu Thr Arg Ile Thr Gly Gly Gly Val Arg Thr Gln 305 310 315 320 Val Phe Tyr Ala Asp His Pro Phe Ile Ser 325 330 204 58 PRT Homo sapiens 204 Met Cys Met Gln Leu Phe Gly Phe Leu Ala Phe Met Ile Phe Met Cys 1 5 10 15 Trp Val Gly Asp Val Tyr Pro Val Tyr Gln Pro Val Gly Pro Lys Gln 20 25 30 Tyr Pro Tyr Asn Asn Leu Tyr Leu Glu Arg Gly Gly Asp Pro Ser Lys 35 40 45 Glu Pro Glu Arg Val Val His Tyr Glu Ile 50 55 205 392 PRT Homo sapiens 205 Met Asp Ala Leu Val Glu Asp Asp Ile Cys Ile Leu Asn His Glu Lys 1 5 10 15 Ala His Lys Arg Asp Thr Val Thr Pro Val Ser Ile Tyr Ser Gly Asp 20 25 30 Glu Ser Val Ala Ser His Phe Ala Leu Val Thr Ala Tyr Glu Asp Ile 35 40 45 Lys Lys Arg Leu Lys Asp Ser Glu Lys Glu Asn Ser Leu Leu Lys Lys 50 55 60 Arg Ile Arg Phe Leu Glu Glu Lys Leu Ile Ala Arg Phe Glu Glu Glu 65 70 75 80 Thr Ser Ser Val Gly Arg Glu Gln Val Asn Lys Ala Tyr His Ala Tyr 85 90 95 Arg Glu Val Cys Ile Asp Arg Asp Asn Leu Lys Ser Lys Leu Asp Lys 100 105 110 Met Asn Lys Asp Asn Ser Glu Ser Leu Lys Val Leu Asn Glu Gln Leu 115 120 125 Gln Ser Lys Glu Val Glu Leu Leu Gln Leu Arg Thr Glu Val Glu Thr 130 135 140 Gln Gln Val Met Arg Asn Leu Asn Pro Pro Ser Ser Asn Trp Glu Val 145 150 155 160 Glu Lys Leu Ser Cys Asp Leu Lys Ile His Gly Leu Glu Gln Glu Leu 165 170 175 Glu Leu Met Arg Lys Glu Cys Ser Asp Leu Lys Ile Glu Leu Gln Lys 180 185 190 Ala Lys Gln Thr Asp Pro Tyr Gln Glu Asp Asn Leu Lys Ser Arg Asp 195 200 205 Leu Gln Lys Leu Ser Ile Ser Ser Asp Asn Met Gln His Ala Tyr Trp 210 215 220 Glu Leu Lys Arg Glu Met Ser Asn Leu His Leu Val Thr Gln Val Gln 225 230 235 240 Ala Glu Leu Leu Arg Lys Leu Lys Thr Ser Thr Ala Ile Lys Lys Ala 245 250 255 Cys Ala Pro Val Gly Cys Ser Glu Asp Leu Gly Arg Asp Ser Thr Lys 260 265 270 Leu His Leu Met Asn Phe Thr Ala Thr Tyr Thr Arg His Pro Pro Leu 275 280 285 Leu Pro Asn Gly Lys Ala Leu Cys His Thr Thr Ser Ser Pro Leu Pro 290 295 300 Gly Asp Val Lys Val Leu Ser Glu Lys Ala Ile Leu Gln Ser Trp Thr 305 310 315 320 Asp Asn Glu Arg Ser Ile Pro Asn Asp Gly Thr Cys Phe Gln Glu His 325 330 335 Ser Ser Tyr Gly Arg Asn Ser Leu Glu Asp Asn Ser Trp Val Phe Pro 340 345 350 Ser Pro Pro Lys Ser Ser Glu Thr Ala Phe Gly Glu Thr Lys Thr Lys 355 360 365 Thr Leu Pro Leu Pro Asn Leu Pro Pro Leu His Tyr Leu Asp Gln His 370 375 380 Asn Gln Asn Cys Leu Tyr Lys Asn 385 390 206 26 PRT Homo sapiens 206 Met His His His Thr Gln Leu Met Phe Ile Tyr Leu Phe Ile Tyr Leu 1 5 10 15 Phe Ile Leu Gly Val Phe Phe Phe Phe Phe 20 25 207 38 PRT Homo sapiens 207 Met Asn Cys Ile Leu Leu Leu Tyr Leu Leu Ile Pro Thr Ile Ser Ile 1 5 10 15 Ser Val Val Pro Tyr Val Ala Leu Asn Ile Lys Tyr Ile Lys Glu Cys 20 25 30 Thr Glu Asn Ser Phe Tyr 35 208 45 PRT Homo sapiens MISC_FEATURE (28) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 208 Met Lys Lys Ser Leu Glu Asn Leu Asn Arg Leu Gln Val Met Leu Leu 1 5 10 15 His Leu Thr Ala Ala Phe Leu Gln Arg Ala His Xaa Ile Leu Thr Thr 20 25 30 Arg Met Ser Leu Gly Phe Gln Ser Pro His Leu Thr Met 35 40 45 209 81 PRT Homo sapiens 209 Met Ser Lys Arg Ser Ala Ser Phe Ile Leu Leu Pro Leu Leu Phe Leu 1 5 10 15 Lys Gly Ser Phe Ala Lys Leu Asn Ala Arg Ile Ser Asp Cys Leu Glu 20 25 30 Glu Arg Tyr Cys His Asn Leu Trp Met Val Phe Gln Gly Cys Val Ile 35 40 45 Thr Glu Leu His Leu Ser Arg Met Ser Lys Thr Leu Ser Ser Leu Cys 50 55 60 Tyr Asp Phe Val Ile Asn Val Tyr Ile Phe Phe Lys Phe Leu Asp Ile 65 70 75 80 Thr 210 49 PRT Homo sapiens 210 Met Cys Ser Leu Phe Glu Ser Arg Phe Phe Cys Phe Val Leu Phe Ser 1 5 10 15 Glu Lys Ile Ile Gln Leu Cys Ala Ser Ile Ala Phe Leu Cys Phe Val 20 25 30 Lys His Val Pro Trp Pro Lys Trp Lys Arg Lys Cys Leu Ile Asn Ala 35 40 45 Phe 211 203 PRT Homo sapiens 211 Met Thr Leu Arg Pro Ser Leu Leu Pro Leu His Leu Leu Leu Leu Leu 1 5 10 15 Leu Leu Ser Ala Ala Val Cys Arg Ala Glu Ala Gly Leu Glu Thr Glu 20 25 30 Ser Pro Val Arg Thr Leu Gln Val Glu Thr Leu Val Glu Pro Pro Glu 35 40 45 Pro Cys Ala Glu Pro Ala Ala Phe Gly Asp Thr Leu His Ile His Tyr 50 55 60 Thr Gly Ser Leu Val Asp Gly Arg Ile Ile Asp Thr Ser Leu Thr Arg 65 70 75 80 Asp Pro Leu Val Ile Glu Leu Gly Gln Lys Gln Val Ile Pro Gly Leu 85 90 95 Glu Gln Ser Leu Leu Asp Met Cys Val Gly Glu Lys Arg Arg Ala Ile 100 105 110 Ile Pro Ser His Leu Ala Tyr Gly Lys Arg Gly Phe Pro Pro Ser Val 115 120 125 Pro Ala Asp Ala Val Val Gln Tyr Asp Val Glu Leu Ile Ala Leu Ile 130 135 140 Arg Ala Asn Tyr Trp Leu Lys Leu Val Lys Gly Ile Leu Pro Leu Val 145 150 155 160 Gly Met Ala Met Val Pro Pro Ser Trp Ala Ser Leu Gly Ile Thr Tyr 165 170 175 Thr Glu Arg Pro Ile Asp Pro Lys Ser Pro Lys Arg Ser Ser Arg Lys 180 185 190 Arg Asn Glu Thr Arg Ala Lys Arg Asn Asn Lys 195 200 212 186 PRT Homo sapiens MISC_FEATURE (122) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 212 Met Lys Thr Leu Met Thr Ile Cys Pro Gly Thr Val Leu Leu Val Phe 1 5 10 15 Ser Ile Ser Leu Trp Ile Ile Ala Ala Trp Thr Val Arg Val Cys Glu 20 25 30 Ser Pro Glu Ser Pro Ala Gln Pro Ser Gly Ser Ser Leu Pro Ala Trp 35 40 45 Tyr His Asp Gln Gln Asp Val Thr Ser Asn Phe Leu Gly Ala Met Trp 50 55 60 Leu Ile Ser Ile Thr Phe Leu Ser Ile Gly Tyr Gly Asp Met Val Pro 65 70 75 80 His Thr Tyr Cys Gly Lys Gly Val Cys Leu Leu Thr Gly Ile Met Gly 85 90 95 Ala Gly Cys Thr Ala Leu Val Val Ala Val Val Ala Arg Lys Leu Glu 100 105 110 Leu Thr Lys Ala Glu Lys His Val His Xaa Phe Met Met Asp Thr Gln 115 120 125 Leu Thr Lys Arg Ile Lys Asn Xaa Ala Ala Asn Val Leu Xaa Glu Thr 130 135 140 Trp Leu Ile Tyr Lys His Thr Lys Leu Leu Lys Lys Ile Asp His Ala 145 150 155 160 Lys Val Arg Asn Thr Arg Gly Ser Ser Ser Lys Tyr Pro Pro Val Glu 165 170 175 Glu Arg Gln Asp Gly Thr Glu Glu Ala Glu 180 185 213 90 PRT Homo sapiens 213 Met Lys Phe Leu Ala Val Leu Val Leu Leu Gly Val Ser Ile Phe Leu 1 5 10 15 Val Ser Ala Gln Asn Pro Thr Thr Ala Ala Pro Ala Asp Thr Tyr Pro 20 25 30 Ala Thr Gly Pro Ala Asp Asp Glu Ala Pro Asp Ala Glu Thr Thr Ala 35 40 45 Ala Ala Thr Thr Ala Thr Thr Ala Ala Pro Thr Thr Ala Thr Thr Ala 50 55 60 Ala Ser Thr Thr Ala Arg Lys Asp Ile Pro Val Leu Pro Lys Trp Val 65 70 75 80 Gly Asp Leu Pro Asn Gly Arg Val Cys Pro 85 90 214 48 PRT Homo sapiens 214 Met Ser Ser Ala Ala Ala Asp His Trp Ala Trp Leu Leu Val Leu Ser 1 5 10 15 Phe Val Phe Gly Cys Asn Val Leu Arg Ile Leu Leu Pro Ser Phe Ser 20 25 30 Ser Phe Met Ser Arg Val Leu Gln Lys Asp Ala Asp Arg Ser His Arg 35 40 45 215 70 PRT Homo sapiens 215 Met Thr Ala Pro Leu Pro Pro Leu Ser Gly Leu Ala Leu Phe Leu Ile 1 5 10 15 Val Phe Phe Ser Leu Gly Val Phe Cys Ile Cys His Ser His Trp Tyr 20 25 30 His Thr Leu Gln Gln Met Ala Gly Thr Glu Pro Lys Ala Leu Leu Leu 35 40 45 Ser Pro Pro Ala Ala Thr Thr Phe Val Thr Val Thr His Glu Val Trp 50 55 60 Lys Glu Gln Ala Leu Ala 65 70 216 83 PRT Homo sapiens 216 Met Thr Cys Ser Val Ala Leu Leu Leu Ile Leu Gly Leu Arg Cys Ser 1 5 10 15 Gly Val Arg