CA2379968A1

CA2379968A1 - Gtp-binding protein associated factors

Info

Publication number: CA2379968A1
Application number: CA002379968A
Authority: CA
Inventors: Henry Yue; Y. Tom Tang; Olga Bandman; Jennifer L. Hillman; Preeti Lal; Janice Au-Young; Roopa Reddy; Junming Yang; Mariah R. Baughn; Dyung Aina M. Lu; Yalda Azimzai; Chandra Patterson
Original assignee: Individual
Current assignee: Incyte Corp
Priority date: 1999-07-19
Filing date: 2000-07-19
Publication date: 2001-01-25
Also published as: EP1196575A2; AU6223700A; JP2003505029A; WO2001005970A2; WO2001005970A3

Abstract

The invention provides human GTP-binding associated proteins (GBAP) and polynucleotides which identify and encode GBAP. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for diagnosing, treating, or preventing disorders associated with expression of GBAP.

Description

GTP-BINDING ASSOCIATED PROTEINS
TECHNICAL FIELD
This invention relates to nucleic acid and amino acid sequences of GTP-binding associated proteins and to the use of these sequences in the diagnosis, treatment, and prevention of immune system, reproductive, nervous system, and cell signaling disorders, and cell proliferative disorders including cancer.
BACKGROUND OF THE INVENTION
Guanine nucleotide binding proteins (GTP-binding proteins) are present in all eukaryotic cells and function in processes including metabolism, cellular growth, differentiation, signal transduction, cytoskeletal. organization, and intracellular vesicle transport and secretion.
In higher organisms they are involved in signaling that regulates such processes as the immune response (Aussel, C. et al. (1988) J.
Immunol. 140:215-220), apoptosis, differentiation, and cell proliferation including oncogenesis (Dhanasekaran, N. et al. (1998) Oncogene 17:1383-1394).
The superfamily of GTP-binding proteins can be subdivided into groups such as translational factors, heterotrimeric GTP-binding proteins involved in transmembrane signaling processes (also called G-proteins), proto-oncogene Ras proteins, other low molecular weight GTP-binding proteins including the products of rab, rap, rho, rac, smg2l, smg25, YPT, SEC4, and ARF
genes, and tubulins (Kaziro, Y. et al. (1991) Annu. Rev. Biochem. 60:349-400).
GTP-binding proteins are involved in protein biosynthesis and include initiation factor 2 (IF-2), elongation factor 2 (EF-Tu), and elongation factor G (EF-G), observed in prokaryotes; and initiation factor 2 (eIF-2), elongation factor Ia (EF-Ia), elongation factor 2 (EF-2), and release factor 3 (eRF3) observed in eukaryotes (Kaziro, su ra). IF-2 promotes the GTP-dependent binding of the tRNA to the small subunit of the ribosome, the step that initiates protein translation.
Elongation factors promote the binding of tRNA and GTP and the displacement of GDP after hydrolysis as protein biosynthesis proceeds. eRF3 participates in the recognition of stop codons and the release of nascent proteins from ribosomes.
Heterotrimeric GTP-binding proteins are composed of 3 subunits (a, (3 and y) which, in the resting state, associate as a trimer at the inner face of the plasma membrane.
Heterotrimeric G-proteins may be classified based on the sequence similarity of a subunits into the Gs, Gi, Gq and G12 subgroups. In the resting state, the a subunit binds guanosine diphosphate (GDP), and stimulation of the G-protein by an activated receptor leads to exchange of GDP for guanosine triphosphate (GTP).
This exchange results in the separation of the a from the (3 and y subunits, which remain tightly SUBSTITUTE SHEET (RULE 26) associated as a dimer. Both the a subunit and (3-y dimer are then able to interact with effectors, either individually or in a cooperative manner. The intrinsic GTPase activity of the a subunit hydrolyzes the bound GTP to GDP. This returns the a subunit to its inactive conformation and allows it to reassociate with the (3-y complex, thus restoring the system to its resting state (Kaziro, su ra). Some a subunits show tissue-specific expression indicating a specialized signaling role (Dhanasekaran, supra).
The a-s class of G-protein subunits is sensitive to ADP-ribosylation by pertussis toxin which uncouples the receptor:G-protein interaction. This uncoupling blocks signal transduction to receptors that decrease CAMP levels. cAMP levels regulate ion channels and activate phospholipases. The inhibitory a-I class is also susceptible to modification by pertussis toxin, which prevents a-I from lowering cAMP levels. Two novel classes of a subunits refractory to pertussis toxin modification are a-q, which activates phospholipase C, and a-12, which has sequence homology with the Drosophila gene concertina and may contribute to the regulation of embryonic development (Simon, M.I. (1991) Science 252:802-808).
The mammalian G-protein (3 and y subunits, each about 340 amino acids long, share more than 80% homology. The ~i subunit (also called (3-transducin) contains seven repeating units, each about 43 amino acids long. This WD-repeat, or G-beta repeat motif, is found in a variety of proteins with regulatory function such as Secl3, a yeast WD repeat protein involved in vesicular traffic; coronin-2, a mammalian WD repeat protein involved in regulation of the actin cytoskeleton; and Bopl, a mammalian WD repeat protein involved in growth suppression (Garcia-Higuera, I.
et al. (1998) J.
Biol. Chem. 273:9041-9049; Okumura, M. et al. (1998) DNA Cell Biol. 17:779-787; Pestov, D.G. et al. (1998) Oncogene 17:3187-3197). The activity of the ~3 and y subunits may be regulated by other proteins such as calmodulin, phosducin, or the neural protein GAP 43 (Clapham, D.E. and E.J. Neer (1993) Nature 365:403-406). The ~3 subunit sequences are highly conserved among species, suggesting that they perform a fundamentally important role in the organization and function of G-protein linked systems (Van tier Voorn, L. and H.L. Ploegh (1992) FEBS Lett. 307:131-134).
Mutations and variant expression of (3-transducin proteins are linked with various disorders.
Mutations in LIS 1, a subunit of the human platelet activating factor acetylhydrolase, cause Miller-Dieker lissencephaly. RACKl binds activated protein kinase C, and RbAp48 binds retinoblastoma protein. CstF is required for polyadenylation of mammalian pre-mRNA in vitro and associates with subunits of cleavage-stimulating factor. Defects in the regulation of (3-catenin contribute to the neoplastic transformation of human cells. The WD40 repeats of the human F-box protein (3TrCP
mediate binding to (3-catenin, thus regulating the targeted degradation of (3-catenin by ubiquitin ligase (Neer, E.J. et al. (1994) Nature 371:297-300; Hart, M. et al. (1999) Curr.
Biol. 9:207-210).
The y subunit sequences are more variable than those of the ~i subunits. They are often post-translationally modified by isoprenylation and carboxyl-methylation of a cysteine residue four amino SUBSTITUTE SHEET (RULE 26) acids from the C-terminus. These modifications appear to be necessary for the interaction of the /3-y dimer with the membrane and with other GTP-binding proteins. The (3-'y dimer has been shown to modulate the activity of adenylyl cyclase isoforms, phospholipase C, and some ion channels. It is involved in receptor phosphorylation via specific kinases and has been implicated in the p2lras-dependent activation of the MAP kinase cascade and the recognition of specific receptors by GTP-binding proteins (Clapham and Neer, sera).
G-proteins interact with a variety of effectors including adenylyl cyclase (Clapham and Neer, supra). The signaling pathway mediated by cAMP is mitogenic in hormone-dependent endocrine tissues such as adrenal cortex, thyroid, ovary, pituitary, and testes. Cancers in these tissues have been related to a mutationally activated form of a Gas known as the gsp (Gs protein) oncogene (Dhanasekaran, su ra). Another effector is phosducin, a retinal phosphoprotein, which forms a specific complex with retinal G-protein ~i and ~y subunits and modulates the ability of the (3-y dimer to interact with retinal a subunits (Clapham and Neer, supra). Additional G-protein effectors include RINI (Ras interaction/interference), which acts as an effector of H-Ras and interferes with the Ras signal transduction pathway; Rabin3, which associates with the Ras-like GTPase Rab3A;
and Rhotekin, a protein that binds with, and inhibits, Rho GTPase activity (Han, L. and J.
Colicelli (1995) Mol. Cell Biol. 15:1318-1323; Brondyk, W.H. et al. (1995) Mol. Cell Biol. 15:1137-1143;
and Reid, T. et al.
(1996) J. Biol. Chem. 27:13556-13560).
The low molecular weight GTP-binding proteins regulate cell growth, cell cycle control, protein secretion, and intracellular vesicle interaction. These GTP-binding proteins respond to extracellular signals from receptors and activating proteins by transducing mitogenic signals (Tavitian, A. (1995) C.
R. Seances Soc. Biol. Fil. 189:7-12). Low molecular weight GTP-binding proteins consist of single polypeptides of 21-30kD which, like the a subunit of heterotrimeric GTP-binding proteins, are able to bind to and hydrolyze GTP, thus cycling from an inactive to an active state.
The intrinsic rate of GTP
hydrolysis of these GTP-binding proteins is typically very slow, but it can be stimulated by several orders of magnitude by GTPase-activating proteins (GAPs), such as (32-chimaerin (Geyer, M. and Wittinghofer, A. (1997) Curr. Opin. Struct. Biol. 7:786-792; Caloca, M. J. et al. (1997) J. Biol. Chem.
272:26488-26496).
Low molecular weight GTP-binding proteins play critical roles in cellular protein trafficking events, such as the translocation of proteins and soluble complexes from the cytosol to the membrane through an exchange of GDP for GTP (Ktistakis, N.T. (1998) BioEssays 20:495-504). In vesicle transport, the interaction between vesicle- and target- specific identifiers (v-SNAREs and tSNAREs) docks the vesicle to the acceptor membrane. The budding process is regulated by GTPases such as the closely related ADP ribosylation factors (ARFs) and SAR proteins, while GTPases such as Rab allow assembly of SNARE complexes and may play a role in removal of defective complexes (Rothman, J.E.
SUBSTITUTE SHEET (RULE 26) and F.T. Wieland (1996) Science 272:227-234). The rab proteins control the translocation of vesicles to and from membranes for protein localization, protein processing, and secretion. The rho GTP-binding proteins control signal transduction pathways that link growth factor receptors to actin polymerization which is necessary for normal cellular growth and division. The ran GTP-binding proteins are located in the nucleus of cells and have a key role in nuclear protein import, the control of DNA synthesis, and cell-cycle progression (Hall, A. (1990) Science 249:635-640; Scheffzek, K. et al.
(1995) Nature 374:378-381).
The Ras proteins Rasl, Ras2 and Gsa stimulate adenylyl cyclase (Kaziro, su ra) which affects a broad array of cellular processes including determination of whether cells continue to grow or become terminally differentiated. Stimulation of cell surface receptors activates Ras which, in turn, activates cytoplasmic kinases. These kinases translocate to the nucleus and activate key transcription factors that control gene expression and protein synthesis (Barbacid, M.
(1987) Annu. Rev. Biochem.
56:779-827; Treisman, R. (1994) Curr. Opin. Genet. Dev. 4:96-101). Mutant Ras-family proteins which bind but cannot hydrolyze GTP are permanently activated and are thus rendered oncogenic (Drivas, G.T. et al. (1990) Mol. Cell. Biol. 10:1793-1798).
Ras-like proteins have also been implicated in tumor suppression. For example, NOEY2, a novel gene encoding a Ras-like protein, is expressed in normal ovarian and breast epithelial cells.
However, NOEY2 expression is reduced or abrogated in ovarian and breast carcinomas, suggesting a role for the NOEY2 gene product in tumor suppression (Yu, Y. et al. (1999) Proc. Natl. Acad. Sci.
USA 96:214-219).
Irregularities in GTP-binding protein signaling cascades may result in abnormal activation of leukocytes and lymphocytes, leading to the tissue damage and destruction seen in many inflammatory and autoimmune diseases such as rheumatoid arthritis, biliary cirrhosis, hemolytic anemia, lupus erythematosus, and thyroiditis. Abnormal cell proliferation, including cyclic AMP-mediated stimulation of brain, thyroid, adrenal, and ~gonadal tissue proliferation is regulated by G proteins.
Mutations in Ga subunits have been found in growth-hormone-secreting pituitary somatotroph tumors, hyperfunctioning thyroid adenomas, and ovarian and adrenal neoplasms (Meij, J.T.A. (1996) Mol. Cell. Biochem. 157:31-38; Aussel, supra).
The discovery of new GTP-binding associated proteins and the polynucleotides encoding them satisfies a need in the art by providing new compositions which are useful in the diagnosis, prevention, and treatment of immune system, reproductive, nervous system, and cell signaling disorders, and cell proliferative disorders including cancer.
SUMMARY OF THE INVENTION
The invention features purified polypeptides, GTP-binding associated proteins, referred to SUBSTITUTE SHEET (RULE 26) collectively as "GBAP" and individually as "GBAP-1," "GBAP-2," "GBAP-3," "GBAP-4," "GBAP-" "GBAP-6," "GBAP-7," "GBAP-8," "GBAP-9," "GBAP-10," "GBAP-11," "GBAP-12,"
"GBAP-13," "GBAP-14," "GBAP-15," "GBAP-16," "GBAP-17," "GBAP-18," "GBAP-19," "GBAP-20,"
"GBAP-21," "GBAP-22," "GBAP-23," "GBAP-24," "GBAP-25," "GBAP-26," "GBAP-27,"
5 "GBAP-28," "GBAP-29," "GBAP-30," "GBAP-31," "GBAP-32," "GBAP-33," "GBAP-34,"
"GBAP-35," "GBAP-36," "GBAP-37," "GBAP-38," "GBAP-39," "GBAP-40," "GBAP-41,"
"GBAP-42," "GBAP-43," "GBAP-44," "GBAP-45," "GBAP-46," "GBAP-47," "GBAP-48,"
"GBAP-49," "GBAP-50," "GBAP-51," "GBAP-52," "GBAP-53," "GBAP-54," "GBAP-55,"
"GBAP-56," "GBAP-57," "GBAP-58," "GBAP-59," "GBAP-60," "GBAP-61," "GBAP-62,"
"GBAP-63," "GBAP-64," "GBAP-65," and "GBAP-66." In one aspect, the invention provides an isolated polypeptide comprising an amino acid sequence selected from the group consisting of a) an amino acid sequence selected from the group consisting of SEQ ID NO:l-66, b) a naturally occurring amino acid sequence having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO:1-66, c) a biologically active fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1-66, and d) an immunogenic fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1-66. In one alternative, the invention provides an isolated polypeptide comprising the amino acid sequence of SEQ ID
NO:1-66.
The invention further provides an isolated polynucleotide encoding a polypeptide comprising an amino acid sequence selected from the group consisting of a) an amino acid sequence selected from the group consisting of SEQ ID NO:1-66, b) a naturally occurring amino acid sequence having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO:1-66, c) a biologically active fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1-66, and d) an immunogenic fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1-66. In one alternative, the polynucleotide encodes a polypeptide selected from the group consisting of SEQ ID NO:1-66. In another alternative, the polynucleotide is selected from the group consisting of SEQ ID N0:67-132.
Additionally, the invention provides a recombinant polynucleotide comprising a promoter sequence operably linked to a polynucleotide encoding a polypeptide comprising an amino acid sequence selected from the group consisting of a) an amino acid sequence selected from the group consisting of SEQ ID N0:1-66, b) a naturally occurring amino acid sequence having at least 90%
sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO:1-66, c) a biologically active fragment of an amino acid sequence selected from the group consisting of SEQ ID
NO:1-66, and d) an immunogenic fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1-66. In one alternative, the invention provides a cell transformed with the recombinant polynucleotide. In another alternative, the invention provides a transgenic organism SUBSTITUTE SHEET (RULE 26) comprising the recombinant polynucleotide.
The invention also provides a method for producing a polypeptide comprising an amino acid sequence selected from the group consisting of a) an amino acid sequence selected from the group consisting of SEQ ID NO:1-66, b) a naturally occurring amino acid sequence having at least 90%
sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO:1-66, c) a biologically active fragment of an amino acid sequence selected from the group consisting of SEQ ID
NO:1-66, and d) an immunogenic fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1-66. The method comprises a) culturing a cell under conditions suitable for expression of the polypeptide, wherein said cell is transformed with a recombinant polynucleotide comprising a promoter sequence operably linked to a polynucleotide encoding the polypeptide, and b) recovering the polypeptide so expressed.
Additionally, the invention provides an isolated antibody which specifically binds to a .
polypeptide comprising an amino acid sequence selected from the group consisting of a) an amino acid sequence selected from the group consisting of SEQ ID NO:1-66, b) a naturally occurring amino acid sequence having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO:1-66, c) a biologically active fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1-66, and d) an immunogenic fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1-66.
The invention further provides an isolated polynucleotide comprising a polynucleotide sequence selected from the group consisting of a) a polynucleotide sequence selected from the group consisting of SEQ ID N0:67-132, b) a naturally occurring polynucleotide sequence having at least 70% sequence identity to a polynucleotide sequence selected from the group consisting of SEQ ID N0:67-132, c) a polynucleotide sequence complementary to a), d) a polynucleotide sequence complementary to b), and e) an RNA equivalent of a)-d). In one alternative, the polynucleotide comprises at least 60 contiguous nucleotides.
Additionally, the invention provides a method for detecting a target polynucleotide in a sample, said target polynucleotide having a sequence of a polynucleotide comprising a polynucleotide sequence selected from the group consisting of a) a polynucleotide sequence selected from the group consisting of SEQ ID N0:67-132, b) a naturally occurring polynucleotide sequence having at least 70% sequence identity to a polynucleotide sequence selected from the group consisting of SEQ ID N0:67-132, c) a polynucleotide sequence complementary to a), d) a polynucleotide sequence complementary to b), and e) an RNA equivalent of a)-d). The method comprises a) hybridizing the sample with a probe comprising at least 20 contiguous nucleotides comprising a sequence complementary to said target polynucleotide in the sample, and which probe specifically hybridizes to said target polynucleotide, under conditions whereby a hybridization complex is formed between said probe and said target polynucleotide or SUBSTITUTE SHEET (RULE 26) fragments thereof, and b) detecting the presence or absence of said hybridization complex, and optionally, if present, the amount thereof. In one alternative, the probe comprises at least 60 contiguous nucleotides.
'The invention further provides a method for detecting a target polynucleotide in a sample, said target polynucleotide having a sequence of a polynucleotide comprising a polynucleotide sequence selected from the group consisting of a) a polynucleotide sequence selected from the group consisting of SEQ ID N0:67-132, b) a naturally occurring polynucleotide sequence having at least 70% sequence identity to a polynucleotide sequence selected from the group consisting of SEQ ID N0:67-132, c) a polynucleotide sequence complementary to a), d) a polynucleotide sequence complementary to b), and e) an RNA equivalent of a)-d). The method comprises a) amplifying said target polynucleotide or fragment thereof using polymerase chain reaction amplification, and b) detecting the presence or absence of said amplified target polynucleotide or fragment thereof, and, optionally, if present, the amount thereof.
The invention further provides a composition comprising an effective amount of a polypeptide comprising an amino acid sequence selected from the group consisting of a) an amino acid sequence selected from the group consisting of SEQ ID NO:1-66, b) a naturally occurring amino acid sequence having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO:1-66, c) a biologically active fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1-66, and d) an immunogenic liagment of an amino acid sequence selected from the group consisting of SEQ ID NO:1-66, and a pharmaceutically acceptable excipient In one embodiment, the 1 composition comprises an amino acid sequence selected from the group consisting of SEQ ID NO:l-66. The invention additionally provides a method of treating a disease or condition associated with decreased expression of functional GBAP, comprising administering to a patient in need of such treatment the composition.
The invention also provides a method for screening a compound for effectiveness as an agonist of a polypeptide comprising an amino acid sequence selected from the group consisting of a) an amino acid sequence selected from the group consisting of SEQ ID NO:1-66, b) a naturally occurring amino acid sequence having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO:l-66, c) a biologically active fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1-66, and d) an immunogenic fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1-66. The method comprises a) exposing a sample comprising the polypeptide to a compound, and b) detecting agonist activity in the sample. In one alternative, the invention provides a composition comprising an agonist compound identified by the method and a pharmaceutically acceptable excipient. In another alternative, the invention provides a method of treating a disease or condition associated with decreased expression of SUBSTITUTE SHEET (RULE 26) functional GBAP, comprising administering to a patient in need of such treatment the composition.
Additionally, the invention provides a method for screening a compound for effectiveness as an antagonist of a polypeptide comprising an amino acid sequence selected from the group consisting of a) an amino acid sequence selected from the group consisting of SEQ ID NO:1-66, b) a naturally occurring amino acid sequence having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO:1-66, c) a biologically active fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1-66, and d) an immunogenic fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1-66. The method comprises a) exposing a sample comprising the polypeptide to a compound, and b) detecting antagonist activity in the sample. In one alternative, the invention provides a composition comprising an antagonist compound identified by the method and a pharmaceutically acceptable excipient. In another alternative, the invention provides a method of treating a disease or condition associated with overexpression of functional GBAP, comprising administering to a patient in need of such treatment the composition.
The invention further provides a method of screening for a compound that specifically binds to a polypeptide comprising an amino acid sequence selected from the group consisting of a) an amino acid sequence selected from the group consisting of SEQ ID NO:1-66, b) a naturally occurring amino acid sequence having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO:1-66, c) a biologically active fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1-66, and d) an immunogenic fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1-66. The method comprises a) combining the polypeptide with at least one test compound under suitable conditions, and b) detecting binding of the polypeptide to the test compound, thereby identifying a compound that specifically binds to the polypeptide.
The invention further provides a method of screening for a compound that modulates the activity of a polypeptide comprising an amino acid sequence selected from the group consisting of a) an amino acid sequence selected tiom the group consisting of SEQ ID NO:1-66, b) a naturally occurring amino acid sequence having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO:1-66, c) a biologically active fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1-66, and d) an immunogenic fragment of an amino acid sequence selected from the group consisting of SEQ
ID NO:1-66. The method comprises a) combining the polypeptide with at least one test compound under conditions permissive for the activity of the polypeptide, b) assessing the activity of the polypeptide in the presence of the test compound, and c) comparing the activity of the polypeptide in the presence of the test compound with the activity of the polypeptide in the absence of the test compound, wherein a SUBSTITUTE SHEET (RULE 26) change in the activity of the.polypeptide in the presence of the test compound is indicative of a compound that modulates the activity of the polypeptide.
The invention further provides a method for screening a compound for effectiveness in altering expression of a target polynucleotide, wherein said target polynucleotide comprises a sequence selected from the group consisting of SEQ ID N0:67-132, the method comprising a) exposing a sample comprising the target polynucleotide to a compound, and b) detecting altered expression of the target polynucleotide.
The invention further provides a method for assessing toxicity of a test compound, said method comprising a) treating a biological sample containing nucleic acids with the test compound;
b) hybridizing the nucleic acids of the treated biological sample with a probe comprising at least 20 contiguous nucleotides of a polynucleotide comprising a polynucleotide sequence selected from the group consisting of i) a polynucleotide sequence selected from the group consisting of SEQ ID
N0:67-132, ii) a naturally occurring polynucleotide sequence having at least 70% sequence identity to a polynucleotide sequence selected from the group consisting of SEQ ID
N0:67-132, iii) a polynucleotide sequence complementary to i), iv) a polynucleotide sequence complementary to ii), and v) an RNA equivalent of i)-iv). Hybridization occurs under conditions whereby a specific hybridization complex is formed between said probe and a target polynucleotide in the biological sample, said target polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID N0:67-132, ii) a naturally occurring polynucleotide sequence having at least 70% sequence identity to a polynucleotide sequence selected from the group consisting of SEQ ID
N0:67-132, iii) a polynucleotide sequence complementary to i), iv) a polynucleotide sequence complementary to ii), and v) an RNA equivalent of i)-iv). Alternatively, the target polynucleotide comprises a fragment of the above polynucleotide sequence; c) quantifying the amount of hybridization complex; and d) comparing the amount of hybridization complex in the treated biological sample with the amount of hybridization complex in an untreated biological sample, wherein a difference in the amount of hybridization complex in the treated biological sample is indicative of toxicity of the test compound.
BRIEF DESCRIPTION OF THE TABLES
Table 1 shows polypeptide and nucleotide sequence identification numbers (SEQ
ID NOs), clone identification numbers (clone IDs), cDNA libraries, and cDNA fragments used to assemble full-length sequences encoding GBAP.
Table 2 shows features of each polypeptide sequence, including potential motifs, homologous sequences, and methods, algorithms, and searchable databases used for analysis of GBAP.
Table 3 shows selected fragments of each nucleic acid sequence; the tissue-specific expression SUBSTITUTE SHEET (RULE 26) patterns of each nucleic acid sequence as determined by northern analysis;
diseases, disorders, or conditions associated with these tissues; and the vector into which each cDNA
was cloned.
Table 4 describes the tissues used to construct the eDNA libraries from which cDNA clones encoding GBAP were isolated.
Table 5 shows the tools, programs, and algorithms used to analyze the polynucleotides and polypeptides of the invention, along with applicable descriptions, references, and threshold parameters.
DESCRIPTION OF THE INVENTION
Before the present proteins, nucleotide sequences, and methods are described, it is understood that this invention is not limited to the particular machines, materials and methods described, as these may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention which will be limited only by the appended claims.
It must be noted that as used herein and in the appended claims, the singular forms "a," "an,"
and "the" include plural reference unless the context clearly dictates otherwise. Thus, for example, a reference to "a host cell" includes a plurality of such host cells, and a reference to "an antibody" is a reference to one or more antibodies and equivalents thereof known to those skilled in the art, and so forth.
Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any machines, materials, and methods similar or equivalent to those described herein can be used to practice or test the present invention, the preferred machines, materials and methods are now described.
All publications mentioned herein are cited for the purpose of describing and disclosing the cell lines, protocols, reagents and vectors which are reported in the publications and which might be used in connection with the invention. Nothing herein is to be construed as an admission that the invention is not entitled to antedate such disclosure by virtue of prior invention.
DEFINITIONS
"GBAP" refers to the amino acid sequences of substantially purified GBAP
obtained from any species, particularly a mammalian species, including bovine, ovine, porcine, murine, equine, and human, and from any source, whether natural, synthetic, semi-synthetic, or recombinant.
The term "agonist" refers to a molecule which intensifies or mimics the biological activity of GBAP. Agonists may include proteins, nucleic acids, carbohydrates, small molecules, or any other compound or composition which modulates the activity of GBAP either by directly interacting with GBAP or by acting on components of the biological pathway in which GBAP
participates.
An "allelic variant" is an alternative form of the gene encoding GBAP. Allelic variants may SUBSTITUTE SHEET (RULE 26) result from at least one mutation in the nucleic acid sequence and may result in altered mRNAs or in polypeptides whose structure or function may or may not be altered. A gene may have none, one, or many allelic variants of its naturally occurring form. Common mutational changes which give rise to allelic variants are generally ascribed to natural deletions, additions, or substitutions of nucleotides.
Each of these types of changes may occur alone, or in combination with the others, one or more times in a given sequence.
"Altered" nucleic acid sequences encoding GBAP include those sequences with deletions, insertions, or substitutions of different nucleotides, resulting in a polypeptide the same as GBAP or a polypeptide with at least one functional characteristic of GBAP. Included within this definition are polymorphisms which may or may not be readily detectable using a particular oligonucleotide probe of the polynucleotide encoding GBAP, and improper or unexpected hybridization to allelic variants, with a locus other than the normal chromosomal locus for the polynucleotide sequence encoding GBAP. The encoded protein may also be "altered," and may contain deletions, insertions, or substitutions of amino acid residues which produce a silent change and result in a functionally equivalent GBAP. Deliberate amino acid substitutions may be made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity, and/or the amphipathic nature of the residues, as long as the biological or immunological activity of GBAP is retained. For example, negatively charged amino acids may include aspartic acid and glutamic acid, and positively charged amino acids may include lysine and arginine. Amino acids with uncharged polar side chains having similar hydrophilicity values may include: asparagine and glutamine; and serine and threonine. Amino acids with uncharged side chains having similar hydrophilicity values may include: leucine, isoleucine, and valine; glycine and alanine;
and phenylalanine and tyrosine.
The terms "amino acid" and "amino acid sequence" refer to an oligopeptide, peptide, polypeptide, or protein sequence, or a fragment of any of these, and to naturally occurring or synthetic molecules. Where "amino acid sequence" is recited to refer to a sequence of a naturally occurring protein molecule, "amino acid sequence" and like terms are not meant to limit the amino acid sequence to the complete native amino acid sequence associated with the recited protein molecule.
"Amplification" relates to the production of additional copies of a nucleic acid sequence.
Amplification is generally carried out using polymerase chain reaction (PCR) technologies well known in the art.
The term "antagonist" refers to a molecule which inhibits or attenuates the biological activity of GBAP. Antagonists may include proteins such as antibodies, nucleic acids, carbohydrates, small molecules, or any other compound or composition which modulates the activity of GBAP either by directly interacting with GBAP or by acting on components of the biological pathway in which GBAP
participates.

SUBSTITUTE SHEET (RULE 26) The term "antibody" refers to intact immunoglobulin molecules as well as to fragments thereof, such as Fab, F(ab')2, and Fv fragments, which are capable of binding an epitopic determinant.
Antibodies that bind GBAP polypeptides can be prepared using intact polypeptides or using fragments containing small peptides of interest as the immunizing antigen. The polypeptide or oligopeptide used to immunize an animal (e.g., a mouse, a rat, or a rabbit) can be derived from the translation of RNA, or synthesized chemically, and can be conjugated to a carrier protein if desired.
Commonly used carriers that are chemically coupled to peptides include bovine serum albumin, thyroglobulin, and keyhole limpet hemocyanin (KLH). The coupled peptide is then used to immunize the animal.
The term "antigenic determinant" refers to that region of a molecule (i.e., an epitope) that makes contact with a particular antibody. When a protein or a fragment of a protein is used to immunize a host animal, numerous regions of the protein may induce the production of antibodies which bind specifically to antigenic determinants (particular regions or three-dimensional structures on the protein). An antigenic determinant may compete with the intact antigen (i.e., the immunogen used to elicit the immune response) for binding to an antibody.
The term "antisense" refers to any composition capable of base-pairing with the "sense"
(coding) strand of a specific nucleic acid sequence. Antisense compositions may include DNA; RNA;
peptide nucleic acid (PNA); oligonucleotides having modified backbone linkages such as phosphorothioates, methylphosphonates, or benzylphosphonates; oligonucleotides having modified sugar groups such as 2'-methoxyethyl sugars or 2'-methoxyethoxy sugars; or oligonucleotides having modified bases such as 5-methyl cytosine, 2'-deoxyuracil, or 7-deaza-2'-deoxyguanosine. Antisense molecules may be produced by any method including chemical synthesis or transcription. Once introduced into a cell, the complementary antisense molecule base-pairs with a naturally occurring nucleic acid sequence produced by the cell to form duplexes which block either transcription or translation. The designation "negative" or "minus" can refer to the antisense strand, and the designation "positive" or "plus" can refer to the sense strand of a reference DNA molecule.
The term "biologically active" refers to a protein having structural, regulatory, or biochemical functions of a naturally occurring molecule. Likewise, "immunologically active" or "immunogenic"
refers to the capability of the natural, recombinant, or synthetic GBAP, or of any oligopeptide thereof, to induce a specific immune response in appropriate animals or cells and to bind with specific antibodies.
"Complementary" describes the relationship between two single-stranded nucleic acid sequences that anneal by base-pairing. For example, 5'-AGT-3' pairs with its complement, 3'-TCA-5'.
A "composition comprising a given polynucleotide sequence" and a "composition comprising a given amino acid sequence" refer broadly to any composition containing the given polynucleotide or SUBSTITUTE SHEET (RULE 26) amino acid sequence. The composition may comprise a dry formulation or an aqueous solution.
Compositions comprising polynucleotide sequences encoding GBAP or fragments of GBAP may be employed as hybridization probes. The probes may be stored in freeze-dried form and may be associated with a stabilizing agent such as a carbohydrate. In hybridizations, the probe may be deployed in an aqueous solution containing salts (e.g., NaCl), detergents (e.g., sodium dodecyl sulfate;
SDS), and other components (e.g., Denhardt's solution, dry milk, salmon sperm DNA, etc.).
"Consensus sequence" refers to a nucleic acid sequence which has been subjected to repeated DNA sequence analysis to resolve uncalled bases, extended using the XL-PCR kit (PE Biosystems, Foster City CA) in the 5' and/or the 3' direction, and resequenced, or which has been assembled from one or more overlapping cDNA, EST, or genomic DNA fragments using a computer program for fragment assembly, such as the GELVIEW fragment assembly system (GCG, Madison WI) or Phrap (University of Washington, Seattle WA). Some sequences have been both extended and assembled to produce the consensus sequence.
"Conservative amino acid substitutions" are those substitutions that are predicted to least interfere with the properties of the original protein, i.e., the structure and especially the function of the protein is conserved and not significantly changed by such substitutions. The table below shows amino acids which may be substituted for an original amino acid in a protein and which are regarded as conservative amino acid substitutions.
Original Residue Conservative Substitution Ala Gly, Ser ~'g His, Lys ~n Asp, Gln, His ~p Asn, Glu Cys Ala, Ser Gln Asn, Glu, His Glu Asp, Gln, His Gly Ala His Asn, Arg, Gln, Glu Ile Leu, Val Leu 11e, Val Lys Arg, Gln, Glu Met Leu, Ile Phe His, Met, Leu, Trp, Tyr Ser Cys, Thr Thr Ser, Val TrP Phe, Tyr TYr His, Phe, Trp Val Ile, Leu, Thr Conservative amino acid substitutions generally maintain (a) the structure of the polypeptide backbone in the area of the substitution, for example, as a beta sheet or alpha helical conformation, (b) the charge or hydrophobicity of the molecule at the site of the substitution, and/or (c) the bulk of the SUBSTITUTE SHEET (RULE 26) side chain.
A "deletion" refers to a change in the amino acid or nucleotide sequence that results in the absence of one or more amino acid residues or nucleotides.
The term "derivative" refers to a chemically modified polynucleotide or polypeptide. Chemical modifications of a polynucleotide sequence can include, for example, replacement of hydrogen by an alkyl, acyl, hydroxyl, or amino group. A derivative polynucleotide encodes a polypeptide which retains at least one biological or immunological function of the natural molecule. A
derivative polypeptide is one modified by glycosylation, pegylation, or any similar process that retains at least one biological or immunological function of the polypeptide from which it was derived.
A "detectable label" refers to a reporter molecule or enzyme that is capable of generating a measurable signal and is covalently or noncovalently joined to a polynucleotide or polypeptide.
A "fragment" is a unique portion of GBAP or the polynucleotide encoding GBAP
which is identical in sequence to but shorter in length than the parent sequence. A
fragment may comprise up to the entire length of the defined sequence, minus one nucleotide/amino acid residue. For example, a fragment may comprise from 5 to 1000 contiguous nucleotides or amino acid residues. A fragment used as a probe, primer, antigen, therapeutic molecule, or for other purposes, may be at least 5, 10, 15, 16, 20, 25, 30, 40, 50, 60, 75, 100, 150, 250 or at least 500 contiguous nucleotides or amino acid residues in length. Fragments may be preferentially selected from certain regions of a molecule. For example, a polypeptide fragment may comprise a certain length of contiguous amino acids selected fiom the first 250 or 500 amino acids (or first 25% or 50% of a polypeptide) as shown in a certain defined sequence. Clearly these lengths are exemplary, and any length that is supported by the specification, including the Sequence Listing, tables, and figures, may be encompassed by the present embodiments.
A fragment of SEQ ID N0:67-132 comprises a region of unique polynucleotide sequence that specifically identifies SEQ ID N0:67-132, for example, as distinct from any other sequence in the genome liom which the fragment was obtained. A fragment of SEQ ID N0:67-132 is useful, for example, in hybridization and amplification technologies and in analogous methods that distinguish SEQ ID N0:67-132 from related polynucleotide sequences. The precise length of a fragment of SEQ
ID N0:67-132 and the region of SEQ ID N0:67-132 to which the liagment corresponds are routinely determinable by one of ordinary skill in the art based on the intended purpose for the fragment.
A fragment of SEQ ID NO:1-66 is encoded by a fragment of SEQ ID N0:67-132. A
fragment of SEQ ID NO:1-66 comprises a region of unique amino acid sequence that specifically identifies SEQ ID NO:1-66. For example, a fragment of SEQ ID NO:1-66 is useful as an immunogenic peptide for the development of antibodies that specifically recognize SEQ ID NO:1-66.
The precise length of a fragment of SEQ ID NO:l-66 and the region of SEQ ID
NO:1-66 to which the SUBSTITUTE SHEET (RULE 26) fragment corresponds are routinely determinable by one of ordinary skill in the art based on the intended purpose for the fragment.
A "full-length" polynucleotide sequence is one containing at least a translation initiation codon (e.g., methionine) followed by an open reading frame and a translation termination codon. A "full-y length" polynucleotide sequence encodes a "full-length" polypeptide sequence.
"Homology" refers to sequence similarity or, interchangeably, sequence identity, between two or more polynucleotide sequences or two or more polypeptide sequences.
The terms "percent identity" and "% identity," as applied to polynucleotide sequences, refer to the percentage of residue matches between at least two polynucleotide sequences aligned using a standardized algorithm. Such an algorithm may insert, in a standardized and reproducible way, gaps in the sequences being compared in order to optimize alignment between two sequences, and therefore achieve a more meaningful comparison of the two sequences.
Percent identity between polynucleotide sequences may be determined using the default parameters of the CLUSTAL V algorithm as incorporated into the MEGALIGN
version 3.12e sequence alignment program. This program is part of the LASERGENE software package, a suite of molecular biological analysis programs (DNASTAR, Madison WI). CLUSTAL V is described in Higgins, D.G.
and P.M. Sharp (1989) CABIOS 5:151-153 and in Higgins, D.G. et al. ,(1992) CABIOS 8:189-191.
For pairwise alignments of polynucleotide sequences, the default parameters are set as follows:
Ktuple=2, gap penalty=5, window=4, and "diagonals saved"=4. The "weighted"
residue weight table is selected as the default. Percent identity is reported by CLUSTAL V as the "percent similarity" between aligned polynucleotide sequences.
Alternatively, a suite of commonly used and freely available sequence comparison algorithms is provided by the National Center for Biotechnology Information (NCBI) Basic Local Alignment Search Tool (BLAST) (Altschul, S.F. et al. (1990) J. Mol. Biol. 215:403-410), which is available from several sources, including the NCBI, Bethesda, MD, and on the Internet at http://www.ncbi.nlm.nih.gov/BLAST/. The BLAST software suite includes various sequence analysis programs including "blastn," that is used to align a known polynucleotide sequence with other polynucleotide sequences from a variety of databases. Also available is a tool called "BLAST 2 Sequences" that is,used for direct pairwise comparison of two nucleotide sequences. "BLAST 2 Sequences" can be accessed and used interactively at http://www.ncbi.nlm.nih.gov/gorf/bl2.html. The "BLAST 2 Sequences" tool can be used for both blastn and blastp (discussed below). BLAST
programs are commonly used with gap and other parameters set to default settings. For example, to compare two nucleotide sequences, one may use blastn with the "BLAST 2 Sequences" tool Version 2Ø12 (April-21-2000) set at default parameters. Such default parameters may be, for example:
Matrix: BLOSUM62 SUBSTITUTE SHEET (RULE 26) Reward for match: 1 Penalty for mismatch: -2 Open Gap: 5 and Extension Gap: 2 penalties Gap x drop-off. 50 Expect: l0 Word Size: 11 Filter: on Percent identity may be measured over the length of an entire defined sequence, for example, as defined by a particular SEQ ID number, or may be measured over a shorter length, for example, over the length of a fragment taken liom a larger, defined sequence, for instance, a fragment of at least 20, at least 30, at least 40, at least 50, at least 70, at least 100, or at least 200 contiguous nucleotides. Such lengths are exemplary only, and it is understood that any fragment length supported by the sequences shown herein, in the tables, figures, or Sequence Listing, may be used to describe a length over which percentage identity may be measured.
Nucleic acid sequences that do not show a high degree of identity may nevertheless encode similar amino acid sequences due to the degeneracy of the genetic code. It is understood that changes in a nucleic acid sequence can be made using this degeneracy to produce multiple nucleic acid sequences that all encode substantially the same protein.
The phrases "percent identity" and "% identity," as applied to polypeptide sequences, refer to the percentage of residue matches between at least two polypeptide sequences aligned using a standardized algorithm. Methods of polypeptide sequence alignment are well-known. Some alignment methods take into account conservative amino acid substitutions. Such conservative substitutions, explained in more detail above, generally preserve the charge and hydrophobicity at the site of substitution, thus preserving the structure (and therefore function) of the polypeptide.
Percent identity between polypeptide sequences may be determined using the default parameters of the CLUSTAL V algorithm as incorporated into the MEGALIGN version 3.12e sequence alignment program (described and referenced above). For pairwise alignments of polypeptide sequences using CLUSTAL V, the default parameters are set as follows: Ktuple=1, gap penalty=3, window=5, and "diagonals saved"=5. The PAM250 matrix is selected as the default residue weight table. As with polynucleotide alignments, the percent identity is reported by CLUSTAL V as the "percent similarity"
between aligned polypeptide sequence pairs.
Alternatively the NCBI BLAST software suite may be used. For example, for a pairwise comparison of two polypeptide sequences, one may use the "BLAST 2 Sequences"
tool Version 2Ø12 (Apr-21-2000) with blastp set at default parameters. Such default parameters may be, for example:
Matrix: BLOSUM62 SUBSTITUTE SHEET (RULE 26) Open Gap: 11 and Extension Gap: 1 penalties Gap x drop-off.' S0 Expect: 10 Word Size: 3 Filter: on Percent identity may be measured over the length of an entire defined polypeptide sequence, for example, as defined by a particular SEQ ID number, or may be measured over a shorter length, for example, over the length of a fragment taken from a larger, defined polypeptide sequence, for instance, a fragment of at least 15, at least 20, at least 30, at least 40, at least 50, at least 70 or at least 150 contiguous residues. Such lengths are exemplary only, and it is understood that any fragment length supported by the sequences shown herein, in the tables, figures or Sequence Listing, may be used to describe a length over which percentage identity may be measured.
"Human artificial chromosomes" (HACs) are linear microchromosomes which may contain DNA sequences of about 6 kb to 10 Mb in size, and which contain all of the elements required for chromosome replication, segregation and maintenance.
The term "humanized antibody" refers to an antibody molecule in which the amino acid sequence in the non-antigen binding regions has been altered so that the antibody more closely resembles a human antibody, and still retains its original binding ability.
"Hybridization" refers to the process by which a polynucleotide strand anneals with a complementary strand through base pairing under defined hybridization conditions. Specific hybridization is an indication that two nucleic acid sequences share a high degree of complementarity.
Specific hybridization complexes form under permissive annealing conditions and remain hybridized after the "washing" step(s). The washing steps) is particularly important in determining the stringency of the hybridization process, with more stringent conditions allowing less non-specific binding, i.e., binding between pairs of nucleic acid strands that are not perfectly matched.
Permissive conditions for annealing of nucleic acid sequences are routinely determinable by one of ordinary skill in the art and may be consistent among hybridization experiments, whereas wash conditions may be varied among experiments to achieve the desired stringency, and therefore hybridization specificity. Permissive annealing conditions occur, for example, at 68°C in the presence of about 6 x SSC, about 1 % (w/v) SDS, and about 100 ~~ml sheared, denatured salmon sperm DNA.
Generally, stringency of hybridization is expressed, in part, with reference to the temperature under which the wash step is carried out. Such wash temperatures are typically selected to be about 5°C to 20°C lower than the thermal melting point (T~ for the specific sequence at a defined ionic strength and pH. The Tm is the temperature (under defined ionic strength and pH) at which 50% of the target sequence hybridizes to a perfectly matched probe. An equation for calculating Tm and conditions SUBSTITUTE SHEET (RULE 26) for nucleic acid hybridization are well known and can be found in Sambrook, J.
et al., 1989, Molecular Cloning: A Laboratory Manual, 2°d ed., vol. 1-3, Cold Spring Harbor Press, Plainview NY; specifically see volume 2, chapter 9.
High stringency conditions for hybridization between polynucleotides of the present invention include wash conditions of 68°C in the presence of about 0.2 x SSC and about 0.1 % SDS, for 1 hour.
Alternatively, temperatures of about 65°C, 60°C, 55°C, or 42°C may be used. SSC concentration may be varied from about 0.1 to 2 x SSC, with SDS being present at about 0.1 %.
Typically, blocking reagents are used to block non-specific hybridization. Such blocking reagents include, for instance, sheared and denatured salmon sperm DNA at about 100-200 pg~ml. Organic solvent, such as formamide at a concentration of about 35-50% v/v, may also be used under particular circumstances, such as for RNA:DNA hybridizations. Useful variations on these wash conditions will be readily apparent to those of ordinary skill in the art. Hybridization, particularly under high stringency conditions, may be suggestive of evolutionary similarity between the nucleotides. Such similarity is strongly indicative of a similar role for the nucleotides and their encoded polypeptides.
The term "hybridization complex" refers to a complex formed between two nucleic acid sequences by virtue of the formation of hydrogen bonds between complementary bases. A hybridization complex may be formed in solution (e.g., Cot or Rot analysis) or formed between one nucleic acid sequence present in solution and another nucleic acid sequence immobilized on a solid support (e.g., paper, membranes, filters, chips, pins or glass slides, or any other appropriate substrate to which cells or their nucleic acids have been fixed).
The words "insertion" and "addition" refer to changes in an amino acid or nucleotide sequence resulting in the addition of one or more amino acid residues or nuclwtides, respectively.
"Immune response" can refer to conditions associated with inflammation, trauma, immune disorders, or infectious or genetic disease, etc. These conditions can be characterized by expression of various factors, e.g., cytokines, chemokines, and other signaling molecules, which may affect cellular and systemic defense systems.
An "immunogenic fiagment" is a polypeptide or oligopeptide fragment of GBAP
which is capable of eliciting an immune response when introduced into a living organism, for example, a mammal. The term "immunogenic fragment" also includes any polypeptide or oligopeptide fragment of GBAP which is useful in any of the antibody production methods disclosed herein or known in the art.
The term "microarray" refers to an arrangement of a plurality of polynucleotides, polypeptides, or other chemical compounds on a substrate.
The terms "element" and "array element" refer to a polynucleotide, polypeptide, or other chemical compound having a unique and defined position on a microarray.
The term "modulate" refers to a change in the activity of GBAP. For example, modulation SUBSTITUTE SHEET (RULE 26) may cause an increase or a decrease in protein activity, binding characteristics, or any other biological, functional, or immunological properties of GBAP.
The phrases "nucleic acid" and "nucleic acid sequence" refer to a nucleotide, oligonucleotide, polynucleotide, or any fragment thereof. These phrases also refer to DNA or RNA of genomic or synthetic origin which may be single-stranded or double-stranded and may represent the sense or the antisense strand, to peptide nucleic acid (PNA), or to any DNA-like or RNA-like material.
"Operably linked" refers to the situation in which a first nucleic acid sequence is placed in a functional relationship with a second nucleic acid sequence. For instance, a promoter is operably linked to a coding sequence if the promoter affects.the transcription or expression of the coding sequence. Operably linked DNA sequences may be in close proximity or contiguous and, where necessary to join two protein coding regions, in the same reading frame.
"Peptide nucleic acid" (PNA) refers to an antisense molecule or anti-gene agent which comprises an oligonucleotide of at least about 5 nucleotides in length linked to a peptide backbone of amino acid residues ending in lysine. The terminal lysine confers solubility to the composition. PNAs preferentially bind complementary single stranded DNA or RNA and stop transcript elongation, and may be pegylated to extend their lifespan in the cell.
"Post-translational modification" of an GBAP may involve lipidation, glycosylation, phosphorylation, acetylation, racemization, proteolytic cleavage, and other modifications known in the art. These processes may occur synthetically or biochemically. Biochemical modifications will vary by cell type depending on the enzymatic milieu of GBAP.
"Probe" refers to nucleic acid sequences encoding GBAP, their complements, or fragments thereof, which are used to detect identical, allelic or related nucleic acid sequences. Probes are isolated oligonucleotides or polynucleotides attached to a detectable label or reporter molecule. Typical labels include radioactive isotopes, ligands, chemiluminescent agents, and enzymes. "Primers" are short nucleic acids, usually DNA oligonucleotides, which may be annealed to a target polynucleotide by complementary base-pairing. The primer may then be extended along the target DNA strand by a DNA
polymerise enzyme. Primer pairs can be used for amplification (and identification) of a nucleic acid sequence, e.g., by the polymerise chain reaction (PCR).
Probes and primers as used in the present invention typically comprise at least 15 contiguous nucleotides of a known sequence. In order to enhance specificity, longer probes and primers may also be employed, such as probes and primers that comprise at least 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, or at least 150 consecutive nucleotides of the disclosed nucleic acid sequences. Probes and primers may be considerably longer than these examples, and it is understood that any length supported by the specification, including the tables, figures, and Sequence Listing, may be used.
Methods for preparing and using probes and primers are described in the references, for SUBSTITUTE SHEET (RULE 26) example Sambrook, J. et al., 1989, Molecular Cloning: A Laboratory Manual, 2°d ed., vol. 1-3, Cold Spring Harbor Press, Plainview NY; Ausubel, F.M. et a1.,1987, Current Protocols in Molecular Biolo , Greene Publ. Assoc. & Wiley-Intersciences, New York NY; Innis, M. et al., 1990, PCR
Protocols A Guide to Methods and Applications, Academic Press, San Diego CA.
PCR primer pairs can be derived from a known sequence, for example, by using computer programs intended for that purpose such as Primer (Version 0.5, 1991, Whitehead Institute for Biomedical Research, Cambridge MA).
Oligonucleotides for use as primers are selected using software known in the art for such purpose. For example, OLIGO 4.06 software is useful for the selection of PCR
primer pairs of up to 100 nucleotides each, and for the analysis of oligonucleotides and larger polynucleotides of up to 5,000 nucleotides from an input polynucleotide sequence of up to 32 kilobases.
Similar primer selection programs have incorporated additional features for expanded capabilities. For example, the PrimOU
primer selection program (available to the public from the Genome Center at University of Texas South West Medical Center, Dallas TX) is capable of choosing specific primers from megabase sequences and is thus useful for designing primers on a genome-wide scope. The Primer3 primer selection program (available to the public from the Whitehead Institute/MIT Center for Genome Research, Cambridge MA) allows the user to input a "mispriming library," in which sequences to avoid as primer binding sites are user-specified. Primer3 is useful, in particular, for the selection of oligonucleotides for microarrays. (The source code for the latter two primer selection programs may also be obtained from their respective sources and modified to meet the user's specific needs.) The PrimeGen program (available to the public from the UK Human Genome Mapping Project Resource Centre, Cambridge UK) designs primers based on multiple sequence alignments, thereby allowing selection of primers that hybridize to either the most conserved or least conserved regions of aligned nucleic acid sequences.
Hence, this program is useful for identification of both unique and conserved oligonucleotides and polynucleotide fragments. The oligonucleotides and polynucleotide fragments identified by any of the above selection methods are useful in hybridization technologies, for example, as PCR or sequencing primers, microarray elements, or specific probes to identify fully or partially complementary polynucleotides in a sample of nucleic acids. Methods of oligonucleotide selection are not limited to those described above.
A "recombinant nucleic acid" is a sequence that is not naturally occurring or has a sequence that is made by an artificial combination of two or more otherwise separated segments of sequence.
This artificial combination is often accomplished by chemical synthesis or, more commonly, by the artificial manipulation of isolated segments of nucleic acids, e.g., by genetic engineering techniques such as those described in Sambrook, su ra. The term recombinant includes nucleic acids that have been altered solely by addition, substitution, or deletion of a portion of the nucleic acid. Frequently, a SUBSTITUTE SHEET (RULE 26) recombinant nucleic acid may include a nucleic acid sequence operably linked to a promoter sequence.
Such a recombinant nucleic acid may be part of a vector that is used, for example, to transform a cell.
Alternatively, such recombinant nucleic acids may be part of a viral vector, e.g., based on a vaccinia virus, that could be use to vaccinate a mammal wherein the recombinant nucleic acid is expressed, inducing a protective immunological response in the mammal.
A "regulatory element" refers to a nucleic acid sequence usually derived from untranslated regions of a gene and includes enhancers, promoters, introns, and 5' and 3' untranslated regions (UTRs~.
Regulatory elements interact with host or viral proteins which control transcription, translation, or RNA
stability.
"Reporter molecules" are chemical or biochemical moieties used for labeling a nucleic acid, amino acid, or antibody. Reporter molecules include radionuclides; enzymes;
fluorescent, chemiluminescent, or chromogenic agents; substrates; cofactors; inhibitors;
magnetic particles; and other moieties known in the art.
An "RNA equivalent," in reference to a DNA sequence, is composed of the same linear sequence of nucleotides as the reference DNA sequence with the exception that all occurrences of the nitrogenous base thymine are replaced with uracil, and the sugar backbone is composed of ribose instead of deoxyribose.
The term "sample" is used in its broadest sense. A sample suspected of containing nucleic acids encoding GBAP, or tiagments thereof, or GBAP itself, may comprise a bodily fluid; an extract from a cell, chromosome, organelle, or membrane isolated tiom a cell; a cell;
genomic DNA, RNA, or cDNA, in solution or bound to a substrate; a tissue; a tissue print; etc.
The terms "specific binding" and "specifically binding" refer to that interaction between. a protein or peptide and an agonist, an antibody, an antagonist, a small molecule, or any natural or synthetic binding composition. The interaction is dependent upon the presence of a particular structure of the protein, e.g., the antigenic determinant or epitope, recognized by the binding molecule. For example, if an antibody is specific for epitope "A," the presence of a polypeptide comprising the epitope A, or the presence of free unlabeled A, in a reaction containing free labeled A and the antibody will reduce the amount of labeled A that binds to the antibody.
The term "substantially purified" refers to nucleic acid or amino acid sequences that are removed from their natural environment and are isolated or separated, and are at least 60% free, preferably at least 75% free, and most preferably at least 90% free from other components with which they are naturally associated.
A "substitution" refers to the replacement of one or more amino acid residues or nucleotides by different amino acid residues or nucleotides, respectively.
"Substrate" refers to any suitable rigid or semi-rigid support including membranes, filters, SUBSTITUTE SHEET (RULE 26) chips, slides, wafers, fibers, magnetic or nonmagnetic beads, gels, tubing, plates, polymers, microparticles and capillaries. The substrate can have a variety of surface forms, such as wells, trenches, pins, channels and pores, to which polynucleotides or polypeptides are bound.
A "transcript image" refers to the collective pattern of gene expression by a particular cell type or tissue under given conditions at a given time.
"Transformation" describes a process by which exogenous DNA is introduced into a recipient cell. Transformation may occur under natural or artificial conditions according to various methods well known in the art, and may rely on any known method for the insertion of foreign nucleic acid sequences into a prokaryotic or eukaryotic host cell. The method for transformation is selected based on the type of host cell being transformed and may include, but is not limited to, bacteriophage or viral infection, electroporation, heat shock, lipofection, and particle bombardment. The term "transformed" cells includes stably transformed cells in which the inserted DNA is capable of replication either as an autonomously replicating plasmid or as part of the host chromosome, as well as transiently transformed cells which express the inserted DNA or RNA for limited periods of time.
A "transgenic organism," as used herein, is any organism, including but not limited to animals and plants, in which one or more of the cells of the organism contains heterologous nucleic acid introduced by way of human intervention, such as by transgenic techniques well known in the art. The nucleic acid is introduced into the cell, directly or indirectly by introduction into a precursor of the cell, by way of deliberate genetic manipulation, such as by microinjection or by infection with a recombinant virus. The term genetic manipulation does not include classical cross-breeding, or in vitro fertilization, but rather is directed to the introduction of a recombinant DNA molecule. The transgenic organisms contemplated in accordance with the present invention include bacteria, cyanobacteria, fungi, plants, and animals. The isolated DNA of the present invention can be introduced into the host by methods known in the art, for example infection, transfection, transformation or transconjugation. Techniques for transferring the DNA of the present invention into such organisms are widely known and provided in references such as Sambrook et al. (1989), su ra.
A "variant" of a particular nucleic acid sequence is defined as a nucleic acid sequence having at least 40% sequence identity to the particular nucleic acid sequence over a certain length of one of the nucleic acid sequences using blastn with the "BLAST 2 Sequences" tool Version 2Ø9 (May-07-1999) set at default parameters. Such a pair of nucleic acids may show, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95% or at least 98% or greater sequence identity over a certain defined length. A variant may be described as, for example, an "allelic"
(as defined above), "splice," "species," or "polymorphic" variant. A splice variant may have significant identity to a reference molecule, but will generally have a greater or lesser number of polynucleotides SUBSTITUTE SHEET (RULE 26) due to alternative splicing of exons during mRNA processing. The corresponding polypeptide may possess additional functional domains or lack domains that are present in the reference molecule.
Species variants are polynucleotide sequences that vary from one species to another. The resulting polypeptides generally will have significant amino acid identity relative to each other. A polymorphic variant is a variation in the polynucleotide sequence of a particular gene between individuals of a given species. Polymorphic variants also may encompass "single nucleotide polymorphisms" (SNPs) in which the polynucleotide sequence varies by one nucleotide base. The presence of SNPs may be indicative of, for example, a certain population, a disease state, or a propensity for a disease state.
A "variant" of a particular polypeptide sequence is defined as a polypeptide sequence having at least 40% sequence identity to the particular polypeptide sequence over a certain length of one of the polypeptide sequences using blastp with the "BLAST 2 Sequences" tool Version 2Ø9 (May-07-1999) set at default parameters. Such a pair of polypeptides may show, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98%
or greater sequence identity over a certain defined length of one of the polypeptides.

The invention is based on the discovery of new human GTP-binding associated proteins (GBAP), the polynucleotides encoding GBAP, and the use of these compositions for the diagnosis, treatment, or prevention of immune system, reproductive, nervous system, and cell signaling disorders, and cell proliferative disorders including cancer.
Table 1 lists the Incyte clones used to assemble full length nucleotide sequences encoding GBAP. Columns 1 and 2 show the sequence identification numbers (SEQ ID NOs) of the polypeptide and nucleotide sequences, respectively. Column 3 shows the clone IDs of the Incyte clones in which nucleic acids encoding each GBAP were identified, and column 4 shows the eDNA
libraries from which these clones were isolated. Column 5 shows Incyte clones and their corresponding cDNA libraries.
Clones for which cDNA libraries are not indicated were derived from pooled cDNA libraries. In some cases, GenBank sequence identifiers are also shown in column 5. The Incyte clones and GenBank cDNA sequences, where indicated, in column 5 were used to assemble the consensus nucleotide sequence of each GBAP and are useful as fragments in hybridization technologies.
The columns of Table 2 show various properties of each of the polypepddes of the invention:
column 1 references the SEQ ID NO; column 2 shows the number of amino acid residues in each polypeptide; column 3 shows potential phosphorylation sites; column 4 shows potential glycosylation sites; column 5 shows the amino acid residues comprising signature sequences and motifs; column 6 shows homologous sequences as identified by BLAST analysis; and column 7 shows analytical methods and in some cases, searchable databases to which the analytical methods were applied. The methods of column 7 were used to characterize each polypeptide through sequence homology and protein motifs.

SUBSTITUTE SHEET (RULE 26) The columns of Table 3 show the tissue-specificity and diseases, disorders, or conditions associated with nucleotide sequences encoding GBAP. The first column of Table 3 lists the nucleotide SEQ ID NOs. Column 2 lists fragments of the nucleotide sequences of column 1.
These liagments are useful, for example, in hybridization or amplification technologies to identify SEQ ID N0:67-132 and to distinguish between SEQ ID N0:67-132 and related polynucleotide sequences.
The polypeptides encoded by these fragments are useful, for example, as immunogenic peptides.
Column 3 lists tissue categories which express GBAP as a fraction of total tissues expressing GBAP.
Column 4 lists diseases, disorders, or conditions associated with those tissues expressing GBAP as a fraction of total tissues expressing GBAP. Column 5 lists the vectors used to subclone each cDNA
library. Of particular note is the expression of SEQ ID N0:84 in lung tissues, and the tissue-specific expression of SEQ ID N0:132. Over 90% of tissues expressing SEQ ID N0:132 are derived from the nervous system, particularly the brain.
The columns of Table 4 show descriptions of the tissues used to construct the cDNA libraries from which cDNA clones encoding GBAP were isolated. Column 1 references the nucleotide SEQ ID
IS NOs, column 2 shows the cDNA libraries from which these clones were isolated, and column 3 shows the tissue origins and other descriptive information relevant to the cDNA
libraries in column 2.
SEQ ID N0:70 maps to chromosome 7 within the interval liom 111.6 to 123.4 centiMorgans.
This interval contains a gene that is down regulated in adenoma. SEQ ID N0:74 maps to chromosome 11 within the interval from 104.8 to 123.5 centiMorgans. This interval contains a gene associated with the cerebellar degenerative disorder, ataxia telangiectasia. SEQ ID N0:75 maps to chromosome 17 within the interval from 62.9 to 65.0 centiMorgans. SEQ ID N0:77 maps to chromosome 3 within the interval from 12.9 to 16.5 centiMorgans. SEQ ID N0:80 maps to chromosome 9 within the interval from 42.0 to 57.3 centiMorgans. SEQ ID N0:86 maps to chromosome 1 within the interval from 159.6 to 164.1 centiMorgans. SEQ ID N0:87 maps to chromosome 11 within the interval from 147.2 to 151.6. SEQ ID N0:90 maps to chromosome 1 within the interval from 219.2 to 223.0 centiMorgans.
This interval contains a gene encoding a RAB interacting protein. SEQ ID N0:92 and SEQ ID
N0:106 both map to chromosome 1 within the interval from 48.8 to 81.6 centiMorgans. This interval also contains genes associated with familial hypercholesterolemia, glucose transport defect, infantile hypophosphatasia, infantile neuronal ceroid lipofuscinosis, Kostmann disease, multiple epiphyseal dysplasia, porphyria cutanea tarda, and T-cell acute lymphocytic leukemia 1.
SEQ ID N0:93 maps to chromosome 12 within the interval from 76.5 to 87.6 centiMorgans. This interval also contains genes associated with mucopolysaccharidosis type IIID, pseudovitamin D deficiency rickets, and renal amyloidosis. SEQ ID N0:94 and SEQ ID N0:109 both map to chromosome 1 within the interval from 143.1 to 146.6 centiMorgans, to chromosome 14 within the interval from 46.8 to 50.9 centiMorgans, to chromosome 16 within the interval from 88.1 to 90.2 centiMorgans, and to chromosome 19 within the SUBSTITUTE SHEET (RULE 26) interval from 58.7 to 97.5 centiMorgans. The interval on chromosome 14 from 46.8 to 50.9 centiMorgans also contains a gene associated with dopa-responsive dystonia.
The interval on chromosome 19 from 58.7 to 97.5 centiMorgans also contains genes associated with colorectal cancer, DNA ligase I deficiency, glutaricaciduria IIB, myotonic dystrophy, renal amyloidosis, T-cell acute lymphoblastic leukemia, and xeroderma pigmentosum D. SEQ ID N0:97 maps to chromosome 2 within the interval from 236.2 to 269.5 centiMorgans. This interval also contains genes associated with Crigler-Najjar syndrome, familial hypercholesterolemia, Oguchi disease, and primary hyperoxaluria.
SEQ ID NO:101 maps to chromosome 2 within the interval from 225.6 to 233.1 centiMorgans, to chromosome 6 within the interval from 132.7 to 144.4 centiMorgans, and to chromosome 11 within the interval from 117.9 to 120.8 centiMorgans. The interval on chromosome 2 from 225.6 to 233.1 centiMorgans also contains a gene associated with Waardenburg syndrome 1. The interval on chromosome 6 from 132.7 to 144.4 centiMorgans also contains genes associated with familial disseminated atypical mycobacterial infection and rhizomelic chondrodysplasia punctata. The interval on chromosome 11 from 117.9 to 120.8 centiMorgans also contains a gene associated with acute intermittent porphyria. SEQ ID NO:111 maps to chromosome 19 within the interval from 35.5 to 49.4 centiMorgans, to chromosome 1 within the interval from the p-terminus to 16.4 centiMorgans, and to chromosome 11 within the interval from 147.2 centiMorgans to the q-terminus.
SEQ ID N0:112 maps to chromosome 19 within the interval from 41.7 to 49.4 centiMorgans. SEQ ID
N0:113 maps to chromosome 9 within the interval from 136.2 to 163.0 centiMorgans. SEQ ID
NO:115 maps to chromosome 14 within the interval from 95.5 to 103.7 centiMorgans and to the X
chromosome (23) within the interval from the p-terminus to 55.5 centiMorgans. SEQ ID N0:117 maps to chromosome 13 at 46.9 centiMorgans. SEQ ID N0:118 maps to chromosome 1 within the interval from 16.4 to 22.9 centiMorgans. SEQ ID N0:121 maps to chromosome 12 within the interval from 116.6 to 118.9 centiMorgans. SEQ ID N0:128 maps to chromosome 1 within the interval from the p-terminus to 16.4 centiMorgans.
The invention also encompasses GBAP variants. A preferred GBAP variant is one which has at least about 80%, or alternatively at least about 90%, or even at least about 95% amino acid sequence identity to the GBAP amino acid sequence, and which contains at least one functional or structural characteristic of GBAP.
The invention also encompasses polynucleotides which encode GBAP. In a particular embodiment, the invention encompasses a polynucleotide sequence comprising a sequence selected from the group consisting of SEQ ID N0:67-132, which encodes GBAP. The polynucleotide sequences of SEQ ID N0:67-132, as presented in the Sequence Listing, embrace the equivalent RNA sequences, wherein occurrences of the nitrogenous base thynune are replaced with uracil, and the sugar backbone is composed of ribose instead of deoxyribose.
SUBSTITUTE SHEET (RULE 26) The invention also encompasses a variant of a polynucleotide sequence encoding GBAP. In particular, such a variant polynucleotide sequence will have at least about 70%, or alternatively at least about 85%, or even at least about 95% polynucleotide sequence identity to the polynucleotide sequence encoding GBAP. A particular aspect of the invention encompasses a variant of a polynucleotide sequence comprising a sequence selected from the group consisting of SEQ ID
N0:67-132 which has at least about 70%, or alternatively at least about 85%, or even at least about 95% polynucleotide sequence identity to a nucleic acid sequence selected from the group consisting of SEQ ID N0:67-132.
Any one of the polynucleotide variants described above can encode an amino acid sequence which contains at least one functional or structural characteristic of GBAP.
It will be appreciated by those skilled in the art that as a result of the degeneracy of the genetic code, a multitude of polynucleotide sequences encoding GBAP, some bearing minimal similarity to the polynucleotide sequences of any known and naturally occurring gene, may be produced. Thus, the invention contemplates each and every possible variation of polynucleotide sequence that could be made by selecting combinations based on possible colon choices. These combinations are made in accordance with the standard triplet genetic code as applied to the polynucleotide sequence of naturally occurring GBAP, and all such variations are to be considered as being specifically disclosed.
Although nucleotide sequences which encode GBAP and its variants are generally capable of hybridizing to the nucleotide sequence of the naturally occurring GBAP under appropriately selected conditions of stringency, it may be advantageous to produce nucleotide sequences encoding GBAP or its derivatives possessing a substantially different colon usage, e.g., inclusion of non-naturally occurring colons. Colons may be selected to increase the rate at which expression of the peptide occurs in a particular prokaryotic or eukaryotic host in accordance with the frequency with which particular colons are utilized by the host. Other reasons for substantially altering the nucleotide sequence encoding GBAP and its derivatives without altering the encoded amino acid sequences include the production of RNA transcripts having more desirable properties, such as a greater half-life, than transcripts produced from the naturally occurring sequence.
The invention also encompasses production of DNA sequences which encode GBAP
and GBAP derivatives, or fragments thereof, entirely by synthetic chemistry. After production, the synthetic sequence may be inserted into any of the many available expression vectors and cell systems using reagents well known in the art. Moreover, synthetic chemistry may be used to introduce mutations into a sequence encoding GBAP or any fragment thereof.
Also encompassed by the invention are polynucleotide sequences that are capable of hybridizing to the claimed polynucleotide sequences, and, in particular, to those shown in SEQ ID
N0:67-132 and fragments thereof under various conditions of stringency. (See, e.g., Wahl, G.M. and S.L. Berger (1987) Methods Enzymol. 152:399-407; Kimmel, A.R. (1987) Methods Enzymol.