Pro Gly Leu Val Gly Glu Gly His Asn Pro Ser Leu Leu 20 25 30 Val Cys Leu Leu Leu Lys Asp Ser Arg Thr Asn Gln Gly Ser Cys Pro 35 40 45 Gly Gly Pro Trp Ser Glu Arg Asp Ile Glu Ser Val Thr Ser Asp Asn 50 55 60 Cys Glu Ala Thr Leu Gly Tyr Arg Asn His Ser Leu Pro Ser Asn Tyr 65 70 75 80 Tyr Asn Ser 217 43 PRT Homo sapiens 217 Met Leu Thr Arg Ser Leu Lys Thr Leu Pro Ser Ala Cys Thr Ala Phe 1 5 10 15 Leu Leu Leu Phe Phe Leu Phe Ser Ser Gly Asp Pro Glu Leu Ser Cys 20 25 30 Ser Cys Thr Leu Arg Thr Gln Ser Ser Trp Ser 35 40 218 184 PRT Homo sapiens MISC_FEATURE (140) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 218 Met Trp Arg Pro Ser Val Leu Leu Leu Leu Leu Leu Leu Arg His Gly 1 5 10 15 Ala Gln Gly Lys Pro Ser Pro Asp Ala Gly Pro His Gly Gln Gly Arg 20 25 30 Val His Gln Ala Ala Pro Leu Ser Asp Ala Pro His Asp Asp Ala His 35 40 45 Gly Asn Phe Gln Tyr Asp His Glu Ala Phe Leu Gly Arg Glu Val Ala 50 55 60 Lys Glu Phe Asp Gln Leu Thr Pro Glu Glu Ser Gln Ala Arg Leu Gly 65 70 75 80 Arg Ile Val Asp Arg Met Asp Arg Ala Gly Asp Gly Asp Gly Trp Val 85 90 95 Ser Leu Ala Glu Leu Arg Ala Trp Ile Ala His Thr Gln Gln Arg His 100 105 110 Ile Arg Asp Ser Val Ser Ala Ala Trp Asp Thr Tyr Asp Thr Asp Arg 115 120 125 Asp Gly Arg Val Gly Trp Glu Glu Leu Arg Asn Xaa Thr Tyr Gly His 130 135 140 Xaa Xaa Pro Xaa Glu Glu Phe His Asp Val Glu Asp Ala Glu Thr Tyr 145 150 155 160 Lys Lys Met Leu Xaa Arg Asp Glu Arg Arg Phe Arg Val Ala Asp Gln 165 170 175 Asp Gly Asp Ser Met Ala Thr Arg 180 219 71 PRT Homo sapiens MISC_FEATURE (40) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 219 Met Trp Leu Phe Ile Leu Leu Ser Leu Ala Leu Ile Ser Asp Ala Met 1 5 10 15 Val Met Asp Glu Lys Val Lys Arg Ser Leu Cys Trp Thr Arg Leu Leu 20 25 30 Pro Ser Ala Thr Thr Met Pro Xaa Thr Arg Ile Thr Pro Asn Thr Gly 35 40 45 Ala Glu Xaa Ile Ser Val Xaa Thr Ala Thr Ser Ser Pro Ser Pro Leu 50 55 60 Thr Ala Pro Ile Met Trp Pro 65 70 220 10 PRT Homo sapiens 220 Met His Val Phe Val Leu Glu Ile Phe Leu 1 5 10 221 138 PRT Homo sapiens 221 Met Ala Val Ala Thr Leu Ala Ser Glu Thr Leu Pro Leu Leu Ala Leu 1 5 10 15 Thr Phe Ile Thr Asp Asn Ser Leu Val Ala Ala Gly His Asp Cys Phe 20 25 30 Pro Val Leu Phe Thr Tyr Asp Ala Ala Ala Gly Met Leu Ser Phe Gly 35 40 45 Gly Arg Leu Asp Val Pro Lys Gln Ser Ser Gln Arg Gly Leu Thr Ala 50 55 60 Arg Glu Arg Phe Gln Asn Leu Asp Lys Lys Ala Ser Ser Glu Gly Gly 65 70 75 80 Thr Ala Ala Gly Ala Gly Leu Asp Ser Leu His Lys Asn Ser Val Ser 85 90 95 Gln Ile Ser Val Leu Ser Gly Gly Lys Ala Lys Cys Ser Gln Phe Cys 100 105 110 Thr Thr Gly Met Asp Gly Gly Met Ser Ile Trp Asp Val Lys Ser Leu 115 120 125 Glu Ser Ala Leu Lys Asp Leu Lys Ile Lys 130 135 222 11 PRT Homo sapiens 222 Met Ser Gly Gly Leu Ser Phe Leu Leu Leu Val 1 5 10 223 23 PRT Homo sapiens 223 Leu Gly Ser Leu Ser Thr Ala Pro Ser Ser Ala Leu Pro Thr Leu Gly 1 5 10 15 Ala Arg Arg Thr Arg Ser Lys 20 224 66 PRT Homo sapiens 224 Met Thr Tyr Phe Ser Gly Leu Leu Val Ile Leu Ala Phe Ala Ala Trp 1 5 10 15 Val Ala Leu Ala Glu Gly Leu Gly Val Ala Val Tyr Ala Ala Ala Val 20 25 30 Leu Leu Gly Ala Gly Cys Ala Thr Ile Leu Val Thr Ser Leu Ala Met 35 40 45 Thr Ala Asp Leu Ile Gly Pro His Thr Asn Ser Gly Leu Ser Cys Thr 50 55 60 Ala Pro 65 225 28 PRT Homo sapiens 225 Gly Lys Pro Thr Gly Lys Ser Leu Pro Leu Met Trp Met Ile Leu Met 1 5 10 15 Gln Pro Ile Ile Met Ile Ser Met Met Ser Asn Gly 20 25 226 61 PRT Homo sapiens 226 Met Gln Gly Lys Phe Met Lys Val Gln Val Tyr Arg Phe Leu Lys Tyr 1 5 10 15 Leu Leu Met Leu Leu Cys Met Phe Val Asn Arg Gly Met Ser Lys Asp 20 25 30 Ser Thr Lys Lys Pro Gly Gln Glu Lys Leu Lys Val Ser Leu Gly Ser 35 40 45 Ile Leu Asn Met Lys Ser Gln Arg Pro Leu Ser Trp Cys 50 55 60 227 29 PRT Homo sapiens 227 Met Met Glu Arg Ser Met Met Ile Leu Leu Met Ala Ala Ser Met Thr 1 5 10 15 Met Thr Ser Thr Gln Leu Trp Ser Phe Cys Cys Val His 20 25 228 18 PRT Homo sapiens 228 Met Trp Tyr Gln Leu Ala Lys Glu Glu Pro Gly Val Gly Ala Cys Ala 1 5 10 15 Leu Asp 229 72 PRT Homo sapiens 229 Met Leu Ile Cys Arg Leu Val Leu Leu Ala Asp Pro Gly Pro Val Asn 1 5 10 15 Phe Met Val Arg Leu Phe Val Val Ile Val Met Phe Ala Trp Ser Ile 20 25 30 Val Ala Ser Thr Ala Phe Leu Ala Asp Ser Gln Pro Pro Asn Arg Arg 35 40 45 Ala Leu Ala Val Tyr Pro Val Phe Leu Phe Tyr Phe Val Ile Ser Trp 50 55 60 Met Ile Leu Thr Phe Thr Pro Gln 65 70 230 142 PRT Homo sapiens MISC_FEATURE (47) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 230 Met Arg Ser Leu Leu Leu Leu Ser Ala Phe Cys Leu Leu Glu Ala Ala 1 5 10 15 Leu Ala Ala Glu Val Lys Lys Pro Ala Ala Ala Ala Ala Pro Gly Thr 20 25 30 Ala Glu Lys Leu Ser Pro Lys Ala Ala Thr Leu Ala Glu Arg Xaa Arg 35 40 45 Pro Gly Leu Gln Leu Val Pro Gly His Gly Gln Gly Pro Gly Ser Gly 50 55 60 Glu His Pro Gly Val Thr Arg Gly Gly Gly Leu Val Ala Gly Ala Arg 65 70 75 80 Val Ala Gly Arg Gln Gly Asp His Gly Val Ala Gly Gln Gly Ser Ala 85 90 95 Glu Arg Arg Ala Ala Ala Arg Arg Gly Gly Ala Arg Arg Pro Gly Arg 100 105 110 Ala Ala Ala Leu Thr Gln Gln Leu Xaa Gly Ala Gln Arg Asp Leu Glu 115 120 125 Ala Gly Gln Pro Thr Val Arg Thr Gln Leu Ser Glu Leu Arg 130 135 140 231 54 PRT Homo sapiens 231 Asp Pro Glu Ala Ala Asp Ser Gly Glu Pro Gln Asn Lys Arg Thr Pro 1 5 10 15 Asp Leu Pro Glu Glu Glu Tyr Val Lys Glu Glu Ile Gln Glu Asn Glu 20 25 30 Glu Ala Val Lys Lys Met Leu Val Glu Ala Thr Arg Glu Phe Glu Glu 35 40 45 Val Val Val Asp Glu Ser 50 232 63 PRT Homo sapiens 232 Gln Lys Leu Lys Arg Lys Ala Glu Glu Asp Pro Glu Ala Ala Asp Ser 1 5 10 15 Gly Glu Pro Gln Asn Lys Arg Thr Pro Asp Leu Pro Glu Glu Glu Tyr 20 25 30 Val Lys Glu Glu Ile Gln Glu Asn Glu Glu Ala Val Lys Lys Met Leu 35 40 45 Val Glu Ala Thr Arg Glu Phe Glu Glu Val Val Val Asp Glu Ser 50 55 60 233 113 PRT Homo sapiens 233 Lys Ala Met Glu Lys Ser Ser Leu Thr Gln His Ser Trp Gln Ser Leu 1 5 10 15 Lys Asp Arg Tyr Leu Lys His Leu Arg Gly Gln Glu His Lys Tyr Leu 20 25 30 Leu Gly Asp Ala Pro Val Ser Pro Ser Ser Gln Lys Leu Lys Arg Lys 35 40 45 Ala Glu Glu Asp Pro Glu Ala Ala Asp Ser Gly Glu Pro Gln Asn Lys 50 55 60 Arg Thr Pro Asp Leu Pro Glu Glu Glu Tyr Val Lys Glu Glu Ile Gln 65 70 75 80 Glu Asn Glu Glu Ala Val Lys Lys Met Leu Val Glu Ala Thr Arg Glu 85 90 95 Phe Glu Glu Val Val Val Asp Glu Ser Pro Pro Asp Phe Glu Ile His 100 105 110 Ile 234 148 PRT Homo sapiens 234 Leu Pro Ser Tyr Asp Glu Ala Glu Arg Thr Lys Ala Glu Ala Thr Ile 1 5 10 15 Pro Leu Val Pro Gly Arg Asp Glu Asp Phe Val Gly Arg Asp Asp Phe 20 25 30 Asp Asp Ala Asp Gln Leu Arg Ile Gly Asn Asp Gly Ile Phe Met Leu 35 40 45 Thr Phe Phe Met Ala Phe Leu Phe Asn Trp Ile Gly Phe Phe Leu Ser 50 55 60 Phe Cys Leu Thr Thr Ser Ala Ala Gly Arg Tyr Gly Ala Ile Ser Gly 65 70 75 80 Phe Gly Leu Ser Leu Ile Lys Trp Ile Leu Ile Val Arg Phe Ser Thr 85 90 95 Tyr Phe Pro Gly Tyr Phe Asp Gly Gln Tyr Trp Leu Trp Trp Val Phe 100 105 110 Leu Val Leu Gly Phe Leu Leu Phe Leu Arg Gly Phe Ile Asn Tyr Ala 115 120 125 Lys Val Arg Lys Met Pro Glu Thr Phe Ser Asn Leu Pro Arg Thr Arg 130 135 140 Val Leu Phe Ile 145 235 24 PRT Homo sapiens 235 Ala Gly Arg Tyr Gly Ala Ile Ser Gly Phe Gly Leu Ser Leu Ile Lys 1 5 10 15 Trp Ile Leu Ile Val Arg Phe Ser 20 236 51 PRT Homo sapiens 236 Met Lys His Leu Ser Ala Trp Asn Phe Thr Lys Leu Thr Phe Leu Gln 1 5 10 15 Leu Trp Glu Ile Phe Glu Gly Ser Val Glu Asn Cys Gln Thr Leu Thr 20 25 30 Ser Tyr Ser Lys Leu Gln Ile Lys Tyr Thr Phe Ser Arg Gly Ser Thr 35 40 45 Phe Tyr Ile 50 237 213 PRT Homo sapiens 237 Phe Ser Ser Asp Phe Arg Thr Ser Pro Trp Glu Ser Arg Arg Val Glu 1 5 10 15 Ser Lys Ala Thr Ser Ala Arg Cys Gly Leu Trp Gly Ser Gly Pro Arg 20 25 30 Arg Arg Pro Ala Ser Gly Met Phe Arg Gly Leu Ser Ser Trp Leu Gly 35 40 45 Leu Gln Gln Pro Val Ala Gly Gly Gly Gln Pro Asn Gly Asp Ala Pro 50 55 60 Pro Glu Gln Pro Ser Glu Thr Val Ala Glu Ser Ala Glu Glu Glu Leu 65 70 75 80 Gln Gln Ala Gly Asp Gln Glu Leu Leu His Gln Ala Lys Asp Phe Gly 85 90 95 Asn Tyr Leu Phe Asn Phe Ala Ser Ala Ala Thr Lys Lys Ile Thr Glu 100 105 110 Ser Val Ala Glu Thr Ala Gln Thr Ile Lys Lys Ser Val Glu Glu Gly 115 120 125 Lys Ile Asp Gly Ile Ile Asp Lys Thr Ile Ile Gly Asp Phe Gln Lys 130 135 140 Glu Gln Lys Lys Phe Val Glu Glu Gln His Thr Lys Lys Ser Glu Ala 145 150 155 160 Ala Val Pro Pro Trp Val Asp Thr Asn Asp Glu Glu Thr Ile Gln Gln 165 170 175 Gln Ile Leu Ala Leu Ser Ala Asp Lys Arg Asn Phe Leu Arg Asp Pro 180 185 190 Pro Ala Gly Val Gln Phe Asn Phe Asp Phe Asp Gln Met Tyr Pro Val 195 200 205 Ala Leu Val Met Leu 210 238 49 PRT Homo sapiens 238 Met Arg Phe Ala Leu Val Pro Lys Leu Val Lys Glu Glu Val Phe Trp 1 5 10 15 Arg Asn Tyr Phe Tyr Arg Val Ser Leu Ile Lys Gln Ser Ala Gln Leu 20 25 30 Thr Ala Leu Ala Ala Gln Gln Gln Ala Ala Gly Lys Gly Gly Glu Glu 35 40 45 Gln 239 76 PRT Homo sapiens 239 Ser Thr Ser Pro Gly Val Ser Glu Phe Val Ser Asp Ala Phe Asp Ala 1 5 10 15 Cys Asn Leu Asn Gln Glu Asp Leu Arg Lys Glu Met Glu Gln Leu Val 20 25 30 Leu Asp Lys Lys Gln Glu Glu Thr Ala Val Leu Glu Glu Asp Ser Ala 35 40 45 Asp Trp Glu Lys Glu Leu Gln Gln Glu Leu Gln Glu Tyr Glu Val Val 50 55 60 Thr Glu Ser Glu Lys Arg Asp Glu Asn Trp Asp Lys 65 70 75 240 62 PRT Homo sapiens 240 Ser Pro Trp Glu Ser Arg Arg Val Glu Ser Lys Ala Thr Ser Ala Arg 1 5 10 15 Cys Gly Leu Trp Gly Ser Gly Pro Arg Arg Arg Pro Ala Ser Gly Met 20 25 30 Phe Arg Gly Leu Ser Ser Trp Leu Gly Leu Gln Gln Pro Val Ala Gly 35 40 45 Gly Gly Gln Pro Asn Gly Asp Ala Pro Pro Glu Gln Pro Ser 50 55 60 241 65 PRT Homo sapiens 241 Pro Val Ala Gly Gly Gly Gln Pro Asn Gly Asp Ala Pro Pro Glu Gln 1 5 10 15 Pro Ser Glu Thr Val Ala Glu Ser Ala Glu Glu Glu Leu Gln Gln Ala 20 25 30 Gly Asp Gln Glu Leu Leu His Gln Ala Lys Asp Phe Gly Asn Tyr Leu 35 40 45 Phe Asn Phe Ala Ser Ala Ala Thr Lys Lys Ile Thr Glu Ser Val Ala 50 55 60 Glu 65 242 72 PRT Homo sapiens 242 Phe Gln Lys Glu Gln Lys Lys Phe Val Glu Glu Gln His Thr Lys Lys 1 5 10 15 Ser Glu Ala Ala Val Pro Pro Trp Val Asp Thr Asn Asp Glu Glu Thr 20 25 30 Ile Gln Gln Gln Ile Leu Ala Leu Ser Ala Asp Lys Arg Asn Phe Leu 35 40 45 Arg Asp Pro Pro Ala Gly Val Gln Phe Asn Phe Asp Phe Asp Gln Met 50 55 60 Tyr Pro Val Ala Leu Val Met Leu 65 70 243 28 PRT Homo sapiens 243 Pro Phe Ile Cys Val Ala Arg Asn Pro Val Ser Arg Asn Phe Ser Ser 1 5 10 15 Pro Ile Leu Ala Arg Lys Leu Cys Glu Gly Ala Ala 20 25 244 33 PRT Homo sapiens 244 Lys Glu Asp Pro Ala Asn Thr Val Tyr Ser Thr Val Glu Ile Pro Lys 1 5 10 15 Lys Met Glu Asn Pro His Ser Leu Leu Thr Met Pro Asp Thr Pro Arg 20 25 30 Leu 245 227 PRT Homo sapiens 245 Ala Ser Ala Val Leu Leu Asp Leu Pro Asn Ser Gly Gly Glu Ala Gln 1 5 10 15 Ala Lys Lys Leu Gly Asn Asn Cys Val Phe Ala Pro Ala Asp Val Thr 20 25 30 Ser Glu Lys Asp Val Gln Thr Ala Leu Ala Leu Ala Lys Gly Lys Phe 35 40 45 Gly Arg Val Asp Val Ala Val Asn Cys Ala Gly Ile Ala Val Ala Ser 50 55 60 Lys Thr Tyr Asn Leu Lys Lys Gly Gln Thr His Thr Leu Glu Asp Phe 65 70 75 80 Gln Arg Val Leu Asp Val Asn Leu Met Gly Thr Phe Asn Val Ile Arg 85 90 95 Leu Val Ala Gly Glu Met Gly Gln Asn Glu Pro Asp Gln Gly Gly Gln 100 105 110 Arg Gly Val Ile Ile Asn Thr Ala Ser Val Ala Ala Phe Glu Gly Gln 115 120 125 Val Gly Gln Ala Ala Tyr Ser Ala Ser Lys Gly Gly Ile Val Gly Met 130 135 140 Thr Leu Pro Ile Ala Arg Asp Leu Ala Pro Ile Gly Ile Arg Val Met 145 150 155 160 Thr Ile Ala Pro Gly Leu Phe Gly Thr Pro Leu Leu Thr Ser Leu Pro 165 170 175 Glu Lys Val Cys Asn Phe Leu Ala Ser Gln Val Pro Phe Pro Ser Arg 180 185 190 Leu Gly Asp Pro Ala Glu Tyr Ala His Leu Val Gln Ala Ile Ile Glu 195 200 205 Asn Pro Phe Leu Asn Gly Glu Val Ile Arg Leu Asp Gly Ala Ile Arg 210 215 220 Met Gln Pro 225 246 29 PRT Homo sapiens 246 Ser Val Ala Ala Phe Glu Gly Gln Val Gly Gln Ala Ala Tyr Ser Ala 1 5 10 15 Ser Lys Gly Gly Ile Val Gly Met Thr Leu Pro Ile Ala 20 25 247 29 PRT Homo sapiens 247 Ser Val Ala Ala Phe Glu Gly Gln Val Gly Gln Ala Ala Tyr Ser Ala 1 5 10 15 Ser Lys Gly Gly Ile Val Gly Met Thr Leu Pro Ile Ala 20 25 248 22 PRT Homo sapiens 248 His Pro Ile Glu Trp Ala Ile Asn Ala Ala Thr Leu Ser Gln Phe Tyr 1 5 10 15 Ile Asn Lys Leu Cys Phe 20 249 22 PRT Homo sapiens 249 Cys Trp Ile Lys Tyr Cys Leu Thr Leu Met Gln Asn Ala Gln Leu Ser 1 5 10 15 Met Gln Asp Asn Ile Gly 20 250 25 PRT Homo sapiens 250 Lys Val Ser Tyr Leu Arg Pro Leu Asp Phe Glu Glu Ala Arg Glu Leu 1 5 10 15 Phe Leu Leu Gly Gln His Tyr Val Phe 20 25 251 25 PRT Homo sapiens MISC_FEATURE (11) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 251 Met Glu Arg Arg Cys Lys Met His Lys Arg Xaa Ile Ala Met Leu Glu 1 5 10 15 Pro Leu Thr Val Asp Leu Asn Pro Gln 20 25 252 23 PRT Homo sapiens 252 Ser His Ile Val Lys Lys Ile Asn Asn Leu Asn Lys Ser Ala Leu Lys 1 5 10 15 Tyr Tyr Gln Leu Phe Leu Asp 20 253 64 PRT Homo sapiens 253 Phe Thr His Leu Ser Thr Cys Leu Leu Ser Leu Leu Leu Val Arg Met 1 5 10 15 Ser Gly Phe Leu Leu Leu Ala Arg Ala Ser Pro Ser Ile Cys Ala Leu 20 25 30 Asp Ser Ser Cys Phe Val Gln Glu Tyr Cys Ser Ser Tyr Ser Ser Ser 35 40 45 Cys Phe Leu His Gln His Phe Pro Ser Leu Leu Asp His Leu Cys Gln 50 55 60 254 23 PRT Homo sapiens 254 Phe Leu Leu Leu Ala Arg Ala Ser Pro Ser Ile Cys Ala Leu Asp Ser 1 5 10 15 Ser Cys Phe Val Gln Glu Tyr 20 255 53 PRT Homo sapiens 255 Pro Asp Gly Arg Val Thr Asn Ile Pro Gln Gly Met Val Thr Asp Gln 1 5 10 15 Phe Gly Met Ile Gly Leu Leu Thr Phe Ile Arg Ala Ala Glu Thr Asp 20 25 30 Pro Gly Met Val His Leu Ala Leu Gly Ser Asp Leu Thr Thr Leu Gly 35 40 45 Leu Asn Leu Asn Ser 50 256 41 PRT Homo sapiens 256 Glu Asp Leu Leu Phe Tyr Leu Tyr Tyr Met Asn Gly Gly Asp Val Leu 1 5 10 15 Gln Leu Leu Ala Ala Val Glu Leu Phe Asn Arg Asp Trp Arg Tyr His 20 25 30 Lys Glu Glu Arg Val Trp Ile Thr Arg 35 40 257 24 PRT