SUBSTITUTE SHEET (RULE 26) 152:507-511.) Hybridization conditions, including annealing and wash conditions, are described in "Definitions."
Methods for DNA sequencing are well known in the art and may be used to practice any of the embodiments of the invention. The methods may employ such enzymes as the Klenow fragment of DNA polymerise I, SEQUENASE (US Biochemical, Cleveland OH), Taq polymerise (PE
Biosystems, Foster City CA), thermostable T7 polymerise (Amersham Pharmacia Biotech, Piscataway NJ), or combinations of polymerises and proofreading exonucleases such as those found in the ELONGASE
amplification system (Life Technologies, Gaithersburg MD). Preferably, sequence preparation is automated with machines such as the MICROLAB 2200 liquid transfer system (Hamilton, Reno NV), PTC200 thermal cycler (MJ Research, Watertown MA) and ABI CATALYST 800 thermal cycler (PE
Biosystems). Sequencing is then carried out using either the ABI 373 or 377 DNA sequencing system (PE Biosystems), the MEGABACE 1000 DNA sequencing system (Molecular Dynamics, Sunnyvale CA), or other systems known in the art. The resulting sequences are analyzed using a variety of algorithms which are well known in the art. (See, e.g., Ausubel, F.M. (1997) Short Protocols in Molecular BioloQV, John Wiley & Sons, New York NY, unit 7.7; Meyers, R.A.
(1995) Molecular Biolo~y and Biotechnolo~y, Wiley VCH, New York NY, pp. 856-853.) The nucleic acid sequences encoding GBAP may be extended utilizing a partial nucleotide sequence and employing various PCR-based methods known in the art to detect upstream sequences, such as promoters and regulatory elements. For example, one method which may be employed, restriction-site PCR, uses universal and nested primers to amplify unknown sequence from genomic DNA within a cloning vector. (See, e.g., Sarkar, G. (1993) PCR Methods Applic.
2:318-322.) Another method, inverse PCR, uses primers that extend in divergent directions to amplify unknown sequence from a circularized template. The template is derived from restriction fragments comprising a known genomic locus and surrounding sequences. (See, e.g., Triglia, T. et al.
(1988) Nucleic Acids Res. 16:8186.) A third method, capture PCR, involves PCR amplification of DNA
fragments adjacent to known sequences in human and yeast artificial chromosome DNA. (See, e.g., Lagerstrom, M. et al.
(1991) PCR Methods Applic. 1:111-119.) In this method, multiple restriction enzyme digestions and ligations may be used to insert an engineered double-stranded sequence into a region of unknown sequence before performing PCR. Other methods which may be used to retrieve unknown sequences are known in the art. (See, e.g., Parker, J.D. et al. (1991) Nucleic Acids Res. 19:3055-3060).
Additionally, one may use PCR, nested primers, and PROMOTERFINDER libraries (Clontech, Palo Alto CA) to walk genomic DNA. This procedure avoids the need to screen libraries and is useful in finding intron/exon junctions. For all PCR-based methods, primers may be designed using commercially available software, such as OLIGO 4.06 Primer Analysis software (National Biosciences, Plymouth MN) or another appropriate program, to be about 22 to 30 nucleotides in length, to have a SUBSTITUTE SHEET (RULE 26) GC content of about 50% or more, and to anneal to the template at temperatures of about 68°C to 72°C.
When screening for full-length cDNAs, it is preferable to use libraries that have been size-selected to include larger cDNAs. In addition, random-primed libraries, which often include sequences containing the 5' regions of genes, are preferable for situations in which an oligo d(T) library does not yield a full-length cDNA. Genomic libraries may be useful for extension of sequence into 5' non-transcribed regulatory regions.
Capillary electrophoresis systems which are commercially available may be used to analyze the size or confirm the nucleotide sequence of sequencing or PCR products. In particular, capillary sequencing may employ flowable polymers for electrophoretic separation, four different nucleotide-specific, laser-stimulated fluorescent dyes, and a charge coupled device camera for detection of the emitted wavelengths. Output/light intensity may be converted to electrical signal using appropriate software (e.g., GENOTYPER and SEQUENCE NAVIGATOR, PE Biosystems), and the entire process from loading of samples to computer analysis and electronic data display may be computer controlled. Capillary electrophoresis is especially preferable for sequencing small DNA fragments which may be present in limited amounts in a particular sample.
In another embodiment of the invention, polynucleotide sequences or fragments thereof which encode GBAP may be cloned in recombinant DNA molecules that direct expression of GBAP, or fragments or functional equivalents thereof, in appropriate host cells. Due to the inherent degeneracy of the genetic code, other DNA sequences which encode substantially the same or a functionally equivalent amino acid sequence may be produced and used to express GBAP.
The nucleotide sequences of the present invention can be engineered using methods generally known in the art in order to alter GBAP-encoding sequences for a variety of purposes including, but not limited to, modification of the cloning, processing, and/or expression of the gene product. DNA
shuffling by random fragmentation and PCR reassembly of gene fragments and synthetic oligonucleotides may be used to engineer the nucleotide sequences. For example, oligonucleotide-mediated site-directed mutagenesis may be used to introduce mutations that create new restriction sites, alter glycosylation patterns, change codon preference, produce splice variants, and so forth.
The nucleotides of the present invention may be subjected to DNA shuffling techniques such as MOLECULARBREEDING (Maxygen lnc., Santa Clara CA; described in U.S. Patent Number 5,837,458; Chang, C.-C. et al. (1999) Nat. Biotechnol. 17:793-797; Christians, F.C. et al. (1999) Nat.
Biotechnol. 17:259-264; and Crameri, A. et al. (1996) Nat. Biotechnol. 14:315-319) to alter or improve the biological properties of GBAP, such as its biological or enzymatic activity or its ability to bind to other molecules or compounds. DNA shuffling is a process by which a library of gene variants is produced using PCR-mediated recombination of gene fragments. The library is then SUBSTITUTE SHEET (RULE 26) subjected to selection or screening procedures that,identify those gene variants with the desired properties. These preferred variants may then be pooled and further subjected to recursive rounds of DNA shuffling and selection/screening. Thus, genetic diversity is created through "artificial"
breeding and rapid molecular evolution. For example, fragments of a single gene containing random point mutations may be recombined, screened, and then reshuffled until the desired properties are optimized. Alternatively, fragments of a given gene may be recombined with fragments of homologous genes in the same gene family, either from the same or different species, thereby maximizing the genetic diversity of multiple naturally occurnng genes in a directed and controllable manner.
In another embodiment, sequences encoding GBAP may be synthesized, in whole or in part, using chemical methods well known in the art. (See, e.g., Caruthers, M.H. et al. (1980) Nucleic Acids Symp. Ser. 7:215-223; and Horn, T. et al. (1980) Nucleic Acids Symp. Ser.
7:225-232.) Alternatively, GBAP itself or a fragment thereof may be synthesized using chemical methods.
For example, peptide synthesis can be performed using various solution-phase or solid-phase techniques. (See, e.g., Creighton, T. (1984) Proteins Structures and Molecular Properties, WH Freeman, New York NY, pp.
55-60; and Roberge, J.Y. et al. (1995) Science 269:202-204.) Automated synthesis may be achieved using the ABI 431A peptide synthesizer (PE Biosystems). Additionally, the amino acid sequence of GBAP, or any part thereof, may be altered during direct synthesis and/or combined with sequences from other proteins, or any part thereof, to produce a variant polypeptide or a polypeptide having a sequence of a naturally occurring polypeptide.
The peptide may be substantially purified by preparative high performance liquid chromatography. (See, e.g., Chiez, R.M. and F.Z. Regnier (1990) Methods Enzymol. 182:392-421.) The composition of the synthetic peptides may be confirmed by amino acid analysis or by sequencing.
(See, e.g., Creighton, supra, pp. 28-53.) In order to express a biologically active GBAP, the nucleotide sequences encoding GBAP or derivatives thereof may be inserted into an appropriate expression vector, i.e., a vector which contains the necessary elements for transcriptional and translational control of the inserted coding sequence in a suitable host. These elements include regulatory sequences, such as enhancers, constitutive and inducible promoters, and 5' and 3' untranslated regions in the vector and in polynucleotide sequences encoding GBAP. Such elements may vary in their strength and specificity.
Specific initiation signals may also be used to achieve more efficient translation of sequences encoding GBAP. Such signals include the ATG initiation codon and adjacent sequences, e.g. the Kozak sequence. In cases where sequences encoding GBAP and its initiation codon and upstream regulatory sequences are inserted into the appropriate expression vector, no additional transcriptional or translational control signals may be needed. However, in cases where only coding sequence, or a fragment thereof, is inserted, exogenous SUBSTITUTE SHEET (RULE 26) translational control signals including an in-frame ATG initiation codon should be provided by the vector. Exogenous translational elements and initiation codons may be of various origins, both natural and synthetic. The efficiency of expression may be enhanced by the inclusion of enhancers appropriate for the particular host cell system used. (See, e.g., Scharf, D. et al. (1994) Results Probl. Cell Differ.
20:125-162.) Methods which are well known to those skilled in the art may be used to construct expression vectors containing sequences encoding GBAP and appropriate transcriptional and translational control elements. These methods include in vitro recombinant DNA techniques, synthetic techniques, and in vivo genetic recombination. (See, e.g., Sambrook, J. et al. (1989) Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Press, Plainview NY, ch. 4, 8, and 16-17; Ausubel, F.M. et al. (1995) Current Protocols in Molecular Biolo~y, John Wiley & Sons, New York NY, ch. 9, 13, and 16.) A variety of expression vector/host systems may be utilized to contain and express sequences encoding GBAP. These include, but are not limited to, microorganisms such as bacteria transformed with recombinant bacteriophage, plasmid, or cosmid DNA expression vectors;
yeast transformed with yeast expression vectors; insect cell systems infected with viral expression vectors (e.g., baculovirus);
plant cell systems transformed with viral expression vectors (e.g., cauliflower mosaic virus, CaMV, or tobacco mosaic virus, TMV) or with bacterial expression vectors (e.g., Ti or pBR322 plasmids); or animal cell systems. (See, e.g., Sambrook, supra; Ausubel, su ra; Van Heeke, G. and S.M. Schuster (1989) J. Biol. Chem. 264:5503-5509; Bitter, G.A. et al. (1987) Methods Enzymol. 153:516-544;
Scorer, C.A. et al. (1994) Bio/Technology 12:181-184; Engelhard, E.K. et al.
(1994) Proc. Natl.
Acad. Sci. USA 91:3224-3227; Sandig, V. et al. (1996) Hum. Gene Ther. 7:1937-1945; Takamatsu, N. (1987) EMBO J. 6:307-311; Coruzzi, G. et al. (1984) EMBO J. 3:1671-1680;
Broglie, R. et al.
(1984) Science 224:838-843; Winter, J. et al. (1991) Results Probl. Cell Differ. 17:85-105; The McGraw Hill Yearbook of Science and Technology (1992) McGraw Hill, New York NY, pp.
191-196; Logan, J. and T. Shenk (1984) Proc. Natl. Acad. Sci. USA 81:3655-3659; and Harrington, J.J. et al. (1997) Nat. Genet. 15:345-355.) Expression vectors derived from retroviruses, adenoviruses, or herpes or vaccinia viruses, or from various bacterial plasmids; may be used for delivery of nucleotide sequences to the targeted organ, tissue, or cell population. (See, e.g., Di Nicola, M. et al. (1998) Cancer Gen. Ther. 5(6):350-356; Yu, M. et al., (1993) Proc. Natl. Acad. Sci. .
USA 90(13):6340-6344; Buller, R.M. et al. (1985) Nature 317(6040):813-815;
McGregor, D.P, et al.
(1994) Mol. Immunol. 31(3):219-226; and Verma, LM. and N. Somia (1997) Nature 389:239-242.) The invention is not limited by the host cell employed.
In bacterial systems, a number of cloning and expression vectors may be selected depending upon the use intended for polynucleotide sequences encoding GBAP. For example, routine cloning, subcloning, and propagation of polynucleotide sequences encoding GBAP can be achieved using a SUBSTITUTE SHEET (RULE 26) multifunctional E. coli vector such as PBLUESCRIPT (Stratagene, La Jolla CA) or PSPORT1 plasmid (Life Technologies). Ligation of sequences encoding GBAP into the vector's multiple cloning site disrupts the lacZ gene, allowing a colorimetric screening procedure for identification of transformed bacteria containing recombinant molecules. In addition, these vectors may be useful for in vitro transcription, dideoxy sequencing, single strand rescue with helper phage, and creation of nested deletions in the cloned sequence. (See, e.g., Van Heeke, G. and S.M. Schuster (1989) J. Biol. Chem.
264:5503-5509.) When large quantities of GBAP are needed, e.g. for the production of antibodies, vectors which direct high level expression of GBAP may be used. For example, vectors containing the strong, inducible T5 or T7 bacteriophage promoter may be used.
Yeast expression systems may be used for production of GBAP. A number of vectors containing constitutive or inducible promoters, such as alpha factor, alcohol oxidase, and PGH
promoters, may be used in the yeast Saccharomyces cerevisiae or Pichia pastoris. In addition, such vectors direct either the secretion or intracellular retention of expressed proteins and enable integration of foreign sequences into the host genome for stable propagation. (See, e.g., Ausubel, 1995, supra;
Bitter, supra; and Scorer, supra.) Plant systems may also be used for expression of GBAP. Transcription of sequences encoding GBAP may be driven viral promoters, e.g., the 35S and 19S promoters of CaMV
used alone or in combination with the omega leader sequence from TMV (Takamatsu, N. (1987) EMBO
J. 6:307-311).
Alternatively, plant promoters such as the small subunit of RUBISCO or heat shock promoters may be used. (See, e.g., Coruzzi, supra; Brogue, su ra; and Winter, supra.) These constructs can be introduced into plant cells by direct DNA transformation or pathogen-mediated transfection. (See, e.g., The McGraw Hill Yearbook of Science and Technolo~y (1992) McGraw Hill, New York NY, pp.
191-196.) In mammalian cells, a number of viral-based expression systems may be utilized. In cases where an adenovirus is used as an expression vector, sequences encoding GBAP
may be ugated into an adenovirus transcription/translation complex consisting of the late promoter and tripartite leader sequence. Insertion in a non-essential E1 or E3 region of the viral genome may be used to obtain infective virus which expresses GBAP in host cells. (See, e.g., Logan, J. and T. Shenk (1984) Proc.
Natl. Acad. Sci. USA 81:3655-3659.) In addition, transcription enhancers, such as the Rous sarcoma virus (RSV) enhancer, may be used to increase expression in mammalian host cells. SV40 or EBV-based vectors may also be used for high-level protein expression.
Human artificial chromosomes (HACs) may also be employed to deliver larger fragments of DNA than can be contained in and expressed lrom a plasmid. HACs of about 6 kb to 10 Mb are constructed and delivered via conventional delivery methods (liposomes, polycationic amino polymers, or vesicles) for therapeutic purposes. (See, e.g., Harrington, J.J. et al.
(1997) Nat. Genet. 15:345-355.) SUBSTITUTE SHEET (RULE 26) For long term production of recombinant proteins in mammalian systems, stable expression of GBAP in cell lines is preferred. For example, sequences encoding GBAP can be transformed into cell lines using expression vectors which may contain viral origins of replication and/or endogenous expression elements and a selectable marker gene on the same or on a separate vector. Following the introduction of the vector, cells may be allowed to grow for about 1 to 2 days in enriched media before being switched to selective media. The purpose of the selectable marker is to confer resistance to a selective agent, and its presence allows growth and recovery of cells which successfully express the introduced sequences. Resistant clones of stably transformed cells may be propagated using tissue culture techniques appropriate to the cell type.
Any number of selection systems may be used to recover transformed cell lines.
These include, but are not limited to, the herpes simplex virus thymidine kinase and adenine phosphoribosyltransferase genes, for use in tk- and apr cells, respectively. (See, e.g., Wigler, M. et al. (1977) Cell 11:223-232;
Lowy, I. et al. (1980) Cell 22:817-823.) Also, antimetabolite, antibiotic, or herbicide resistance can be used as the basis for selection. For example, dhfr confers resistance to methotrexate; neo confers resistance to the aminoglycosides neomycin and G-418; and als and pat confer resistance to chlorsulfuron and phosphinotricin acetyltransferase, respectively. (See, e.g., Wigler, M. et al. (1980) Proc. Natl. Acad. Sci. USA 77:3567-3570; Colbere-Garapin, F. et al. (1981) J.
Mol. Biol. 150:1-14.) Additional selectable genes have been described, e.g., trpB and hisD, which alter cellular requirements for metabolites. (See, e.g., Hartman, S.C. and R.C. Mulligan (1988) Proc.
Natl. Acad. Sci. USA
85:8047-8051.) Visible markers, e.g., anthocyanins, green fluorescent proteins (GFP; Clontech), B
glucuronidase and its substrate li-glucuronide, or luciferase and its substrate luciferin may be used.
These markers can be used not only to identify transformants, but also to quantify the amount of transient or stable protein expression attributable to a specific vector system. (See, e.g., Rhodes, C.A.
(1995) Methods Mol. Biol. 55:121-131.) Although the presence/absence of marker gene expression suggests that the gene of interest is also present, the presence and expression of the gene may need to be confirmed. For example, if the sequence encoding GBAP is inserted within a marker gene sequence, transformed cells containing sequences encoding GBAP can be identified by the absence of marker gene function. Alternatively, a marker gene can be placed in tandem with a sequence encoding GBAP under the control of a single promoter. Expression of the marker gene in response to induction or selection usually indicates expression of the tandem gene as well.
In general, host cells that contain the nucleic acid sequence encoding GBAP
and that express GBAP may be identified by a variety of procedures known to those of skill in the art. These procedures include, but are not limited to, DNA-DNA or DNA-RNA hybridizations, PCR
amplification, and protein bioassay or immunoassay techniques which include membrane, solution, or chip based SUBSTITUTE SHEET (RULE 26) technologies for the detection and/or quantification of nucleic acid or protein sequences.
Immunological methods for detecting and measuring the expression of GBAP using either specific polyclonal or monoclonal antibodies are known in the art. Examples of such techniques include enzyme-linked immunosorbent assays (ELISAs), radioimmunoassays (RIAs), and fluorescence activated cell sorting (FACS). A two-site, monoclonal-based immunoassay utilizing monoclonal antibodies reactive to two non-interfering epitopes on GBAP is preferred, but a competitive binding assay may be employed. These and other assays are well known in the art. (See, e.g., Hampton, R. et al. (1990) Seroloeical Methods a Laboratory Manual, APS Press, St. Paul MN, Sect. IV; Coligan, J.E.
et al. (1997) Current Protocols in Immunolo~y, Greene Pub. Associates and Wiley-Interscience, New York NY; and Pound, J.D. (1998) Immunochemical Protocols, Humana Press, Totowa NJ.) A wide variety of labels and conjugation techniques are known by those skilled in the art and may be used in various nucleic acid and amino acid assays. Means for producing labeled hybridization or PCR probes for detecting sequences related to polynucleotides encoding GBAP
include oligolabeling, nick translation, end-labeling, or PCR amplification using a labeled nucleotide. Alternatively, the sequences encoding GBAP, or any fragments thereof, may be cloned into a vector for the production of an mRNA probe. Such vectors are known in the art, are commercially available, and may be used to synthesize RNA probes in vitro by addition of an appropriate RNA polymerase such as T7, T3, or SP6 and labeled nucleotides. These procedures may be conducted using a variety of commercially available kits, such as those provided by Amersham Pharmacia Biotech, Promega (Madison WI), and US
Biochemical. Suitable reporter molecules or labels which may be used for ease of detection include radionuclides, enzymes, fluorescent, chemiluminescent, or chromogenic agents, as well as substrates, cofactors, inhibitors, magnetic particles, and the like.
Host cells transformed with nucleotide sequences encoding GBAP may be cultured under conditions suitable for the expression and recovery of the protein from cell culture. The protein produced by a transformed cell may be secreted or retained intracellularly depending on the sequence and/or the vector used. As will be understood by those of skill in the art, expression vectors containing polynucleotides which encode GBAP may be designed to contain signal sequences which direct secretion of GBAP through a prokaryotic or eukaryotic cell membrane.
In addition, a host cell strain may be chosen for its ability to modulate expression of the inserted sequences or to process the expressed protein in the desired fashion.
Such modifications of the polypeptide include, but are not limited to, acetylation, carboxylation, glycosylation, phosphorylation, lipidation, and acylation. Post-translational processing which cleaves a "prepro" or "pro" form of the protein may also be used to specify protein targeting, folding, and/or activity. Different host cells which have specific cellular machinery and characteristic mechanisms for post-translational activities (e.g., CHO, HeLa, MDCK, HEK293, and WI38) are available from the American Type Culture SUBSTITUTE SHEET (RULE 26) Collection (ATCC, Manassas VA) and may be chosen to ensure the correct modification and processing of the foreign protein.
In another embodiment of the invention, natural, modified, or recombinant nucleic acid sequences encoding GBAP may be ligated to a heterologous sequence resulting in translation of a fusion protein in any of the aforementioned host systems. For example, a chimeric GBAP protein containing a heterologous moiety that can be recognized by a commercially available antibody may facilitate the screening of peptide libraries for inhibitors of GBAP activity. Heterologous protein and peptide moieties may also facilitate purification of fusion proteins using commercially available affinity matrices. Such moieties include, but are not limited to, glutathione S-transferase (GST), maltose binding protein (MBP), thioredoxin (Trx), calmodulin binding peptide (CBP), 6-His, FLAG, c-rrcyc, and hemagglutinin (HA). GST, MBP, Trx, CBP, and 6-His enable purification of their cognate fusion proteins on immobilized glutathione, maltose, phenylarsine oxide, calmodulin, and metal-chelate resins, respectively. FLAG, c-myc, and hemagglutinin (HA) enable immunoaffinity purification of fusion proteins using commercially available monoclonal and polyclonal antibodies that 'specifically recognize these epitope tags. A fusion protein may also be engineered to contain a proteolytic cleavage site located between the GBAP encoding sequence and the heterologous protein sequence, so that GBAP
may be cleaved away from the heterologous moiety following purification.
Methods for fusion protein expression and purification are discussed in Ausubel (1995, su ra, eh. 10). A
variety of commercially available kits may also be used to facilitate expression and purification of fusion proteins.
In a further embodiment of the invention, synthesis of radiolabeled GBAP may be achieved in vitro using the TNT rabbit reticulocyte lysate or wheat germ extract system (Promega). These systems couple transcription and translation of protein-coding sequences operably associated with the T7, T3, or SP6 promoters. Translation takes place in the presence of a radiolabeled amino acid precursor, for example, 35S-methionine.
GBAP of the present invention or fragments thereof may be used to screen for compounds that specifically bind to GBAP. At least one and up to a plurality of test compounds may be screened for specific binding to GBAP. Examples of test compounds include antibodies, oligonucleotides, proteins (e.g., receptors), or small molecules.
In one embodirrient, the compound thus identified is closely related to the natural ligand of GBAP, e.g., a ligand or fragment thereof, a natural substrate, a structural or functional mimetic, or a natural binding partner. (See, Coligan, J.E. et al. (1991) Current Protocols in Immunolo~y 1(2):
Chapter 5.) Similarly, the compound can be closely related to the natural receptor to which GBAP
binds, or to at least a fragment of the receptor, e.g., the ligand binding site. In either case, the compound can be rationally designed using known techniques. In one embodiment, screening for these compounds involves producing appropriate cells which express GBAP, either as a secreted SUBSTITUTE SHEET (RULE 26) protein or on the cell membrane. Preferred cells include cells from mammals, yeast, Drosophila, or E.
coli. Cells expressing GBAP or cell membrane fractions which contain GBAP are then contacted with a test compound and binding, stimulation, or inhibition of activity of either GBAP or the compound is analyzed.
An assay may simply test binding of a test compound to the polypeptide, wherein binding is detected by a fluorophore, radioisotope, enzyme conjugate, or other detectable label. For example, the assay may comprise the steps of combining at least one test compound with GBAP, either in solution or affixed to a solid support, and detecting the binding of GBAP to the compound.
Alternatively, the assay may detect or measure binding of a test compound in the presence of a labeled competitor. Additionally, the assay may be carried out using cell-free preparations, chemical libraries, or natural product mixtures, and the test compounds) may be free in solution or affixed to a solid support.
GBAP of the present invention or fragments thereof may be used to screen for compounds that modulate the activity of GBAP. Such compounds may include agonists, antagonists, or partial or inverse agonists. In one embodiment, an assay is performed under conditions permissive for GBAP
activity, wherein GBAP is combined with at least one test compound, and the activity of GBAP in the presence of a test compound is compared with the activity of GBAP in the absence of the test compound. A change in the activity of GBAP in the presence of the test compound is indicative of a compound that modulates the activity of GBAP. Alternatively, a test compound is combined with an in vitro or cell-free system comprising GBAP under conditions suitable for GBAP activity, and the assay is performed. In either of these assays, a test compound which modulates the activity of GBAP
may do so indirectly and need not come in direct contact with the test compound. At least one and up to a plurality of test compounds may be screened.
In another embodiment, polynucleotides encoding GBAP or their mammalian homologs may be "knocked out" in an animal model system using homologous recombination in embryonic stem (ES) cells. Such techniques are well known in the art and are useful for the generation of animal models of human disease. (See, e.g., U.S. Patent No. 5,175,383 and U.S. Patent No. 5,767,337.) For example, mouse ES cells, such as the mouse 129/SvJ cell line, are derived from the early mouse embryo and grown in culture. The ES cells are transformed with a vector containing the gene of interest disrupted by a marker gene, e.g., the neomycin phosphotransferase gene (neo; Capecchi, M.R.
(1989) Science 244:1288-1292). The vector integrates into the corresponding region of the host genome by homologous recombination. Alternatively, homologous recombination takes place using the Cre-loxP system to knockout a gene of interest in a tissue- or developmental stage-specific manner (Marth, J.D. (1996) Clin. Invest. 97:1999-2002; Wagner, K.U. et al.
(1997) Nucleic Acids Res. 25:4323-4330). Transformed ES cells are identified and microinjected into mouse cell blastocysts such as those from the C57BL/6 mouse strain. The blaslocysts are surgically transferred SUBSTITUTE SHEET (RULE 26) to pseudopregnant dams, and the resulting chimeric progeny are genotyped and bred to produce heterozygous or homozygous strains. Transgenic animals thus generated may be tested with potential therapeutic or toxic agents.
Polynucleotides encoding GBAP may also be manipulated in vitro in ES cells derived from human blastocysts. Human ES cells have the potential to differentiate into at least eight separate cell lineages including endoderm, mesoderm, and ectodermal cell types. These cell lineages differentiate into, for example, neural cells, hematopoietic lineages, and cardiomyocytes (Thomson, J.A. et al.
(1998) Science 282:1145-1147).
Polynucleotides encoding GBAP can also be used to create "knockin" humanized animals (pigs) or transgenic animals (mice or rats) to model human disease. With knockin technology, a region of a polynucleotide encoding GBAP is injected into animal ES cells, and the injected sequence integrates into the animal cell genome. Transformed cells are injected into blastulae, and the blastulae are implanted as described above. Transgenic progeny or inbred lines are studied and treated with potential pharmaceutical agents to obtain information on treatment of a human disease.
Alternatively, a mammal inbred to overexpress GBAP, e.g., by secreting GBAP in its milk, may also serve as a convenient source of that protein (Janne, J. et al. (1998) Biotechnol. Annu. Rev. 4:55-74).
THERAPEUTICS
Chemical and structural similarity, e.g., in the context of sequences and motifs, exists between regions of GBAP and GTP-binding associated proteins. In addition, the expression of GBAP
is closely associated with reproductive tissues, inflammation and the immune response, trauma, cell proliferation, and cancer. Therefore, GBAP appears to play a role in immune system, reproductive, nervous system, and cell signaling disorders, and cell proliferative disorders including cancer. In the treatment of disorders associated with increased GBAP expression or activity, it is desirable to decrease the expression or activity of GBAP. In the treatment of disorders associated with decreased GBAP expression or activity, it is desirable to increase the expression or activity of GBAP.
Therefore, in one embodiment, GBAP or a fragment or derivative thereof may be administered to a subject to treat or prevent a disorder associated with decreased expression or activity of GBAP. Examples of such disorders include, but are not limited to, an immune system disorder such as inflammation, actinic keratosis, acquired immunodeficiency syndrome (AIDS), Addison's disease, adult respiratory distress syndrome, allergies, ankylosing spondylitis, amyloidosis, anemia, arteriosclerosis, asthma, atherosclerosis, autoimmune hemolytic anemia, autoimmune thyroiditis, bronchitis, bursitis, cholecystitis, cirrhosis, contact dermatitis, Crohn's disease, atopic dermatitis, dermatomyositis, diabetes mellitus, emphysema, erythroblastosis fetalis, erythema nodosum, atrophic gastritis, glomerulonephritis, Goodpasture's syndrome, gout, Graves' disease, Hashimoto's thyroiditis, paroxysmal nocturnal hemoglobinuria, hepatitis, hypereosinophilia, irritable SUBSTITUTE SHEET (RULE 26) bowel syndrome, episodic lymphopenia with lymphocytotoxins, mixed connective tissue disease (MCTD), multiple sclerosis, myasthenia gravis, myocardial or pericardial inflammation, myelofibrosis, osteoarthritis, osteoporosis, pancreatitis, polycythemia vera, polymyositis, psoriasis, Reiter's syndrome, rheumatoid arthritis, scleroderma, Sjogren's syndrome, systemic anaphylaxis, systemic lupus erythematosus, systemic sclerosis, primary thrombocythemia, thrombocytopenic purpura, ulcerative colitis, uveitis, Werner syndrome, complications of cancer, hemodialysis, and extracorporeal circulation, trauma, and hematopoietic cancer including lymphoma, leukemia, and myeloma; a reproductive disorder such as a disorder of prolactin production, infertility, including tubal disease, ovulatory defects, and endometriosis, a disruption of the estrous cycle, a disruption of the menstrual cycle, polycystic ovary syndrome, ovarian hyperstimulation syndrome, an endometrial or ovarian tumor, a uterine fibroid, autoimmune disorders, an ectopic pregnancy, and teratogenesis, cancer of the breast, fibrocysdc breast disease, and galactorrhea, a disruption of spermatogenesis, abnormal sperm physiology, cancer of the testis, cancer of the prostate, benign prostatic hyperplasia, prostatitis, Peyronie's disease, impotence, carcinoma of the male breast, and gynecomastia; a nervous system disorder such as epilepsy, ischemic cerebrovascular disease, stroke, cerebral neoplasms, Alzheimer's disease, Pick's disease, Huntington's disease, dementia, Parkinson's disease and other extrapyramidal disorders, amyotrophic lateral sclerosis and other motor neuron disorders, progressive neural muscular atrophy, retinitis pigmentosa, hereditary ataxias, multiple sclerosis and other demyelinating diseases, bacterial and viral meningitis, brain abscess, subdural empyema, epidural abscess, suppurative intracranial thrombophlebitis, myelitis and radiculitis, viral central nervous system disease, prion diseases including kuru, Creutzfeldt-Jakob disease, and Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, nutritional and metabolic diseases of the nervous system, neurofibromatosis, tuberous sclerosis, cerebelloretinal hemangioblastomatosis, encephalotrigeminal syndrome, mental retardation and other developmental disorders of the central nervous system, cerebral palsy, neuroskeletal disorders, autonomic nervous system disorders, cranial nerve disorders, spinal cord diseases, muscular dystrophy and other neuromuscular disorders, peripheral nervous system disorders, dermatomyositis and polymyositis, inherited, metabolic, endocrine, and toxic myopathies, myasthenia gravis, periodic paralysis, mental disorders including mood, anxiety, and schizophrenic disorders, akathesia, amnesia, catatonia, diabetic neuropathy, tardive dyskinesia, dystonias, paranoid psychoses, postherpetic neuralgia, and Tourette's disorder; a cell signaling disorder including endocrine disorders such as disorders of the hypothalamus and pituitary resulting from lesions such as primary brain tumors, adenomas, infarction associated with pregnancy, hypophysectomy, aneurysms, vascular malformations, thrombosis, infections, immunological disorders, and complications due to head trauma; disorders associated with hyperpituitarism including acromegaly, giantism, and syndrome of inappropriate antidiuretic hormone (ADH) secretion (SIADH) often caused by benign adenoma; disorders associated with SUBSTITUTE SHEET (RULE 26) hypothyroidism including goiter, myxedema, acute thyroiditis associated with bacterial infection;
disorders associated with hyperparathyroidism including Conn disease (chronic hypercalemia);
pancreatic disorders such as Type I or Type II diabetes mellitus and associated complications;
disorders associated with the adrenals such as hyperplasia, carcinoma, or adenoma of the adrenal cortex, hypertension associated with alkalosis; disorders associated with gonadal steroid hormones such as: in women, abnormal prolactin production, infertility, endometriosis, perturbations of the menstrual cycle, polycysdc ovarian disease, hyperprolactinemia, isolated gonadotropin deficiency, amenorrhea, galactorrhea, hermaphroditism, hirsutism and virilization, breast cancer, and, in post-menopausal women, osteoporosis; and, in men, Leydig cell deficiency, male climacteric phase, and germinal cell aplasia, hypergonadal disorders associated with Leydig cell tumors, androgen resistance associated with absence of androgen receptors, syndrome of 5 a-reductase, and gynecomastia; and a cell proliferative disorder such as actinic keratosis, arteriosclerosis, atherosclerosis, bursitis, cirrhosis, hepatitis, mixed connective tissue disease (MCTD), myelofibrosis, paroxysmal nocturnal hemoglobinuria, polycythemia vera, psoriasis, primary thrombocythemia, and cancers including adenocarcinoma, leukemia, lymphoma, melanoma, myeloma, sarcoma, teratocarcinoma, and, in particular, cancers of the adrenal gland, bladder, bone, bone marrow, brain, breast, cervix, gall bladder, ganglia, gastrointestinal tract, heart, kidney, liver, lung, muscle, ovary, pancreas, parathyroid, penis, prostate, salivary glands, skin, spleen, testis, thymus, thyroid, and uterus.
In another embodiment, a vector capable of expressing GBAP or a fragment or derivative thereof may be administered to a subject to treat or prevent a disorder associated with decreased expression or activity of GBAP including, but not limited to, those described above.
In a further embodiment, a pharmaceutical composition comprising a substantially purified GBAP in conjunction with a suitable pharmaceutical carrier may be administered to a subject to treat or prevent a disorder associated with decreased expression or activity of GBAP
including, but not limited to, those provided above.
In still another embodiment, an agonist which modulates the activity of GBAP
may be administered to a subject to treat or prevent a disorder associated with decreased expression or activity of GBAP including, but not limited to, those listed above.
In a further embodiment, an antagonist of GBAP may be administered to a subject to treat or prevent a disorder associated with increased expression or activity of GBAP.
Examples of such disorders include, but are not limited to, those immune system, reproductive, nervous system, and cell signaling disorders, and cell proliferative disorders including cancer, described above. In one aspect, an antibody which specifically binds GBAP may be used directly as an antagonist or indirectly as a targeting or delivery mechanism for bringing a pharmaceutical agent to cells or tissues which express GBAP.

SUBSTITUTE SHEET (RULE 26) In an additional embodiment, a vector expressing the complement of the polynucleotide encoding GBAP may be administered to a subject to treat or prevent a disorder associated with increased expression or activity of GBAP including, but not limited to, those described above.
In other embodiments, any of the proteins, antagonists, antibodies, agonists, complementary sequences, or vectors of the invention may be administered in combination with other appropriate therapeutic agents. Selection of the appropriate agents for use in combination therapy may be made by one of ordinary skill in the art, according to conventional pharmaceutical principles. The combination of therapeutic agents may act synergistically to effect the treatment or prevention of the various disorders described above. Using this approach, one may be able to achieve therapeutic efficacy with lower dosages of each agent, thus reducing the potential for adverse side effects.
An antagonist of GBAP may be produced using methods which are generally known in the art.
In particular, purified GBAP may be used to produce antibodies or to screen libraries of pharmaceutical agents to identify those which specifically bind GBAP. Antibodies to GBAP may also be generated using methods that are well known in the art. Such antibodies may include, but are not limited to, polyclonal, monoclonal, chimeric, and single chain antibodies, Fab fragments, and fragments produced by a Fab expression library. Neutralizing antibodies (i.e., those which inhibit dimer formation) are generally preferred for therapeutic use.
For the production of antibodies, various hosts including goats, rabbits, rats, mice, humans, and others may be immunized by injection with GBAP or with any fragment or oligopeptide thereof which has immunogenic properties. Depending on the host species, various adjuvants may be used to increase immunological response. Such adjuvants include, but are not limited to, Freund's, mineral gels such as aluminum hydroxide, and surface active substances such as lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, KLH, and dinitrophenol. Among adjuvants used in humans, BCG
(bacilli Calmette-Guerin) and Corynebacterium parvum are especially preferable.
It is preferred that the oligopeptides, peptides, or fragments used to induce antibodies to GBAP
have an amino acid sequence consisting of at least about 5 amino acids, and generally will consist of at least about 10 amino acids. It is also preferable that these oligopeptides, peptides, or fragments are identical to a portion of the amino acid sequence of the natural protein.
Short stretches of GBAP amino acids may be fused with those of another protein, such as KLH, and antibodies to the chimeric molecule may be produced.
Monoclonal antibodies to GBAP may be prepared using any technique which provides for the production of antibody molecules by continuous cell lines in culture. These include, but are not limited to, the hybridoma technique, the human B-cell hybridoma technique, and the EBV-hybridoma technique. (See, e.g., Kohler, G. et al. (1975) Nature 256:495-497; Kozbor, D.
et al. (1985) J.
Immunol. Methods 81:31-42; Cote, R.J. et al. (1983) Proc. Natl. Acad. Sci. USA
80:2026-2030; and SUBSTITUTE SHEET (RULE 26) Cole, S.P. et al. (1984) Mol. Cell Biol. 62:109-120.) In addition, techniques developed for the production of "chimeric antibodies,"
such as the splicing of mouse antibody genes to human antibody genes to obtain a molecule with appropriate antigen specificity and biological activity, can be used. (See, e.g., Morrison, S.L. et al. (1984) Proc.
Natl. Acad. Sci. USA 81:6851-6855; Neuberger, M.S. et al. (1984) Nature 312:604-608; and Takeda, S. et al. (1985) Nature 314:452-454.) Alternatively, techniques described for the production of single chain antibodies may be adapted, using methods known in the art, to produce GBAP-specific single chain antibodies. Antibodies with related specificity, but of distinct idiotypic composition, may be generated by chain shuflHng from random combinatorial immunoglobulin libraries. (See, e.g., Burton, D.R. (1991) Proc. Natl. Acad. Sci. USA 88:10134-10137.) Antibodies may also be produced by inducing in vivo production in the lymphocyte population or by screening immunoglobulin libraries or panels of highly specific binding reagents as disclosed in the literature. (See, e.g., Orlandi, R. et al. (1989) Proc. Natl. Acad. Sci.
USA 86:3833-3837; Winter, G. et al. (1991) Nature 349:293-299.) Antibody fragments which contain specific binding sites for GBAP may also be generated. For example, such fragments include, but are not limited to, F(ab')2 fragments produced by pepsin digestion of the antibody molecule and Fab fragments generated by reducing the disulfide bridges of the F(ab')2 fragments. Alternatively, Fab expression libraries may be constructed to allow rapid and easy identification of monoclonal Fab fragments with the desired specificity. (See, e.g., Huse, W.D. et al.
(1989) Science 246:1275-1281.) Various immunoassays may be used for screening to identify antibodies having the desired specificity. Numerous protocols for competitive binding or immunoradiometric assays using either polyclonal or monoclonal antibodies with established specificities are well known in the art. Such immunoassays typically involve the measurement of complex formation between GBAP and its specific antibody. A two-site, monoclonal-based immunoassay utilizing monoclonal antibodies reactive to two non-interfering GBAP epitopes is generally used, but a competitive binding assay may also be employed (Pound, supra).
Various methods such as Scatchard analysis in conjunction with radioimmunoassay techniques may be used to assess the affinity of antibodies for GBAP. Affinity is expressed as an association constant, Ka, which is defined as the molar concentration of GBAP-antibody complex divided by the molar concentrations of free antigen and free antibody under equilibrium conditions. The Ka determined for a preparation of polyclonal antibodies, which are heterogeneous in their affinities for multiple GBAP epitopes, represents the average affinity, or avidity, of the antibodies for GBAP. The Kd determined for a preparation of monoclonal antibodies, which are monospecific for a particular GBAP
epitope, represents a true measure of affinity. High-affinity antibody preparations with Kd ranging liom SUBSTITUTE SHEET (RULE 26) about 109 to 10'z L/mole are preferred for use in immunoassays in which the GBAP-antibody complex must withstand rigorous manipulations. Low-affinity antibody preparations with Ka ranging from about 106 to 10' L/mole are preferred for use in immunopurification and similar procedures which ultimately require dissociation of GBAP, preferably in active form, from the antibody (Catty, D. (1988) Antibodies, Volume I: A Practical Approach, IRL Press, Washington DC; Liddell, J.E. and A. Cryer (1991) A Practical Guide to Monoclonal Antibodies, John Wiley & Sons, New York NY).
The titer and avidity of polyclonal antibody preparations may be further evaluated to determine the quality and suitability of such preparations for certain downstream applications. For example, a polyclonal antibody preparation containing at least 1-2 mg specific antibody/ml, preferably 5-10 mg specific antibody/ml, is generally employed in procedures requiring precipitation of GBAP-antibody complexes. Procedures for evaluating antibody specificity, titer, and avidity, and guidelines for antibody quality and usage in various applications, are generally available.
(See, e.g., Catty, supra, and Coligan et al., supra.) In another embodiment of the invention, the polynucleotides encoding GBAP, or any fragment or complement thereof, may be used for therapeutic purposes. In one aspect, modifications of gene expression can be achieved by designing complementary sequences or antisense molecules (DNA, RNA, PNA, or modified oligonucleotides) to the coding or regulatory regions of the gene encoding GBAP.
Such technology is well known in the art, and antisense oligonucleotides or larger fragments can be designed from various locations along the coding or control regions of sequences encoding GBAP.
(See, e.g., Agrawal, S., ed. (1996) Antisense Therapeutics, Humana Press Inc., Totawa NJ.) In therapeutic use, any gene delivery system suitable for introduction of the antisense sequences into appropriate target cells can be used. Antisense sequences can be delivered intracellularly in the form of an expression plasmid which, upon transcription, produces a sequence complementary to at least a portion of the cellular sequence encoding the target protein. (See, e.g., Slater, J.E. et al. (1998) J. Allergy Clin. Immunol. 102(3):469-475; and Scanlon, K.J. et al. (1995) 9(13):1288-1296.) Antisense sequences can also be introduced intracellularly through the use of viral vectors, such as retrovirus and adeno-associated virus vectors. (See, e.g., Miller, A.D. (1990) Blood 76:271; Ausubel, supra; Uckert, W. and W. Walther (1994) Pharmacol. Ther.
63(3):323-347.) Other gene delivery mechanisms include liposome-derived systems, artificial viral envelopes, and other systems known in the art. (See, e.g., Rossi, J.J. (1995) Br. Med. Bull.
51(1):217-225; Boado, R.J. et al. (1998) J. Pharm. Sci. 87(11):1308-1315; and Moms, M.C. et al. (1997) Nucleic Acids Res.
25( 14):2730-2736.) In another embodiment of the invention, polynucleotides encoding GBAP may be used for somatic or germline gene therapy. Gene therapy may be performed to (i) correct a genetic deficiency (e.g., in the cases of severe combined immunodeficiency (SCID)-X1 disease characterized by X-linked SUBSTITUTE SHEET (RULE 26) inheritance (Cavazzana-Calvo, M. et al. (2000) Science 288:669-672), severe combined immunodeficiency syndrome associated with an inherited adenosine deaminase (ADA) deficiency (Blaese, R.M. et al. (1995) Science 270:475-480; Bordignon, C. et al. (1995) Science 270:470-475), cystic fibrosis (Zabner, J. et al. (1993) Cell 75:207-216; Crystal, R.G. et al. (1995) Hum. Gene Therapy 6:643-666; Crystal, R.G. et al. (1995) Hum. Gene Therapy 6:667-703), thalassamias, familial hypercholesterolemia, and hemophilia resulting from Factor VIII or Factor IX
deficiencies (Crystal, R.G. (1995) Science 270:404-410; Verma, LM. and Somia, N. (1997) Nature 389:239-242)), (ii) express a conditionally lethal gene product (e.g., in the case of cancers which result from unregulated cell proliferation), or (iii) express a protein which affords protection against intracellular parasites (e.g., against human retroviruses, such as human immunodeficiency virus (HIV) (Baltimore, D. (1988) Nature 335:395-396; Poeschla, E. et al. (1996) Proc. Natl. Acad. Sci. USA.
93:11395-11399), hepatitis B or C virus (HBV, HCV); fungal parasites, such as Candida albicans and Paracoccidioides brasiliensis; and protozoan parasites such as Plasmodium falciparum and Tar panosoma cruzi). In the case where a genetic deficiency in GBAP expression or regulation causes disease, the expression of GBAP from an appropriate population of transduced cells may alleviate the clinical manifestations caused by the genetic deficiency.
1n a further embodiment of the invention, diseases or disorders caused by deficiencies in GBAP
are treated by constructing mammalian expression vectors encoding GBAP and introducing these vectors by mechanical means into GBAP-deficient cells. Mechanical transfer technologies for use with cells in vivo or ex vitro include (i) direct DNA microinjection into individual cells, (ii) ballistic gold particle delivery, (iii) liposome-mediated transfection, (iv) receptor-mediated gene transfer, and (v) the use of DNA transposons (Morgan, R.A. and W.F. Anderson (1993) Annu. Rev.
Biochem. 62:191-217;
Ivics, Z. (1997) Cell 91:501-510; Boulay, J-L. and H. Rec;ipon (1998) Curr.
Opin. Biotechnol. 9:445-450).
Expression vectors that may be effective for the expression of GBAP include, but are not limited to, the PCDNA 3.1, EPITAG, PRCCMV2, PREP, PVAX vectors (Invitrogen, Carlsbad CA), PCMV-SCRIPT, PCMV-TAG, PEGSH/PERV (Stratagene, La Jolla CA), and PTET-OFF, PTET-ON, PTRE2, PTRE2-LUC, PTK-HYG (Clontech, Palo Alto CA). GBAP may be expressed using (i) a constitutively active promoter, (e.g., from cytomegalovirus (CMV), Rous sarcoma virus (RSV), SV40 virus, thymidine lcinase (TK), or (i-actin genes), (ii) an inducible promoter (e.g., the tetracycline-regulated promoter (Gossen, M. and H. Bujard (1992) Proc. Natl.
Acad. Sci. USA
89:5547-5551; Gossen, M. et al. (1995) Science 268:1766-1769; Rossi, F.M.V.
and H.M. Blau (1998) Curr. Opin. Biotechnol. 9:451-456), commercially available in the T-REX
plasmid (Invitrogen)); the ecdysone-inducible promoter (available in the plasmids PVGRXR and PIND;
Invitrogen); the FK506/rapamycin inducible promoter; or the RU486/mifepristone inducible promoter (Rossi, F.M.V.

SUBSTITUTE SHEET (RULE 26) and H.M. Blau, su ra)), or (iii) a tissue-specific promoter or the native promoter of the endogenous gene encoding GBAP from a normal individual.
Commercially available liposome transformation kits (e.g., the PERFECT LIPID
TRANSFECTION HIT, available fiom Invitrogen) allow one with ordinary skill in the art to deliver polynucleotides to target cells in culture and require minimal effort to optimize experimental parameters. In the alternative, transformation is performed using the calcium phosphate method (Graham, F.L. and A.J. Eb (1973) Virology 52:456-467), or by electroporation (Neumann, E. et al.
(1982) EMBO J. 1:841-845). The introduction of DNA to primary cells requires modification of these standardized mammalian transfection protocols.
In another embodiment of the invention, diseases or disorders caused by genetic defects with respect to GBAP expression are treated by constructing a retrovirus vector consisting of (i) the polynucleotide encoding GBAP under the control of an independent promoter or the retrovirus long terminal repeat (LTR) promoter, (ii) appropriate RNA packaging signals, and (iii) a Rev-responsive element (RRE) along with additional retrovirus cis-acting RNA sequences and coding sequences required for efficient vector propagation. Retrovirus vectors (e.g., PFB and PFBNEO) are commercially available (Stratagene) and are based on published data (Riviere, I. et al. (1995) Proc.
Nati. Acad. Sci. USA 92:6733-6737), incorporated by reference herein. The vector is propagated in an appropriate vector producing cell line (VPCL) that expresses an envelope gene with a tropism for receptors on the target cells or a promiscuous envelope protein such as VS Vg (Armentano, D. et al.
(1987) J. Virol. 61:1647-1650; Bender, M.A. et al. (1987) J. Virol. 61:1639-1646; Adam, M.A. and A.D. Miller (1988) J. Virol. 62:3802-3806; Dull, T. et al. (1998) J. Virol.
72:8463-8471; Zufferey, R.
et al. (1998) J. Virol. 72:9873-9880). U.S. Patent Number 5,910,434 to Rigg ("Method for obtaining retrovirus packaging cell lines producing high transducing efficiency retroviral supernatant") discloses a method for obtaining retrovirus packaging cell lines and is hereby incorporated by reference.
Propagation of retrovirus vectors, transduction of a population of cells (e.g., CD4+ T-cells), and the return of transduced cells to a patient are procedures well known to persons skilled in the art of gene therapy and have been well documented (Ranga, U. et al. (1997) J. Virol.
71:7020-7029; Bauer, G. et al. (1997) Blood 89:2259-2267; Bonyhadi, M.L. (1997) J. Virol. 71:4707-4716;
Ranga, U. et al.
(1998) Proc. Natl. Acad. Sci. USA 95:1201-1206; Su, L. (1997) Blood 89:2283-2290).
In the alternative, an adenovirus-based gene therapy delivery system is used to deliver polynucleotides encoding GBAP to cells which have one or more genetic abnormalities with respect to the expression of GBAP. The construction and packaging of adenovirus-based vectors are well known to those with ordinary skill in the art. Replication defective adenovirus vectors have proven to be versatile for importing genes encoding immunoregulatory proteins into intact islets in the pancreas (Csete, M.E. et al. (1995) Transplantation 27:263-268). Potentially useful adenoviral vectors are SUBSTITUTE SHEET (RULE 26) described in U.S. Patent Number 5,707,618 to Armentano ("Adenovirus vectors for gene therapy"), hereby incorporated by reference. For adenoviral vectors, see also Antinozzi, P.A. et al. (1999) Annu.
Rev. Nutr. 19:511-544; and Verma, LM. and N. Somia (1997) Nature 18:389:239-242, both incorporated by reference herein.
In another alternative, a herpes-based, gene therapy delivery system is used to deliver polynucleotides encoding GBAP to target cells which have one or more genetic abnormalities with respect to the expression of GBAP. The use of herpes simplex virus (HSV)-based vectors may be especially valuable for introducing GBAP to cells of the central nervous system, for which HSV has a tropism. The construction and packaging of herpes-based vectors are well known to those with ordinary skill in the art. A replication-competent herpes simplex virus (HSV) type 1-based vector has been used to deliver a reporter gene to the eyes of primates (Liu, X. et al.
(1999) Exp. Eye Res.169:385-395). The construction of a HSV-1 virus vector has also been disclosed in detail in U.S.
Patent Number 5,804,413 to DeLuca ("Herpes simplex virus strains for gene transfer"), which is hereby incorporated by reference. U.S. Patent Number 5,804,413 teaches the use of recombinant HSV
d92 which consists of a genome containing at least one exogenous gene to be transferred to a cell under the control of the appropriate promoter for purposes including human gene therapy. Also taught by this patent are the construction and use of recombinant HSV strains deleted for ICP4, ICP27 and ICP22.
For HSV vectors, see also Goins, W.F. et al. (1999) J. Virol. 73:519-532 and Xu, H. et al. (1994) Dev.
Biol. 163:152-161, hereby incorporated by reference. The manipulation of cloned herpesvirus sequences, the generation of recombinant virus following the transfection of multiple plasmids containing different segments of the large herpesvirus genomes, the growth and propagation of herpesvirus, and the infection of cells with herpesvirus are techniques well known to those of ordinary skill in the art.
In another alternative, an alphavirus (positive, single-stranded RNA virus) vector is used to deliver polynucleotides encoding GBAP to target cells. The biology of the prototypic alphavirus, Semliki Forest Virus (SFV), has been studied extensively and gene transfer vectors have been based on the SFV genome (Garoff, H. and K.-J. Li (1998) Curr. Opin. Biotech. 9:464-469). During alphavirus RNA replication, a subgenomic RNA is generated that normally encodes the viral capsid proteins. This subgenomic RNA replicates to higher levels than the full-length genomic RNA, resulting in the overproduction of capsid proteins relative to the viral proteins with enzymatic activity (e.g., protease and polymerase). Similarly, inserting the coding sequence for GBAP into the alphavirus genome in place of the capsid-coding region results in the production of a large number of GBAP-coding RNAs and the synthesis of high levels of GBAP in vector transduced cells. While alphavirus infection is typically associated with cell lysis within a few days, the ability to establish a persistent infection in hamster normal kidney cells (BHK-21) with a variant of Sindbis virus (SIN) indicates that the lytic SUBSTITUTE SHEET (RULE 26) replication of alphaviruses can be altered to suit the needs of the gene therapy application (Dryga, S.A.
et al. (1997) Virology 228:74-83). The wide host range of alphaviruses will allow the introduction of GBAP into a variety of cell types. The specific transduction of a subset of cells in a population may require the sorting of cells prior to transduction. The methods of manipulating infectious cDNA clones of alphaviruses, performing alphavirus cDNA and RNA transfec;tions, and performing alphavirus infections, are well known to those with ordinary skill in the art.
Oligonucleotides derived from the transcription initiation site, e.g., between about positions -10 and +10 from the start site, may also be employed to inhibit gene expression.
Similarly, inhibition can be achieved using triple helix base-pairing methodology. Triple helix pairing is useful because it causes inhibition of the ability of the double helix to open sufficiently for the binding of polymerases, transcription factors, or regulatory molecules. Recent therapeutic advances using triplex DNA have been described in the literature. (See, e.g., Gee, J.E. et al. (1994) in Huber, B.E. and B.I. Carr, Molecular and Immunolo~ic Approaches, Futura Publishing, Mt. Kisco NY, pp. 163-177.) A
complementary sequence or antisense molecule may also be designed to block translation of mRNA by preventing the transcript from binding to ribosomes.
Ribozymes, enzymatic RNA molecules, may also be used to catalyze the specific cleavage of RNA. The mechanism of ribozyme action involves sequence-specific hybridization of the ribozyme molecule to complementary target RNA, followed by endonucleolytic cleavage.
For example, engineered hammerhead motif ribozyme molecules may specifically and efficiently catalyze endonucleolytic cleavage of sequences encoding GBAP.
Specific ribozyme cleavage sites within any potential RNA target are initially identified by scanning the target molecule for ribozyme cleavage sites, including the following sequences: GUA, GUU, and GUC. Once identified, short RNA sequences of between 15 and 20 ribonucleotides, corresponding to the region of the target gene containing the cleavage site, may be evaluated for secondary structural features which may render the oligonucleotide inoperable.
The suitability of candidate targets may also be evaluated by testing accessibility to hybridization with complementary oligonucleotides using ribonuclease protection assays.
Complementary ribonucleic acid molecules and ribozymes of the invention may be prepared by any method known in the art for the synthesis of nucleic acid molecules. These include techniques for chemically synthesizing oligonucleotides such as solid phase phosphoramidite chemical synthesis.
Alternatively, RNA molecules may be generated by in vitro and in vivo transcription of DNA sequences encoding GBAP. Such DNA sequences may be incorporated into a wide variety of vectors with suitable RNA polymerase promoters such as T7 or SP6. Alternatively, these cDNA
constructs that synthesize complementary RNA, constitutively or inducibly, can be introduced into cell lines, cells, or tissues.
SUBSTITUTE SHEET (RULE 26) RNA molecules may be modified to increase intracellular stability and half-life. Possible modifications include, but are not limited to, the addition of flanking sequences at the 5' and/or 3' ends of the molecule, or the use of phosphorothioate or 2' O-methyl rather than phosphodiesterase linkages within the backbone of the molecule. This concept is inherent in the production of PNAs and can be extended in all of these molecules by the inclusion of nontraditional bases such as inosine, queosine, and wybutosine, as well as acetyl-, methyl-, thio-, and similarly modified forms of adenine, cytidine, guanine, thymine, and uridine which are not as easily recognized by endogenous endonucleases.
An additional embodiment of the invention encompasses a method for screening for a compound which is effective in altering expression of a polynucleotide encoding GBAP. Compounds which may be effective in altering expression of a specific polynucleodde may include, but are not limited to, oligonucleotides, antisense oligonucleotides, triple helix-forming oligonucleotides, transcription factors and other polypeptide transcriptional regulators, and non-macromolecular chemical entities which are capable of interacting with specific polynucleotide sequences. Effective compounds may alter polynucleotide expression by acting as either inhibitors or promoters of polynucleotide expression. Thus, in the treatment of disorders associated with increased GBAP
expression or activity, a compound which specifically inhibits expression of the polynucleotide encoding GBAP may be therapeutically useful, and in the treament of disorders associated with decreased GBAP expression or activity, a compound which specifically promotes expression of the polynucleotide encoding GBAP may be therapeutically useful.
At least one, and up to a plurality, of test compounds may be screened for effectiveness in altering expression of a specific polynucleotide. A test compound may be obtained by any method commonly known in the art, including chemical modification of a compound known to be effective in altering polynucleotide expression; selection from an existing, commercially-available or proprietary library of naturally-occurring or non-natural chemical compounds; rational design of a compound based on chemical and/or structural properties of the target polynucleotide;
and selection from a library of chemical compounds created combinatorially or randomly. A sample comprising a polynucleotide encoding GBAP is exposed to at least one test compound thus obtained. The sample may comprise, for example, an intact or permeabilized cell, or an in vitro cell-free or reconstituted biochemical system. Alterations in the expression of a polynucleotide encoding GBAP are assayed by any method commonly known in the art. Typically, the expression of a specific nucleotide is detected by hybridization with a probe having a nucleotide sequence complementary to the sequence of the polynucleotide encoding GBAP. The amount of hybridization may be quantified, thus forming the basis for a comparison of the expression of the polynucleodde both with and without exposure to one or more test compounds. Detection of a change in the expression of a polynucleotide exposed to a test compound indicates that the test compound is effective in altering the expression of SUBSTITUTE SHEET (RULE 26) the polynucleotide. A screen for a compound effective in altering expression of a specific polynucleotide can be carried out, for example, using a Schizosaccharomyces pombe gene expression system (Atkins, D. et al. (1999) U.S. Patent No. 5,932,435; Arndt, G.M. et al.
(2000) Nucleic Acids Res. 28:E15) or a human cell line such as HeLa cell (Clarke, M.L. et al.
(2000) Biochem. Biophys.
Res. Commun. 268:8-13). A particular embodiment of the present invention involves screening a combinatorial library of oligonucleotides (such as deoxyribonucleotides, ribonucleotides, peptide nucleic acids, and modified oligonucleotides) for antisense activity against a specific polynucleotide sequence (Bruice, T.W. et al. (1997) U.S. Patent No. 5,686,242; Bruice, T.W.
et al. (2000) U.S.
Patent No. 6,022,691).
Many methods for introducing vectors into cells or tissues are available and equally suitable for use in vivo, in vitro, and ex vivo. For ex vivo therapy, vectors may be introduced into stem cells taken from the patient and clonally propagated for autologous transplant back into that same patient.
Delivery by transfection, by liposome injections, or by polycationic amino polymers may be achieved using methods which are well known in the art. (See, e.g., Goldman, C.K. et al. (1997) Nat.
Biotechnol. 15:462-466.) Any of the therapeutic methods described above may be applied to any subject in need of such therapy, including, for example, mammals such as humans, dogs, cats, cows, horses, rabbits, and monkeys.
An additional embodiment of the invention relates to the administration of a pharmaceutical composition which generally comprises an active ingredient formulated with a pharmaceutically acceptable excipient. Excipients may include, for example, sugars, starches, celluloses, gums, and proteins. Various formulations are commonly known and are thoroughly discussed in the latest edition of Remin~ton's Pharmaceutical Sciences (Maack Publishing, Easton PA). Such pharmaceutical compositions may consist of GBAP, antibodies to GBAP, and mimetics, agonists, antagonists, or inhibitors of GBAP.
The pharmaceutical compositions utilized in this invention may be administered by any number of routes including, but not limited to, oral, intravenous, intramuscular, infra-arterial, intramedullary>
intrathecal, intraventricular, pulmonary, transdermal, subcutaneous, intraperitoneal, intranasal, enteral, topical, sublingual, or rectal means.
Pharmaceutical compositions for pulmonary administration may be prepared in liquid or dry powder form. These compositions are generally aerosolized immediately prior to inhalation by the patient. In the case of small molecules (e.g. traditional low molecular weight organic drugs), aerosol delivery of fast-acting formulations is well-known in the art. In the case of macromolecules (e.g. larger peptides and proteins), recent developments in the field of pulmonary delivery via the alveolar region of the lung have enabled the practical delivery of drugs such as insulin to blood circulation (see, e.g., SUBSTITUTE SHEET (RULE 26) Patton, J.S. et al., U.S. Patent No. 5,997,848). Pulmonary delivery has the advantage of administration without needle injection, and obviates the need for potentially toxic penetration enhancers.
Pharmaceutical compositions suitable for use in the invention include compositions wherein the active ingredients are contained in an effective amount to achieve the intended purpose. The determination of an effective dose is well within the capability of those skilled in the art.
Specialized forms of pharmaceutical compositions may be prepared for direct intracellular delivery of macromolecules comprising GBAP or fragments thereof. For example, liposome preparations containing a cell-impermeable macromolecule may promote cell fusion and intracellular delivery of the macromolecule. Alternatively, GBAP or a fragment thereof may be joined to a short cationic N-terminal portion from the HIV Tat-1 protein. Fusion proteins thus generated have been found to transduce into the cells of all tissues, including the brain, in a mouse model system (Schwarze, S.R. et al. (1999) Science 285:1569-1572).
For any compound, the therapeutically effective dose can be estimated initially either in cell culture assays, e.g., of neoplastic cells, or in animal models such as mice, rats, rabbits, dogs, monkeys, or pigs. An animal model may also be used to determine the appropriate concentration range and route of administration. Such information can then be used to determine useful doses and routes for administration in humans.
A therapeutically effective dose refers to that amount of active ingredient, for example GBAP
or fragments thereof, antibodies of GBAP, and agonists, antagonists or inhibitors of GBAP, which ameliorates the symptoms or condition. Therapeutic efficacy and toxicity may be determined by standard pharmaceutical procedures in cell cultures or with experimental animals, such as by calculating the EDSO (the dose therapeutically effective in 50% of the population) or LDSO (the dose lethal to 50% of the population) statistics. The dose ratio of toxic to therapeutic effects is the therapeutic index, which can be expressed as the LDSO/EDSO ratio.
Pharmaceutical compositions which exhibit large therapeutic indices are preferred. The data obtained from cell culture assays and animal studies are used to formulate a range of dosage for human use. The dosage contained in such compositions is preferably within a range of circulating concentrations that includes the EDso with little or no toxicity. The dosage varies within this range depending upon the dosage form employed, the sensitivity of the patient, and the route of administration.
The exact dosage will be determined by the practitioner, in light of factors related to the subject requiring treatment. Dosage and administration are adjusted to provide sufficient levels of the active moiety or to maintain the desired effect. Factors which may be taken into account include the severity of the disease state, the general health of the subject, the age, weight, and gender of the subject, time and frequency of administration, drug combination(s), reaction sensitivities, and response to therapy.
Long-acting pharmaceutical compositions may be administered every 3 to 4 days, every week, or SUBSTITUTE SHEET (RULE 26) biweekly depending on the half-life and clearance rate of the particular formulation.
Normal dosage amounts may vary from about 0.1 ~g to 100,000 ~cg, up to a total dose of about 1 gram, depending upon the route of administration. Guidance as to particular dosages and methods of delivery is provided in the literature and generally available to practitioners in the art.
Those skilled in the art will employ different formulations for nucleotides than for proteins or their inhibitors. Similarly, delivery of polynucleotides or polypeptides will be specific to particular cells, conditions, locations, etc.
DIAGNOSTICS
In another embodiment, antibodies which specifically bind GBAP may be used for the diagnosis of disorders characterized by expression of GBAP, or in assays to monitor patients being treated with GBAP or agonists, antagonists, or inhibitors of GBAP. Antibodies useful for diagnostic purposes may be prepared in the same manner as described above for therapeutics. Diagnostic assays for GBAP
include methods which utilize the antibody and a label to detect GBAP in human body fluids or in extracts of cells or tissues. The antibodies may be used with or without modification, and may be labeled by covalent or non-covalent attachment of a reporter molecule. A wide variety of reporter molecules, several of which are described above, are known in the art and may be used.
A variety of protocols for measuring GBAP, including ELISAs, RIAs, and FACS, are known in the art and provide a basis for diagnosing altered or abnormal levels of GBAP expression. Normal or standard values for GBAP expression are established by combining body fluids or cell extracts taken from normal mammalian subjects, for example, human subjects, with antibody to GBAP under conditions suitable for complex formation. The amount of standard complex formation may be quantitated by various methods, such as photometric means. Quantities of GBAP
expressed in subject, control, and disease samples from biopsied tissues are compared with the standard values. Deviation between standard and subject values establishes the parameters for diagnosing disease.
In another embodiment of the invention, the polynucleotides encoding GBAP may be used for diagnostic purposes. The polynucleotides which may be used include oligonucleotide sequences, complementary RNA and DNA molecules, and PNAs. The polynucleotides may be used to detect and quantify gene expression in biopsied tissues in which expression of GBAP may be correlated with disease. The diagnostic assay may be used to determine absence, presence, and excess expression of GBAP, and to monitor regulation of GBAP levels during therapeutic intervention.
In one aspect, hybridization with PCR probes which are capable of detecting polynucleotide sequences, including genomic sequences, encoding GBAP or closely related molecules may be used to identify nucleic acid sequences which encode GBAP. The specificity of the probe, whether it is made from a highly specific region, e.g., the 5'regulatory region, or from a less specific region, e.g., a conserved motif, and the stringency of the hybridization or amplification will determine whether the SUBSTITUTE SHEET (RULE 26) probe identifies only naturally occurring sequences encoding GBAP, allelic variants, or related sequences.
Probes may also be used for the detection of related sequences, and may have at least 50%
sequence identity to any of the GBAP encoding sequences. The hybridization probes of the subject invention may be DNA or RNA and may be derived from the sequence of SEQ ID
N0:67-132 or from genomic sequences including promoters, enhancers, and introns of the GBAP
gene.
Means for producing specific hybridization probes for DNAs encoding GBAP
include the cloning of polynucleodde sequences encoding GBAP or GBAP derivatives into vectors for the production of mRNA probes. Such vectors are known in the art, are commercially available, and may be used to synthesize RNA probes in vitro by means of the addition of the appropriate RNA
polymerases and the appropriate labeled nucleotides. Hybridization probes may be labeled by a variety of reporter groups, for example, by radionuclides such as 32P or 355, or by enzymatic labels, such as alkaline phosphatase coupled to the probe via avidin/biotin coupling systems, and the like.
Polynucleotide sequences encoding GBAP may be used for the diagnosis of disorders associated with expression of GBAP. Examples of such disorders include, but are not limited to, an immune system disorder such as inflammation, actinic keratosis, acquired immunodeficiency syndrome (AIDS), Addison's disease, adult respiratory distress syndrome, allergies, ankylosing spondylitis, amyloidosis, anemia, arteriosclerosis, asthma, atherosclerosis, autoimmune hemolytic anemia, autoimmune thyroiditis, bronchitis, bursitis, cholecystitis, cirrhosis, contact dermatitis, Crohn's disease, atopic dermatitis, dermatomyositis, diabetes mellitus, emphysema, erythroblastosis fetalis, erythema nodosum, atrophic gastritis, glomerulonephritis, Goodpasture's syndrome, gout, Graves' disease, Hashimoto's thyroiditis, paroxysmal nocturnal hemoglobinuria, hepatitis, hypereosinophilia, irntable bowel syndrome, episodic lymphopenia with lymphocytotoxins, mixed connective tissue disease (MCTD), multiple sclerosis, myasthenia gravis, myocardial or pericardial inflammation, myelofibrosis, osteoarthritis, osteoporosis, pancreatitis, polycythemia vera, polymyositis, psoriasis, Reiter's syndrome, rheumatoid arthritis, scleroderma, Sjogren's syndrome, systemic anaphylaxis, systemic lupus erythematosus, systemic sclerosis, primary thrombocythemia, thrombocytopenic purpura, ulcerative colitis, uveitis, Werner syndrome, complications of cancer, hemodialysis, and extracorporeal circulation, trauma, and hematopoietic cancer including lymphoma, leukemia, and myeloma; a reproductive disorder such as a disorder of prolactin production, infertility, including tubal disease, ovulatory defects, and endometriosis, a disruption of the estrous cycle, a disruption of the menstrual cycle, polycystic ovary syndrome, ovarian hyperstimulation syndrome, an endometrial or ovarian tumor, a uterine fibroid, autoimmune disorders, an ectopic pregnancy, and teratogenesis, cancer of the breast, fibrocystic breast disease, and galactorrhea, a disruption of spermatogenesis, abnormal sperm physiology, cancer of the testis, cancer of the prostate, benign SUBSTITUTE SHEET (RULE 26) prostatic hyperplasia, prostatitis, Peyronie's disease, impotence, carcinoma of the male breast, and gynecomastia; a nervous system disorder such as epilepsy, ischemic cerebrovascular disease, stroke, cerebral neoplasms, Alzheimer's disease, Pick's disease, Huntington's disease, dementia, Parkinson's disease and other extrapyramidal disorders, amyotrophic lateral sclerosis and other motor neuron disorders, progressive neural muscular atrophy, retinitis pigmentosa, hereditary ataxias, multiple sclerosis and other demyelinating diseases, bacterial and viral meningitis, brain abscess, subdural empyema, epidural abscess, suppurative intracranial thrombophlebitis, myelitis and radiculitis, viral central nervous system disease, prion diseases including kuru, Creutzfeldt-Jakob disease, and Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, nutritional and metabolic diseases of the nervous system, neurofibromatosis, tuberous sclerosis, cerebelloretinal hemangioblastomatosis, encephalotrigeminal syndrome, mental retardation and other developmental disorders of the central nervous system, cerebral palsy, neuroskeletal disorders, autonomic nervous system disorders, cranial nerve disorders, spinal cord diseases, muscular dystrophy and other neuromuscular disorders, peripheral nervous system disorders, dermatomyositis and polymyositis, inherited, metabolic, endocrine, and toxic myopathies, myasthenia gravis, periodic paralysis, mental disorders including mood, anxiety, and schizophrenic disorders, akathesia, amnesia, catatonia, diabetic neuropathy, tardive dyskinesia, dystonias, paranoid psychoses, postherpetic neuralgia, and Tourette's disorder; a cell signaling disorder including endocrine disorders such as disorders of the hypothalamus and pituitary resulting from lesions such as primary brain tumors, adenomas, infarction associated with pregnancy, hypophysectomy, aneurysms, vascular malformations, thrombosis, infections, immunological disorders, and complications due to head trauma; disorders associated with hyperpituitarism including acromegaly, giantism, and syndrome of inappropriate antidiuretic hormone (ADH) secretion (SIADH) often caused by benign adenoma; disorders associated with hypothyroidism including goiter, myxedema, acute thyroiditis associated with bacterial infection;
disorders associated with hyperparathyroidism including Conn disease (chronic hypercalemia);
pancreatic disorders such as Type I or Type II diabetes mellitus and associated complications;
disorders associated with the adrenals such as hyperplasia, carcinoma, or adenoma of the adrenal cortex, hypertension associated with alkalosis; disorders associated with gonadal steroid hormones such as: in women, abnormal prolactin production, infertility, endometriosis, perturbations of the menstrual cycle, polycystic ovarian disease, hyperprolactinemia, isolated gonadotropin deficiency, amenorrhea, galactorrhea, hermaphroditism, hirsutism and virilization, breast cancer, and, in post-menopausal women, osteoporosis; and, in men, Leydig cell deficiency, male climacteric phase, and germinal cell aplasia, hypergonadal disorders associated with Leydig cell tumors, androgen resistance associated with absence of androgen receptors, syndrome of 5 a-reductase, and gynecomastia; and a cell proliferative disorder such as actinic keratosis, arteriosclerosis, atherosclerosis, bursitis, cirrhosis, hepatitis, mixed connective tissue disease (MCTD), myelolibrosis, paroxysmal nocturnal SUBSTITUTE SHEET (RULE 26) hemoglobinuria, polycythemia vera, psoriasis, primary thrombocythemia, and cancers including adenocarcinoma, leukemia, lymphoma, melanoma, myeloma, sarcoma, teratocarcinoma, and, in particular, cancers of the adrenal gland, bladder, bone, bone marrow, brain, breast, cervix, gall bladder, ganglia, gastrointestinal tract, heart, kidney, liver, lung, muscle, ovary, pancreas, parathyroid, penis, prostate, salivary glands, skin, spleen, testis, thymus, thyroid, and uterus . The polynucleotide sequences encoding GBAP may be used in Southern or northern analysis, dot blot, or other membrane-based technologies; in PCR technologies; in dipstick, pin, and multiformat ELISA-like assays; and in microarrays utilizing fluids or tissues from patients to detect altered GBAP expression.
Such qualitative or quantitative methods are well known in the art.
In a particular aspect, the nucleotide sequences encoding GBAP may be useful in assays that detect the presence of associated disorders, particularly those mentioned above. The nucleotide sequences encoding GBAP may be labeled by standard methods and added to a fluid or tissue sample from a patient under conditions suitable for the formation of hybridization complexes. After a suitable incubation period, the sample is washed and the signal is quantified and compared with a standard value. If the amount of signal in the patient sample is significantly altered in comparison to a control sample then the presence of altered levels of nucleotide sequences encoding GBAP in the sample indicates the presence of the associated disorder. Such assays may also be used to evaluate the efficacy of a particular therapeutic treatment regimen in animal studies, in clinical trials, or to monitor the treatment of an individual patient.
In order to provide a basis for the diagnosis of a disorder associated with expression of GBAP, a normal or standard profile for expression is established. This may be accomplished by combining body fluids or cell extracts taken from normal subjects, either animal or human, with a sequence, or a fragment thereof, encoding GBAP, under conditions suitable for hybridization or amplification.
Standard hybridization may be quantified by comparing the values obtained from normal subjects with values from an experiment in which a known amount of a substantially purified polynucleotide is used.
Standard values obtained in this manner may be compared with values obtained from samples from patients who are symptomatic for a disorder. Deviation from standard values is used to establish the presence of a disorder.
Once the presence of a disorder is established and a treatment protocol is initiated, hybridization assays may be repeated on a regular basis to determine if the level of expression in the patient begins to approximate that which is observed in the normal subject.
The results obtained from successive assays may be used to show the efficacy of treatment over a period ranging from several days to months.
With respect to cancer, the presence of an abnormal amount of transcript (either under- or overexpressed) in biopsied tissue from an individual may indicate a predisposition for the development SUBSTITUTE SHEET (RULE 26) of the disease, or may provide a means for detecting the disease prior to the appearance of actual clinical symptoms. A more definitive diagnosis of this type may allow health professionals to employ preventative measures or aggressive treatment earlier thereby preventing the development or further progression of the cancer.
Additional diagnostic uses for oligonucleotides designed from the sequences encoding GBAP
may involve the use of PCR. These oligomers may be chemically synthesized, generated enzymatically, or produced in vitro. Oligomers will preferably contain a fragment of a polynucleodde encoding GBAP, or a fragment of a polynucleotide complementary to the polynucleotide encoding GBAP, and will be employed under optimized conditions for identification of a specific gene or condition.
Oligomers may also be employed under less stringent conditions for detection or quantification of closely related DNA or RNA sequences.
In a particular aspect, oligonucleotide primers derived from the polynucleotide sequences encoding GBAP may be used to detect single nucleotide polymorphisms (SNPs).
SNPs are substitutions, insertions and deletions that are a frequent cause of inherited or acquired genetic disease in humans. Methods of SNP detection include, but are not limited to, single-stranded conformation polymorphism (SSCP) and fluorescent SSCP (fSSCP) methods. In SSCP, oligonucleotide primers derived from the polynucleotide sequences encoding GBAP are used to amplify DNA using the polymerase chain reaction (PCR). The DNA may be derived, for example, from diseased or normal tissue, biopsy samples, bodily fluids, and the like. SNPs in the DNA cause differences in the secondary and tertiary structures of PCR products in single-stranded form, and these differences are detectable using gel electrophoresis in non-denaturing gels. In f~SCCP, the oligonucleotide primers are lluorescently labeled, which allows detection of the amplimers in high-throughput equipment such as DNA sequencing machines. Additionally, sequence database analysis methods, termed in silico SNP
(isSNP), are capable of identifying polymorphisms by comparing the sequence of individual overlapping DNA fragments which assemble into a common consensus sequence.
These computer-based methods Iilter out sequence variations due to laboratory preparation of DNA and sequencing errors using statistical models and automated analyses of DNA sequence chromatograms. In the alternative, SNPs may be detected and characterized by mass spectrometry using, for example, the high throughput MASSARRAY system (Sequenom, Inc., San Diego CA).
Methods which may also be used to quantify the expression of GBAP include radiolabeling or biotinylaling nucleotides, coamplification of a control nucleic acid, and interpolating results from standard curves. (See, e.g., Melby, P.C. et al. (1993) J. Immunol. Methods 159:235-244; Duplaa, C. et al. (1993) Anal. Biochem. 212:229-236.) The speed of quantitation of multiple samples may be accelerated by running the assay in a high-throughput format where the oligomer or polynucleotide of interest is presented in various dilutions and a speclrophotometric or colorimetric response gives rapid SUBSTITUTE SHEET (RULE 26) quantitation.
In further embodiments, oligonucleotides or longer fragments derived from any of the polynucleotide sequences described herein may be used as elements on a microarray. The microarray can be used in transcript imaging techniques which monitor the relative expression levels of large numbers of genes simultaneously as described in Seilhamer, J.J. et al., "Comparative Gene Transcript Analysis," U.S. Patent No. 5,840,484, incorporated herein by reference. The microarray may also be used to identify genetic variants, mutations, and polymorphisms. This information may be used to determine gene function, to understand the genetic basis of a disorder, to diagnose a disorder, to monitor progression/regression of disease as a function of gene expression, and to develop and monitor the activities of therapeutic agents in the treatment of disease. In particular, this information may be used to develop a pharmacogenomic profile of a patient in order to select the most appropriate and effective treatment regimen for that patient. For example, therapeutic agents which are highly effective and display the fewest side effects may be selected for a patient based on his/her pharmacogenomic profile.
In another embodiment, antibodies specific for GBAP, or GBAP or fragments thereof may be used as elements on a microarray. The microarray may be used to monitor or measure protein-protein interactions, drug-target interactions, and gene expression profiles, as described above.
A particular embodiment relates to the use of the polynucleotides of the present invention to generate a transcript image of a tissue or cell type. A transcript image represents the global pattern of gene expression by a particular tissue or cell type. Global gene expression patterns are analyzed by quantifying the number of expressed genes and their relative abundance under given conditions and at a given time. (See Seilhamer et al., "Comparative Gene Transcript Analysis,"
U.S. Patent Number 5,840,484, expressly incorporated by reference herein.) Thus a transcript image may be generated by hybridizing the polynucleotides of the present invention or their complements to the totality of transcripts or reverse transcripts of a particular tissue or cell type. In one embodiment, the hybridization takes place in high-throughput format, wherein the polynucleotides of the present invention or their complements comprise a subset of a plurality of elements on a microarray. The resultant transcript image would provide a profile of gene activity.
Transcript images may be generated using transcripts isolated from tissues, cell lines, biopsies, or other biological samples. The transcript image may thus reflect gene expression in vivo, as in the case of a tissue or biopsy sample, or in vitro, as in the case of a cell line.
Transcript images which profile the expression of the polynucleotides of the present invention may also be used in conjunction with in vitro model systems and preclinical evaluation of pharmaceuticals, as well as toxicological testing of industrial and naturally-occurring environmental compounds. All compounds induce characteristic gene expression patterns, frequently termed molecular fingerprints or toxicant signatures, which are indicative of mechanisms of action and toxicity SUBSTITUTE SHEET (RULE 26) (Nuwaysir, E.F. et al. (1999) Mol. Carcinog. 24:153-159; Steiner, S. and N.L.
Anderson (2000) Toxicol. Lett. 112-113:467-471, expressly incorporated by reference herein).
If a test compound has a signature similar to that of a compound with known toxicity, it is likely to share those toxic properties.
These fingerprints or signatures are most useful and refined when they contain expression information from a large number of genes and gene families. Ideally, a genome-wide measurement of expression provides the highest quality signature. Even genes whose expression is not altered by any tested compounds are important as well, as the levels of expression of these genes are used to normalize the rest of the expression data. The normalization procedure is useful for comparison of expression data after treatment with different compounds. While the assignment of gene function to elements of a toxicant signature aids in interpretation of toxicity mechanisms, knowledge of gene function is not necessary for the statistical matching of signatures which leads to prediction of toxicity. (See, for example, Press Release 00-02 from the National Institute of Environmental Health Sciences, released February 29, 2000, available at http://www.niehs.nih.gov/oc/news/toxchip.htm.) Therefore, it is important and desirable in toxicological screening using toxicant signatures to include all expressed gene sequences.
In one embodiment, the toxicity of a test compound is assessed by treating a biological sample containing nucleic acids with the test compound. Nucleic acids that are expressed in the treated biological sample are hybridized with one or more probes specific to the polynucleotides of the present invention, so that transcript levels corresponding to the polynucleotides of the present invention may be quantified. The transcript levels in the treated biological sample are compared with levels in an untreated biological sample. Differences in the transcript levels between the two samples are indicative of a toxic response caused by the test compound in the treated sample.
Another particular embodiment relates to the use of the polypeptide sequences of the present invention to analyze the proteome of a tissue or cell type. The term proteome refers to the global pattern of protein expression in a particular tissue or cell type. Each protein component of a proteome can be subjected individually to further analysis. Proteome expression patterns, or profiles, are analyzed by quantifying the number of expressed proteins and their relative abundance under given conditions and at a given time. A profile of a cell's proteome may thus be generated by separating and analyzing the polypeptides of a particular tissue or cell type. In one embodiment, the separation is achieved using two-dimensional gel electrophoresis, in which proteins from a sample are separated by isoelectric focusing in the first dimension, and then according to molecular weight by sodium dodecyl sulfate slab gel electrophoresis in the second dimension (Steiner and Anderson, supra). The proteins are visualized in the gel as discrete and uniquely positioned spots, typically by staining the gel with an agent such as Coomassie Blue or silver or fluorescent stains. The optical density of each protein spot is generally proportional to the level of the protein in the sample. The optical densities of equivalently SUBSTITUTE SHEET (RULE 26) positioned protein spots from different samples, for example, from biological samples either treated or untreated with a test compound or therapeutic agent, are compared to identify any changes in protein spot density related to the treatment. The proteins in the spots are partially sequenced using, for example, standard methods employing chemical or enzymatic cleavage followed by mass spectrometry.
The identity of the protein in a spot may be determined by comparing its partial sequence, preferably of at least 5 contiguous amino acid residues, to the polypeptide sequences of the present invention. In some cases, further sequence data may be obtained for definitive protein identification.
A proteomic profile may also be generated using antibodies specific for GBAP
to quantify the levels of GBAP expression. In one embodiment, the antibodies are used as elements on a microarray, and protein expression levels are quantified by exposing the microarray to the sample and detecting the levels of protein bound to each array element (Lueking, A. et al. (1999) Anal.
Biochem. 270:103-111;
Mendoze, L.G. et al. (1999) Biotechniques 27:778-788). Detection may be performed by a variety of methods known in the art, for example, by reacting the proteins in the sample with a thiol- or amino-reactive fluorescent compound and detecting the amount of fluorescence bound at each array element.
Toxicant signatures at the proteome level are also useful for toxicological screening, and should be analyzed in parallel with toxicant signatures at the transcript level.
There is a poor correlation between transcript and protein abundances for some proteins in some tissues (Anderson, N.L. and J.
Seilhamer (1997) Electrophoresis 18:533-537), so proteome toxicant signatures may be useful in the analysis of compounds which do not significantly affect the transcript image, but which alter the proteomic profile. In addition, the analysis of transcripts in body fluids is difficult, due to rapid degradation of mRNA, so proteomic profiling may be more reliable and informative in such cases.
In another embodiment, the toxicity of a test compound is assessed by treating a biological sample containing proteins with the test compound. Proteins that are expressed in the treated biological sample are separated so that the amount of each protein can be quantified. The amount of each protein is compared to the amount of the corresponding protein in an untreated biological sample. A difference in the amount of protein between the two samples is indicative of a toxic response to the test compound in the treated sample. Individual proteins are identified by sequencing the amino acid residues of the individual proteins and comparing these partial sequences to the polypeptides of the present invention.
In another embodiment, the toxicity of a test compound is assessed by treating a biological sample containing proteins with the test compound. Proteins from the biological sample are incubated with antibodies specific to the polypeptides of the present invention. The amount of protein recognized by the antibodies is quantified. The amount of protein in the treated biological sample is compared with the amount in an untreated biological sample. A difference in the amount of protein between the two samples is indicative of a toxic response to the test compound in the treated sample.
Microarrays may be prepared, used, and analyzed using methods known in the art. (See, e.g., SUBSTITUTE SHEET (RULE 26) Brennan, T.M. et al. (1995) U.S. Patent No. 5,474,796; Schena, M. et al.
(1996) Proc. Natl. Acad. Sci.
USA 93:10614-10619; Baldeschweiler et al. (1995) PCT application W095/251116;
Shalom D. et al.
(1995) PCT application W095/35505; Heller, R.A. et al. (1997) Proc. Natl.
Acad. Sci. USA 94:2150-2155; and Heller, M.J. et al. (1997) U.S. Patent No. 5,605,662.) Various types of microarrays are well known and thoroughly described in DNA Microarrays: A Practical Approach, M.
Schena, ed. (1999) Oxford University Press, London, hereby expressly incorporated by reference.
In another embodiment of the invention, nucleic acid sequences encoding GBAP
may be used to generate hybridization probes useful in mapping the naturally occurring genomic sequence. Either coding or noncoding sequences may be used, and in some instances, noncoding sequences may be preferable over coding sequences. For example, conservation of a coding sequence among members of a multi-gene family may potentially cause undesired cross hybridization during chromosomal mapping. The sequences may be mapped to a particular chromosome, to a specific region of a chromosome, or to artificial chromosome constructions, e.g., human artificial chromosomes (HACs), yeast artificial chromosomes (YACs), bacterial artificial chromosomes (BACs), bacterial P1 constructions, or single chromosome cDNA libraries. (See, e.g., Harrington, J.J. et al. (1997) Nat.
Genet. 15:345-355; Price, C.M. (1993) Blood Rev. 7:127-134; and Trask, B.J.
(1991) Trends Genet.
7:149-154.) Once mapped, the nucleic acid sequences of the invention may be used to develop genetic linkage maps, for example, which correlate the inheritance of a disease state with the inheritance of a particular chromosome region or restriction fragment length polymorphism (RFLP). (See, e.g., Lander, E.S. and D. Botstein (1986) Proc. Natl. Acad. Sci. USA 83:7353-7357.) Fluorescent in situ hybridization (FISH) may be correlated with other physical and genetic map data. (See, e.g., Heinz-Ulrich, et al. (1995) in Meyers, su ra, pp. 965-968.) Examples of genetic map data can be found in various scientific journals or at the Online Mendelian Inheritance in Man (OMIM) World Wide Web site. Correlation between the location of the gene encoding GBAP on a physical map and a specific disorder, or a predisposition to a specific disorder, may help define the region of DNA
associated with that disorder and thus may further positional cloning efforts.
In situ hybridization of chromosomal preparations and physical mapping techniques, such as linkage analysis using established chromosomal markers, may be used for extending genetic maps.
Often the placement of a gene on the chromosome of another mammalian species, such as mouse, may reveal associated markers even if the exact chromosomal locus is not known.
This information is valuable to investigators searching for disease genes using positional cloning or other gene discovery techniques. Once the gene or genes responsible for a disease or syndrome have been crudely localized by genetic linkage to a particular genomic region, e.g., ataxia-telangiectasia to l 1q22-23, any sequences mapping to that area may represent associated or regulatory genes for further investigation. (See, e.g., Gatti, R.A. et al. (1988) Nature 336:577-580.) The nucleotide sequence of the instant invention may SUBSTITUTE SHEET (RULE 26) also be used to detect differences in the chromosomal location due to translocation, inversion, etc., among normal, carrier, or affected individuals.
In another embodiment of the invention, GBAP, its catalytic or immunogenic fragments, or oligopeptides thereof can be used for screening libraries of compounds in any of a variety of drug screening techniques. The fragment employed in such screening may be free in solution, affixed to a solid support, borne on a cell surface, or located intracellularly. The formation of binding complexes between GBAP and the agent being tested may be measured.
Another technique for drug screening provides for high throughput screening of compounds having suitable binding affinity to the protein of interest. (See, e.g., Geysen, et al. (1984) PCT
application W084/03564.) In this method, large numbers of different small test compounds are synthesized on a solid substrate. The test compounds are reacted with GBAP, or fragments thereof, and washed. Bound GBAP is then detected by methods well known in the art. Purified GBAP can also be coated directly onto plates for use in the aforementioned drug screening techniques. Alternatively, non-neutralizing antibodies can be used to capture the peptide and immobilize it on a solid support.
In another embodiment, one may use competitive drug screening assays in which neutralizing antibodies capable of binding GBAP specifically compete with a test compound for binding GBAP. In this manner, antibodies can be used to detect the presence of any peptide which shares one or more antigenic determinants with GBAP.
In additional embodiments, the nucleotide sequences which encode GBAP may be used in any molecular biology techniques that have yet to be developed, provided the new techniques rely on properties of nucleotide sequences that are currently known, including, but not limited to, such properties as the triplet genetic code and specific base pair interactions.
Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. The following preferred specific embodiments are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.
The disclosures of all patents, applications and publications, mentioned above and below, in particular U.S. Ser. No. 60/144,595, U.S Ser. No. 60/150,460, and U.S. Ser.
No. 60/159,849, are hereby expressly incorporated by reference.
EXAMPLES
I. Construction of eDNA Libraries RNA was purchased from Clontech or isolated from tissues described in Table 4.
Some tissues were homogenized and lysed in guanidinium isothiocyanate, while others were homogenized and lysed in phenol or in a suitable mixture of denaturants, such as TRIZOL (Life Technologies), a monophasic SUBSTITUTE SHEET (RULE 26) solution of phenol and guanidine isothiocyanate. The resulting lysates were centrifuged over CsCI
cushions or extracted with chloroform. RNA was precipitated from the lysates with either isopropanol or sodium acetate and ethanol, or by other routine methods.
Phenol extraction and precipitation of RNA were repeated as necessary to increase RNA
purity. In some cases, RNA was treated with DNase. For most libraries, poly(A+) RNA was isolated using oligo d(T)-coupled paramagnetic particles (Promega), OLIGOTEX latex particles (QIAGEN, Chatsworth CA), or an OLIGOTEX mRNA purification kit (QIAGEN). Alternatively, RNA was isolated directly from tissue lysates using other RNA isolation kits, e.g., the POLY(A)PURE mRNA
purification kit (Ambion, Austin TX).
In some cases, Stratagene was provided with RNA and constructed the corresponding cDNA
libraries. Otherwise, cDNA was synthesized and cDNA libraries were constructed with the UNIZAP
vector system (Stratagene) or SUPERSCRIPT plasmid system (Life Technologies), using the recommended procedures or similar methods known in the art. (See, e.g., Ausubel, 1997, supra, units 5.1-6.6.) Reverse transcription was initiated using oligo d(T) or random primers. Synthetic oligonucleotide adapters were ligated to double stranded cDNA, and the cDNA
was digested with the appropriate restriction enzyme or enzymes. For most libraries, the cDNA was size-selected (300-1000 bp) using SEPHACRYL S 1000, SEPHAROSE CL2B, or SEPHAROSE CL4B column chromatography (Amersham Pharmacia Biotech) or preparative agarose gel electrophoresis. cDNAs were ligated into compatible restriction enzyme sites of the polylinker of a suitable plasmid, e.g., PBLUESCRIPT plasmid (Stratagene), PSPORT1 plasmid (Life Technologies), pcDNA2.1 plasmid (Invitrogen, Carlsbad CA), or pINCY plasmid (Incyte Genomics, Palo Alto CA).
Recombinant plasmids were transformed into competent E. coli cells including XL1-Blue, XL1-BIueMRF, or SOLR
from Stratagene or DHSa, DH10B, or ElectroMAX DH10B from Life Technologies.
II. Isolation of cDNA Clones Plasmids obtained as described in Example I were recovered from host cells by in vivo excision using the UNIZAP vector system (Stratagene) or by cell lysis. Plasmids were purified using at least one of the following: a Magic or WIZARD Minipreps DNA purification system (Promega); an AGTC
Miniprep purification kit (Edge Biosystems, Gaithersburg MD); and QIAWELL 8 Plasmid, QIAWELL
8 Plus Plasmid, QIAWELL 8 Ultra Plasmid purification systems or the R.E.A.L.
PREP 96 plasmid purification kit from QIAGEN. Following precipitation, plasmids were resuspended in 0.1 ml of distilled water and stored, with or without lyophilization, at 4°C.
Alternatively, plasmid DNA was amplified from host cell lysates using direct link PCR in a high-throughput format (Rao, V.B. (1994) Anal. Biochem. 216:1-14). Host cell lysis and thermal cycling steps were carried out in a single reaction mixture. Samples were processed and stored in 384-well plates, and the concentration of amplified plasmid DNA was quantified fluorometrically using SUBSTITUTE SHEET (RULE 26) PICOGREEN dye (Molecular Probes, Eugene OR) and a FLUOROSKAN II fluorescence scanner (Labsystems Oy, Helsinki, Finland).
III. Sequencing and Analysis Incyte eDNA recovered in plasmids as described in Example II were sequenced as follows.
Sequencing reactions were processed using standard methods or high-throughput instrumentation such as the ABI CATALYST 800 (PE Biosystems) thermal cycler or the PTC-200 thermal cycler (MJ
Research) in conjunction with the HYDRA microdispenser (Robbins Scientific) or the MICROLAB
2200 (Hamilton) liquid transfer system. cDNA sequencing reactions were prepared using reagents provided by Amersham Pharmacia Biotech or supplied in ABI sequencing kits such as the ABI
PRISM BIGDYE Terminator cycle sequencing ready reaction kit (PE Biosystems).
Electrophoretic separation of cDNA sequencing reactions and detection of labeled polynucleotides were carried out using the MEGABACE 1000 DNA sequencing system (Molecular Dynamics); the ABI
PRISM 373 or 377 sequencing system (PE Biosystems) in conjunction with standard ABI
protocols and base calling software; or other sequence analysis systems known in the art. Reading dames within the cDNA
sequences were identified using standard methods (reviewed in Ausubel, 1997, su ra, unit 7.7). Some of the cDNA sequences were selected for extension using the techniques disclosed in Example VI.
The polynucleotide sequences derived from cDNA sequencing were assembled and analyzed using a combination of software programs which utilize algorithms well known to those skilled in the art. Table 5 summarizes the tools, programs, and algorithms.used and provides applicable descriptions, references, and threshold parameters. The first column of Table 5 shows the tools, programs, and algorithms used, the second column provides brief descriptions thereof, the third column presents appropriate references, all of which are incorporated by reference herein in their entirety, and the fourth column presents, where applicable, the scores, probability values, and other parameters used to evaluate the strength of a match between two sequences (the higher the score, the greater the homology between two sequences). Sequences were analyzed using MACDNASIS PRO software (Hitachi Software Engineering, South San Francisco CA) and LASERGENE software (DNASTAR).
Polynucleotide and polypeptide sequence alignments were generated using the default parameters specified by the clustal algorithm as incorporated into the MEGALIGN multisequence alignment program (DNASTAR), which also calculates the percent identity between aligned sequences.
The polynucleotide sequences were validated by removing vector, linker, and polyA sequences and by masking ambiguous bases, using algorithms and programs based on BLAST, dynamic programing, and dinucleotide nearest neighbor analysis. The sequences were then queried against a selection of public databases such as the GenBank primate, rodent, mammalian, vertebrate, and eukaryote databases, and BLOCKS, PRINTS, DOMO, PRODOM, and PFAM to acquire annotation using programs based on BLAST, FASTA, and BLIMPS. The sequences were assembled into full SUBSTITUTE SHEET (RULE 26) length polynucleotide sequences using programs based on Phred, Phrap, and Consed, and were screened for open reading frames using programs based on GeneMark, BLAST, and FASTA.
The full length polynucleotide sequences were translated to derive the corresponding full length amino acid sequences, and these full length sequences were subsequently analyzed by querying against databases such as the GenBank databases (described above), SwissProt, BLOCKS, PRINTS, DOMO, PRODOM, Prosite, and Hidden Markov Model (HMM)-based protein family databases such as PFAM. HMM
is a probabilistic approach which analyzes consensus primary structures of gene families. (See, e.g., Eddy, S.R. (1996) Curr. Opin. Struct. Biol. 6:361-365.) The programs described above for the assembly and analysis of full length polynucleotide and amino acid sequences were also used to identify polynucleotide sequence fragments from SEQ ID
N0:67-132. Fragments from about 20 to about 4000 nucleotides which are useful in hybridization and amplification technologies were described in The Invention section above.
IV. Analysis of Polynucleotide Expression Northern analysis is a laboratory technique used to detect the presence of a transcript of a gene and involves the hybridization of a labeled nucleotide sequence to a membrane on which RNAs from a particular cell type or tissue have been bound. (See, e.g., Sambrook, supra, ch. 7; Ausubel, 1995, supra, ch. 4 and 16.) Analogous computer techniques applying BLAST were used to search for identical or related molecules in cDNA databases such as GenBank or LIFESEQ (Incyte Genomics). This analysis is much faster than multiple membrane-based hybridizations. 1n addition, the sensitivity of the computer search can be modified to determine whether any particular match is categorized as exact or similar.
The basis of the search is the product score, which is defined as:
BLAST Score x Percent Identity 5 x minimum {length(Seq. 1), length(Seq. 2)}
The product score takes into account both the degree of similarity between two sequences and the length of the sequence match. The product score is a normalized value between 0 and 100, and is calculated as follows: the BLAST score is multiplied by the percent nucleotide identity and the product is divided by (5 times the length of the shorter of the two sequences). The BLAST score is calculated by assigning a score of +5 for every base that matches in a high-scoring segment pair (HSP), and -4 for every mismatch. Two sequences may share more than one HSP (separated by gaps).
If there is more than one HSP, then the pair with the highest BLAST score is used to calculate the product score. The product score represents a balance between fractional overlap and quality in a BLAST alignment. For example, a product score of 100 is produced only for 100% identity over the entire length of the shorter of the two sequences being compared. A product score of 70 is produced either by 100% identity and SUBSTITUTE SHEET (RULE 26) 70% overlap at one end, or by 88% identity and 100% overlap at the other. A
product score of 50 is produced either by 100% identity and 50% overlap at one end, or 79% identity and 100% overlap.
The results of northern analyses are reported as a percentage distribution of libraries in which the transcript encoding GBAP occurred. Analysis involved the categorization of cDNA libraries by organ/tissue and disease. The organ/dssue categories included cardiovascular, dermatologic, developmental, endocrine, gastrointestinal, hematopoietic/immune, musculoskeletal, nervous, reproductive, and urologic. The disease/condition categories included cancer, inflammation, trauma, cell proliferation, neurological, and pooled. For each category, the number of libraries expressing the sequence of interest was counted and divided by the total number of libraries across all categories.
Percentage values of tissue-specific and disease- or condition-specific expression are reported in Table 3.
V. Chromosomal Mapping of GBAP Encoding Polynucleotides The cDNA sequences which were used to assemble SEQ ID N0:67-132 were compared with sequences from the Incyte LIFESEQ database and public domain databases using BLAST and other implementations of the Smith-Waterman algorithm. Sequences from these databases that matched SEQ ID N0:67-132 were assembled into clusters of contiguous and overlapping sequences using assembly algorithms such as Phrap (Table 5). Radiation hybrid and genetic mapping data available from public resources such as the Stanford Human Genome Center (SHGC), Whitehead Institute for Genome Research (WIGR), and Gen~thon were used to determine if any of the clustered sequences had been previously mapped. Inclusion of a mapped sequence in a cluster resulted in the assignment of all sequences of that cluster, including its particular SEQ ID NO:, to that map location.
The genetic map locations of SEQ ID N0:70, 74, 75, 77, 80, 86, 87, 90, 92, 93, 94, 97, 101, 106, 109, 111, 112, 113, 1 I5, 117, 118, 121, and 128 are described in The Invention as ranges, or intervals, of human chromosomes. More than one map location is reported for SEQ ID N0:94, 101, 109, 111, and 115, indicating that previously mapped sequences having similarity, but not complete identity, to SEQ ID N0:94, 101, 109, 111, and 115 were assembled into their respective clusters.
The map position of an interval, in centiMorgans, is measured relative to the terminus of the chromosome's p-arm. (The centiMorgan (cM) is a unit of measurement based on recombination frequencies between chromosomal markers. On average, 1 cM is roughly equivalent to 1 megabase (Mb) of DNA in humans, although this can vary widely due to hot and cold spots of recombination.) The eM distances are based on genetic markers mapped by Genethon which provide boundaries for radiation hybrid markers whose sequences were included in each of the clusters.
VI. Extension of GBAP Encoding Polynucleotides The full length nucleic acid sequences of SEQ ID N0:67-132 were produced by extension of an appropriate fragment of the full length molecule using oligonucleotide primers designed from this SUBSTITUTE SHEET (RULE 26) fragment. One primer was synthesized to initiate 5' extension of the known fragment, and the other primer, to initiate 3' extension of the known fragment. The initial primers were designed using OLIGO

4.06 software (National Biosciences), or another appropriate program, to be about 22 to 30 nucleotides in length, to have a GC content of about 50% or more, and to anneal to the target sequence at temperatures of about 68°C to about 72°C. Any stretch of nucleotides which would result in hairpin structures and primer-primer dimerizations was avoided.
Selected human cDNA libraries were used to extend the sequence. If more than one extension was necessary or desired, additional or nested sets of primers were designed.
High fidelity amplification was obtained by PCR using methods well known in the art. PCR
was performed in 96-well plates using the PTC-200 thermal cycler (MJ Research, Inc.). The reaction mix contained DNA template, 200 nmol of each primer, reaction buffer containing Mg2+, (NH4)2S04, and ~3-mercaptoethanol, Taq DNA polymerase (Amersham Pharmacia Biotech), ELONGASE enzyme (Life Technologies), and Pfu DNA polymerase (Stratagene), with the following parameters for primer pair PCI A and PCI B: Step 1: 94°C, 3 min; Step 2: 94°C, 15 sec;
Step 3: 60°C, 1 min; Step 4: 68°C, 2 min; Step 5: Steps 2, 3, and 4 repeated 20 times; Step 6: 68°C, 5 min; Step 7: storage at 4°C. In the alternative, the parameters for primer pair T7 and SK+ were as follows: Step 1: 94°C, 3 min; Step 2:
94°C, 15 sec; Step 3: 57°C, 1 min; Step 4: 68°C, 2 min;
Step 5: Steps 2, 3, and 4 repeated 20 times;
Step 6: 68°C, 5 min; Step 7: storage at 4°C.
The concentration of DNA in each well was determined by dispensing 100 p1 PICOGREEN
quantitation reagent (0.25% (v/v) PICOGREEN; Molecular Probes, Eugene OR) dissolved in IX TE
and 0.5 p1 of undiluted PCR product into each well of an opaque tluorimeter plate (Corning Costar, Acton MA), allowing the DNA to bind to the reagent. The plate was scanned in a Fluoroskan II
(Labsystems Oy, Helsinki, Finland) to measure the fluorescence of the sample and to quantify the concentration of DNA. A 5 ~1 to 10 gel aliquot of the reaction mixture was analyzed by electrophoresis on a 1 % agarose mini-gel to determine which reactions were successful in extending the sequence.
The extended nucleotides were desalted and concentrated, transferred to 384-well plates, digested with CviJI cholera virus endonuclease (Molecular Biology Research, Madison WI), and sonicated or sheared prior to religation into pUC 18 vector (Amersham Pharmacia Biotech). For shotgun sequencing, the digested nucleotides were separated on low concentration (0.6 to 0.8%) agarose gels, fragments were excised, and agar digested with Agar ACE (Promega).
Extended clones were religated using T4 ligase (New England Biolabs, Beverly MA) into pUC 18 vector (Amersham Pharmacia Biotech), treated with Pfu DNA polymerase (Stratagene) to till-in restriction site overhangs, and transfected into competent E. coli cells. Transformed cells were selected on antibiotic-containing media, and individual colonies were picked and cultured overnight at 37 °C in 384-well plates in LB/2x curb liquid media.

SUBSTITUTE SHEET (RULE 26) The cells were lysed, and DNA was amplified by PCR using Taq DNA polymerase (Amersham Pharmacia Biotech) and Pfu DNA polymerase (Stratagene) with the following parameters: Step 1:
94°C, 3 min; Step 2: 94°C, 15 .sec; Step 3: 60°C, 1 min;
Step 4: 72°C, 2 min; Step 5: steps 2, 3, and 4 repeated 29 times; Step 6: 72°C, 5 min; Step 7: storage at 4°C.
DNA was quantified by PICOGREEN
reagent (Molecular Probes) as described above. Samples with low DNA recoveries were reamplified using the same conditions as described above. Samples were diluted with 20%
dimethysulfoxide (1:2, v/v), and sequenced using DYENAMIC energy transfer sequencing primers and the DYENAMIC
DIRECT kit (Amersham Pharmacia Biotech) or the ABI PRISM BIGDYE Terminator cycle sequencing ready reaction kit (PE Biosystems).
In like manner, the polynucleotide sequences of SEQ ID N0:67-132 are used to obtain 5' regulatory sequences using the procedure above, along with oligonucleotides designed for such extension, and an appropriate genomic library.
VII. Labeling and Use of Individual Hybridization Probes Hybridization probes derived from SEQ ID N0:67-132 are employed to screen cDNAs, genomic DNAs, or mRNAs. Although the labeling of oligonucleotides, consisting of about 20 base pairs, is specifically described, essentially the same procedure is used with larger nucleotide fragments.
Oligonucleotides are designed using state-of the-art software such as OLIGO
4.06 software (National Biosciences) and labeled by combining 50 pmol of each oligomer, 250 ~cCi of [~y 32P] adenosine triphosphate (Amersham Pharmacia Biotech), and T4 polynucleodde kinase (DuPont NEN, Boston MA). The labeled oligonucleotides are substantially purified using a SEPHADEX
G-25 superfine size exclusion dextran bead column (Amersham Pharmacia Biotech). An aliquot containing 10' counts per minute of the labeled probe is used in a typical membrane-based hybridization analysis of human genomic DNA digested with one of the following endonucleases: Ase I, Bgl II, Eco RI, Pst I, Xba I, or Pvu II (DuPont NEN).
The DNA from each digest is fractionated on a 0.7% agarose gel and transferred to nylon membranes (Nytran Plus, Schleicher & Schuell, Durham NH). Hybridization is carried out for 16 hours at 40°C. To remove nonspecific signals, blots are sequentially washed at room temperature under conditions of up to, for example, 0.1 x saline sodium citrate and 0.5%
sodium dodecyl sulfate.
Hybridization patterns are visualized using autoradiography or an alternative imaging W ears and compared.
VIII. Microarrays The linkage or synthesis of array elements upon a microarray can be achieved utilizing photolithography, piezoelectric printing (ink-jet printing, See, e.g., Baldeschweiler, supra), mechanical microspotting technologies, and derivatives thereof. The substrate in each of the aforementioned technologies should be uniform and solid with a non-porous surface (Schena (1999), su ra). Suggested SUBSTITUTE SHEET (RULE 26) substrates include silicon, silica, glass slides, glass chips, and silicon wafers. Alternatively, a procedure analogous to a dot or slot blot may also be used to arrange and link elements to the surface of a substrate using thermal, UV, chemical, or mechanical bonding procedures. A
typical array may be produced using available methods and machines well known to those of ordinary skill in the art and may contain any appropriate number of elements. (See, e.g., Schena, M. et al.
(1995) Science 270:467-470;
Shalom D. et al. (1996) Genome Res. 6:639-645; Marshall, A. and J. Hodgson (1998) Nat. Biotechnol.
16:27-31.) Full length cDNAs, Expressed Sequence Tags (ESTs), or fragments or oligomers thereof may comprise the elements of the microarray. Fragments or oligomers suitable for hybridization can be selected using software well known in the art such as LASERGENE software (DNASTAR). The array elements are hybridized with polynucleotides in a biological sample. The polynucleotides in the biological sample are conjugated to a fluorescent label or other molecular tag for ease of detection.
After hybridization, nonhybridized nucleotides from the biological sample are removed, and a fluorescence scanner is used to detect hybridization at each array element.
Alternatively, laser desorbtion and mass spectrometry may be used for detection of hybridization.
The degree of complementarity and the relative abundance of each polynucleotide which hybridizes to an element on the microarray may be assessed. In one embodiment, microarray preparation and usage is described in detail below.
Tissue or Cell Sample Preparation Total RNA is isolated from tissue samples using the guanidinium thiocyanate method and poly(A)+ RNA is purified using the oligo-(dT) cellulose method. Each poly(A)+
RNA sample is reverse transcribed using MMLV reverse-transcriptase, 0.05 pg/Nl oligo-(dT) primer (21 mer), 1X first strand buffer, 0.03 units/fil RNase inhibitor, 500 ~M dATP, 500 pIVI dGTP, 500 NM dTTP, 40 pM
dCTP, 40 pM dCTP-Cy3 (BDS) or dCTP-Cy5 (Amersham Pharmacia Biotech). The reverse transcription reaction is performed in a 25 ml volume containing 200 ng poly(A)+ RNA with GEMBRIGHT kits (lncyte). Specific control poly(A)+ RNAs are synthesized by in vitro transcription from non-coding yeast genomic DNA. After incubation at 37 °C for 2 hr, each reaction sample (one with Cy3 and another with Cy5 labeling) is treated with 2.5 ml of 0.5M sodium hydroxide and incubated for 20 minutes at 85 °C to the stop the reaction and degrade the RNA. Samples are purified using two successive CHROMA SPIN 30 gel filtration spin columns (CLONTECH
Laboratories, Inc.
(CLONTECH), Palo Alto CA) and after combining, both reaction samples are ethanol precipitated using 1 ml of glycogen (1 mg/ml), 60 ml sodium acetate, and 300 ml of 100%
ethanol. The sample is then dried to completion using a SpeedVAC (Savant Instruments Inc., Holbrook NY) and resuspended in 14 ~.il 5X SSC/0.2% SDS.
Microarray Preparation SUBSTITUTE SHEET (RULE 26) Sequences of the present invention are used to generate array elements. Each array element is amplified from bacterial cells containing vectors with cloned cDNA inserts.
PCR amplification uses primers complementary to the vector sequences flanking the cDNA insert. Array elements are amplified in thirty cycles of PCR from an initial quantity of 1-2 ng to a final quantity greater than 5 fig. Amplified array elements are then purified using SEPHACRYL-400 (Amersham Pharmacia Biotech).
Purified array elements are immobilized on polymer-coated glass slides. Glass microscope slides (Corning) are cleaned by ultrasound in 0.1 % SDS and acetone, with extensive distilled water washes between and after treatments. Glass slides are etched in 4%
hydrofluoric acid (VWR
Scientific Products Corporation (VWR), West Chester PA), washed extensively in distilled water, and coated with 0.05% aminopropyl silane (Sigma) in 95% ethanol. Coated slides are cured in a 110°C
oven.
Array elements are applied to the coated glass substrate using a procedure described in US
Patent No. 5,807,522, incorporated herein by reference. 1 Eil of the array element DNA, at an average concentration of 100 ng/Lil, is loaded into the open capillary printing element by a high-speed robotic apparatus. The apparatus then deposits about 5 n1 of array element sample per slide.
Microarrays are UV-crosslinked using a STRATALINKER UV-crosslinker (Stratagene).
Microarrays are washed at room temperature once in 0.2% SDS and three times in distilled water.
Non-specific binding sites are blocked by incubation of microarrays in 0.2%
casein in phosphate buffered saline (PBS) (Tropix, Inc., Bedford MA) for 30 minutes at 60 °C followed by washes in 0.2% SDS and distilled water as before.
Hybridization Hybridization reactions contain 9 Erl of sample mixture consisting of 0.2 pg each of Cy3 and Cy5 labeled cDNA synthesis products in SX SSC, 0.2% SDS hybridization buffer.
The sample mixture is heated to 65 °C for 5 minutes and is aliquoted onto the microarray surface and covered with an 1.8 cm2 coverslip. The arrays are transferred to a waterproof chamber having a cavity just slightly larger than a microscope slide. The chamber is kept at 100% humidity internally by the addition of 140 Nl of SX SSC in a corner of the chamber. The chamber containing the arrays is incubated for about 6.5 hours at 60°C. The arrays are washed for 10 min at 45 °C in a first wash buffer (1X SSC, 0.1 % SDS), three times for 10 minutes each at 45 °C in a second wash buffer (0.1X SSC), and dried.
Detection Reporter-labeled hybridization complexes are detected with a microscope equipped with an Innova 70 mixed gas 10 W laser (Coherent, Inc., Santa Clara CA) capable of generating spectral lines at 488 nm for excitation of Cy3 and at 632 nm for excitation of CyS. The excitation laser light is focused on the array using a 20X microscope objective (Nikon, Inc., Melville NY). 'The slide SUBSTITUTE SHEET (RULE 26) containing the array is placed on a computer-controlled X-Y stage on the microscope and raster-scanned past the objective. The 1.8 cm x 1.8 cm array used in the present example is scanned with a resolution of 20 micrometers.
In two separate scans, a mixed gas multiline laser excites the two fluorophores sequentially.
Emitted light is split, based on wavelength, into two photomultiplier tube detectors (PMT 81477, Hamamatsu Photonics Systems, Bridgewater NJ) corresponding to the two fluorophores. Appropriate filters positioned between the array and the photomultiplier tubes are used to filter the signals. The emission maxima of the fluorophores used are 565 nm for Cy3 and 650 nm for CyS. Each array is typically scanned twice, one scan per fluorophore using the appropriate filters at the laser source, although the apparatus is capable of recording the spectra from both fluorophores simultaneously.
The sensitivity of the scans is typically calibrated using the signal intensity generated by a cDNA control species added to the sample mixture at a known concentration. A
specific location on the array contains a complementary DNA sequence, allowing the intensity of the signal at that location to be correlated with a weight ratio of hybridizing species of 1:100,000. When two samples from different sources (e.g., representing test and control cells), each labeled with a different fluorophore, are hybridized to a single array for the purpose of identifying genes that are differentially expressed, the calibration is done by labeling samples of the calibrating cDNA
with the two fluorophores and adding identical amounts of each to the hybridization mixture.
The output of the photomultiplier tube is digitized using a 12-bit RTI-835H
analog-to-digital (A/D) conversion board (Analog Devices, Inc., Norwood MA) installed in an IBM-compatible PC
computer. The digitized data are displayed as an image where the signal intensity is mapped using a linear 20-color transformation to a pseudocolor scale ranging from blue (low signal) to red (high signal). The data is also analyzed quantitatively. Where two different fluorophores are excited and measured simultaneously, the data are first corrected for optical crosstalk (due to overlapping emission spectra) between the fluorophores using each fluorophore's emission spectrum.
A grid is superimposed over the fluorescence signal image such that the signal from each spot is centered in each element of the grid. The fluorescence signal within each element is then integrated to obtain a numerical value corresponding to the average intensity of the signal. The software used for signal analysis is the GEMTOOLS gene expression analysis program (Incyte).
IX. Complementary Polynucleotides Sequences complementary to the GBAP-encoding sequences, or any parts thereof, are used to detect, decrease, or inhibit expression of naturally occurring GBAP. Although use of oligonucleotides comprising from about 15 to 30 base pairs is described, essentially the same procedure is used with smaller or with larger sequence fragments. Appropriate oligonucleotides are designed using OLIGO
4.06 software (National Biosciences) and the coding sequence of GBAP. To inhibit transcription, a SUBSTITUTE SHEET (RULE 26) complementary oligonucleotide is designed from the most unique 5' sequence and used to prevent promoter binding to the coding sequence. To inhibit translation, a complementary oligonucleotide is designed to prevent ribosomal binding to the GBAP-encoding transcript.
X. Expression of GBAP
Expression and purification of GBAP is achieved using bacterial or virus-based expression systems. For expression of GBAP in bacteria, cDNA is subcloned into an appropriate vector containing an antibiotic resistance gene and an inducible promoter that directs high levels of eDNA
transcription. Examples of such promoters include, but are not limited to, the trp-lac (tae) hybrid promoter and the TS or T7 bacteriophage promoter in conjunction with the lac operator regulatory element. Recombinant vectors are transformed into suitable bacterial hosts, e.g., BL21 (DE3).
Antibiotic resistant bacteria express GBAP upon induction with isopropyl beta-D-thiogalactopyranoside (IPTG). Expression of GBAP in eukaryotic cells is achieved by infecting insect or mammalian cell lines with recombinant Autog-raphica californica nuclear polyhedrosis virus (AcMNPV), commonly known as baculovirus. The nonessential polyhedrin gene of baculovirus is replaced with cDNA encoding GBAP by either homologous recombination or bacterial-mediated transposition involving transfer plasmid intermediates. Viral infecdvity is maintained and the strong polyhedrin promoter drives high levels of cDNA transcription. Recombinant baculovirus is used to infect Spodoptera frugiperda (Sf9) insect cells in most cases, or human hepatocytes, in some cases.
Infection of the latter requires additional genetic modifications to baculovirus. (See Engelhard, E.K. et al. (1994) Proc. Natl. Acad. Sci. USA 91:3224-3227; Sandig, V. et al. (1996) Hum. Gene Ther.
7:1937-1945.) In most expression systems, GBAP is synthesized as a fusion protein with, e.g., glutathione S-transferase (GST) or a peptide epitope tag, such as FLAG or 6-His, permitting rapid, single-step, affinity-based purification of recombinant fusion protein from crude cell lysates. GST, a 26-kilodalton enzyme from Schistosoma Lponicum, enables the purification of fusion proteins on immobilized glutathione under conditions that maintain protein activity and antigenicity (Amersham Pharmacia Biotech). Following purification, the GST moiety can be proteolytically cleaved from GBAP at specifically engineered sites. FLAG, an 8-amino acid peptide, enables immunoaffinity purification using commercially available monoclonal and polyclonal anti-FLAG antibodies (Eastman Kodak). 6-His, a stretch of six consecutive histidine residues, enables purification on metal-chelate resins (QIAGEN). Methods for protein expression and purification are discussed in Ausubel (1995, supra, eh. 10 and 16). Purified GBAP obtained by these methods can be used directly in the assays shown in Examples XI and XV.
XI. Demonstration of GBAP Activity GTP-binding activity of GBAP is determined in an assay that measures the binding of GBAP

SUBSTITUTE SHEET (RULE 26) to a-P32-labeled GTP. Purified GBAP is first blotted onto filters and rinsed in a suitable buffer. The filters are then incubated in buffer containing radiolabeled a-32P-GTP. The filters are washed in buffer to remove unbound GTP and counted in a radioisotope counter. Non-specific binding is determined in an assay that contains a 100-fold excess of unlabeled GTP. The amount of specific binding is proportional to the activity of GBAP.
GTPase activity of GBAP is determined in an assay that measures the conversion of a-32P-GTP
to a-32P-GDP. GBAP is incubated with a-32P-GTP in buffer for an appropriate period of time, and the reaction is terminated by heating or acid precipitation followed by centrifugation. An aliquot of the supernatant is subjected to polyacrylamide gel electrophoresis (PAGE) to separate GDP and GTP
together with unlabeled standards. The GDP spot is cut out and counted in a radioisotope counter. The amount of radioactivity recovered in GDP is proportional to GTPase activity of GBAP.
XII. Functional Assays GBAP function is assessed by expressing the sequences encoding GBAP at physiologically elevated levels in mammalian cell culture systems. cDNA is subcloned into a mammalian expression vector containing a strong promoter that drives high levels of cDNA
expression. Vectors of choice include pCMV SPORT plasmid (Life Technologies) and pCR3.1 plasmid (Invitrogen), both of which contain the cytomegalovirus promoter. 5-10 ~g of recombinant vector are transiently transfected into a human cell line, for example, an endothelial or hematopoietic cell fine, using either liposome formulations or electroporation. 1-2 ~cg of an additional plasmid containing sequences encoding a marker protein are co-transfected. Expression of a marker protein provides a means to distinguish.
transfected cells from nontransfected cells and is a reliable predictor of eDNA expression from the recombinant vector. Marker proteins of choice include, e.g., Green Fluorescent Protein (GFP;
Clontech), CD64, or a CD64-GFP fusion protein. Flow cytometry (FCM), an automated, laser optics-based technique, is used to identify transfected cells expressing GFP or CD64-GFP and to evaluate the apoptotic state of the cells and other cellular properties. FCM detects and quantifies the uptake of fluorescent molecules that diagnose events preceding or coincident with cell death. These events include changes in nuclear DNA content as measured by staining of DNA with propidium iodide; changes in cell size and granularity as measured by forward light scatter and 90 degree side light scatter; down-regulation of DNA synthesis as measured by decrease in bromodeoxyuridine uptake; alterations in expression of cell surface and intracellular proteins as measured by reactivity with specific antibodies;
and alterations in plasma membrane composition as measured by the binding of fluorescein-conjugated Annexin V protein to the cell surface. Methods in flow cytometry are discussed in Ormerod, M.G.
(1994) Flow Cytometry, Oxford, New York NY.
The influence of GBAP on gene expression can be assessed using highly purified populations of cells transfected with sequences encoding GBAP and either CD64 or CD64-GFP.
CD64 and CD64-SUBSTITUTE SHEET (RULE 26) GFP are expressed on the surface of transfected cells and bind to conserved regions of human immunoglobulin G (IgG). Transfected cells are efficiently separated from nontransfected cells using magnetic beads coated with either human IgG or antibody against CD64 (DYNAL, Lake Success NY).
mRNA can be purified from the cells using methods well known by those of skill in the art. Expression of mRNA encoding GBAP and other genes of interest can be analyzed by northern analysis or microarray techniques.
X1II. Production of GBAP Specific Antibodies GBAP substantially purified using polyacrylamide gel electrophoresis (PAGE;
see, e.g., Harrington, M.G. (1990) Methods Enzymol. 182:488-495), or other purification techniques, is used to immunize rabbits and to produce antibodies using standard protocols.
Alternatively, the GBAP amino acid sequence is analyzed using LASERGENE
software (DNASTAR) to determine regions of high immunogenicity, and a corresponding oligopeptide is synthesized and used to raise antibodies by means known to those of skill in the art. Methods for selection of appropriate epitopes, such as those near the C-terminus or in hydrophilic regions are well described in the art. (See, e.g., Ausubel, 1995, su ra, ch. 11.) Typically, oligopeptides of about 15 residues in length are synthesized using an ABI 431A
peptide synthesizer (PE Biosystems) using FMOC chemistry and coupled to KL,H
(Sigma-Aldrich, St.
Louis MO) by reaction with N-maleimidobenzoyl-N-hydroxysuccinimide ester (MBS) to increase immunogenicity. (See, e.g., Ausubel, 1995, supra.) Rabbits are immunized with the oligopeptide-KLH
complex in complete Freund's adjuvant. Resulting antisera are tested for antipeptide and anti-GBAP
activity by, for example, binding the peptide or GBAP to a substrate, blocking with 1 % BSA, reacting with rabbit antisera, washing, and reacting with radio-iodinated goat anti-rabbit IgG.
XIV. Purification of Naturally Occurring GBAP Using Specific Antibodies Naturally occurring or recombinant GBAP is substantially purified by immunoaflinity chromatography using antibodies specific for GBAP. An immunoaffinity column is constructed by covalently coupling anti-GBAP antibody to an activated chromatographic resin, such as CNBr-activated SEPHAROSE (Amersham Pharmacia Biotech). After the coupling, the resin is blocked and washed according to the manufacturer's instructions.
Media containing GBAP are passed over the immunoaflinity column, and the column is washed under conditions that allow the preferential absorbance of GBAP (e.g., high ionic strength buffers in the presence of detergent). The column is eluted under conditions that disrupt antibody/GBAP binding (e.g., a buffer of pH 2 to pH 3, or a high concentration of a chaotrope, such as urea or thiocyanate ion), and GBAP is collected.
XV. Identification of Molecules Which Interact with GBAP
GBAP, or biologically active fragments thereof, are labeled with'ZSI Bolton-Hunter reagent.
SUBSTITUTE SHEET (RULE 26) (See, e.g., Bolton A.E. and W.M. Hunter (1973) Biochem. J. 133:529-539.) Candidate molecules previously arrayed in the wells of a multi-well plate are incubated with the labeled GBAP, washed, and any wells with labeled GBAP complex are assayed. Data obtained using different concentrations of GBAP are used to calculate values for the number, affinity, and association of GBAP with the candidate molecules.
Alternatively, molecules interacting with GBAP are analyzed using the yeast two-hybrid system as described in Fields, S. and O. Song (1989, Nature 340:245-246), or using commercially available kits based on the two-hybrid system, such as the MATCHMAKER system (Clontech).
GBAP may also be used in the PATHCALLING process (CuraGen Corp., New Haven CT) which employs the yeast two-hybrid system in a high-throughput manner to determine all interactions between the proteins encoded by two large libraries of genes (Nandabalan, K.
et al. (2000) U.S. Patent No. 6,057,1 O1).
Various modifications and variations of the described methods and systems of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention.
Although the invention has been described in connection with certain embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments.
Indeed, various modifications of the described modes for carrying out the invention which are obvious to those skilled in molecular biology or related fields are intended to be within the scope of the following claims.

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G. G. 0. G. U 'J~7 SUBSTITUTE SHEET (RULE 26) SEQUENCE LISTING
<110> INCYTE GENOMICS, INC.
YUE, Henry TANG, Y. Tom BANDMAN, Olga HILLMAN, Jennifer L.
LAL, Preeti AU-YOUNG, Janice REDDY, Roopa YANG, Junming BAUGHN, Mariah R.
LU, Dyung Aina M.
AZIMZAI, Yalda PATTERSON, Chandra <120> GTP-BINDING ASSOCIATED PROTEINS
<130> PF-0714 PCT
<140> To Be Assigned <141> Herewith <150> 60/144,595; 60/150,460; 60/159,849 <151> 1999-07-19; 1999-08-23; 1999-10-15 <160> 132 <170> PERL Program <210> 1 <211> 269 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 1405545CD1 <400> 1 Met Pro Ala Val Leu Glu Arg Leu Ser Arg Tyr Asn Ser Thr Ser Gln Ala Phe Ala Glu Val Leu Arg Leu Pro Lys Gln Gln Leu Arg Lys Leu Leu Tyr Pro Leu Gln Glu Val Glu Arg Phe Leu Ala Pro Tyr Gly Arg Gln Asp Leu His Leu Arg Ile Phe Asp Pro Ser Pro Glu Asp Ile Ala Arg Ala Asp Asn Ile Phe Thr Ala Thr Glu Arg Asn Arg Ile Asp Tyr Val Ser Ser Ala Val Arg Ile Asp His Ala Pro Asp Leu Pro Arg Pro Glu Val Cys Phe Ile Gly Arg Ser Asn Val Gly Lys Ser Ser Leu Ile Lys Ala Leu Phe Ser Leu Ala Pro Glu Val Glu Val Arg Val Ser Lys Lys Pro Gly His Thr Lys Lys Met Asn Phe Phe Lys Val Gly Lys His Phe Thr Val Val Asp Met Pro Gly Tyr Gly Phe Arg Ala Pro Glu Asp Phe Val Asp Met Val Glu Thr Tyr Leu Lys Glu Arg Arg Asn Leu Lys Arg Thr Phe Leu Leu Val Asp Ser Val Val Gly Ile Gln Lys Thr Asp Asn Ile Ala Ile Glu Met Cys Glu Glu Phe Ala Leu Pro Tyr Val Ile Val Leu Thr Lys Ile Asp Lys Ser Ser Lys Gly His Leu Leu Lys Gln Val Leu Gln Ile Gln Lys Phe Val Asn Met Lys Thr Gln Gly Cys Phe Pro Gln Leu Phe Pro Val Ser Ala Val Thr Phe Ser Gly Ile His Leu Leu Arg Cys Phe Ile Ala Ser Val Thr Gly Ser Leu Asp <210> 2 <211> 428 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 1451265CD1 <400> 2 Met Glu Val Ala Val Cys Thr Asp Ser Ala Ala Pro Met Trp Ser Cys Ile Val Trp Glu Leu His Ser Gly Ala Asn Leu Leu Thr Tyr Arg Gly Gly Gln Ala Gly Pro Arg Gly Leu Ala Leu Leu Asn Gly Glu Tyr Leu Leu Ala Ala Gln Leu Gly Lys Asn Tyr Ile Ser Ala Trp Glu Leu Gln Arg Lys Asp Gln Leu Gln Gln Lys Ile Met Cys Pro Gly Pro Val Thr Cys Leu Thr Ala Ser Pro Asn Gly Leu Tyr Val Leu Ala Gly Val Ala Glu Ser Ile His Leu Trp Glu Val Ser Thr Gly Asn Leu Leu Val Ile Leu Ser Arg His Tyr Gln Asp Val Ser Cys Leu Gln Phe Thr Gly Asp Ser Ser His Phe Ile Ser Gly Gly Lys Asp Cys Leu Val Leu Val Trp Ser Leu Cys Ser Val Leu Gln Ala Asp Pro Ser Arg Ile Pro Ala Pro Arg His Val Trp Ser His His Thr Leu Pro Ile Thr Asp Leu His Cys Gly Phe Gly Gly Pro Leu Ala Arg Val Ala Thr Ser Ser Leu Asp Gln Thr Val Lys Leu Trp Glu Val Ser Ser Gly Glu Leu Leu Leu Ser Val Leu Phe Asp Val Ser Ile Met Ala Val Thr Met Asp Leu Ala Glu His His Met Phe Cys Gly Gly Ser Glu Gly Ser Ile Phe Gln Val Asp Leu Phe Thr Trp Pro Gly Gln Arg Glu Arg Ser Phe His Pro Glu Gln Asp Ala Gly Lys Val Phe Lys Gly His Arg Asn Gln Val Thr Cys Leu Ser Val Ser Thr Asp Gly Ser Val Leu Leu Ser Gly Ser His Asp Glu Thr Val Arg Leu Trp Asp Val Gln Ser Lys Gln Cys Ile Arg Thr Val Ala Leu Lys Gly Pro Val Thr Asn Ala Ala Ile Leu Leu Ala Pro Val Ser Met Leu Ser Ser Asp Phe Arg Pro Ser Leu Pro Leu Pro His Phe Asn Lys His Leu Leu Gly Ala Glu His Gly Asp Glu Pro Arg His Gly Gly Leu Thr Leu Arg Leu Gly Leu His Gln Gln Gly Ser Glu Pro Ser Tyr Leu Asp Arg Thr Glu Gln Leu Gln Ala Val Leu Cys Ser Thr Met Glu Lys Ser Val Leu Gly Gly Gln Asp Gln Leu Arg Val Arg Val Thr Glu Leu Glu Asp Glu Val Arg Asn Leu Arg Lys Ile Asn Arg Asp Leu Phe Asp Phe Ser Thr Arg Phe Ile Thr Arg Pro Ala Lys <210> 3 <211> 562 <212> PRT , <213> Homo Sapiens <220>
<221> misC_feature <223> Incyte ID No: 1556311CD1 <400> 3 Met Pro Glu Thr Val Asn His Asn Lys His Gly Asn Val Ala Leu Pro Gly Thr Lys Pro Thr Pro Ile Pro Pro Pro Arg Leu Lys Lys Gln Ala Ser Phe Leu Glu Ala Glu Gly Gly Ala Lys Thr Leu Ser Gly Gly Arg Pro Gly Ala Gly Pro Glu Leu Glu Leu Gly Thr Ala Gly Ser Pro Gly Gly Ala Pro Pro Glu Ala Ala Pro Gly Asp Cys Thr Arg Ala Pro Pro Pro Ser Ser Glu Ser Arg Pro Pro Cys His Gly Gly Arg Gln Arg Leu Ser Asp Met Ser Ile Ser Thr Ser Ser Ser Asp Ser Leu Glu Phe Asp Arg Ser Met Pro Leu Phe Gly Tyr Glu Ala Asp Thr Asn Ser Ser Leu Glu Asp Tyr Glu Gly Glu Ser Asp Gln Glu Thr Met Ala Pro Pro Ile Lys Ser Lys Lys Lys Arg Ser Ser Ser Phe Val Leu Pro Lys Leu Val Lys Ser Gln Leu Gln Lys Val Ser Gly Val Phe Ser Ser Phe Met Thr Pro Glu Lys Arg Met Val Arg Arg Ile Ala Glu Leu Ser Arg Asp Lys Cys Thr Tyr Phe Gly Cys Leu Val Gln Asp Tyr Val Ser Phe Leu Gln Glu Asn Lys Glu Cys His Val Ser Ser Thr Asp Met Leu Gln Thr Ile Arg Gln Phe Met Thr Gln Val Lys Asn Tyr Leu Ser Gln Ser Ser Glu Leu Asp Pro Pro Ile Glu Ser Leu Ile Pro Glu Asp Gln Ile Asp Val Val Leu Glu Lys Ala Met His Lys Cys Ile Leu Lys Pro Leu Lys Gly His Val Glu Ala Met Leu Lys Asp Phe His Met Ala Asp Gly Ser Trp Lys Gln Leu Lys Glu Asn Leu Gln Leu Val Arg Gln Arg Asn Pro Gln Glu Leu Gly Val Phe Ala Pro Thr Pro Asp Phe Val Asp Val Glu Lys Ile Lys Val Lys Phe Met Thr Met Gln Lys Met Tyr Ser Pro Glu Lys Lys Val Met Leu Leu Leu Arg Val Cys Lys Leu Ile Tyr Thr Val Met Glu Asn Asn Ser Gly Arg Met Tyr Gly Ala Asp Asp Phe Leu Pro Val Leu Thr Tyr Val Ile Ala Gln Cys Asp Met Leu Glu Leu Asp Thr Glu Ile Glu Tyr Met Met Glu Leu Leu Asp Pro Ser Leu Leu His Gly Glu Gly Gly Tyr Tyr Leu Thr Ser Ala Tyr Gly Ala Leu Ser Leu Ile Lys Asn Phe Gln Glu Glu Gln Ala Ala Arg Leu Leu Ser Ser Glu Thr Arg Asp Thr Leu Arg Gln Trp His Lys Arg Arg Thr Thr Asn Arg Thr Ile Pro Ser Val Asp Asp Phe Gln Asn Tyr Leu Arg Val Ala Phe Gln Glu Val Asn Ser Gly Cys Thr Gly Lys Thr Leu Leu Val Arg Pro Tyr Ile Thr Thr Glu Asp Val Cys Gln Ile Cys Ala Glu Lys Phe Lys Val Gly Asp Pro Glu Glu Tyr Ser Leu Phe Leu Phe Val Asp Glu Thr Trp Gln Gln Leu Ala Glu Asp Thr Tyr Pro Gln Lys Ile Lys Ala Glu Leu His Ser Arg Pro Gln Pro His Ile Phe His Phe Val Tyr Lys Arg Ile Lys Asn Asp Pro Tyr Gly Ile Ile Phe Gln Asn Gly Glu Glu Asp Leu Thr Thr Ser <210> 4 <211> 229 <212> PRT
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 1901373CD1 <400> 4 Met Ala Glu Asp Lys Thr Lys Pro Ser Glu Leu Asp Gln Gly Lys Tyr Asp Ala Asp Asp Asn Val Lys Ile Ile Cys Leu Gly Asp Ser Ala Val Gly Lys Ser Lys Leu Met Glu Arg Phe Leu Met Asp Gly Phe Gln Pro Gln Gln Leu Ser Thr Tyr Ala Leu Thr Leu Tyr Lys His Thr Ala Thr Val Asp Gly Arg Thr Ile Leu Val Asp Phe Trp Asp Thr Ala Gly Gln Glu Arg Phe Gln Ser Met His Ala Ser Tyr Tyr His Lys Ala His Ala Cys Ile Met Val Phe Asp Val Gln Arg Lys Val Thr Tyr Arg Asn Leu Ser Thr Trp Tyr Thr Glu Leu Arg Glu Phe Arg Pro Glu Ile Pro Cys Ile Val Val Ala Asn Lys Ile Asp Ala Asp Ile Asn Val Thr Gln Lys Ser Phe Asn Phe Ala Lys Lys Phe Ser Leu Pro Leu Tyr Phe Val Ser Ala Ala Asp Gly Thr Asn Val Val Lys Leu Phe Asn Asp Ala Ile Arg Leu Ala Val Ser Tyr Lys Gln Asn Ser Gln Asp Phe Met Asp Glu Ile Phe Gln Glu Leu Glu Asn Phe Ser Leu Glu Gln Glu Glu Glu Asp Val Pro Asp Gln Glu Gln Ser Ser Ser Ile Glu Thr Pro Ser Glu Glu Val Ala Ser Pro His Ser <210> 5 <211> 360 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 2367767CD1 <400> 5 Met Phe Val Ala Arg Ser Ile Ala Ala Asp His Lys Asp Leu Ile His Asp Val Ser Phe Asp Phe His Gly Arg Arg Met Ala Thr Cys Ser Ser Asp Gln Ser Val Lys Val Trp Asp Lys Ser Glu Ser Gly Asp Trp His Cys Thr Ala Ser Trp Lys Thr His Ser Gly Ser Val Trp Arg Val Thr Trp Ala His Pro Glu Phe Gly Gln Val Leu Ala Ser Cys Ser Phe Asp Arg Thr Ala Ala Val Trp Glu Glu Ile Val Gly Glu Ser Asn Asp Lys Leu Arg Gly Gln Ser His Trp Val Lys Arg Thr Thr Leu Val Asp Ser Arg Thr Ser Val Thr Asp Val Lys Phe Ala Pro Lys His Met Gly Leu Met Leu Ala Thr Cys Ser Ala Asp Gly Ile Val Arg Ile Tyr Glu Ala Pro Asp Val Met Asn Leu Ser Gln Trp Ser Leu Gln His Glu Ile Ser Cys Lys Leu Ser Cys Ser Cys Ile Ser Trp Asn Pro Ser Ser Ser Arg Ala His Ser Pro Met Ile Ala Val Gly Ser Asp Asp Ser Ser Pro Asn Ala Met Ala Lys Val Gln Ile Phe Glu Tyr Asn Glu Asn Thr Arg Lys Tyr Ala Lys Ala Glu Thr Leu Met Thr Val Thr Asp Pro Val His Asp Ile Ala Phe Ala Pro Asn Leu Gly Arg Ser Phe His Ile Leu Ala Ile Ala Thr Lys Asp Val Arg Ile Phe Thr Leu Lys Pro Val Arg Lys $/115 Glu Leu Thr Ser Ser Gly Gly Pro Thr Lys Phe Glu Ile His Ile Val Ala Gln Phe Asp Asn His Asn Ser Gln Val Trp Arg Val Ser Trp Asn Ile Thr Gly Thr Val Leu Ala Ser Ser Gly Asp Asp Gly Cys Val Arg Leu Trp Lys Ala Asn Tyr Met Asp Asn Trp Lys Cys Thr Gly Ile Leu Lys Gly Asn Gly Ser Pro Val Asn Gly Ser Ser Gln Gln Gly Thr Ser Asn Pro Ser Leu Gly Ser Asn Ile Pro Ser Leu Gln Asn Ser Leu Asn Gly Ser Ser Ala Gly Arg Lys His Ser <210> 6 <211> 460 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 3090433CD1 <400> 6 Met Ala Asn Asp Pro Leu Glu Gly Phe His Glu Val Asn Leu Ala Ser Pro Thr Ser Pro Asp Leu Leu Gly Val Tyr Glu Ser Gly Thr Gln Glu Gln Thr Thr Ser Pro Ser Val Ile Tyr Arg Pro His Pro Ser Ala Leu Ser Ser Val Pro Ile Gln Ala Asn Ala Leu Asp Val Ser Glu Leu Pro Thr Gln Pro Val Tyr Ser Ser Pro Arg Arg Leu Asn Cys Ala Glu Ile Ser Ser Ile Ser Phe His Val Thr Asp Pro Ala Pro Cys Ser Thr Ser Gly Val Thr Ala Gly Leu Thr Lys Leu Thr Thr Arg Lys Asp Asn Tyr Asn Ala Glu Arg Glu Phe Leu Gln Gly Ala Thr Ile Thr Glu Ala Cys Asp Gly Ser Asp Asp Ile Phe Gly Leu Ser Thr Asp Ser Leu Ser Arg Leu Arg Ser Pro Ser Val Leu Glu Val Arg Glu Lys Gly Tyr Glu Arg Leu Lys Glu Glu Leu Ala Lys Ala Gln Arg Glu Leu Lys Leu Lys Asp Glu Glu Cys Glu Arg Leu Ser Lys Val Arg Asp Gln Leu Gly Gln Glu Leu Glu Glu Leu Thr Ala Ser Leu Phe Glu Glu Ala His Lys Met Val Arg Glu Ala Asn Ile Lys Gln Ala Thr Ala Glu Lys Gln Leu Lys Glu Ala Gln Gly Lys Ile Asp Val Leu Gln Ala Glu-Val Ala Ala Leu Lys Thr Leu Val Leu Ser Ser Ser Pro Thr Ser Pro Thr Gln Glu Pro Leu Pro Gly Gly Lys Thr Pro Phe Lys Lys Gly His Thr Arg Asn Lys Ser Thr Ser Ser Ala Met Ser Gly Ser His Gln Asp Leu Ser Val Ile Gln Pro Ile Val Lys Asp Cys Lys Glu Ala Asp Leu Ser Leu Tyr Asn Glu Phe Arg Leu Trp Lys Asp Glu Pro Thr Met Asp Arg Thr Cys Pro Phe Leu Asp Lys Ile Tyr Gln Glu Asp Ile Phe Pro Cys Leu Thr Phe Ser Lys Ser Glu Leu Ala Ser Ala Val Leu Glu Ala Val Glu Asn Asn Thr Leu Ser Ile Glu Pro Val Gly Leu Gln Pro Ile Arg Phe Val Lys Ala Ser Ala Val Glu Cys Gly Gly Pro Lys Lys Cys Ala Leu Thr Gly Gln Ser Lys Ser Cys Lys His Arg Ile Lys Leu Gly Asp Ser Ser Asn Tyr Tyr Tyr Ile Ser Pro Phe Cys Arg Tyr Arg Ile Thr Ser Val Cys Asn Phe Phe Thr Tyr Ile Arg Tyr Ile Gln Gln Gly Leu Val Lys Gln Gln Asp Val Asp Gln Met Phe Trp Glu Val Met Gln Leu Arg Lys Glu Met Ser Leu Ala Lys Leu Gly Tyr Phe Lys Glu Glu Leu <210> 7 <211> 239 <212> PRT
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 3800591CD1 <400> 7 Met Gln Asp Pro Asn Ala Asp Thr Glu Trp Asn Asp Ile Leu Arg Lys Lys Gly Ile Leu Pro Pro Lys Glu Ser Leu Lys Glu Leu Glu Glu Glu Ala Glu Glu Glu Gln Arg Ile Leu Gln Gln Ser Val Val Lys Thr Tyr Glu Asp Met Thr Leu Glu Glu Leu Glu Asp His Glu Asp Glu Phe Asn Glu Glu Asp Glu Arg Ala Ile Glu Met Tyr Arg Arg Arg Arg Leu Ala Glu Trp Lys Ala Thr Lys Leu Lys Asn Lys Phe Gly Glu Val Leu Glu Ile Ser Gly Lys Asp Tyr Val Gln Glu Val Thr Lys Ala Gly Glu Gly Leu Trp Val Ile Leu His Leu Tyr Lys Gln Gly Ile Pro Leu Cys Ala Leu Ile Asn Gln His Leu Ser Gly Leu Ala Arg Lys Phe Pro Asp Val Lys Phe Ile Lys Ala Ile Ser Thr Thr Cys Ile Pro Asn Tyr Pro Asp Arg Asn Leu Pro Thr Ile Phe Val Tyr Leu Glu Gly Asp Ile Lys Ala Gln Phe Ile Gly Pro Leu Val Phe Gly Gly Met Asn Leu Thr Arg Asp Glu Leu Glu Trp Lys Leu Ser Glu Ser Gly Ala Ile Met Thr Asp Leu Glu Glu Asn Pro Lys Lys Pro Ile Glu Asp Val Leu Leu Ser Ser Val Arg Arg Ser Val Leu Met Lys Arg Asp Ser Asp Ser Glu Gly Asp <210> 8 <211> 334 <212> PRT
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 5308471CD1 <400> 8 Met Arg Leu Thr Pro Arg Ala Leu Cys Ser Ala Ala Gln Ala Ala Trp Arg Glu Asn Phe Pro Leu Cys Gly Arg Asp Val Ala Arg Trp Phe Pro Gly His Met Ala Lys Gly Leu Lys Lys Met Gln Ser Ser Leu Lys Leu Val Asp Cys Ile Ile Glu Val His Asp Ala Arg Ile Pro Leu Ser Gly Arg Asn Pro Leu Phe Gln Glu Thr Leu Gly Leu Lys Pro His Leu Leu Val Leu Asn Lys Met Asp Leu Ala Asp Leu Thr Glu Gln Gln Lys Ile Met Gln His Leu Glu Gly Glu Gly Leu Lys Asn Val Ile Phe Thr Asn Cys Val Lys Asp Glu Asn Val Lys Gln Ile Ile Pro Met Val Thr Glu Leu Ile Gly Arg Ser His Arg Tyr His Arg Lys Glu Asn Leu Glu Tyr Cys Ile Met Val Ile Gly Val Pro Asn Val Gly Lys Ser Ser Leu Ile Asn Ser Leu Arg Arg Gln His Leu Arg Lys Gly Lys Ala Thr Arg Val Gly Gly Glu Pro Gly Ile Thr Arg Ala Val Met Ser Lys Ile Gln Val Ser Glu Arg Pro Leu Met Phe Leu Leu Asp Thr Pro Gly Val Leu Ala Pro Arg Ile Glu Ser Val Glu Thr Gly Leu Lys Leu Ala Leu Cys Gly Thr Val Leu Asp His Leu Val Gly Glu Glu Thr Met Ala Asp Tyr Leu Leu Tyr Thr Leu Asn Lys His Gln Arg Phe Gly Tyr Val Gln His Tyr Gly Leu Gly Ser Ala Cys Asp Asn Val Glu Arg Val Leu Lys Ser Val Ala Val Lys Leu Gly Lys Thr Gln Lys Val Lys Val Leu Thr Gly Thr Gly Asn Val Asn Val Ile Gln Pro Asn Tyr Pro Ala Ala Ala Arg Asp Phe Leu Gln Thr Phe Arg Arg Gly Leu Leu Gly Ser Val Met Leu Asp Leu Asp Val Leu Arg Gly His Pro Pro Ala Glu Thr Leu Pro <210> 9 <211> 341 <212> PRT
g/1 1$

<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 5324322CD1 <400> 9 Met Glu Arg Ala Val Pro Leu Ala Val Pro Leu Gly Gln Thr Glu Val Phe Gln Ala Leu Gln Arg Leu His Met Thr Ile Phe Ser Gln Ser Val Ser Pro Cys Gly Lys Phe Leu Ala Ala Gly Asn Asn Tyr Gly Gln Ile Ala Ile Phe Ser Leu Ser Ser Ala Leu Ser Ser Glu Ala Lys Glu Glu Ser Lys Lys Pro Val Val Thr Phe Gln Ala His Asp Gly Pro Val Tyr Ser Met Val Ser Thr Asp Arg His Leu Leu Ser Ala Gly Asp Gly Glu Val Lys Ala Trp Leu Trp Ala Glu Met Leu Lys Lys Gly Cys Lys Glu Leu Trp Arg Arg Gln Pro Pro Tyr Arg Thr Ser Leu Glu Val Pro Glu Ile Asn Ala Leu Leu Leu Val Pro Lys Glu Asn Ser Leu Ile Leu Ala Gly Gly Asp Cys Gln Leu His Thr Met Asp Leu Glu Thr Gly Thr Phe Thr Arg Val Leu Arg Gly His Thr Asp Tyr Ile His Cys Leu Ala Leu Arg Glu Arg Ser Pro Glu Val Leu Ser Gly Gly Glu Asp Gly Ala Val Arg Leu Trp Asp Leu Arg Thr Ala Lys Glu Val Gln Thr Ile Glu Val Tyr Lys His Glu Glu Cys Ser Arg Pro His Asn Gly Arg Trp Ile Gly Cys Leu Ala Thr Asp Ser Asp Trp Met Val Cys Gly Gly Gly Pro Ala Leu Thr Leu Trp His Leu Arg Ser Ser Thr Pro Thr Thr Ile Phe Pro Ile Arg Ala Pro Gln Lys His Val Thr Phe Tyr Gln Asp Leu Ile Leu Ser Ala Gly Gln Gly Arg Cys Val Asn Gln Trp Gln Leu Ser Gly Glu Leu Lys Ala Gln Val Pro Gly Ser Ser Pro Gly Leu Leu Ser Leu Ser Leu Asn Gln Gln Pro Ala Ala Pro Glu Cys Lys Val Leu Thr Ala Ala Gly Asn Ser Cys Arg Val Asp Val Phe Thr Asn Leu Gly Tyr Arg Ala Phe Ser Leu Ser Phe <210> 10 <211> 513 <212> PRT
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 067184CD1 <400> 10 Met Ser Ile Glu Ile Glu Ser Ser Asp Val Ile Arg Leu Ile Met Gln Tyr Leu Lys Glu Asn Ser Leu His Arg Ala Leu Ala Thr Leu Gln Glu Glu Thr Thr Val Ser Leu Asn Thr Val Asp Ser Ile Glu Ser Phe Val Ala Asp Ile Asn Ser Gly His Trp Asp Thr Val Leu Gln Ala Ile Gln Ser Leu Lys Leu Pro Asp Lys Thr Leu Ile Asp Leu Tyr Glu Gln Val Val Leu Glu Leu Ile Glu Leu Arg Glu Leu Gly Ala Ala Arg Ser Leu Leu Arg Gln Thr Asp Pro Met Ile Met Leu Lys Gln Thr Gln Pro Glu Arg Tyr Ile His Leu Glu Asn Leu Leu Ala Arg Ser Tyr Phe Asp Pro Arg Glu Ala Tyr Pro Asp Gly Ser Ser Lys Glu Lys Arg Arg Ala Ala Ile Ala Gln Ala Leu Ala Gly Glu Val Ser Val Val Pro Pro Ser Arg Leu Met Ala Leu Leu Gly Gln Ala Leu Lys Trp Gln Gln His Gln Gly Leu Leu Pro Pro Gly Met Thr Ile Asp Leu Phe Arg Gly Lys Ala Ala Val Lys Asp Val Glu Glu Glu Lys Phe Pro Thr Gln Leu Ser Arg His Ile Lys 200 . 205 210 Phe Gly Gln Lys Ser His Val Glu Cys Ala Arg Phe Ser Pro Asp Gly Gln Tyr Leu Val Thr Gly Ser Val Asp Gly Phe Ile Glu Val 230 . 235 240 Trp Asn Phe Thr Thr Gly Lys Ile Arg Lys Asp Leu Lys Tyr Gln Ala Gln Asp Asn Phe Met Met Met Asp Asp Ala Val Leu Cys Met Cys Phe Ser Arg Asp Thr Glu Met Leu Ala Thr Gly Ala Gln Asp Gly Lys Ile Lys Val Trp Lys Ile Gln Ser Gly Gln Cys Leu Arg Arg Phe Glu Arg Ala His Ser Lys Gly Val Thr Cys Leu Ser Phe Ser Lys Asp Ser Ser Gln Ile Leu Ser Ala Ser Phe Asp Gln Thr Ile Arg Ile His Gly Leu Lys Ser Gly Lys Thr Leu Lys Glu Phe Arg Gly His Ser Ser Phe Val Asn Glu Ala Thr Phe Thr Gln Asp Gly His Tyr Ile Ile Ser Ala Ser Ser Asp Gly Thr Val Lys Ile Trp Asn Met Lys Thr Thr Glu Cys Ser Asn Thr Phe Lys Ser Leu Gly Ser Thr Ala Gly Thr Asp Ile Thr Val Asn Ser Val Ile Leu Leu Pro Lys Asn Pro Glu His Phe Val Val Cys Asn Arg Ser Asn Thr Val Val Ile Met Asn Met Gln Gly Gln Ile Val Arg Ser Phe Ser Ser Gly Lys Arg Glu Gly Gly Asp Phe Val Cys Cys Ala Leu Ser Pro Arg Gly Glu Trp Ile Tyr Cys Val Gly Glu Asp Phe Val Leu Tyr Cys Phe Ser Thr Val Thr Gly Lys Leu Glu Arg Thr Leu Thr Val His Glu Lys Asp Val Ile Gly Ile Ala His His Pro His Gln Asn Leu Ile Ala Thr Tyr Ser Glu Asp Gly Leu Leu Lys Leu Trp Lys Pro <210> 11 <211> 186 <212> PRT
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 722896CD1 <400> 11 Met Ile Ala Leu Phe Asn Lys Leu Leu Asp Trp Phe Lys Ala Leu Phe Trp Lys Glu Glu Met Glu Leu Thr Leu Val Gly Leu Gln Tyr Ser Gly Lys Thr Thr Phe Val Asn Val Ile Ala Ser Gly Gln Phe Asn Glu Asp Met Ile Pro Thr Val Gly Phe Asn Met Arg Lys Ile Thr Lys Gly Asn Val Thr Ile Lys Leu Trp Asp Ile Gly Gly Gln Pro Arg Phe Arg Ser Met Trp Glu Arg Tyr Cys Arg Gly Val Ser Ala Ile Val Tyr Met Val Asp Ala Ala Asp Gln Glu Lys Ile Glu Ala Ser Lys Asn Glu Leu His Asn Leu Leu Asp Lys Pro Gln Leu Gln Gly Ile Pro Val Leu Val Leu Gly Asn Lys Arg Asp Leu Pro Gly Ala Leu Asp Glu Lys Glu Leu Ile Glu Lys Met Asn Leu Ser Ala Ile Gln Asp Arg Glu Ile Cys Cys Tyr Ser Ile Ser Cys Lys Glu Lys Asp Asn Ile Asp Ile Thr Leu Gln Trp Leu Ile Gln His Ser Lys Ser Arg Arg Ser <210> 12 <211> 204 <212> PRT
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 1571739CD1 <400> 12 Met Asn Asp Val Lys Leu Ala Val Leu Gly Gly Glu Gly Thr Gly Lys Ser Ala Leu Thr Val Arg Phe Leu Thr Lys Arg Phe Ile Gly Glu Tyr Ala Ser Asn Phe Glu Ser Ile Tyr Lys Lys His Leu Cys Leu Glu Arg Lys Gln Leu Asn Leu Glu Ile Tyr Asp Pro Cys Ser Gln Thr Gln Lys Ala Lys Phe Ser Leu Thr Ser Glu Leu His Trp Ala Asp Gly Phe Val Ile Val Tyr Asp Ile Ser Asp Arg Ser Ser Phe Ala Phe Ala Lys Ala Leu Ile Tyr Arg Ile Arg Glu Pro Gln Thr Ser His Cys Lys Arg Ala Val Glu Ser Ala Val Phe Leu Val Gly Asn Lys Arg Asp Leu Cys His Val Arg Glu Val Gly Trp Glu Glu Gly Gln Lys Leu Ala Leu Glu Asn Arg Cys Gln Phe Cys Glu Leu Ser Ala Ala Glu Gln Ser Leu Glu Val Glu Met Met Phe Ile Arg Ile Ile Lys Asp Ile Leu Ile Asn Phe Lys Leu Lys Glu Lys 170 ' 175 180 Arg Arg Pro Ser Gly Ser Lys Ser Met Ala Lys Leu Ile Asn Asn Val Phe Gly Lys Arg Arg Lys Ser Val <210> 13 <211> 100 <212> PRT
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 1739479CD1 <400> 13 Met Trp Asp Ser Lys Lys Ile Gly Leu Arg Gln His His Cys Arg Lys Cys Gly Lys Ala Val Cys Gly Lys Cys Ser Ser Lys Arg Ser Ser Ile Pro Leu Met Gly Phe Glu Phe Glu Val Arg Val Cys Asp Ser Cys His Glu Ala Ile Thr Asp Glu Glu Arg Ala Pro Thr Ala Thr Phe His Asp Ser Lys His Asn Ile Val His Val His Phe Asp Ala Thr Arg Gly Trp Leu Leu Thr Ser Gly Thr Asp Lys Val Ile Lys Leu Trp Asp Met Thr Pro Val Val Ser <210> 14 <211> 795 <212> PRT
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 1999147CD1 <400> 14 Met Thr Ser Gly Ala Thr Arg Tyr Arg Leu Ser Cys Ser Leu Arg 1 5 . 10 15 Gly His Glu Leu Asp Val Arg Gly Leu Val Cys Cys Ala Tyr Pro Pro Gly Ala Phe Val Ser Val Ser Arg Asp Arg Thr Thr Arg Leu Trp Ala Pro Asp Ser Pro Asn Arg Ser Phe Thr Glu Met His Cys Met Ser Gly His Ser Asn Phe Val Ser Cys Val Cys Ile Ile Pro Ser Ser Asp Ile Tyr Pro His Gly Leu Ile Ala Thr Gly Gly Asn Asp His Asn Ile Cys Ile Phe Ser Leu Asp Ser Pro Met Pro Leu Tyr Ile Leu Lys Gly His Lys Asn Thr Val Cys Ser Leu Ser Ser Gly Lys Phe Gly Thr Leu Leu Ser Gly Ser Trp Asp Thr Thr Ala Lys Val Trp Leu Asn Asp Lys Cys Met Met Thr Leu Gln Gly His Thr Ala Ala Val Trp Ala Val Lys Ile Leu Pro Glu Gln Gly Leu Met Leu Thr Gly Ser Ala Asp Lys Thr Val Lys Leu Trp Lys Ala Gly Arg Cys Glu Arg Thr Phe Ser Gly His Glu Asp Cys Val Arg Gly Leu Ala Ile Leu Ser Glu Thr Glu Phe Leu Ser Cys Ala Asn Asp Ala Ser Ile Arg Arg Trp Gln Ile Thr Gly Glu Cys Leu Glu Val Tyr Tyr Gly His Thr Asn Tyr Ile Tyr Ser Ile Ser Val Phe Pro Asn Cys Arg Asp Phe Val Thr Thr Ala Glu Asp Arg Ser Leu Arg Ile Trp Lys His Gly Glu Cys Ala Gln Thr Ile Arg Leu Pro Ala Gln Ser Ile Trp Cys Cys Cys Val Leu Asp Asn Gly Asp Ile Val Val Gly Ala Ser Asp Gly Ile Ile Arg Val Phe Thr Glu Ser Glu Asp Arg Thr Ala Ser Ala Glu Glu Ile Lys Ala Phe Glu Lys Glu Leu Ser His Ala Thr Ile Asp Ser Lys Thr Gly Asp Leu Gly Asp Ile Asn Ala Glu Gln,Leu Pro Gly Arg Glu His Leu Asn Glu Pro Gly Thr Arg Glu Gly Gln Thr Arg Leu Ile Arg Asp Gly Glu Lys Val Glu Ala Tyr Gln Trp Ser Val Ser Glu Gly Arg Trp Ile Lys Ile Gly Asp Val Val Gly Ser Ser Gly Ala Asn Gln Gln Thr Ser Gly Lys Val Leu Tyr Glu Gly Lys Glu Phe Asp Tyr Val Phe Ser Ile Asp Val Asn Glu Gly Gly Pro Ser Tyr Lys Leu Pro Tyr Asn Thr Ser Asp Asp Pro Trp Leu Thr Ala Tyr Asn Phe Leu Gln Lys Asn Asp Leu Asn Pro Met Phe Leu Asp Gln Val Ala Lys Phe Ile Ile Asp Asn Thr Lys Gly Gln Met Leu Gly Leu Gly Asn Pro Ser Phe Ser Asp Pro Phe Thr Gly Gly Gly Arg Tyr Val Pro Gly Ser Ser Gly Ser Ser Asn Thr Leu Pro Thr Ala Asp Pro Phe Thr Gly Ala Gly Arg Tyr Val Pro Gly Ser Ala Ser Met Gly Thr Thr Met Ala Gly Val Asp Pro Phe Thr Gly Asn Ser Ala Tyr Arg Ser Ala Ala Ser Lys Thr Met Asn Ile Tyr Phe Pro Lys Lys Glu Ala Val Thr Phe Asp Gln Ala Asn Pro Thr Gln Ile Leu Gly Lys Leu Lys Glu Leu Asn Gly Thr Ala Pro Glu Glu Lys Lys Leu Thr Glu Asp Asp Leu Ile Leu Leu Glu Lys Ile Leu Ser Leu Ile Cys Asn Ser Ser Ser Glu Lys Pro Thr Val Gln Gln Leu Gln Ile Leu Trp Lys Ala Ile Asn Cys Pro Glu Asp Ile Val Phe Pro Ala Leu Asp Ile Leu Arg Leu Ser Ile Lys His Pro Ser Val Asn Glu Asn Phe Cys Asn Glu Lys Glu Gly Ala Gln Phe Ser Ser His Leu Ile Asn Leu Leu Asn Pro Lys Gly Lys Pro Ala Asn Gln Leu Leu Ala Leu Arg Thr Phe Cys Asn Cys Phe Val Gly Gln Ala Gly Gln Lys Leu Met Met Ser Gln Arg Glu Ser Leu Met Ser His Ala Ile Glu Leu Lys Ser Gly Ser Asn Lys Asn Ile His Ile Ala Leu Ala Thr Leu Ala Leu Asn Tyr Ser Val Cys Phe His Lys Asp His Asn Ile Glu Gly Lys Ala Gln Cys Leu Ser Leu Ile Ser Thr Ile Leu Glu Val Val Gln Asp Leu Glu Ala Thr Phe Arg Leu Leu Val Ala Leu Gly Thr Leu Ile Ser Asp Asp Ser Asn Ala Val Gln Leu Ala Lys Ser Leu Gly Val Asp Ser Gln Ile Lys Lys Tyr Ser Ser Val Ser Glu Pro Ala Lys Val Ser Glu Cys Cys Arg Phe Ile Leu Asn Leu Leu <210> 15 <211> 393 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 2182085CD1 <400> 15 Met Glu Asp Phe Glu Asp Asp Pro Arg Ala Leu Gly Ala Arg Gly His Arg Arg Ser Val Ser Arg Gly Ser Tyr Gln Leu Gln Ala Gln Met Asn Arg Ala Val Tyr Glu Asp Arg Pro Pro Gly Ser Val Val Pro Thr Ser Ala Ala Glu Ala Ser Arg Ala Met Ala Gly Asp Thr Ser Leu Ser Glu Asn Tyr Ala Phe Ala Gly Met Tyr His Val Phe Asp Gln His Val Asp Glu Ala Val Pro Arg Val Arg Phe Ala Asn Asp Asp Arg His Arg Leu Ala Cys Cys Ser Leu Asp Gly Ser Ile Ser Leu Cys Gln Leu Val Pro Ala Pro Pro Thr Val Leu Arg Val Leu Arg Gly His Thr Arg Gly Val Ser Asp Phe Ala Trp Ser Leu Ser Asn Asp Ile Leu Val Ser Thr Ser Leu Asp Ala Thr Met Arg Met Ala Gly Val Asp Pro Phe Thr Gly Asn Ser Ala Ty Ile Trp Ala Ser Glu Asp Gly Arg Cys Ile Arg Glu Ile Pro Asp Pro Asp Ser Ala Glu Leu Leu Cys Cys Thr Phe Gln Pro Val Asn Asn Asn Leu Thr Val Val Gly Asn Ala Lys His Asn Val His Val Met Asn Ile Ser Thr Gly Lys Lys Val Lys Gly Gly Ser Ser Lys Leu Thr Gly Arg Val Leu Ala Leu Ser Phe Asp Ala Pro Gly Arg Leu Leu Trp Ala Gly Asp Asp Arg Gly Ser Val Phe Ser Phe Leu Phe Asp Met Ala Thr Gly Lys Leu Thr Lys Ala Lys Arg Leu Val Val His Glu Gly Ser Pro Val Thr Ser Ile Ser Ala Arg Ser Trp Val Ser Arg Glu Ala Arg Asp Pro Ser Leu Leu Ile Asn Ala Cys Leu Asn Lys Leu Leu Leu Tyr Arg Val Val Asp Asn Glu Gly Thr Leu Gln Leu Lys Arg Ser Phe Pro Ile Glu Gln Ser Ser His Pro Val Arg Ser Ile Phe Cys Pro Leu Met Ser Phe Arg Gln Gly Ala Cys Val Val Thr Gly Ser Glu Asp Met Cys Val His Phe Phe Asp Val Glu Arg Ala Ala Lys Ala Ala Val Asn Lys Leu Gln Gly His Ser Ala Pro Val Leu Asp Val Ser Phe Asn Cys Asp Glu Ser Leu Leu Ala Ser Ser Asp Ala Ser Gly Met Val Ile Val Trp Arg Arg Glu Gln Lys <210> 16 <211> 485 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 2216640CD1 <400> 16 Met Ala Ala Ala Val Ala Asp Glu Ala Val Ala Arg Asp Val Gln Arg Leu Leu Val Gln Phe Gln Asp Glu Gly Gly Gln Leu Leu Gly Ser Pro Phe Asp Val Pro Val Asp Ile Thr Pro Asp Arg Leu Gln Leu Val Cys Asn Ala Leu Leu Ala Gln Glu Asp Pro Leu Pro Leu Ala Phe Phe Val His Asp Ala Glu Ile Val Ser Ser Leu Gly Lys Thr Leu Glu Ser Gln Ala Val Glu Thr Glu Lys Val Leu Asp Ile Ile Tyr Gln Pro Gln Ala Ile Phe Arg Val Arg Ala Val Thr Arg Cys Thr Ser Ser Leu Glu Gly His Ser Glu Ala Val Ile Ser Val Ala Phe Ser Pro Thr Gly Lys Tyr Leu Ala Ser Gly Ser Gly Asp Thr Thr Val Arg Phe Trp Asp Leu Ser Thr Glu Thr Pro His Phe Thr Cys Lys Gly His Arg His Trp Val Leu Ser Ile Ser Trp Ser Pro Asp Gly Lys Lys Leu Ala Ser Gly Cys Lys Asn Gly Gln Ile Leu Leu Trp Asp Pro Ser Thr Gly Lys Gln Val Gly Arg Thr Leu Ala Gly His Ser Lys Trp Ile Thr Gly Leu Ser Trp Glu Pro Leu His Ala Asn Pro Glu Cys Arg Tyr Val Ala Ser Ser Ser Lys Asp Gly Ser Val Arg Ile Trp Asp Thr Thr Ala Gly Arg Cys Glu Arg Ile Leu Thr Gly His Thr Gln Ser Val Thr Cys Leu Arg Trp Gly Gly Asp Gly Leu Leu Tyr Ser Ala Ser Gln Asp Arg Thr Ile Lys Val Trp Arg Ala His Asp Gly Val Leu Cys Arg Thr Leu Gln Gly His Gly His Trp Val Asn Thr Met Ala Leu Ser Thr Asp Tyr Ala Leu Arg Thr Gly Ala Phe Glu Pro Ala Glu Ala Ser Val Asn Pro Gln Asp Leu Gln Gly Ser Leu Gln Glu Leu Lys Glu Arg Ala Leu Ser Arg Tyr Asn Leu Val Arg Gly Gln Gly Pro Glu Arg Leu Val Ser Gly Ser Asp Asp Phe Thr Leu Phe Leu Trp Ser Pro Ala Glu Asp Lys Lys Pro Leu Thr Arg Met Thr Gly His Gln Ala Leu Ile Asn Gln Val Leu Phe Ser Pro Asp Ser Arg Ile Val Ala Ser Ala Ser Phe Asp Lys Ser Ile Lys Leu Trp Asp Gly Arg Thr Gly Lys Tyr Leu Ala Ser Leu Arg Gly His Val Ala Ala Val Tyr Gln Ile Ala Trp Ser Ala Asp Ser Arg Leu Leu Val Ser Gly Ser Ser Asp Ser Thr Leu Lys Val Trp Asp Val Lys Ala Gln Lys Leu Ala Met Asp Leu Pro Gly His Ala Asp Glu Val Tyr Ala Val Asp Trp Ser Pro Asp Gly Gln Arg Val Ala Ser Gly Gly Lys Asp Lys Cys Leu Arg Ile Trp Arg Arg <210> 17 <211> 199 <212> PRT
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 2417361CD1 <400> 17 Met Asn Pro Arg Lys Lys Val Asp Leu Lys Leu Ile Ile Val Gly Ala Ile Gly Val Gly Lys Thr Ser Leu Leu His Gln Tyr Val His Lys Thr Phe Tyr Glu Glu Tyr Gln Thr Thr Leu Gly Ala Ser Ile Leu Ser Lys Ile Ile Ile Leu Gly Asp Thr Thr Leu Lys Leu Gln Ile Trp Asp Thr Gly Gly Gln Glu Arg Phe Arg Ser Met Val Ser Thr Phe Tyr Lys Gly Ser Asp Gly Cys Ile Leu Ala Phe Asp Val Thr Asp Leu Glu Ser Phe Glu Ala Leu Asp Ile Trp Arg Gly Asp Val Leu Ala Lys Ile Val Pro Met Glu Gln Ser Tyr Pro Met Val Leu Leu Gly Asn Lys Ile Asp Leu Ala Asp Arg Lys Val Pro Gln Glu Val Ala Gln Gly Trp Cys Arg Glu Lys Asp Ile Pro Tyr Phe Glu Val Ser Ala Lys Asn Asp Ile Asn Val Val Gln Ala Phe Glu Met Leu Ala Ser Arg Ala Leu Ser Arg Tyr Gln Ser Ile Leu Glu Asn His Leu Thr Glu Ser Ile Lys Leu Ser Pro Asp Gln Ser Arg Ser Arg Cys Cys <210> 18 <211> 163 <212> PRT
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 2454384CD1 <400> 18 Met Glu Gly Pro Ser Leu Arg Gly Pro Ala Leu Arg Leu Ala Gly Leu Pro Thr Gln Gln Asp Cys Asn Ile Gln Glu Lys Ile Asp Leu Glu Ile Arg Met Arg Glu Gly Ile Trp Lys Leu Leu Ser Leu Ser Thr Gln Lys Asp Gln Val Leu His Ala Val Lys Asn Leu Met Val Cys Asn Ala Arg Leu Met Ala Tyr Thr Ser Glu Leu Gln Lys Leu Glu Glu Gln Ile Ala Asn Gln Thr Gly Arg Cys Asp Val Lys Phe Glu Ser Lys Glu Arg Thr Ala Cys Lys Gly Lys Ile Ala Ile Ser Asp Ile Arg Ile Pro Leu Met Trp Lys Asp Ser Asp His Phe Ser Asn Lys Glu Arg Ser Arg Arg Tyr Ala Ile Phe Cys Leu Phe Lys Met Gly Ala Asn Val Phe Asp Thr Asp Val Val Asn Val Asp Lys Thr Ile Thr Asp Ile Cys Phe Glu Asn Val Thr Ile Leu <210> 19 <211> 290 <212> PRT
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 2610262CD1 <400> 19 Met Ala Ala Glu Ile Gln Pro Lys Pro Leu Thr Arg Lys Pro Ile Leu Leu Gln Arg Met Glu Gly Ser Gln Glu Val Val Asn Met Ala Val Ile Val Pro Lys Glu Glu Gly Val Ile Ser Val Ser Glu Asp Arg Thr Val Arg Val Trp Leu Lys Arg Asp Ser Gly Gln Tyr Trp Pro Ser Val Tyr His Ala Met Pro Ser Pro Cys Ser Cys Met Ser Phe Asn Pro Glu Thr Arg Arg Leu Ser Ile Gly Leu Asp Asn Gly Thr Ile Ser Glu Phe Ile Leu Ser Glu Asp Tyr Asn Lys Met Thr Pro Val Lys Asn Tyr Gln Ala His Gln Ser Arg Val Thr Met Ile Leu Phe Val Leu Glu Leu Glu Trp Val Leu Ser Thr Gly Gln Asp Lys Gln Phe Ala Trp His Cys Ser Glu Ser Gly Gln Arg Leu Gly Gly Tyr Arg Thr Ser Ala Val Ala Ser Gly Leu Gln Phe Asp Val Glu Thr Arg His Val Phe Ile Gly Asp His Ser Gly Gln Val Thr Ile Leu Lys Leu Glu Gln Glu Asn Cys Thr Leu Val Thr Thr Phe Arg Gly His Thr Gly Gly Val Thr Ala Leu Cys Trp Asp Pro Val Gln Arg Val Leu Phe Ser Gly Ser Ser Asp His Ser Val Ile Met Trp Asp Ile Gly Gly Arg Lys Gly Thr Ala Ile Glu Leu Gln Gly His Asn Asp Arg Val Gln Ala Leu Ser Tyr Ala Gln His Thr Arg Gln Leu Ile Ser Cys Gly Gly Asp Gly Gly Ile Val Val Trp Asn Met Asp Val Glu Arg Gln Glu Pro Leu Trp Ser Cys Phe Val Val Met Ile Ser Ala Val <210> 20 <211> 705 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 2700075CD1 <400> 20 Met Gly Thr Trp Glu His Leu Val Ser Thr Gly Phe Asn Gln Met Arg Glu Arg Glu Val Lys Leu Trp Asp Thr Arg Phe Phe Ser Ser Ala Leu Ala Ser Leu Thr Leu Asp Thr Ser Leu Gly Cys Leu Val Pro Leu Leu Asp Pro Asp Ser Gly Leu Leu Val Leu Ala Gly Lys Gly Glu Arg Gln Leu Tyr Cys Tyr Glu Val Val Pro Gln Gln Pro Ala Leu Ser Pro Val Thr Gln Cys Val Leu Glu Ser Val Leu Arg Gly Ala Ala Leu Val Pro Arg Gln Ala Leu Ala Val Met Ser Cys Glu Val Leu Arg Val Leu Gln Leu Ser Asp Thr Ala Ile Val Pro Ile Gly Tyr His Val Pro Arg Lys Ala Val Glu Phe His Glu Asp Leu Phe Pro Asp Thr Ala Gly Cys Val Pro Ala Thr Asp Pro His Ser Trp Trp Ala Gly Asp Asn Gln Gln Val Gln Lys Val Ser Leu Asn Pro Ala Cys Arg Pro His Pro Ser Phe Thr Ser Cys Leu Val Pro Pro Ala Glu Pro Leu Pro Asp Thr Ala Gln Pro Ala Val Met Glu Thr Pro Val Gly Asp Ala Asp Ala Ser Glu Gly Phe Ser Ser Pro Pro Ser Ser Leu Thr Ser Pro Ser Thr Pro Ser Ser Leu Gly .