Homo sapiens 257 Val His Leu Ala Leu Gly Ser Asp Leu Thr Thr Leu Gly Leu Asn Leu 1 5 10 15 Asn Ser Pro Glu Asn Leu Tyr Pro 20 258 41 PRT Homo sapiens 258 Glu Asp Leu Leu Phe Tyr Leu Tyr Tyr Met Asn Gly Gly Asp Val Leu 1 5 10 15 Gln Leu Leu Ala Ala Val Glu Leu Phe Asn Arg Asp Trp Arg Tyr His 20 25 30 Lys Glu Glu Arg Val Trp Ile Thr Arg 35 40 259 11 PRT Homo sapiens 259 His Asn Glu Asp Phe Pro Ala Leu Pro Gly Ser 1 5 10 260 75 PRT Homo sapiens 260 Gly Arg Ile Ile Asp Thr Ser Leu Thr Arg Asp Pro Leu Val Ile Glu 1 5 10 15 Leu Gly Gln Lys Gln Val Ile Pro Gly Leu Glu Gln Ser Leu Leu Asp 20 25 30 Met Cys Val Gly Glu Lys Arg Arg Ala Ile Ile Pro Ser His Leu Ala 35 40 45 Tyr Gly Lys Arg Gly Phe Pro Pro Ser Val Pro Ala Asp Ala Val Val 50 55 60 Gln Tyr Asp Val Glu Leu Ile Ala Leu Ile Arg 65 70 75 261 16 PRT Homo sapiens 261 Ile His Tyr Thr Gly Ser Leu Val Asp Gly Arg Ile Ile Asp Thr Ser 1 5 10 15 262 20 PRT Homo sapiens 262 Cys Glu Ser Pro Glu Ser Pro Ala Gln Pro Ser Gly Ser Ser Leu Pro 1 5 10 15 Ala Trp Tyr His 20 263 95 PRT Homo sapiens 263 Glu Glu Ala Gly Ala Gly Arg Arg Cys Ser His Gly Gly Ala Arg Pro 1 5 10 15 Ala Gly Leu Gly Asn Glu Gly Leu Gly Leu Gly Gly Asp Pro Asp His 20 25 30 Thr Asp Thr Gly Ser Arg Ser Lys Gln Arg Ile Asn Asn Trp Lys Glu 35 40 45 Ser Lys His Lys Val Ile Met Ala Ser Ala Ser Ala Arg Gly Asn Gln 50 55 60 Asp Lys Asp Ala His Phe Pro Pro Pro Ser Lys Gln Ser Leu Leu Phe 65 70 75 80 Cys Pro Lys Ser Lys Leu His Ile His Arg Ala Glu Ile Ser Lys 85 90 95 264 23 PRT Homo sapiens 264 Ser Lys Gln Arg Ile Asn Asn Trp Lys Glu Ser Lys His Lys Val Ile 1 5 10 15 Met Ala Ser Ala Ser Ala Arg 20 265 32 PRT Homo sapiens MISC_FEATURE (20) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 265 Leu Phe His Trp Ala Cys Leu Asn Glu Arg Ala Ala Gln Leu Pro Arg 1 5 10 15 Asn Thr Ala Xaa Ala Gly Tyr Gln Cys Pro Ser Cys Asn Gly Pro Ser 20 25 30 266 185 PRT Homo sapiens 266 Phe Tyr Ile Tyr Tyr Arg Pro Thr Asp Ser Asp Asn Asp Ser Asp Tyr 1 5 10 15 Lys Lys Asp Met Val Glu Gly Asp Lys Tyr Trp His Ser Ile Ser His 20 25 30 Leu Gln Pro Glu Thr Ser Tyr Asp Ile Lys Met Gln Cys Phe Asn Glu 35 40 45 Gly Gly Glu Ser Glu Phe Ser Asn Val Met Ile Cys Glu Thr Lys Ala 50 55 60 Arg Lys Ser Ser Gly Gln Pro Gly Arg Leu Pro Pro Pro Thr Leu Ala 65 70 75 80 Pro Pro Gln Pro Pro Leu Pro Glu Thr Ile Glu Arg Pro Val Gly Thr 85 90 95 Gly Ala Met Val Ala Arg Ser Ser Asp Leu Pro Tyr Leu Ile Val Gly 100 105 110 Val Val Leu Gly Ser Ile Val Leu Ile Ile Val Thr Phe Ile Pro Phe 115 120 125 Cys Leu Trp Arg Ala Trp Ser Lys Gln Lys His Thr Thr Asp Leu Gly 130 135 140 Phe Pro Arg Ser Ala Leu Pro Pro Ser Cys Pro Tyr Thr Met Val Pro 145 150 155 160 Leu Gly Gly Leu Pro Gly His Gln Ala Val Asp Ser Pro Thr Ser Val 165 170 175 Ala Ser Val Asp Gly Pro Val Leu Met 180 185 267 66 PRT Homo sapiens 267 Tyr Ile Tyr Tyr Arg Pro Thr Asp Ser Asp Asn Asp Ser Asp Tyr Lys 1 5 10 15 Lys Asp Met Val Glu Gly Asp Lys Tyr Trp His Ser Ile Ser His Leu 20 25 30 Gln Pro Glu Thr Ser Tyr Asp Ile Lys Met Gln Cys Phe Asn Glu Gly 35 40 45 Gly Glu Ser Glu Phe Ser Asn Val Met Ile Cys Glu Thr Lys Ala Arg 50 55 60 Lys Ser 65 268 30 PRT Homo sapiens 268 Asn Val Arg Ala Leu Leu His Arg Met Pro Glu Pro Pro Lys Ile Asn 1 5 10 15 Thr Ala Lys Phe Asn Asn Asn Lys Arg Lys Asn Leu Ser Leu 20 25 30 269 185 PRT Homo sapiens 269 Asn Thr Asn Gln Arg Glu Ala Leu Gln Tyr Ala Lys Asn Phe Gln Pro 1 5 10 15 Phe Ala Leu Asn His Gln Lys Asp Ile Gln Val Leu Met Gly Ser Leu 20 25 30 Val Tyr Leu Arg Gln Gly Ile Glu Asn Ser Pro Tyr Val His Leu Leu 35 40 45 Asp Ala Asn Gln Trp Ala Asp Ile Cys Asp Ile Phe Thr Arg Asp Ala 50 55 60 Cys Ala Leu Leu Gly Leu Ser Val Glu Ser Pro Leu Ser Val Ser Phe 65 70 75 80 Ser Ala Gly Cys Val Ala Leu Pro Ala Leu Ile Asn Ile Lys Ala Val 85 90 95 Ile Glu Gln Arg Gln Cys Thr Gly Val Trp Asn Gln Lys Asp Glu Leu 100 105 110 Pro Ile Glu Val Asp Leu Gly Lys Lys Cys Trp Tyr His Ser Ile Phe 115 120 125 Ala Cys Pro Ile Leu Arg Gln Gln Thr Thr Asp Asn Asn Pro Pro Met 130 135 140 Lys Leu Val Cys Gly His Ile Ile Ser Arg Asp Ala Leu Asn Lys Met 145 150 155 160 Phe Asn Gly Ser Lys Leu Lys Cys Pro Tyr Cys Pro Met Glu Gln Ser 165 170 175 Pro Gly Asp Ala Lys Gln Ile Phe Phe 180 185 270 65 PRT Homo sapiens 270 Ser Tyr Leu Ser Ala Cys Phe Ala Gly Cys Asn Ser Thr Asn Leu Thr 1 5 10 15 Gly Cys Ala Cys Leu Thr Thr Val Pro Ala Glu Asn Ala Thr Val Val 20 25 30 Pro Gly Lys Cys Pro Ser Pro Gly Cys Gln Glu Ala Phe Leu Thr Phe 35 40 45 Leu Cys Val Met Cys Ile Cys Ser Leu Ile Gly Ala Met Ala Arg His 50 55 60 Pro 65 271 84 PRT Homo sapiens 271 Pro Ser Val Ile Ile Leu Ile Arg Thr Val Ser Pro Glu Leu Lys Ser 1 5 10 15 Tyr Ala Leu Gly Val Leu Phe Leu Leu Leu Arg Leu Leu Gly Phe Ile 20 25 30 Pro Pro Pro Leu Ile Phe Gly Ala Gly Ile Asp Ser Thr Cys Leu Phe 35 40 45 Trp Ser Thr Phe Cys Gly Glu Gln Gly Ala Cys Val Leu Tyr Asp Asn 50 55 60 Val Val Tyr Arg Tyr Leu Tyr Val Ser Ile Ala Ile Ala Leu Lys Ser 65 70 75 80 Phe Ala Phe Ile 272 182 PRT Homo sapiens MISC_FEATURE (29) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 272 Gln Ser Leu Phe Thr Arg Phe Val Arg Val Gly Val Pro Thr Val Asp 1 5 10 15 Leu Asp Ala Gln Gly Arg Ala Arg Ala Ser Leu Cys Xaa Xaa Tyr Asn 20 25 30 Trp Arg Tyr Lys Asn Leu Gly Asn Leu Pro His Val Gln Leu Leu Pro 35 40 45 Glu Phe Ser Thr Ala Asn Ala Gly Leu Leu Tyr Asp Phe Gln Leu Ile 50 55 60 Asn Val Glu Asp Phe Gln Gly Val Gly Glu Ser Glu Pro Asn Pro Tyr 65 70 75 80 Phe Tyr Gln Asn Leu Gly Glu Ala Glu Tyr Val Val Ala Leu Phe Met 85 90 95 Tyr Met Cys Leu Leu Gly Tyr Pro Ala Asp Lys Ile Ser Ile Leu Thr 100 105 110 Thr Tyr Asn Gly Gln Lys His Leu Ile Arg Asp Ile Ile Asn Arg Arg 115 120 125 Cys Gly Asn Asn Pro Leu Ile Gly Arg Pro Asn Lys Val Thr Thr Val 130 135 140 Asp Arg Phe Gln Gly Gln Gln Asn Asp Tyr Ile Leu Leu Ser Leu Val 145 150 155 160 Arg Thr Arg Ala Val Gly His Leu Arg Asp Val Arg Arg Leu Val Val 165 170 175 Ala Met Ser Arg Ala Arg 180 273 77 PRT Homo sapiens 273 Leu Val Lys Glu Ala Lys Ile Ile Ala Met Thr Cys Thr His Ala Ala 1 5 10 15 Leu Lys Arg His Asp Leu Val Lys Leu Gly Phe Lys Tyr Asp Asn Ile 20 25 30 Leu Met Glu Glu Ala Ala Gln Ile Leu Glu Ile Glu Thr Phe Ile Pro 35 40 45 Leu Leu Leu Gln Asn Pro Gln Asp Gly Phe Ser Arg Leu Lys Arg Trp 50 55 60 Ile Met Ile Gly Asp His His Gln Leu Pro Pro Val Ile 65 70 75 274 125 PRT Homo sapiens MISC_FEATURE (16) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 274 Asp Thr Tyr Pro Asn Glu Glu Lys Gln Gln Glu Arg Val Phe Pro Xaa 1 5 10 15 Xaa Ser Ala Met Val Asn Asn Gly Ser Leu Ser Tyr Asp His Glu Arg 20 25 30 Asp Gly Arg Pro Thr Glu Leu Gly Gly Cys Xaa Ala Ile Val Arg Asn 35 40 45 Leu His Tyr Asp Thr Phe Leu Val Ile Arg Tyr Val Lys Arg His Leu 50 55 60 Thr Ile Met Met Asp Ile Asp Gly Lys His Glu Trp Arg Asp Cys Ile 65 70 75 80 Glu Val Pro