Pro Ser Leu Ser Ser Thr Ser Gly Ile Gly Thr Ser Pro Ser Leu Arg Ser Leu Gln Ser Leu Leu Gly Pro Ser Ser Lys Phe Arg His Ala Gln Gly Thr Val Leu His Arg Asp Ser His Ile Thr Asn Leu Lys Gly Leu Asn Leu Thr Thr Pro Gly Glu Ser Asp Gly Phe Cys Ala Asn Lys Leu Arg Val Ala Val Pro Leu Leu Ser Ser Gly Gly Gln Val Ala Val Leu Glu Leu Arg Lys Pro Gly Arg Leu Pro Asp Thr Ala Leu Pro Thr Leu Gln Asn Gly Ala Ala Val Thr Asp Leu Ala Trp Asp Pro Phe Asp Pro His Arg Leu Ala Val Ala Gly Glu Asp Ala Arg Ile Arg Leu Trp Arg Val Pro Ala Glu Gly Leu Glu Glu Val Leu Thr Thr Pro Glu Thr Val Leu Thr Gly His Thr Glu Lys Ile Cys Ser Leu Arg Phe His Pro Leu Ala Ala Asn Val Leu Ala Ser Ser Ser Tyr Asp Leu Thr Val Arg Ile Trp Asp Leu Gln Ala Gly Ala Asp Arg Leu Lys Leu Gln Gly His Gln Asp Gln Ile Phe Ser Leu Ala Trp Ser Pro Asp Gly Gln Gln Leu Ala Thr Val Cys Lys Asp Gly Arg Val Arg Val Tyr Arg Pro Arg Ser Gly Pro Glu Pro Leu Gln Glu Gly Pro Gly Pro Lys Gly Gly Arg Gly Ala Arg Ile Val Trp Val Cys Asp Gly Arg Cys Leu Leu Val Ser Gly Phe. Asp Ser Gln Ser Glu Arg Gln Leu Leu Leu Tyr Glu Ala Glu Ala Leu Ala Gly Gly Pro Leu Ala Val Leu Gly Leu Asp Val Ala Pro Ser Thr Leu Leu Pro Ser Tyr Asp Pro Asp Thr Gly Leu Val Leu Leu Thr Gly Lys Gly Asp Thr Arg Val Phe Leu Tyr Glu Leu Leu Pro Glu Ser Pro Phe Phe Leu Glu Cys Asn Ser Phe Thr Ser Pro Asp Pro His Lys Gly Leu Val Leu Leu Pro Lys Thr Glu Cys Asp Val Arg Glu Val Glu Leu Met Arg Cys Leu Arg Leu Arg Gln Ser Ser Leu Glu Pro Val Ala Phe Arg Leu Pro Arg Val Arg Lys Glu Phe Phe Gln Asp Asp Val Phe Pro Asp Thr Ala Val Ile Trp Glu Pro Val Leu Ser Ala Glu Ala Trp Leu Gln Gly Ala Asn Gly Gln Pro Trp Leu Leu Ser Leu Gln Pro Pro Asp Met Ser Pro Val Ser Gln Ala Pro Arg Glu Ala Pro Ala Arg Arg Ala Pro Ser Ser Ala Gln Tyr Leu Glu Glu Lys Ser Asp Gln Gln Lys Lys Glu Glu Leu Leu Asn Ala Met Val Ala Lys Leu Gly Asn Arg Glu Asp Pro Leu Pro Gln Asp Ser Phe Glu Gly Val Asp Glu Asp Glu Trp Asp <210> 21 <211> 454 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 2786701CD1 <400> 21 Met Ala Ser Ser Glu Val Ala Arg His Leu Leu Phe Gln Ser His Met Ala Thr Lys Thr Thr Cys Met Ser Ser Gln Gly Ser Asp Asp Glu Gln Ile Lys Arg Glu Asn Ile Arg Ser Leu Thr Met Ser Gly His Val Gly Phe Glu Ser Leu Pro Asp Gln Leu Val Asn Arg Ser Ile Gln Gln Gly Phe Cys Phe Asn Ile Leu Cys Val Gly Glu Thr Gly Ile Gly Lys Ser Thr Leu Ile Asp Thr Leu Phe Asn Thr Asn Phe Glu Asp Tyr Glu Ser Ser His Phe Cys Pro Asn Val Lys Leu Lys Ala Gln Thr Tyr Glu Leu Gln Glu Ser Asn Val Gln Leu Lys Leu Thr Ile Val Asn Thr Val Gly Phe Gly Asp Gln Ile Asn Lys Glu Glu Ser Tyr Gln Pro Ile Val Asp Tyr Ile Asp Ala Gln Phe Glu Ala Tyr Leu Gln Glu Glu Leu Lys Ile Lys Arg Ser Leu Phe Thr Tyr His Asp Ser Arg Ile His Val Cys Leu Tyr Phe Ile Ser Pro Thr Gly His Ser Leu Lys Thr Leu Asp Leu Leu Thr Met Lys Asn Leu Asp Ser Lys Val Asn Ile Ile Pro Val Ile Ala Lys Ala Asp Thr Val Ser Lys Thr Glu Leu Gln Lys Phe Lys Ile Lys Leu Met Ser Glu Leu Val Ser Asn Gly Val Gln Ile Tyr Gln Phe Pro Thr Asp Asp Asp Thr Ile Ala Lys Val Asn Ala Ala Met Asn Gly Gln Leu Pro Phe Ala Val Val Gly Ser Met Asp Glu Val Lys Val Gly Asn Lys Met Val Lys Ala Arg Gln Tyr Pro Trp Gly Val Val Gln Val Glu Asn Glu Asn His Cys Asp Phe Val Lys Leu Arg Glu Met Leu Ile Cys Thr Asn Met Glu Asp Leu Arg Glu Gln Thr His Thr Arg His Tyr Glu Leu Tyr Arg Arg Cys Lys Leu Glu Glu Met Gly Phe Thr Asp Val Gly Pro Glu Asn Lys Pro Val Ser Val Gln Glu Thr Tyr Glu Ala Lys Arg His Glu Phe His Gly Glu Arg Gln Arg Lys Glu Glu Glu Met Lys Gln Met Phe Val Gln Arg Val Lys Glu Lys Glu Ala Ile Leu Lys Glu Ala Glu Arg Glu Leu Gln Ala Lys Phe Glu His Leu Lys Arg Leu His Gln Glu Glu Arg Met Lys Leu Glu Glu Lys Arg Arg Leu Leu Glu Glu Glu Ile Ile Ala Phe Ser Lys Lys Lys Ala Thr Ser Glu Ile Phe His Ser Gln Ser Phe Leu Ala Thr Gly Ser Asn Leu Arg Lys Asp Lys Asp Arg Lys Asn Ser Asn Phe Leu <210> 22 <211> 433 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 3068538CD1 <400> 22 Met Ala Gly Gln Asp Pro Ala Leu Ser Thr Ser His Pro Phe Tyr Asp Val Ala Arg His Gly Ile Leu Gln Val Ala Gly Asp Asp Arg Phe Gly Arg Arg Val Val Thr Phe Ser Cys Cys Arg Met Pro Pro Ser His Glu Leu Asp His Gln Arg Leu Leu Glu Tyr Leu Lys Tyr Thr Leu Asp Gln Tyr Val Glu Asn Asp Tyr Thr Ile Val Tyr Phe His Tyr Gly Leu Asn Ser Arg Asn Lys Pro Ser Leu Gly Trp Leu Gln Ser Ala Tyr Lys Glu Phe Asp Arg Lys Tyr Lys Lys Asn Leu Lys Ala Leu Tyr Val Val His Pro Thr Ser Phe Ile Lys Val Leu Trp Asn Ile Leu Lys Pro Leu Ile Ser His Lys Phe Gly Lys Lys Val Ile Tyr Phe Asn Tyr Leu Ser Glu Leu His Glu His Leu Lys Tyr Asp Gln Leu Val Ile Pro Pro Glu Val Leu Arg Tyr Asp Glu Lys Leu Gln Ser Leu His Glu Gly Arg Thr Pro Pro Pro Thr Lys Thr Pro Pro Pro Arg Pro Pro Leu Pro Thr Gln Gln Phe Gly Val Ser Leu Gln Tyr Leu Lys Asp Lys Asn Gln Gly Glu Leu Ile Pro Pro Val Leu Arg Phe Thr Val Thr Tyr Leu Arg Glu Lys Gly Leu Arg Thr Glu Gly Leu Phe Arg Arg Ser Ala Ser Val Gln Thr Val Arg Glu Ile Gln Arg Leu Tyr Asn Gln Gly Lys Pro Val Asn Phe Asp Asp Tyr Gly Asp Ile His Ile Pro Ala Val Ile Leu Lys Thr Phe Leu Arg Glu Leu Pro Gln Pro Leu Leu Thr Phe Gln Ala Tyr Glu Gln Ile Leu Gly Ile Thr Cys Val Glu Ser Ser Leu Arg Val Thr Gly Cys Arg Gln Ile Leu Arg Ser Leu Pro Glu His Asn Tyr Val Val Leu Arg Tyr Leu Met Gly Phe Leu His Ala Val Ser Arg Glu Ser Ile Phe Asn Lys Met Asn Ser Ser Asn Leu Ala Cys Val Phe Gly Leu Asn Leu Ile Trp Pro Ser Gln Gly Val Ser Ser Leu Ser Ala Leu Val Pro Leu Asn Met Phe Thr Glu Leu Leu Ile Glu Tyr Tyr Glu Lys Ile Phe Ser Thr Pro Glu Ala Pro Gly Glu His Gly Leu Ala Pro Trp Glu Gln Gly Ser Arg Ala Ala Pro Leu Gln Glu Ala Val Pro Arg Thr Gln Ala Thr Gly Leu Thr Lys Pro Thr Leu Pro Pro Ser Pro Leu Met Ala Ala Arg Arg Arg Leu <210> 23 <211> 406 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 5159072CD1 <400> 23 Met Ala Asp Gly Asn Glu Asp Leu Arg Ala Asp Asp Leu Pro Gly Pro Ala Phe Glu Ser Tyr Glu Ser Met Glu Leu Ala Cys Pro Ala Glu Arg Ser Gly His Val Ala Val Ser Asp Gly Arg His Met Phe Val Trp Gly Gly Tyr Lys Ser Asn Gln Val Arg Gly Leu Tyr Asp Phe Tyr Leu Pro Arg Glu Glu Leu Trp Ile Tyr Asn Met Glu Thr Gly Arg Trp Lys Lys Ile Asn Thr Glu Gly Asp Val Pro Pro Ser Met Ser Gly Ser Cys Ala Val Cys Val Asp Arg Val Leu Tyr Leu Phe Gly Gly His His Ser Arg Gly Asn Thr Asn Lys Phe Tyr Met Leu Asp Ser Arg Ser Thr Asp Arg Val Leu Glri Trp Glu Arg Ile Asp Cys Gln Gly Ile Pro Pro Ser Ser Lys Asp Lys Leu Gly Val Trp Val Tyr Lys Asn Lys Leu Ile Phe Phe Gly Gly Tyr Gly Tyr Leu Pro Glu Asp Lys Val Leu Gly Thr Phe Glu Phe Asp,Glu Thr Ser Phe Trp Asn Ser Ser His Pro Arg Gly Trp Asn Asp His Val His Ile Leu Asp Thr Glu Thr Phe Thr Trp Ser Gln Pro Ile Thr Thr Gly Lys Ala Pro Ser Pro Arg Ala Ala His Ala Cys Ala Thr Val Gly Asn Arg Gly Phe Val Phe Gly Gly Arg Tyr Arg Asp Ala Arg Met Asn Asp Leu His Tyr Leu Asn Leu Asp Thr Trp Glu Trp Asn Glu Leu Ile Pro Gln Gly Ile Cys Pro Val Gly Arg Ser Trp His Ser Leu Thr Pro Val Ser Ser Asp His Leu Phe Leu Phe Gly Gly Phe Thr Thr Asp Lys Gln Pro Leu Ser Asp Ala Trp Thr Tyr Cys Ile Ser Lys Asn Glu Trp Ile Gln Phe Asn His Pro Tyr Thr Glu Lys Pro Arg Leu Trp His Thr Ala Cys Ala Ser Asp Glu Gly Glu Val Ile Val Phe Gly Gly Cys Ala Asn Asn Leu Leu Val His His Arg Ala Ala His Ser Asn Glu Ile Leu Ile Phe Ser Val Gln Pro Lys Ser Leu Val Arg Leu Ser Leu Glu Ala Val Ile Cys Phe 365 370 ' 375 Lys Glu Met Leu Ala Asn Ser Trp Asn Cys Leu Pro Lys His Leu Leu His Ser Val Asn Gln Arg Phe Gly Ser Asn Asn Thr Ser Gly Ser <210> 24 <211> 229 <212> PRT
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 5519057CD1 <400> 24 Met Ala Glu Glu Met Glu Ser Ser Leu Glu Ala Ser Phe Ser Ser Ser Gly Ala Val Ser Gly Ala Ser Gly Phe Leu Pro Pro Ala Arg Ser Arg Ile Phe Lys Ile Ile Val Ile Gly Asp Ser Asn Val Gly Lys Thr Cys Leu Thr Tyr Arg Phe Cys Ala Gly Arg Phe Pro Asp Arg Thr Glu Ala Thr Ile Gly Val Asp Phe Arg Glu Arg Ala Val Glu Ile Asp Gly Glu Arg Ile Lys Ile Gln Leu Trp Asp Thr Ala Gly Gln Glu Arg Phe Arg Lys Ser Met Val Gln His Tyr Tyr Arg Asn Val His Ala Val Val Phe Val Tyr Asp Met Thr Asn Met Ala Ser Phe His Ser Leu Pro Ser Trp Ile Glu Glu Cys Lys Gln His Leu Leu Ala Asn Asp Ile Pro Arg Ile Leu Val Gly Asn Lys Cys Asp Leu Arg Ser Ala Ile Gln Val Pro Thr Asp Leu Ala Gln Lys Phe Ala Asp Thr His Ser Met Pro Leu Phe Glu Thr Ser Ala Lys Asn Pro Asn Asp Asn Asp His Val Glu Ala Ile Phe Met Thr Leu Ala His Lys Leu Lys Cys His Lys Pro Leu Met Leu Ser Gln Pro Pro Asp Asn Gly Ile Ile Leu Lys Pro Glu Pro Lys Pro Ala Met Thr Cys Trp Cys <210> 25 <211> 670 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 035379CD1 <400> 25 Met Ser Ser Gly Lys Ser Ala Arg Tyr Asn Arg Phe Ser Gly Gly Pro Ser Asn Leu Pro Thr Pro Asp Val Thr Thr Gly Thr Arg Met Glu Thr Thr Phe Gly Pro Ala Phe Ser Ala Val Thr Thr Ile Thr Lys Ala Asp Gly Thr Ser Thr Tyr Lys Gln His Cys Arg Thr Pro Ser Ser Ser Ser Thr Leu Ala Tyr Ser Pro Arg Asp Glu Glu Asp Ser Met Pro Pro Ile Ser Thr Pro Arg Arg Ser Asp Ser Ala Ile Ser Val Arg Ser Leu His Ser Glu Ser Ser Met Ser Leu Arg Ser Thr Phe Ser Leu Pro Glu Glu Glu Glu Glu Pro Glu Pro Leu Val Phe Ala Glu Gln Pro Ser Val Lys Leu Cys Cys Gln Leu Cys Cys Ser Val Phe Lys Asp Pro Val Ile Thr Thr Cys Gly His Thr Phe Cys Arg Arg Cys Ala Leu Lys Ser Glu Lys Cys Pro Val Asp Asn Val Lys Leu Thr Val Val Val Asn Asn Ile Ala Val Ala Glu Gln Ile Gly Glu Leu Phe Ile His Cys Arg His Gly Cys Arg Val Ala Gly Ser Gly Lys Pro Pro Ile Phe Glu.Va1 Asp Pro Arg Gly Cys Pro Phe Thr Ile Lys Leu Ser Ala Arg Lys Asp His Glu Gly Ser Cys Asp Tyr Arg Pro Val Arg Cys Pro Asn Asn Pro Ser Cys Pro Pro Leu Leu Arg Met Asn Leu Glu Ala His Leu Lys Glu Cys Glu His Ile Lys Cys Pro His Ser Lys Tyr Gly Cys Thr Phe Ile Gly Asn Gln Asp Thr Tyr Glu Thr His Leu Glu Thr Cys Arg Phe Glu Gly Leu Lys Glu Phe Leu Gln Gln Thr Asp Asp Arg Phe His Glu Met His Val Ala Leu Ala Gln Lys Asp Gln Glu Ile Ala Phe Leu Arg Ser Met Leu Gly Lys Leu Ser Glu Lys Ile Asp Gln Leu Glu Lys Ser Leu Glu Leu Lys Phe Asp Val Leu Asp Glu Asn Gln Ser Lys Leu Ser Glu Asp Leu Met Glu Phe Arg Arg Asp Ala Ser Met Leu Asn Asp Glu Leu Ser His Ile Asn Ala Arg Leu Asn Met Gly Ile Leu Gly Ser Tyr Asp Pro Gln Gln Ile Phe Lys Cys Lys Gly Thr Phe Val Gly His Gln Gly Pro Val Trp Cys Leu Cys Val Tyr Ser Met Gly Asp Leu Leu Phe Ser Gly Ser Ser Asp Lys Thr Ile Lys Val Trp Asp Thr Cys Thr Thr Tyr Lys Cys Gln Lys Thr Leu Glu Gly His Asp Gly Ile Val Leu Ala Leu Cys Ile Gln Gly Cys Lys Leu Tyr Ser Gly Ser Ala Asp Cys Thr Ile Ile Val Trp Asp Ile Gln Asn Leu Gln Lys Val Asn Thr Ile Arg Ala His Asp Asn Pro Val Cys Thr Leu Val Ser Ser His Asn Val Leu Phe Ser Gly Ser Leu Lys Ala Ile Lys Val Trp Asp Ile Val Gly Thr Glu Leu Lys Leu Lys Lys Glu Leu Thr Gly Leu Asn His Trp Val Arg Ala Leu Val Ala Ala Gln Ser Tyr Leu Tyr Ser Gly Ser Tyr Gln Thr Ile Lys Ile Trp Asp Ile Arg Thr Leu Asp Cys Ile His Val Leu Gln Thr Ser Gly Gly Ser Val Tyr Ser Ile Ala Val Thr Asn His His Ile Val Cys Gly Thr Tyr Glu Asn Leu Ile His Val Trp Asp Ile Glu Ser Lys Glu Gln Val Arg Thr Leu Thr Gly His Val Gly Thr Val Tyr Ala Leu Ala Val Ile Ser Thr Pro Asp Gln Thr Lys Val Phe Ser Ala Ser Tyr Asp Arg Ser Leu Arg Val Trp Ser Met Asp Asn Met Ile Cys Thr Gln Thr Leu Leu Arg His Gln Ser Ser Val Thr Ala Leu Ala Val Ser Arg Gly Arg Leu Phe Ser Gly Ala Val Asp Ser Thr Val Lys Val Trp Thr Cys <210> 26 <211> 445 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 275354CD1 <400> 26 Met Lys Val Lys Met Leu Ser Arg Asn Pro Asp Asn Tyr Val Arg Glu Thr Lys Leu Asp Leu Gln Arg Val Pro Arg Asn Tyr Asp Pro Ala Leu His Pro Phe Glu Val Pro Arg Glu Tyr Val Arg Ala Leu Asn Ala Thr Lys Leu Glu Arg Val Phe Ala Lys Pro Phe Leu Ala Ser Leu Asp Gly His Arg Asp Gly Val Asn Cys Leu Ala Lys His Pro Glu Lys Leu Ala Thr Val Leu Ser Gly Ala Cys Asp Gly Glu Val Arg Ile Trp Asn Leu Thr Gln Arg Asn Cys Ile Arg Thr Ile Gln Ala His Glu Gly Phe Val Arg Gly Ile Cys Thr Arg Phe Cys Gly Thr Ser Phe Phe Thr Val Gly Asp Asp Lys Thr Val Lys Gln Trp Lys Met Asp Gly Pro Gly Tyr Gly Asp Glu Glu Glu Pro Leu His Thr Ile Leu Gly Lys Thr Val Tyr Thr Gly Ile Asp His His Trp Lys Glu Ala Val Phe Ala Thr Cys Gly Gln Gln Val Asp Ile Trp Asp Glu Gln Arg Thr Asn Pro Ile Cys Ser Met Thr Trp Gly Phe Asp Ser Ile Ser Ser Val Lys Phe Asn Pro Ile Glu Thr Phe Leu Leu Gly Ser Cys Ala Ser Asp Arg Asn Ile Val Leu Tyr Asp Met Arg Gln Ala Thr Pro Leu Lys Lys Val Ile Leu Asp Met Arg Thr Asn Thr Ile Cys Trp Asn Pro Met Glu Ala Phe Ile Phe Thr Ala Ala Asn Glu Asp Tyr Asn Leu Tyr Thr Phe Asp Met Arg Ala Leu Asp Thr Pro Val Met Val His Met Asp His Val Ser Ala Val Leu Asp Val Asp Tyr Ser Pro Thr Gly Lys Glu Phe Val Ser Ala Ser Phe Asp Lys Ser Ile Arg Ile Phe Pro Val Asp Lys Ser Arg Ser Arg Glu Val Tyr His Thr Lys Arg Met Gln His Val Ile Cys Val Lys Trp Thr Ser Asp Ser Lys Tyr Ile Met Cys Gly Ser Asp Glu Met Asn Ile Arg Leu Trp Lys Ala Asn Ala Ser Glu Lys Leu Gly Val Leu Thr Ser Arg Glu Lys Ala Ala Lys Asp Tyr Asn Gln Lys Leu Lys Glu Lys Phe Gln His Tyr Pro His Ile Lys Arg Ile Ala Arg His Arg His Leu Pro Lys Ser Ile Tyr Ser Gln Ile Gln Glu Gln Arg Ile Met Lys Glu Ala Arg Arg Arg Lys Glu Val Asn Arg Ile Lys His Ser Lys Pro Gly Ser Val Pro Leu Val Ser Glu Lys Lys Lys His Val Val Ala Val Val Lys <210> 27 <211> 236 <212> PRT

<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 311658CD1 <400> 27 Met Ser Asp Leu Leu Ser Pro Leu Leu Tyr Val Met Glu Asn Glu Val Asp Ala Phe Trp Cys Phe Ala Ser Tyr Met Asp Gln Met His Gln Asn Phe Glu Glu Gln Met Gln Gly Met Lys Thr Gln Leu Ile Gln Leu Ser Thr Leu Leu Arg Leu Leu Asp Ser Gly Phe Cys Ser Tyr Leu Glu Ser Gln Asp Ser Gly Tyr Leu Tyr Phe Cys Phe Arg Trp Leu Leu Ile Arg Phe Lys Arg Glu Phe Ser Phe Leu Asp Ile Leu Arg Leu Trp Glu Val Met Trp Thr Glu Leu Pro Cys Thr Asn Phe His Leu Leu Leu Cys Cys Ala Ile Leu Glu Ser Glu Lys Gln Gln Ile Met Glu Lys His Tyr Gly Phe Asn Glu Ile Leu Lys His Ile Asn Glu Leu Ser Met Lys Ile Asp Val Glu Asp Ile Leu Cys Lys Ala Glu Ala Ile Ser Leu Gln Met Val Lys Cys Lys Glu Leu Pro Gln Ala Val Cys Glu Ile Leu Gly Leu Gln Gly Ser Glu Val Thr Thr Pro Asp Ser Asp Val Gly Glu Asp Glu Asn Val Val Met Thr Pro Cys Pro Thr Ser Ala Phe Gln Ser Asn Ala Leu Pro Thr Leu Ser Ala Ser Gly Ala Arg Asn Asp Ser Pro Thr Gln Ile Pro Val Ser Ser Asp Val Cys Arg Leu Thr Pro Ala <210> 28 <211> 498 <212> PRT
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 1251632CD1 <400> 28 Met Gln Glu Ser Gly Cys Arg Leu Glu His Pro Ser Ala Thr Lys Phe Arg Asn His Val Met Glu Gly Asp Trp Asp Lys Ala Glu Asn Asp Leu Asn Glu Leu Lys Pro Leu Val His Ser Pro His Ala Ile Val Arg Met Lys Phe Leu Leu Leu Gln Gln Lys Tyr Leu Glu Tyr Leu Glu Asp Gly Lys Val Leu Glu Ala Leu Gln Val Leu Arg Cys Glu Leu Thr Pro Leu Lys Tyr Asn Thr Glu Arg Ile His Val Leu Ser Gly Tyr Leu Met Cys Ser His Ala Glu Asp Leu Arg Ala Lys Ala Glu Trp Glu Gly Lys Gly Thr Ala Ser Arg Ser Lys Leu Leu Asp Lys Leu Gln Thr Tyr Leu Pro Pro Ser Val Met Leu Pro Pro Arg Arg Leu Gln Thr Leu Leu Arg Gln Ala Val Glu Leu Gln Arg Asp Arg Cys Leu Tyr His Asn Thr Lys Leu Asp Asn Asn Leu Asp Ser Val Ser Leu Leu Ile Asp His Val Cys Ser Arg Arg Gln Phe Pro Cys Tyr Thr Gln Gln Ile Leu Thr Glu His Cys Asn Glu Val Trp Phe Cys Lys Phe Ser Asn Asp Gly Thr Lys Leu Ala Thr Gly Ser Lys Asp Thr Thr Val Ile Ile Trp Gln Val Asp Pro Asp Thr His Leu Leu Lys Leu Leu Lys Thr Leu Glu Gly His Ala Tyr Gly Val Ser Tyr Ile Ala Trp Ser Pro Asp Asp Asn Tyr Leu Val Ala Cys Gly Pro Asp Asp Cys Ser Glu Leu Trp Leu Trp Asn Val Gln Thr Gly Glu Leu Arg Thr Lys Met Ser Gln Ser His Glu Asp Ser Leu Thr Ser Val Ala Trp Asn Pro Asp Gly Lys Arg Phe Val Thr Gly Gly Gln Arg Gly Gln Phe Tyr Gln Cys Asp Leu.Asp Gly Asn Leu Leu Asp Ser Trp Glu Gly Val Arg Val Gln Cys Leu Trp Cys Leu Ser Asp Gly Lys Thr Val Leu Ala Ser Asp Thr His Gln Arg Ile Arg Gly Tyr Asn Phe Glu Asp Leu Thr Asp Arg Asn Ile Val Gln Glu Asp His Pro Ile Met Ser Phe Thr Ile Ser Lys Asn Gly Arg Leu Ala Leu Leu Asn Val Ala Thr Gln Gly Val His Leu Trp Asp Leu Gln Asp Arg Val Leu Val Arg Lys Tyr Gln Gly Val Thr Gln Gly Phe Tyr Thr Ile His Ser Cys Phe Gly Gly His Asn Glu Asp Phe Ile Ala Ser Gly Ser Glu Asp His Lys Val Tyr Ile Trp His Lys Arg Ser Glu Leu Pro Ile Ala Glu Leu Thr Gly His Thr Arg Thr Val Asn Cys Val Ser Trp Asn Pro Gln Ile Pro Ser Met Met Ala Ser Ala Ser Asp Asp Gly Thr Val Arg Ile Trp Gly Pro Ala Pro Phe Ile Asp His Gln Asn Ile Glu Glu Glu Cys Ser Ser Met Asp Ser <210> 29 <211> 334 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 1331955CD1 <400> 29 Met Ala Thr Glu Glu Lys Lys Pro Glu Thr Glu Ala Ala Arg Ala Gln Pro Thr Pro Ser Ser Ser Ala Thr Gln Ser Lys Pro Thr Pro Val Lys Pro Asn Tyr Ala Leu Lys Phe Thr Leu Ala Gly His Thr Lys Ala Val Ser Ser Val Lys Phe Ser Pro Asn Gly Glu Trp Leu Ala Ser Ser Ser Ala Asp Lys Leu Ile Lys Ile Trp Gly Ala Tyr Asp Gly Lys Phe Glu Lys Thr Ile Ser Gly His Lys Leu Gly Ile Ser Asp Val Ala Trp Ser Ser Asp Ser Asn Leu Leu Val Ser Ala Ser Asp Asp Lys Thr Leu Lys Ile Trp Asp Val Ser Ser Gly Lys Cys Leu Lys Thr Leu Lys Gly His Ser Asn Tyr Val Phe Cys Cys Asn Phe Asn Pro Gln Ser Asn Leu Ile Val Ser Gly Ser Phe Asp Glu Ser Val Arg Ile Trp Asp Val Lys Thr Gly Lys Cys Leu Lys Thr Leu Pro Ala His Ser Asp Pro Val Ser Ala Val His Phe Asn Arg Asp Gly Ser Leu Ile Val Ser Ser Ser Tyr Asp Gly Leu Cys Arg Ile Trp Asp Thr Ala Ser Gly Gln Cys Leu Lys Thr Leu Ile Asp Asp Asp Asn Pro Pro Val Ser Phe Val Lys Phe Ser Pro Asn Gly Lys Tyr Ile Leu Ala Ala Thr Leu Asp Asn Thr Leu Lys Leu Trp Asp Tyr Ser Lys Gly Lys Cys Leu Lys Thr Tyr Thr Gly His Lys Asn Glu Lys Tyr Cys Ile Phe Ala Asn Phe Ser Val Thr Gly Gly Lys Trp Ile Val Ser Gly Ser Glu Asp Asn Leu Val Tyr Ile Trp Asn Leu Gln Thr Lys Glu Ile Val Gln Lys Leu Gln Gly His Thr Asp Val Val Ile Ser Thr Ala Cys His Pro Thr Glu Asn Ile Ile Ala Ser Ala Ala Leu Glu Asn Asp Lys Thr Ile Lys Leu Trp Lys Ser Asp Cys <210> 30 <211> 292 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 1412614CD1 <400> 30 Met Met Ala Phe Ala Pro Pro Lys Asn Thr Asp Gly Pro Lys Met Gln Thr Lys Met Ser Thr Trp Thr Pro Leu Asn His Gln Leu Leu Asn Asp Arg Val Phe Glu Glu Arg Arg Ala Leu Leu Gly Lys Trp Phe Asp Lys Trp Thr Asp Ser Gln Arg Arg Arg Ile Leu Thr Gly Leu Leu Glu Arg Cys Ser Leu Ser Gln Gln Lys Phe Cys Cys Arg Lys Leu Gln Glu Lys Ile Pro Ala Glu Ala Leu Asp Phe Thr Thr Lys Leu Pro Arg Val Leu Ser Leu Tyr Ile Phe Ser Phe Leu Asp Pro Arg Ser Leu Cys Arg Cys Ala Gln Val Cys Trp His Trp Lys Asn Leu Ala Glu Leu Asp Gln Leu Trp Met Leu Lys Cys Leu Arg Phe Asn Trp Tyr Ile Asn Phe Ser Pro Thr Pro Phe Glu Gln Gly Ile Trp Lys Lys His Tyr Ile Gln Met Val Lys Glu Leu His Ile Thr Lys Pro Lys Thr Pro Pro Lys Asp Gly Phe Val Ile Ala Asp Val Gln Leu Val Thr Ser Asn Ser Pro Glu Glu Lys Gln Ser Pro Leu Ser Ala Phe Arg Ser Ser Ser Ser Leu Arg Lys Lys Asn Asn Ser Gly Glu Lys Ala Leu Pro Pro Trp Arg Ser Ser Asp Lys His Pro Thr Asp Ile Ile Arg Phe Asn Tyr Leu Asp Asn Arg Asp Pro Met Glu Thr Val Gln Gln Gly Arg Arg Lys Arg Asn Gln Ile Thr Pro Asp Phe Ser Arg Gln Ser His Asp Lys Lys Asn Lys Leu Gln Asp Arg Thr Arg Leu Arg Lys Ala Gln Ser Met Met Ser Arg Arg Asn Pro Phe Pro Leu Cys Pro <210> 31 <211> 588 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 1750781CD1 <400> 31 Met Ser Ser Gly Leu Arg Ala Ala Asp Phe Pro Arg Trp Lys Arg His Ile Ser Glu Gln Leu Arg Arg Arg Asp Arg Leu Gln Arg Gln Ala Phe Glu Glu Ile Ile Leu Gln Tyr Asn Lys Leu Leu Glu Lys Ser Asp Leu His Ser Val Leu Ala Gln Lys Leu Gln Ala Glu Lys His Asp Val Pro Asn Arg His Glu Ile Ser Pro Gly His Asp Gly Thr Trp Asn Asp Asn Gln Leu Gln~Glu Met Ala Gln Leu Arg Ile Lys His Gln Glu Glu Leu Thr Glu Leu His Lys Lys Arg Gly Glu Leu Ala Gln Leu Val Ile Asp Leu Asn Asn Gln Met Gln Arg Lys Asp Arg Glu Met Gln Met Asn Glu Ala Lys Ile Ala Glu Cys Leu Gln Thr Ile Ser Asp Leu Glu Thr Glu Cys Leu Asp Leu Arg Thr Lys Leu Cys Asp Leu Glu Arg Ala Asn Gln Thr Leu Lys Asp Glu Tyr Asp Ala Leu Gln Ile Thr Phe Thr Ala Leu Glu Gly Lys Leu Arg Lys Thr Thr Glu Glu Asn Gln Glu Leu Val Thr Arg Trp Met Ala Glu Lys Ala Gln Glu Ala Asn Arg Leu Asn Ala Glu Asn Glu Lys Asp Ser Arg Arg Arg Gln Ala Arg Leu Gln Lys Glu Leu Ala Glu Ala Ala Lys Glu Pro Leu Pro Val Glu Gln Asp Asp Asp Ile Glu Val Ile Val Asp Glu Thr Ser Asp His Thr Glu Glu Thr Ser Pro Val Arg Ala Ile Ser Arg Ala Ala Thr Arg Arg Ser Val Ser Ser Phe Pro Val Pro Gln Asp Asn Val Asp Thr His Pro Gly Ser Gly Lys Glu Val Arg Val Pro Ala Thr Ala Leu Cys Val Phe Asp Ala His Asp Gly Glu Val Asn Ala Val Gln Phe Ser Pro Gly Ser Arg Leu Leu Ala Thr Gly Gly Met Asp Arg Arg Val Lys Leu Trp Glu Val Phe Gly Glu Lys Cys Glu Phe Lys Gly Ser Leu Ser Gly Ser Asn Ala Gly Ile Thr Ser Ile Glu Phe Asp Ser Ala Gly Ser Tyr Leu Leu Ala Ala Ser Asn Asp Phe Ala Ser Arg Ile Trp Thr Val Asp Asp Tyr Arg Leu Arg His Thr Leu Thr Gly His Ser Gly Lys Val Leu Ser Ala Lys Phe Leu Leu Asp Asn Ala Arg Ile Val Ser Gly Ser His Asp Arg Thr Leu Lys Leu Trp Asp Leu Arg Ser Lys Val Cys Ile Lys Thr Val Phe Ala Gly Ser Ser Cys Asn Asp Ile Val Cys Thr Glu Gln Cys Val Met Ser Gly His Phe Asp Lys Lys Ile Arg Phe Trp Asp Ile Arg Ser Glu Ser Ile Val Arg Glu Met Glu Leu Leu Gly Lys Ile Thr Ala Leu Asp Leu Asn Pro Glu Arg Thr Glu Leu Leu Ser Cys Ser Arg Asp Asp Leu Leu Lys Val Ile Asp Leu Arg Thr Asn Ala Ile Lys Gln Thr Phe Ser Ala Pro Gly Phe Lys Cys Gly Ser Asp Trp Thr Arg Val Val Phe Ser Pro Asp Gly Ser Tyr Val Ala Ala Gly Ser Ala Glu Gly Ser Leu Tyr Ile Trp Ser Val Leu Thr Gly Lys Val Glu Lys Val Leu Ser Lys Gln His Ser Ser Ser Ile Asn Ala Val Ala Trp Ser Pro Ser Gly Ser His Val Val Ser Val Asp Lys Gly Cys Lys Ala Val Leu Trp Ala Gln Tyr <210> 32 <211> 326 <212> PRT
<213> Homo sapiens <220>
<221> misC_feature <223> Incyte ID No: 1821658CD1 <400> 32 Met Lys Gln Asp Ala Ser Arg Asn Ala Ala Tyr Thr Val Asp Cys Glu Asp Tyr Val His Val Val Glu Phe Asn Pro Phe Glu Asn Gly Asp Ser Gly Asn Leu Ile Ala Tyr Gly Gly Asn Asn Tyr Val Val Ile Gly Thr Cys Thr Phe Gln Glu Glu Glu Ala Asp Val Glu Gly Ile Gln Tyr Lys Thr Leu Arg Thr Phe His His Gly Val Arg Val Asp Gly Ile Ala Trp Ser Pro Glu Thr Arg Leu Asp Ser Leu Pro Pro Val Ile Lys Phe Cys Thr Ser Ala Ala Asp Met Lys Ile Arg Leu Phe Thr Ser Asp Leu Gln Asp Lys Asn Glu Tyr Lys Val Leu Glu Gly His Thr Asp Phe Ile Asn Gly Leu Val Phe Asp Pro Lys Glu Gly Gln Glu Ile Ala Ser Val Ser Asp Asp His Thr Cys Arg Ile Trp Asn Leu Glu Gly Val Gln Thr Ala His Phe Val Leu His Ser Pro Gly Met Ser Val Cys Trp His Pro Glu Glu Thr Phe Lys Leu Met Val Ala Glu Lys Asn Gly Thr Ile Arg Phe Tyr Asp Leu Leu Ala Gln Gln Ala Ile Leu Ser Leu Glu Ser Glu Gln Val Pro Leu Met Ser Ala His Trp Cys Leu Lys Asn Thr Phe Lys Val Gly Ala Val Ala Gly Asn Asp Trp Leu Ile Trp Asp Ile Thr Arg Ser Ser Tyr Pro Gln Asn Lys Arg Pro Val His Met Asp Arg Ala Cys Leu Phe Arg Trp Ser Thr Ile Ser Glu Asn Leu Phe Ala Thr Thr Gly Tyr Pro Gly Lys Met Ala Ser Gln Phe Gln Ile His His Leu Gly His Pro Gln Pro Ile Leu Met Gly Ser Val Ala Val Gly Ser Gly Leu Ser Trp His Arg Thr Leu Pro Leu Cys Val Ile Gly Gly Asp His Lys Leu Leu Phe Trp Val Thr Glu Val <210> 33 <211> 453 <212> PRT
<213> Homo sapiens <220>
<221> misC_feature <223> Incyte ID No: 1872574CD1 <400> 33 Met Ala Arg Lys Val Val Ser Arg Lys Arg Lys Ala Pro Ala Ser Pro Gly Ala Gly Ser Asp Ala Gln Gly Pro Gln Phe Gly Trp Asp His Ser Leu His Lys Arg Lys Arg Leu Pro Pro Val Lys Arg Ser Leu Val Tyr Tyr Leu Lys Asn Arg Glu Val Arg Leu Gln Asn Glu Thr Ser Tyr Ser Arg Val Leu His Gly Tyr Ala Ala Gln Gln Leu Pro Ser Leu Leu Lys Glu Arg Glu Phe His Leu Gly Thr Leu Asn Lys Val Phe Ala Ser Gln Trp Leu Asn His Arg Gln Val Val Cys Gly Thr Lys Cys Asn Thr Leu Phe Val Val Asp Val Gln Thr Ser Gln Ile Thr Lys Ile Pro Ile Leu Lys Asp,Arg Glu Pro Gly Gly Val Thr Gln Gln Gly Cys Gly Ile His Ala Ile Glu Leu Asn Pro Ser Arg Thr Leu Leu Ala Thr Gly Gly Asp Asn Pro Asn Ser Leu Ala Ile Tyr Arg Leu Pro Thr Leu Asp Pro Val Cys Val Gly Asp Asp Gly His Lys Asp Trp Ile Phe Ser Ile Ala Trp Ile Ser Asp Thr Met Ala Val Ser Gly Ser Arg Asp Gly Ser Met Gly Leu Trp Glu Val Thr Asp Asp Val Leu Thr Lys Ser Asp Ala Arg His Asn Val Ser Arg Val Pro Val Tyr Ala His Ile Thr His Lys Ala Leu Lys Asp Ile Pro Lys Glu Asp Thr Asn Pro Asp Asn Cys Lys Val Arg Ala Leu Ala Phe Asn Asn Lys Asn Lys Glu Leu Gly Ala Val Ser Leu Asp Gly Tyr Phe His Leu Trp Lys Ala Glu Asn Thr Leu Ser Lys Leu Leu Ser Thr Lys Leu Pro Tyr Cys Arg Glu Asn Val Cys Leu Ala Tyr Gly Ser Glu Trp Ser Val Tyr Ala Val Gly Ser Gln Ala His Val Ser Phe Leu Asp Pro Arg Gln Pro Ser Tyr Asn Val Lys Ser Val Cys Ser Arg Glu Arg Gly Ser Gly Ile Arg Ser Val Ser Phe Tyr Glu His Ile Ile Thr Val Gly Thr Gly Gln Gly Ser Leu Leu Phe Tyr Asp Ile Arg Ala Gln Arg Phe Leu Glu Glu Arg Leu Ser Ala Cys Tyr Gly Ser Lys Pro Arg Leu Ala Gly Glu Asn Leu Lys Leu Thr Thr Gly Lys Gly Trp Leu Asn His Asp Glu Thr Trp Arg Asn Tyr Phe Ser Asp Ile Asp Phe Phe Pro Asn Ala Val Tyr Thr His Cys Tyr Asp Ser Ser Gly Thr Lys Leu Phe Val Ala Gly Gly Pro Leu Pro Ser Gly Leu His Gly Asn Tyr Ala Gly Leu Trp Ser <210> 34 <211> 161 <212> PRT
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 2590967CD1 <400> 34 Met Ala Thr Glu Gly Gly Gly Lys Glu Met Asn Glu Ile Lys Thr Gln Phe Thr Thr Arg Glu Gly Leu Tyr Lys Leu Leu Pro His Ser Glu Tyr Ser Arg Pro Asn Arg Val Pro Phe Asn Ser Gln.Gly Ser Asn Pro Val Arg Val Ser Phe Val Asn Leu Asn Asp Gln Ser Gly Asn Gly Asp Arg Leu Cys Phe Asn Val Gly Arg Glu Leu Tyr Phe Tyr Ile Tyr Lys Gly Val Arg Lys Ala Ala Asp Leu Ser Lys Pro Ile Asp Lys Arg Ile Tyr Lys Gly Thr Gln Pro Thr Cys His Asp Phe Asn His Leu Thr Ala Thr Ala Glu Ser Val Ser Leu Leu Val Gly Phe Ser Ala Gly Gln Val Gln Leu Ile Asp Pro Ile Lys Lys Glu Thr Ser Lys Leu Phe Asn Glu Glu Gly Ser Leu Ser Ser Pro Ser Gln Ala Ser Ser Pro Gly Gly Thr Val Val <210> 35 <211> 684 <212> PRT
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 2824491CD1 <400> 35 Met Ala Arg His Arg Asn Val Arg Gly Tyr Asn Tyr Asp Glu Asp Phe Glu Asp Asp Asp Leu Tyr Gly Gln Ser Val Glu Asp Asp Tyr Cys Ile Ser Pro Ser Thr Ala Ala Gln Phe Ile Tyr Ser Arg Arg Asp Lys Pro Ser Val Glu Pro Val Glu Glu Tyr Asp Tyr Glu Asp Leu Lys Glu Ser Ser Asn Ser Val Ser Asn His Gln Leu Ser Gly Phe Asp Gln Ala Arg Leu Tyr Ser Cys Leu Asp His Met Arg Glu Val Leu Gly Asp Ala Val Pro Asp Glu Ile Leu Ile Glu Ala Val Leu Lys Asn Lys Phe Asp Val Gln Lys Ala Leu Ser Gly Val Leu Glu Gln Asp Arg Val Gln Ser Leu Lys Asp Lys Asn Glu Ala Thr Val Ser Thr Gly Lys Ile Ala Lys Gly Lys Pro Val Asp Ser Gln Thr Ser Arg Ser Glu Ser Glu Ile Val Pro Lys Val Ala Lys Met Thr Val Ser Gly Lys Lys Gln Thr Met Gly Phe Glu Val Pro Gly Val Ser Ser Glu Glu Asn Gly His Ser Phe His Thr Pro Gln Lys Gly Pro Pro Ile Glu Asp Ala Ile Ala Ser Ser Asp Val Leu Glu Thr Ala Ser Lys Ser Ala Asn Pro Pro His Thr Ile Gln Ala Ser Glu Glu Gln Ser Ser Thr Pro Ala Pro Val Lys Lys Ser Gly Lys Leu Arg Gln Gln Ile Asp Val Lys Ala Glu Leu Glu Lys Arg Gln Gly Gly Lys Gln Leu Leu Asn Leu Val Val Ile Gly His Val Asp Ala Gly Lys Ser Thr Leu Met Gly His Met Leu Tyr Leu Leu Gly Asn Ile Asn Lys Arg Thr Met His Lys Tyr Glu Gln Glu Ser Lys 290 ' 295 300 Lys Ala Gly Lys Ala Ser Phe Ala Tyr Ala Trp Val Leu Asp Glu Thr Gly Glu Glu Arg Glu Arg Gly Val Thr Met Asp Val Gly Met Thr Lys Phe Glu Thr Thr Thr Lys Val Ile Thr Leu Met Asp Ala Pro Gly His Lys Asp Phe Ile Pro Asn Met Ile Thr Gly Ala Ala Gln Ala Asp Val Ala Val Leu Val Val Asp Ala Ser Arg Gly Glu Phe Glu Ala Gly Phe Glu Thr Gly Gly Gln Thr Arg Glu His Gly Leu Leu Val Arg Ser Leu Gly Val Thr Gln Leu Ala Val Ala Val Asn Lys Met Asp Gln Val Asn Trp Gln Gln Glu Arg Phe Gln Glu Ile Thr Gly Lys Leu Gly His Phe Leu Lys Gln Ala Gly Phe Lys Glu Ser Asp Val Gly Phe Ile Pro Thr Ser Gly Leu Ser Gly Glu Asn Leu Ile Thr Arg Ser Gln Ser Ser Glu Leu Thr Lys Trp Tyr Lys Gly Leu Cys Leu Leu Glu Gln Ile Asp Ser Phe Lys Pro Pro 470 475 ~ 480 Gln Arg Ser Ile Asp Lys Pro Phe Arg Leu Cys Val Ser Asp Val Phe Lys Asp Gln Gly Ser Gly Phe Cys Ile Thr Gly Lys Ile Glu Ala Gly Tyr Ile Gln Thr Gly Asp Arg Leu Leu Ala Met Pro Pro Asn Glu Thr Cys Thr Val Lys Gly Ile Thr Leu His Asp Glu Pro Val Asp Trp Ala Ala Ala Gly Asp His Val Ser Leu Thr Leu Val Gly Met Asp Ile Ile Lys Ile Asn Val Gly Cys Ile Phe Cys Gly Pro Lys Val Pro Ile Lys Ala Cys Thr Arg Phe Arg Ala Arg Ile Leu Ile Phe Asn Ile Glu Ile Pro Ile Thr Lys Gly Phe Pro Val Leu Leu His Tyr Gln Thr Val Ser Glu Pro Ala Val Ile Lys Arg Leu Ile Ser Val Leu Asn Lys Ser Thr Gly Glu Val Thr Lys Lys Lys Pro Lys Phe Leu Thr Lys Gly Gln Asn Ala Leu Val Glu Leu Gln Thr Gln Arg Pro Ile Ala Leu Glu Leu Tyr Lys Asp Phe Lys Glu Leu Gly Arg Phe Met Leu Arg Tyr Gly Gly Ser Thr Ile Ala Ala Gly Val Val Thr Glu Ile Lys Glu <210> 36 <211> 366 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 2825460CD1 <400> 36 Met Ala Ala Ala Ala Ala Arg Trp Asn His Val Trp Val Gly Thr Glu Thr Gly Ile Leu Lys Gly Val Asn Leu Gln Arg Lys Gln Ala Ala Asn Phe Thr Ala Gly Gly Gln Pro Arg Arg Glu Glu Ala Val Ser Ala Leu Cys Trp Gly Thr Gly Gly Glu Thr Gln Met Leu Val Gly Cys Ala Asp Arg Thr Val Lys His Phe Ser Thr Glu Asp Gly Ile Phe Gln Gly Gln Arg His Cys Pro Gly Gly Glu Gly Met Phe Arg Gly Leu Ala Gln Ala Asp Gly Thr Leu Ile Thr Cys Val Asp Ser Gly Ile Leu Arg Val Trp His Asp Lys Asp Lys Asp Thr Ser Ser Asp Pro Leu Leu Glu Leu Arg Val Gly Pro Gly Val Cys Arg Met Arg Gln Asp Pro Ala His Pro His Val Val Ala Thr Gly Gly Lys Glu Asn Ala Leu Lys Ile Trp Asp Leu Gln Gly Ser Glu Glu Pro Val Phe Arg Ala Lys Asn Val Arg Asn Asp Trp Leu Asp Leu 170 ~ 175 180 Arg Val Pro Ile Trp Asp Gln Asp Ile Gln Phe Leu Pro Gly Ser Gln Lys Leu Val Thr Cys Thr Gly Tyr His Gln Val Arg Val Tyr Asp Pro Ala Ser Pro Gln Arg Arg Pro Val Leu Glu Thr Thr Tyr Gly Glu Tyr Pro Leu Thr Ala Met Thr Leu Thr Pro Gly Gly Asn Ser Val Ile Val Gly Asn Thr His Gly Gln Leu Ala Glu Ile Asp Leu Arg Gln Gly Arg Leu Leu Gly Cys Leu Lys Gly Leu Ala Gly Ser Val Arg Gly Leu Gln Cys His Pro Ser Lys Pro Leu Leu Ala Ser Cys Gly Leu Asp Arg Val Leu Arg Ile His Arg Ile Gln Asn Pro Arg Gly Leu Glu His Lys Asp Glu Pro Gln Glu Pro Gln Glu Pro Asn Lys Val Pro Leu Glu Asp Thr Glu Thr Asp Glu Leu Trp 320 325 ' 330 Ala Ser Leu Glu Ala Ala Ala Lys Arg Lys Leu Ser Gly Leu Glu Gln Pro Gln Gly Ala Leu Gln Thr Arg Arg Arg Lys Lys Lys Arg 36/115' Pro Gly Ser Thr Ser Pro <210> 37 <211> 339 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 2871116CD1 <400> 37 Met Ala Thr Glu Ile Gly Ser Pro Pro Arg Phe Phe His Met Pro Arg Phe Gln His Gln Ala Pro Arg Gln Leu Phe Tyr Lys Arg Pro Asp Phe Ala Gln Gln Gln Ala Met Gln Gln Leu Thr Phe Asp Gly Lys Arg Met Arg Lys Ala Val Asn Arg Lys Thr Ile Asp Tyr Asn Pro Ser Val Ile Lys Tyr Leu Glu Asn Arg Ile Trp Gln Arg Asp Gln Arg Asp Met Arg Ala Ile Gln Pro Asp Ala Gly,Tyr Tyr Asn Asp Leu Val Pro Pro Ile Gly Met Leu Asn Asn Pro Met Asn Ala Val Thr Thr Lys Phe Val Arg Thr Ser Thr Asn Lys Val Lys Cys Pro Val Phe Val Val Arg Leu Gln Glu Glu Phe Glu Ser Leu Ser Val Leu Lys Ser Trp Thr Pro Glu Gly Arg Arg Leu Val Thr Gly Ala Ser Ser Gly Glu Phe Thr Leu Trp Asn Gly Leu Thr Phe Asn Phe Glu Thr Ile Leu Gln Ala His Asp Ser Pro Val Arg Ala Met Thr Trp Ser His Asn Asp Met Trp Met Leu Thr Ala Asp His Gly Gly Tyr Val Lys Tyr Trp Gln Ser Asn Met Asn Asn Val Lys Met Phe Gln Ala His Lys Glu Ala Ile Arg Glu Ala Arg Phe Ile His Asn Ile Pro Phe Ser Val Val Pro Ile Val Met Val Lys Leu Phe Ser Lys Cys Ile Leu Gly Ala Glu Met His Gly Leu Cys Gln Phe Leu Gly Asn Phe Leu His Pro Ile Asn Thr Ile Phe Phe Phe Val Phe Thr His Ser Pro Phe Cys Trp His Leu Ser Glu Val Val Leu Ser Arg Tyr Gln Pro Leu Gln Tyr Val Arg Asp Val Leu Ser Ala Ala Phe Cys Thr Gly Phe Leu Phe Ser Phe Met Ile Asn Asn Val Tyr Thr Leu Phe Leu Phe Ile Ile Tyr Cys Val Arg Gln Glu Tyr Phe Ile Pro Asn Lys Glu Phe Ser Leu <210> 38 <211> 213 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 2942212CD1 <400> 38 Met Glu Ala Ile Trp Leu Tyr Gln Phe Arg Leu Ile Val Ile Gly Asp Ser Thr Val Gly Lys Ser Cys Leu Ile Arg Arg Phe Thr Glu Gly Arg Phe Ala Gln Val Ser Asp Pro Thr Val Gly Val Asp Phe Phe Ser Arg Leu Val Glu Ile Glu Pro Gly Lys Arg Ile Lys Leu Gln Ile Trp Asp Thr Ala Gly Gln Glu Arg Phe Arg Ser Ile Thr Arg Ala Tyr Tyr Arg Asn Ser Val Gly Gly Leu Leu Leu Phe Ala Ile Thr Asn Arg Arg Ser Phe Gln Asn Val His Glu Trp Leu Glu Glu Thr Lys Val His Val Gln Pro Tyr Gln Ile Val Phe Val Leu Val Gly His Lys Cys Asp Leu Asp Thr Gln Arg Gln Val Thr Arg His Glu Ala Glu Lys Leu Ala Ala Ala Tyr Gly Met Lys Tyr Ile Glu Thr Ser Ala Arg Asp Ala Ile Asn Val Glu Lys Ala Phe Thr Asp Leu Thr Arg Asp Ile Tyr Glu Leu Val Lys Arg Gly Glu Ile Thr Ile Gln Glu Gly Trp Glu Gly Val Lys Ser Gly Phe Val Pro Asn Val Val His Ser Ser Glu Glu Val Val Lys Ser Glu Arg Arg Cys Leu Cys <210> 39 <211> 393 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 3685151CD1 <400> 39 Met Glu Leu Val Ala Gly Cys Tyr Glu Gln Val Leu Phe Gly Phe Ala Val His Pro Glu Pro Glu Ala Cys Gly Asp His Glu Gln Gln Trp Thr Leu Val Ala Asp Phe Thr His His Ala His Thr Ala Ser Leu Ser Ala Val Ala Val Asn Ser Arg Phe Val Val Thr Gly Ser Lys Asp Glu Thr Ile His Ile Tyr Asp Met Lys Lys Lys Ile Glu His Gly Ala Leu Val His His Ser Gly Thr Ile Thr Cys Leu Thr Phe Tyr Gly Asn Arg His Leu Ile Ser Gly Ala Glu Asp Gly Leu Ile Cys Ile Trp Asp Ala Lys Lys Trp Glu Ser Leu Thr Ser Ile Lys Ala His Lys Gly Gln Val Thr Phe Leu Ser Ile His Pro Ser Gly Lys Leu Ala Leu Ser Val Gly Thr Asp Lys Thr Leu Arg Thr Trp Asn Leu Val Glu Gly Arg Ser Ala Phe Ile Lys Asn Ile Lys Gln Asn Ala His Ile Val Glu Trp Ser Pro Arg Gly Glu Gln Tyr Val Val Ile Ile Gln Asn Lys Ile Asp Ile Tyr Gln Leu Asp Thr Ala Ser Ile Ser Gly Thr Ile Thr Asn Glu Lys Arg Ile Ser Ser Val Lys Phe Leu Ser Glu Ser Val Leu Ala Val Ala Gly Asp Glu Glu Val Ile Arg Phe Phe Asp Cys Asp Ser Leu Val Cys Leu Cys Glu Phe Lys Ala His Glu Asn Arg Val Lys Asp Met Phe Ser Phe Glu Ile Pro Glu His His Val Ile Val Ser Ala Ser Ser Asp Gly Phe Ile Lys Met Trp Lys Leu Lys Gln Asp Lys Lys Val Pro Pro Ser Leu Leu Cys Glu Ile Asn Thr Asn Ala Arg Leu Thr Cys Leu Gly Val Trp Leu Asp Lys Val Ala Asp Met Lys Glu Ser Leu Pro Pro Ala Ala Glu Pro Ser Pro Val Ser Lys Glu Gln Ser Lys Ile Gly Lys Lys Glu Pro Gly Asp Thr Val His Lys Glu Glu Lys Arg Ser Lys Pro Asn Thr Lys Lys Arg Gly Leu Thr Gly Asp Ser Lys Lys Ala Thr Lys Glu Ser Gly Leu Ile Ser Thr Lys Lys Arg Lys Met Val Glu Met Leu Glu Lys Lys Arg Lys Lys Lys Lys Ile Lys Thr Met Gln <210> 40 <211> 399 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 4881515CD1 <400> 40 Met Ser Leu Gln Tyr Gly Ala Glu Glu Thr Pro Leu Ala Gly Ser Tyr Gly Ala Ala Asp Ser Phe Pro Lys Asp Phe Gly Tyr Gly Val Glu Glu Glu Glu Glu Glu Ala Ala Ala Ala Gly Gly Gly Val Gly Ala Gly Ala Gly Gly Gly Cys Gly Pro Gly Gly Ala Asp Ser Ser Lys Pro Arg Ile Leu Leu Met Gly Leu Arg Arg Ser Gly Lys Ser Ser Ile Gln Lys Val Val Phe His Lys Met Ser Pro Asn Glu Thr Leu Phe Leu Glu Ser Thr Asn Lys Ile Tyr Lys Asp Asp Ile Ser Asn Ser Ser Phe Val Asn Phe Gln Ile Trp Asp Phe Pro Gly Gln Met Asp Phe Phe Asp Pro Thr Phe Asp Tyr Glu Met Ile Phe Arg Gly Thr Gly Ala Leu Ile Tyr Val Ile Asp Ala Gln Asp Asp Tyr Met Glu Ala Leu Thr Arg Leu His Ile Thr Val Ser Lys Ala Tyr Lys Val Asn Pro Asp Met Asn Phe Glu Val Phe Ile His Lys Val Asp Gly Leu Ser Asp Asp His Lys Ile Glu Thr Gln Arg Asp Ile His Gln Arg Ala Asn Asp Asp Leu Ala Asp Ala Gly Leu Glu Lys Leu His Leu Ser Phe Tyr Leu Thr Ser Ile Tyr Asp His Ser Ile Phe Glu Ala Phe Ser Lys Val Val Gln Lys Leu Ile Pro Gln Leu Pro Thr Leu Glu Asn Leu Leu Asn Ile Phe Ile Ser Asn Ser Gly Ile Glu Lys Ala Phe Leu Phe Asp Val Val Ser Lys Ile Tyr Ile Ala Thr Asp Ser Ser Pro Val Asp Met Gln Ser Tyr Glu Leu Cys Cys Asp Met Ile Asp Val Val Ile Asp Val Ser Cys Ile Tyr Gly Leu Lys Glu Asp Gly Ser Gly Ser Ala Tyr Asp Lys Glu Ser Met Ala Ile Ile Lys Leu Asn Asn Thr Thr Val Leu Tyr Leu Lys Glu Val Thr Lys Phe Leu Ala Leu Val Cys Ile Leu Arg Glu Glu Ser Phe Glu Arg Lys Gly Leu Ile Asp Tyr Asn Phe His Cys Phe Arg Lys Ala Ile His Glu Val Phe Glu Val Gly Val Thr Ser His Arg Ser Cys Gly His Gln Thr Ser Ala Ser Ser Leu Lys Ala Leu Thr His Asn Gly Thr Pro~Arg Asn Ala Ile <210> 41 <211> 412 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 5324681CD1 <400> 41 Met Ala Gly Ser Val Gly Leu Ala Leu Cys Gly Gln Thr Leu Val Val Arg Gly Gly Ser Arg Phe Leu Ala Thr Ser Ile Ala Ser Ser Asp Asp Asp Ser Leu Phe Ile Tyr Asp Cys Ser Ala Ala Glu Lys Lys Ser Gln Glu Asn Lys Gly Glu Asp Ala Pro Leu Asp Gln Gly Ser Gly Ala Ile Leu Ala Ser Thr Phe Ser Lys Ser Gly Ser Tyr Phe Ala Leu Thr Asp Asp Ser Lys Arg Leu Ile Leu Phe Arg Thr Lys Pro Trp Gln Cys Leu Ser Val Arg Thr Val Ala Arg Arg Cys Thr Ala Leu Thr Phe Ile Ala Ser Glu Glu Lys Val Leu Val Ala Asp Lys Ser Gly Asp Val Tyr Ser Phe Ser Val Leu Glu Pro His Gly Cys Gly Arg Leu Glu Leu Gly His Leu Ser Met Leu Leu Asp Val Ala Val Ser Pro Asp Asp Arg Phe Ile Leu Thr Ala Asp Arg Asp Glu Lys Ile Arg Val Ser Trp Ala Ala Ala Pro His Ser Ile Glu Ser Phe Cys Leu Gly His Thr Glu Phe Val Ser Arg Ile Ser Val Val Pro ~Thr Gln Pro Gly Leu Leu Leu Ser Ser Ser Gly Asp Gly Thr Leu Arg Leu Trp Glu Tyr Arg Ser Gly Arg Gln Leu His Cys Cys His Leu Ala Ser Leu Gln Glu Leu Val Asp Pro Gln Ala Pro Gln Lys Phe Ala Ala Ser Arg Ile Ala Phe Trp Cys Gln Glu Asn Cys Val Ala Leu Leu Cys Asp Gly Thr Pro Val Val Tyr Ile Phe Gln Leu Asp Ala Arg Arg Gln Gln Leu Val Tyr Arg Gln Gln Leu Ala Phe Gln His Gln Val Trp Asp Val Ala Phe Glu Glu Thr Gln Gly Leu Trp Val Leu Gln Asp Cys Gln Glu Ala Pro Leu Val Leu Tyr Arg Pro Val Gly Asp Gln Trp Gln Ser Val Pro Glu Ser Thr Val Leu Lys Lys Val Ser Gly Val Leu Arg Gly Asn Trp Ala Met Leu Glu Gly Ser Ala Gly Ala Asp Ala Ser Phe Ser Ser Leu Tyr Lys Ala Thr Phe Asp Asn Val Thr Ser Tyr Leu Lys Lys Lys Glu Glu Arg Leu Gln Gln Gln Leu Glu Lys Lys Gln Arg Arg Arg Ser Pro Pro Pro Gly Pro Asp Gly His Ala Lys Lys Met Arg Pro Gly Glu Ala Thr Leu Ser Cys <210> 42 <211> 163 <212> PRT
<213> Homo sapiens <220>
' <221> misc_feature <223> Incyte ID No: 5387651CD1 <400> 42 Met Asp Ala Leu Glu Gly Glu Ser Phe Ala Leu Ser Phe Ser Ser Ala Ser Asp Ala Glu Phe Asp Ala Val Val Gly Tyr Leu Glu Asp Ile Ile Met Asp Asp Glu Phe Gln Leu Leu Gln Arg Asn Phe Met Asp Lys Tyr Tyr Leu Glu Phe Glu Asp Thr Glu Glu Asn Lys Leu Ile Tyr Thr Pro Ile Phe Asn Glu Tyr Ile Ser Leu Val Glu Lys Tyr Ile Glu Glu Gln Leu Leu Gln Arg Ile Pro Glu Phe Asn Met Ala Ala Phe Thr Thr Thr Leu Gln His His Lys Asp Glu Val Ala Gly Asp Ile Phe Asp Met Leu Leu Thr Phe Thr Asp Phe Leu Ala Phe Lys Glu Met Phe Leu Asp Tyr Arg Ala Glu Lys Glu Gly Arg Gly Leu Asp Leu Ser Ser Gly Leu Val Val Thr Ser Leu Cys Lys Ser Ser Ser Leu Pro Ala Ser Gln Asn Asn Leu Arg His <210> 43 <211> 514 <212> PRT
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 5595679CD1 <400> 43 Met Gln Glu Ser Gly Cys Arg Leu Glu His Pro Ser Ala Thr Lys Phe Arg Asn His Val Met Glu Gly Asp Trp Asp Lys Ala Glu Asn Asp Leu Asn Glu Leu Lys Pro Leu Val His Ser Pro His,Ala Ile Val Val Arg Gly Ala Leu Glu Ile Ser Gln Thr Leu Leu Gly Ile Ile Val Arg Met Lys Phe Leu Leu Leu Gln Gln Lys Tyr Leu Glu Tyr Leu Glu Asp Gly Lys Val Leu Glu Ala Leu Gln Val Leu Arg Cys Glu Leu Thr Pro Leu Lys Tyr Asn Thr Glu Arg Ile His Val Leu Ser Gly Tyr Leu Met Cys Ser His Ala Glu Asp Leu Arg Ala Lys Ala Glu Trp Glu Gly Lys Gly Thr Ala Ser Arg Ser Lys Leu Leu Asp Lys Leu Gln Thr Tyr Leu Pro Pro Ser Val Met Leu Pro Pro Arg Arg Leu Gln Thr Leu Leu Arg Gln Ala Val Glu Leu Gln Arg Asp Arg Cys Leu Tyr His Asn Thr Lys Leu Asp Asn Asn Leu Asp Ser Val Ser Leu Leu Ile Asp His Val Cys Ser Arg Arg Gln Phe Pro Cys Tyr Thr Gln Gln Ile Leu Thr Glu His Cys Asn Glu Val Trp Phe Cys Lys Phe Ser Asn Asp Gly Thr Lys Leu Ala Thr Gly Ser Lys Asp Thr Thr Val Ile Ile Trp Gln Val Asp Pro Asp Thr His Leu Leu Lys Leu Leu Lys Thr Leu Glu Gly His Ala Tyr Gly Val Ser Tyr Ile Ala Trp Ser Pro Asp Asp Asn Tyr Leu Val Ala Cys Gly Pro Asp Asp Cys Ser Glu Leu Trp Leu Trp Asn Val Gln Thr Gly Glu Leu Arg Thr Lys Met Ser Gln Ser His Glu Asp Ser Leu Thr Ser Val Ala Trp Asn Pro Asp Gly Lys Arg Phe Val Thr Gly Gly Gln Arg Gly Gln Phe Tyr Gln Cys Asp Leu Asp Gly Asn Leu Leu Asp Ser Trp Glu Gly Val Arg Val Gln Cys Leu Trp Cys Leu Ser Asp Gly Lys Thr Val Leu Ala Ser Asp Thr His Gln Arg Ile Arg Gly Tyr Asn Phe Glu Asp Leu Thr Asp Arg Asn Ile Val Gln Glu Asp His Pro Ile Met Ser Phe Thr Ile Ser Lys Asn Gly Arg Leu Ala Leu Leu Asn Val Ala Thr Gln Gly Val His Leu Trp Asp Leu Gln Asp Arg Val Leu Val Arg Lys Tyr Gln Gly Val Thr Gln Gly Phe Tyr Thr Ile His Ser Cys Phe Gly Gly His Asn Glu Asp Phe Ile Ala Ser Gly Ser Glu Asp His Lys Val Tyr Ile Trp His Lys Arg Ser Glu Leu Pro Ile Ala Glu Leu Thr Gly His Thr Arg Thr Val Asn Cys Val Ser Trp Asn Pro Gln Ile Pro Ser Met Met Ala Ser Ala Ser Asp Asp Gly Thr Val Arg Ile Trp Gly Pro Ala Pro Phe Ile Asp His Gln Asn Ile Glu Glu Glu Cys Ser Ser Met Asp Ser .
<210> 44 <211> 67 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 5782457CD1 <400> 44 Met Glu Glu Trp Asp Val Pro Gln Met Lys Lys Glu Val Glu Ser Leu Lys Tyr Gln Leu Ala Phe Gln Arg Glu Met Ala Ser Lys Thr Ile Pro Glu Leu Leu Lys Trp Ile Glu Asp Gly Ile Pro Lys Asp Pro Phe Leu Asn Pro Asp Leu Met Lys Asn Asn Pro Trp Val Glu Lys Gly Lys Cys Thr Ile Leu <210> 45 <211> 315 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 760677CD1 <400> 45 Met Ala Phe Pro Glu Pro Lys Pro Arg Pro Pro Glu Leu Pro Gln Lys Arg Leu Lys Thr Leu Asp Cys Gly Gln Gly Ala Val Arg Ala Val Arg Phe Asn Val Asp Gly Asn Tyr Cys Leu Thr Cys Gly Ser Asp Lys Thr Leu Lys Leu Trp Asn Pro Leu Arg Gly Thr Leu Leu Arg Thr Tyr Ser Gly His Gly Tyr Glu Val Leu Asp Ala Ala Gly Ser Phe Asp Asn Ser Ser Leu Cys Ser Gly Gly Gly Asp Lys Ala Val Val Leu Trp Asn Val Ala Ser Gly Gln Val Val Arg Lys Phe Arg Gly His Ala Gly Lys Val Asn Thr Val Gln Phe Ser Glu Glu Ala Thr Val Ile Leu Ser Gly Ser Ile Asp Ser Ser Ile Arg Cys Trp Asp Cys Arg Ser Arg Arg Pro Glu Pro Val Gln Thr Leu Asp Glu Ala Arg Asp Gly Val Ser Ser Val Lys Val Ser Asp His Glu Ile Leu Ala Gly Ser Val Asp Gly Arg Val Arg Arg Tyr Asp Leu Arg Met Gly Gln Leu Phe Ser Asp Tyr Val Gly Ser Pro Ile Thr Cys Thr Cys Phe Ser Arg Asp Gly Gln Cys Thr Leu Val Ser Ser Leu Asp Ser Thr Leu Arg Leu Leu Asp Lys Asp Thr Gly Glu Leu Leu Gly Glu Tyr Lys Gly His Lys Asn Gln Glu Tyr Lys Leu Asp Cys Cys Leu Ser Glu Arg Asp Thr His Val Val Ser Cys Ser Glu Asp Gly Lys Val Phe Phe Trp Asp Leu Val Glu Gly Ala Leu Ala Leu Ala Leu Pro Val Gly Ser Gly Val Val Gln Ser Leu Asp Tyr His Pro Thr Glu Pro Cys Leu Leu Thr Ala Met Gly Gly Ser Val Gln Cys Trp Arg Glu Glu Ala Tyr Glu Ala Glu Asp Gly Ala Gly <210> 46 <211> 504 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 1348567CD1 <400> 46 Met Ser Leu Ile Cys Ser Ile Ser Asn Glu Val Pro Glu His Pro Cys Val Ser Pro Val Ser Asn His Val Tyr Glu Arg Arg Leu Ile Glu Lys Tyr Ile Ala Glu Asn Gly Thr Asp Pro Ile Asn Asn Gln Pro Leu Ser Glu Glu Gln Leu Ile Asp Ile Lys Val Ala His Pro Ile Arg Pro Lys Pro Pro Ser Ala Thr Ser Ile Pro Ala Ile Leu Lys Ala Leu Gln Asp Glu Trp Asp Ala Val Met Pro His Ser Phe Thr Leu Arg Gln Gln Leu Gln Thr Thr Arg Gln Glu Leu Ser His Ala Leu Tyr Gln His Asp Ala Ala Cys Arg Val Ile Ala Arg Leu Thr Lys Glu Val Thr Ala Ala Arg Glu Ala Leu Ala Thr Leu Lys Pro Gln Ala Gly Leu Ile Val Pro Gln Ala Val Pro Ser Ser Gln Pro Ser Val Val Gly Ala Gly Glu Pro Met Asp Leu Gly Glu Leu Val Gly Met Thr Pro Glu Ile Ile Gln Lys Leu Gln Asp Lys Ala Thr Val Leu Thr Thr Glu Arg Lys Lys Arg Gly Lys Thr Val Pro Glu Glu Leu Val Lys Pro Glu Glu Leu Ser Lys Tyr Arg Gln Val Ala Ser His Val Gly Leu His Ser Ala Ser Ile Pro Gly Ile Leu Ala Leu Asp Leu Cys Pro Ser Asp Thr Asn Lys Ile Leu Thr Gly Gly Ala Asp Lys Asn Val Val Val Phe Asp Lys Ser Ser Glu Gln Ile Leu Ala Thr Leu Lys Gly His Thr Lys Lys Val Thr Ser Val Val Phe His Pro Ser Gln Asp Leu Val Phe Ser Ala Ser Pro Asp Ala Thr Ile Arg Ile Trp Ser Val Pro Asn Ala Ser Cys Val Gln Val Val Arg Ala His Glu Ser Ala Val Thr Gly Leu Ser Leu His Ala Thr Gly Asp Tyr Leu Leu Ser Ser Ser Asp Asp Gln Tyr Trp Ala Phe Ser Asp Ile Gln Thr Gly Arg Val Leu Thr Lys Val Thr Asp Glu Thr Ser Gly Cys Ser Leu Thr Cys Ala Gln Phe His Pro Asp Gly Leu Ile Phe Gly Thr Gly Thr Met Asp Ser Gln Ile Lys Ile Trp Asp Leu Lys Glu Arg Thr Asn Val Ala Asn Phe Pro Gly His Ser Gly Pro Ile Thr Ser Ile Ala Phe Ser Glu Asn Gly Tyr Tyr Leu Ala Thr Ala Ala Asp Asp Ser Ser Val Lys Leu Trp Asp Leu Arg Lys Leu Lys Asn Phe Lys Thr Leu Gln Leu Asp Asn Asn Phe Glu Val Lys Ser Leu Ile Phe Asp Gln Ser Gly Thr Tyr Leu Ala Leu Gly Gly Thr Asp Val Gln Ile Tyr Ile Cys Lys Gln Trp Thr Glu Ile Leu His Phe Thr Glu His Ser Gly Leu Thr Thr Gly Val Ala Phe Gly His His Ala Lys Phe Ile Ala Ser Thr Gly Met Asp Arg Ser Leu Lys Phe Tyr Ser Leu <210> 47 <211> 522 <212> PRT
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 1751354CD1 <400> 47 Met Ala Phe Leu Asp Asn Pro Thr Ile Ile Leu Ala His Ile Arg Gln Ser His Val Thr Ser Asp Asp Thr Gly Met Cys Glu Met Val Leu Ile Asp His Asp Val Asp Leu Glu Lys Ile His Pro Pro Ser Met Pro Gly Asp Ser Gly Ser Glu Ile Gln Gly Ser Asn Gly Glu Thr Gln Gly Tyr Val Tyr Ala Gln Ser Val Asp Ile Thr Ser Ser Trp Asp Phe Gly Ile Arg Arg Arg Ser Asn Thr Ala Gln Arg Leu Glu Arg Leu Arg Lys Glu Arg Gln Asn Gln Ile Lys Cys Lys Asn Ile Gln Trp Lys Glu Arg Asn Ser Lys Gln Ser Ala Gln Glu Leu Lys Ser Leu Phe Glu Lys Lys Ser Leu Lys Glu Lys Pro Pro Ile Ser Gly Lys Gln Ser Ile Leu Ser Val Arg Leu Glu Gln Cys Pro Leu Gln Leu Asn Asn Pro Phe Asn Glu Tyr Ser Lys Phe Asp Gly Lys Gly His Val Gly Thr Thr Ala Thr Lys Lys Ile Asp Val Tyr Leu Pro Leu His Ser Ser Gln Asp Arg Leu Leu Pro Met Thr Val Val Thr Met Ala Ser Ala Arg Val Gln Asp Leu Ile Gly Leu Ile Cys Trp Gln Tyr Thr Ser Glu Gly Arg Glu Pro Lys Leu Asn Asp Asn Val Ser Ala Tyr Cys Leu His Ile Ala Glu Asp Asp Gly Glu Val Asp Thr Asp Phe Pro Pro Leu Asp Ser Asn Glu Pro Ile His Lys Phe Gly Phe Ser Thr Leu Ala Leu Val Glu Lys Tyr Ser Ser Pro Gly Leu Thr Ser Lys Glu Ser Leu Phe Val Arg Ile Asn Ala Ala His Gly Phe Ser Leu Ile Gln Val Asp Asn Thr Lys Val Thr Met Lys Glu Ile Leu Leu Lys Ala Val Lys Arg Arg Lys Gly Ser Gln Lys Val Ser Gly Pro Gln Tyr Arg Leu Glu Lys Gln Ser Glu Pro Asn Val Ala Val Asp Leu Asp Ser Thr Leu Glu Ser Gln Ser Ala Trp Glu Phe Cys Leu Val Arg Glu Asn Ser Ser Arg Ala Asp Gly Val Phe Glu Glu Asp Ser Gln Ile Asp Ile Ala Thr Val Gln Asp Met Leu Ser Ser His His Tyr Lys Ser Phe Lys Val Ser Met Ile His Arg Leu Arg Phe Thr Thr Asp Val Gln Leu Gly Ile Ser Gly Asp Lys Val Glu Ile Asp Pro Val Thr Asn Gln Lys Ala Ser Thr Lys Phe Trp Ile Lys Gln Lys Pro Ile Ser Ile Asp Ser Asp Leu Leu Cys Ala Cys Asp Leu Ala Glu Giu Lys Ser Pro Ser His Ala Ile Phe Lys Leu Thr Tyr Leu Ser Asn His Asp Tyr Lys His Leu Tyr Phe Glu Ser Asp Ala Ala Thr Val Asn Glu Ile Val Leu Lys Val Asn Tyr Ile Leu Glu Ser Arg Ala Ser Thr Ala Arg Ala Asp Tyr Phe Ala Gln Lys Gln Arg Lys Leu Asn Arg Arg Thr Ser Phe Ser Phe Gln Lys Glu Lys Lys Ser Gly Gln Gln <210> 48 <211> 316 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 1976780CD1 <400> 48 Met Ala Ser Lys Asp Lys Ser Ser Lys Lys Asn Val Phe Glu Leu Lys Thr Arg Gln Gly Thr Glu Leu Leu Ile Gln Ser Asp Asn Asp Thr Val Ile Asn Asp Trp Phe Lys Val Leu Ser Ser Thr Ile Asn Asn Gln Ala Val Glu Thr Asp Glu Gly Ile Glu Glu Glu Ile Pro Asp Ser Pro Gly Ile Glu Lys His Asp Lys Glu Lys Glu Gln Lys Asp Pro Lys Lys Leu Arg Ser Phe Lys Val Ser Ser Ile Asp Ser Ser Glu Gln Lys Lys Thr Lys Lys Asn Leu Lys Lys Phe Leu Thr Arg Arg Pro Thr Leu Gln Ala Val Arg Glu Lys Gly Tyr Ile Lys Asp Gln Val Phe Gly Ser Asn Leu Ala Asn Leu Cys Gln Arg Glu Asn Gly Thr Val Pro Lys Phe Val Lys Leu Cys Ile Glu His Val Glu Glu His Gly Leu Asp Ile Asp Gly Ile Tyr Arg Val Ser Gly Asn Leu Ala Val Ile Gln Lys Leu Arg Phe Ala Val Asn His Asp Glu Lys Leu Asp Leu Asn Asp Ser Lys Trp Glu Asp Ile His Val Ile Thr Gly Ala Leu Lys Met Phe Phe Arg Glu Leu Pro Glu Pro Leu Phe Thr Phe Asn His Phe Asn Asp Phe Val Asn Ala Ile Lys Gln Glu Pro Arg Gln Arg Val Ala Ala Val Lys Asp Leu Ile Arg Gln Leu Pro Lys Pro Asn Gln Asp Thr Met Gln Ile Leu Phe Arg His Leu Arg Arg Val Ile Glu Asn Gly Glu Lys Asn Arg Met Thr Tyr Gln Ser Ile Ala Ile Val Phe Gly Pro Thr Leu Leu Lys Pro Glu Lys Glu Thr Gly Asn Ile Ala Val His Thr Val Tyr Gln Asn Gln Ile Val Glu Leu Ile Leu Leu Glu Leu Ser Ser Ile Phe Gly Arg <210> 49 <211> 387 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 2048234CD1 <400> 49 Met Val His Cys Ser Cys Val Leu Phe Arg Lys Tyr Gly Asn Phe Ile Asp Lys Leu Arg Leu Phe Thr Arg Gly Gly Ser Gly Gly Met Gly Tyr Pro Arg Leu Gly Gly Glu Gly Gly Lys Gly Gly Asp Val Trp Val Val Ala Gln Asn Arg Met Thr Leu Lys Gln Leu Lys Asp Arg Tyr Pro Arg Lys Arg Phe Val Ala Gly Val Gly Ala Asn Ser Lys Ile Ser Ala Leu Lys Gly Ser Lys Gly Lys Asp Trp Glu Ile Pro Val Pro Val Gly Ile Ser Val Thr Asp Glu Asn Gly Lys Ile Ile Gly Glu Leu Ser Lys Glu Asn Asp Arg Ile Leu Val Ala Gln Gly Gly Leu Gly Gly Lys Leu Leu Thr Asn Phe Leu Pro Leu Lys Gly Gln Lys Arg Ile Ile His Leu Asp Leu Lys Leu Ile Ala Asp Val Gly Leu Val Gly Phe Pro Asn Ala Gly Lys Ser Ser Leu Leu Ser Cys Val Ser His Ala Lys~Pro Ala Ile Ala Asp Tyr Ala Phe Thr Thr Leu Lys Leu Lys Leu Gly Lys Ile Met Tyr Ser Asp Phe Lys Gln Ile Ser Val Ala Asp Leu Pro Gly Leu Ile Glu Gly Ala His Met Asn Lys Gly Met Gly His Lys Phe Leu Lys His Ile Glu Arg Thr Arg Gln Leu Leu Phe Val Val Asp Ile Ser Gly Phe Gln Leu Ser Ser His Thr Gln Tyr Arg Thr Ala Phe Glu Thr Ile Ile Leu Leu Thr Lys Glu Leu Glu Leu Tyr Lys Glu Glu Leu Gln Thr Lys Pro Ala Leu Leu Ala Val Asn Lys Met Asp Leu Pro Asp Ala Gln Asp Lys Phe His Glu Leu Met Ser Gln Leu Gln Asn Pro Lys Asp Phe Leu His Leu Phe Glu Lys Asn Met Ile Pro Glu Arg Thr Val Glu Phe Gln His Ile Ile Pro Ile Ser Ala Val Thr Gly Glu Gly Ile Glu Glu Leu Lys Asn Cys Ile Arg Lys Ser Leu Asp Glu Gln Ala Asn Gln Glu Asn Asp Ala Leu His Lys Lys Gln Leu Leu Asn Leu Trp Ile Ser Asp Thr Met Ser Ser Thr Glu Pro Pro Ser Lys His Ala Val Thr Thr Ser Lys Met Asp Ile Ile <210> 50 <211> 334 <212> PRT
<213> Homo Sapiens <220>

<221> misc_feature <223> Incyte ID No: 2111754CD1 <400> 50 Met Pro Ser Gly Pro Arg Ala Ala Leu Arg Trp Ala Ser Pro Ser Gln Leu Val Ser Tyr His Val Leu Arg Asn Gly Ile Tyr Ala Cys Tyr Pro His Ser Leu Arg Pro Arg Thr Pro Leu Leu Cys Ala Ser Arg Asn Ile Lys Pro Arg Arg Ser Glu Leu Leu Gly Cys Pro Val Gly Cys Arg Gly Ser Leu Ser Glu Gln Arg Ile Cys Leu Leu Gly Cys Leu Val Arg Ala Ser Glu Lys Gly Val Ser Cys Cys Gln Leu Ser Val Gly Glu Leu Val His Val Ser Pro Leu Arg Ile Pro Thr Met Gly Asn Ala Ser Phe Gly Ser Lys Glu Gln Lys Leu Leu Lys Arg Leu Arg Leu Leu Pro Ala Leu Leu Ile Leu Arg Ala Phe Lys Pro His Arg Lys Ile Arg Asp Tyr Arg Val Val Val Val Gly Thr Ala Gly Val Gly Lys Ser Thr Leu Leu His Lys Trp Ala Ser Gly Asn Phe Arg His Glu Tyr Leu Pro Thr Ile Glu Asn Thr Tyr Cys Gln Leu Leu Gly Cys Ser His Gly Val Leu Ser Leu His Ile Thr Asp Ser Lys Ser Gly Asp Gly Asn Arg Ala Leu Gln Arg His Val Ile Ala Arg Gly His Ala Phe Val Leu Val Tyr Ser Val Thr Lys Lys Glu Thr Leu Glu Glu Leu Lys Ala Phe Tyr Glu Leu Ile Cys Lys Ile Lys Gly Asn Asn Leu His Lys Phe Pro Ile Val Leu Val Gly Asn Lys Ser Asp Asp Thr His Arg Glu Val Ala Leu Asn Asp Gly Ala Thr Cys Ala Met Glu Trp Asn Cys Ala Phe Met Glu Ile Ser Ala Lys Thr Asp Val Asn Val Gln Glu Leu Phe His Met Leu Leu Asn Tyr Lys Lys Lys Pro Thr Thr Gly Leu Gln Glu Pro Glu Lys Lys Ser Gln Met Pro Asn Thr Thr Glu Lys Leu Leu Asp Lys Cys Ile Ile Met <210> 51 <211> 551 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 2123286CD1 <400> 51 Met Glu Glu Glu Leu Pro Leu Phe Ser Gly Asp Ser Gly Lys Pro Val Gln Ala Thr Leu Ser Ser Leu Lys Met Leu Asp Val Gly Lys Trp Pro Ile Phe Ser Leu Cys Ser Glu Glu Glu Leu Gln Leu Ile Arg Gln Ala Cys Val Phe Gly Ser Ala Gly Asn Glu Val Leu Tyr Thr Thr Val Asn Asp Glu Ile Phe Val Leu Gly Thr Asn Cys Cys Gly Cys Leu Gly Leu Gly Asp Val Gln Ser Thr Ile Glu Pro Arg Arg Leu Asp Ser Leu Asn Gly Lys Lys Ile Ala Cys Leu Ser Tyr Gly Ser Gly Pro His Ile Val Leu Ala Thr Thr Glu Gly Glu Val Phe Thr Trp Gly His Asn Ala Tyr Ser Gln Leu Gly Asn Gly Thr Thr Asn His Gly Leu Val Pro Cys His Ile Ser Thr Asn Leu Ser Asn Lys Gln Val Ile Glu Val Ala Cys Gly Ser Tyr His Ser Leu Val Leu Thr Ser Asp Gly Glu Val Phe Ala Trp Gly Tyr Asn Asn Ser Gly Gln Val Gly Ser Gly Ser Thr Val Asn Gln Pro Ile Pro Arg Arg Val Thr Gly Cys Leu Gln Asn Lys Val Val Val Thr Ile Ala Cys Gly Gln Met Cys Cys Met Ala Val Val Asp Thr Gly Glu Val Tyr Val Trp Gly Tyr Asn Gly Asn Gly Gln Leu Gly Leu Gly Asn Ser Gly Asn Gln Pro Thr Pro Cys Arg Val Ala Ala Leu Gln Gly Ile Arg Val Gln Arg Val Ala Cys Gly Tyr Ala His Thr Leu Val Leu Thr Asp Glu Gly Gln Val Tyr Ala Trp Gly Ala Asn Ser Tyr Gly Gln Leu Gly Thr Gly Asn Lys Ser Asn Gln Ser Tyr Pro Thr Pro Val Thr Val Glu Lys Asp Arg Ile Ile Glu Ile Ala Ala Cys His Ser Thr His Thr Ser Ala Ala Lys Thr Gln Gly Gly His Val Tyr Met Trp Gly Gln Cys Arg Gly Gln Ser Val Ile Leu Pro His Leu Thr His Phe Ser Cys Thr Asp Asp Val Phe Ala Cys Phe Ala Thr Pro Ala Val Thr Trp Arg Leu Leu Ser Val Glu Pro Asp Asp His Leu Thr Val Ala Glu Ser Leu Lys Arg Glu Phe Asp Asn Pro Asp Thr Ala Asp Leu Lys Phe Leu Val Asp Gly Lys Tyr Ile Tyr Ala His Lys Val Leu Leu Lys Ile Arg Cys Glu His Phe Arg Ser Ser Leu Glu Asp Asn Glu Asp Asp Ile Val Glu Met Ser Glu Phe Ser Tyr Pro Val Tyr Arg Ala Phe Leu Glu Tyr Leu Tyr Thr Asp Ser Ile Ser Leu Ser Pro Glu Glu Ala Val Gly Leu Leu Asp Leu Ala Thr Phe Tyr Arg Glu Asn Arg Leu Lys Lys Leu Cys Gln Gln Thr Ile Lys Gln Gly Ile Cys Glu Glu Asn Ala Ile Ala Leu Leu Ser Ala Ala Val Lys Tyr Asp Ala Gln Asp Leu Glu Glu Phe Cys Phe Arg Phe Cys Ile Asn His Leu Thr Val Val Thr Gln Thr Ser Gly Phe Ala Glu Met Asp His Asp Leu Leu Lys Asn Phe Ile Ser Lys Ala Ser Arg Val Gly Ala Phe Lys Asn <210> 52 <211> 308 <212> PRT
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 2477507CD1 <400> 52 Met Ile His Asp Ala Gln Met Asp Tyr Tyr Gly Thr Arg Leu Ala Thr Cys Ser Ser Asp Arg Ser Val Lys Ile Phe Asp Val Arg Asn Gly Gly Gln Ile Leu Ile Ala Asp Leu Arg Gly His Glu Gly Pro Val Trp Gln Val Ala Trp Ala His Pro Met Tyr Gly Asn Ile Leu Ala Ser Cys Ser Tyr Asp Arg Lys Val Ile Ile Trp Arg Glu Glu Asn Gly Thr Trp Glu Lys Ser His Glu His Ala Gly His Asp Ser Ser Val Asn Ser Val Cys Trp Ala Pro His Asp Tyr Gly Leu Ile Leu Ala Cys Gly Ser Ser Asp Gly Ala Ile Ser Leu Leu Thr Tyr Thr Gly Glu Gly Gln Trp Glu Val Lys Lys Ile Asn Asn Ala His Thr Ile Gly Cys Asn Ala Val Ser Trp Ala Pro Ala Val Val Pro Gly Ser Leu Ile Asp His Pro Ser Gly Gln Lys Pro Asn Tyr Ile Lys Arg Phe Ala Ser Gly Gly Cys Asp Asn Leu Ile Lys Leu Trp Lys Glu Glu Glu Asp Gly Gln Trp Lys Glu Glu Gln Lys Leu Glu Ala His Ser Asp Trp Val Arg Asp Val Ala Trp Ala Pro Ser Ile Gly Leu Pro Thr Ser Thr Ile Ala Ser Cys Ser Gln Asp Gly Arg Val Phe Ile Trp Thr Cys Asp Asp Ala Ser Ser Asn Thr Trp Ser Pro Lys Leu Leu His Lys Phe Asn Asp Val Val Trp His Val Ser Trp Ser Ile Thr Ala Asn Ile Leu Ala Val Ser Gly Gly Asp Asn Lys Val Thr Leu Trp Lys Glu Ser Val Asp Gly Gln Trp Val Cys Ile Ser Asp Val Asn Lys Gly Gln Gly Ser Val Ser Ala Ser Val Thr Glu Gly Gln Gln Asn Glu Gln <210> 53 <211> 949 <212> PRT

<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 2759119CD1 <400> 53 Met Asp Ala Leu Glu Asp Tyr Val Trp Pro Arg Ala Thr Ser Glu Leu Ile Leu Leu Pro Val Thr Gly Leu Glu Cys Val Gly Asp Arg 20 ' 25 30 Leu Leu Ala Gly Glu Gly Pro Asp Val Leu Val Tyr Ser Leu Asp Phe Gly Gly His Leu Arg Met Ile Lys Arg Val Gln Asn Leu Leu Gly His Tyr Leu Ile His Gly Phe Arg Val Arg Pro Glu Pro Asn Gly Asp Leu Asp Leu Glu Ala Met Val Ala Val Phe Gly Ser Lys Gly Leu Arg Val Val Lys Ile Ser Trp Gly Gln Gly His Phe Trp Glu Leu Trp Arg Ser Gly Leu Trp Asn Met Ser Asp Trp Ile Trp Asp Ala Arg Trp Leu Glu Gly Asn Ile Ala Leu Ala Leu Gly His Asn Ser Val Val Leu Tyr Asp Pro Val Val Gly Cys Ile Leu Gln Glu Val Pro Cys Thr Asp Arg Cys Thr Leu Ser Ser Ala Cys Leu Ile Gly Asp Ala Trp Lys Glu Leu Thr Ile Val Ala Gly Ala Val Ser Asn Gln Leu Leu Val Trp Tyr Pro Ala Thr Ala Leu Ala Asp Asn Lys Pro Val Ala Pro Asp Arg Arg Ile Ser Gly His Val Gly Ile Ile Phe Ser Met Ser Tyr Leu Glu Ser Lys Gly Leu Leu Ala Thr Ala Ser Glu Asp Arg Ser Val Arg Ile Trp Lys Val Gly Asp Leu Arg Val Pro Gly Gly Arg Val Gln Asn Ile Gly His Cys Phe Gly His Ser Ala Arg Val Trp Gln Val Lys Leu Leu Glu Asn Tyr Leu Ile Ser Ala Gly Glu Asp Cys Val Cys Leu Val Trp Ser His Glu Gly Glu Ile Leu Gln Ala Phe Arg Gly His Gln Gly Arg Gly Ile Arg Ala Ile Ala Ala His Glu Arg Gln Ala Trp Val Ile Thr Gly Gly Asp Asp Ser Gly Ile Arg Leu Trp His Leu Val Gly Arg Gly Tyr Arg Gly Leu Gly Val Ser Ala Leu Cys Phe Lys Ser Arg Ser Arg Pro Gly Thr Leu Lys Ala Val Thr Leu Ala Gly Ser Trp Arg Leu Leu Ala Val Thr Asp Thr Gly Ala Leu Tyr Leu Tyr Asp Val Glu Val Lys Cys Trp Glu Gln Leu Leu Glu Asp Lys His Phe Gln Ser Tyr Cys Leu Leu Glu Ala Ala Pro Gly Pro Glu Gly Phe Gly Leu Cys Ala Met Ala Asn Gly Glu Gly Arg Val Lys Val Val Pro Ile Asn Thr Pro Thr Ala Ala Val Asp Gln Thr Leu Phe Pro Gly Lys Val His Ser Leu Ser Trp Ala Leu Arg Gly Tyr Glu Glu Leu Leu Leu Leu Ala Ser Gly Pro Gly Gly Val Val Ala Cys Leu Glu Ile Ser Ala Ala Pro Ser Gly Lys Ala Ile Phe Val Lys Glu Arg Cys Arg Tyr Leu Leu Pro Pro Ser Lys Gln Arg Trp His Thr Cys Ser Ala Phe Leu Pro Pro Gly Asp Phe Leu Val Cys Gly Asp Arg Arg Gly Ser Val Leu Leu Phe Pro Ser Arg Pro Gly Leu Leu Lys Asp Pro Gly Val Gly Gly Lys Ala Arg Ala Gly Ala Gly Ala Pro Val Val Gly Ser Gly Ser Ser Gly Gly Gly Asn Ala Phe Thr Gly Leu Gly Pro Val Ser Thr Leu Pro Ser Leu His Gly Lys Gln Gly Val Thr Ser Val Thr Cys His Gly Gly Tyr Val Tyr Thr Ile Gly Arg Asp Gly Ala Tyr Tyr Gln Leu Phe Val Arg Asp Gly Gln Leu Gln Pro Val Leu Arg Gln Lys Ser Cys Arg Gly Met Asn Trp Leu Ala Gly Leu Arg Ile Val Pro Asp Gly Ser Met Val Ile Leu Gly Phe His Ala Asn Glu Phe Val Val Trp Asn Pro Arg Ser His Glu Lys Leu His Ile Val Asn Cys Gly Gly Gly His Arg Ser Trp Ala Phe Ser Asp Thr Glu Ala Ala Met Ala Phe Ala Tyr Leu Lys Asp Gly Asp Val Met Leu Tyr Arg Ala Leu Gly Gly Cys Thr Arg Pro His Val Ile Leu Arg Glu Gly Leu His Gly Arg Glu Ile Thr Cys Val Lys Arg Val Gly Thr Ile Thr Leu Gly Pro Glu Tyr Gly Val Pro Ser Phe Met Gln Pro Asp Asp Leu Glu Pro Gly Ser Glu Gly Pro Asp Leu Thr Asp Ile Val Ile Thr Cys Ser Glu Asp Thr Thr Val Cys Val Leu Ala Leu Pro Thr Thr Thr Gly Ser Ala His Ala Leu Thr Ala Val Cys Asn His Ile Ser Ser Val Arg Ala Val Ala Val Trp Gly Ile Gly Thr Pro Gly Gly Pro Gln Asp Pro Gln Pro Gly Leu Thr Ala His Val Val Ser Ala Gly Gly Arg Ala Glu Met His Cys Phe Ser Ile Met Val Thr Pro Asp Pro Ser Thr Pro Ser Arg Leu Ala Cys His Val Met His Leu Ser Ser His Arg Leu Asp Glu Tyr Trp Asp Arg Gln Arg Asn Arg His Arg Met Val Lys Val Asp Pro Glu Thr Arg Tyr Met Ser Leu Ala Val Cys Glu Leu Asp Gln Pro Gly Leu Gly Pro Leu Val Ala Ala Ala Cys Ser Asp Gly Ala Val Ser Ser Phe Phe Cys Arg Ile Leu Gly Gly Phe Cys Ser Ser Leu Leu Lys Pro Ser Thr Ile Ser Asp Val Ser Ser Arg Ser Thr Pro Leu His Thr Arg His Pro Thr Arg Gly Gly Gly Ser Ser Cys Ala Ala Gln Leu Leu Met Ala Ala Trp Leu Ser Gly Ile Ser Pro Pro Cys <210> 54 <211> 227 <212> PRT
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 2823818CD1 <400> 54 Met Arg His Glu Ala Pro Met Gln Met Ala Ser Ala Gln Asp Ala Arg Tyr Gly Gln Lys Asp Ser Ser Asp Gln Asn Phe Asp Tyr Met Phe Lys Leu Leu Ile Ile Gly Asn Ser Ser Val Gly Lys Thr Ser Phe Leu Phe Arg Tyr Ala Asp Asp Ser Phe Thr Ser Ala Phe Val Ser Thr Val Gly Ile Asp Phe Lys Val Lys Thr Val Phe Lys Asn Val Lys Arg Ile Lys Leu Gln Ile Trp Asp Thr Ala Gly Gln Glu Arg Tyr Arg Thr Ile Thr Thr Ala Tyr Tyr Arg Gly Ala Met Gly Phe Ile Leu Met Tyr Asp Ile Thr Asn Glu Glu Ser Phe Asn Ala Val Gln Asp Trp Ser Thr Gln Ile Lys Thr Tyr Ser Trp Asp Asn Ala Gln Val Ile Leu Val Gly Asn Lys Cys Asp Met Glu Asp Glu Arg Val Ile Ser Thr Glu Arg Gly Gln His Leu Gly Glu Gln Leu Gly Phe Glu Phe Phe Glu Thr Ser Ala Lys Asp Asn Ile Asn Val Lys Gln Thr Phe Glu Arg Leu Val Asp Ile Ile Cys Asp Lys Met Ser Glu Ser Leu Glu Thr Asp Pro Ala Ile Thr Ala Ala Lys Gln Asn Thr Arg Leu Lys Glu Thr Pro Pro Pro Pro Gln Pro Asn Cys Ala Cys <210> 55 <211> 474 <212> PRT
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 2859730CD1 <400> 55 Met Arg Arg Val Val Arg Gln Ser Lys Phe Arg His Val Phe Gly Gln Ala Val Lys Asn Asp Gln Cys Tyr Asp Asp Ile Arg Val Ser Arg Val Thr Trp Asp Ser Ser Phe Cys Ala Val Asn Pro Arg Phe Val Ala Ile Ile Ile Glu Ala Ser Gly Gly Gly Ala Phe Leu Val Leu Pro Leu Arg Lys Thr Gly Arg Ile Asp Lys Ser Tyr Pro Thr Val Cys Gly His Thr Gly Pro Val Leu Asp Ile Asp Trp Cys Pro His Asn Asp Gln Val Ile Ala Ser Gly Ser Glu Asp Cys Thr Val Met Val Trp Gln Ile Pro Glu Asn Gly Leu Thr Leu Ser Leu Thr Glu Pro Val Val Ile Leu Glu Gly His Ser Lys Arg Val Gly Ile Val Ala Trp His Pro Thr Ala Arg Asn Val Leu Leu Ser Ala Gly Cys Asp Asn Ala Ile Ile Ile Trp Asn Val Gly Thr Gly Glu Ala Leu Ile Asn Leu Asp Asp Met His Ser Asp Met Ile Tyr Asn Val Ser Trp Asn Arg Asn Gly Ser Leu Ile Cys Thr Ala Ser Lys Asp Lys Lys Val Arg Val Ile Asp Pro Arg Lys Gln Glu Ile Val Ala Glu Lys Glu Lys Ala His Glu Gly Ala Arg Pro Met Arg Ala Ile Phe Leu Ala Asp Gly Asn Val Phe Thr Thr Gly Phe Ser Arg Met Ser Glu Arg Gln Leu Ala Leu Trp Asn Pro Lys Asn Met Gln Glu 245 250 . 255 Pro Ile Ala Leu His Glu Met Asp Thr Ser Asn Gly Val Leu Leu Pro Phe Tyr Asp Pro Asp Thr Ser Ile Ile Tyr Leu Cys Gly Lys Gly Asp Ser Ser Ile Arg Tyr Phe Glu Ile Thr Asp Glu Ser Pro Tyr Val His Tyr Leu Asn Thr Phe Ser Ser Lys Glu Pro Gln Arg Gly Met Gly Tyr Met Pro Lys Arg Gly Leu Asp Val Asn Lys Cys Glu Ile Ala Arg Phe Phe Lys Leu His Glu Arg Lys Cys Glu Pro Ile Ile Met Thr Val Pro Arg Lys Ser Asp Leu Phe Gln Asp Asp Leu Tyr Pro Asp Thr Ala Gly Pro Glu Ala Ala Leu Glu Ala Glu Glu Trp Phe Glu Gly Lys Asn Ala Asp Pro Ile Leu Ile Ser Leu Lys His Gly Tyr Ile Pro Gly Lys Asn Arg Asp Leu Lys Val Val Lys Lys Asn Ile Leu Asp Ser Lys Pro Thr Ala Asn Lys Lys Cys Asp Leu Ile Ser Ile Pro Lys Lys Thr Thr Asp Thr Ala Ser Val Gln Asn Glu Ala Lys Leu Asp Glu Ile Leu Lys Glu Ile Lys Ser Ile Lys Asp Thr Ile Cys Asn Gln Asp Glu Arg Ile Ser Lys Leu Glu Gln Gln Met Ala Lys Ile Ala Ala <210> 56 5$/115 <211> 547 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 2861155CD1 <400> 56 Met Lys Thr Leu Glu Thr Gln Pro Leu Ala Pro Asp Cys Cys Pro 1 5 10 ~ 15 Ser Asp Gln Asp Pro Ala Pro Ala His Pro Ser Pro His Ala Ser Pro Met Asn Lys Asn Ala Asp Ser Glu Leu Met Pro Pro Pro Pro Glu Arg Gly Asp Pro Pro Arg Leu Ser Pro Asp Pro Val Ala Gly Ser Ala Val Ser Gln Glu Leu Arg Glu Gly Asp Pro Val Ser Leu Ser Thr Pro Leu Glu Thr Glu Phe Gly Ser Pro Ser Glu Leu Ser Pro Arg Ile Glu Glu Gln Glu Leu Ser Glu Asn Thr Ser Leu Pro Ala Glu Glu Ala Asn Gly Ser Leu Ser Glu Glu Glu Ala Asn Gly _Pro Glu Leu Gly Ser Gly Lys Ala Met Glu Asp Thr Ser Gly Glu Pro Ala Ala Glu Asp Glu Gly Asp Thr Ala Trp Asn Tyr Ser Phe Ser Gln Leu Pro Arg Phe Leu Ser Gly Ser Trp Ser Glu Phe Ser Thr Gln Pro Glu Asn Phe Leu Lys Gly Cys Lys Trp Ala Pro Asp Gly Ser Cys Ile Leu Thr Asn Ser Ala Asp Asn Ile Leu Arg Ile Tyr Asn Leu Pro Pro Glu Leu Tyr His Glu Gly Glu Gln Val Glu Tyr Ala Glu Met Val Pro Val Leu Arg Met Val Glu Gly Asp Thr Ile Tyr Asp Tyr Cys Trp Tyr Ser Leu Met Ser Ser Ala Gln Pro Asp Thr Ser Tyr Val Ala Ser Ser Ser Arg Glu Asn Pro Ile His Ile Trp Asp Ala Phe Thr Gly Glu Leu Arg Ala Ser Phe Arg Ala Tyr Asn His Leu Asp Glu Leu Thr Ala Ala His Ser Leu Cys Phe Ser Pro Asp Gly Ser Gln Leu Phe Cys Gly Phe Asn Arg Thr Val Arg Val Phe Ser Thr Ala Arg Pro Gly Arg Asp Cys Glu Val Arg Ala Thr Phe Ala Lys Lys Gln Gly Gln Ser Gly Ile Ile Ser Cys Ile Ala Phe Ser Pro Ala Gln Pro Leu Tyr Ala Cys Gly Ser Tyr 335 ° 340 345 Gly Arg Ser Leu Gly Leu Tyr Ala Trp Asp Asp Gly Ser Pro Leu Ala Leu Leu Gly Gly His Gln Gly Gly Ile Thr His Leu Cys Phe His Pro Asp Gly Asn Arg Phe Phe Ser Gly Ala Arg Lys Asp Ala Glu Leu Leu Cys Trp Asp Leu Arg Gln Ser Gly Tyr Pro Leu Trp Ser Leu Gly Arg Glu Val Thr Thr Asn Gln Arg Ile Tyr Phe Asp Leu Asp Pro Thr Gly Gln Phe Leu Val Ser Gly Ser Thr Ser Gly Ala Val Ser Val Trp Asp Thr Asp Gly Pro Gly Asn Asp Gly Lys Pro Glu Pro Val Leu Ser Phe Leu Pro Gln Lys Asp Cys Thr Asn Gly Val Ser Leu His Pro Ser Leu Pro Leu Leu Ala Thr Ala Ser Gly Gln Arg Val Phe Pro Glu Pro Thr Glu Ser Gly Asp Glu Gly Glu Glu Leu Gly Leu Pro Leu Leu Ser Thr Arg His Val His Leu Glu Cys Arg Leu Gln Leu Trp Trp Cys Gly Gly Gly Pro Asp Ser Ser Ile Pro Asp Asp His Gln Gly Glu Lys Gly Gln Gly Gly Thr Gly Gly Arg Ser Trp Gly Ala <210> 57 <211> 686 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 3002667CD1 <400> 57 Met Gly Glu Phe Lys Val His Arg Val Arg Phe Phe Asn Tyr Val Pro Ser Gly Ile Arg Cys Val Ala Tyr Asn Asn Gln Ser Asn Arg Leu Ala Val Ser Arg Thr Asp Gly Thr Val Glu Ile Tyr Asn Leu Ser Ala Asn Tyr Phe Gln Glu Lys Phe Phe Pro Gly His Glu Ser Arg Ala Thr Glu Ala Leu Cys Trp Ala Glu Gly Gln Arg Leu Phe Ser Ala Gly Leu Asn Gly Glu Ile Met Glu Tyr Asp Leu Gln Ala Leu Asn Ile Lys Tyr Ala Met Asp Ala Phe Gly Gly Pro Ile Trp Ser Met Ala Ala Ser Pro Ser Gly Ser Gln Leu Leu Val Gly Cys Glu Asp Gly Ser Val Lys Leu Phe Gln Ile Thr Pro Asp Lys Ile Gln Phe Glu Arg Asn Phe Asp Arg Gln Lys Ser Arg Ile Leu Ser Leu Ser Trp His Pro Ser Gly Thr His Ile Ala Ala Gly Ser Ile Asp Tyr Ile Ser Val Phe Asp Val Lys Ser Gly Ser Ala Val His Lys Met Ile Val Asp Arg Gln Tyr Met Gly Val Ser Lys Arg Lys Cys Ile Val Trp Gly Val Ala Phe Leu Ser Asp Gly Thr Ile Ile Ser Val Asp Ser Ala Gly Lys Val Gln Phe Trp Asp Ser Ala Thr Gly Thr Leu Val Lys Ser His Leu Ile Ala Asn Ala Asp Val Gln Ser Ile Ala Val Ala Asp Gln Glu Asp Ser Phe Val Val Gly Thr Ala Glu Gly Thr Val Phe His Phe Gln Leu Val Pro Val Thr Ser Asn Ser Ser Glu Lys Gln Trp Val Arg Thr Lys Pro Phe Gln His His Thr His Asp Val Arg Thr Val Ala His Ser Pro Thr Ala Leu Ile Ser Gly Gly Thr Asp Thr His Leu Val Phe Arg Pro Leu Met Glu Lys Val Glu Val Lys Asn Tyr Asp Ala Ala Leu Arg Lys Ile Thr Phe Pro His Arg Cys Leu Ile Ser Cys Ser Lys Lys Arg Gln Leu Leu Leu Phe Gln Phe Ala His His Leu Glu Leu Trp Arg Leu Gly Ser Thr Val Ala Thr Gly Lys Asn Gly Asp Thr Leu Pro Leu Ser Lys Asn Ala Asp His Leu Leu His Leu Lys Thr Lys Gly Pro Glu Asn Ile Ile Cys Ser Cys Ile Ser Pro Cys Gly Ser Trp Ile Ala Tyr Ser Thr Val Ser Arg Phe Phe Leu Tyr Arg Leu Asn Tyr Glu His Asp Asn Ile Ser Leu Lys Arg Val Ser Lys Met Pro Ala Phe Leu Arg Ser Ala Leu Gln Ile Leu Phe Ser Glu Asp Ser Thr Lys Leu Phe Val Ala Ser Asn Gln Gly Ala Leu His Ile Val Gln Leu Ser Gly Gly Ser Phe Lys His Leu His Ala Phe Gln Pro Gln Ser Gly Thr Val Glu Ala Met Cys Leu Leu Ala Val Ser Pro Asp Gly Asn Trp Leu Ala Ala Ser Gly Thr Ser Ala Gly Val His Val Tyr Asn Val Lys Gln Leu Lys Leu His Cys Thr Val Pro Ala Tyr Asn Phe Pro Val Thr Ala Met Ala Ile Ala Pro Asn Thr Asn Asn Leu Val Ile Ala His Ser Asp Gln Gln Val Phe Glu Tyr Ser Ile Pro Asp Lys Gln Tyr Thr Asp Trp Ser Arg Thr Val Gln Lys Gln Gly Phe His His Leu Trp Leu Gln Arg Asp Thr Pro Ile Thr His Ile Ser Phe His Pro Lys Arg Pro Met His Ile Leu Leu His Asp Ala Tyr Met Phe Cys Ile Ile Asp Lys Ser Leu Pro Leu Pro Asn Asp Lys Thr Leu Leu Tyr Asn Pro Phe Pro Pro Thr Asn Glu Ser Asp Val Ile Arg Arg Arg Thr Ala His Ala Phe Lys Ile Ser Lys Ile Tyr Lys Pro Leu Leu Phe Met Asp Leu Leu Asp Glu Arg Thr Leu Val Ala Val Glu Arg Pro Leu Asp Asp Ile Ile Ala Gln Leu Pro Pro Pro Ile Lys Lys Lys Lys Phe Gly Thr <210> 58 <211> 93 <212> PRT
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 3043734CD1 <400> 58 Met Thr Ser Lys Arg Lys Pro Cys Gln Thr Gln Leu Arg Arg Ser Ile Ser Glu Gln Leu Arg Asp Ser Thr Ala Arg Ala Trp Asp Leu Leu Trp Lys Asn Val Arg Glu Arg Arg Leu Ala Glu Ile Glu Ala Lys Glu Ala Cys Asp Trp Leu Arg Ala Ala Gly Phe Pro Gln Tyr Ala Gln Leu Tyr Glu Asp Ser Gln Phe Pro Ile Asn Ile Val Ala Val Lys Asn Asp His Asp Phe Leu Glu Lys Asp Leu Val Glu Pro Leu Cys Arg <210> 59 <211> 521 <212> PRT
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 3294893CD1 <400> 59 Met Arg Arg Gly His Gly Gln Arg Arg Gly Gln Glu Ala Ile Leu Glu Ala His Asn Ser Lys Leu Pro Gly Ser Ile Gln His Val Tyr Gly Ala Gln His Pro Pro Phe Asp Pro Leu Leu His Gly Thr Leu Leu Arg Ser Thr Ala Lys Met Pro Thr Thr Pro Val Lys Ala Lys Arg Val Ser Thr Phe Gln Glu Phe Glu Ser Asn Thr Ser Asp Ala Trp Asp Ala Gly Glu Asp Asp Asp Glu Leu Leu Ala Met Ala Ala Glu Ser Leu Asn Ser Glu Val Val Met Glu Thr Ala Asn Arg Val Leu Arg Asn His Ser Gln Arg Gln Gly Arg Pro Thr Leu Gln Glu Gly Pro Gly Leu Gln Gln Lys Pro Arg Pro Glu Ala Glu Pro Pro Ser Pro Pro Ser Gly Asp Leu Arg Leu Val Lys Ser Val Ser Glu Ser His Thr Ser Cys Pro Ala Glu Ser Ala Ser Asp Ala Ala Pro Leu Gln Arg Ser Gln Ser Leu Pro His Ser Ala Thr Val Thr Leu Gly Gly Thr Ser Asp Pro Ser Thr Leu Ser Ser Ser Ala Leu Ser Glu Arg Glu Ala Ser Arg Leu Asp Lys Phe Lys Gln Leu Leu Ala Gly Pro Asn Thr Asp Leu Glu Glu Leu Arg Arg Leu Ser Trp Ser Gly Ile Pro Lys Pro Val Arg Pro Met Thr Trp Lys Leu Leu Ser Gly Tyr Leu Pro Ala Asn Val Asp Arg Arg Pro Ala Thr Leu Gln Arg Lys Gln Lys Glu Tyr Phe Ala Phe Ile Glu His Tyr Tyr Asp Ser Arg Asn Asp Glu Val His Gln Asp Thr Tyr Arg Gln Ile His Ile Asp Ile Pro Arg Met Ser Pro Glu Ala Leu Ile Leu Gln Pro Lys Val Thr Glu Ile Phe Glu Arg Ile Leu Phe Ile Trp Ala Ile Arg His Pro Ala Ser Gly Tyr Val Gln Gly Ile Asn Asp Leu Val Thr Pro Phe Phe Val Val Phe Ile Cys Glu Tyr Ile Glu Ala Glu Glu Val Asp Thr Val Asp Val Ser Gly Val Pro Ala Glu Val Leu Cys Asn Ile Glu Ala Asp Thr Tyr Trp Cys Met Ser Lys Leu Leu Asp Gly Ile Gln Asp Asn Tyr Thr Phe Ala Gln Pro Gly Ile Gln Met Lys Val Lys Met Leu Glu Glu Leu Val Ser Arg Ile Asp Glu Gln Val His Arg His Leu Asp Gln His Glu Val Arg Tyr Leu Gln Phe Ala Phe Arg Trp Met Asn Asn Leu Leu Met Arg Glu Val Pro Leu Arg Cys Thr Ile Arg Leu Trp Asp Thr Tyr Gln Ser Glu Pro Asp Gly Phe Ser His Phe His Leu Tyr Val Cys Ala Ala Phe Leu Val Arg Trp Arg Lys Glu Ile Leu Glu Glu Lys Asp Phe Gln Glu Leu Leu Leu Phe Leu Gln Asn Leu Pro Thr Ala His Trp Asp Asp Glu Asp Ile Ser Leu Leu Leu Ala Glu Ala Tyr Arg Leu Lys Phe Ala Phe Ala Asp Ala Pro Asn His Tyr Lys Lys <210> 60 <211> 751 <212> PRT
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 3349052CD1 <400> 60 Met Arg Leu Leu Gly Ala Ala Ala Val Ala Ala Leu Gly Arg Gly Arg Ala Pro Ala Ser Leu Gly Trp Gln Arg Lys Gln Val Asn Trp Lys Ala Cys Arg Trp Ser Ser Ser Gly Val Ile Pro Asn Glu Lys Ile Arg Asn Ile Gly Ile Ser Ala His Ile Asp Ser Gly Lys Thr Thr Leu Thr Glu Arg Val Leu Tyr Tyr Thr Gly Arg Ile Ala Lys Met His Glu Val Lys Gly Lys Asp Gly Val Gly Ala Val Met Asp Ser Met Glu Leu Glu Arg Gln Arg Gly Ile Thr Ile Gln Ser Ala Ala Thr Tyr Thr Met Trp Lys Asp Val Asn Ile Asn Ile Ile Asp Thr Pro Gly His Val Asp Phe Thr Ile Glu Val Glu Arg Ala Leu Arg Val Leu Asp Gly Ala Val Leu Val Leu Cys Ala Val Gly Gly Val Gln Cys Gln.Thr Met Thr Val Asn Arg Gln Met Lys Arg Tyr Asn Val Pro Phe Leu Thr Phe Ile Asn Lys Leu Asp Arg Met Gly Ser Asn Pro Ala Arg Ala Leu Gln Gln Met Arg Ser Lys Leu Asn His Asn Ala Ala Phe Met Gln Ile Pro Met Gly Leu Glu Gly Asn Phe Lys Gly Ile Ile Asp Leu Ile Glu Glu Arg Ala Ile Tyr Phe Asp Gly Asp Phe Gly Gln Ile Val Arg Tyr Gly Glu Ile Pro Ala Glu Leu Arg Ala Ala Ala Thr Asp His Arg Gln Glu Leu Ile Glu Cys Val Ala Asn Ser Asp Glu Gln Leu Gly Glu Met Phe Leu Glu Glu Lys Ile Pro Ser Ile Ser Asp Leu Lys Leu Ala Ile Arg Arg Ala Thr Leu Lys Arg Ser Phe Thr Pro Val Phe Leu Gly Ser Ala Leu Lys Asn Lys Gly Val Gln Pro Leu Leu Asp Ala Val Leu Glu Tyr Leu Pro Asn Pro Ser Glu Val Gln Asn Tyr Ala Ile Leu Asn Lys Glu Asp Asp Ser Lys Glu Lys Thr Lys Ile Leu Met Asn Ser Ser Arg Asp Asn Ser His Pro Phe Val Gly Leu Ala Phe Lys Leu Glu Val Gly Arg Phe Gly Gln Leu Thr Tyr Val Arg Ser Tyr Gln Gly Glu Leu Lys Lys Gly Asp Thr Ile Tyr Asn Thr Arg Thr Arg Lys Lys Val Arg Leu Gln Arg Leu.Ala Arg Met His Ala Asp Met Met Glu Asp Val Glu Glu Val Tyr Ala Gly Asp Ile Cys Ala Leu Phe Gly Ile Asp Cys Ala Ser Gly Asp Thr Phe Thr Asp Lys Ala Asn Ser Gly Leu Ser Met Glu Ser Ile His Val Pro Asp Pro Val Ile Ser Ile Ala Met Lys Pro Ser Asn Lys Asn Asp Leu Glu Lys Phe Ser Lys Gly Ile Gly Arg Phe Thr Arg Glu Asp Pro Thr Phe Lys Val Tyr Phe Asp Thr Glu Asn Lys Glu Thr Val Ile Ser Gly Met Gly Glu Leu His Leu Glu Ile Tyr Ala Gln Arg Leu Glu Arg Glu Tyr Gly Cys Pro Cys Ile Thr Gly Lys Pro Lys Val Ala Phe Arg Glu Thr Ile Thr Ala Pro Val Pro Phe Asp Phe Thr His Lys Lys Gln Ser Gly Gly Ala Gly Gln Tyr Gly Lys Val Ile Gly Val Leu Glu Pro Leu Asp Pro Glu Asp Tyr Thr Lys Leu Glu Phe Ser Asp Glu Thr Phe Gly Ser Asn Ile Pro Lys Gln Phe Val Pro Ala Val Glu Lys Gly Phe Leu Asp Ala Cys Glu Lys Gly Pro Leu Ser Gly His Lys Leu Ser Gly Leu Arg Phe Val Leu Gln Asp Gly Ala His His Met Val Asp Ser Asn Glu Ile Ser Phe Ile Arg Ala Gly Glu Gly Ala Leu Lys Gln Ala Leu Ala Asn Ala Thr Leu Cys Ile Leu Glu Pro Ile Met Ala Val Glu Val Val Ala Pro Asn Glu Phe Gln Gly Gln Val Ile Ala Gly Ile Asn Arg Arg His Gly Val Ile Thr Gly Gln Asp Gly Val Glu Asp Tyr Phe Thr Leu Tyr Ala Asp Val Pro Leu Asn Asp Met Phe Gly Tyr Ser Thr Glu Leu Arg Ser Cys Thr Glu Gly Lys Gly Glu Tyr Thr Met Glu Tyr Ser Arg Tyr Gln Pro Cys Leu Pro Ser Thr Gln Glu Asp Val Ile Asn Lys Tyr Leu Glu Ala Thr Gly Gln Leu Pro Val Lys Lys Gly Lys Ala Lys Asn <210> 61 <211> 666 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 3357264CD1 <220>
<221> unsure <222> 281 <223> unknown or other <400> 61 Met Cys Gly Ala Val Ile Pro Leu His Lys Pro Ala Gly Arg Lys 1 5 10 ' 15 Leu Gln Asn Gln Arg Ala Ala Leu Asn Gln Gln Ile Leu Lys Ala Val Arg Met Arg Thr Gly Ala Glu Asn Leu Leu Lys Val Ala Thr Asn Ser Lys Val Arg Glu Gln Val Arg Leu Glu Leu Ser Phe Val Asn Ser Asp Leu Gln Met Leu Lys Glu Glu Leu Glu Gly Leu Asn Ile Ser Val Gly Val Tyr Gln Asn Thr Glu Glu Ala Phe Thr Ile Pro Leu Ile Pro Leu Gly Leu Lys Glu Thr Lys Asp Val Asp Phe Ala Val Val Leu Lys Asp Phe Ile Leu Glu His Tyr Ser Glu Asp Gly Tyr Leu Tyr Glu Asp Glu Ile Ala Asp Leu Met Asp Leu Arg Gln Ala Cys Arg Thr Pro Ser Arg Asp Glu Ala Gly Val Glu Leu Leu Met Thr Tyr Phe Ile Gln Leu Gly Phe Val Glu Ser Arg Phe Phe Pro Pro Thr Arg Gln Met Gly Leu Leu Phe Thr Trp Tyr Asp Ser Leu Thr Gly Val Pro Val Ser Gln Gln Asn Leu Leu Leu Glu Lys Ala Ser Val Leu Phe Asn Thr Gly Ala Leu Tyr Thr Gln Ile Gly Thr Arg Cys Asp Arg Gln Thr Gln Ala Gly Leu Glu Ser Ala Ile Asp Ala Phe Gln Arg Ala Ala Gly Val Leu Asn Tyr Leu Lys Asp Thr Phe Thr His Thr Pro Ser Tyr Asp Met Ser Pro Ala Met Leu Ser Val Leu Val Lys Met Met Leu Ala Gln Ala Gln Glu Ser Val Phe Glu Lys Ile Ser Leu Pro Gly Ile Xaa Asn Glu Phe Phe Met Leu Val Lys Val Ala Gln Glu Ala Ala Lys Val Gly Glu Val Tyr Gln Gln Leu His Ala Ala Met Ser Gln Ala Pro Val Lys Glu Asn Ile Pro Tyr Ser Trp Ala Ser Leu Ala Cys Val Lys Ala His His Tyr Ala Ala Leu Ala His Tyr Phe Thr Ala Ile Leu Leu Ile Asp His Gln Val Lys Pro Gly Thr Asp Leu Asp His Gln Glu Lys Cys Leu Ser Gln Leu Tyr Asp His Met Pro Glu Gly Leu Thr Pro Leu Ala Thr Leu Lys Asn Asp Gln Gln Arg Arg Gln Leu Gly Lys Ser His Leu Arg Arg Ala Met Ala His His Glu Glu Ser Val Arg Glu Ala Ser Leu Cys Lys Lys Leu Arg Thr Ile Glu Val Leu Gln Lys Val Leu Cys Ala Ala Gln Glu Arg Ser Arg Leu Thr Tyr Ala Gln His Gln Glu Glu Asp Asp Leu Leu Asn Leu Ile Asp Ala Pro Ser Val Val Ala Lys Thr Glu Gln Glu Val Asp Ile Ile Leu Pro Gln Phe Ser Lys Leu Thr Val Thr Asp Phe Phe Gln Lys Leu Gly Pro Leu Ser Val Phe Ser Ala Asn Lys Arg Trp Thr Pro Pro Arg Ser Ile Arg Phe Thr Ala Glu Glu Gly Asp Leu Gly Phe Thr Leu Arg Gly Asn Ala Pro Val Gln Val His Phe Leu Asp Pro Tyr Cys Ser Ala Ser Val Ala Gly Ala Arg Glu Gly Asp Tyr Ile Val Ser Ile Gln Leu Val Asp Cys Lys Trp Leu Thr Leu Ser Glu Val Met Lys Leu Leu Lys Ser Phe Gly Glu Asp Glu Ile Glu Met Lys Val Val Ser Leu Leu Asp Ser Thr Ser Ser Met His Asn Lys Ser Ala Thr Tyr Ser Val Gly Met Gln Lys Thr Tyr Ser Met Ile Cys Leu Ala Ile Asp Asp Asp Asp Lys Thr Asp Lys Thr Lys Lys Ile Ser Lys Lys Leu Ser Phe Leu Ser Trp Gly Thr Asn Lys Asn Arg Gln Lys Ser Ala Ser Thr Leu Cys Leu Pro Ser Val Gly Ala Ala Arg Pro Gln Val Lys Lys Lys Leu Pro Ser Pro Phe Ser Leu Leu Asn Ser Asp Ser Ser Trp Tyr <210> 62 <211> 746 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 3576329CD1 <400> 62 Met Ala Gly Ser Arg Gly Ala Gly Arg Thr Ala Ala Pro Ser Val Arg Pro Glu Lys Arg Arg Ser Glu Pro Glu Leu Glu Pro Glu Pro Glu Pro Glu Pro Pro Leu Leu Cys Thr Ser Pro Leu Ser His Ser Thr Gly Ser Asp Ser Gly Val Ser Asp Ser Glu Glu Ser Val Phe Ser Gly Leu Glu Asp Ser Gly Ser Asp Ser Ser Glu Asp Asp Asp Glu Gly Asp Glu Glu Gly Glu Asp Gly Ala Leu Asp Asp Glu Gly His Ser Gly Ile Lys Lys Thr Thr Glu Glu Gln Val Gln Ala Ser Thr Pro Cys Pro Arg Thr Glu Met Ala Ser Ala Arg Ile Gly Asp Glu Tyr Ala Glu Asp Ser Ser Asp Glu Glu Asp Ile Arg Asn Thr Val Gly Asn Val Pro Leu Glu Trp Tyr Asp Asp Phe Pro His Val Gly Tyr Asp Leu Asp Gly Arg Arg Ile Tyr Lys Pro Leu Arg Thr Arg Asp Glu Leu Asp Gln Phe Leu Asp Lys Met Asp Asp Pro Asp Tyr Trp Arg Thr Val Gln Asp Pro Met Thr Gly Arg Asp Leu Arg Leu Thr Asp Glu Gln Val Ala Leu Val Arg Arg Leu Gln Ser Gly Gln Phe Gly Asp Val Gly Phe Asn Pro Tyr Glu Pro Ala Val Asp Phe Phe Ser Gly Asp Val Met Ile His Pro Val Thr Asn Arg Pro Ala Asp Lys Arg Ser Phe Ile Pro Ser Leu Val Glu Lys Glu Lys Val Ser Arg Met Val His Ala Ile Lys Met Gly Trp Ile Gln Pro Arg Arg Pro Arg Asp Pro Thr Pro Ser Phe Tyr Asp Leu Trp Ala Gln Glu Asp Pro Asn Ala Val Leu Gly Arg His Lys Met His Val Pro Ala Pro Lys Leu Ala Leu Pro Gly His Ala Glu Ser Tyr Asn Pro Pro Pro Glu Tyr Leu Leu Ser Glu Glu Glu Arg Leu Ala Trp Glu Gln Gln Glu Pro Gly Glu Arg Lys Leu Gly Phe Leu Pro Arg Lys Phe Pro Ser Leu Arg Ala Val Pro Ala Tyr Gly Arg Phe Ile Gln Glu Arg Phe Glu Arg Cys Leu Asp Leu Tyr Leu Cys Pro Arg Gln Arg Lys Met Arg Val Asn Val Asp Pro Glu Asp Leu Ile Pro Lys Leu Pro Arg Pro Arg Asp Leu Gln Pro Phe Pro Thr Cys Gln Ala Leu Val Tyr Arg Gly His Ser Asp Leu Val Arg Cys Leu Ser Val Ser Pro Gly Gly Gln Trp Leu Val Ser Gly Ser Asp Asp Gly Ser Leu Arg Leu Trp Glu Val Ala Thr Ala Arg Cys Val Arg Thr Val Pro Val Gly Gly Val Val Lys Ser Val Ala Trp Asn Pro Ser Pro Ala Val Cys Leu Val Ala Ala Ala Val Glu Asp Ser Val Leu Leu Leu Asn Pro Ala Leu Gly Asp Arg Leu Val Ala Gly Ser Thr Asp Gln Leu Leu Ser Ala Phe Val Pro Pro Glu Glu Pro Pro Leu Gln Pro Ala Arg Trp Leu Glu Ala Ser Glu Glu Glu Arg Gln Val Gly Leu Arg Leu Arg Ile Cys His Gly Lys Pro Val Thr Gln Val Thr Trp His Gly Arg Gly Asp Tyr Leu Ala Val Val Leu Ala Thr Gln Gly His Thr Gln Val Leu Ile His Gln Leu Ser Arg Arg Arg Ser Gln Ser Pro Phe Arg Arg Ser His Gly Gln Val Gln Arg Val Ala Phe His Pro Ala Arg Pro Phe Leu Leu Val Ala Ser Gln Arg Ser Val Arg Leu Tyr His Leu Leu Arg Gln Glu Leu Thr Lys Lys Leu Met Pro Asn Cys Lys Trp Val Ser Ser Leu Ala Val His Pro Ala Gly Asp Asn Val Ile Cys Gly Ser Tyr Asp Ser Lys Leu Val Trp Phe Asp Leu Asp Leu Ser Thr Lys Pro Tyr Arg Met Leu Arg His His Lys Lys Ala Leu Arg Ala Val Ala Phe His Pro Arg Tyr Pro Leu Phe Ala Ser Gly Ser Asp Asp Gly Ser Val Ile Val Cys His Gly Met Val Tyr Asn Asp Leu Leu Gln Asn Pro Leu Leu Val Pro Val Lys Val Leu Lys Gly His Val Leu Thr Arg Asp Leu Gly Val Leu Asp Val Ile Phe His Pro Thr Gln Pro Trp Val Phe Ser Ser Gly Ala Asp Gly Thr Val Arg Leu Phe Thr <210> 63 <211> 212 <212> PRT
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 3805550CD1 <400> 63 Met Ala Gly Pro Gly Pro Gly Pro Gly Asp Pro Asp Glu Gln Tyr Asp Phe Leu Phe Lys Leu Val Leu Val Gly Asp Ala Ser Val Gly Lys Thr Cys Val Val Gln Arg Phe Lys Thr Gly Ala Phe Ser Glu Arg Gln Gly Ser Thr Ile Gly Val Asp Phe Thr Met Lys Thr Leu Glu Ile Gln Gly Lys Arg Val Lys Leu Gln Ile Trp Asp Thr Ala Gly Gln Glu Arg Phe Arg Thr Ile Thr Gln Ser Tyr Tyr Arg Ser Ala Asn Gly Ala Ile Leu Ala Tyr Asp Ile Thr Lys Arg Ser Ser Phe Leu Ser Val Pro His Trp Ile Glu Asp Val Arg Lys Tyr Ala Gly Ser Asn Ile Val Gln Leu Leu Ile Gly Asn Lys Ser Asp Leu Ser Glu Leu Arg Glu Val Ser Leu Ala Glu Ala Gln Ser Leu Ala Glu His Tyr Asp Ile Leu Cys Ala Ile Glu Thr Ser Ala Lys Asp Ser Ser Asn Val Glu Glu Ala Phe Leu Arg Val Ala Thr Glu Leu 170 ' 175 180 Ile Met Arg His Gly Gly Pro Leu Phe Ser Glu Lys Ser Pro Asp His Ile Gln Leu Asn Ser Lys Asp Ile Gly Glu Gly Trp Gly Cys Gly Cys <210> 64 <211> 307 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 4546403CD1 <400> 64 Met Arg Cys Leu His Ser Glu Lys Ala His Asp Leu Gly Ile Thr Cys Cys Asp Phe Ser Ser Gln Pro Val Ser Asp Gly Glu Gln Gly Leu Gln Phe Phe Arg Leu Ala Ser Cys Gly Gln Asp Cys Gln Val Lys Ile Trp Ile Val Ser Phe Thr His Ile Leu Gly Phe Glu Leu Lys Tyr Lys Ser Thr Leu Ser Gly His Cys Ala Pro Val Leu Ala Cys Ala Phe Ser His Asp Gly Gln Met Leu Val Ser Gly Ser Val 80 ~ 85 90 Asp Lys Ser Val Ile Val Tyr Asp Thr Asn Thr Glu Asn Ile Leu His Thr Leu Thr Gln His Thr Arg Tyr Val Thr Thr Cys Ala Phe Ala Pro Asn Thr Leu Leu Leu Ala Thr Gly Ser Met Asp Lys Thr Val Asn Ile Trp Gln Phe Asp Leu Glu Thr Leu Cys Gln Ala Arg Ser Thr Glu His Gln Leu Lys Gln Phe Thr Glu Asp Trp Ser Glu Glu Asp Val Ser Thr Trp Leu Cys Ala Gln Asp Leu Lys Asp Leu Val Gly Ile Phe Lys Met Asn Asn Ile Asp Gly Lys Glu Leu Leu Asn Leu Thr Lys Glu Ser Leu Ala Asp Asp Leu Lys Ile Glu Ser Leu Gly Leu Arg Ser Lys Val Leu Arg Lys Ile Glu Glu Leu Arg Thr Lys Val Lys Ser Leu Ser Ser Gly Ile Pro Asp Glu Phe Ile Cys Pro Ile Thr Arg Glu Leu Met Lys Asp Pro Val Ile Ala Ser Asp Gly Tyr Ser Tyr Glu Lys Glu Ala Met Glu Asn Trp Ile Ser Lys Lys Lys Arg Thr Ser Pro Met Thr Asn Leu Val Leu Pro Ser Ala Val Leu Thr Pro Asn Arg Thr Leu Lys Met Ala Ile Asn Arg Trp Leu Glu Thr His Gln Lys <210> 65 <211> 378 <212> PRT
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 4767318CD1 <400> 65 Met Arg Ala Ala Ala Ala Pro Gly Leu Thr Ala Pro Trp Arg Leu Leu Gln Cys Cys Glu Leu Glu Ala Gly Glu Leu Gly Met Ala Val Pro Ala Ala Ala Met Gly Pro Ser Ala Leu Gly Gln Ser Gly Pro Gly Ser Met Ala Pro Trp Cys Ser Val Ser Ser Gly Pro Ser Arg Tyr Val Leu Gly Met Gln Glu Leu Phe Arg Gly His Ser Lys Thr Arg Glu Phe Leu Ala His Ser Ala Lys Val His Ser Val Ala Trp Ser Cys Asp Gly Arg Arg Leu Ala Ser Gly Ser Phe Asp Lys Thr Ala Ser Val Phe Leu Leu Glu Lys Asp Arg Leu Val Lys Glu Asn Asn Tyr Arg Gly His Gly Asp Ser Val Asp Gln Leu Cys Trp His Pro Ser Asn Pro Asp Leu Phe Val Thr Ala Ser Gly Asp Lys Thr Ile Arg Ile Trp Asp Val Arg Thr Thr Lys Cys Ile Ala Thr Val Asn Thr Lys Gly Glu Asn Ile Asn Ile Cys Trp Ser Pro Asp Gly Gln Thr Ile Ala Val Gly Asn Lys Asp Asp Val Val Thr Phe Ile Asp Ala Lys Thr His Arg Ser Lys Ala Glu Glu Gln Phe Lys Phe Glu Val Asn Glu Ile Ser Trp Asn Asn Asp Asn Asn Met Phe Phe Leu Thr Asn Gly Asn Gly Cys Ile Asn Ile Leu Ser Tyr Pro Glu Leu Lys Pro Val Gln Ser Ile Asn Ala His Pro Ser Asn Cys Ile Cys Ile Lys Phe Asp Pro Met Gly Lys Tyr Phe Ala Thr Gly Ser Ala Asp Ala Leu Val Ser Leu Trp Asp Val Asp Glu Leu Val Cys Val Arg Cys Phe Ser Arg Leu Asp Trp Pro Val Arg Thr Leu Ser Phe Ser His Asp Gly Lys Met Leu Ala Ser Ala Ser Glu Asp His Phe Ile Asp Ile Ala Glu Val Glu Thr Gly Asp Lys Leu Trp Glu Val Gln Cys Glu Ser Pro Thr Phe Thr Val Ala Trp His Pro Lys Arg Pro Leu Leu Ala Phe Ala Cys Asp Asp Lys Asp Gly Lys Tyr Asp Ser Ser Arg Glu Ala Gly Thr Val Lys Leu Phe Gly Leu Pro Asn Asp Ser <210> 66 <211> 466 <212> PRT
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 4834527CD1 <400> 66 Met Pro Gln Thr Leu Ser Ala Ser Asp Met Val Thr Pro Gly Ser Leu Ser Pro Pro Pro Thr Glu Pro Thr Asp Gly Glu Gln Ala Gly Gln Pro Leu Leu Asp Gly Ala Pro Ser Ser Ala Ser Leu Glu Thr Leu Ile Gln His Leu Val Pro Thr Ala Asp Tyr Tyr Pro Glu Lys Ala Tyr Ile Phe Thr Phe Leu Leu Ser Ser Arg Leu Phe Ile Glu Pro Arg Glu Leu Leu Ala Arg Val Cys His Leu Cys Ile Glu Gln Gln Gln Leu Asp Lys Pro Val Leu Asp Lys Ala Arg Val Arg Lys Phe Gly Pro Lys Leu Leu Gln Leu Leu Ala Glu Trp Thr Glu Thr Phe Pro Arg Asp Phe Gln Glu Glu Ser Thr Ile Gly His Leu Lys Asp Val Val Gly Arg Ile Ala Pro Cys Asp Glu Ala Tyr Arg Lys Arg Met His Gln Leu Leu Gln Ala Leu His Gln Lys Leu Ala Ala Leu Arg Gln Gly Pro Glu Gly Leu Val Gly Ala Asp Lys Pro Ile Ser Tyr Arg Thr Lys Pro Pro Ala Ser Ile His Arg Glu Leu Leu Gly Val Cys Ser Asp Pro Tyr Thr Leu Ala Gln Gln Leu Thr His Val Glu Leu Glu Arg Leu Arg His Ile Gly Pro Glu Glu Phe Val Gln Ala Phe Val Asn Lys Asp Pro Leu Ala Ser Thr Lys Pro Cys Phe Ser Asp Lys Thr Ser Asn Leu Glu Ala Tyr Val Lys Trp Phe Asn Arg Leu Cys Tyr Leu Val Ala Thr Glu Ile Cys Met Pro Ala Lys Lys Lys Gln Arg Ala Gln Val Ile Glu Phe Phe Ile Asp Val Ala Arg Glu Cys Phe Asn Ile Gly Asn Phe Asn Ser Leu Met Ala Ile Ile Ser Gly Met Asn Met Ser Pro Val Ser Arg Leu Lys Lys Thr Trp Ala Lys Val Arg Thr Ala Lys Phe Phe Ile Leu Glu His Gln Met Asp Pro Thr Gly Asn Phe Cys Asn Tyr Arg Thr Ala Leu Arg Gly Ala Ala His Arg Ser Leu Thr Ala His Ser Ser Arg Glu Lys Ile Val Ile Pro Phe Phe Ser Leu Leu Ile Lys Asp Ile Tyr Phe Leu Asn Glu Gly Cys Ala Asn Arg Leu Pro Asn Gly His Val Asn Phe Glu Lys Phe Leu Glu Leu Ala Lys Gln Val Gly Glu Phe Ile Thr Trp Lys Gln Val Glu Cys Pro Phe Glu Gln Asp Ala Ser Ile Thr His Tyr Leu Tyr Thr Ala Pro Ile Phe Ser Glu Asp Gly Leu Tyr Leu Ala Ser Tyr Glu Ser Glu Ser Pro Glu Asn Gln Thr Glu Lys Glu Arg Trp Lys Ala Leu Arg Ser Ser Ile Leu Gly Lys Thr <210> 67 <211> 891 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 1405545CB1 <400> 67 ggagaatggc ggcgccgggc tgcggctggg agcgggaaga ctctttgaaa tgcctgcggt 60 gctagagcga ctgagccgct ataatagcac gtcccaagct tttgctgagg tgctgcggct 120 gccgaagcag cagctgagga agctgctgta cccgctgcag gaagtagagc ggttcctcgc 180 cccctacggg aggcaagacc ttcacctgcg tatctttgac ccaagcccgg aggacatagc 240 cagggcggac aacatcttca cggccactga acggaaccgc atcgactacg tcagctccgc 300 cgtccgtatc gaccacgccc cggaccttcc gcggccagag gtgtgtttta taggcagaag 360 caatgttgga aaatcatctc taatcaaggc tttattttca ctggcccctg aggttgaagt 420 cagagtctcc aaaaaaccag gacacacaaa gaaaatgaat tttttcaaag ttggaaaaca 480 ttttacagtg gtggacatgc caggttatgg ctttagagca cctgaagatt ttgttgacat 540 ggtagagacc tatctaaaag aacgaaggaa cttgaagaga acatttttat tagtggatag 600 cgttgttgga attcaaaaaa cagacaatat tgccatagaa atgtgtgaag aatttgcatt 660 accttatgtg attgtattaa caaaaattga caaatcttcc aagggacatc ttttaaaaca 720 agtgcttcag atccagaaat ttgttaacat gaaaactcaa ggatgttttc ctcagttgtt 780 tcctgtaagt gctgtgacct tttctggaat ccacctgttg agatgcttta tagccagtgt 840 aacaggaagt cttgactaat ggttcccggt ttagctgaag attcaaaaaa a 891 <210> 68 <211> 1512 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 1451265CB1 <400> 68 gcccatggag gtggccgtgt gtacggactc ggcggccccg atgtggagct gcatcgtgtg 60 ggaacttcac tcgggcgcca acctgctcac ctaccgcggc ggccaggcgg gaccccgcgg 120 cctggcgctg ctcaatggcg agtatctgct ggcggcgcag ctgggcaaga attacatcag 180 cgcctgggag ctccagcgga aggaccagct ccagcagaag atcatgtgcc ccgggcctgt 240 cacctgtctg actgcatcac ccaatggtct ctacgtcctg gcaggagttg cagaaagcat 300 ccacctgtgg gaggtctcca ccgggaacct tctggtcatc ctgagtcgac actaccagga 360 cgtctcctgc cttcagttca caggggacag cagccacttc atctcagggg gcaaggactg 420 cctggtgctg gtttggagcc tctgcagcgt gctgcaggcc gacccctcca ggattccggc 480 gcccaggcac gtctggtctc accacacgct ccccatcacg gacctgcact gcggctttgg 540 gggccccctg gcccgggtgg ccacctcctc actggaccag acggtgaagc tatgggaggt 600 ctcctcgggg gagctgctgc tctccgtcct ctttgacgtg tccatcatgg cagtgaccat 660 ggacctggct gagcaccata tgttctgcgg gggcagtgag ggctccatct tccaggtcga 720 cctcttcacc tggcccggac agagggagag gagcttccac ccagagcagg acgccgggaa 780 ggtcttcaaa gggcacagga accaggtgac ttgcctgtca gtgtccactg acggcagcgt 840 gctgctctca ggctcccacg acgagaccgt gcgcctctgg gacgtgcaga gcaagcagtg 900 catccggacg gtggccctca aaggcccagt caccaatgcc gccatcctgc tggcgcccgt 960 cagcatgctg agctcagact tcaggcccag cctgccgctg ccccacttca acaagcacct 1020 gctgggcgcc gagcacgggg acgagccgcg ccacgggggc ctcactctgc gcctgggcct 1080 ccaccagcag ggctcggagc ccagctacct ggaccgcacg gagcagctgc aggccgtcct 1140 gtgcagcacc atggagaaga gcgtgctcgg cggccaggac cagctgcgcg tccgtgtgac 1200 ggagctggag gacgaggtgc gcaacctgcg caagatcaat cgggacctgt tcgacttctc 1260 cacgcgcttc atcacgcggc cggccaagtg aggcccggag accccggccc gaggcgccca 1320 ggcctgagcc ccatgcctcc cagcaaccag ggcccgcggg tgtggccccc accagcccag 1380 gcctggactc tcctcagttc tgtgtcgtgt tcgggttttt cctctgtgac tgggccgtct 1440 tggtgtctcg tggcacgcgt cacagtggtg ctagtctgtt tttaacaaaa gaggatgaaa 1500 aaaaaaaaaa as 1512 <210> 69 <211> 2536 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 1556311CB1 <400> 69 caactcttgt tgaagctttt aggcgtcgca gactcttcat ttgtgagggc gacctctccc 60 gaggggctct tttcacacaa atatccccac ggcgtttctc ggaggcaccc ccgtcatacg 120 tcttgtctct cgcgacaatt ctctttgaag gcgaggcatt tcaccacaac tcttttcaac 180 caacctggcg acaacaccca gagcttacat tgaccccaat ttgaattttc atcggcccaa 240 ggctttcttt acactcaggg aactctcaca ctccttaggg ggaaaaaggc ttcgttaagg 300 gccttgcaag ggttaccggg ttccggaatt ttcccggggg cccctcggct ggccaggact 360 gaaacccaga cgagcatgcc agaaacagtc aaccataaca aacatgggaa cgtagctctc 420 cctggaacga aaccaactcc catccctcca ccccggctga agaagcaggc ttcttttctg 480 gaagcagagg gcggtgcaaa gaccttgagc ggcggccggc cgggcgcagg cccggagctg 540 gagctgggca cagctggcag cccaggtggg gccccgcctg aggccgcccc gggggattgc 600 acaagggccc cgccgcccag ctctgaatca cggcccccgt gccatggagg ccggcagcgg 660 ctgagcgaca tgagcatttc tacttcctcc tccgactcgc tggagttcga ccggagcatg 720 cctctgtttg gctacgaggc ggacaccaac agcagcctgg aggactacga gggggaaagt 780 gaccaagaga ccatggcgcc ccccatcaag tccaaaaaga aaaggagcag ctccttcgtg 840 ctgcccaagc tcgtcaagtc ccagctgcag aaggtgagcg gggtgttcag ctccttcatg 900 accccggaga agcggatggt ccgcaggatc gccgagcttt cccgggacaa atgcacctac 960 ttcgggtgct tagtgcagga ctacgtgagc ttcctgcagg agaacaagga gtgccacgtg 1020 tccagcaccg acatgctgca gaccatccgg cagttcatga cccaggtcaa gaactatttg 1080 tctcagagct cggagctgga cccccccatc gagtcgctga tccctgaaga ccaaatagat 1140 gtggtgctgg aaaaagccat gcacaagtgc atcttgaagc ccctcaaggg gcacgtggag 1200 gccatgctga aggactttca catggccgat ggctcatgga agcaactcaa ggagaacctg 1260 cagcttgtgc ggcagaggaa tccgcaggag ctgggggtct tcgccccgac ccctgatttt 1320 gtggatgtgg agaaaatcaa agtcaagttc atgaccatgc agaagatgta ttcgccggaa 1380 aagaaggtca tgctgctgct gcgggtctgc aagctcattt acacggtcat ggagaacaac 1440 tcagggagga tgtatggcgc tgatgacttc ttgccagtcc tgacctatgt catagcccag 1500 tgtgacatgc ttgaattgga cactgaaatc gagtacatga tggagctcct agacccatcg 1560 ctgttacatg gagaaggagg ctattacttg acaagcgcat atggagcact ttctctgata 1620 aagaatttcc aagaagaaca agcagcgcga ctgctcagct cagaaaccag agacaccctg 1680 aggcagtggc acaaacggag aaccaccaac cggaccatcc cctctgtgga cgacttccag 1740 7~/11S