Gly Val Arg Leu Pro Arg Gly Tyr Tyr Phe Gly Thr Ser 85 90 95 Ser Ile Thr Gly Asp Leu Ser Asp Asn His Asp Val Ile Ser Leu Lys 100 105 110 Leu Phe Glu Leu Thr Val Glu Arg Thr Pro Glu Glu Glu 115 120 125 275 85 PRT Homo sapiens 275 Leu Lys Arg Glu His Ser Leu Ser Lys Pro Tyr Gln Gly Val Gly Thr 1 5 10 15 Gly Ser Ser Ser Leu Trp Asn Leu Met Gly Asn Ala Met Val Met Thr 20 25 30 Gln Tyr Ile Arg Leu Thr Pro Asp Met Gln Ser Lys Gln Gly Ala Leu 35 40 45 Trp Asn Arg Val Pro Cys Phe Leu Arg Asp Trp Glu Leu Gln Val His 50 55 60 Phe Lys Ile His Gly Gln Gly Lys Lys Asn Leu His Gly Asp Gly Leu 65 70 75 80 Ala Ile Trp Tyr Thr 85 276 32 PRT Homo sapiens 276 Pro Gly Thr Leu Gln Cys Ser Ala Leu His His Asp Pro Gly Cys Ala 1 5 10 15 Asn Cys Ser Arg Phe Cys Arg Asp Cys Ser Pro Pro Ala Cys Gln Cys 20 25 30 277 27 PRT Homo sapiens MISC_FEATURE (8) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 277 Phe Leu Tyr Asp Val Leu Met Xaa His Glu Ala Val Met Arg Thr His 1 5 10 15 Gln Ile Gln Leu Pro Asp Pro Glu Phe Pro Ser 20 25 278 92 PRT Homo sapiens MISC_FEATURE (4) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 278 Pro Ala Asp Xaa Lys Pro Val Val Ser Thr Glu Ala Pro Pro Ile Ile 1 5 10 15 Phe Ala Thr Pro Thr Lys Leu Thr Ser Asp Ser Thr Val Tyr Asp Tyr 20 25 30 Ala Gly Lys Asn Lys Val Pro Glu Leu Gln Lys Phe Phe Gln Lys Ala 35 40 45 Asp Gly Val Pro Val Tyr Leu Lys Arg Gly Leu Pro Asp Gln Met Leu 50 55 60 Tyr Arg Thr Thr Met Ala Leu Thr Val Gly Gly Thr Ile Tyr Cys Leu 65 70 75 80 Ile Ala Leu Tyr Met Ala Ser Gln Pro Lys Asn Lys 85 90 279 63 PRT Homo sapiens MISC_FEATURE (45) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 279 Ser Phe Ser Gly Ala Val Ala Leu Ala Ala Asp Ala Gly Ser Arg Thr 1 5 10 15 Leu Gly Val Met Tyr Tyr Lys Phe Ser Gly Phe Thr Gln Lys Leu Ala 20 25 30 Gly Ala Trp Ala Ser Glu Ala Tyr Ser Pro Gln Ile Xaa Ser Leu Trp 35 40 45 Phe Pro Gln Lys His His Leu Ser Tyr Leu Pro His Gln Leu Asn 50 55 60 280 6 PRT Homo sapiens 280 Gly Trp Tyr Trp Cys Gly 1 5 281 129 PRT Homo sapiens 281 Met Lys Val Gly Ala Arg Ile Arg Val Lys Met Ser Val Asn Lys Ala 1 5 10 15 His Pro Val Val Ser Thr His Trp Arg Trp Pro Ala Glu Trp Pro Gln 20 25 30 Met Phe Leu His Leu Ala Gln Glu Pro Arg Thr Glu Val Lys Ser Arg 35 40 45 Pro Leu Gly Leu Ala Gly Phe Ile Arg Gln Asp Ser Lys Thr Arg Lys 50 55 60 Pro Leu Glu Gln Glu Thr Ile Met Ser Ala Ala Asp Thr Ala Leu Trp 65 70 75 80 Pro Tyr Gly His Gly Asn Arg Glu His Gln Glu Asn Glu Leu Gln Lys 85 90 95 Tyr Leu Gln Tyr Lys Asp Met His Leu Leu Asp Ser Gly Gln Ser Leu 100 105 110 Gly His Thr His Thr Leu Gln Gly Ser His Asn Leu Thr Ala Leu Asn 115 120 125 Ile 282 49 PRT Homo sapiens 282 Ser Leu His Lys Asn Ser Val Ser Gln Ile Ser Val Leu Ser Gly Gly 1 5 10 15 Lys Ala Lys Cys Ser Gln Phe Cys Thr Thr Gly Met Asp Gly Gly Met 20 25 30 Ser Ile Trp Asp Val Lys Ser Leu Glu Ser Ala Leu Lys Asp Leu Lys 35 40 45 Ile 283 21 PRT Homo sapiens 283 Glu Ala Ser Lys Ser Ser His Ala Gly Leu Asp Leu Phe Ser Val Ala 1 5 10 15 Ala Cys His Arg Phe 20 284 21 PRT Homo sapiens 284 Tyr Met Gly Lys Gly Ser Met Thr Gly Leu Ala Leu Lys His Met Phe 1 5 10 15 Glu Arg Ser Phe Thr 20 285 27 PRT Homo sapiens 285 Val Thr Gly Ile Ile Asp Ser Leu Thr Ile Ser Pro Lys Ala Ala Arg 1 5 10 15 Val Gly Leu Leu Gln Tyr Ser Thr Gln Val His 20 25 286 24 PRT Homo sapiens 286 Thr Glu Phe Thr Leu Arg Asn Phe Asn Ser Ala Lys Asp Met Lys Lys 1 5 10 15 Ala Val Ala His Met Lys Tyr Met 20 287 27 PRT Homo sapiens 287 Gly Lys Gly Ser Met Thr Gly Leu Ala Leu Lys His Met Phe Glu Arg 1 5 10 15 Ser Phe Thr Gln Gly Glu Gly Ala Arg Pro Phe 20 25 288 44 PRT Homo sapiens 288 Ser Thr Arg Val Pro Arg Ala Ala Ile Val Phe Thr Asp Gly Arg Ala 1 5 10 15 Gln Asp Asp Val Ser Glu Trp Ala Ser Lys Ala Lys Ala Asn Gly Ile 20 25 30 Thr Met Tyr Ala Val Gly Val Gly Lys Ala Ile Glu 35 40 289 42 PRT Homo sapiens 289 Glu Glu Leu Gln Glu Ile Ala Ser Glu Pro Thr Asn Lys His Leu Phe 1 5 10 15 Tyr Ala Glu Asp Phe Ser Thr Met Asp Glu Ile Ser Glu Lys Leu Lys 20 25 30 Lys Gly Ile Cys Glu Ala Leu Glu Asp Ser 35 40 290 11 PRT Homo sapiens 290 Thr Gln Arg Leu Glu Glu Met Thr Gln Arg Met 1 5 10 291 10 PRT Homo sapiens 291 Pro Gln Gly Cys Pro Glu Gln Pro Leu His 1 5 10 292 33 PRT Homo sapiens 292 Arg Cys Lys Lys Cys Thr Glu Gly Pro Ile Asp Leu Val Phe Val Ile 1 5 10 15 Asp Gly Ser Lys Ser Leu Gly Glu Glu Asn Phe Glu Val Val Lys Gln 20 25 30 Phe 293 193 PRT Homo sapiens MISC_FEATURE (35) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 293 Gly Trp Glu Thr Leu Pro Lys Lys Asp Val Cys Lys Ser Thr His His 1 5 10 15 Gly Cys Glu His Ile Cys Val Asn Asn Gly Asn Ser Tyr Ile Cys Lys 20 25 30 Cys Ser Xaa Gly Phe Val Leu Ala Glu Asp Gly Arg Arg Cys Lys Lys 35 40 45 Cys Thr Glu Gly Pro Ile Asp Leu Val Phe Val Ile Asp Gly Ser Lys 50 55 60 Ser Leu Gly Glu Glu Asn Phe Glu Val Val Lys Gln Phe Val Thr Gly 65 70 75 80 Ile Ile Asp Ser Leu Thr Ile Ser Pro Lys Ala Ala Arg Val Gly Leu 85 90 95 Leu Gln Tyr Ser Thr Gln Val His Thr Glu Phe Thr Leu Arg Asn Phe 100 105 110 Asn Ser Ala Lys Asp Met Lys Lys Ala Val Ala His Met Lys Tyr Met 115 120 125 Gly Lys Gly Ser Met Thr Gly Leu Ala Leu Lys His Met Phe Glu Arg 130 135 140 Ser Phe Thr Gln Gly Glu Gly Ala Arg Pro Phe Pro Gln Gly Cys Pro 145 150 155 160 Glu Gln Pro Leu Cys Ser Pro Thr Asp Gly Leu Arg Met Thr Ser Pro 165 170 175 Ser Gly Pro Val Lys Pro Arg Pro Met Val Ser Leu Cys Met Leu Leu 180 185 190 Gly 294 193 PRT Homo sapiens 294 Lys Phe Tyr Pro Arg Arg Arg Gly Gln Ala Leu Ser Thr Arg Val Pro 1 5 10 15 Arg Ala Ala Ile Val Phe Thr Asp Gly Arg Ala Gln Asp Asp Val Ser 20 25 30 Glu Trp Ala Ser Lys Ala Lys Ala Asn Gly Ile Thr Met Tyr Ala Val 35 40 45 Gly Val Gly Lys Ala Ile Glu Glu Glu Leu Gln Glu Ile Ala Ser Glu 50 55 60 Pro Thr Asn Lys His Leu Phe Tyr Ala Glu Asp Phe Ser Thr Met Asp 65 70 75 80 Glu Ile Ser Glu Lys Leu Lys Lys Gly Ile Cys Glu Ala Leu Glu Asp 85 90 95 Ser Asp Gly Arg Gln Asp Ser Pro Ala Gly Glu Leu Pro Lys Thr Val 100 105 110 Gln Gln Pro Thr Val Gln His Arg Tyr Leu Phe Glu Glu Asp Asn Leu 115 120 125 Leu Arg Ser Thr Gln Lys Leu Ser His Ser Thr Lys Pro Ser Gly Ser 130 135 140 Pro Leu Glu Glu Lys His Asp Gln Cys Lys Cys Glu Asn Leu Ile Met 145 150 155 160 Phe Gln Asn Leu Ala Asn Glu Glu Val Arg Lys Leu Thr Gln Arg Leu 165 170 175 Glu Glu Met Thr Gln Arg Met Glu Ala Leu Glu Asn Arg Leu Arg Tyr 180 185 190 Arg 295 60 PRT Homo sapiens 295 Met Ala Ala Leu Leu Leu Arg His Val Gly Arg His Cys Leu Arg Ala 1 5 10 15 His Phe Ser Pro Gln Leu Cys Ile Arg Asn Ala Val Pro Leu Gly Thr 20 25 30 Thr Ala Lys Glu Glu Met Glu Arg Phe Trp Asn Lys Asn Ile Gly Ser 35 40 45 Asn Arg Pro Leu Ser Pro His Ile Thr Ile Tyr Ser 50 55 60 296 32 PRT Homo sapiens 296 Val Phe Pro Leu Met Tyr His Thr Trp Asn Gly Ile Arg His Leu Met 1 5 10 15 Trp Asp Leu Gly Lys Gly Leu Lys Ile