aattacctcc gagttgcatt tcaggaggtc aacagtggtt gcacaggaaa gaccctcctt 1800 gtgagacctt acatcaccac tgaggatgtg tgtcagatct gcgctgagaa gttcaaggtg 1860 ggggaccctg aggagtacag cctctttctc ttcgttgacg agacatggca gcagctggca 1920 gaggacactt accctcaaaa aatcaaggcg gagctgcaca gccgaccaca gccccacatc 1980 ttccactttg tctacaaacg catcaagaac gatccttatg gcatcatttt ccagaacggg 2040 gaagaagacc tcaccacctc ctagaagaca ggcgggactt cccagtggtg catccaaagg 2100 ggagctggaa gccttgcctt cccgcttcta catgcttgag cttgaaaagc agtcacctcc 2160 tcggggaccc ctcagtgtag tgactaagcc atccacaggc caactcggcc aagggcaact 2220 ttagccacgc aaggtagctg aggtttgtga aacagtagga ttctcttttg gcaatggaga 2280 attgcatctg atggttcaag tgtcctgaga ttgtttgcta cctaccccca gtcaggttct 2340 aggttggctt acaggtatgt atatgtgcag aagaaacact taagatacaa gttcttttga 2400 attcaacagc agatgcttgc gatgcagtgc gtcaggtgat tctcactcct gtggatggct 2460 tcatccctgc cttccttcct ttctttttcc tttgtgtgtt tttttttttt ttttaaaaaa 2520 gccttcgggt tttaaa 2536 <210> 70 <211> 1415 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 1901373CB1 <400> 70 gcgaggacgc gggccgagcc ggaagtggag tgcgctgcgg cgcgagctgg gccggcgggc 60 gtggttcgag agcgcgcaga gtccagactg gcggcagggc ccgaggggcc gacccgcagc 120 gtccctggtc tctccagccc tcactcggaa ccgcactgac aataccctcc cctcccttgg 180 gctggacccc tctctacagc taggagccaa tggcagaaga caaaaccaaa ccgagtgagt 240 tggaccaagg gaagtatgat gctgatgaca acgtgaagat catctgcctg ggagacagcg 300 cagtgggcaa atccaaactc atggagagat ttctcatgga tggctttcag ccacagcagc 360 tgtccacgta cgccctgacc ctgtacaagc acacagccac ggtagatgga aggaccatcc 420 ttgtggactt ttgggacacg gcaggccagg agcggttcca gagcatgcat gcctcctact 480 accacaaggc ccacgcctgc atcatggtgt ttgatgtaca gaggaaagtc acctatagga 540 acctgagcac ctggtataca gagcttcggg agttcaggcc agagatccca tgcatcgtgg 600 tggccaataa aattgatgca gacataaacg tgacccaaaa aagcttcaat tttgccaaga 660 agttctccct gcccctgtat ttcgtctcgg ctgctgatgg taccaatgtt gtgaagctct 720 tcaatgatgc aattcgatta gctgtgtctt acaaacagaa ctcccaggac ttcatggatg 780 agatttttca ggagctcgag aacttcagct tggagcagga agaggaggac gtgccagacc 840 aggaacagag cagcagcatc gagaccccat cagaggaggt ggcctctccc cacagctgag 900 gggctggggc taggggtggg tggagccctt ttaaaatacc.cttcccttca acaactctcc 960 agctctgaat ggagaaactc tctaggccat cccctcttct acctcctgca acccacccat 1020 cctattagcc tcccacattc aaggcccgtg atacagggat gaggtcagca ccagcaaact 1080 ctggactggt ggaagaattc cccaccagat ctccttgaag cagaattagg gatcagcatc 1140 attaacacct tccccacccc ctccccgcag gcagacagtg aagagaatca gaaaacatga 1200 ttatgtgtca ctttaataca ggaaatttag gtgttttttg gtgtttttgt ttttgttttt 1260 gttttctttc caaagctcac ctcggggaca attccttggg cttctcctga ggtaatgatt 1320 taccccccca cccacagctg agtctgtgag gccccatcct ttccctacgt tttctcccat 1380 cttttttcct cttcagtctc ccagtcatct ggttt 1415 <210> 71 <211> 1902 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 2367767CB1 <400> 71 gcgaggtctg gctaggctac gggccacgcg ccgccgccgc tgccgccgcc actgtcctct 60 tcggaggcgc gggcccgacg gaaaccatgt ttgtggctcg cagcatcgcg gcggaccaca 120 aggatctcat ccacgatgtc tctttcgact tccacgggcg gcggatggca acctgctcca 180 ~1/11S

gcgatcagag cgttaaggtc tgggataaaa gtgaaagtgg tgattggcat tgtactgcta 240 gctggaagac acatagtgga tctgtatggc gtgtgacatg ggcccatcct gaatttgggc 300 aggttttggc ttcctgttct tttgaccgaa cagctgctgt atgggaagaa atagtaggag 360 aatcaaatga taaactgcga ggacagagcc actgggttaa aaggacaact ctggtggata 420 gcagaacatc tgttactgat gtgaagtttg ctcccaagca catgggtctt atgttagcaa 480 cctgttccgc agatggtata gtaagaatct atgaggcacc agatgttatg aatctcagcc 540 agtggtcttt gcagcatgag atctcatgta agctaagctg tagttgtatt tcttggaacc 600 cttcaagctc tcgtgctcat tcccccatga tcgccgtagg aagtgatgac agtagcccca 660 acgcaatggc caaggttcag atttttgaat ataatgaaaa caccaggaaa tatgcaaaag 720 ctgaaactct tatgacagtc actgatcctg ttcatgatat tgcattcgct ccaaatttgg 780 gaagatcttt ccatattcta gcaatagcga ccaaagatgt gagaattttt acattaaagc 840 ctgtgaggaa agaactgact tcctctggtg ggccaacaaa gtttgaaatc catatagtgg 900 ctcagttcga taatcataat tctcaggtct ggcgagtgag ttggaatata acaggaacgg 960 tgctagcatc ttcaggagat gatgggtgtg taagattgtg gaaagctaat tatatggaca 1020 attggaagtg tactggtatt ttgaaaggta atgggagccc agtcaatggg agttctcagc 1080 agggaacctc aaatccttcc ctaggttcaa atattccaag tcttcagaat tcattaaatg 1140 gatcttctgc tggcagaaag cacagctgag tacaagctaa ctggagtaac tttgctgttt 1200 tgctgcttgt tgcatgcaca caggaatgga aagcgagctc cttttcccct tccccagcgc 1260 cgtttgacct ctcccaagat acaccagcag cctgcttact actaaacgca atccaaaagg 1320 cctttaaaaa tacagtgtat attttttgta ctagtcagtt tattgacact atttgaaact 1380 tttgaaatat aaacggagag gctttctgtt gagacattgt caccaaaaca attttttgaa 1440 atgttcctga aactaatttg ggtttaaaga ttaaaagggt tgttaccatt cttatctgag 1500 tagttgggag gaggggaata ccactttagt tcatttggaa aatatagaca tatttctttt 1560 gctttcttaa aacagcttaa aatgatgaac ttttataatt ttaatttgaa gattgaataa 1620 atatttttta taaagattgt tttgagtgct gatttgttta ctttttgtag atttgcttta 1680 tccatgatat tcagtacaac tctgtcattt ctttgtaata tttaaaaaat attagtaaag 1740 gagtgaatta ataaagtagt aatagtaaaa tgaaaggaac ttgactgtac agtttgtagc 1800 caggttaagc atttggtatt gtttcattta caatttggga ctaagatgga aacacttttt 1860 ttataagttt ttaattcata gtcactaaag agataaatgt tt 1902 <210> 72 <211> 1681 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 3090433CB1 <400> 72 gggcagggct ttgctatggc taatgatccc ttggaaggct tccatgaagt aaaccttgct 60 tcacctactt ctccggacct tcttggtgtg tatgaatcag gaactcaaga gcagactacc 120 tcaccaagtg tcatctaccg gccacaccct tcagctttat cctctgtacc tatccaggca 180 aatgcattag atgtttctga acttcctaca caacccgtgt attcatcccc cagacgttta 240 aattgtgcgg aaatatctag tatcagcttt catgttacag acccagcccc ttgctctacc 300 tctggagtca cagctggatt aactaaatta actacaagaa aggacaacta taatgcagag 360 agagagtttt tacagggtgc tactataaca gaggcttgcg atggcagtga tgatattttt 420 gggttgagta ctgatagtct gtctcgttta cgaagcccat ctgttttgga agttagagaa 480 aagggctatg aacgattaaa agaagaactc gcaaaagctc agagggaact gaagttaaaa 540 gatgaagaat gtgagaggct ttcaaaagtg cgagatcaac ttggacagga attggaagaa 600 ctcacagcta gtctatttga ggaagctcat aaaatggtga gagaagcaaa tatcaagcag 660 gcaacagcag aaaaacagct aaaagaagca caaggaaaaa ttgatgtact tcaagctgaa 720 gtagctgcat tgaagacact tgtattgtcc agttctccaa catcacctac gcaggagcct 780 ttgccaggtg gaaagacacc ttttaaaaag gggcatacaa gaaataaaag cacaagcagt 840 gctatgagtg gcagtcatca ggacctcagt gtgatacagc caattgtaaa agactgcaaa 900 gaggctgact tatccttgta taatgaattc cgattgtgga aggatgagcc cacaatggac 960 aggacgtgtc ctttcttaga caaaatctac caggaagata tctttccatg tttaacattc 1020 tcaaaaagtg agttggcttc agctgttctg gaggctgtgg aaaacaatac tctaagcatt 1080 gaaccagtgg gattacaacc tatccggttt gtgaaagctt ctgcagttga atgcggagga 1140 ccaaaaaaat gtgctctcac tggccagagt aagtcctgta aacacagaat taaattaggg 1200 gactcaagca actattatta tatttctcct ttttgcagat acaggatcac ttctgtatgt 1260 aactttttta catacattcg atacattcag cagggactcg tgaaacagca ggatgttgat 1320 cagatgtttt gggaggttat gcagttgaga aaagagatgt cattggcaaa gctgggttat 1380 ttcaaagagg aactctgatg ctctgcgtgg gaccatgcct gaactccccg aataactgaa 1440 aaatggctga atatttttat ggttacttga tatttatttc caaggagtga gcctaagact 1500 tttttcccct tttgcaaatt gctctaagaa gtaccatgat ttcttttaaa ctgatctatg 1560 ctgtgtttgc ttattcttta gttgaacaca ctatgaagaa ttccaggtgt actagtgaat 1620 gtaatttata gttgccaaaa aaaaaacaaa cctgaaataa ataaatgtta gattgaaaaa 1680 a 1681 <210> 73 <211> 1378 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 3800591CB1 <400> 73 ggcagatcct atctggcgca tgcgaacgct tctgtgccga ttccttgaag agcaggcgca 60 gactcaaggc tgttgcttcc gcccttactc cccgccgctc gtccctgggc ggggcgaagg 120 ctgggctggg ggaagaggcg tggcggcgct gtgcgcgtgc acaaaagaga gctgaggggc 180 gggggcgctg cggcacagct ggtttgagca actgaactgg aaacaagatg caggacccca 240 acgcagacac tgaatggaat gacatcttac gcaaaaaggg tatcttaccc cccaaggaaa 300 gtctgaaaga attggaagag gaggcagaag aggagcagcg catcctccag cagtcagtgg 360 tgaaaacata tgaagatatg actttggaag agctggagga tcatgaagac gagtttaatg 420 aggaggatga acgtgctatt gaaatgtaca gacggcggag actggctgag tggaaagcaa 480 ctaaactgaa gaataaattc ggagaagttt tggagatctc agggaaggat tatgttcaag 540 aagttaccaa agctggcgag ggcttgtggg tcatcttgca cctttacaaa caaggaattc 600 ccctctgtgc cctgataaat cagcacctca gtggacttgc caggaagttt cctgatgtca 660 aatttatcaa agccatttca acaacctgca tacccaatta tcctgatagg aatctgccca 720 cgatatttgt ttacctggaa ggagatatca aggctcagtt tattggtcct ctggtgtttg 780 gcggcatgaa cctgacaaga gatgagttgg aatggaaact gtctgaatct ggagcaatta 840 tgacagacct ggaggaaaac cctaagaagc cgattgaaga cgtgttgctg tcctcagtgc 900 ggcgctctgt cctcatgaag agggacagcg attccgaggg tgactgaggc tacagcttct 960 atcacatgcc gaactttctt gtgacaaatt gtctggattt tttaaaaaag gaaaaagcaa 1020 gaatgaatcc ttgtggtttt tagttttgta taaattatgt ttcaaatctt tacattttgg 1080 aaataatcat tgctggagat tctgttaaat attttggaac tctttttttt ttaaattata 1140 gtatttcctc taaaaaaaat taaaaccagc catttgtatg gcaaaaaaaa aaaagatact 1200 tcaatattac aattcaggtt tcctaatttt ctaaaaccta tgggaatttt ctaggatgga 1260 cgatcttagg aaggatcact tttggctgtt gtgagaaaca caaaataatt ttattacact 1320 ttaaaaatgt tttgtcataa tttagttaat attaaccttg tttaacttta tagaaaga 1378 <210> 74 <211> 1444 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 5308471CB1 <400> 74 gcacgcagtg ccggaggccg cagcgccgga acctcagagg cgggtcgcag cggcgcagag 60 gaggtcagct gcgggagcgt ttccggggac ggtgccgcca tgagattgac cccgcgcgcg 120 ctgtgcagcg ccgcccaggc cgcctggcgg gagaacttcc ccctgtgcgg tcgcgacgtg 180 gcgcgctggt tcccgggcca catggccaag gggctgaaga agatgcagag cagcctgaag 240 ctggtggact gtatcatcga ggtccacgat gcccggatcc cactttcagg ccgcaaccct 300 ctgtttcagg aaacccttgg gcttaagcct cacttgctgg tcctcaacaa gatggacttg 360 gcggatctta cagagcagca gaaaattatg caacacttag aaggagaagg cctaaaaaat 420 gtcattttta ccaactgtgt aaaggatgaa aatgtcaagc agatcatccc gatggtcact 480 gaactgattg ggagaagcca ccgctaccac cgaaaagaga acctggagta ctgtatcatg 540 gtcattgggg tccccaacgt gggcaagtcc tccctcatca actccctccg gaggcagcac 600 ctcaggaaag ggaaagccac cagggtgggt ggcgagcctg ggatcaccag agctgtgatg 660 tccaaaattc aggtctctga gcggcccctg atgttcctgt tggacactcc tggcgtgctg 720 gctcctcgga ttgaaagtgt ggagacaggc ctgaagctgg ccctgtgtgg aacggtgctg 780 gaccacctgg tcggggagga gaccatggct gactacctgc tgtacaccct caacaaacac 840 cagcgctttg ggtacgtgca gcactacggc ctgggcagtg cctgtgacaa cgtagagcgc 900 gtgctgaaga gtgtggctgt gaagctgggg aagacgcaga aggtgaaggt gctcacgggc 960 acgggtaacg tgaacgttat tcagcctaac tatcctgcgg cagcccgtga cttcctgcag 1020 actttccgcc gtgggctgct gggttccgtg atgctggacc tcgacgtcct gcggggccac 1080 cccccggctg agactttgcc ctgaacttgt ccgggtaggg agggccggag gcatgtggcc 1140 tcccagacct cctgacctgg gtggttgagg ctcaagacag ctcacccggt ccagaagctc 1200 catgctggtc actagggtgc tgtgctctct ggcgccccac agcctggcca gctccaggga 1260 ccccagttgc agggcccaag caggtgggag tggacaccag gcttcccagt ggacgtccct 1320 gagcagctcc gcatgcttgg ttctcccgga gcttcctgct caggcctctt gagaaatgga 1380 tgctgtctca gaaggagtta aagctataac ctgtaacctt taaaatctca aaaaaaaaaa 1440 aaaa 1444 <210> 75 <211> 2067 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 5324322CB1 <400> 75 ggcactgtcc accagcactc agagctccat tatgtcccca gctggggttg cagggtaggg 60 gggactgggg tgtcccccag cctcagcaga cggagggcct cagggatgag gctgccagga 120 tagcgccaga gaagcagctc agagcaaggg ctcctgagtg ggggcagggc tggggagaag 180 gtcatggggg ggctgcagta ggggtggtca ttgtgcaggc tgagttgaga gaagtgggtg 240 gccatgttct cctcagacag aaactgcttg cgcagaggct ccctggggag agatggcaga 300 gaggcaggct gggatactga cacaggaggc agcctgttgg ggaccagagg tgacagagat 360 cttgttggga gtccctccct gcccccaaac tcactgctcc tcctccaggc gccgcttggt 420 gctcatgggc acagctcctc ggagagggga gctggcgtcc aggccccaag tcacccccaa 480 ggcggcccgc gggaggcgct gggcccctcc ctgggggcct cgctgcaagg gctgctgcag 540 gatcattggg ttttggggtc ctgcgggtgg gatctgggcg acaggggagg agtctctgag 600 ggcgtggcca agagaggatg ggcgtggctt taggcgggca cagccgcgag gttctgcgcg 660 ggcgcggaag acgggcggcg cgtggcggaa ggcaggcttg ctcctcgggg tgggggaggg 720 tatccggctt aagggggctg cggtggacac cacttcttaa tgtcgggggt cttcgcggcg 780 ctcacctcgg ctcctagggt tcgggacggt acgcaccagc caccttcgcg ccgaaggcgg 840 tagggcgcca cggagaggaa ccgctctagg cacgtaaggc ctcgtgaggt tgcgtcgcgc 900 gcggagcact ctgggacttg tagttctgga gatggagcga gctgtgccgc tcgcggtgcc 960 tctgggtcag acagaggtgt tccaggcctt gcagcggctc catatgacca tcttctccca 1020 gagcgtctca ccatgtggga agtttctggc ggctggcaac aattacgggc agattgccat 1080 cttcagcttg tcctctgctt tgagctcaga agccaaagag gaaagtaaga agccggtggt 1140 gactttccaa gcccatgatg ggcccgtcta tagcatggtt tccaccgatc gacatctgct 1200 tagtgctggg gatggggagg tgaaggcctg gctttgggcg gagatgctca agaagggctg 1260 taaggagctg tggcgtcgtc agcctccata caggaccagc ctggaagtgc ctgagatcaa 1320 cgctttgctg ctggtcccca aggagaattc cctcatcctg gctgggggag actgtcagtt 1380 gcacactatg gaccttgaaa ctgggacttt cacgagggtc ctccggggcc acacagacta 1440 catccactgc ctggcactgc gggaaaggag cccagaggtg ctgtcaggtg gcgaggatgg 1500 agctgttcga ctttgggacc tgcgcacagc caaggaggtc cagacgatcg aggtctataa 1560 gcacgaggag tgctcgaggc cccacaatgg gcgctggatt ggatgtttgg caactgattc 1620 cgactggatg gtctgtggag ggggcccagc cctcaccctc tggcacctcc gatcctccac 1680 acccaccacc atcttcccca tccgggcgcc acagaagcac gtcaccttct accaggacct 1740 gattctgtca gctggccagg gccgctgcgt caaccagtgg cagctgagcg gggagctgaa 1800 ggcccaggtg cctggctcct ccccagggct gctcagcctc agcctcaacc agcagcctgc 1860 cgcgcctgag tgcaaggtcc tgacagctgc aggcaacagc tgccgggtgg atgtcttcac 1920 caacctgggt taccgagcct tctccctgtc cttctgatct ctgacgacac ccccagccag 1980 ctcagggttt tagagtgttt ttcattttct tttttttttt ttttttacaa taaagtttca 2040 ggctttttta ccaaaaaaaa aaaaaaa 2067 <210> 76 <211> 2085 <212> DNA

<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 067184CB1 <400> 76 gtgttgcgcg actggccttg agggagagct ggggcctgct cccggagaga tacggctatg 60 tcgatcgaaa tcgaatcttc ggatgtgatc cgccttatta tgcagtactt gaaggagaac 120 agtttacatc gggcgttagc caccttgcag gaggagacta ctgtgtctct gaatactgtg 180 gacagcattg agagttttgt ggctgacatt aacagtggcc attgggatac tgtgttgcag 240 gctatacagt ctctgaaatt gccagacaaa accctcattg acctctatga acaggttgtt 300 ctggaattga tagagctccg tgaattgggt gctgccaggt cacttttgag acagactgat 360 cccatgatca tgttaaaaca aacacagcca gagcgatata ttcatctgga gaaccttttg 420 gccaggtctt actttgatcc tcgtgaggca tacccagatg gaagtagcaa agaaaagaga 480 agagcagcaa ttgcccaggc cttagctggc gaagtcagtg tggtgcctcc atctcgtctc 540 atggcattgc tgggacaggc actgaagtgg cagcagcatc agggattgct tcctcctggt 600 atgaccatag atttgtttcg aggcaaggca gctgtcaaag atgtggaaga agaaaagttt 660 cctacacaac tgagcaggca tattaagttt ggtcagaaat cacatgtgga gtgtgctcga 720 ttttctccag atggtcagta tttggtcact gggtctgttg atggattcat tgaagtatgg 780 aactttacta ctggaaaaat cagaaaggat cttaagtacc aggcccaaga taactttatg 840 atgatggatg atgctgtcct ctgcatgtgt ttcagcagag atacagaaat gttagcaact 900 ggggcccaag atggaaaaat caaggtgtgg aagattcaga gtggacaatg tttaaggaga 960 tttgagaggg cacacagtaa gggtgtcacc tgtctaagct tttctaagga tagcagtcag 1020 atccttagtg cttcttttga ccagacaatt agaattcatg gtttaaaatc tgggaaaacc 1080 ctgaaggaat ttcgtggcca ttcctccttt gttaacgaag caacatttac acaagatgga 1140 cattacatta ttagtgcatc ctctgatggc actgtaaaga tctggaatat gaagaccaca 1200 gaatgttcaa atacctttaa atccctgggc agcaccgcag ggacagatat taccgtcaac 1260 agtgtgattc tacttcctaa aaaccctgag cactttgtgg tgtgcaacag atcaaacacg 1320 gtggtcatca tgaacatgca ggggcagatt gtcagaagct tcagttctgg taaaagagaa 1380 ggtggggact ttgtttgctg tgccctctct ccccgtggtg aatggatcta ctgtgtaggg 1440 gaggactttg tgctctactg tttcagtaca gtcactggca aactggagag aactttgaca 1500 gtgcacgaga aggatgtgat tggtattgca catcaccctc atcagaacct gattgctacc 1560 tacagtgaag atggactcct aaagctctgg aaaccataat tcaacttttc tttttaaatc 1620 agctcgaaag catgtactta aatgaagcat attcatgtaa tgtgcttttt tttttttttt 1680 gccagctttt ctaagcaaat agattgtctg aattagtcac agaataattt tgtgaaaatt 1740 catgtttaag tagcaactac cctttctttt tttatatatt tttaaggtat tagtttatct 1800 tcttctaact ggtgcagtca cttaatgttt tcattaatct tcgacctgga gagtgaaata 1860 ctgatatttc tagaaaaaaa ttctactcct ctgattattt gaaatgctga ggaaaatgtc 1920 cctcccatag taaaacttgt aaataaggaa ctatatcata ttcagtagct gtgttctgtt 1980 ccatcttttt tttttttttt gagatggagt tttgcttgtt gcccaggctg gagtgcagcg 2040 gcacgatctt ggttcactgc aacctccgcc tcccaggttc aagcg 2085 <210> 77 <211> 2061 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 722896CB1 <400> 77 cgagccgcgg gacccgggcc gtaccgggga ggggccgctc cgggccgcag cgcgagggca 60 gcgaggggcg gcggggacct ggcaccgggc ggggccggcg gcagcgacca tgatcgcttt 120 gttcaacaag ctgctggact ggttcaaggc cctattctgg aaggaggaga tggagctcac 180 gctggtcggg cttcagtact cgggcaagac caccttcgtc aacgtgatcg cgtcaggaca 240 gttcaacgag gacatgatcc ccaccgtggg tttcaacatg cgcaaaatca ccaaagggaa 300 tgtgactatc aagctctggg acattggggg acagccgcgt ttccgcagca tgtgggagcg 360 ctactgccga ggagtgagcg ccatcgtgta catggtggat gctgctgacc aggagaagat 420 tgaggcctct aagaacgagc tccacaacct actggacaaa cctcagctgc agggcatccc 480 ggtcttagtc ctgggtaaca agcgagacct tccgggagca ttggatgaga aggagctgat 540 tgagaaaatg aatctgtctg ccatccagga ccgagagatc tgctgctact ccatctcttg 600 ~S/I 1S

caaagaaaag gacaacattg acatcaccct acagtggctt attcaacact cgaagtcacg 660 gagaagctga gactccagcc cttctccctc agaccaggga ccgtcatcat ctaaacctga 720 agccgagctc cccgcccacc cctgtcgtcc ccctaagccc acccctcctc acccagtgtg 780 aggagggccc tctggggacc ccagagtcct gttctgctga ggtttgaact cctgttttta 840 ttgtaaaata aattgccccc cattctggtc ccctaacttc tcacccttcc ccgctgcctt 900 tgtcccatca cccagccctg cctccctccc agcagccctg ggccacagcc cccgcccctg 960 gcttttcccc ggcccggtct tgtacctccc ttttcaacac tctctgttat tgtcctgtgt 1020 gtacagtata tatatgtata tatattttaa ttttttaatt taagcaaaga ctaaaatcaa 1080 ccatttgatg ctgcaggggc ctttcaggat ctgggagggg gcagtctgga gagaaggagg 1140 gagacgcagg tggacttggg gcaagttcag atcagaagag gtgcaggctg gcacctgcgg 1200 caggtaccag cctgggcact ggtggccgcc tccctgtccc gtgtgtttcc accgcccaat 1260 ctggcttgtc ctggcagtgc ttgaatgcca caggctggca ggggcctctg ggggcccctc 1320 ccctcgaccc ccagcctggg tagagccacc aggtacgacg accaggtacc agaaaccacc 1380 aggcacacgg ggcagaaagc cagcgtccat gccccagcag ccccctcctg cctgttcctg 1440 gctcccagct cccgcccctc cccagggccc ccacctccac ggcccacttc attttctgtt 1500 c.tcattttgc agagttgcac aaggagagaa ctcagcatgg ggggttggtt ctttgggttc 1560 tgtttgttta tttgtttaat ttaatgattt gtaaagtgat gttcctcttc cttttttaca 1620 cttttcagct catatttaac ctctgtttgg aaaatgattc ttgtaactgt acattttttt 1680 gcttcctaat aacaatgaca acaaaaaaaa taaatgacca gttttgtgtt ggggggggtg 1740 tatggtgctg gttacttttc cgcagttggc atgggttgcc ctacaggccc acagggccac 1800 cagcacaccc ccgcacgctg ggcaccaaca gagccacgga gcgcgagcac atgcccgccc 1860 ggggagcaca atggcgctgc acaaaacggc ctcccacacg tgcgtccagg ctcttgcgcc 1920 acctccttct cattctcttt tcagactttc atgtagtccc agctttgagc cagcagctgc 1980 cacttggggc tgcagcgctc tgttgaggga actgcccagg gctgggtaga ggcagcaagg 2040 ggacagggct gggtgctgtt t 2061 <210> 78 <211> 981 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 1571739CB1 <400> 78 gtagttccag aaaataggac tgaccaagaa gcagaaaagc aagatgaatg atgtgaagct 60 tgctgtcttg ggtggtgaag gaacaggcaa atctgccctt acagtgaggt ttcttactaa 120 gcgattcatt ggagaatatg cttctaattt tgaatctatc tataagaagc acttgtgttt 180 ggaaaggaaa caactaaatc tagaaatata tgacccttgt tctcaaacac agaaagcaaa 240 attctccctc acaagtgagc ttcactgggc agatgggttt gttattgtgt atgacatcag 300 tgataggtct tcatttgctt ttgcaaaagc gctgatctac agaatccggg agccacaaac 360 tagtcattgt aaaagagctg tggaatcagc agtgtttttg gttggcaaca aacgagatct 420 ttgtcatgtg cgagaggttg gctgggaaga agggcaaaag ctggcactgg aaaaccgatg 480 ccaattctgt gaactgtctg cagcagagca gtctctggag gtggaaatga tgtttatcag 540 aattatcaag gacatcctga taaacttcaa actcaaagaa aagagacgtc ccagtggatc 600 taaatcaatg gccaaattga tcaataatgt atttggaaag agaaggaaat ctgtttagta 660 gacaggtaat cctgggagat ttcctatatc agagagtttc aaacattcac atgataatta 720 aactaacctt tgtatgcaat ttttttttgg taaaaagaat tctcttggag atatgaaatg 780 attgagtatg aaccacagct gtgttttcaa atatgtagtt tgcctttttg gttgttgtac 840 cctgctcact ctccttcaca cagaaccttt catttattgt acaacatcac actcacccta 900 acctactggc ggacagcgat cccagtttgc cttgccaaat aaactctgtt tatgtgaatt 960 tattaaacga caaaaaaaaa a 981 <210> 79 <211> 1375 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 1739479CB1 <400> 79 aattctgtgc ttctccctct tgggccttca cacacttatg cttatgtaaa taattattaa 60 tcatattttc atgatggtgg agattcttat tcaccactac atcccatccc cagggcctgc 120 cacagaatag gcattcagta aatatttttt gaatgattga ctgagaaatc acacctctgt 180 ttcttttaaa cacatcctga tagctccata agtttcatca gggtcagtgg tttccattgt 240 cctgactgct ggccacagtg acctgttctg tgctttattt gacaagaccc ctgaatggtt 300 ggacagtgat tcctgccaaa agtgtgatca gcctttcttc tggaacttca agcaaatgtg 360 ggacagtaag aaaattggtc taagacagca ccactgccgc aagtgtggga aggccgtctg 420 tggcaagtgc agctccaagc gctcctccat ccccctgatg ggcttcgagt ttgaagtgag 480 ggtctgtgac agctgccacg aggccatcac agatgaagaa cgtgcaccca cagccacctt 540 ccatgacagt aaacataaca ttgtgcatgt gcatttcgat gcaaccagag gatggttact 600 gacttctgga actgacaagg ttattaagtt gtgggatatg accccagtcg tgtcttgatg 660 actctcccag gaatcagaaa gatagtattt actaaagaaa cggttgtttt aacccaaatc 720 attaccagag tggtaaagca gacatgtgag aagtaagaaa gaaactaaag accctgaatg 780 aatttgcaga ttacccatgt gcacagtggg gacctggcca gtgagcactc gcaaggggac 840 tcttccaact tgttcataca atataaaaga agctattttt ttaacaaatg gtttatacag 900 tctggctgtg ctgcattgtt ttgagtgtac cgaaaaatct gtgtggggtg tttaattttt 960 atacttttca acaccccatt ttatttgttg ctttgtcaga gaaataaggg aggtatctac 1020 tcagagtatt ttggtcatta tactttctgt gtttacttca acatgtgtca cgtggccagc 1080 ggctttttct tctcttccct ctgcacctac ctgcaccttc tctgcctttc ctggagggga 1140 tgtatttatg ttatttattc ccagtgtttc tgctttcatg tcctcctcag tggagagatt 1200 tggaaactca tcatgtggat tcaccagcca gctgctggaa ttgcctgaag agcgatttgt 1260 ttgtaatgtc tgcctcattc acgttcttat gaagtagaaa agactgtgtt tctgcctcag 1320 ttgcctctgt ctttcccaca ttaaaaaaaa aaatgctgtg agaaaaaaaa aaaaa 1375 <210> 80 <211> 2833 <212> DNA .
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 1999147CB1 <400> 80 cggttgggac gcacacactc tgcgtcatgg agggctgagg ccgatgatga attccggagt 60 gcctgtcagg cttgctgtgt cactcggccc gctcggcgcg ccccttccca gccgcccttc 120 cgtaccggct ctcgggctct tccggtctcc ggccgcccct tacctgcagg ctcttctccc 180 gccgcggccc ggcgctctcc gagtcgcccc tgcggactgg tctcgcacag tgcctgggca 240 ccgggcgcca gacagacact ggccatgacg agcggcgcaa ccaggtaccg gctgagctgc 300 tcgctccggg gccacgagct ggacgtacgg ggcctggtgt gctgcgccta tccgccggga 360 gcctttgtgt ccgtgtcccg agaccgcacc acccgcctct gggccccaga cagtccaaac 420 aggagcttta cagaaatgca ctgtatgagt ggccattcca attttgtatc ttgtgtatgc 480 atcataccct caagtgacat ctaccctcat ggcctaattg ccaccggtgg aaatgaccac 540 aatatatgca ttttctcact ggacagtcca atgccacttt atattctaaa aggccacaaa 600 aatactgttt gtagtctatc atctggaaaa tttgggacat tacttagtgg ttcatgggac 660 accactgcta aagtctggct gaatgacaag tgcatgatga ccttgcaggg tcatacagct 720 gcagtgtggg cggtaaagat cttacctgaa cagggcttaa tgttgactgg atcagcagac 780 aagactgtta aactgtggaa ggctggaaga tgtgagagga ctttttcagg gcatgaagac 840 tgtgtaagag gtttggcaat tttgagtgaa acagaatttc tttcctgtgc aaatgatgct 900 agtattagaa ggtggcaaat cactggcgag tgtcttgaag tatattatgg acatacaaat 960 tatatttata gcatatccgt ttttccaaat tgtagagact ttgtgacaac agcagaggac 1020 agatctctga gaatctggaa acatggggaa tgtgctcaaa ctatccgact tccagctcag 1080 tctatatggt gctgctgtgt gctcgacaat ggtgacattg tggttggtgc gagtgatggc 1140 attattagag tgtttacaga atcagaagat cgaacagcaa gtgctgaaga aatcaaggct 1200 tttgaaaaag aactgtctca cgcaaccatt gattctaaaa ctggcgattt aggggacatc 1260 aatgctgagc agcttcctgg gagggaacat cttaatgaac ctggtactag agaaggacag 1320 actcgtctaa tcagagatgg ggagaaagtc gaagcctatc agtggagtgt tagtgaaggg 1380 aggtggataa aaattggtga tgttgttggc tcatctggtg ctaatcagca aacatctgga 1440 aaagttttat atgaagggaa agaatttgat tatgttttct caattgatgt caatgaaggt 1500 ggaccatcat ataaattgcc atataatacc agtgatgacc cttggttaac tgcatacaac 1560 ttcttacaga agaatgattt gaatcctatg tttctggatc aagtagctaa atttattatt 1620 gataacacaa aaggtcaaat gttgggactt gggaatccca gcttttcaga tccatttaca 1680 ggtggtggtc ggtatgttcc gggctcttcg ggatcttcta acacactacc cacagcagat 1740 ccttttacag gtgctggtcg ttatgtacca ggttctgcaa gtatgggaac taccatggcc 1800 ggagttgatc catttacagg gaatagtgcc taccgatcag ctgcatctaa aacaatgaat 1860 atttatttcc ctaaaaaaga ggctgtcaca tttgaccaag caaaccctac acaaatatta 1920 ggtaaactga aggaacttaa tggaactgca cctgaagaga agaagttaac tgaggatgac 1980 ttgatacttc ttgagaagat actgtctcta atatgtaata gttcttcaga aaaacccaca 2040 gtccagcaac ttcagatttt gtggaaagct attaactgtc ctgaagatat tgtctttcct 2100 gcacttgaca ttcttcggtt gtcaattaaa caccccagtg tgaatgagaa cttctgcaat 2160 gaaaaggaag gggctcagtt cagcagtcat cttatcaatc ttctgaaccc taaaggaaag 2220 ccagcaaacc agctgcttgc tctcaggact ttttgcaatt gttttgttgg ccaggcagga 2280 caaaaactca tgatgtccca gagggaatca ctgatgtccc atgcaataga actgaaatca 2340 gggagcaata agaacattca cattgctctg gctacattgg ccctgaacta ttctgtttgt 2400 tttcataaag accataacat tgaagggaaa gcccaatgtt tgtcactaat tagcacaatc 2460 ttggaagtag tacaagacct agaagccact tttagacttc ttgtggctct tggaacactt 2520 atcagtgatg attcaaatgc tgtacaatta gccaagtctt taggtgttga ttctcaaata 2580 aaaaagtatt cctcagtatc agaaccagct aaagtaagtg aatgctgtag atttatccta 2640 aatttgctgt agcagtgggg aagagggacg gatattttta attgattagt gtttttttcc 2700 tcacatttga catgactgat aacagataat taaaaaaaga gaatacggtg gattaagtaa 2760 aattttacat cttgtaaagt ggtggggagg ggaaacagaa ataaaatttt tgcactgctg 2820 aaaaaaaaaa aaa 2833 <210> 81 <211> 1752.
<212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 2182085CB1 <400> 81 gcaggcagcc atcttgcctg gagcctgaga aagggaggag agacagaagg aaccggcgac 60 agtggtctca gggccgctcc ggggggcctc aagaaccgga ggcagccccg gaggctgccg 120 cgggcggaca cgccagagga ggaggccggg gaatggccgc ggtgtggcag caagtcttag 180 cagtggacgc gaggtacaac gcgtaccgca caccaacgtt tccacagttt cggacgcagt 240 atatccgccg gcgcagcagc tgctgcggga gaatgccaag gctgggcacc ccccagcgct 300 gcgtcggcag tacctgaggc ttcgggggca gctgctgggc cagcgctacg ggcccctctc 360 cgagccaggc agtgctcgtg cctatagcaa cagcatcgtc cgcagtagcc gcactactct 420 tgaccgcatg gaggactttg aggatgatcc tcgggccctg ggggcccgtg ggcaccgtcg 480 ttctgtcagc agaggctcct accagctgca ggcgcagatg aaccgtgccg tctatgagga 540 caggccccct ggcagcgtgg tgcccacgtc agcagcagag gcaagtcggg ccatggccgg 600 ggacacgtca ctgagcgaga actatgcctt tgcgggcatg tatcatgttt ttgaccagca 660 cgtggatgag gcagtcccaa gggtgcgctt cgccaatgat gaccgacacc gcctggcctg 720 ctgctcactc gacggcagca tctccctgtg ccagctggtg cctgccccac ccacagtgct 780 tcgcgtgcta cggggccaca cccgtggtgt ctccgacttc gcctggtccc tctccaatga 840 catcctcgtg tccacctcac tggatgccac catgcgcatc tgggcctctg aggatggtcg 900 ctgcatccga gagatccctg accccgatag cgctgaactg ctctgctgca ccttccagcc 960 tgtcaacaac aacctcactg tggtggggaa cgccaagcac aacgtgcatg tcatgaacat 1020 ctccacaggc aagaaagtga aggggggctc cagcaagctg acaggccgtg tccttgctct 1080 gtcctttgat gcccctggcc ggctgctctg ggcgggtgat gaccgtggca gtgtcttctc 1140 tttcctcttt gatatggcca cagggaagct gaccaaagcc aagcgtttgg tggtgcatga 1200 ggggagccct gtgaccagca tctcagcccg gtcctgggtc agccgcgagg cccgggatcc 1260 ctcactgctc atcaatgctt gcctcaacaa gttgctgctc tacagggtgg tagacaacga 1320 ggggaccctg cagctgaaga gaagcttccc catcgagcag agctcacatc ctgtgcgcag 1380 catcttctgt cccctcatgt ccttccgcca gggggcctgc gtggtgacgg gcagtgagga 1440 catgtgcgtg cacttctttg atgtggagcg ggcggccaag gctgctgtca acaagctgca 1500 gggccacagt gcacctgtgc ttgatgtcag cttcaactgc gacgagagcc tactggcctc 1560 cagtgacgcc agcggcatgg tcatcgtctg gaggcgggag cagaagtagg gtcctgtcgg 1620 ccctgctgct gtcctccatc ccacccctct tactccagcc tcgtgttgta aataaagttt 1680 cggtggtcat gctgagggcc ggctcccagc tctgccgggg acggacaggg cagagggcag 1740 cgggcagctg ca 1752 <210> 82 <211> 1854 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 2216640CB1 <400> 82 cccacgcgtc cgcgcaggat ggcggcagca gtggcggacg aggcggtggc gcgcgatgtg 60 cagcggttgc tagtgcagtt ccaggatgag ggcgggcagc tgctgggttc cccgttcgac 120 gtgcccgtgg acatcacccc ggacaggctg cagctcgtgt gcaacgcgct actggcccag 180 gaggatcccc tgccactggc tttctttgtc cacgatgctg agatcgtctc ctcactgggg 240 aagacgttgg agtcccaggc agtggagaca gagaaggtcc tagacatcat ctaccagcca 300 caggctatct tcagagtccg ggctgtgact cgctgcacca gctccttgga gggtcacagt 360 gaggcagtca tttctgtggc cttcagccct acgggaaagt acctggccag tggctctgga 420 gacaccaccg tgcgcttctg ggatctcagc acagagacac cacatttcac atgcaaggga 480 cacagacact gggtccttag tatatcctgg tctccagatg gcaagaagct ggcctcaggc 540 tgcaagaatg gccagattct cctctgggac ccaagcacag ggaagcaggt gggcaggacc 600 ctcgctggcc acagcaagtg gatcacaggc ctgagctggg agcccctcca tgcgaaccct 660 gagtgccgct atgtggccag cagctccaag gatggcagtg tgcggatctg ggacacaact 720 gcaggccgct gtgagcgcat cctcaccggg cacacccagt cggtcacctg tctccggtgg 780 ggaggggacg ggcttctcta ctctgcctcc caggaccgca ccatcaaagt ctggagagct 840 catgacggtg tgctgtgccg gactctgcaa ggccacggcc actgggtgaa caccatggcc 900 ctcagcactg actatgccct gcgcactggg gcctttgaac ctgctgaggc ctcagttaat 960 ccccaagacc tccaaggatc cttgcaggag ttgaaggaga gggctctgag ccgatacaac 1020 ctcgtgcggg gccagggtcc agagaggctg gtgtctggct ccgacgactt caccttattc 1080 ctgtggtccc cagcagagga caaaaagcct ctcactcgga tgacaggaca ccaagctctc 1140 atcaaccagg tgctcttctc tcctgactcc cgcatcgtgg ctagtgcctc ctttgacaag 1200 tccatcaagc tgtgggatgg caggacgggc aagtacctgg cttccctacg cggccacgtg 1260 gctgccgtgt accagattgc gtggtcagct gacagtcggc tcctggtcag cggcagcagt 1320 gacagcacac tgaaggtgtg ggatgtgaag gcccagaagc tggccatgga cctgcccggc 1380 cacgcggatg aggtatatgc tgttgactgg agtccagatg gccagagagt ggcaagtggt 1440 gggaaggaca aatgcctccg gatatggagg agatgagacg gcccgaagtt ctctctgacc 1500 cccacctcga ctcggcctct gccagctgcc ttccctgcca gagaacaaag gctgagatgg 1560 cagtgcacac accctcccca ccagtgggga cctgagaatg cgtgtggcct gctgtcctcg 1620 atagaccgga atggggtttt cccacagatc cccgcctgtg gcacacccca gagccagaaa 1680 tcgaaggtca caggaagttg tcactgaact tggcccgtgt ctgctactct gtaccttgct 1740 ggtacagaca ggggtggtgg gcagccaggc tctatgagtg ggcccctagt gtcagctctg 1800 tacagggtca gatcccaggt tctatgacca aataagtaac ttaaaaaaaa aaaa 1854 <210> 83 <211> 862 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 2417361CB1 <400> 83 ggcgtggctt caacagactt tcttttgcct gtctttgtcc cagagcctct tccctggccc 60 tgctgagacc actgctctaa gaagagacca ccagactgag agaggactcc cagctgccct 120 cagagcggag gccgagtgct gcacagccac agctgctctg aagcccttcc atgaatcccc 180 ggaagaaggt ggacctgaaa ctcattatcg tcggagccat tggtgtggga aagacctccc 240 tccttcacca atatgtgcac aagacgtttt atgaggaata ccagaccaca ctgggggcca 300 gcatcctctc caagattatc atattgggtg acacaacttt gaagttacag atctgggaca 360 cgggcggtca ggagcggttc cgctccatgg tgtccacgtt ctacaagggc tccgatggct 420 gcatcctagc ttttgatgtc accgacctgg agtcttttga agccctggat atctggcggg 480 gtgatgtcct ggccaagatt gtccccatgg agcagtccta ccccatggtg ttgttgggga 540 acaagatcga tctggcagac cggaaggtac cccaggaagt agctcaaggc tggtgtagag 600 agaaagatat tccttacttt gaagtcagtg ccaagaatga catcaatgtg gtgcaagcgt 660 ttgagatgct ggccagtagg gctctgtcga ggtaccagag catcttagaa aatcacctca 720 cagaatccat caagctctcg ccagaccagt caaggagcag atgctgctga cctccagacg 780 cctgctctgg aagcccagaa acagagcctg ccccgagcct ggtcacccca ggcttgagaa 840 caggtgacca tccccctcca gc 862 <210> 84 <211> 1406 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 2454384CB1 <400> 84 ctagagcctg gggtctcggc aacttccggc ggcgggagct gcagagcgca aggcccgccc 60 actgcgcgtg cgcttcggcc cggctcctcc tgcgcccccg gcccctgcga ctgggacttg 120 gtacggccgg gcggttggcg tcctctgcgg ctcctgccag gggcgggctt ttcaaatctt 180 ccctttgaag gagtggcgac ggcccggaca gttcgcgttg gagatggagg ggccgagcct 240 gaggggtcct gcgctccgcc tggcggggct tcccacccag caggactgca acattcaaga 300 aaaaatagac ttagaaattc gaatgcgaga aggaatatgg aaactccttt ctctgagcac 360 tcagaaagat caagttttac atgcagttaa gaatctcatg gtgtgcaatg ctcgactaat 420 ggcctataca tcggagctac agaaattaga agaacagatt gcaaatcaga ctggaagatg 480 tgatgtgaaa tttgaaagta aagaacgaac agcatgtaaa ggaaagattg ccatatcaga 540 tattcgaata ccactaatgt ggaaagactc tgatcacttc agcaataaag aacgatcacg 600 acgctatgcc attttttgtt tattcaaaat gggagctaat gtgtttgata ctgatgtggt 660 gaatgtggat aaaacaatca cagatatatg ttttgaaaat gtaaccatat tgtaagtatt 720 ttttaatctt cagagaataa aaataattta aaattcttct tttttaaaag aaagttctta 780 ttattggttc tttggattca ttttatgttt aaatgtttaa gtgatcttta aatgtttaat 840 atgattttaa aaattatttt gttcagaaga agtccatttc tctatctgca gttttctgat 900 gtgaaataaa aatggaaatc ttgtaattac tattagcagt aaatatttga cttattagat 960 atgacccatt tttaaattgt taataaatat agttcagtta ttaacaaagc tatgcataca 1020 acagaatatc ctgtaatgtt atttgatata gagagaattt aagcataaaa caggattttt 1080 atctcatgta ggatatttgg ttgcagaaat actaaaatag tatagcgact ttatttacaa 1140 gatagtcctg aagtacatgc tatataggaa gagcactttg aaattttggg gtgttctttt 1200 tcttatggtg cacttctttc atgtacttca aagcaataaa aaaaaatggg tgatctcagg 1260 gctgttttta ttgtccctgc tcttttacag gctcatttta ttgtggtcat aatacagaac 1320 aagaaggaac tccttgggta gccatagaaa tcatttttaa cttacatagt ttttcctgcc 1380 ctccttcaaa ggttctatgt gcctaa 1406 <210> 85 <211> 1184 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 2610262CB1 <400> 85 gcggttttgg tgcctgaagc agggagcgcg gagtcgttcc cgagagaggc ggccaggcta 60 tgctcgccgg tttccggcgt tccgctccgg ccagccagag tctctgtctc aacctgtgtc 120 cgtgctccag cagtctcctc agcccggccc cgcggcgcgg ttggcggcgg cgccccaggc 180 gcgccccctc ctccgatggc ggcggagatc cagcccaagc ctctgacccg caagccgatc 240 ctgctgcagc ggatggaggg gtcccaggag gtggtgaata tggccgtgat cgtgcccaaa 300 gaggagggcg tcatcagcgt ctccgaggac aggacagttc gtgtttggtt aaagagagac 360 agtggacagt attggccaag cgtataccat gcaatgcctt ctccatgttc atgcatgtct 420 tttaacccgg aaacaagaag actgtccata ggtctagaca atggtacaat ctcagagttt 480 atattgtcag aagattataa caagatgact cctgtgaaaa actatcaagc gcatcagagc 540 agagtgacga tgatcctgtt tgtcctggag ctggagtggg tgctgagcac aggacaggac 600 aagcaatttg cctggcactg ctctgagagt gggcagcgcc tgggaggtta tcggaccagt 660 gctgtggcct caggcctgca atttgatgtt gaaacccggc atgtgtttat cggtgaccac 720 tcaggccaag taacaatcct caaactggag caagaaaact gcaccctggt cacaacattc 780 agaggacaca caggtggggt gaccgctctc tgttgggacc cagtccagcg ggtgttgttc 840 g~/11$

tcaggcagtt cagatcactc tgtcatcatg tgggacatcg gtgggagaaa aggaacagcc 900 atcgagctcc aaggacacaa cgacagagtc caggccctct cctatgcaca gcacacgcga 960 caattgatct cctgtggcgg tgatggtggg attgtcgtct ggaacatgga cgtggagagg 1020 caggagcctc tgtggagctg cttcgtggtt atgataagtg ctgtgtgatg ctcaccttgg 1080 gaggtctgcg acatatattg aagtcatctc taacctgaag tactgacaga ctttctggaa 1140 gaaaaggctt gtaggaggaa acttcagaat tctattaaat ggtg 1184 <210> 86 <211> 2965 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 2700075CB1 <400> 86 ggcaccactg tgaaggtctg ggacgcagcc aagcagcagc ccctgacaga gctggcagcc 60 catggggacc tggtgcagag cgccgtctgg agccgagatg gagccctggt gggcacggcg 120 tgcaaggaca agcagctgcg gatctttgac cccagaacaa agccgcgggc ctctcagagc 180 acgcaggccc atgagaacag cagggatagc cggctggcat ggatgggcac ctgggagcac 240 cttgtgtcta ctggattcaa ccagatgcgt gagcgcgaag tgaagctgtg ggacacgcgg 300 ttcttctcca gcgccctggc ctccctcacc ttggacacct cgcttgggtg tctcgtgcct 360 ctgctggacc ctgactctgg gctcctggtc ctggcaggaa agggcgagag gcagctgtac 420 tgttacgagg tggtcccgca gcagccggcg ctgagcccag tgacccagtg tgtcctggag 480 agcgtgctgc gtggggctgc ccttgtgccc cggcaggcgc tggccgtcat gagctgcgag 540 gtactccgcg tcctacagct gagcgacaca gccatcgtgc ccatcggcta ccatgtgccc 600 cgcaaggctg tggagttcca cgaggacctg ttcccggaca ctgccggctg tgtgcctgcc 660 accgaccccc atagctggtg ggctggggac aaccagcagg tgcagaaggt cagcctcaac 720 cccgcctgcc ggccccaccc gagcttcact tcctgtctgg tgccccctgc ggagcccctc 780 cctgacacag cccagcctgc ggtgatggag acacccgtgg gtgatgcaga cgcaagcgag 840 ggtttctctt cccctcccag ttcgctgacc tcgccctcca cgccctccag cctggggccc 900 tcactctcca gcaccagtgg catcgggacc agccccagtt tgaggtcgct gcagagcctg 960 ctgggcccca gttccaagtt ccgccatgct cagggcactg tcctgcaccg agacagccac 1020 atcaccaacc tcaaggggct caacctcacc acacctggtg agagtgacgg cttctgtgcc 1080 aacaagctgc gtgtggccgt gccgctgctc agcagcgggg gacaggtggc tgtgcttgag 1140 ctacggaagc ctggccgcct gcccgacacg gcactgccca cgctgcagaa tggggcagct 1200 gtgactgatc tggcctggga cccctttgac ccccatcgcc tcgctgtggc tggtgaggac 1260 gccaggatcc gactgtggcg ggtacccgca gagggcctgg aagaggtgct caccacgcca 1320 gagactgtgc tcacaggcca cacggagaag atctgctccc tgcgcttcca cccactggca 1380 gccaatgtgc tggcctcgtc ctcctatgac ctcactgttc gcatctggga ccttcaggct 1440 ggagctgatc ggctgaagct gcagggccac caagaccaga tcttcagcct ggcctggagt 1500 cctgatgggc agcagctggc cactgtctgc aaggatgggc gtgtgcgggt ctacaggccc 1560 cggagtggcc ctgagcccct gcaggaaggc ccagggccca agggaggacg cggagctcgc 1620 attgtctggg tatgtgatgg tcgctgtctg ctggtgtctg gctttgacag ccaaagtgag 1680 cgccagctgc tcctatatga agctgaggcc ctggccggcg gacccttggc agtgttgggc 1740 ctggacgtgg ctccctcaac cctgctgccc agctacgacc cagacactgg cctggtgctc 1800 ctgaccggca agggcgacac ccgtgtattc ctgtacgagc tgctccccga gtcccctttc 1860 ttcctggagt gcaacagctt cacgtcgcct gacccccaca agggcctcgt cctcctgcct 1920 aagacggagt gcgacgtgcg ggaagtggag ctgatgcggt gcctgcggct gcgtcagtcc 1980 tccctggagc ctgtggcctt ccggctgccc cgagtccgga aagagttctt ccaggatgac 2040 gtgttcccag acacggctgt gatctgggag cctgtgctca gtgccgaggc ctggctgcaa 2100 ggcgctaatg ggcagccctg gcttctcagc ctgcagcctc ctgacatgag cccagtgagc 2160 caagcccccc gagaggcccc tgctcgtcgg gccccatcct cagcgcagta cctggaagaa 2220 aagtctgacc agcaaaagaa ggaggagctg ctgaatgcca tggtggcaaa actggggaac 2280 cgggaggacc cactccccca ggactccttt gaaggcgtgg acgaggacga gtgggactag 2340 CCtgCgCCCC cgtcacctcc acctcacctg tgctgccact tcctagtgca cacctcacgg 2400 ctcatcctca agctggaaga tacctctctg gccccggcac atgtcacccc tgcactcctg 2460 ccttcccgtg ggcacttcca catcctctgg gcctctggca gttcccaggg actgttttca 2520 cctctgctgt ctctggggtc agctgctgct catcagctgc ccgctagcat gtggccaggg 2580 gtgcagggtg gcggggggtc agcagcatgt ccctgggcag gccctgggca ccctgtctcc 2640 cctggtctca ctgctgacct gggctggtcc cagcctggat tggcctcatc caggatcttt 2700 ggtcacccca cgctgcccca tcttgcctgc tgttccagtt ctggtcaagg gccttggggg 2760 ctggcccccc accaggcctt ctagagcagc accagtctca gggccctggg accagctgcc 2820 ctacttccca ggtttgtagc caggagaagg gggcatcaca gagctgatgg tccaataagg 2880 ggggtgtgag ccccgcaggg actggcccgc acctgccttg gatgttttca gcaattaaac 2940 ttttttaagc tggcaaaaaa aaaaa 2965 <210> 87 <211> 2823 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 2786701CB1 <400> 87 cggaggcagc ctagcctcgc gccccgcccg ttgcttctgc cctccggcct tcccgccgcc 60 gtcgccggga ccagccgctc ggggccgggc tgatacagcc gcttcaccgt gcccctgccc 120 gcgaccatgg cctcctccga ggtggcgcgg cacctgctct ttcagtctca catggcaacg 180 aaaacaactt gtatgtcttc acaaggatca gatgatgaac agataaaaag agaaaacatt 240 cgttcgttga ctatgtctgg ccatgttggt tttgagagtt tgcctgatca gctggtgaac 300 agatccattc agcaaggttt ctgctttaat attctctgtg tgggggaaac tggaattgga 360 aaatcaacac tgattgacac attgtttaat actaattttg aagactatga atcctcacat 420 ttttgcccaa atgttaaact taaagctcag acatatgaac tccaggaaag taatgttcaa 480 ttgaaattga ccattgtgaa tacagtggga tttggtgacc aaataaataa agaagagagc 540 taccaaccaa tagttgacta catagatgct cagtttgagg cctatctcca agaagaactg 600 aagattaagc gttctctctt tacctaccat gattctcgca tccatgtgtg tctctacttc 660 atttcaccga caggccactc tctgaagaca cttgatctct taaccatgaa gaaccttgac 720 agcaaggtaa acattatacc agtgattgcc aaagcagata cggtttctaa aactgaatta 780 cagaagttta agatcaagct catgagtgaa ttggtcagca atggcgtcca gatataccag 840 ttcccaacgg atgatgacac tattgctaag gtcaacgctg caatgaatgg acagttgccg 900 tttgctgttg tgggaagtat ggatgaggta aaagtcggaa acaagatggt caaagctcgc 960 cagtaccctt ggggtgttgt acaagtggaa aatgaaaacc actgtgactt tgtaaagctg 1020 cgggaaatgc tcatttgtac aaatatggag gacctgcgag agcagaccca taccaggcac 1080 tatgagcttt acaggcgctg caaactggag gaaatgggct ttacagatgt gggcccagaa 1140 aacaagccag tcagtgttca agagacctat gaagccaaaa gacatgagtt ccatggtgaa 1200 cgtcagagga aggaagaaga aatgaaacag atgtttgtgc agcgagtaaa ggagaaagaa 1260 gccatattga aagaagctga gagagagcta caggccaaat ttgagcacct taagagactt 1320 caccaagaag agagaatgaa gcttgaagaa aagagaagac ttttggaaga agaaataatt 1380 gctttctcta aaaagaaagc tacctccgag atatttcaca gccagtcctt tctggcaaca 1440 ggcagcaacc tgaggaagga caaggaccgt aagaactcca attttttgta aaacagaagt 1500 tccagagcac agaaggtcat catcacaagc aaactttatt aaaaaaaaac tagaagtgtg 1560 ctttgatttt gctgttattt gttttatcac ttctatattt ggtgaacagc cacagttact 1620 gatatttatg gaaaagtact ttcaagtaca aggtcaatac ataagccaga gtgaatgata 1680 ctacaagttg agcatctcta attcaaaaat ctgaaatcca gaagcttcaa aatctgaatc 1740 tttttgagca ctgacttgac cccacaagtg gaaaattccc cacccgacac ctttgctttc 1800 tgatggttca gtttaaacag attttgtttc ttgcacaaaa tttttgtata aattactttc 1860 aggctatatg tataaggtgg atgtgaaaca tgaattatgt aattagagtc gggtcccgtt 1920 gtgtatatgc agatattcca aacctgaaat ccaaaacact tctggtccct agcattttgg 1980 ataagggata ctcagcttgt acctatatat tcatatatat tcactgttgt tagaaatgtt 2040 taagttgctg ttctgtgatg aatctaaatc ttttctcttg ctaccaagct attgtcactg 2100 cagtgcatta taccaaagag cgaagtcagt gccactgaaa atacagaacc cattaatatc 2160 gtggctatct gattacattt atattccaag atgaaccttt tttatatatg ctaaaaattt 2220 tggggaatat gttttgggat gtattatgga gctaaaactc taacctctta atagttttat 2280 agaacttaaa aattttttat acaattaccc aattggtgat atgatcttaa gcttttgtgt 2340 cagattattt aatatgatga cttcatgctt tattatgcct tattatggct gacgtattac 2400 tgtggtgaaa caaaatatct ttaaaagtta aaacatccag atatataagc tattttttcc 2460 taaggataaa gtacctttga gcatgagtgt atcacagctt tcattaggaa aacttttcat 2520 tacatacttg tttaaactct gtcttccagg gtaaaaataa taaggttgaa tcattttatt 2580 aaaaatactt tttaagaaaa taactatgaa catctgaata ttaaagatat aaaaatgcac 2640 ataattcata tttcaggtgg tatttgcatt cagtgcctta ctggtattct cagaacattt 2700 taatgatttc taacatttct taacagtcat agatatatac attttcattt tttgtacttg 27'00 aatattctaa ataaaactga catttactct tgacaaataa aacatatatt tactaaaaaa 2820 aaa 2823 <210> 88 <211> 1549 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 3068538CB1 <400> 88 gcagacccgg cacgcaggtg ggggccggcg gggtccgtgg ccagagctgc agagagacaa 60 ggcggcggcg gctgctgtgc tgggtgcagt gaggaagagg ccctcggtgg tgcccatggc 120 tggccaggat cctgcgctga gcacgagtca cccgttctac gacgtggcca gacatggcat 180 tctgcaggtg gcaggggatg accgctttgg aagacgtgtt gtcacgttca gctgctgccg 240 gatgccaccc tcccacgagc tggaccacca gcggctgctg gagtatttga agtacacact 300 ggaccaatac gttgagaacg attataccat cgtctatttc cactacgggc tgaacagccg 360 gaacaagcct tccctgggct ggctccagag cgcatacaag gagttcgata ggaagtacaa 420 gaagaacttg aaggccctct acgtggtgca ccccaccagc ttcatcaagg tcctgtggaa 480 catcttgaag cccctcatca gtcacaagtt tgggaagaaa gtcatctatt tcaactacct 540 gagtgagctc cacgaacacc ttaaatacga ccagctggtc atccctcccg aagttttgcg 600 gtacgatgag aagctccaga gcctgcacga gggccggacg ccgcctccca ccaagacacc 660 tccgccgcgg cccccgctgc ccacacagca gtttggcgtc agtctgcaat acctcaaaga 720 caaaaatcaa ggcgaactca tcccccctgt gctgaggttc acagtgacgt acctgagaga 780 gaaaggcctg cgcaccgagg gcctgttccg gagatccgcc agcgtgcaga ccgtccgcga 840 gatccagagg ctctacaacc aagggaagcc cgtgaacttt gacgactacg gggacattca 900 catccctgcc gtgatcctga agaccttcct gcgagagctg ccccagccgc ttctgacctt 960 ccaggcctac gagcagattc tcgggatcac ctgtgtggag agcagcctgc gtgtcactgg 1020 ctgccgccag atcttacgga gcctcccaga gcacaactac gtcgtcctcc gctacctcat 1080 gggcttcctg catgcggtgt cccgggagag catcttcaac aaaatgaaca gctctaacct 1140 ggcctgtgtc ttcgggctga atttgatctg gccatcccag ggggtctcct ccctgagtgc 1200 ccttgtgccc ctgaacatgt tcactgaact gctgatcgag tactatgaaa agatcttcag 1260 caccccggag gcacctgggg agcacggcct ggcaccatgg gaacagggga gcagggcagc 1320 ccctttgcag gaggctgtgc cacggacaca agccacgggc ctcaccaagc ctaccctacc 1380 tccgagtccc ctgatggcag ccagaagacg tctctagtgt tgcgaacact ctgtatattt 1440 cgagctacct cccacacctg tctgtgcact tgtatgtttt ataaacttgg catctgtaaa 1500 aataaccagc cattagatga attcagaacc ttctaatgaa aaaaaaaaa 1549 <210> 89 <211> 1722 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 5159072CB1 <400> 89 gcaagaggga gccggcccga cgcggaccgc ttccctgcag tgccccgagt cccgggcccg 60 cgccgccgcc gcccggctcc gctcgcggcc cctctgtctg caggcgtgcc ccggcggcgg 120 cggagagccg tcctcggccg aggaggctgg gaaacgcgag cgcaggcggc agagaggcct 180 caacgccgtc cctttcgcca ccgccttttc cttgcctcgc gccgctgtgc atttctctcc 240 ttttcctttg tttttttggc ccctcgcggg tgtgggcatt gttggttagc aaaagtgcag 300 cctcaagatg gctgatggca acgaggatct gcgggctgac gacttgcctg ggccagcctt 360 cgagagctat gagtccatgg agcttgcctg ccccgctgag cgcagcggcc acgtagccgt 420 cagcgacggg cgccacatgt tcgtctgggg cggctacaag agtaatcaag tcagaggatt 480 atatgacttt tatctgccta gagaagaact atggatctac aacatggaga ctggaagatg 540 gaaaaaaatc aacactgaag gtgatgttcc tccttctatg tcaggaagct gtgctgtgtg 600 tgtagacagg gtgctgtact tgtttggagg acaccattca agaggcaata ccaataagtt 660 ctacatgctg gattcaaggt ctacagacag agtgttacag tgggaaagaa ttgattgcca 720 aggaattcct ccatcatcaa aggacaaact tggtgtctgg gtatataaaa acaagttaat 780 attttttgga gggtatggat atttgcctga agataaagta ttgggaactt ttgaattcga 840 tgaaacatct ttttggaatt caagtcatcc aagaggatgg aatgatcatg tacatatttt 900 agatactgaa acatttacct ggagccagcc tataactact ggtaaagcac cttcacctcg 960 tgctgcccat gcctgtgcaa ctgtcggaaa tagaggcttc gtgtttggag gcagatatcg 1020 agatgctaga atgaatgatc ttcactatct taatctggat acatgggagt ggaatgaatt 1080 aattccacaa ggcatatgcc cagttggtcg atcttggcac tcactaacac cagtttcttc 1140 agatcatctt tttctctttg gaggatttac cactgataaa cagccactaa gtgatgcctg 1200 gacttactgc atcagtaaaa atgaatggat acaatttaat catccatata ccgaaaaacc 1260 aaggttatgg cacacagctt gtgccagcga tgaaggagaa gtaattgttt ttggtggatg 1320 tgccaacaac ttgcttgtcc atcacagagc tgcacacagt aatgaaatac taatattttc 1380 agttcaacca aaatctcttg tacggctaag cttagaagca gtcatttgct ttaaagaaat 1440 gttagccaac tcatggaact gccttccaaa acacttactt cacagtgtta atcagaggtt 1500 tggtagtaac aacacttctg gatcttaagg cttcataaat aatgcctatg atcaccttgc 1560 atggacagca atcctgtaaa catcacagag tggcatcatt tgtataatta tatgcattgt 1620 tgtagtttgc acctgttggt tttaatgtgc atgtgaatgg cctagagaac ctatttttgt 1680 gtctaaagtt tacaataaat gtatttaaca ccaaaaaaaa as 1722 <210> 90 <211> 1264 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 5519057CB1 <400> 90 agcgcgcgct cttgcggtgg cgtaatctct cagcctttct gtgtctcctt tcctccgcct 60 cagtttggtg cgggtcgggg gaatggctga ggagatggag tcgtcgctcg aggcaagctt 120 ttcgtccagc ggggcagtgt caggggcctc agggtttttg cctcctgccc gctcccgcat 180 cttcaagata atcgtgatcg gcgactccaa tgtgggcaag acatgcctga cctaccgctt 240 ctgcgctggc cgcttccccg accgcaccga ggccacgata ggggtggatt tccgagaacg 300 agcggtggag attgatgggg agcgcatcaa gatccagcta tgggacacag caggacaaga 360 acgattcaga aagagcatgg ttcagcacta ctacagaaat gtacatgctg ttgtcttcgt 420 gtatgatatg accaacatgg ctagttttca tagcctacca tcttggatag aagaatgcaa 480 acaacatttg ctagccaatg atataccacg gattcttgtt ggaaataaat gtgacttgag 540 aagtgccata caggtaccca cagacttggc acaaaaattt gctgacacac acagtatgcc 600 tttgtttgaa acgtctgcta aaaaccccaa tgataatgac catgtggaag ctatatttat 660 gaccttggct cataagctta agtgccacaa accattaatg cttagtcagc cccctgataa 720 tggaattatc ctgaagcctg aaccaaagcc tgcaatgacg tgctggtgct aaataacagt 780 ctttattata ttatctaatt ttgactaaag aaatactttt gaagtatgac agtattaagt 840 cataagattt aatctcaact ataatgggtc atcttgacac tttgctgttt gtcattgtca 900 cgcttttgta ttttgtatct acttaagttt gtcactgtga caacacagga aaagttggtt 960 ttcaggtgag attgaaaatg aagcaaagat aggatgaatc tgaacatctc tccatctaga 1020 gcccaatgaa ggaagcttca aatgagaaca tgatggaatc agtaaccatt caatcttttg 1080 tcctaggatt ggaaaaaaat gttaaaggtt taggacacac ctaatagtat gtcctttgaa 1140 tgggaagttt tcttaatagg ataaaaactg gtatttcctt ctccccagag tacttttttg 1200 ttttttccat agagacgggg tcttgctatg ttgtccaggc tggccttgag ctcctgggct 1260 caag 1264 <210> 91 <211> 2640 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 035379CB1 <400> 91 cggccgaggg ggcatcatga agcgggctgg cggcgctgcg tcccgggcgc gcgcgggcgg 60 gaggtgcttc ccaaggaccg tagatgcctc tctagagcat gagctcaggc aagagtgccc 120 gctacaaccg cttctccggg gggcccagca atcttcccac cccagacgtc accacaggga 180 ccagaatgga aacgaccttc ggacccgcct tttcagccgt caccaccatc acaaaagctg 240 acgggaccag cacctacaag cagcactgca ggacaccctc ctcctccagc acccttgcct 300 actccccgcg ggacgaggag gacagcatgc cccccatcag cactccccgc cgctccgact 360 ccgccatctc tgtccgctcc ctgcactcag agtccagcat gtctctgcgc tccacattct 420 cactgcccga ggaggaggag gagccggagc cactggtgtt tgcggagcag ccctcggtga 480 agctgtgctg tcagctctgc tgcagcgtct tcaaagaccc cgtgatcacc acgtgtgggc 540 acacgttctg taggagatgc gccttgaagt cagagaagtg tcccgtggac aacgtcaaac 600 tgaccgtggt ggtgaacaac atcgcggtgg ccgagcagat cggggagctc ttcatccact 660 gccggcacgg ctgccgggta gcgggcagcg ggaagccccc catctttgag gtggaccccc 720 gagggtgccc cttcaccatc aagctcagcg cccggaagga ccacgagggc agctgtgact 780 acaggcctgt gcggtgtccc aacaacccca gctgcccccc gctgctcagg atgaacctgg 840 aggcccacct caaggagtgc gagcacatca aatgccccca ctccaagtac gggtgcacgt 900 tcatcgggaa ccaggacact tacgagaccc acctggagac ttgccgcttc gagggcctga 960 aggagtttct gcagcagacg gatgaccgct tccacgagat gcacgtggct ctggcccaga 1020 aggaccagga gatcgccttc ctgcgctcca tgctgggaaa gctctcggag aagatcgacc 1080 agctagagaa gagcctggag ctcaagtttg acgtcctgga cgaaaaccag agcaagctca 1140 gcgaggacct catggagttc cggcgggacg catccatgtt aaatgacgag ctgtcccaca 1200 tcaacgcgcg gctgaacatg ggcatcctag gctcctacga ccctcagcag atcttcaagt 1260 gcaaagggac ctttgtgggc caccagggcc ctgtgtggtg tctctgcgtc tactccatgg 1320 gtgacctgct cttcagtggc tcctctgaca agaccatcaa ggtgtgggac acatgtacca 1380 cctacaagtg tcagaagaca ctggagggcc atgatggcat cgtgctggct ctctgcatcc 1440 aggggtgcaa actctacagc ggctctgcag actgcaccat cattgtgtgg gacatccaga 1500 acctgcagaa ggtgaacacc atccgggccc atgacaaccc ggtgtgcacg ctggtctcct 1560 cacacaacgt gctcttcagc ggctccctga aggccatcaa ggtctgggac atcgtgggca 1620 ctgagctgaa gttgaagaag gagctcacag gcctcaacca ctgggtgcgg gccctggtgg 1680 ctgcccagag ctacctgtac agcggctcct accagacaat caagatctgg gacatccgaa 1740 cccttgactg catccacgtc ctgcagacgt ctggtggcag cgtctactcc attgctgtga 1800 caaatcacca cattgtctgt ggcacctacg agaacctcat ccacgtgtgg gacattgagt 1860 ccaaggagca ggtgcggacc ctcacgggcc acgtgggcac cgtgtatgcc ctggcggtca 1920 tctcgacgcc agaccagacc aaagtcttca gtgcatccta cgaccggtcc ctcagggtct 1980 ggagtatgga caacatgatc tgcacgcaga ccctgctgcg tcaccagagc agtgtcaccg 2040 cgctggctgt gtcccggggc cgactcttct caggggctgt ggatagcact gtgaaggttt 2100 ggacttgcta acaggatcca ggccaggctg tggtttcccc tgaaccagcc ctggaccttt 2160 ctgagccagg ctggccacat ggggtggtct cggggtttct gcctgccccg tgggcatagg 2220 tggacaggct ctggcagccg ggcagtgccc tccccgtccc atgctcggcg agcctccctc 2280 tactcggcac tgtccttgct gcccagcccc tctctgggtg ccaggtacga cgcttgcccc 2340 ggcccaccct ccatccccac cctccatccc caccctagat ggagcgaggg cctttttact 2400 caccttttct accgttttta gactgtatgt agattggtta cctcctggtt gaaataaatg 2460 ctccacagac tgtggctgtg agtggggaca gctcctcggg acaagggggc tgtgtgtggc 2520 cttgaggttg gtgtgcacag gcactggctg ctgtgagtgg gggggcatgg ggcagtttcc 2580 tttggtggac cccaggactt cggcccactc cggggcctcc cctccctgct aggaggtaac 2640 <210> 92 <211> 2071 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 275354CB1 <400> 92 gtgggcggaa ctcctagcgg acacctcgtg gagtccggcc ggaagagcaa ccgagatgaa 60 ggtgaagatg ctgagccgga atccggacaa ttatgtccgc gaaaccaagt tggacttaca 120 gagagttcca agaaactatg atcctgcttt acatcctttt gaggtcccac gagaatatgt 180 aagagcttta aatgctacca aactggaacg agtatttgca aaaccattcc ttgcttcgct 240 ggatggtcac cgtgatggag tcaattgctt ggcaaagcat ccagagaagc tggctactgt 300 cctttctggg gcgtgtgatg gagaggttag aatttggaat ctaactcagc ggaattgtat 360 ccgtacaata caagcacatg aaggctttgt acgaggaata tgtactcgct tttgtgggac 420 ttcttttttc actgttggtg atgacaaaac tgtgaagcag tggaaaatgg atgggccagg 480 ctatggagac gaggaagagc cattacatac aatattagga aagacagtgt atactgggat 540 tgatcatcac tggaaagaag ctgtttttgc cacatgtgga cagcaagtag acatttggga 600 tgaacaaaga actaatccta tatgttcaat gacctgggga tttgacagta taagtagtgt 660 taaatttaac ccaattgaga catttctctt gggaagttgt gcatctgaca ggaatatagt 720 actgtacgat atgaggcaag ctactccttt gaaaaaggtt atcttagata tgagaacaaa 780 tacaatctgt tggaacccta tggaagcttt catttttaca gcagcaaatg aagattataa 840 cttatatact tttgatatgc gtgcactgga cactcctgta atggtccata tggatcatgt 900 atctgcagtg cttgatgtgg attactctcc cactgggaag gagtttgtgt ctgctagttt 960 cgataaatct attcgaatct ttcctgtaga caaaagtcga agcagggagg tatatcatac 1020 aaagagaatg caacatgtta tctgtgtaaa atggacttct gacagcaagt atattatgtg 1080 tggatctgat gaaatgaaca ttcgcctgtg gaaagctaat gcttctgaaa aattgggtgt 1140 gcttacatca cgagaaaaag cagccaagga ttataaccag aaattgaagg agaaatttca 1200 gcattatcct catataaaac gtatagctcg tcatcgacat ctaccaaaat ctatctatag 1260 ccagattcag gaacagcgca tcatgaaaga agctcgtcga cgaaaggaag tgaatcgtat 1320 taaacacagc aagcctggat ctgtgccact tgtgtcagag aagaagaaac acgtagtggc 1380 agttgtaaaa taattggtat tcctaacaat cctgatgtat aattatttgt tacttttgat 1440 ttgagaactc tacaaataaa agtgctggga ctagattaat tgcaaacatt ttagttatat 1500 gtgtagagct ttattgttac tccttttagc taccctgaaa aatgatcctt aaaggtggcc 1560 tagttggtaa gactgtttta tccttaatct gcattcttct ttcattgtag aatacagtat 1620 ttgcaactca ttttttcttg tttttattac agatatactt actttctctt tgatctatta 1680 ttgtagacac tatacattca aattgacatt taagaccaaa catctcttat gttatcttta 1740 atattacttt gaataatgat tgcaatgatg tttcttcctg tgattccaca taacatttag 1800 aataatgatg tcaatttttt acaactgaat ttatttctag tgctttactt atatttggct 1860 ttttgactct tttaaaacaa tcagcctgca tttatataac ttttataaat aataatataa 1920 tttgggtcaa gttaagatat taaaagttcc tttcagcatt gaaactttgg cctatttttg 1980 gtaaataatt ttcaatctca ctaaatccta aatagctctg tgtaacatag gtttttcttt 2040 ttttaatcat aaacttaata aactttgtgg a 2071 <210> 93 <211> 2149 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 311658CB1 <400> 93 cattattttt aaaaatatta cccactcttg atagtgtatc tgcactgaga cacgtactgg 60 aagctatata ttgtttgaca tcccaatcta aaacaactca tctttcttac ttatgactag 120 agttcctcct cttcatttat attcttttct tggtgaacat cagtgtctac caatttctaa 180 atgcaaagga gaaagataca attttaagcg aaatggtggt gatatgcaca acttgcagaa 240 ggttacataa aacttgggtt ttcagagatg attttttctc ttctttttag gatatgttca 300 aggaatgagt gatttacttt cccctctttt atatgtgatg gaaaatgaag tggatgcctt 360 ttggtgcttt gcctcttaca tggaccaaat gcatcagaat tttgaagaac aaatgcaagg 420 catgaagacc cagctaattc agctgagtac cttacttcga ttgttagaca gtggattttg 480 cagttactta gaatctcagg actctggata cctttatttt tgcttcaggt ggcttttaat 540 cagattcaaa agggaattta gttttctaga tattcttcga ttatgggagg taatgtggac 600 cgaactacca tgtacaaatt tccatcttct tctctgttgt gctattctgg aatcagaaaa 660 gcagcaaata atggaaaagc attatggctt caatgaaata cttaagcata tcaatgaatt 720 gtccatgaaa attgatgtgg aagatatact ctgcaaggca gaagcaattt ctctacagat 780 ggtaaaatgc aaggaattgc cacaagcagt ctgtgagatc cttgggcttc aaggcagtga 840 agttacaaca ccagattcag acgttggtga agacgaaaat gttgtcatga ctccttgtcc 900 tacatctgca tttcaaagta atgccttgcc tacactctct gccagtggag ccagaaatga 960 cagcccaaca cagataccag tgtcctcaga tgtctgcaga ttaacacctg catgatcact 1020 gttcttgctt ttttgggaag agacactttg ttgcaaccct ttttcaagta cttgaaagtt 1080 gaaaatttga aatcttggta ttgatcatgc tttaaggttt atgtaaagaa agtgtactga 1140 tgttcttaca ttaaagcttt acaaagattt aaactaatta tttttgtagt tacttctacc 1200 aaatagcctt tccttttcga taacattcct cagtattttt atagccaagt acattttatt 1260 ttcttgctga tgaactggaa ttggataaat attgcaagtg gatgagttgg aaattatgca 1320 ctttgaaaaa cattcacttt gtttaagctt attgggtttc agatttgatt aaattaaatg 1380 tggaggcttt ctatagcatt ctaagctgag aagtagattg ttacccagta atgaaataaa 1440 aaataaaaat aaaaggattt ttttctctat tgtttacgac agtactcagc ttaaatattt 1500 atgctggtca aatgtgattt aaattggaca ttttcatcaa tgcagtctaa tgtgtagata 1560 aatatttcaa ccataataag tggattggca gtatattttt tacattgaac ttttcttcac 1620 ttgtatataa agattatata taagtactta tttatgagta taagaaaggt taggcatatt 1680 ttcattaact gaataaacga cttgatttat ataacctggt ttatcaaaat ttaacatggc 1740 ttcagtatga gatctttttc aaaactattt tcttaaacat ttatttcatg agattatgtt 1800 caaccctgta cctggtgtaa ttttaaaatt aattgcttgt aacctcactt tactaataat 1860 gtttattatc tttcctaata atgcattaac tgattaatca ggtgtttaaa tttttataaa 1920 atactcttgc aaaaagttta tttgaaaaat ttctagatgg tctcatgagt ttcaaaataa 1980 taatttttgt gtatgaacaa agctgttgtt tttaccatgc agtattgcat gattttaagt 2040 tatgtggaat taacataact gattttgttt taattgtaag ttgttaactc ctgtatatat 2100 cattaaaata aatctgaagt tgaagtagtg tttttagtta aattatact 2149 <210> 94 <211> 2332 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 1251632CB1 <400> 94 gccaccccag aactgggcag cagcctcaag aagaagaagc ggctctccca gtcagatgag 60 gatgtcatta ggctaatagg acagcacttg aatggcttag ggctcaacca gactgttgat 120 ctcctcatgc aagagtcagg atgtcgttta gaacatcctt ctgctaccaa attccgaaat 180 catgtcatgg aaggagactg ggataaggca gaaaatgacc tgaatgaact aaagccttta 240 gtgcattctc ctcatgctat tgtgaggatg aagtttttgc tgctgcagca gaagtaccta 300 gaatacctgg aggatggcaa ggtcctggag gcacttcaag ttctacgctg tgaattgacg 360 ccgctgaaat acaatacaga gcgcattcat gttcttagtg ggtatctgat gtgtagccat 420 gcagaagacc tacgtgcaaa agcagaatgg gaaggcaaag ggacagcttc ccgatctaaa 480 ctattggata aacttcagac ctatttacca ccatcagtga tgcttccccc acggcgttta 540 cagactctcc tgcggcaggc ggtggaacta caaagggatc ggtgcctata tcacaatacc 600 aaacttgata ataatctaga ttctgtgtct ctgcttatag accatgtttg tagtaggagg 660 cagttcccat gttatacgca gcagatactt acggagcatt gtaatgaagt gtggttctgt 720 aaattctcta atgatggcac taaactagca acaggatcaa aagatacaac agttatcata 780 tggcaagttg atccggatac acacctgcta aaactgctta aaacattaga aggacatgct 840 tatggcgttt cttatattgc atggagtcca gatgacaact atcttgttgc ttgtggccca 900 gatgactgct ctgagctttg gctttggaat gtacaaacag gagaactaag gacaaaaatg 960 agccagtctc atgaagacag tttgacaagt gtggcttgga atccagatgg gaagcgcttt 1020 gtgactggag gtcagcgtgg gcagttctat cagtgtgact tagatggtaa tctccttgac 1080 tcctgggaag gggtaagagt gcaatgcctt tggtgcttga gtgatggaaa gactgttctg 1140 gcatcagata cacaccagcg aattcggggc tataacttcg aggaccttac agataggaac 1200 atagtacaag aagatcatcc tattatgtct tttactattt caaaaaatgg ccgattagct 1260 ttgttaaatg tagcaactca gggagttcat ttatgggact tgcaagacag agttttagta 1320 agaaagtatc aaggtgttac acaagggttt tatacaattc attcatgttt tggaggccat 1380 aatgaagact tcatcgctag tggcagtgaa gatcacaagg tttacatctg gcacaaacgt 1440 agtgaactgc caattgcgga gctgacaggg cacacacgta cagtaaactg tgtgagctgg 1500 aacccacaga ttccatccat gatggccagc gcctcagatg atggcactgt tagaatatgg 1560 ggaccagcac cttttataga ccaccagaat attgaagagg aatgcagtag catggatagt 1620 tgatggtgaa tttggagcag acgacttctg tttaacttaa aattagtcgt attttaatgg 1680 cttgggattt ggtgcaaaca aacatgattg atagctggac agacatgctc gtcatgaaaa 1740 aagaaccatt tctgaagccc gattggggcc aaacatttac accttgcttc atagtaacca 1800 gttgagatga agcacgtcgt tagaacgttg ttggacacca tgttgaatta ttcccccatc 1860 ggttgtgaag aactgtgcta cattcaggct tacccattga actcagtata tatatttttt 1920 ttccttcctg tcttttgtct ggcaggatac cattcttgtt gctcttctgt gtaatgaagt 1980 ttaaatgctt gtttggaaaa ctttatttaa cagtttagaa ggcttgatag aaagagtgca 2040 ttagtctgaa gagtatacat tggataggaa agaatttcct tcttttgttt ctccaaatct 2100 ttccgcctta tttagcttga gatctttgca gcttggttca tggattctag ccttgcccgt 2160 tgcgcagtat atactgatcc agatgataaa ccagtgaact atgtcaaaag cactctcaat 2220 attacatttg acaaaaagtt ttgtactttt cacatagctt gttgccccgt aaaagggtta 2280 acagcacaat tttttaaaaa taaattaaga agtatttata ggaaaaaaaa as 2332 <210> 95 <211> 1751 <212> DNA
<213> Homo sapiens <220>
<221> misc feature <223> Incyte ID No: 1331955CB1 <400> 95 gcccgaatcg actccggaga caacgccggg cgacgccacc tgcgcaggtc ccggaggccg 60 ctggtgtctg tgtacagggc gtgctgtctg tggaaacgcg agggcacact agcactttcc 120 tggaaggacc ccagacccac caagccactc agtccctgga cgagtttcca ctcaccccga 180 ctgcctctgt caccgggtcc ctccaccctt gtctcctgtg cggccagcgt cagagccatg 240 gcgacggagg agaagaagcc cgagaccgag gccgccagag cacagccaac cccttcgtca 300 tccgccactc agagcaagcc tacacctgtg aagccaaact atgctctaaa gttcaccctt 360 gctggccaca ccaaagcagt gtcctccgtg aaattcagcc cgaatggaga gtggctggca 420 agttcatctg ctgataaact tattaaaatt tggggcgcgt atgatgggaa atttgagaaa 480 accatatctg gtcacaagct gggaatatcc gatgtagcct ggtcg.tcaga ttctaacctt 540 cttgtttctg cctcagatga caaaaccttg aagatatggg acgtgagctc gggcaagtgt 600 ctgaaaaccc tgaagggaca cagtaattat gtcttttgct gcaacttcaa tccccagtcc 660 aaccttattg tctcaggatc ctttgacgaa agcgtgagga tatgggatgt gaaaacaggg 720 aagtgcctca agactttgcc agctcactcg gatccagtct cggccgttca ttttaatcgt 780 gatggatcct tgatagtttc aagtagctat gatggtctct gtcgcatctg ggacaccgcc 840 tcaggccagt gcctgaagac gctcatcgat gacgacaacc cccccgtgtc ttttgtgaag 900 ttctccccga acggcaaata catcctggcc gccacgctgg acaacactct gaagctctgg 960 gactacagca aggggaagtg cctgaagacg tacactggcc acaagaatga gaaatactgc 1020 atatttgcca atttctctgt tactggtggg aagtggattg tgtctggctc agaggataac 1080 cttgtttaca tctggaacct tcagacgaaa gagattgtac agaaactaca aggccacaca 1140 gatgtcgtga tctcaacagc ttgtcaccca acagaaaaca tcatcgcctc tgctgcgcta 1200 gaaaatgaca aaacaattaa actgtggaag agtgactgct aagtcccttt gctcctgccc 1260 gcgagagact gtcgggaagt tgacccggat tggcaagaaa cagggtgtct tggaggtggt 1320 cccccagatc tgcgcctggg ggtcaggaca gggcctgatt tgagcctcct ctctgaagat 1380 gatttggccg agcggaaggt gtggaccacc ggaaagttct taaaagttgc tggtgacatt 1440 tcttgccaat tctaacactg tctagggaag agttcctagt ctattgtgtt caaacagagt 1500 caacaaaagt ttttaatttt ttattacaga agggtgaagt tcaatttaac atgcgttgtg 1560 ttttttcagt aaacgttctg tatctttttg atattccatg acccagtgca cgctgtggcc 1620 tgtcaccgcc accgtggccc cgccagctgg cctccccttt ggcccacgcc ggccgccccc 1680 attctctgct gcgtagatgc cctggcccag ggcctgactc tccattcccg ccagtagggg 1740 taccgagctc g 1751 <210> 96 <211> 1285 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 1412614CB1 <400> 96 cggagaaaaa gctgacctaa tgaaactgtg gcaacgtcag cgcttgaggc ttgaagaggg 60 agacaagcta aaagaggata tccagttgtt tcatgatggc atttgcacct ccaaaaaaca 120 cagatggtcc caaaatgcag acaaagatga gcacctggac acccctaaac catcagctat 180 tgaatgaccg ggtatttgaa gaaagaagag ccctgcttgg caaatggttt gacaaatgga 240 cagactctca aagaagaaga atcctcacag gcctgttgga gcgctgctcg ctgtcccagc 300 aaaagttctg ctgtcgaaag cttcaagaga aaattccagc agaagccctg gactttacaa 360 ccaagcttcc aagggtgtta tctttataca tcttttcttt cctggaccct cggagccttt 420 gtcgttgtgc acaggtgtgc tggcattgga agaaccttgc tgagctggac cagctctgga 480 tgctgaaatg tttacggttt aactggtaca tcaatttctc tccaactccc tttgagcagg 540 ggatctggaa gaagcactat attcaaatgg tgaaagaact tcatattacc aagcctaaga 600 cacccccaaa ggatggattt gtaatcgctg acgttcaact agttacaagc aattctccag 660 aggaaaaaca gtccccttta tcagcttttc ggtcctcttc ctctttaaga aagaagaata 720 actcagggga gaaagcactt ccaccctggc gatcttctga taagcaccca acagatatca 780 ttcgttttaa ttacctagac aaccgtgacc ccatggagac tgtccagcaa ggaagaagaa 840 aaagaaacca aataacccca gacttcagcc gacagtcaca tgataagaaa aataaattgc 900 aggacagaac taggctaaga aaagcacaat caatgatgtc gaggagaaat cccttcccac 960 tatgtcccta agtgccagct ctcccctaaa agttccagct catctcgcct ggcctccccc 1020 tgagtcagtg ggactcccag ccactgccac cacagctgaa attctcatgc agcatcctca 1080 caggcaccct gggccccaag catgactcat ccaggttcca gagccaaagt ggactgaaca 1140 88/11$

tgggaagact tttattatag aaatgacaag atgctttgca cagtggagag ctgaatttac 1200 ttggctccca ttagaaactc tttcagctta agtacttatt gtggtagtga gtcctacggt 1260 atttcagtaa aaaggaattc atggc 1285 <210> 97 <211> 3260 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 1750781CB1 <400> 97 ccggaagacc gtcccggatg gcctcgggga ctgccagtgt gtggaggtga gctccgggat 60 tgccggcatt cccgcttctg ctggttgctt catgctgcag gctgcggccg tcagccctcg 120 ctcgcattgg tggcgctgag gtgccggggc agcaagtgac atgtcgtcgg gcctccgcgc 180 cgctgacttc ccccgctgga agcgccacat ctcggagcaa ctgaggcgcc gggaccggct 240 gcagagacag gcgttcgagg agatcatcct gcagtataac aaattgctgg aaaagtcaga 300 tcttcattca gtgttggccc agaaactaca ggctgaaaag catgacgtac caaacaggca 360 cgagataagt cccggacatg atggcacatg gaatgacaat cagctacaag aaatggccca 420 actgaggatt aagcaccaag aggaactgac tgaattacac aagaaacgtg gggagttagc 480 tcaactggtg attgacctga ataaccaaat gcagcggaag gacagggaga tgcagatgaa 540 tgaagcaaaa attgcagaat gtttgcagac tatctctgac ctggagacgg agtgcctaga 600 cctgcgcact aagctttgtg accttgaaag agccaaccag accctgaagg atgaatatga 660 tgccctgcag atcactttta ctgccttgga gggaaaactg aggaaaacta cggaagagaa 720 ccaggagctg gtcaccagat ggatggctga gaaagcccag gaagccaatc ggcttaatgc 780 agagaatgaa aaagactcca ggaggcggca agcccggctg cagaaagagc ttgcagaagc 840 agcaaaggaa cctctaccag tcgaacagga tgatgacatt gaggtcattg tggatgaaac 900 ttctgatcac acagaagaga cctctcctgt gcgagccatc agcagagcag ccacgagacg 960 ctctgtctct tccttcccag tcccccagga caatgtggat actcatcctg gttctggtaa 1020 agaagtgagg gtaccagcta ctgccttgtg tgtcttcgat gcacatgatg gggaagtcaa 1080 cgctgtgcag ttcagtccag gttcccggtt actggccact ggaggcatgg accgcagggt 1140 taagctttgg gaagtatttg gagaaaaatg tgagttcaag ggttccctat ctggcagtaa 1200 tgcaggaatt acaagcattg aatttgatag tgctggatct tacctcttag cagcttcaaa 1260 tgattttgca agccgaatct ggactgtgga tgattatcga ttacggcaca cactcacggg 1320 acacagtggg aaagtgctgt ctgctaagtt cctgctggac aatgcgcgga ttgtctcagg 1380 aagtcacgac cggactctca aactctggga tctacgcagc aaagtctgca taaagacagt 1440 gtttgcagga tccagttgca atgatattgt ctgcacagag caatgtgtaa tgagtggaca 1500 ttttgacaag aaaattcgtt tctgggacat tcgatcagag agcatagttc gagagatgga 1560 gctgttggga aagattactg ccctggactt aaacccagaa aggactgagc tcctgagctg 1620 ctcccgtgat gacttgctaa aagttattga tctccgaaca aatgctatca agcagacatt 1680 cagtgcacct gggttcaagt gcggctctga ctggaccaga gttgtcttca gccctgatgg 1740 cagttacgtg gcggcaggct ctgctgaggg ctctctgtat atctggagtg tgctcacagg 1800 gaaagtggaa aaggttcttt caaagcagca cagctcatcc atcaatgcgg tggcgtggtc 1860 gccctctggc tcgcacgttg tcagtgtgga caaaggatgc aaagctgtgc tgtgggcaca 1920 gtactgacgg ggctctcagg gctgggagga ccccagtgcc ctcctcagaa gaagcacatg 1980 ggctcctgca gccctgtcct ggcaggtgat gtgctgggta tagcatggac ctcccagaga 2040 agctcaagct atgtggcact gtagctttgc cgtgaatggg atttctgaag atttgactga 2100 ggtctctctt ggcctggaag aataacactg aaaaaacctg acgctgcggt cacttagcag 2160 aggctcaggt tcttgccttg ggaaacacta ctagctctga ccttccatac ctcacttggg 2220 ggagcacagg gccccgctgg gcctcctcac caacggcagt gccaaaatca gcccccacat 2280 caaggtggtg ttctctgtgc tttctctcgt ccttccaaag tcggttctgg cctaacgcat 2340 gtcccaacac cttgggttca tttgcccggt gaactcactt taagcattgg attaacggaa 2400 actcccgaac tacagacccc tccctggtgg gttgcatgaa tgtgtctcat tactgctgaa 2460 atgtcctcac atctcttcca ctgttcttca gagctttctg gctctctttc cccacaaaat 2520 tcgacacatt taaaaatctc cgtgtggctt taaaaaatgg ttttttgttt ttttgttttt 2580 ttgaggtggg agaggatgtg tgaaaatctt ttccagggaa atgggttcgc tgcagaggta 2640 aggatgtgtt cctgtatcga tctgcagaca cccagaaggt gggtgcacac tgcatgcttg 2700 ggggtgccaa gggattcgag acctccaaca tacttgtctg aaggtggtga ttctggccat 2760 ggcccctctg ccaagcctgt gtgcgatgcc cttggtgctt tagtgcaaga agcctaggct 2820 cagaagcaca gcagcgccat ctttccgttt caggggttgt gatgaaggcc aaggaaaaac 2880 atttatcttt actattttac ctacgtataa agttttagtt cattgggtgt gcgaaacacc 2940 ctttttatca cttttaaatt tgcactttat tttttttctt ccatgcttgt tctctggaca 3000 tttggggatg tgagtgttag agctggtgag agaggagtca ggcggccttc ccaccgatgg 3060 tcctggcctc cacctgccct ctcttccctg cctgatcacc gctttccaat ttgcccttca 3120 gagaacttaa gtcaaggaga gttgaaattc acaggccagg gcacatcttt tatttatttc 3180 attatgttgg ccaacagaac ttgattgtaa ataataataa agaaatctgt tatatacttt 3240 tcaaaaaaaa aaaaaaaaaa 3260 <210> 98 <211> 1276 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 1821658CB1 <400> 98 gcggcacccc caaggaagac cagcctgcct ctggtcggtt cctggcgctc tgcgtttcgt 60 gaccttgtcc agtagaaggc tatttaattt tcacaactgc ttgaattttg acatacaaga 120 tgaagcaaga tgcctcaaga aatgctgcct acactgtgga ttgtgaagat tatgtgcatg 180 tggtagaatt taatcccttt gagaatgggg attcaggaaa cctaattgca tatggtggca 240 ataattatgt ggtcattggc acgtgtacgt ttcaggaaga agaagcagac gttgaaggca 300 ttcagtataa aacacttcga acatttcacc atggagtcag ggttgatggc atagcttgga 360 gcccagagac tagacttgat tcattgcctc cagtaatcaa attttgtact tcagctgctg 420 atatgaaaat tagattattt acttcagatc ttcaggataa aaatgaatat aaggttttag 480 agggccatac cgatttcatt aatggtttgg tgtttgatcc caaagaaggc caagaaattg 540 caagtgtgag tgacgatcac acctgcagga tttggaactt ggaaggagtg caaacagctc 600 attttgttct tcattctcct ggcatgagtg tgtgctggca tcctgaggag acttttaagc 660 taatggttgc agagaagaat ggaacaatcc ggttttatga tcttttggcc caacaggcta 720 ttttatctct tgaatcagaa caagtgccat taatgtcagc acactggtgc ttaaaaaaca 780 ccttcaaagt tggagccgtt gcaggaaatg attggttaat ttgggatatt actcggtcca 840 gttatcctca aaataagaga cctgttcaca tggatcgagc ctgcttattc aggtggtcca 900 caattagtga aaatctgttt gcaaccactg gttatcctgg caaaatggca agccagtttc 960 aaattcatca tttaggacac cctcagccca tcctcatggg ttctgtagcc gttggatctg 1020 gactgtcctg gcatcgaact ctccctctgt gtgtaattgg aggagaccac aagctgttgt 1080 tttgggtgac tgaagtataa agtgttttct gtaccttaga ttcacaaact ttgtattttt 1140 agtacatatt ttgaagaatt tctatagtac atattttgaa gaatttttat atcaaatata 1200 ccgtatactt tagaaaatgt ctcagttgct tttattaaat aaaatgttga tggtttgaaa 1260 aattaaaaaa aaaaaa 1276 <210> 99 <211> 3608 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 1872574CB1 <400> 99 gttttggttc tagccgctcg ccgtccttgc aggctctgcc gtcggaaagc cgctcattct 60 cgcttcccct tccctttccc ggctcaagtc cttcctctct ctttcctttc tttccgccta 120 tcttttttct gctgccgctc cgggtccggg ccattttccg ggccgggcgc actaaggtgc 180 gcggccccgg ggcccagtat atgacccgcc gtcctgctat ccttcgcttc ccccgcccca 240 tgtggctgcg gggccgcggc ggcgctgccc actatggccc ggaaagtagt tagcaggaag 300 cggaaagcgc ccgcctcgcc gggagctggg agcgacgctc agggcccgca gtttggctgg 360 gatcactcgc ttcacaaaag gaaaagactt cctcctgtga agagatcctt agtatactac 420 ttgaagaacc gggaagtcag gctacagaat gaaaccagct actctcgagt gttgcatggt 480 tatgcagcac agcaacttcc cagtctcctg aaggagagag agtttcacct tgggaccctt 540 aataaagtgt ttgcatctca gtggttgaat cataggcaag tggtgtgtgg cacaaaatgc 600 aacacgctat ttgtcgtaga tgtccagaca agccagatca ccaagatccc cattctgaaa 660 gaccgggagc ctggaggtgt gacccagcag ggctgtggta tccatgccat cgagctgaat 720 ccttctagaa cactgctagc cactggagga gacaacccca acagtcttgc catctatcga 780 ctacctacgc tggatcctgt gtgtgtagga gatgatggac acaaggactg gatcttttcc 840 atcgcatgga tcagcgacac tatggcagtg tctggctcac gtgatggttc tatgggactc 900 tgggaggtga cagatgatgt tttgaccaaa agtgatgcga gacacaatgt gtcacgggtc 960 cctgtgtatg cacacatcac tcacaaggcc ttaaaggaca tccccaaaga agacacaaac 1020 cctgacaact gcaaggttcg ggctctggcc ttcaacaaca agaacaagga actgggagca 1080 gtgtctctgg atggctactt tcatctctgg aaggctgaaa atacactatc taagctcctc 1140 tccaccaaac tgccatattg ccgtgagaat gtgtgtctgg cttatggtag tgaatggtca 1200 gtttatgcag tgggctccca agctcatgtc tccttcttgg atccacggca gccatcatac 1260 aacgtcaagt ctgtctgttc cagggagcga ggcagtggaa tccggtcagt gagtttctac 1320 gagcacatca tcactgtggg aacagggcag ggctccctgc tgttctatga catccgagct 1380 cagagatttc tggaagagag gctctcagct tgttatgggt ccaagcccag actagcaggg 1440 gagaatctga aactaaccac tggcaaaggc tggctgaatc atgatgaaac ctggaggaat 1500 tacttttcag acattgactt cttccccaat gctgtttaca cccactgcta cgactcgtct 1560 ggaacgaaac tctttgtggc aggaggtccc ctcccttcag ggctccatgg aaactatgct 1620 gggctctgga gttaatgaca actccccaaa tgcagagatt tacactaact tccattctca 1680 gtttccttgt ttcttttgat tttttttttc ctaattgtgt gaggctcttg tgttttagtg 1740 ggaacaccaa agtttgccta tagtttaggc acttaatagg aagaagctct gtacagaaat 1800 ctgaaagttg ttttgctttt tgttttcccc tttggtaatc aaaattttac tatcttttat 1860 tatttctggc ttttcaacca aacattgttg ctaatcccta tttttcttta agtgacacac 1920 attctcctgt ctctggcttc ttcaggctga aatgacatag tctttctcac ccttacttca 1980 ctcttgagag gtagggctcc tttataatta catggttgct ctcagacttt ctgtgaaagt 2040 ttgggagctg tgtgtgtctg tgtgtgtgtg agagagagat cttgtctgcg tgtgtgtgtg 2100 tgatcttgtg tgcctgtagg tactgtgtgt cactgaaatt acctggagtg aggattactt 2160 gtaattaaaa tatttataaa agaaacaact ttattcacag agtccagctt tgggactagt 2220 ctgtatcttg ttttttaagt ctaacaacac tgataatagg aagtaaaaac agaaaggaaa 2280 agaaattacc actgggaaaa tctttttagt tagattgtag gcttcctggg gcctcccatg 2340 ccaggactgc aaagtgatcc agccctacct gtcttcccac ctgtgtgtcc cccgtgtggg 2400 aagttggtgt cacttcccct tcccaccctc acatctgctt agccagtagc cacaccccta 2460 aaacatcaga ctcaccatcc aggtgcagct ccagaggcta caaaaggctt catgggactt 2520 gaatccccat cctagcttct ctctccttcc cctcaagacc tgatctggtt ttaaggggcc 2580 tggagctggg agtctcaagt ctgctaagat tcacatccat agcccccgtg gctttgagga 2640 gaatcctctc tgccattctt ccaatctccc cagtgggttt tgctattatt ttctaaattg 2700 ggttaagtct aagaaggtgg gggtgagcag ggggtttatc tgtgtgtagt gagtgcttca 2760 tgtgtggaat attcattttc ttactgcagt gggacttggg gttgaagcca cccctcctac 2820 tctgttggct tagccctgag atggtgacag gctggcctgc agtcagcatc attgtgcatg 2880 tgacagcatc aatgtgatta gtaatttgtc tgttcctccc ttgaactgtc tgtttagtct 2940 gaggttttta aacttgcagg cagctgactg tgatgtccac ttgttccctg atttttacac 3000 atcatgtcaa agataacagc tgttcccacc caccagttcc tctaagcaca tactctgctt 3060 ttctgtcaac atcccatttt ggggaaagga aaagtcatat ttattcctgc accccagttt 3120 tttaacttgt tctcccagtt gtccccctct tctctgggtg taagaaggga aattggaaaa 3180 aaaattatat atatattctc cttttaatgg tggggggcta ctggagagga gagacagcaa 3240 gtccacccta acttgttaca cagcacatac cacaggttct ggaattctca tcttcgaacc 3300 tagagaaata ggtgctataa acagggaatt aagcaaaatg ctggatgcta tagatctttt 3360 aattgtctta attttttttc tattattaaa ctacaggctg tagatttctt agttctcaca 3420 gaacttctat cattttaaac tgacttgtat atttaaaaaa aaaatcttca gtaggatgtt 3480 ttgtactatt gctagaccct cttctgtaat gggtaatgcg tttgattgtt tgagattttc 3540 tgtttttaaa aatgtagcac ttgacttttt gccaaggaaa aaaataaaaa ttattccagt 3600 gcaaaaaa 3608 <210> 100 <211> 1311 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 2590967CB1 <400> 100 ggcaggatga acgctgcttt ccaagatggc gacggaggga ggagggaagg agatgaacga 60 gattaagacc caattcacca cccgggaagg tctgtacaag ctgctgccgc actcggagta 120 cagccggccc aaccgggtgc ccttcaactc gcagggatcc aaccctgtcc gcgtctcctt 180 cgtaaacctc aacgaccagt ctggcaacgg cgaccgcctc tgcttcaatg tgggccggga 240 gctgtacttc tatatctaca agggggtccg caaggctgct gacttgagta aaccaataga 300 taaaaggata tacaaaggaa cacagcctac ttgtcatgac ttcaaccacc taacagccac 360 agcagaaagt gtctctctcc tagtgggctt ttccgcaggc caagtccagc ttatagaccc 420 aatcaaaaaa gaaactagca aactttttaa tgaggaaggc tcattgtcat ccccaagcca 480 ggccagttct ccaggtggaa ctgtagtgta gcgacctcac tgctgcgcgc acagtctccc 540 gggacttgga ctcgagggag tgacgaggag gagctccgag ctgcgcctga gccgtgccag 600 ccggcggacc tcaggcggtg gacgtcggcg atagccgtgt ggacggtgac cggctcactc 660 tgcggcgccg tgctcccgct gctcacccaa agaagttgtt tccattttaa accggtcttt 720 tggggctgca gtaaaaaata agaaatggag ttttcttgct ttttactcta aaattcaatg 780 taattaaatt tcatatatat ataatatata catatataca tagtgtaaaa taaaatgttt 840 cttggacaag aaatcccctg aaattcagct gttatagtgc ttcactgttt ttgcactgat 900 ttttctatac cttaggtggt cagaagacaa ccttgaatgc actcatagag aaaactgtta 960 ctttctgacg taatgtaatt caggaagaca gacgctgcaa tcacagattt taaaaaattg 1020 tttgcactta aaaatagttg aatgctggtg gaaagttact ttgcagatgg gtgtaaggac 1080 tcatggccct ctgaggtgcg gcgtgaagat gcccttttta cccgttgacg tttattttac 1140 gtaaaataaa ctgttgtttc caatgcaatc aactctgtat tatatgtata aatattgtaa 1200 ttctgcaatt ggggaaaata gttacttcac tagtaatttt catcatttaa gagtgatatt 1260 tctaattcac aaaagttaat attaaaacta tcttgaatat aaaaaaaaaa a 1311 <210> 101 <211> 2839 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 2824491CB1 <400> 101 ggcctgcggg aagccaagat ggcgcatagg ggttctccag gctgcagttg gcgccttatc 60 agtatctaag cggagtgttt tggaaggagt taaggggctg tggcaaacgc c.ctctccgcc 120 gtcatggccc ggcatcggaa tgttcgaggc tataactacg atgaagattt tgaagatgat 180 gatctctacg gccagtctgt agaggatgat tattgtattt cgccgtcaac agctgctcag 240 tttatttatt cacggcgtga caaaccttcc gttgagcctg tggaagaata tgattatgaa 300 gatctgaaag aatcttccaa ttctgtttca aaccatcagc tcagtggatt tgatcaagct 360 cgtctttatt catgccttga tcacatgaga gaggtacttg gagatgctgt gccagatgaa 420 atattaattg aagcagttct gaagaacaag tttgatgtgc agaaggcttt gtcaggggtt 480 ctggaacaag atagagtgca gagtttgaag gacaagaatg aggcaacagt atctacagga 540 aagatagcaa aaggaaaacc agtagattcc cagacatcgc gaagtgaatc tgaaattgtg 600 ccaaaagttg ctaaaatgac tgtatctgga aagaagcaaa ctatgggatt tgaagtgcct 660 ggagtatctt ctgaagaaaa tggtcatagt ttccacacac ctcaaaaagg accgcccatt 720 gaagatgcca ttgcttcttc cgatgttctt gagactgctt ctaaatctgc taatccaccc 780 cacacgattc aagcatcaga agagcagagt tcaaccccag caccggtgaa aaagtctggc 840 aagctgaggc agcaaataga tgtgaaggcg gaactggaga agcggcaagg agggaagcag 900 ctactcaact tagtggtcat tggtcatgtt gatgctggga aaagtactct gatgggccat 960 atgctttatc ttctgggtaa tataaacaaa agaactatgc ataagtatga acaggagtct 1020 aaaaaggctg gcaaagcttc gtttgcatat gcatgggtct tggatgaaac tggcgaagaa 1080 agggaaaggg gagtaaccat ggatgttggt atgacaaagt ttgaaaccac aaccaaagtt 1140 attacattaa tggatgctcc aggccataag gacttcattc caaatatgat tacaggagca 1200 gcccaggcgg atgtagctgt tttagttgta gatgccagca ggggagagtt tgaagctgga 1260 tttgagactg gaggacaaac acgagagcat ggactcttgg tccgttctct gggagtgacg 1320 cagcttgcag ttgcagttaa taaaatggat caggttaatt ggcaacaaga aaggtttcaa 1380 gagattactg gaaaacttgg gcactttctt aagcaagcag gttttaagga gagtgatgta 1440 ggttttattc ctacaagtgg tctcagtggt gaaaatctaa tcacaagatc tcagtcaagt 1500 gaactcacaa aatggtataa aggactatgt ttattagaac aaattgattc ctttaagcct 1560 ccccagcgat ctattgacaa accttttaga ttatgtgtgt ccgatgtttt caaagatcaa 1620 ggatctggat tttgcataac tggtaaaata gaagctggtt atatccaaac tggtgaccga 1680 ctactggcaa tgcctcctaa tgaaacttgt accgtgaaag gaatcactct gcatgatgaa 1740 cctgtcgact gggcggcagc aggcgatcat gttagtctta ctttggttgg gatggatatc 1800 atcaaaatca atgttggctg catattttgt ggccccaaag tacccattaa agcttgcact 1860 cgtttcagag cccgaatcct catctttaat attgaaattc ctatcactaa aggatttcct 1920 gtgctgttac actaccaaac tgtcagtgaa cccgccgtta ttaaacgatt gattagtgtc 1980 ttaaacaaaa gcacgggtga agtcacaaag aaaaagccta agtttttgac taaaggccag 2040 aatgcattgg tagagctaca gacacaaaga ccaatagctc ttgagctata taaagacttt 2100 aaagagctgg ggaggttcat gctacgttac ggtggttcta caatagctgc tggtgttgtc 2160 actgagataa aagaatgatg ggtcagaatt tctaccacgt ttctggatac agtgaaatag 2220 ctaacctctg tttcaagaat gcagttatta agtcaaagga acaatgtgca attgatatgt 2280 ttttagatga gagagaaaaa ttaaagctaa aattagctgc aaagaagtat taataatcac 2340 ctctgcaaaa attctaagtt gccaactggc aaagaaagtc taatgttaaa aacaactttg 2400 cctttgaaac gttaataaat ggatttactt tgctaagatt tatggcaagt gtcaaaaata 2460 gtatctgaag atactgaatc atcatgaaat gaactctact tctggccaaa gcacaatgta 2520 tttgcagttt tctcttttga ttcaattata ctgcacatgt tttaaggaaa agtaacttaa 2580 ttgggttttt caggcagttg atatttgacc taagcttttt tttttttttt tttttttttt 2640 tccagttaat gctaagaaaa gatttgggga aggttataat aaaagtattt tgtggtgacc 2700 ataagaatgt ccctccccaa acaagtaaac ttgtgaaagt ttaatttgga attagtggaa 2760 gctgttcctt tgaaagccaa gatattattt aagttgtaaa gccagctaat aaaatgcctt 2820 agtttgagca taaaaaaaa 2839 <210> 102 <211> 1676 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 2825460CB1 <400> 102 gggaggcgga ggttgaggtg agaggagatc gcgccattgc actccagcct gggcaacaag 60 ggcgaagttc tctcaaaaga aaaaaaaaaa tcgtcggttt ccttttccca tctttctttc 120 gtgacttata ttccagaacg aagccccaca catcattaat gatttgaatc gtttctaaag 180 tgtttcttaa atcgtttctt aaatcgtttg ttgtttcttg tctaacagtc cagaacacat 240 attacataat ggagccggga gacagactag ggctggcttg atccggccac gcagtccagg 300 aaaggtgctt ttcaccccca agtgcaaaat gatcaatgta ttcttccgat ctacataaac 360 aagcacctcc tggtttcatt ttcgtaaagc aaaacaagca tggaagcttt actgtttcgg 420 ctcttcaaac ttccagcaac tacactgcgc tgcatcggac tcgacgcccg ctggtgacgc 480 acacgctgcg ccggaagtgt gaactgtctg cctccaggct ttgtcatggc ggctgctgct 540 gcacgctgga accatgtgtg ggtcggcacc gagactggga tcttgaaagg ggtaaatctt 600 cagcgaaaac aggcggcgaa cttcacggcc ggaggacagc cgcggcgcga ggaggcagtg 660 agcgccctgt gttggggcac cggcggcgag acccagatgc tggtgggctg cgcggacagg 720 acggtgaagc acttcagcac cgaggatggc atattccagg gtcagagaca ctgcccgggc 780 ggggagggca tgttccgtgg cctcgcccag gccgacggca ccctcatcac atgtgtggat 840 tctgggattc tcagagtctg gcatgacaag gacaaggaca catcctctga cccactcctg 900 gaactgagag tgggccctgg ggtgtgtagg atgcgccaag acccagcaca cccccatgtg 960 gttgccacag gtgggaaaga gaatgctttg aagatatggg acctgcaggg ctctgaggaa 1020 cctgtgttca gggccaagaa cgtgcggaat gactggctgg acttgcgggt tcccatctgg 1080 gaccaggaca tacagtttct cccaggatca cagaagcttg tcacctgcac agggtaccac 1140 caggtccgtg tttatgatcc agcatccccc cagcgccggc cagtcctaga gaccacctat 1200 ggagagtacc cactaacagc catgaccctc actccgggag gcaactcagt gattgtggga 1260 aacactcatg ggcagctggc agaaattgac cttcggcaag ggcgtctact gggctgtctg 1320 aaggggctgg caggcagtgt gcgtgggttg cagtgccacc cttcaaagcc tctactagcc 1380 tcctgtggct tggacagagt cttgaggata cacaggatcc agaatccacg gggtctggag 1440 cataaggatg agccccaaga gcctcaagaa cccaacaagg tgcccctaga agacacagag 1500 acagatgaac tttgggcatc cttggaggca gctgccaagc ggaagctctc gggtttggag 1560 cagccccaag gagctctcca aacgagacgg agaaagaaga agcggcctgg gtccaccagc 1620 ccctgacgcc cctgtgccca ctttgtaaat aaactgctga acacccaaaa aaaaaa 1676 <210> 103 <211> 3206 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 2871116CB1 <400> 103 ccagagcgtg cgttcggtgg cccatagggg aagatggcgg ctgctccttt ggaggagcgg 60 gattgagagg atcggggtgg ggagaccaaa caagagagac atttctggct ctgaaggcga 120 acgcttcgct ggccatttag gagctctgct caaagccaga cgtatcctag aaggaaaaca 180 tcaccatggc tacagaaatt ggttctcctc ctcgtttttt ccatatgcca aggttccagc 240 accaggcacc tcgacagctg ttttataagc gacctgattt tgcacaacag caagcaatgc 300 aacagcttac ttttgatgga aaacgaatga gaaaagctgt gaaccgaaaa accatagact 360 acaatccatc tgtaattaag tatttggaga acagaatatg gcaaagagac cagagagata 420 tgcgggcaat tcagcctgat gcaggttatt acaatgatct ggtcccacct ataggaatgt 480 tgaataatcc tatgaatgca gtaacaacaa aatttgttcg gacatcaaca aataaagtaa 540 agtgtcctgt atttgttgtt aggctgcagg aagagtttga aagcctcagt gtccttaaat 600 cgtggactcc agaaggaaga cgcttggtca ctggagcttc tagtggggag tttaccctgt 660 ggaatggact cactttcaat tttgaaacaa tattacaggc tcacgacagc ccagtgaggg 720 ccatgacgtg gtcacataat gacatgtgga tgttgacagc agaccacgga ggatatgtga 780 aatattggca gtcgaacatg aacaacgtca agatgttcca ggcacataag gaggcgatta 840 gagaggccag gtttatacac aatataccat tttctgtagt ccctattgtc atggttaaat 900 tattctctaa gtgtattctg ggtgcagaga tgcatgggct ctgtcagttt ctgggaaact 960 ttctgcaccc tataaacaca atatttttct ttgttttcac acattcacca ttttgctggc 1020 acctttctga agtagtgttg tcccggtatc agcctttgca atatgttaga gatgtactgt 1080 ctgccgcatt ttgcactggt tttctctttt catttatgat taataatgtg tatacgttat 1140 tcctttttat tatctactgt gtaagacaag aatatttcat tccaaataaa gaattcagtc 1200 tttaattatg caactgaata aaatctaaag cctacagaaa.acaacttcag aattcacaca 1260 aagtggaaaa aggcttaagt gaagacctgg ttggcttggt tatgccacga cttccaaagg 1320 aaagtatagg actaaaaccc tcacagataa ctggatgtgg caaacattaa cggagtaatg 1380 aatgggttct tcaagctttg cagctgtaag cagatcattg tcaagaagac tctaggactt 1440 ttcttctgat tcactgttga taacatcact tatgcaaatg tatacaataa gtggagttta 1500 aaatattttc agtgagttgt atatttttac acatcagtga ggtatgtata gtaaaactgg 1560 gggaaaaagt tccaaataca agcctgaaga attgctgcag cctcagaata aagctaagca 1620 gcattcttta aggttgtgcc acccatgtgt gggaggaggt tgacatcttt atggaaacat 1680 catccactgt agtcatttgt tcatactttc agaatcttaa cagaaattgt tggatgaaca 1740 tgcttctgct ttgtagattt tgccttagtg tcatgcccat acattgagtt tacacagctg 1800 gtccttcata ggattccaaa gttcaaggga gtttttagag ttagttgaga aacttgatga 1860 tctttcactg ctgggaaaaa ctgactcctt cttgcagcag attctttggc tttacacaca 1920 agtctgaatg tccttatttt aaagttttcc tcaaaggtgc aacattcatg gaatagcttg 1980 ccaggaagat gtgaaacttt tctacagacc tttgaaatgg atgagaaaca ttgtatgtag 2040 ggatgtttag caatcagtct tttaatagac agcccacatt gtttcagctt atttcatgaa 2100 gtgtctgagg cagaagctga tgataatttt gggagcagta ttcgtgtgtg atttaaaaga 2160 ctgcaggaat actgcaaaaa tagaatccat ttattttcac cacttaaggc agcttcatgt 2220 gatttcctcg tatcatagaa aatagagaag gaacatggat agcattagca ctaataatac 2280 acacttgaag ttctcagaat actgatgatt gaaaactcaa acaactgctc tgttgaagtc 2340 ttcttttgat gagatgccta tgttagctga cgacattcac tttaagggct tcttcactgg 2400 attcttccct ctcctgttta taatgcagca cagtgttttt atttttccct gtctgagaag 2460 cacagattat ctgttaaatg ctgacttctt tcccctgctg tgtgtcttca tgtaacagtt 2520 tctcacccac ggataataaa tttgctacat gctctgatga cggcactgtt agaatctggg 2580 actttcttcg ttgccatgag gaaagaattc tccgaggtac gtgtactaac agtactgatt 2640 ggaatattta aatagggaag acatttgtgg ttaaatcatc acaaaaccac aatactggct 2700 tacacctcca ttcaattttt tttacatata cacaccgtct caggctcttc aaaaaaaccc 2760 agcactttct ctgactcaca gtcattttgt aggtttttac taccagtgtt atctttgaat 2820 ttttcagctg taaattaaat acaagagtgc ctccccctta cttgcttatc tgtatgcatc 2880 ttttagggct gtattccttt tccttccttg tagccagggt acttgttccc aacatattga 2940 cactgtggtt tgatttagat agccgtcatt ctcctggcag tccttttaca atatgaatta 3000 accgacaaga tagaggtatc aaagctacac ttcttagtgt tactattttt gaaagcagtt 3060 ggtttttcag tacaccacat ttgtactaca tggccggctt gttactaagt tcgggtggca 3120 ttgctgcttg tttacttttg ttgattttat aattaataaa cctctatgaa attacttcat 3180 tccgtaactg aaaaaaaaaa aaaaaa 3206 <210> 104 <211> 921 <212> DNA
<213> Homo sapiens <220>
<221> misc feature <223> Incyte ID No: 2942212CB1 <400> 104 ggtgctgatg ctgctgccat ttcatcacct ttgcgagcgc acatccatcc ctccgctctc 60 ccggcgcctg ggcctaccca gcttcgggct cccaggccag cgatgcgctc gcggctgagc 120 tagatcctgc cgagccgcgc tctctgaggc gtcggcgggg cgccccctcc cgccgtcccc 180 ggtccgggcc aaggagacct gcagagccgc ggccatggag gccatctggc tgtaccagtt 240 ccggctcatt gtcatcgggg attccacagt gggcaagtcc tgcctgatcc gccgcttcac 300 cgagggtcgc tttgcccagg tttctgaccc caccgtgggg gtggattttt tctcccgctt 360 ggtggagatc gagccaggaa aacgcatcaa gctccagatc tgggataccg cgggtcaaga 420 gaggttcaga tccatcactc gcgcctacta caggaactca gtaggtggtc ttctcttatt 480 tgccattacc aaccgcaggt ccttccagaa tgtccatgag tggttagaag agaccaaagt 540 acacgttcag ccctaccaaa ttgtatttgt tctggtgggt cacaagtgtg acctggatac 600 acagaggcaa gtgactcgcc acgaggccga gaaactggct gctgcatacg gcatgaagta 660 cattgaaacg tcagcccgag atgccattaa tgtggagaaa gccttcacag acctgacaag 720 agacatatat gagctggtta aaagggggga gattacaatc caggagggct gggaaggggt 780 gaagagtgga tttgtaccaa atgtggttca ctcttcagaa gaggttgtca aatcagagag 840 gagatgtttg tgctagtcag ttcttttatt tccaaaacat gctctcctac ttgaactgaa 900 aagtaagaga aataaataga a 921 <210> 105 <211> 1367 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 3685151CB1 <400> 105 aagaggcacg tgcgctgctg aatggagctg gtcgctggtt gctacgagca ggtcctcttt 60 gggttcgctg tacacccgga gcccgaggct tgcggcgacc acgagcagca atggactctt 120 gtggctgact tcactcacca tgctcacact gcctccttgt cagcagtagc tgtaaatagt 180 cgttttgtgg tcactgggag caaagatgaa acaattcaca tttatgacat gaaaaagaag 240 attgagcatg gggctctagt gcatcacagt ggtacaataa cttgcctgac attctatggc 300 aacaggcatt taatcagtgg agcggaagat ggactcatct gtatctggga tgcaaagaaa 360 tgggaatccc tgacgtcaat taaagctcac aaaggacagg tgaccttcct ttctattcac 420 ccatctggca agttggccct gtcggttggt acagataaaa ctttaagaac gtggaatctt 480 gtagaaggaa gatcagcatt cataaaaaat ataaaacaaa atgctcacat agtagaatgg 540 tccccaagag gagagcagta tgtagttatc atacagaata aaatagacat ctatcagctt 600 gacactgcat ccattagtgg caccatcaca aatgaaaaga gaatttcctc tgttaaattt 660 ctttcagagt ctgtccttgc agtggctgga gatgaagaag ttataaggtt ttttgactgt 720 gattcactag tgtgcctctg cgaatttaaa gctcatgaaa acagggtaaa ggacatgttc 780 agttttgaaa ttccagagca tcatgttatt gtttcagcat cgagtgatgg tttcatcaaa 840 atgtggaagc ttaagcagga taagaaagtt cccccatctt tactctgtga aataaacact 900 aatgccaggc tgacgtgtct tggagtgtgg ctagacaaag tggcagacat gaaagaaagc 960 cttcctccag ctgcagagcc ttctcctgta agtaaagaac agtccaaaat tggcaaaaag 1020 gagcctggtg acacagtgca caaagaagaa aagcggtcaa aacctaacac aaagaaacgc 1080 ggtttaacag gtgacagtaa gaaagcaaca aaagaaagtg gcctgatatc aaccaagaag 1140 aggaaaatgg tagaaatgtt ggaaaagaag aggaaaaaga agaaaataaa aacaatgcag 1200 tgaatcacag atgtctcctg aaagaactct tttagatgaa atcattctac tcaaatgtac 1260 cttaattttt tttttttccc tgagtaaaag caagaaattt cttcctttgg aaaaaatata 1320 tatattaaaa aaccactttt agatggtttt ttttaaaaaa aaaaaaa 1367 <210> 106 <211> 1560 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 4881515CB1 <400> 106 aggcggactg gggaggcggc ggcctggctc ggcctggcct ggcctgtcag ggcgcgggcg 60 gcggcggctc cagcaccatg tccctgcagt acggggcgga ggagacgccc ctcgccggca 120 gttacggcgc ggccgattcg tttccaaagg acttcggcta cggcgtggag gaggaggaag 180 aggaggcggc ggcggcgggc ggaggggttg gggcaggggc aggcggtggc tgtggtccgg 240 ggggcgctga cagctccaag ccgaggattc tgctcatggg actccggcgc agcggcaagt 300 cctccatcca gaaggtggtg tttcataaga tgtcacccaa cgagaccctc tttttggaaa 360 gtaccaacaa gatttataag gatgacattt ccaatagctc ctttgtgaat ttccagatat 420 gggattttcc tgggcaaatg gacttttttg acccaacctt tgactatgag atgatcttca 480 ggggaacagg agcattgata tacgtcattg acgcacagga tgactacatg gaggctttaa 540 caagacttca cattactgtt tctaaagcct acaaagttaa cccagacatg aattttgagg 600 tttttattca caaagttgat ggtctgtctg atgatcacaa aatagaaaca cagagggaca 660 ttcatcaaag ggccaatgat gaccttgcag atgctgggct agaaaaactc catcttagct 720 tttatctgac tagtatctat gaccattcaa tatttgaagc ctttagtaag gtggtgcaga 780 aactcattcc acaactgccg accttggaaa acctattaaa tatctttata tcaaattcag 840 gtattgaaaa agcttttctc tttgatgttg tcagcaaaat ctacattgca acagacagtt 900 cccctgtgga tatgcaatct tatgaacttt gctgtgacat gatcgatgtt gtaattgatg 960 tgtcttgtat atatgggtta aaggaagatg gaagtggaag tgcttatgac aaagaatcta 1020 tggcaattat caagctgaat aatacaactg tcctttattt aaaggaggtg actaaatttt 1080 tggcactggt ctgcattcta agggaagaaa gctttgaaag aaaaggttta atagactaca 1140 acttccactg tttccgaaaa gctattcatg aggtttttga ggtgggtgtg acttctcaca 1200 ggagctgtgg tcaccagact agtgcctcca gtctgaaagc gctgacacac aatggcacgc 1260 cacgaaacgc catctagtct gaatcccagc gtcggggctc tgtgccagct tactcttcac 1320 tccagggtcg gatgccacgt gctacaggac atgggagctg ctgcttgtgg gaatctggtg 1380 cctgttccac tagagacaag gggtagagtt tctcatttgg atgaaaaccc cttcaactgg 1440 tggtgtacaa ctgaagctac tatatctttt ttgaaaatgg caaaaaaaaa aaaaaaaaat 1500 tctggagacc acagaactca agtgtgtgtt tctcctcttt tgggtcccct ttaagtagtt 1560 <210> 107 <211> 1495 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 5324681CB1 <400> 107 gaagaggctc tgggctggca catgtgtatg gcggtgaggc gggcgggtac atggcgggct 60 ctgtgggact ggcgttgtgc gggcagacgt tggtggtgcg gggcggcagc cgattcctgg 120 ccacctccat agcaagcagt gatgatgaca gcctcttcat ctatgactgc agtgctgcag 180 aaaagaagtc acaagaaaat aaaggggagg acgcgccctt ggaccagggg agcggtgcga 240 ttctggcgtc caccttctcc aagtctggca gctattttgc tttaaccgat gacagtaagc 300 gtctgattct tttccgtaca aaaccatggc aatgtctgag tgtcaggacc gtggcaagga 360 ggtgtacagc cctgactttc atagcctcgg aggagaaggt cttggtggcc gacaagtctg 420 gagacgtcta ctccttttcg gtgctggagc cacacgggtg tggccgtcta gagctggggc 480 acctgtctat gctgttagat gtggctgtga gtcctgatga ccgcttcatc ctcactgccg 540 accgggacga gaagatccga gtcagctggg ccgcggcgcc ccatagcatc gagtccttct 600 gcttggggca cacagagttt gtgagccgta tctccgtggt gccaactcag cccgggctgc 660 ttctgtcctc ctctggggac ggcaccctga ggctctggga gtacaggagc ggccgccagc 720 tgcactgctg tcacctggcc agtctgcagg agctggtgga cccccaggcc ccccagaagt 780 ttgccgcgtc caggattgca ttctggtgcc aggagaactg cgtggcgctc ctgtgcgacg 840 gcactcctgt ggtctacatc ttccagctgg acgcccgcag acagcagttg gtgtacaggc 900 agcagctggc gttccagcac caagtgtggg acgtggcttt cgaggagacc caggggctgt 960 gggtgctcca ggactgccag gaagcccccc tggtgctcta caggcctgtg ggcgaccagt 1020 ggcagtctgt tcctgagagc accgtgttaa agaaagtctc tggtgttctt cgtgggaact 1080 gggccatgct ggaaggctct gccggcgcag acgccagctt cagcagtctc tacaaggcca 1140 cgttcgacaa cgtgacctcc tacctgaaga agaaagagga gagactgcag cagcagctag 1200 agaagaagca gcggcgccgg agtcccccgc ctgggcccga cgggcatgcc aagaagatga 1260 gaccggggga ggcgacgcta agttgctgat cgtggcggtc tgtttctgtc gactgtggac 1320 cacttatgtg cgatccgtgg accacttgcg tgcgatctgt cggccgacga tgagcttgtt 1380 cggatgtagc tccatcgtaa gtcgaggagc atctgtgatt tgtcctctgc ttatgggata 1440 tgtttttccg ctactgagtc tgtgtagtaa atttttgact aggaaaaaaa aaaaa 1495 <210> 108 <211> 1919 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 5387651CB1 <400> 108 cgccctgcat gcgagttggg ccgcgggcgg ggttggagcc tactcggggc gactgcgatg 60 gacgccttag aaggagagag ctttgcgctg tctttctcct ccgcctctga tgcagaattt 120 gatgctgtgg ttggatattt agaggacatt atcatggatg acgagttcca gttattacag 180 agaaatttca tggacaagta ctacctggag tttgaagaca cagaagagaa taaactcatc 240 tacacaccta tttttaatga atacatttct ttggtagaaa aatacattga agaacagctg 300 ctgcagcgga ttcctgagtt caacatggca gccttcacca-caacattaca gcaccataag 360 gatgaagtgg ctggtgacat attcgacatg ctgctcacct tcacagattt tctggctttt 420 aaagaaatgt ttttggacta cagagcagaa aaagaaggcc gaggactgga cttaagcagt 480 ggcttagtgg tgacttcatt gtgcaaatca tcttctctgc cagcttccca gaacaatctg 540 cggcactagg tcctacctcc agccaatgaa tgggatcatt ctggatgtca ccagcccaat 600 aggctcagct catgatgaca gaacacatct tggaaagact gactctgtta tgtaactctt 660 catttatgtt aagtattaat aggtcaaaac caaaatgacc taaccctcct ggacctattt 720 atcctgaaac accttcttgt attcattaac catagtactc ctccccacct caagtagaca 780 cctctctcag gagcttctga gtcagacgcc tctggagcga gccctatgtc aggcactcca 840 cctggggggc ccttccccag catacctgct ggtgtgtaag tgtggactaa cccgccgcca 900 ccaccctctg ttccagcagg ctctgcatga atctttgtgc acttgcacct ctttttcaca 960 tgggccacag tttcagtact tcagcctcag tggggttcct gatgtttatc tagggtgtta 1020 ctcaagccca gtttgagatt ttggagtctc ctgtgatcac atcttgtctc ggctgtagga 1080 atcaacagaa ggagacgtcc tctacataaa agctccatgt gaaaagctac tcctagtctt 1140 aacatttgca gtccttgtgt cactgtcttc tggtcctgat gtagtcccac tgtttctaga 1200 agtctctttt aagcattatt tttgaaaaaa aaaatatttt tatagatgaa tactcaggct 1260 aacctagtgg atgtgatctt ggaacttcca tgattatcca cttaaagatc aaagtattat 1320 atgctgtgtg ctttttaggt gtttgttagt actgtgaagg caaaaatgct ttctacattg 1380 acattcattc ctattttact gggcacctat gaatgtatgc tgtgtgctag aaatagacta 1440 aaacatattc ctatagcatg ttagtgtgtt tgcatgtttg ctgaaaatcc tttgtgtata 1500 aaccagtttg taaggttctc tgggttaggt agggactctg cagtttcttc ctgtcaaaat 1560 ctctcctacc aagatggtgt tccactgtcc agcccagcat gagtagcagg tagagcacag 1620 ctttactggc tgtttgtatg ctttggttta gtgcaatgtg tggtagatta cttatcagaa 1680 aacatatatg tcatctctag aacgaagaaa aagcatagta gttcaattcc cagtgtgtcc 1740 ctttgatttt ttttttttaa tagtaaaaat aagaatctgt actgactttt cacttggcca 1800 ttctggtttt aaaggacaag ctacaagctc tgtgtttctg tactgatgtg tcacttatta 1860 aatacttttg taccatgagt aaaacttcag gtgtttcgca agaaccacca ttctcaaaa 1919 <210> 109 <211> 2941 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 5595679CB1 <400> 109 attaggctaa taggacagca cttgaatggc ttagggctca accagactgt tgatctcctc 60 atgcaagagt caggatgtcg tttagaacat ccttctgcta ccaaattccg aaatcatgtc 120 atggaaggag actgggataa ggcagaaaat gacctgaatg aactaaagcc tttagtgcat 180 tctcctcatg ctattgtggt aagaggcgca cttgaaatct ctcaaacgtt gttgggaata 240 attgtgagga tgaagttttt gctgctgcag cagaagtacc tagaatacct ggaggatggc 300 aaggtcctgg aggcacttca agttctacgc tgtgaattga cgccgctgaa atacaataca 360 gagcgcattc atgttcttag tgggtatctg atgtgtagcc atgcagaaga cctacgtgca 420 aaagcagaat gggaaggcaa agggacagct tcccgatcta aactattgga taaacttcag 480 acctatttac caccatcagt gatgcttccc ccacggcgtt tacagactct cctgcggcag 540 gcggtggaac tacaaaggga tcggtgccta tatcacaata ccaaacttga taataatcta 600 gattctgtgt ctctgcttat agaccatgtt tgtagtagga ggcagttccc atgttatacg 660 cagcagatac ttacggagca ttgtaatgaa gtgtggttct gtaaattctc taatgatggc 720 actaaactag caacaggatc aaaagataca acagttatca tatggcaagt tgatccggat 780 acacacctgc taaaactgct taaaacatta gaaggacatg cttatggcgt ttcttatatt 840 gcatggagtc cagatgacaa ctatcttgtt gcttgtggcc cagatgactg ctctgagctt 900 tggctttgga atgtacaaac aggagaacta aggacaaaaa tgagccagtc tcatgaagac 960 agtttgacaa gtgtggcttg gaatccagat gggaagcgct ttgtgactgg aggtcagcgt 1020 gggcagttct atcagtgtga cttagatggt aatctccttg actcctggga aggggtaaga 1080 gtgcaatgcc tttggtgctt gagtgatgga aagactgttc tggcatcaga tacacaccag 1140 cgaattcggg gctataactt cgaggacctt acagatagga acatagtaca agaagatcat 1200 cctattatgt cttttactat ttcaaaaaat ggccgattag ctttgttaaa tgtagcaact 1260 cagggagttc atttatggga cttgcaagac agagttttag taagaaagta tcaaggtgtt 1320 acacaagggt tttatacaat tcattcatgt tttggaggcc ataatgaaga cttcatcgct 1380 agtggcagtg aagatcacaa ggtttacatc tggcacaaac gtagtgaact gccaattgcg 1440 gagctgacag ggcacacacg tacagtaaac tgtgtgagct ggaacccaca gattccatcc 1500 atgatggcca gcgcctcaga tgatggcact gttagaatat ggggaccagc accttttata 1560 gaccaccaga atattgaaga ggaatgcagt agcatggata gttgatggtg aatttggagc 1620 agacgacttc tgtttaactt aaaattagtc gtattttaat ggcttgggat ttggtgcaaa 1680 caaacatgat tgatagctgg acagacatgc tcgtcatgaa aaaagaacca tttctgaagc 1740 ccgattgggg ccaaacattt acaccttgct tcatagtaac cagttgagat gaagcacgtc 1800 gttagaacgt tgttggacac catgttgaat tattccccca tcggttgtga agaactgtgc 1860 tacattcagg cttacccatt gaactcagta tatatatttt tttccttcct gtcttttgtc 1920 tggcaggata ccattcttgt tgctcttctg tgtaatgaag tttaaatgct tgtttggaaa 1980 actttattta acagtttaga aggcttgata gaaagagtgc attagtctga agagtataca 2040 ttggatagga aagaatttcc ttcttttgtt tctccaaatc tttccgcctt atttagcttg 2100 agatctttgc agcttggttc atggattcta gccttgcccg ttgcgcagta tatactgatc 2160 cagatgataa accagtgaac tatgtcaaaa gcactctcaa tattacattt gacaaaaagt 2220 tttgtacttt tcacatagct tgttgccccg taaaagggtt aacagcacaa ttttttaaaa 2280 ataaattaag aagtatttat aggattaaag tgacttcatt tgtatacatt tggaatctaa 2340 accagcttaa aaacagtttc ctcaatgact tagatacaca gtataactga tgctcttctg 2400 gaataccaca tgagacatgg tcagaaacag tgcttggaag gacattacac aagaaattca 2460 gagtaatgct ttgaagattt cccccctttt gttttattcc tgaaggaaca tcagtacccg 2520 atcttgaaga aattcaagat tcaaaaagaa ttttaaatac accaacatga gacatcagta 2580 gtcagttggt tttcagtaaa gcttgttcca agttgttctc aacttaggaa gtaattttgg 2640 tgtgatctag caaaagagta ggaatcagcg atacaaccac tttggaagtt tatagtataa 2700 ttgaaattat tagaagaatt cagcaggtta cagacatact taaactggga ttaaaacctc 2760 atagtcattt ttcttaattg cccttaatat tttgacatat agggatacat aaatttaaag 2820 aatatttttt ctcagttttt tcagatattg ccatactgaa cctcattcta aactggtgct 2880 gtggatagtc tttccctctc ccctcctgtt ttagtttaag gaaaggtttc cttcatggaa 2940 a 2941 <210> 110 <211> 710 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 5782457CB1 <400> 110 ctcgcggtcg cctggccgtt gtcattgtcc ctccgctgtc accttttcaa gccccaggct 60 ggctgcttca gaagcccctg accccatgga ggagtgggac gtgccacaga tgaagaaaga 120 ggtggagagc ctcaagtacc agctggcctt ccagcgggag atggcgtcca agaccatccc 180 cgagctgctg aagtggatcg aggacgggat ccccaaggac cccttcctga accccgacct 240 gatgaagaac aacccatggg tggaaaaggg caaatgcacc atcctgtgag ccccgcaccc 300 ggcccctctc acaccatcct gtgagaccac gcccggcccc actcccacca tcttgtaaga 360 ctgtgcccag ccccactcac tccatcctgt gagtcccact cccagcccca ctcccaccat 420 cctgtgagcc catgcccggc cccactcaca ccaacctgtg agccccactc ccggccccac 480 tcacaacatc ttgtaagact gtgcccggcc ccattcactc catcctgtga gaccacgccc 540 ggccccactc actctatcct gtgagaccac gcctggcccc actcccacca tcctgtgagc 600 cccactcctg gccccactca caccatccta tgagcccacg cccggcccca ctcccaccat 660 cctgtgaacc ccactccact cgcacgtgat tacagtctgt aaaggtgtga 710 <210> 111 <211> 1351 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 760677CB1 <400> 111 ccaggcctag tggatagaca gggtccaaaa tgtgaccctt ctaggctggt atcaccatgg 60 gggcgtcatg ggctgaggat tctgcagata ggacatcacc acggcagaga tggacagcct 120 gagacaggag agaggtgtca gtctaggatg gccaggctgg gtccccccac cccttactca 180 agagtcactt gttctgtagg gcaagtctca catgaagcta ctcatcattt gcttcgtgtc 240 ctccgagctc cgagagttgg caaagctgat gaaggagcag tagacagcga cccaagcaca 300 ccacttcagc tagggaaaga ccgatttaag gctgcaagga aggagtcctg ggagcatggc 360 tttccctgag ccaaagccgc ggcctccaga gctgccgcag aaacggttga agacgctgga 420 ctgcgggcag ggggcagtgc gagccgtacg atttaatgtg gatggcaatt actgcctgac 480 gtgcggcagt gacaagacgc tgaagctgtg gaacccgctt cgggggacgc tgctgcggac 540 gtacagcggc cacggctacg aggtgctgga tgcggccggc tcctttgaca acagtagtct 600 ctgctccggc ggcggggaca aggcggtggt tctgtggaat gtggcatcag ggcaggtcgt 660 gcgcaaattc cggggccacg cagggaaggt gaacacggtg cagtttagtg aagaggccac 720 agttatcctg tccggctcta ttgattccag tatccgctgt tgggattgcc gctcacggag 780 gcctgagcca gtgcagacgc tggatgaggc cagagatggc gtgtccagtg tgaaggtgtc 840 agaccacgag atcctggcag gctccgtgga tggccgcgtg agacgctatg acctaaggat 900 ggggcagctc ttctcagact acgtgggcag ccccatcacc tgcacctgct tcagccggga 960 tgggcagtgc accctggtgt ccagcctgga ctccacattg cggctcctgg acaaagacac 1020 aggggagctg ctgggcgagt acaagggcca taagaaccag gaatacaagc tggactgctg 1080 cctgagcgag cgtgacacac atgtggtcag ctgttctgag gacgggaagg tgttcttctg 1140 ggacctggtg gagggtgcgc tggctctggc cctgcctgtg ggttccggtg tggtgcagtc 1200 gctggactac cacccaacag agccctgcct gctgaccgcc atgggaggca gcgtccagtg 1260 ctggcgagag gaggcctatg aggcagagga tggagcaggc tgaagccagg ggacccacca 1320 acaggaccaa ggaccgagac acagacatgg c 1351 <210> 112 <211> 1783 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 1348567CB1 <400> 112 cccacgcgtc cgcggacgcg tgggctgaag gctgtggcgc gcggctgtcc ccattcccac 60 gtgaagcgct acgctagcat cgctcggctg gcggctccca gctcgccgcg gagcagtccc 120 ggcagcagcg ggggaccgga agtggctcgc ggaggctcag aagctagtcc cggagcccgg 180 cgtgtggcgc ctcggagcgc ggtgacggcg ccatgtccct aatctgctcc atctctaacg 240 aagtgccgga gcacccatgt gtatcccctg tctctaatca tgtttatgag cggcggctca 300 tcgagaagta cattgcggag aatggtaccg accccatcaa caaccagcct ctctccgagg 360 agcagctcat cgacatcaaa gttgctcacc caatccggcc caagcctccc tcagccacca 420 gcatcccggc cattctgaaa gctttgcagg atgagtggga tgcagtcatg ccgcacagct 480 tcactctgcg ccagcagctg cagacaaccc gccaagagct gtcacacgct ctgtaccagc 540 acgatgccgc ctgccgtgtc attgcccgtc tcaccaagga agtcactgct gcccgagaag 600 ctctggctac cctgaaacca caggctggcc tcattgtgcc ccaggctgtg ccaagttccc 660 aaccaagtgt tgtgggtgcg ggtgagccaa tggatttggg tgagctggtg ggaatgaccc 720 cagagattat tcagaagctt caagacaaag ccactgtgct aaccacggag cgcaagaaga 780 gagggaagac tgtgcctgag gagctggtga agccagaaga gctcagcaaa taccggcagg 840 tggcatccca cgtggggttg cacagtgcca gcattcctgg gatcctggcc ctggacctct 900 gcccgtccga caccaacaag atcctcactg gtggggcgga taaaaatgtc gttgtgtttg 960 acaaaagttc tgaacaaatc ctggctaccc tcaaaggcca taccaagaag gtcaccagcg 1020 tggtgtttca cccttcccag gacctggtgt tttctgcttc ccccgatgcc actatcagga 1080 tttggtcggt ccccaatgcc tcttgtgtac aggtggttcg ggcccatgag agtgctgtga 1140 caggcctcag ccttcatgcc actggcgact atctcctgag ctcctccgat gatcagtact 1200 gggctttctc tgacatccag acagggcgtg tgctcaccaa ggtgacagat gagacctccg 1260 gctgctctct cacctgtgca cagttccacc ctgacggact catctttgga acaggaacca 1320 tggactctca gatcaagatc tgggacttga aggaacgtac taatgtggcc aacttccctg 1380 gccactcggg ccccatcact agcatcgcct tctctgagaa tggttactac ctggctacag 1440 cggctgatga ctcctctgtc aagctctggg atctgcgcaa gcttaagaac tttaagactt 1500 tgcagctgga taacaacttt gaggtaaagt cactgatctt tgaccagagt ggtacctacc 1560 tggctcttgg gggcacggat gtccagatct acatctgcaa acaatggacg gagattcttc 1620 actttacaga gcatagcggc ctgaccacag gggtggcctt cgggcatcac gccaagttca 1680 tcgcttcaac aggcatggac agaagcctca agttctacag cctgtaggcc ctggcccttc 1740 tgatggaagc tgggcctcat ctcagtagag gggtagaatt agg 1783 <210> 113 <211> 3453 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 1751354CB1 <400> 113 ggcttgcgca ctacgtcccc agccagaggc tcctacccgg tcggggactt ccggaacgcc 60 ggggtgtggt tccgggtcgt gtgcggctcg gggtaatagg gctgctgctc ggccggccgg 120 cggcggcgag cagcaggggc atgagggcta acccgggaag cggcagctga gcgggccggg 180 aggagcgccg gtccccgtgg atcccgagag tgcagagctc ggggcagggg ccgggaggcg 240 tgggggagcc gggccctccc ctcaggaacg tgtcccgggg ccgacccggc ccgtagtgtg 300 gaagcagctt caggtaggtg agctcgtgaa acaatatgaa gaggagaaaa tagcctttta 360 aggaaattgg cccacagaaa ggatggcctt cttggacaat ccaactatca ttctagctca 420 tattcgacag tcacatgtga ccagtgatga cacgggaatg tgtgagatgg ttctcattga 480 tcatgatgtt gacctagaga agattcatcc tccttcaatg cctggagaca gtgggtcaga 540 aattcaggga agcaatggtg agactcaggg ctatgtatat gcccagtcag tcgatattac 600 ctcaagttgg gactttggta ttagaagacg ctcaaacaca gctcaaagat tagaacgact 660 ccgaaaagag agacaaaacc agatcaaatg caaaaatatt cagtggaaag aaagaaattc 720 taagcaatca gcccaggagt taaagtcact gtttgaaaaa aaatctctca aagagaagcc 780 tccaatttct gggaagcagt cgatattatc tgtacgccta gaacagtgcc ctctgcagct 840 gaataaccct tttaacgagt attccaaatt tgatggcaag ggtcatgtag gtacaacagc 900 aaccaagaag atcgatgtct acctccctct gcactcgagc caggacagac tgctgccaat 960 gaccgtggtg acaatggcca gcgccagggt gcaggacctg atcgggctca tctgctggca 1020 gtatacaagc gaaggacggg agccgaagct caatgacaat gtcagtgcct actgcctgca 1080 tattgctgag gatgatgggg aggtggacac cgatttcccc ccgctggatt ccaatgagcc 1140 cattcataag tttggcttca gtactttggc cctggttgaa aagtactcat ctcctggtct 1200 gacatccaaa gagtcactct ttgttcgaat aaatgctgct catggattct cccttattca 1260 ggtggacaac acaaaggtta ccatgaagga aatcttactg aaggcagtga agcgaagaaa 1320 aggatcccag aaagtttcag gccctcagta ccgcctggag aagcagagcg agcccaatgt 1380 cgccgttgac ctggacagca ctttggagag ccagagcgca tgggagttct gcctggtccg 1440 cgagaacagt tcaagggcag acggggtttt tgaggaggat tcgcaaattg acatagccac 1500 agtacaggat atgcttagca gccaccatta caagtcattc aaagtcagca tgatccacag 1560 actgcgattc acaaccgacg tacagctagg tatctctgga gacaaagtag agatagaccc 1620 tgttacgaat cagaaagcca gcactaagtt ttggattaag cagaaaccca tctcaatcga 1680 ttccgacctg ctctgtgcct gtgaccttgc tgaagagaaa agccccagtc acgcaatatt 1740 taaactcacg tatctaagca atcacgacta taaacacctc tactttgaat cggacgctgc 1800 taccgtcaat gaaattgtgc tcaaggttaa ctacatcctg gaatcgcgag ctagcactgc 1860 ccgggctgac tactttgctc aaaaacaaag aaaactgaac agacgtacga gcttcagctt 1920 ccagaaggag aagaaatccg ggcagcagtg acactggcct ccagcctcaa tctgttccgt 1980 agctcagagc ctgcctgcca gggccaagtg ccctagagcc cacccggtgt cctgaagtcc 2040 tcggggggag gccagcccct ggctcactgg cacagggcag gtgggctctc ggggaaggtg 2100 tcgggggccc cctaggaggg agcgctgggg acattgccat gggacggaag tctgcttggc 2160 agtggctttg ataagcgatg cttgggggtc agaccacccc ctagaggagc cacgtgccgc 2220 ccagccacct tcaatgcctg ccaccctgcc cgaggatgta cagagccgtg cccacacatt 2280 tccttgcaac ttgatcaaat ttcttaaagc aaacaacaaa aatgtacatt tctgtttttc 2340 cttttaataa acaggtgtac tctttatcat ggttggtatg atggaccatt ctttggggcg 2400 gaggattgat tatgttactc tctttaaaat ctgttcccat attgaacagg cagattggaa 2460 100/11$