Pro Gln Leu Tyr Gln Ser Gly 20 25 30 297 17 PRT Homo sapiens 297 Met Ala Ala Leu Leu Leu Arg His Val Gly Arg His Cys Leu Arg Ala 1 5 10 15 His 298 18 PRT Homo sapiens 298 Val Lys Ser Leu Cys Leu Gly Pro Ala Leu Ile His Thr Ala Lys Phe 1 5 10 15 Ala Leu 299 23 PRT Homo sapiens 299 Val Phe Pro Leu Met Tyr His Thr Trp Asn Gly Ile Arg His Leu Met 1 5 10 15 Trp Asp Leu Gly Lys Gly Leu 20 300 22 PRT Homo sapiens 300 Arg Val Trp Asp Val Arg Pro Phe Ala Pro Lys Glu Arg Cys Val Lys 1 5 10 15 Ile Phe Gln Gly Asn Val 20 301 30 PRT Homo sapiens 301 His Asn Phe Glu Lys Asn Leu Leu Arg Cys Ser Trp Ser Pro Asp Gly 1 5 10 15 Ser Lys Ile Ala Ala Gly Ser Ala Asp Arg Phe Val Tyr Val 20 25 30 302 30 PRT Homo sapiens 302 Trp Asp Thr Thr Ser Arg Arg Ile Leu Tyr Lys Leu Pro Gly His Ala 1 5 10 15 Gly Ser Ile Asn Glu Val Ala Phe His Pro Asp Glu Pro Ile 20 25 30 303 141 PRT Homo sapiens 303 Tyr Gln Gly Leu Gly Leu Arg Gln Asn Lys Leu Thr Tyr Thr Met Arg 1 5 10 15 Gly His Ala Asp Ser Val Thr Gly Leu Ser Leu Ser Ser Glu Gly Ser 20 25 30 Tyr Leu Leu Ser Asn Ala Met Asp Asn Thr Val Arg Val Trp Asp Val 35 40 45 Arg Pro Phe Ala Pro Lys Glu Arg Cys Val Lys Ile Phe Gln Gly Asn 50 55 60 Val His Asn Phe Glu Lys Asn Leu Leu Arg Cys Ser Trp Ser Pro Asp 65 70 75 80 Gly Ser Lys Ile Ala Ala Gly Ser Ala Asp Arg Phe Val Tyr Val Trp 85 90 95 Asp Thr Thr Ser Arg Arg Ile Leu Tyr Lys Leu Pro Gly His Ala Gly 100 105 110 Ser Ile Asn Glu Val Ala Phe His Pro Asp Glu Pro Ile Ile Ile Ser 115 120 125 Ala Ser Ser Asp Lys Arg Leu Tyr Met Gly Glu Ile Gln 130 135 140 304 45 PRT Homo sapiens 304 Arg Lys Lys Ala Ala Ile Gln Thr Phe Gln Asn Thr Tyr Gln Val Leu 1 5 10 15 Ala Val Thr Phe Asn Asp Thr Ser Asp Gln Ile Ile Ser Gly Gly Ile 20 25 30 Asp Asn Asp Ile Lys Val Trp Asp Cys Ala Arg Thr Ser 35 40 45 305 20 PRT Homo sapiens 305 Val Arg Gly Arg Thr Val Leu Arg Pro Gly Leu Asp Ala Glu Pro Glu 1 5 10 15 Leu Ser Pro Glu 20 306 19 PRT Homo sapiens 306 Glu Gln Arg Val Leu Glu Arg Lys Leu Lys Lys Glu Arg Lys Lys Glu 1 5 10 15 Glu Arg Gln 307 13 PRT Homo sapiens 307 Arg Leu Arg Glu Ala Gly Leu Val Ala Gln His Pro Pro 1 5 10 308 17 PRT Homo sapiens 308 Gly Arg Ile Pro Ala Pro Ala Pro Ser Val Pro Ala Gly Pro Asp Ser 1 5 10 15 Arg 309 61 PRT Homo sapiens 309 Ala Arg Arg Ser Gly Ala Glu Leu Ala Trp Asp Tyr Leu Cys Arg Trp 1 5 10 15 Ala Gln Lys His Lys Asn Trp Arg Phe Gln Lys Thr Arg Gln Thr Trp 20 25 30 Leu Leu Leu His Met Tyr Asp Ser Asp Lys Val Pro Asp Glu His Phe 35 40 45 Ser Thr Leu Leu Ala Tyr Leu Glu Gly Leu Gln Gly Arg 50 55 60 310 42 PRT Homo sapiens 310 Thr Gly Cys Val Leu Val Leu Ser Arg Asn Phe Val Gln Tyr Ala Cys 1 5 10 15 Phe Gly Leu Phe Gly Ile Ile Ala Leu Gln Thr Ile Ala Tyr Ser Ile 20 25 30 Leu Trp Asp Leu Lys Phe Leu Met Arg Asn 35 40 311 55 PRT Homo sapiens 311 Ser Arg Ser Glu Gly Lys Ser Met Phe Ala Gly Val Pro Thr Met Arg 1 5 10 15 Glu Ser Ser Pro Lys Gln Tyr Met Gln Leu Gly Gly Arg Val Leu Leu 20 25 30 Val Leu Met Phe Met Thr Leu Leu His Phe Asp Ala Ser Phe Phe Ser 35 40 45 Ile Val Gln Asn Ile Val Gly 50 55 312 60 PRT Homo sapiens 312 Gly Thr Ala Glu Asp Phe Ala Asp Gln Phe Leu Arg Val Thr Lys Gln 1 5 10 15 Tyr Leu Pro His Val Ala Arg Leu Cys Leu Ile Ser Thr Phe Leu Glu 20 25 30 Asp Gly Ile Arg Met Trp Phe Gln Trp Ser Glu Gln Arg Asp Tyr Ile 35 40 45 Asp Thr Thr Trp Asn Cys Gly Tyr Leu Leu Ala Ser 50 55 60 313 17 PRT Homo sapiens 313 Ala Ser Phe Leu Leu Ser Arg Thr Ser Trp Gly Thr Ala Leu Met Ile 1 5 10 15 Leu 314 8 PRT Homo sapiens 314 Leu Met Arg Asn Glu Ser Arg Ser 1 5 315 13 PRT Homo sapiens 315 Ala Ser Phe Leu Leu Ser Arg Thr Ser Trp Gly Thr Ala 1 5 10 316 17 PRT Homo sapiens 316 Ala Ser Phe Leu Leu Ser Arg Thr Ser Trp Gly Thr Ala Leu Met Ile 1 5 10 15 Leu 317 72 PRT Homo sapiens 317 Pro Ser Phe Thr Leu Thr Pro Ala Ser Phe Leu Leu Ser Arg Thr Ser 1 5 10 15 Trp Gly Thr Ala Leu Met Ile Leu Val Ala Ile Gly Phe Lys Thr Lys 20 25 30 Leu Ala Ala Leu Thr Leu Val Val Trp Leu Phe Ala Ile Asn Val Tyr 35 40 45 Phe Asn Ala Phe Trp Thr Ile Pro Val Tyr Lys Pro Met His Asp Phe 50 55 60 Leu Lys Tyr Asp Phe Phe Gln Thr 65 70 318 236 PRT Homo sapiens MISC_FEATURE (115) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 318 Arg Thr Glu Pro Pro Pro Gly Thr Ser Cys Gly Gly Arg Ser Gly Cys 1 5 10 15 Gly Arg Arg Arg Ala Arg Ala Ser Glu Arg Ala Ser Glu Pro Ser Arg 20 25 30 Ala Ser Arg Arg Arg His Gly Pro Glu Arg Pro Asp Gly His Gly Arg 35 40 45 Gly Leu Arg Arg Pro Val Pro Pro Cys His Lys Ala Val Pro Ala Pro 50 55 60 Arg Gly Ala Pro Leu Ser Asp Gln His Leu Pro Gly Gly Arg His Pro 65 70 75 80 Tyr Val Val Pro Val Glu Arg Ala Ala Arg Leu His Arg His His Leu 85 90 95 Glu Leu Arg Leu Pro Ala Gly Leu Val Leu Arg Leu Pro Gln Leu Ala 100 105 110 Gly Thr Xaa Thr Gly Cys Val Leu Val Leu Ser Arg Asn Phe Val Gln 115 120 125 Tyr Ala Cys Phe Gly Leu Phe Gly Ile Ile Ala Leu Gln Thr Ile Ala 130 135 140 Tyr Ser Ile Leu Trp Asp Leu Lys Phe Leu Met Arg Asn Leu Ala Leu 145 150 155 160 Gly Gly Gly Leu Leu Leu Leu Leu Ala Glu Ser Arg Ser Glu Gly Lys 165 170 175 Ser Met Phe Ala Gly Val Pro Thr Met Arg Glu Ser Ser Pro Lys Gln 180 185 190 Tyr Met Gln Leu Gly Gly Arg Val Leu Leu Val Leu Met Phe Met Thr 195 200 205 Leu Leu His Phe Asp Ala Ser Phe Phe Ser Ile Val Gln Asn Ile Val 210 215 220 Gly His Ser Ser Asp Asp Phe Ser Gly His Trp Phe 225 230 235 319 114 PRT Homo sapiens MISC_FEATURE (2) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 319 Gly Xaa Ser Arg Arg Arg Ala Leu Pro Val Glu Ala Ala Ala Gly Ala 1 5 10 15 Gly Ala Asp Gly Arg Glu Pro Ala Ser Glu Arg Ala Ser Arg Ala Glu 20 25 30 Pro Pro Ala Val Ala Met Gly Gln Asn Asp Leu Met Gly Thr Ala Glu 35 40 45 Asp Phe Ala Asp Gln Phe Leu Arg Val Thr Lys Gln Tyr Leu Pro His 50 55 60 Val Ala Arg Leu Cys Leu Ile Ser Thr Phe Leu Glu Asp Gly Ile Arg 65 70 75 80 Met Trp Phe Gln Trp Ser Glu Gln Arg Asp Tyr Ile Asp Thr Thr Trp 85 90 95 Asn Cys Gly Tyr Leu Leu Ala Ser Ser Phe Val Phe Leu Asn Leu Leu 100 105 110 Gly Xaa 320 63 PRT Homo sapiens 320 Trp Val Phe Leu Phe Leu Leu Ala Leu Gly Gly Leu Gly Pro Asp Ser 1 5 10 15 Gly Arg Cys Leu Cys Arg Glu Gly Arg Ile Ser Gly Ile Tyr Gln Leu 20 25 30 Ile Leu Ala Lys Gln Phe Leu Arg Phe Phe Cys Phe Met Trp Glu Thr 35 40 45 Asp Leu Asn Leu Ile Leu Cys Cys Ile Leu Tyr Leu Ser Cys Val 50 55 60 321 106 PRT Homo sapiens 321 Ser Met Ser Ala Leu Thr Arg Leu Ala Ser Phe Ala Arg Val Gly Gly 1 5 10 15 Arg Leu Phe Arg Ser Gly Cys Ala Arg Thr Ala Gly Asp Gly Gly Val 20 25 30 Arg His Ala Gly Gly Gly Val His Ile Glu Pro Arg Tyr Arg Gln Phe 35 40 45 Pro Gln Leu Thr Arg Ser Gln Val Phe Gln Ser Glu Phe Phe Ser Gly 50 55 60 Leu Met Trp Phe Trp Ile Leu Trp Arg Phe Trp His Asp Ser Glu Glu 65 70 75 80 Val Leu Gly His Phe Pro Tyr Pro Asp Pro Ser Gln Trp Thr Asp Glu 85 90 95 Glu Leu Gly Ile Pro Pro Asp Asp Glu Asp 100 105 322 20 PRT Homo sapiens 322 Phe Ile Ser Phe Ala Asn Ser Arg Ser Ser Glu Asp Thr Lys Gln Met 1 5 10 15 Met Ser Ser Phe 20 323 27 PRT Homo sapiens 323 Asp Pro Arg Arg Pro Asn Lys Val Leu Arg Tyr Lys Pro Pro Pro Ser 1 5 10 15 Glu Cys Asn Pro Ala Leu Asp Asp Pro Thr Pro 20 25 324 30 PRT Homo sapiens 324 Asp Tyr Met Asn Leu Leu Gly Met Ile Phe Ser Met Cys Gly Leu Met 1 5 10 15 Leu Lys Leu Lys Trp Cys Ala Trp Val Ala Val Tyr Cys Ser 20 25 30 325 22 PRT Homo sapiens 325 Met Leu Ser Ile Ser Ala Val Val Met Ser Tyr Leu Gln Asn Pro Gln 1 5 10 15 Pro Met Thr Pro Pro Trp 20 326 52 PRT Homo sapiens MISC_FEATURE (35) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 326 Ala Ala Gly Asp Gly Asp Val Lys Leu Gly Thr Leu Gly Ser Gly Ser 1 5 10 15 Glu Ser Ser Asn Asp Gly Gly Ser Glu Ser Pro Gly Asp Ala Gly Ala 20 25 30 Ala Ala Xaa Gly Gly Gly Trp Ala Ala Ala Ala Leu Ala Leu Leu Thr 35 40 45 Gly Gly Gly Glu 50 327 62 PRT Homo sapiens MISC_FEATURE (45) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 327 Ser Thr His Ala Ser Gly Arg Ala Val Met Ala Ala Gly Asp Gly Asp 1 5 10 15 Val Lys Leu Gly Thr Leu Gly Ser Gly Ser Glu Ser Ser Asn Asp Gly 20 25 30 Gly Ser Glu Ser Pro Gly Asp Ala Gly Ala Ala Ala Xaa Gly Gly Gly 35 40 45 Trp Ala Ala Ala Ala Leu Ala Leu Leu Thr Gly Gly Gly Glu 50 55 60 328 177 PRT Homo sapiens MISC_FEATURE (26) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 328 Ala Ala Asp Asn Tyr Gly Ile Pro Arg Ala Cys Arg Asn Ser Ala Arg 1 5 10 15 Ser Tyr Gly Ala Ala Trp Leu Leu Leu Xaa Pro Ala Gly Ser Ser Arg 20 25 30 Val Glu Pro Thr Gln Asp Ile Ser Ile Ser Asp Gln Leu Gly Gly Gln 35 40 45 Asp Val Pro Val Phe Arg Asn Leu Ser Leu Leu Val Val Gly Val Gly 50 55 60 Ala Val Phe Ser Leu Leu Phe His Leu Gly Thr Arg Glu Arg Arg Arg 65 70 75 80 Pro His Ala Xaa Glu Pro Gly Glu His Thr Pro Leu Leu Ala Pro Ala 85 90 95 Thr Ala Gln Pro Leu Leu Leu Trp Lys His Trp Leu Arg Glu Xaa Ala 100 105 110 Phe Tyr Gln Val Gly Ile Leu Tyr Met Thr Thr Arg Leu Ile Val Asn 115 120 125 Leu Ser Gln Thr Tyr Met Ala Met Tyr Leu Thr Tyr Ser Leu His Leu 130 135 140 Pro Lys Lys Phe Ile Ala Thr Ile Pro Leu Val Met Tyr Leu Ser Gly 145 150 155 160 Phe Leu Ser Ser Phe Leu Met Lys Pro Ile Asn Lys Cys Ile Gly Arg 165 170 175 Asn 329 79 PRT Homo sapiens MISC_FEATURE (7) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 329 Cys Thr Leu Ala Met Trp Xaa Leu Gly His Cys Asp Pro Arg Arg Cys 1 5 10 15 Thr Gly Arg Lys Leu Ala Arg Leu Gly Leu Val Arg Cys Leu Arg Leu 20 25 30 Gly His Arg Phe Gly Gly Leu Val Leu Ser Pro Val Gly Lys Gln Tyr 35 40 45 Ala Ser Pro Ala Asp Arg Gln Leu Val Ala Gln Ser Gly Val Ala Val 50 55 60 Ile Asp Cys Ser Trp Ala Arg Leu Asp Glu Thr Pro Phe Gly Lys 65 70 75 330 72 PRT Homo sapiens 330 Ser Gly Arg Gly Ala Arg Ser Asp Val Thr Ala Met Ala Gly Ile Lys 1 5 10 15 Ala Leu Ile Ser Leu Ser Phe Gly Gly Ala Ile Gly Leu Met Phe Leu 20 25 30 Met Leu Gly Cys Ala Leu Pro Ile Tyr Asn Lys Tyr Trp Pro Leu Phe 35 40 45 Val Leu Phe Phe Tyr Ile Leu Ser Pro Ile Pro Tyr Cys Ile Ala Arg 50 55 60 Arg Leu Val Asp Asp Thr Asp Ala 65 70 331 32 PRT Homo sapiens MISC_FEATURE (5) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 331 Ala Arg Val Arg Xaa Arg Gly Ala Leu Ser Leu Ser Val Gly Ala Ala 1 5 10 15 Cys Gly Leu Val Ala Leu Trp Gln Arg Arg Arg Gln Asp Ser Gly Thr 20 25 30 332 45 PRT Homo sapiens 332 Leu Ser Asn Asn Ala Gln Asn Trp Gly Met Gln Arg Ala Thr Asn Val 1 5 10 15 Thr Tyr Gln Ala His His Val Ser Arg Asn Lys Arg Gly Gln Val Val 20 25 30 Gly Thr Arg Gly Gly Phe Arg Gly Cys Thr Val Trp Leu 35 40 45 333 38 PRT Homo sapiens 333 Val Ser Met Ala Leu Glu Glu Tyr Leu Val Cys His Gly Ile Pro Cys 1 5 10 15 Tyr Thr Leu Asp Gly Asp Asn Ile Arg Gln Gly Leu Asn Lys Asn Leu 20 25 30 Gly Phe Ser Pro Glu Asp 35 334 39 PRT Homo sapiens 334 Thr Gln Asp Arg Asn Asn Ala Arg Gln Ile His Glu Gly Ala Ser Leu 1 5 10 15 Pro Phe Phe Glu Val Phe Val Asp Ala Pro Leu His Val Cys Glu Gln 20 25 30 Arg Asp Val Lys Gly Leu Tyr 35 335 40 PRT Homo sapiens 335 Phe Thr Gly Ile Asp Ser Glu Tyr Glu Lys Pro Glu Ala Pro Glu Leu 1 5 10 15 Val Leu Lys Thr Asp Ser Cys Asp Val Asn Asp Cys Val Gln Gln Val 20 25 30 Val Glu Leu Leu Gln Glu Arg Asp 35 40 336 41 PRT Homo sapiens 336 Ala Glu Thr Leu Pro Ala Leu Lys Ile Asn Lys Val Asp Met Gln Trp 1 5 10 15 Val Gln Val Leu Ala Glu Gly Trp Ala Thr Pro Leu Asn Gly Phe Met 20 25 30 Arg Glu Arg Glu Tyr Leu Gln Cys Leu 35 40 337 30 PRT Homo sapiens 337 Val Pro Ile Val Leu Thr Ala Thr His Glu Asp Lys Glu Arg Leu Asp 1 5 10 15 Gly Cys Thr Ala Phe Ala Leu Met Tyr Glu Gly Arg Arg Val 20 25 30 338 39 PRT Homo sapiens 338 Ile Gly Gly Asp Leu Gln Val Leu Asp Arg Val Tyr Trp Asn Asp Gly 1 5 10 15 Leu Asp Gln Tyr Arg Leu Thr Pro Thr Glu Leu Lys Gln Lys Phe Lys 20 25 30 Asp Met Asn Ala Asp Ala Val 35 339 37 PRT Homo sapiens 339 Gly His Ala Leu Leu Met Gln Asp Thr His Lys Gln Leu Leu Glu Arg 1 5 10 15 Gly Tyr Arg Arg Pro Val Leu Leu Leu His Pro Leu Gly Gly Trp Thr 20 25 30 Lys Asp Asp Asp Val 35 340 41 PRT Homo sapiens 340 Met Tyr Ala Gly Pro Thr Glu Val Gln Trp His Cys Arg Ala Arg Met 1 5 10 15 Val Ala Gly Ala Asn Phe Tyr Ile Val Gly Arg Asp Pro Ala Gly Met 20 25 30 Pro His Pro Glu Thr Gly Lys Asp Leu 35 40 341 34 PRT Homo sapiens 341 Leu Thr Met Ala Pro Gly Leu Ile Thr Leu Glu Ile Val Pro Phe Arg 1 5 10 15 Val Ala Ala Tyr Asn Lys Lys Lys Lys Arg Met Asp Tyr Tyr Asp Ser 20 25 30 Glu His 342 19 PRT Homo sapiens 342 Gly Phe Met Ala Pro Lys Ala Trp Thr Val Leu Thr Glu Tyr Tyr Lys 1 5 10 15 Ser Leu Glu 343 243 PRT Homo sapiens MISC_FEATURE (30) Xaa equals any of the L-amino acids commonly found in naturally occurring proteins 343 Arg Ile Thr Asp Asn Pro Glu Gly Lys Trp Leu Gly Arg Thr Ala Arg 1 5 10 15 Gly Ser Tyr Gly Tyr Ile Lys Thr Thr Ala Val Glu Ile Xaa Tyr Asp 20 25 30 Ser Leu Lys Leu Lys Lys Asp Ser Leu Gly Ala Pro Ser Arg Pro Ile 35 40 45 Glu Asp Asp Gln Glu Val Tyr Asp Asp Val Ala Glu Gln Asp Asp Ile 50 55 60 Ser Ser His Ser Gln Ser Gly Ser Gly Gly Ile Phe Pro Pro Pro Pro 65 70 75 80 Asp Asp Asp Ile Tyr Asp Gly Ile Glu Glu Glu Asp Ala Asp Asp Gly 85 90 95 Phe Pro Ala Pro Pro Lys Gln Leu Asp Met Gly Asp Glu Val Tyr Asp 100 105 110 Asp Val Asp Thr Ser Asp Phe Pro Val Ser Ser Ala Glu Met Ser Gln 115 120 125 Gly Thr Asn Val Gly Lys Ala Lys Thr Glu Glu Lys Asp Leu Lys Lys 130 135 140 Leu Lys Lys Gln Xaa Lys Glu Xaa Lys Asp Phe Arg Lys Lys Phe Lys 145 150 155 160 Tyr Asp Gly Glu Ile Arg Val Leu Tyr Ser Thr Lys Val Thr Thr Ser 165 170 175 Ile Thr Ser Lys Lys Trp Gly Thr Arg Asp Leu Gln Val Lys Pro Gly 180 185 190 Glu Ser Leu Glu Val Ile Gln Thr Thr Asp Asp Thr Lys Val Leu Cys 195 200 205 Arg Asn Glu Glu Gly Lys Tyr Gly Tyr Val Leu Arg Ser Tyr Leu Ala 210 215 220 Asp Asn Asp Gly Glu Ile Tyr Asp Asp Ile Ala Asp Gly Cys Ile Tyr 225 230 235 240 Asp Asn Asp

Claims

1. An isolated antibody or portion thereof that specifically binds to a protein whose sequence consists of amino acid residues 29 to 99 of SEQ ID NO:142.

2. The isolated antibody or portion thereof of claim 1, wherein said protein specifically bound by said antibody or portion thereof is glycosylated.

3. The isolated antibody or portion thereof of claim 1 which is a monoclonal antibody.

4. The isolated antibody or portion thereof of claim 1 which is a polyclonal antibody.

5. The isolated antibody or portion thereof of claim 1 which is a chimeric antibody.

6. The isolated antibody or portion thereof of claim 1 which is a humanized antibody.

7. The isolated antibody or portion thereof of claim 1 which is a human antibody.

8. The isolated antibody or portion thereof of claim 1 which is a Fab fragment.

9. The isolated antibody or portion thereof of claim 1 which is labeled.

10. The isolated antibody of claim 9, wherein the label is selected from the group consisting of:

(a) an enzyme label;

(b) a radioisotope; and

(c) a fluorescent label.

11. An isolated cell that produces the isolated antibody of claim 1.

12. A hybridoma that produces the isolated antibody of claim 1.

13. A hybridoma that produces the isolated antibody of claim 3.

14. An isolated antibody produced by immunizing an animal with a protein whose sequence comprises of amino acid residues 29 to 99 of SEQ ID NO:142, wherein said antibody or portion thereof specifically binds to the protein of SEQ ID NO:142.

15. The isolated antibody of claim 14, wherein said protein specifically bound by said antibody is glycosylated.

16. The isolated antibody of claim 14 which is a monoclonal antibody.

17. The isolated antibody of claim 14 which is a polyclonal antibody.

18. The isolated antibody of claim 14 which is labeled.

19. The isolated antibody of claim 18, wherein the label is selected from the group consisting of:

(d) an enzyme label;

(e) a radioisotope; and

(f) a fluorescent label.

20. An isolated cell that produces the isolated antibody of claim 14.

21. A hybridoma that produces the isolated antibody of claim 14.

22. A hybridoma that produces the isolated antibody of claim 16.

23. An isolated antibody or portion thereof that specifically binds to a protein whose sequence consists of amino acid residues 1 to 99 of SEQ ID NO:142.

24. The isolated antibody or portion thereof of claim 23 wherein said protein specifically bound by said antibody or portion thereof is glycosylated.

25. The isolated antibody or portion thereof of claim 23 which is a monoclonal antibody.

26. The isolated antibody or portion thereof of claim 23 which is a polyclonal antibody.

27. The isolated antibody or portion thereof of claim 23 which is a chimeric antibody.

28. The isolated antibody or portion thereof of claim 23 which is a humanized antibody.

29. The isolated antibody or portion thereof of claim 23 which is a human antibody.

30. The isolated antibody or portion thereof of claim 23 which is a Fab fragment.

31. The isolated antibody or portion thereof of claim 23 which is labeled.

32. The isolated antibody of claim 31, wherein the label is selected from the group consisting of:

(a) an enzyme label;

(b) a radioisotope; and

(c) a fluorescent label.

33. An isolated cell that produces the isolated antibody of claim 23.

34. A hybridoma that produces the isolated antibody of claim 23.

35. A hybridoma that produces the isolated antibody of claim 25.

36. An isolated antibody or portion thereof that specifically binds to a protein whose sequence consists of the amino acid sequence of the secreted polypeptide encoded by the HFEAF41 cDNA contained in ATCC Deposit Number 97923.

37. The isolated antibody or portion thereof of claim 36, wherein said protein specifically bound by said antibody or portion thereof is glycosylated.

38. The isolated antibody or portion thereof of claim 36 which is a monoclonal antibody.

39. The isolated antibody or portion thereof of claim 36 which is a polyclonal antibody.

40. The isolated antibody or portion thereof of claim 36 which is a chimeric antibody.

41. The isolated antibody or portion thereof of claim 36 which is a humanized antibody.

42. The isolated antibody or portion thereof of claim 36 which is a human antibody.

43. The isolated antibody or portion thereof of claim 36 which is a Fab fragment.

44. The isolated antibody or portion thereof of claim 36 which is labeled.

45. Th e isolated antibody of claim 44, wherein the label is selected from the group consisting of:

(a) an enzyme label;

(b) a radioisotope; and

(c) a fluorescent label.

46. An isolated cell that produces the isolated antibody of claim 36.

47. A hybridoma that produces the isolated antibody of claim 36.

48. A hybridoma that produces the isolated antibody of claim 38.

49. An isolated antibody produced by immunizing an animal with a protein whose sequence comprises the amino acid sequence of the secreted polypeptide encoded by the HFEAF41 cDNA contained in ATCC Deposit Number 97923, wherein said antibody or portion thereof specifically binds to the polypeptide encoded by the HFEAF41 cDNA contained in ATCC Deposit Number 97923.

50. The isolated antibody of claim 49, wherein said protein specifically bound by said antibody is glycosylated.

51. The isolated antibody of claim 49 which is a monoclonal antibody.

52. The isolated antibody of claim 49 which is a polyclonal antibody.

53. The isolated antibody of claim 49 which is labeled.

54. The isolated antibody of claim 53, wherein the label is selected from the group consisting of:

(g) an enzyme label;

(h) a radioisotope; and

(i) a fluorescent label.

55. An isolated cell that produces the isolated antibody of claim 49.

56. A hybridoma that produces the isolated antibody of claim 49.

57. A hybridoma that produces the isolated antibody of claim 51.

58. An isolated antibody or portion thereof that specifically binds to a protein whose sequence consists of the amino acid sequence of the full-length polypeptide encoded by the HFEAF41 cDNA contained in ATCC Deposit Number 97923;

59. The isolated antibody or portion thereof of claim 58 wherein said protein specifically bound by said antibody or portion thereof is glycosylated.

60. The isolated antibody or portion thereof of claim 58 which is a monoclonal antibody.

61. The isolated antibody or portion thereof of claim 58 which is a polyclonal antibody.

62. The isolated antibody or portion thereof of claim 58 which is a chimeric antibody.

63. The isolated antibody or portion thereof of claim 58 which is a humanized antibody.

64. The isolated antibody or portion thereof of claim 58 which is a human antibody.

65. The isolated antibody or portion thereof of claim 58 which is a Fab fragment.

66. The isolated antibody or portion thereof of claim 58 which is labeled.

67. The isolated antibody of claim 66 wherein the label is selected from the group consisting of:

(a) an enzyme label;

a radioisotope; and

(c) a fluorescent label.

68. An isolated cell that produces the isolated antibody of claim 58.

69. A hybridoma that produces the isolated antibody of claim 58.

70. A hybridoma that produces the isolated antibody of claim 60.