aagctatggt tcgatttctc agaagaaatg tttaggtctt agtcaatagt tttaactatg 2520 ccatttgttt aaatgagtgc atttgcttcg agggtagtgt cttactaaaa gttaggaaca 2580 gagacctagt ggtgtgtcca aggccgtgtc actttcccct tcagcacacc ccagcttctg 2640 acctcagagc ccaggagctg cgtggacagt gtggggtgcc aggaggaggg gcggtggctg 2700 gtcctcaggc acgctgcact cccagccaga catggtcttt ccgtttctta agtagcaagt 2760 gtaggtttca gctggcagtt ccacctgcat gttctctgct tcgctgcctt ggaaggggcc 2820 acattcccca ttcctcttct ccttacagcg cctgcctcct ttttcaagca ggcggaaagc 2880 tgctgtttct cacgtttcag ggagaggggt gagcggaggg agacctgtgt ccgtgccgtc 2940 cggctccctg ggtgggaaca ggcaagggat cagatgcccc tgacaccacg cctctggcca 3000 caccagatgc ctctgcagtc ctcgacagcc tcttcagtgt ccctcctgcg gtgatgtcct 3060 tactgtcccc agccagggcc ggggaccggt gtttcactga ggacctgcat tagaaacatt 3120 ttttaaattg ttgtacagga agagatgtgt ctaaaacagc atcttaaagc tgagtgtatt 3180 tctttgcaca aggggtcatg ctgatgaatt cttctttcat tctgatcttt gttcagccaa 3240 caggagcgtc cttttctaat gtcttccatt cctacccccc acccaaaaac aaaagaaata 3300 tttgtagctt gctatctgta tttgaatttt tagcaatttt atatttagat actttgaaaa 3360 atgtaaatga ctaatttggt cattaaatct tgtgacatat tcgatattaa aatgatatta 3420 aaataaaagt catataaata cacaaaaaaa aaa 3453 <210> 114 <211> 2663 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 1976780CB1 <400> 114 gaaaaaggtt cgaaagaact ggttgtcttc ttgggcggtg ttgcagggtt catctttact 60 ttttaccaaa actcaaggaa gtagcacaag ttggtttggc agtaatcagt ccaaaccaga 120 gttcacagtg gacctcaagg gggcaacaat tgagatggct tcaaaggata aatccagcaa 180 aaagaatgta tttgagctga aaactcgtca aggaacagaa ctgctaattc agtctgacaa 240 tgacactgtt attaatgatt ggtttaaagt tcttagtagt acaatcaata atcaggcagt 300 agaaactgat gaaggaattg aagaggagat accggattca ccaggaatag aaaagcatga 360 taaagaaaag gaacaaaagg atcccaaaaa gcttcgttcc tttaaagtat ctagcataga 420 ttcttcagaa cagaaaaaaa ccaagaaaaa cttaaagaag tttcttacac gacgccccac 480 tttgcaagct gttcgtgaaa aaggttatat taaagatcag gtatttggat ccaatctcgc 540 taatctgtgt cagagagaga atggcacagt accaaagttt gtgaagttat gtattgaaca 600 tgttgaagaa catggtttgg atattgatgg gatatacaga gtaagtggca acctcgcagt 660 gatccagaaa ctaaggtttg cagtcaatca tgatgagaaa ttggacttga atgacagtaa 720 atgggaagat attcatgtca ttactggagc cctcaaaatg ttttttcgag aattaccaga 780 acctcttttt acatttaatc attttaatga ttttgttaat gcaattaagc aagaaccaag 840 acagcgagtc gctgctgtta aggacctaat cagacagttg ccaaagccaa accaagacac 900 aatgcagatt cttttccgac atctcagaag agttatagaa aatggagaga aaaatcgaat 960 gacctatcag agtatagcaa ttgtttttgg tcccactcta ttaaaaccag aaaaagagac 1020 tggtaatata gcagttcata ctgtgtacca gaatcagatt gtagaattaa ttcttctgga 1080 actgagttcc atcttcggac gttgattctt actgaagaca acctgtggaa tagaagctgg 1140 attccatcag atttcaaatg tttatacaca atgtatttta ttttttggac caagcagtga 1200 ctctttgatt ttgcactttt tttttgaggg atcagaaggg aaggggagag tcgagatgtg 1260 tgttaggccc tcatatttgc tgctttgttg caagttgata taactgcgtg taattatgaa 1320 ttcattttat cctgaatgtt tgcatttcat actctgaatt tcagtaaaaa tcaaaactta 1380 aaattctaac cagtcatata cactggataa tttggtaaga aaactgtatt ttttttccct 1440 gaaattggat aatgtacttt cttctcaaga ttcatgactt gatagaacaa tactttcagt 1500 tatgttgcaa aggctcttgg gcattttaaa caaaatgaag tatatccatt ttgaaacctg 1560 tgtatttctt tttcggggtt tctgcatgca gtggcagtct taagtgccaa aattcattat 1620 aaccccaaaa taaccccttg atgaaggctt gctgtctttt actgtgttac acagcatcct 1680 tactggatat cttagttgct tgtttgggca gcacactaat attacttaaa acactgtgat 1740 atactggagt tttagttagc ggaagtcagt tcagggcatt ttagggctgt cttgctatac 1800 tgaattgtag ctaacaatcc taattatatc tagtaccata ctgagttatt ggtatgaccc 1860 tgtggaaaca cacattattt tatgtaaata taggctaaag acttaatgtc ctttagcttg 1920 tgtatataat tgtgttgtat agtctcagag tacattctaa ccctacattt ctaatcattg 1980 ttattggtaa tcttttctgt gaatattagg tttcctccag aaatggtccg ttatttggga 2040 aagttaactg tgtgcacttt tagatattaa ctacatttac aggcaaatca ctgtaatgag 2100 aatggtactg gaaaaatact gaatagactt gctaaatggc acatgcacta caagaggaac 2160 cttttgggtt atttaatatg tacagaaaac attagaaaaa atttattaca gaattctaat 2220 tccagtatga atagtggaaa cccatctgta aattagatgg atgttggatg gaaaatgaca 2280 ttgctaaatt tgagaatttc tttttaccta ctaatgtaga ttgctttgta taataaaaca 2340 cagggtttgg aaggttttgt tacagggagc atggtctgtt gaagattttt aaaatgtatt 2400 tttctagatt aacttctgta catgaaatgt ctaataaaac tataagaggt ttagagattt 2460 ttccattgga aatgtgcatt ttggtttcta atttttttgt tttttcattt actggcatac 2520 tgttatacct catttttaaa aatcaactga atccaatatt tcctgtggca aataacactt 2580 tcctcatttc ataccttttc tcctctcttc catgccaaca tttctccacc cacaacgtac 2640 actgtttatt tctcatcaat att 2663 <210> 115 <211> 1218 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 2048234CB1 <400> 115 gcctgttgca gccatggtgc attgcagttg cgtgttgttc agaaagtatg gaaatttcat 60 cgataagcta agactcttca ccaggggagg atccggtgga atgggttatc ctcgtttagg 120 tggagaaggt ggaaaaggtg gtgatgtctg ggttgtagcc cagaacagaa tgactttaaa 180 acaacttaaa gacaggtatc ctcggaaacg gtttgtggct ggagtaggag caaacagcaa 240 aattagtgca ctgaaaggct ccaaaggaaa agactgggaa atccctgtgc ctgtgggtat 300 ttcagtaact gatgaaaatg gtaaaattat aggagaactc agtaaagaaa atgacagaat 360 tttggtagct caaggaggtc ttggtggtaa attacttaca aatttcttac cattgaaagg 420 ccagaaacga ataattcacc ttgatctaaa acttatagct gatgtaggcc tagtaggatt 480 cccaaatgct ggaaaatcct ctttgctaag ttgtgtttct catgcaaaac ctgcaattgc 540 agattacgca tttacaacat taaagctgaa gctcggaaag ataatgtaca gtgatttcaa 600 acagatatca gtagctgatc ttccgggttt aatagaagga gcacatatga acaaaggaat 660 gggccacaaa ttcctcaagc atatagaaag aactagacaa ctactttttg ttgttgatat 720 ttctggattt cagctttctt ctcacactca atacaggaca gcttttgaaa ccataatact 780 gcttacaaaa gagttggaat tgtacaaaga ggaacttcag acaaaacctg cactcttggc 840 agttaataaa atggacttgc cagatgccca agataagttc catgaattga tgagccagct 900 ccagaatcct aaagattttc tgcatttatt tgaaaaaaac atgattccag agaggactgt 960 agagttccaa catatcatcc ccatatctgc agttactgga gaaggaatcg aagaattaaa 1020 gaattgtata agaaagtcac tggatgaaca ggccaaccag gaaaatgatg cacttcataa 1080 gaaacagttg cttaatttgt ggatttctga tacaatgtct tctactgagc caccatcaaa 1140 gcatgctgtt actacttcca aaatggatat aatttaaata tattaaaaat ggtattgatg 1200 gaacagtaaa aaaaaaaa 1218 <210> 116 <211> 1286 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 2111754CB1 <400> 116 cccgccttga acttctggac tagcccctcg attgttgtag atgccaagcg gacctcgcgc 60 cgctctgcgt tgggccagcc cctcacagct ggtttcttac cacgtattgc gcaacggaat 120 ctatgcctgt tacccacact ccctgcgccc ccgcaccccg ctcctgtgcg caagtcggaa 180 tataaaaccg cggaggagtg agctcttggg gtgtccagtt ggttgccgcg gcagtctctc 240 cgagcagcgc atttgtcttc taggctgctt ggttcgtgcc tccgagaaag gggtctcctg 300 ctgccagcta agtgtgggag aacttgtgca cgtatctccc ctccgaatcc caacgatggg 360 taacgccagc tttggctcca aggaacagaa gctgctgaag cggttgcggc ttctgcccgc 420 cctgcttatc ctccgcgcct tcaagcccca caggaagatc agagattacc gcgtcgtggt 480 agtcggcacc gctggtgtgg ggaaaagtac gctgctgcac aagtgggcga gcggcaactt 540 ccgtcatgag tacctgccga ccattgaaaa tacctactgc cagttgctgg gctgcagcca 600 cggtgtgctt tccctgcaca tcaccgacag caagagtggc gacggcaacc gcgctctgca 660 gcgccacgtt atagcccggg gccacgcctt cgtcctggtc tactcagtca ccaagaagga 720 aaccctggaa gagctgaagg ccttctatga gctgatctgc aagatcaaag gtaacaacct 780 gcataagttc cccatcgtgc tggtgggcaa taaaagtgat gacacccacc gggaggtggc 840 cctgaatgat ggtgccacct gtgcgatgga gtggaattgc gccttcatgg agatttcagc 900 caagaccgat gtgaatgtgc aggagctgtt ccacatgctg ctgaattaca agaaaaagcc 960 caccaccggc ctccaggagc ccgagaagaa atcccagatg cccaacacca ctgagaagct 1020 gcttgacaag tgcataatca tgtgagccct gggccttaag agccagctct tcctatcctg 1080 tagcgtgtag aaaacgtgga ctcatttcac tatgttacat gtacatggtt gattttgtgc 1140 tgttgtttgg actgtaacat ccatgttgtc aatacgtata ccttgtaagt ggataacttt 1200 tctttttccc aggccagaga attcaaattg ttaaaacatt ggcatttgaa gaggagaaca 1260 aaatgtagca tgatgtattt aaagta 1286 <210> 117 <211> 3057 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 2123286CB1 <400> 117 caaggctccg gcctgcgagg agtcacatta actttgctct agaagacaac tttacaagga 60 tctaaaagga acaggattaa agatgactga atactgggtt ccagaaattt aaaacaatca 120 gcttagcaaa tcatatattc ttctgtggag ctgagaattg atgtccgctc ttccccgtga 180 tttggaactt tccaatccca gagaaaagtt gacaaaggga ctgcccagga ctgagtccat 240 atggaagaag aacttcctct tttctctgga gacagtggca agccagtaca ggctactctg 300 tcatctttga agatgttaga tgtgggaaag tggccaattt tttccctttg ttctgaagaa 360 gaactacagt taattcgtca ggcttgtgtc tttggcagtg ctggcaatga agttttatac 420 actacagtaa atgatgagat ttttgtgctt ggcacaaact gctgtggctg tttggggtta 480 ggtgacgtcc agagcaccat tgaacctcgg agactggatt ctttaaatgg caaaaaaata 540 gcctgcctca gctatgggag tggtccacat attgtccttg caacaacaga aggagaagtc 600 tttacctggg gtcataatgc ttatagccag ctgggcaatg ggacaactaa tcatggttta 660 gtgccctgtc atatctctac taatctgtca aacaaacaag tcattgaagt tgcctgtggg 720 tcttaccatt ctttggtgct aacatctgat ggagaggtat ttgcctgggg ttataataac 780 tctgggcagg taggatctgg atcaacagtt aatcagccaa tccctcgaag agtcactggc 840 tgcctacaaa ataaagtagt tgtgaccata gcatgtgggc agatgtgctg catggcagta 900 gtagacacgg gggaggtcta tgtctggggt tacaacggaa acgggcagct tggactcggc 960 aacagtggca accagccaac cccttgcaga gtggcagctt tgcaaggcat ccgtgtccag 1020 agggtcgcct gtggctacgc acacacatta gtattaacag atgaaggcca agtgtatgct 1080 tggggcgcca attcttatgg gcagttgggc actggcaata aaagcaacca gtcctatcct 1140 actcctgtca ctgtggaaaa ggacaggatt atcgagattg cagcctgtca ctccacacac 1200 acgtctgcgg ccaagacgca gggtgggcac gtgtacatgt ggggccagtg ccggggtcag 1260 tccgtgatcc tcccgcacct cacccacttc tcctgcactg acgacgtgtt tgcctgcttt 1320 gccacgcccg ccgtcacgtg gcgcctcctc tccgtggaac ctgatgacca cctcacagtg 1380 gctgagtcac tgaagaggga atttgacaac ccggacactg cagacctgaa gtttctagtt 1440 gatggaaagt acatttatgc acataaagtc cttctcaaga ttcgatgtga gcattttcgt 1500 tcgtcattgg aagataacga ggatgatatt gtagaaatga gtgaattttc atatcctgtt 1560 taccgggcct tcctggaata cctatacaca gacagcatca gcctttctcc tgaggaggca 1620 gtaggactgc tagacttggc tacattttat agagaaaatc gtttgaaaaa gctctgccaa 1680 caaactatca agcaaggcat ctgcgaggag aatgccatcg ctctgctctc ggctgcggtg 1740 aagtatgatg cacaggattt agaagaattc tgcttcaggt tttgcataaa ccatctgact 1800 gtagtaacac aaacatcagg ttttgcagaa atggaccatg atctcctgaa gaactttatc 1860 agcaaagcaa gcagagttgg agcctttaaa aattgatccc atctgcagga aagtttttga 1920 gcctttccat ttcccctgca aaagccagag atgaatcact tctctttaat taatagtatg 1980 tatgatgagc tatgtttggc tgagtacttg taactgtcag aagaaggatg gtggtgagtg 2040 gtctttgtct gcctaaaccc agagtttatg tagaaagcat tgaatgttct gatcagatgt 2100 gactaaggtc aaggaaaaaa aattgaaata tcttatttac catttcctct ttttgagtca 2160 cttaaattgg acacctttgg taccctggtc tcagtatatg ctattctggc ccaaatgttc 2220 cattattcag ctggctgata ccacatagat agcttgacaa ggagtgctgt ctgtccttac 2280 cacattttca gcactcagca cagtgccttg tgtataatag gcactcaatt tattataaat 2340 cttcagtatg tcctgagaac agctttagtc atggaatact gggagaagga ataactttca 2400 caaaataaac ttaaaacagc ctgtaattat tgaggttcat attcttctgg tatatcattc 2460 tgagaaattg tggctaattt agaacattgt ttagaattga caaaaggccc tggcaattaa 2520 attgtcaagg cccaagggct aattttaatt ttctttttac ttggagtcat tcattaattt 2580 ctcacatggg attatggagt atgaagtatt atctttgaat gaaattcctg ggctgatctg 2640 ccttacataa tcacataagg tcctttgctt ttctttgtgt taagagggac ttgcctctgt 2700 aaatgaaaat gacaatgtgc ttttcttgta gttgactttc atgtcactca ctataaaata 2760 ggtctcttaa cctggcacca gtataactat aaagcactag ctgagaagga actgatactt 2820 acatttcatg gacagcatta acaagaatga gataaatttg tactttttag atcaaaacaa 2880 attacctaat tgcaaaagag aaactgaaat ggaacatagt ctcagattct tctaatgtgt 2940 atctcacaat gtcatgtaat gtaaaggaaa cccttttgga attagaattc ttgttctgat 3000 gctgaactat ttggtaataa agtgcttatt tgcagataac agaaaaaaaa aaaaaaa 3057 <210> 118 <211> 1803 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 2477507CB1 <400> 118 ggtcgcggcc ttcacgggtt cctcggccgt cctgagtccc aaatcccaag ctggagccgt 60 tcagctcccc tccaccgctt agagatttgg ggggctctgg ccccgtcctt gcggaccatt 120 ccgaggggag tccagaggtg aggccgagga acctccctga ctttgcgggg cgcgccgctc 180 ctgcgtctcc tgccagtctc ccttccttct tttcggtcaa caattgaaaa caaaacgagg 240 aacagcagag gagctactgt ataccgagcc ctcagcattg ttcgtaatct ccgcctgcta 300 acagccttgt gaagaaggtg ctattcttct caacacttta cagatgagga cacttgaggt 360 tcggagacgt ggagcctctt gcacagctgc ttaagtggtg gtagagccga gatttgaacc 420 ctcctaacca ttcctttctg ccgcctactg cagctcccag cagagatgat tgaactgttg 480 ctcggggtag ggcccccagg tgtcagtaat taacactgtg gatacctccc atgaggacat 540 gattcacgac gcccagatgg actactatgg cacccgcctg gcaacctgct catcagacag 600 gtccgtcaaa atctttgatg tgcgcaatgg agggcagatc cttatcgccg acctcagggg 660 tcatgagggt cctgtgtggc aagtggcctg ggctcacccc atgtacggca acatcctggc 720 atcgtgctcc tatgaccgga aagtcattat ctggagagag gaaaacggca cctgggagaa 780 gagccacgag catgcgggac acgactcctc agtgaactcg gtgtgctggg ccccccatga 840 ctacggcctg atcctggcct gtgggagctc ggatggggcc atctccctgc tgacttacac 900 cggggaaggc caatgggaag taaagaagat caacaacgct cacaccattg gctgcaatgc 960 cgtcagctgg gcccctgctg ttgtacctgg aagcctcata gaccacccat cggggcagaa 1020 acccaattac atcaagaggt ttgcatcagg tggctgtgac aacctcatca agctgtggaa 1080 ggaggaggag gacggccagt ggaaggagga gcagaagcta gaagcgcaca gtgactgggt 1140 tcgagatgtg gcctgggccc cctccatcgg cctgcccacc agcaccatcg ccagctgctc 1200 ccaggatggt cgtgtgttca tttggacctg tgatgatgcc tcaagcaata cgtggtcccc 1260 taaattgttg cacaagttca acgatgtggt gtggcatgtg agctggtcca tcacagccaa 1320 catcctggct gtctctggtg gagacaataa ggtgaccctg tggaaggagt cagttgatgg 1380 gcagtgggtg tgcatcagtg atgtcaacaa gggccagggc tccgtatcag catcagtgac 1440 agagggccag cagaacgagc agtgacaaga caggtggggc ctggctcccc acccgccagc 1500 tccaggactg ccccttcctg ggccaactaa ccagacaact gggaagagcc cccaactcca 1560 acaggattat tttcccagga ggagttacag atgcagccac.agattgatca tctgccttaa 1620 cgtgatcgga gatgctttgt aatctactgt ccagctgaaa gcactcatgt tacgaggaag 1680 aaactacaag tgatgttcaa atctattttg ggtcattttt atgtaccttt gggttcaggc 1740 attatttggg gggttttgtt tccaaaggaa ctaaataaag tcatattgct tataaaaaaa 1800 aaa 1803 <210> 119 <211> 4407 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 2759119CB1 <220>
<221> unsure <222> 4373, 4379 <223> a, t, c, g, or other <400> 119 ggtcgtcatt ggacaaccgc cgcggggccc tggtctctgc tacctgtagc tgagggtgct 60 gttgatgggc agcgcggcgc gctgggaagg ctcgttctcg cgagagttca gctcccttct 120 atacccgtgg ctgcctcagc acctcgagga tcgacatgga cgctctcgag gactacgttt 180 ggccgcgggc aacctcggag cttatactcc tcccagtgac gggtctggag tgcgtggggg 240 accggctgtt ggcgggtgag ggtcccgatg tcctggtgta cagcttggac tttggtgggc 300 atctgcggat gataaagcga gtgcagaacc tgcttggcca ctatcttatc catggcttcc 360 gggtacggcc agagcctaat ggagaccttg acttggaggc catggtggct gtgtttggaa 420 gcaagggact ccgagttgtg aaaattagct ggggacaggg ccacttctgg gagctttggc 480 gctctggcct gtggaacatg tctgactgga tttgggatgc acgctggctt gagggaaata 540 tagccttggc cctgggccac aactcagtgg tgctatatga ccctgtagta gggtgcatcc 600 tgcaagaggt gccctgcaca gacaggtgca ccctctcttc agcctgcctg attggagacg 660 cctggaagga gctgaccata gtggcaggtg ctgtttccaa ccagctcttg gtctggtacc 720 cagcaactgc cttagcagac aacaaacctg tagcacctga ccgacgaatc agtgggcatg 780 tgggcatcat cttcagcatg tcatacctgg aaagcaaggg attgctggct acagcttcag 840 aagaccgaag cgttcgtatc tggaaggtgg gcgacctgcg agtgcctggg ggtcgggtgc 900 agaatattgg gcactgcttt gggcacagcg cccgtgtgtg gcaggtcaag cttctagaga 960 attaccttat cagtgcagga gaggattgtg tctgcttggt gtggagccat gaaggtgaga 1020 tcctccaggc ctttcgggga caccagggac gtgggatccg ggccatagct gcccatgaga 1080 ggcaggcctg ggtgatcact gggggtgatg actcaggcat tcggctgtgg cacttggtag 1140 ggcgtgggta ccggggattg ggggtctcgg ctctctgctt caagtcccgt agtaggccag 1200 gtacactcaa ggctgtgact ctggctggct cttggcgact gctggcagtg actgatacag 1260 gggccctgta tctctatgac gtcgaggtca agtgctggga gcagctgcta gaggataaac 1320 atttccagtc ctactgcctg ctggaggcag ctcctggtcc cgagggcttc ggattgtgtg 1380 ctatggccaa tggggaaggt cgtgtcaagg ttgtccccat caacactcca actgctgctg 1440 tggaccagac cctgtttcct gggaaggtgc acagcttgag ctgggccctg cgtggttatg 1500 aggagctcct gttgctggca tcgggccctg gcggggtagt agcttgccta gagatctcag 1560 ccgcaccctc tggcaaggcc atctttgtca aggaacgttg tcggtacctg ctgcccccaa 1620 gcaagcagag atggcacaca tgcagtgcct tcctaccccc aggtgacttc ctggtgtgtg 1680 gtgaccgccg gggctctgtg ctgctattcc cctccagacc aggtctgctc aaggaccctg 1740 gggtgggagg caaggctcgg gctggtgctg gggcacctgt agtgggtagt ggtagtagtg 1800 ggggtgggaa tgctttcact gggttgggcc cagtgtctac cctgccctct ctgcacggga 1860 agcagggtgt gacctcagtc acatgccatg gtggctatgt gtataccata gggcgtgatg 1920 gagcctacta ccagctgttt gtacgagacg gccagctcca gccagtccta aggcagaagt 1980 cctgtcgagg catgaactgg ctagctgggc tccgtatagt gcccgatggg agcatggtta 2040 tcctgggttt ccatgccaat gagtttgtgg tgtggaaccc tcggtcacac gagaagctgc 2100 acatcgtcaa ctgtggtgga gggcaccgtt cgtgggcatt ctctgatact gaggcggcca 2160 tggcctttgc ttacctcaag gatggggatg tcatgctgta cagggctctg ggtggctgca 2220 cccggccaca cgtgattctc cgggagggtc tgcatggccg tgagatcact tgtgtaaagc 2280 gtgtgggcac cattaccctg gggcctgaat atggagtgcc cagcttcatg cagcctgatg 2340 acctggagcc tggcagtgag gggcccgact tgactgacat tgtgatcaca tgtagtgagg 2400 acactactgt ctgtgtccta gcactcccta caaccacagg ctcagcccac gcactcacag 2460 ctgtttgtaa ccatatctcc tcggtacgtg ctgtggctgt gtggggcatt ggcaccccag 2520 gtggccctca ggatcctcag ccaggcctga ctgcccatgt ggtgtctgcg ggggggcggg 2580 ctgagatgca ctgcttcagc atcatggtta ctccggaccc cagcacccca agccgcctcg 2640 cctgccatgt catgcacctt tcgtcccacc ggctagatga gtattgggac cggcaacgca 2700 atcggcatcg gatggttaag gtagacccag agaccaggta catgtccctt gctgtgtgtg 2760 aacttgacca gcccggcctt ggcccccttg tggctgcagc ctgtagtgat ggggccgtaa 2820 gctctttctt ttgcaggatt ctgggcggat tctgcagctc cttgctgaaa ccttccacca 2880 taagcgatgt gtcctcaagg tccactcctt tacacacgag gcacccaacc agaggcggag 2940 gctcctcctg tgcagcgcag ctactgatgg cagcctggct ttctgggatc tcaccaccat 3000 gctagaccat gactccactg tcctggagcc tccagtggat cctgggcttc cctaccggct 3060 tggcaccccc tccctgactc tccaggccca cagctgtggt atcaacagcc tgcacacctt 3120 gcccacccgt gagggccacc atctcgtggc cagtggcagt gaagatggat ccctccatgt 3180 cttcgtgctt gctgtggaga tgctacagct agaagaggct gtgggagagg ctgggctggt 3240 accccagctg cgtgtgctag aggaatactc tgtcccctgt gcacatgctg cccatgtgac 3300 aggcctcaag atcctaagcc caagcatcat ggtctcagcc tccattgatc aacggctgac 3360 cttctggcgt ctggggcatg gtgaacccac cttcatgaat agcactgtgt tccatgtgcc 3420 tgatgtggct gacatggact gctggcctgt gagccctgag tttggccacc gttgtgccct 3480 tgggggtcag gggcttgagg tttacaactg gtatgactga ggtatcctgc ggtggctggc 3540 gtgctgggca tggggcctgc tcacagacag catggagcag ggaagggctg tctgtgccca 3600 tgctcagcat gccttgaggg gaggaggtgg tggccgtggg ttcctgatgt cggtgcagga 3660 gctgaaggtg agtggagtgc tgccaagaat atgcccgact ccccatgaca agacagaact 3720 ttgtaacaaa cagtaccaat ttattttggc cgtgggtttt tgcttttttt ccagttgatg 3780 actttgtgaa cattcccagg tattggagcc tctgtggcct taaatgtggc tcagtggagg 3840 gagacccagc atagccaggc cagtatggag cacctcacgc acagctctca gaagctgcag 3900 gcggacgaac atctgaccaa agaggtgtgg tcgaggctcc tgaaagagaa agggcctgct 3960 ggtctcatcc tctgcttcct ttgcctttac cctatacctc tctgcacgtc ccaccccgtt 4020 ttgctgtgtg ctcaccccca ggatgtgtac ccggttgtag taggagctga aatccatgct 4080 gagctgtacc aggaacttgc atatctagag acagagactg agtcactggc ccatctcttt 4140 gctcttgtgc cccaggccag aataaagaat agagtgtaga gtgtcctggt tgtctatgcc 4200 tcaccatctc tgtgcgtaca gcaatgtgga ccccggggct gtgcagtcca gcactgctgt 4260 ccggctcagc agatccggaa agggaggata ctgttgaaga gcaacaacca ctcaccctgt 4320 ttggggagaa aagtgcttgg aaggggaatc caggctcctt gtgccagtaa cangagggnc 4380 aatcactcat catgtagcag tgagaag 4407 <210> 120 <211> 959 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No. 2823818CB1 <400> 120 cccacgcgtc cgcccacgcg tccgggagcg tggagcgccg ggactgtgca cgcttgaccg 60 gaagcccaga ccagtgcggt cctagccaga gagaaaggac atttgccaac aatgagacac 120 gaagcgccca tgcagatggc ctctgcccaa gatgccaggt acggccagaa agactcctct 180 gatcagaact ttgactacat gttcaaatta ctcatcatcg gcaatagcag tgtggggaaa 240 acatcttttc tattccgtta tgcagatgac tcctttacat ctgcattcgt cagcacagtt 300 gggatcgatt tcaaagtaaa aactgtattc aaaaatgtaa agagaatcaa gcttcagatt 360 tgggacacag caggccagga aagatacagg actatcacca cagcctatta tcgtggagcc 420 atgggcttta ttttaatgta tgacattaca aatgaagaat ccttcaatgc agtacaagat 480 tggtcaactc aaatcaaaac atactcttgg gacaatgccc aagttattct ggttgggaac 540 aagtgtgaca tggaagacga gcgggtcatc tcaactgagc gaggtcaaca tttaggagaa 600 cagcttgggt ttgagttttt tgaaacaagt gccaaggaca acattaatgt caagcagaca 660 tttgagcgcc ttgtggatat catctgcgac aaaatgtcag agagtttgga gactgatcct 720 gccatcactg ctgcaaagca gaacacgaga ctcaaggaaa ctcctcctcc accgcagccc 780 aactgtgcct gctagtgtcc ccgtgcacac aggcagctcc agggggctct ggttgccaac 840 aaacagcatt tgtaaatggt ctattagcct tcatttatac tgcctaacaa ttatttgaag 900 gaataaattg atgtcaatgg ctcgtaaaaa aaaaaaaaaa aagtaaaaaa aaaaaaaaa 959 <210> 121 <211> 1809 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 2859730CB1 <400> 121 ggcagcggtt ggaggcttcg cccggctttg cagcggggac ttcggcggcg gcgcctcagg 60 cacctcggcc cggacacgat gaggcgagtg gtacgacaga gcaagtttcg gcatgtattt 120 gggcaagcgg tgaaaaatga ccagtgctat gatgacatcc gggtttctcg tgtgacctgg 180 gatagttcct tttgtgctgt caatcccaga tttgttgcca taatcataga ggcaagtggg 240 ggaggagcgt tccttgtcct ccctctgcgc aagactggtc gaattgacaa atcttaccct 300 acagtatgtg gccacacagg accagtgctg gacatagact ggtgcccaca taacgatcag 360 gtcattgcca gcggttcaga ggactgcacg gtcatggtat ggcagatccc agaaaatgga 420 ctcacccttt ccctgactga acctgtggtg attttggaag gccactcaaa gagagtcggc 480 atcgtggctt ggcatccaac ggcccgcaat gtgcttctta gtgcaggctg tgataatgcc 540 attatcatct ggaatgtggg aacaggggaa gcccttataa acttggacga tatgcattca 600 gacatgattt acaatgtgag ctggaaccgg aatggcagtc tgatctgcac agcttccaaa 660 gacaagaaag tgagagtcat tgatcccagg aaacaagaga ttgttgctga gaaggagaaa 720 gcacatgaag gagcaagacc catgagagcc atcttcctgg ccgatggcaa tgtcttcacc 780 actgggttca gccgcatgag cgagcggcag ctggctctct ggaatccgaa aaatatgcag 840 gaaccaattg ctcttcatga gatggacact agcaatgggg tgttgctgcc tttctatgac 900 cctgacacca gcatcattta cttatgtgga aagggtgaca gcagtattcg ctattttgag 960 atcacggatg aatccccgta cgtccactac ctcaacacat tcagcagcaa ggagcctcag 1020 agagggatgg gttacatgcc caagagggga cttgatgtta acaaatgtga gattgccaga 1080 ttcttcaaac ttcatgagag aaagtgtgaa cctattatta tgactgttcc caggaagtct 1140 gaccttttcc aagatgacct gtatcctgac acagcggggc cagaggccgc gctggaggca 1200 gaagagtggt tcgaaggcaa gaatgcagac ccaatcctca tctccttgaa gcacgggtac 1260 attccaggca aaaacaggga tctcaaggtg gtcaagaaga acattctgga tagcaagccc 1320 actgcaaaca agaagtgcga cctgatcagc atccccaaga aaaccacaga cacggccagt 1380 gtgcaaaatg aagccaagtt ggatgagatt ttaaaagaga tcaaatctat aaaagacaca 1440 atctgcaatc aagatgagcg tatttccaag ttagaacagc agatggcaaa gatagcagcc 1500 tgaaggtccc acccccaccc ctacagaaaa aatgggagca agaacttgtg cttgggagct 1560 ggttattggt gtggtcctag ggagggcgga aagggaggca ctgccatttg gagacattcc 1620 atttcagatt tgtcaaccag cgataggcca cattccagta agaactcaat ttgtctccca 1680 aatttgcaga aacaaaacgt gatttaaaag ctgagctttt tatcagaaag cttttttgat 1740 gttttaagtg ttatgtgact tgttgaactt tttaaaaagt gctactttta aaatcccaga 1800 tactctgaa 1809 <210> 122 <211> 2028 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 2861155CB1 <220>
<221> unsure <222> 1943, 2003 <223> a, t, c, g, or other <400> 122 tggcgggttc cgtgggtcgc ccgcgaaatc tgatccggga tgcggcggcc caatcggaag 60 gtggaccgaa atcccgcgac agcaagaggc ccgtagcgac ccgcggtgct aaggaacaca 120 gtgctttcaa aagaattggc gtccgctgtt cgcctctcct cccgggagtc ttctgcctac 180 tcccagaaga ggagggaagc acaggtgggt ttctttagct ctgcgtcgga tccctgagaa 240 cttcgaagcc atcctggctg aggctaatct ccgctgtgct tcctctgcag tatgaagact 300 ttggagactc aaccgttagc tccggactgc tgtccttcag accaggaccc agctccagcc 360 catccttctc cccacgcttc cccgatgaat aaaaatgcgg actctgaact gatgccaccg 420 cctcccgaaa ggggggatcc gccccggttg tccccagatc ctgtggctgg ctcagctgtg 480 tcccaggagc tacgggaggg ggacccagtt tctctctcca ctcccctgga aacagagttt 540 ggttccccta gtgagttgag tcctcgaatc gaggagcaag aactttctga aaatacaagc 600 cttcctgcag aagaagcaaa cgggagcctt tctgaagaag aagcgaacgg gccagagttg 660 gggtctggaa aagccatgga agatacctct ggggaacccg ctgcagagga cgagggagac 720 accgcttgga actacagctt ctcccagctg cctcgatttc tcagtggttc ctggtcagag 780 ttcagcaccc aacctgagaa cttcttgaaa ggctgtaagt gggctcctga cggttcctgc 840 atcttgacca atagtgctga taacatcttg cgaatttata acctgccccc agagctgtac 900 catgaggggg agcaggtgga atatgcagaa atggtccctg tccttcgaat ggtggaaggt 960 gataccatct atgattactg ctggtattct ctgatgtcct cagcccagcc agacacctcc 1020 tacgtggcca gcagcagccg ggagaacccg attcatatct gggacgcatt cactggagag 1080 ctccgggctt cctttcgcgc ctacaaccac ctggatgagc tgacggcagc ccattcgctc 1140 tgcttctccc cggatggctc ccagctcttc tgtggcttca accggactgt gcgtgttttt 1200 tccacggccc ggcctggccg agactgcgag gtccgagcca catttgcaaa aaagcagggc 1260 cagagcggca tcatctcctg catagccttc agcccagccc agcccctcta tgcctgtggc 1320 tcctacggcc gctccctggg tctgtatgcc tgggatgatg gctcccctct cgccttgctg 1380 ggagggcacc aagggggcat cacccacctc tgctttcatc ccgatggcaa ccgcttcttc 1440 tcaggagccc gcaaggatgc tgagctcctg tgctgggatc tccggcagtc tggttaccca 1500 ctgtggtccc tgggtcgaga ggtgaccacc aatcagcgca tctacttcga tctggacccg 1560 accgggcagt tcctagtgag tggcagcacg agcggggctg tctctgtgtg ggacacggac 1620 gggcctggca atgatgggaa gccggagccc gtgttgagtt ttctgcccca gaaggactgc 1680 accaatggcg tgagcctgca ccctagcctg cctctcctgg ccactgcctc cggtcagcgt 1740 gtgtttcctg agcccacaga gagtggggac gaaggagagg agctgggcct tcccttgctc 1800 tccacgcgcc acgtccacct tgaatgtcgg cttcagctct ggtggtgtgg gggggggcca 1860 gactccagca tccctgatga tcaccagggc gagaaagggc agggaggaac aggagggagg 1920 tcgtgggggg cgtgatataa aanggtgttt gagtggctgt gactccttcc tacacagggc 1980 cctgataagc ctaggaatgc canagcccag ctgtagggtc ccagtccc 2028 <210> 123 <211> 2223 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 3002667CB1 <400> 123 gcgcgcacgt ggggccgggg cggagagagg cgagcaccgg gaaggggagc gtggggccgc 60 tggaatgggt gaatttaagg tccatcgagt acgtttcttt aattatgttc catcaggaat 120 ccgctgtgtg gcttacaata accagtcaaa cagattggct gtttcacgaa cagatggcac 180 tgtggaaatt tataacttgt cagcaaacta ctttcaggag aaatttttcc caggtcatga 240 gtctcgggct acagaagctt tgtgctgggc agaaggacag cgactcttta gtgctgggct 300 caatggcgag attatggagt atgatttaca ggcgttaaac atcaagtatg ctatggatgc 360 ctttggagga cctatttgga gcatggctgc cagccccagt ggctctcaac ttttggttgg 420 ttgtgaagat ggatctgtga aactatttca aattacccca gacaaaatcc agtttgaaag 480 aaattttgat cggcagaaaa gtcgcatcct gagtctcagc tggcatccct ctggtaccca 540 cattgcagct ggttccatag actacattag tgtgtttgat gtcaaatcag gcagcgctgt 600 tcataagatg attgtggaca ggcagtatat gggcgtgtct aagcggaagt gcatcgtgtg 660 gggtgtcgcc ttcttgtccg atggcactat cataagtgtg gactctgctg ggaaggtgca 720 gttctgggac tcagccactg ggacgcttgt gaagagccat ctcatcgcta atgctgacgt 780 gcagtccatt gctgtagctg accaagaaga cagtttcgtg gtgggcacag ccgagggaac 840 agtcttccat tttcagctgg tccctgtgac atctaacagc agtgagaagc agtgggtgcg 900 gacaaaaccg ttccagcatc acactcatga cgtgcgcact gtggcccaca gcccaacagc 960 gctgatatct ggaggcactg acacccactt agtctttcgt cctctcatgg agaaggtgga 1020 agtaaagaat tacgatgccg ctctccgaaa aatcaccttt ccccaccgat gtctcatctc 1080 ctgttctaaa aagaggcagc ttctcctctt ccagtttgct catcacttag aactttggcg 1140 actgggatcc acagttgcaa caggcaagaa tggggatact cttccactct ctaaaaatgc 1200 agatcattta ctgcacctaa agacaaaggg tcctgagaac attatctgta gctgtatctc 1260 cccatgtgga agttggatag cctattctac agtttctcgg ttttttctct atcggctgaa 1320 ttatgaacat gacaacataa gcctcaaaag ggtttccaaa atgccagcat tccttcgctc 1380 tgcccttcag attttgtttt ctgaagattc aacaaagctc tttgtagcat caaatcaagg 1440 agctctgcat attgttcagc tgtcaggagg aagcttcaag cacctgcatg ctttccagcc 1500 tcagtcagga acagtggagg ccatgtgtct tttggcagtc agtccagatg ggaattggct 1560 agctgcatca ggtaccagtg ctggagtcca tgtctacaac gtaaaacagc taaagcttca 1620 ctgcacggtg cctgcttaca atttcccagt gactgctatg gctattgccc ccaataccaa 1680 caaccttgtc atcgctcatt cggaccagca ggtatttgag tacagcatcc cagacaaaca 1740 gtatacagat tggagccgga ctgtccagaa gcagggcttt caccaccttt ggctccaaag 1800 ggatactcct atcacacaca tcagttttca tcccaagaga ccgatgcaca tccttctcca 1860 tgatgcctac atgttctgca tcattgacaa gtcattgccc cttccaaatg acaaaacctt 1920 actctacaat ccatttcctc ccacgaatga atcagatgtc atccggaggc gcacagctca 1980 tgcttttaaa atttctaaga tatataagcc tctactcttc atggatcttt tggatgaaag 2040 aacactcgtg gcagtagaac ggcctctgga tgacatcatt gctcagctcc caccacccat 2100 taaaaagaag aaatttggaa cctaaaacag ggcactgtct gtgtccttcc ttgaactgtc 2160 taccctgttg cttttcacaa atcatggtaa taaaacaagt tattcttgag gaaaaaaaaa 2220 aaa 2223 <210> 124 <211> 728 <212> DNA

<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 3043734CB1 <400> 124 gcggcgtttc tggtggccag gcatcccggt cctcgcgcgt ggcgcagctc ccatcgccgg 60 accgacccat gtcgcgcccg cattgggtcc cgggaccccg gcgggagtgc cgcgtccgtc 120 ctttccagtc gccgggagtc tgagtcgcgg gccacgcggg agtggcggtg gagagcccgc 180 cggtcgttat gaggacggat ctaaaatgac cagcaaacgg aaaccttgcc aaacgcagct 240 caggagatcc atcagtgagc agttgcggga ctccacggcc agagcctggg atctgctgtg 300 gaagaacgtc cgggagaggc ggctggcaga aattgaggca aaagaagcat gtgactggct 360 ccgtgctgcc gggttcccgc aatacgctca gttatatgag gattcacaat ttcccatcaa 420 cattgtggct gtcaagaatg atcatgattt tcttgaaaag gaccttgtag aacctctttg 480 caggtaaacc atgtgaagta tttttgtttc tttccactgt tcagtctgca acaggcatca 540 ctatactgaa gggcgagctc agctattcgg caagtattca ctgagtgcct accatgtgcc 600 tgacccaggt gcaggttcta aatgtactac tgttaatgag catgatcagt ttgtgttttc 660 atggagctta aatcctagca ggggcctttg gacactagat taggaaaatg acagagaaag 720 aagagaga 728 <210> 125 <211> 2161 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 3294893CB1 <400> 125 gaggcggaag agcttctcgg ctctaggctc tggagtcccg ggagcagtga ggggccaccc 60 ggggcacagg aaagggccgc taggggaggg ccgggtgcac tcggggtgtc tgggccgcgg 120 gtctgaggga tgaggagggg ccatggccag cgacggggcc aggaagcaat tctggaagcg 180 cacaacagca agctcccggg cagcatccag cacgtgtatg gtgcccagca cccccccttt 240 gatccactgt tacatggcac tttgctcagg tccacggcca agatgccgac cacaccagtg 300 aaggccaaga gggtcagcac cttccaggag tttgagagca ataccagcga tgcctgggac 360 gctggggagg acgacgatga gctcctggcc atggcggcgg agagcctgaa ctccgaggtg 420 gtcatggaga cggccaaccg tgtgctgcgt aaccacagcc agcggcaggg gcggcccacg 480 ctgcaggagg ggccagggct tcagcagaag cccaggcccg aggcagagcc gccctcaccc 540 cccagcggcg acctccggct ggtgaagtcg gtcagtgaga gccacacgtc ctgtcctgca 600 gaaagtgcca gcgatgccgc ccctctgcag aggtcccagt ctctcccaca ctcggccacc 660 gtcacgctgg gtggcacatc tgaccccagc actctcagca gctcagcgct gagcgaaaga 720 gaggcctccc ggctcgacaa gttcaagcag ctgcttgccg gccccaacac ggaccttgag 780 gaattacgga ggttgagctg gtccggaatc cctaagccag tgcgtccaat gacgtggaag 840 ctcctctcag gttaccttcc cgccaatgta gaccggagac cagccactct ccagagaaaa 900 caaaaagaat attttgcatt tattgagcac tattacgatt ctaggaacga cgaagttcac 960 caggacacat acaggcagat ccacatagac atccctcgca tgagccctga agcgttgatc 1020 ctgcagccca aggtgacgga gatttttgaa aggatcttgt tcatatgggc gatccgccac 1080 ccagccagtg gatacgttca gggtataaat gatctcgtca ctcctttctt tgtggtcttc 1140 atttgtgaat acatagaggc agaggaggtg gacacggtgg acgtctccgg cgtgcccgca 1200 gaggtgctgt gcaacatcga ggccgacacc tactggtgca tgagcaagct gctggatggc 1260 attcaggaca actacacctt tgcccaacct gggattcaaa tgaaagtgaa aatgttagaa 1320 gaactcgtga gccggattga tgagcaagtg caccggcacc tggaccaaca cgaagtgaga 1380 tacctgcagt ttgccttccg ctggatgaac aacctgctga tgagggaggt gcccctgcgt 1440 tgtaccatcc gcctgtggga cacctaccag tctgaaccgg acggcttttc tcatttccac 1500 ttgtacgtgt gcgctgcttt tctcgtgaga tggaggaagg aaatactaga agaaaaagat 1560 tttcaagagc tgctgctctt cctccagaac ctgcccacag cccactggga tgatgaggac 1620 atcagcctgt tgctggccga ggcctaccgc ctcaagtttg cttttgccga cgcccccaat 1680 cactacaaga aatgagccca ggcccacccg cagctggcct cactgtcccg ggtggcgcgc 1740 cccacctgcc tggctggtgg taggcccctg tgagctggtc ccgggctgct aaaaggcctt 1800 gtgaggtggc cccaccctcc aggggagctg gtgaagatgg gccacagacc tggtctaggg 1860 ctgacaaaga cagggacagc ctttgttttc tgagatacca aagagagcca ggggagggcc 1920 ccgggttcgg cggccagagg caggtcaggg gtcccctctc cctctccctg caatgtcctt 1980 gccaaatgac tgcctcctgc tgcccctagt ccggggcagc ctaggaggcc caccctcttt 2040 ggagtcctgc tgtctgggtg ccagggccgg aacgaggtag tggccatctc atacctactc 2100 tgaaatgcaa aacttctatt ctgttgagtg aaaaaataaa atgtagacaa aaaaaaaaaa 2160 c 2161 <210> 126 <211> 2782 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 3349052CB1 <400> 126 attagctgcc ggcgtgactt tgaccgcttc ccggtgcgtt accggcagct gaacccaccc 60 ggcgtcacgg gactttgacg cgtgctctgc gcttgccatg agactcctgg gagccgcagc 120 cgtcgcggct ctggggcgcg gaagggcccc cgcctcccta ggctggcaga ggaagcaggt 180 taattggaag gcctgccgat ggtcttcatc aggggtgatt cctaatgaaa aaatacgaaa 240 tattggaatc tcagctcaca ttgattctgg gaaaactaca ttaacagaac gagtccttta 300 ctacactggc agaattgcaa agatgcatga ggtgaaaggt aaagatggag ttggtgctgt 360 catggattcc atggaactag agagacaaag aggaatcact attcagtcag cagccactta 420 caccatgtgg aaagatgtca atattaacat tatagatact cctgggcatg tggacttcac 480 aatagaagtg gaaagggccc tgagagtgtt ggatggtgca gtccttgttc tctgtgctgt 540 tggaggggta cagtgccaga ccatgactgt caatcgtcag atgaagcgct acaacgttcc 600 gtttctaact tttattaaca aattggaccg aatgggctcc aacccagcca gggccctgca 660 gcaaatgagg tctaaactaa atcataatgc agcgtttatg cagataccca tgggtttgga 720 gggtaatttt aaaggtatta tagatcttat tgaggaacga gccatctatt ttgatggaga 780 ctttggtcag attgttcgat atggtgagat tccagctgaa ttaagggcgg cggccactga 840 ccaccggcag gagctaattg aatgtgttgc caattcagat gaacagcttg gtgagatgtt 900 tctggaagaa aaaatcccct cgatttctga tttaaagcta gcaattcgaa gagctactct 960 gaaaagatca tttactcctg tatttttggg aagcgccttg aagaacaaag gagttcagcc 1020 tcttttagat gctgttttag aatacctccc aaatccatct gaagtccaga actatgctat 1080 tctcaataaa gaggatgact caaaagagaa aaccaaaatc ctaatgaact ccagtagaga 1140 caattcccac ccatttgtag gcctggcttt taaactggag gtaggtcgat ttggacaatt 1200 aacttatgtt cgcagttatc agggagagct aaagaagggt gacaccatct ataacacaag 1260 gacaagaaag aaagtacggt tgcaacggct ggctcgcatg catgccgaca tgatggagga 1320 tgttgaggaa gtatatgccg gagacatctg tgcattgttt ggcattgact gtgctagtgg 1380 agacacattc acagacaaag ccaacagcgg cctttctatg gagtcaattc atgttcctga 1440 tcctgtcatt tcaatagcaa tgaagccttc taacaagaac gatctggaaa aattttcaaa 1500 aggtattggc aggtttacaa gagaagatcc cacatttaaa gtatactttg acactgagaa 1560 caaagagaca gttatatctg gaatgggaga attacacctg gaaatctatg ctcagaggct 1620 ggaaagagag tatggctgtc cttgtatcac aggaaagcca aaagttgcct ttcgagagac 1680 cattactgcc cctgtcccgt ttgactttac acataaaaaa caatcaggtg gtgcaggcca 1740 gtatggaaaa gtaataggtg tcctggagcc tctggaccca gaggactaca ctaaattgga 1800 attttcagat gaaacattcg gatcaaatat tccaaagcag tttgtgcctg ctgtagaaaa 1860 ggggttttta gatgcctgcg agaagggccc tctttctggt cacaagctct ctgggctccg 1920 gtttgtcctg caagatggag cacaccacat ggttgattct aatgaaatct ctttcatccg 1980 agcaggagaa ggtgctctta aacaagcctt ggcaaatgca acattatgta ttcttgaacc 2040 tattatggct gtggaagttg tagctccaaa tgaatttcag ggacaagtaa ttgcaggaat 2100 taaccgacgc catggggtaa tcactgggca agatggagtt gaggactatt ttacactgta 2160 tgcagatgtc cctctaaatg atatgtttgg ttattccact gaacttaggt catgcacaga 2220 gggaaaggga gaatacacaa tggagtatag caggtatcag ccatgtttac catccacaca 2280 agaagacgtc attaataagt atttggaagc tacaggtcaa cttcctgtta aaaaaggaaa 2340 agccaagaac taactttgtt tactgtgagt tgactgactc taattgaatc tgcgtggttt 2400 tgatactttg atggattcca gtggaataaa ttcaggctgc tgaaacaaga aattctgagc 2460 ccaggaagcg ggctcttctt tcttcaaaag aagcccttct tgttcatatt caggagcttc 2520 tgttatattc aaaggtaatt ctatgtctat ctcaactcta ttgattggtt ttatagttta 2580 ttgaaaatcc tcaaataaaa tataattatt actgaaatat gtttaatatt taaggggaaa 2640 agagactaat ttcagttata cttttaagct tagaatgtat gttcatttcc aaattttgta 2700 tcataagagt tttcaacata gagaaaagct gaaaaaatgc aaagaataac cacatacttt 2760 ccatctacct tcctttggta ac 2782 <210> 127 <211> 3019 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 3357264CB1 <220>
<221> unsure <222> 985 <223> a, t, c, g, or other <400> 127 tggctgggtc cgcgggcggg ggaaggtgtc ctagcggccc gagcctgcgc tccggattct 60 caggcccatc ctgtggtagg ccgtcccagg caggagttgc ctcggaggat ttggcagcca 120 cgacatccca tcctagcccc gcgatgtgcg gggctgtaat ccccttgcac aaaccggccg 180 gacgtaaatt gcagaatcaa agagctgctt tgaatcagca gatcctgaaa gccgtgcgga 240 tgaggaccgg agcggaaaac cttctgaaag tggccacaaa ctcaaaggtg cgggagcaag 300 tgcggctgga gctgagcttc gtcaactcag acctgcagat gctcaaggaa gagctggagg 360 ggctgaacat ctcggtgggc gtctatcaga acacagagga ggcatttacg attcccctga 420 ttcctcttgg cctgaaggaa acgaaagacg tcgactttgc agtcgtcctc aaggatttta 480 tcctggaaca ttacagtgaa gatggctatt tatatgaaga tgaaattgca gatcttatgg 540 atctgagaca agcttgtcgg acgcctagcc gggatgaggc cggggtggaa ctgctgatga 600 catacttcat ccagctgggc tttgtcgaga gtcgattctt cccgcccaca cggcagatgg 660 gactcctgtt cacctggtat gactctctca ccggggttcc ggtcagccag cagaacctgc 720 tgctggagaa ggccagtgtc ctgttcaaca ctggggccct ctacacccag attgggaccc 780 ggtgtgatcg gcagacgcag gctgggctgg agagtgccat agatgccttt cagagagccg 840 caggggtttt aaattacctg aaagacacat ttacccatac tccaagttac gacatgagcc 900 ctgccatgct cagcgtgctc gtcaaaatga tgcttgcaca agcccaagaa agcgtgtttg 960 agaaaatcag ccttcctggg atccngaatg aattcttcat gctggtgaag gtggctcagg 1020 aggctgctaa ggtgggagag gtctaccaac agctacacgc agccatgagc caggcgccgg 1080 tgaaagagaa catcccctac tcctgggcca gcttagcctg cgtgaaggcc caccactacg 1140 cggccctggc ccactacttc actgccatcc tcctcatcga ccaccaggtg aagccaggca 1200 cggatctgga ccaccaggag aagtgcctgt cccagctcta cgaccacatg ccagaggggc 1260 tgacaccctt ggccacactg aagaatgatc agcagcgccg acagctgggg aagtcccact 1320 tgcgcagagc catggctcat cacgaggagt cggtgcggga ggcgagcctc tgcaagaagc 1380 tgcggacgat tgaggtgcta cagaaggtgc tgtgtgccgc acaggaacgc tcccggctca 1440 cgtacgccca gcaccaggag gaggatgacc tgctgaacct gatcgacgcc cccagtgttg 1500 ttgctaaaac tgagcaagag gttgacatta tattgcccca gttctccaag ctgacagtca 1560 cggacttctt ccagaagctg ggccccttat ctgtgttttc ggctaacaag cggtggacgc 1620 ctcctcgaag catccgcttc actgcagaag aaggggactt ggggttcacc ttgagaggga 1680 acgcccccgt tcaggttcac ttcctggatc cttactgctc tgcctcggtg gcaggagccc 1740 gggaaggaga ttatattgtc tccattcagc ttgtggattg taagtggctg acgctgagtg 1800 aggttatgaa gctgctgaag agctttggcg aggacgagat cgagatgaaa gtcgtgagcc 1860 tcctggactc cacatcatcc atgcataata agagtgccac atactccgtg ggaatgcaga 1920 aaacgtactc catgatctgc ttagccattg atgatgacga caaaactgat aaaaccaaga 1980 aaatctccaa gaagctttcc ttcctgagtt ggggcaccaa caagaacaga cagaagtcag 2040 ccagcacctt gtgcctccca tcggtcgggg ctgcacggcc tcaggtcaag aagaagctgc 2100 cctccccttt cagccttctc aactcagaca gttcttggta ctaatgtgag gaaacaaaca 2160 tgttcaggcc ccgaacattt ccggtgctga ctcggcctta aacgtttgtg ccataatgga 2220 aaatatctat ctatctgttc tcaaatcctg tttttctcat agtgtaaact cacatttgat 2280 gtgtttttat gaaggaaagt aaccaagaaa cctctaggaa ttagtgaaaa aagaactttt 2340 ttgaggtgtg ttactatact gctgtaagtt atttattata taaagtattg taaatagaat 2400 agtgttgaag atatgaaata tggctatttt taatggtgac aattatgact tttagtcact 2460 attaaattgg ggttacctat atcagtacaa tttgtagttg tttccaggtt tggctaataa 2520 tcattcctta acctagaatt cagatgatcc tggaattaag gcaggtcaga ggactgtaat 2580 gatagaatta aattagtgtc actaaaaact gtcccaaagt gctgcttcct aataggaatt 2640 cattaaccta aaacaagatg ttactattat atcgatagac tatgaatgct atttctagaa 2700 aaagtctagt gccaaatttg tcttattaaa taaaaacaat gtaggagcag cttttcttct 2760 agtttgatgt catttaagaa ttactaacac agtggcagtg ttagatgaag atgctgtcta 2820 caaggtagat aatatactgt ttgatactca aaacattttt cattttgttt aaagtagaag 2880 ttacataatt ctatatttta agtcttgggt aaaaaagtag ttttacattt tataaagtaa 2940 agatgtaaat gattcagctt taaagctcta tttgacttcc ttcttttgtc tgagatagcg 3000 tccagactgc gaaaagcga 3019 <210> 128 <211> 2312 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 3576329CB1 <400> 128 gccggcgcgc ggtggggcat ggcgggttcg cggggtgcgg ggcgcacggc ggcgccgagc 60 gtgcggccgg agaagcggcg gtctgagccc gaactggagc ctgagcccga gccggagccc 120 cccctcctct gcacctctcc tctcagccac agcaccggca gcgattctgg cgtctccgac 180 agcgaggaga gtgtgttctc aggcctggaa gattccggca gtgacagcag tgaggatgat 240 gacgaaggcg acgaggaggg agaggacgga gcccttgatg acgagggcca cagtgggatt 300 aaaaagacca ctgaggagca ggtgcaggcc agcactcctt gcccgaggac agagatggcg 360 agcgcccgga ttggggatga gtatgcggag gacagctctg atgaggagga catccggaac 420 acggtgggca acgtgccctt ggagtggtac gatgacttcc cccacgtggg ctacgacctg 480 gatggcaggc gcatctacaa gcccctgcgg acccgggatg agctggacca gttcctggac 540 aagatggacg atcctgacta ctggcgcacc gtgcaggacc cgatgacagg gcgggacctg 600 agactgacgg atgagcaggt ggccctggtg cggcggctgc agagtggcca gtttggggat 660 gtgggcttca acccctatga gccggctgtc gacttcttca gcggggacgt catgatccac 720 ccggtgacca accgcccggc cgacaagcgc agcttcatcc cctccctggt ggagaaggag 780 aaggtctctc gcatggtgca cgccatcaag atgggctgga tccagcctcg ccggccccga 840 gaccccaccc ccagcttcta tgacctgtgg gcccaggagg accccaacgc cgtgctcggg 900 cgccacaaga tgcacgtacc tgctcccaag ctggccctgc caggccacgc cgagtcgtac 960 aacccacccc ctgaatacct gctcagcgag gaggagcgct tggcgtggga acagcaggag 1020 ccaggcgaga ggaagctggg ctttttgcca cgcaagttcc cgagcctgcg ggccgtgcct 1080 gcctacggac gcttcatcca ggaacgcttc gagcgctgcc ttgacctgta cctgtgccca 1140 cggcagcgca agatgagggt gaatgtagac cctgaggacc tcatccccaa gctgcctcgg 1200 ccgagggacc tgcagccctt ccccacgtgc caggccctgg tctacagggg ccacagtgac 1260 cttgtccggt gcctcagtgt ctctcctggg ggccagtggc tggtttcagg ctctgacgac 1320 ggctccctgc ggctctggga ggtggccact gcccgctgtg tgaggactgt tcccgtgggg 1380 ggcgtggtga agagtgtggc ctggaacccc agccccgctg tctgcctggt ggctgcagcc 1440 gtggaggact cggtgctgct gctgaaccca gctctggggg accggctggt ggcgggcagc 1500 acagatcagc tgttgagcgc cttcgtcccg cctgaggagc cccccttgca gccggcccgc 1560 tggctggagg cctcagagga ggagcgccaa gtgggcctgc ggctgcgcat ctgccacggg 1620 aagccagtga cgcaggtgac ctggcacggg cgtggggact acctggccgt ggtgctggcc 1680 acccaaggcc acacccaggt gctgattcac cagctgagcc gtcgccgcag ccagagtccg 1740 ttccgccgca gccacggaca ggtgcagcga gtggccttcc accctgcccg gcccttcctg 1800 ttggtggcgt cccagcgcag cgtccgcctc taccacctgc tgcgccagga gctcaccaag 1860 aagctgatgc ccaactgcaa gtgggtgtcc agcctggcgg tgcaccctgc aggtgacaac 1920 gtcatctgtg ggagctacga tagcaagctg gtgtggtttg acctggatct ttccaccaag 1980 ccatacagga tgctgagaca ccacaagaag gctctgcggg ctgtggcctt ccacccgcgg 2040 tacccactct ttgcgtcagg ctcggacgac ggcagtgtca tcgtctgcca tggcatggtg 2100 tacaatgacc ttctgcagaa ccccttgctg gtgcccgtca aggtgctgaa gggacacgtg 2160 ctgacccgag atctgggagt gctggacgtc atcttccacc ccacccagcc gtgggtcttc 2220 tcctcggggg cagacgggac tgtccgcctc ttcacctagc tgttctgcct gcctggggct 2280 ggggtggtcg tgctgaagtc aacagagcct tc 2312 <210> 129 <211> 921 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 3805550CB1 <400> 129 aggcggagtc ggggcggtgt gctgaggtgg gcctgagggc ggagtcgagg tcgggctgaa 60 ggcggagtcg gggagggctg aggtgggcct gaaggcagag tcgaggccat ggcagggccg 120 ggcccaggcc cgggggaccc ggacgagcag tacgatttcc tgttcaagct ggtgctggtg 180 ggcgacgcaa gcgtgggcaa gacgtgcgtg gtgcagcgct tcaagaccgg cgccttctcg 240 gagcgccagg gaagcaccat cggcgtcgac ttcaccatga agacgctgga gatccagggc 300 aagcgggtca agctgcagat ctgggacacg gccggccagg agcggttccg caccatcacc 360 cagagctact accgcagtgc caatggggcc atccttgcct acgacatcac caagaggagc 420 tccttcctgt cggtgcctca ctggattgag gatgtgagga agtatgcggg ctccaacatt 480 gtgcagctgc tgatcgggaa caagtcagac ctcagcgagc ttcgggaggt ctccttggct 540 gaggcacaga gcctggctga gcactatgac atcctgtgtg ccattgagac gtctgccaag 600 gactcgagca acgtggagga ggccttcctg agggtggcca cggagctcat catgcggcac 660 gggggcccct tgttcagcga gaagagcccc gaccacatcc agctgaacag caaggacatc 720 ggagaaggct ggggctgcgg gtgctgacca ggggccgggc cggcagactg ggggttcccc 780 acctccttgc tctccccagc ctgccaagcc cagccctcca gagccagccc tcctgggtac 840 cggcaactac agcagccggg tgaagctctg gagctctgca tcctgtggcc tggctgcggg 900 atggaggctc tccttgagga a 921 <210> 130 <211> 1291 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 4546403CB1 <400> 130 ctcgagcgaa tcggctcgag agatggctcc ttggcggcat gtgcattttc tcctaatgga 60 agcttctttg tcactggcac ttcatgtggt gatttaacag tgtgggatga tcaaatgagg 120 tgtctgcata gtgaaaaagc acatgatctt ggaattacct gctgcgattt ttcttcacag 180 ccagtttctg atggagaaca aggtcttcag ttttttcgac tggcatcatg tggtcaggat 240 tgccaagtca aaatttggat tgtttctttt acccatatct taggttttga attaaaatat 300 aaaagtacac tgagtgggca ctgtgctcct gttctggctt gtgctttttc ccatgatggg 360 cagatgctag tctcagggtc agtggataag tctgtcatag tatatgatac taatactgag 420 aatatacttc acacattgac tcagcacacc aggtatgtca caacttgtgc ttttgcacct 480 aatacccttt tacttgctac tggttcaatg gacaaaacag tgaacatctg gcaatttgac 540 ctggaaacac tttgccaagc aaggagcaca gaacatcagc tgaagcaatt taccgaagat 600 tggtcagagg aggatgtctc aacatggctt tgtgcacaag atttaaaaga tcttgttggt 660 attttcaaga tgaataacat tgatggaaaa gaactgttga atcttacaaa agaaagtctg 720 gctgatgatt tgaaaattga atctctagga ctgcgtagta aagtgctgag gaaaattgaa 780 gagctcagga ccaaggttaa atccctttct tcaggaattc ctgatgaatt tatatgtcca 840 ataactagag aacttatgaa agatccggtc atcgcatcag atggctattc atatgaaaag 900 gaagcaatgg aaaattggat cagcaaaaag aaacgtacaa gtcccatgac aaatcttgtt 960 cttccttcag cggtacttac accaaatagg actctgaaaa tggccatcaa tagatggctg 1020 gagacacacc aaaagtaaaa ttgttgatat tgtattattt atattttcag tgatctcatt 1080 tgaatgattt ataggtaaat actaatcaga cattattaaa agcaaaacag gaaaaaggta 1140 aacttcttaa atttagttac ctataaaaat tgtcaatttt cattctttaa aaacacatgg 1200 acttactata aaagcctttt tgtactagtg aaaagaatct tcagctatat agaaataaag 1260 ttatacttta aattgcaaaa aaaaaaaaaa a 1291 <210> 131 <211> 1836 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 4767318CB1 <400> 131 ttttagaagg ttagtgttgg ttcttttatt cgattaaaca ggaatacaca tatgtctacc 60 aaagaatagg taagggagaa ataagaacac taaaaaaact cggaatcgtt aagtgtgaag 120 catatttgga gttaaaagaa ccaaatatta ctaagtaagc agacgcgggc acgcgctgca 180 taccgggatt tgtagtccct tccggggcgg ggtacagcgc gcctgcgcag aggggccgtc 240 gctcttccgg gcgcatgcgt gcggcagcgg cgccaggact gactgcgccg tggaggctgc 300 tgcagtgttg tgagttggaa gctggggagc tcggcatggc ggtccccgct gcagccatgg 360 ggccctcggc gttgggccag agcggccccg gctcgatggc cccgtggtgc tcagtgagca 420 gcggcccgtc gcgctacgtg cttgggatgc aggagctgtt ccggggccac agcaagacgc 480 gcgagttcct ggcgcacagc gccaaggtgc actcggtggc ctggagttgc gacgggcgtc 540 gcctagcctc ggggtccttc gacaagacgg ccagcgtctt cttgctggag aaggaccggt 600 tggtcaaaga aaacaattat cggggacatg gggatagtgt ggaccagctt tgttggcatc 660 caagtaatcc tgacctattt gttacggcgt ctggagataa aaccattcgc atctgggatg 720 tgaggactac aaaatgcatt gccactgtga acactaaagg ggagaacatt aatatctgct 780 ggagtcctga tgggcagacc attgctgtag gcaacaagga tgatgtggtg acctttattg 840 atgccaagac acaccgttcc aaagcagaag agcagttcaa gttcgaggtc aacgaaatct 900 cctggaacaa tgacaataat atgttcttcc tgacaaatgg caatggttgt atcaacatcc 960 tcagctaccc agaactgaag cctgtgcagt ccatcaacgc ccatccttcc aactgcatct 1020 gtatcaagtt tgaccccatg gggaagtact ttgccacagg aagtgcggat gctttggtca 1080 gcctctggga tgtggatgag ttagtgtgtg ttcggtgctt ttccaggctg gattggcctg 1140 taagaaccct cagtttcagc catgatggga aaatgctggc gtcagcatcg gaagatcatt 1200 ttattgacat tgctgaagtg gagacagggg acaaactatg ggaggtacag tgtgagtctc 1260 cgaccttcac agtggcgtgg caccccaaaa ggcctctgct ggcatttgcc tgtgatgaca 1320 aagacggcaa atatgacagc agccgggaag ccggaactgt gaagctgttt gggcttccta 1380 atgattcttg agaggaggtt gtagggagag gaggccccgg cagaggtctt ccttcatgtg 1440 gttagtttgg tctgttctct cggagttggt gggcacccta aatatttgta agttggtata 1500 aattgtaaac gtctctggtc aggctgcgca tttcgttctt ttgctttgtc tgtgtattag 1560 ctctttccat tctttgcccc cagcatgagt taactcgcgt ggactctgca gtgcgagtag 1620 tgaccccagc ataccttgtc ctctggacct cctgtcttct ctgcttctgg gtgcatggta 1680 gactttgtgg catttgatac aacttggaca atacctagtt tggagggagg ggaatggaag 1740 ggcatggaag tttttttaaa taattaaaaa tatatacata taattttgag aattgagcat 1800 ttaataaact gacttttgtt attatggaaa aaaaaa 1836 <210> 132 <211> 2136 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 4834527CB1 <400> 132 ggcgcgccgg gagccggcag acatgccaca gacgctgagt gcctccgaca tggtcacccc 60 aggcagcctc agcccacccc ccaccgagcc cacagatggc gaacaggctg ggcagcccct 120 cctggatgga gcgccatcct cagcctccct ggaaacactg atccagcacc tggtgcccac 180 agccgactac taccccgaga aagcctacat cttcaccttc ctgctgagct ctcgcctctt 240 catcgagccc cgggagctcc tggcccgggt ctgccacctg tgcatcgagc agcagcagct 300 ggacaagccg gtgctggaca aggcccgggt ccggaagttc ggccccaaac tgctgcagct 360 gttggccgag tggaccgaga ccttcccaag ggacttccag gaagagtcga ctatcgggca 420 ccttaaggac gtcgtgggcc gcatcgcccc ctgtgacgag gcataccgga agaggatgca 480 tcagctccta caggctctgc accagaagct ggcggctctg cgccaggggc cagaaggtct 540 ggtgggtgcc gacaagccca tctcctacag gaccaagcca ccagcctcca tccacaggga 600 gctccttggt,gtctgcagcg acccctacac actggcccag cagctgaccc acgtggaact 660 ggagcggctg cggcacatcg ggcctgagga gtttgtccag gcctttgtga acaaggaccc 720 tctggccagc acaaagccct gcttcagtga caagaccagc aacctggagg cttatgtgaa 780 atggttcaac aggctgtgct acctggtggc aactgagatc tgcatgccag ccaagaagaa 840 gcagagggcc caggtgattg agttcttcat cgacgtggcc cgcgagtgct tcaacatcgg 900 caacttcaac tccctcatgg ccatcatctc cggcatgaac atgagccctg tctccaggct 960 gaagaagacc tgggccaaag tgaggacggc caagtttttc atcctcgagc accagatgga 1020 cccaacgggg aatttctgca actacaggac agccctgcgc ggggcggccc accgctccct 1080 gacggcccac agcagccgag agaagattgt cattcctttc ttcagcctgc tcatcaaaga 1140 catctacttc ctgaatgagg gctgcgccaa ccgccttccc aatggacacg tcaactttga 1200 gaaattcctg gagctggcca agcaggtggg ggagttcatc acctggaaac aagtggagtg 1260 tcccttcgag caagacgcca gcatcaccca ctacctgtac accgccccca tcttcagtga 1320 ggatggtctt tatttggctt cttatgaaag tgagagccca gagaaccaaa cagaaaaaga 1380 aagatggaaa gctctaagat cttctatttt ggggaagaca tgaaagcgct gagctgaggg 1440 acgaggaaga gctggagccc gcagaagccg tccacagccc tgcctcagtg gcccagtggg 1500 cagaggccag ggagtgcctc actattttgc aaatgccgac cctgtggcct gctgcccgcc 1560 ccccgccccc cacagtggcc atacgggcac aggagacctt ttatgggact ttggccctgg 1620 caggacccag ggcctccaga cgtgcgggcg gcacatgcct tggggacatc ctgccttcag 1680 gaccgtgggg cctggtcagt ctgtccatcc tcggcaagga cacaacactg ccccagaggg 1740 tgggaccact gcaagctcga gaccttgctt ggtgacatgt gccactttgg ccaccaccca 1800 cagtctgtca ccacgtggct tgggaacttc tggagccaca gcaggcatca cggtgcgacg 1860 tgagatgcct gcgccagccc cgagcccact ggcagccact gccattccac ccatggtccc 1920 tcaccctgcc ctgccgacga gcttgtctct gcagccccag gtaccccctt cctggatgct 1980 gctggcccca ggagatagct ttccggtgac agctgtggaa cgcgtcagca ggacaaactg 2040 gacacatgga gttacagtgt gtacacggca gtcccgccac ccagccccct tgtaaactct 2100 agtcactata aacacacccg tacgcctaaa aaaaaa 2136

Claims

What is claimed is:

1. An isolated polypeptide comprising an amino acid sequence selected from the group consisting of:

a) an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID
NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID
NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID
NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID
NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID
NO:27, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID
NO:34, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID
NO:41, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID
NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID
NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID
NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, and SEQ ID NO:66, b) a naturally occurring amino acid sequence having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID
NO:2, SEQ ID
NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID
NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID
NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID
NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID
NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID
NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID
NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID
NO:49, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID
NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID
NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, and SEQ ID NO:66, c) a biologically active fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID
NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ 1D NO:11, SEQ
ID
NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID
NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID
NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID
NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID
NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID
NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:52, SEQ ID

NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID
NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID
NO:65, and SEQ ID NO:66, and d) an immunogenic fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID
NO:6, SEQ
ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID
NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID
NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID
NO:26, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID
NO:33, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID
NO:40, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID
NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:53, SEQ ID
NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID
NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, and SEQ
ID NO:66.

2. An isolated polypeptide of claim 1 selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID
NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ
ID
NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID
NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID
NO:27, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID
NO:34, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID
NO:41, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID
NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID
NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID
NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, and SEQ ID
NO:66.

3. An isolated polynucleotide encoding a polypeptide of claim 1.

4. An isolated polynucleotide encoding a polypeptide of claim 2.

5. An isolated polynucleotide of claim 4 selected from the group consisting of SEQ ID
NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID
NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID
NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID

NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:91, SEQ ID
NO:92, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID
NO:99, SEQ ID NO:100, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID
NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ
ID
NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID
NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ
ID
NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID
NO:129, SEQ ID NO:130, SEQ ID NO:131, and SEQ ID NO:132.

6. A recombinant polynucleotide comprising a promoter sequence operably linked to a polynucleotide of claim 3.

7. A cell transformed with a recombinant polynucleotide of claim 6.

8. A transgenic organism comprising a recombinant polynucleotide of claim 6.

9. A method for producing a polypeptide of claim 1, the method comprising:
a) culturing a cell under conditions suitable for expression of the polypeptide, wherein said cell is transformed with a recombinant polynucleotide, and said recombinant polynucleotide comprises a promoter sequence operably linked to a polynucleotide encoding the polypeptide of claim 1, and b) recovering the polypeptide so expressed.

10. An isolated antibody which specifically binds to a polypeptide of claim 1.

11. An isolated polynucleotide comprising a polynucleotide sequence selected from the group consisting of:

a) a polynucleotide sequence selected from the group consisting of SEQ ID
NO:67, SEQ ID
NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID
NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID
NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID
NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID
NO:93, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID
NO:100, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID
NO:106, SEQ ID NO:107, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ
ID
NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO: 116, SEQ ID NO:118, SEQ ID
NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ
ID
NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID
NO:130, SEQ ID NO:131, and SEQ ID NO:132, b) a naturally occurring polynucleotide sequence having at least 70% sequence identity to a polynucleotide sequence selected from the group consisting of SEQ ID NO:67, SEQ ID NO:68, SEQ
ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID
NO:74, SEQ
ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID
NO:80, SEQ
ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID
NO:86, SEQ
ID NO:87, SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID
NO:93, SEQ
ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID
NO:100, SEQ
ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID
NO:107, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ
ID
NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:118, SEQ ID NO:119, SEQ ID
NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ
ID
NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID
NO:131, and SEQ ID NO:132, c) a polynucleotide sequence complementary to a), d) a polynucleotide sequence complementary to b), and e) an RNA equivalent of a)-d).

12. An isolated polynucleotide comprising at least 60 contiguous nucleotides of a polynucleotide of claim 11.

13. A method for detecting a target polynucleotide in a sample, said target polynucleotide having a sequence of a polynucleotide of claim 11, the method comprising:

a) hybridizing the sample with a probe comprising at least 20 contiguous nucleotides comprising a sequence complementary to said target polynucleotide in the sample, and which probe specifically hybridizes to said target polynucleotide, under conditions whereby a hybridization complex is formed between said probe and said target polynucleotide or fragments thereof, and b) detecting the presence or absence of said hybridization complex, and, optionally, if present, the amount thereof.

14. A method of claim 13, wherein the probe comprises at least 60 contiguous nucleotides.

15. A method for detecting a target polynucleotide in a sample, said target polynucleotide having a sequence of a polynucleotide of claim 11, the method comprising:

a) amplifying said target polynucleotide or fragment thereof using polymerase chain reaction amplification, and b) detecting the presence or absence of said amplified target polynucleotide or fragment thereof, and, optionally, if present, the amount thereof.

16. A composition comprising an effective amount of a polypeptide of claim 1 and a pharmaceutically acceptable excipient.

17. A composition of claim 16, wherein the polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO:67, SEQ ID NO:68, SEQ ID
NO:69, SEQ ID
NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID
NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID
NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID
NO:88, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:95, SEQ ID
NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:102, SEQ ID
NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID
NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ
ID
NO:115, SEQ ID NO:116, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID
NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ
ID
NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, and SEQ ID
NO:132.

18. A method for treating a disease or condition associated with decreased expression of functional GBAP, comprising administering to a patient in need of such treatment the pharmaceutical composition of claim 16.

19. A method for screening a compound for effectiveness as an agonist of a polypeptide of claim 1, the method comprising:
a) exposing a sample comprising a polypeptide of claim 1 to a compound, and b) detecting agonist activity in the sample.

20. A composition comprising an agonist compound identified by a method of claim 19 and a pharmaceutically acceptable excipient.

21. A method for treating a disease or condition associated with decreased expression of functional GBAP, comprising administering to a patient in need of such treatment a pharmaceutical composition of claim 20.

22. A method for screening a compound for effectiveness as an antagonist of a polypeptide of claim 1, the method comprising:
a) exposing a sample comprising a polypeptide of claim 1 to a compound, and b) detecting antagonist activity in the sample.

23. A composition comprising an antagonist compound identified by a method of claim 22 and a pharmaceutically acceptable excipient.

24. A method for treating a disease or condition associated with overexpression of functional GBAP, comprising administering to a patient in need of such treatment a pharmaceutical composition of claim 23.

25. A method of screening for a compound that specifically binds to the polypeptide of claim 1, said method comprising the steps of:
a) combining the polypeptide of claim 1 with at least one test compound under suitable conditions, and b) detecting binding of the polypeptide of claim 1 to the test compound, thereby identifying a compound that specifically binds to the polypeptide of claim 1.

26. A method of screening for a compound that modulates the activity of the polypeptide of claim 1, said method comprising:
a) combining the polypeptide of claim 1 with at least one test compound under conditions permissive for the activity of the polypeptide of claim 1, b) assessing the activity of the polypeptide of claim 1 in the presence of the test compound, and c) comparing the activity of the polypeptide of claim 1 in the presence of the test compound with the activity of the polypeptide of claim 1 in the absence of the test compound, wherein a change in the activity of the polypeptide of claim 1 in the presence of the test compound is indicative of a compound that modulates the activity of the polypeptide of claim 1.

27. A method for screening a compound for effectiveness in altering expression of a target polynucleotide, wherein said target polynucleotide comprises a sequence of claim 5, the method comprising:
a) exposing a sample comprising the target polynucleotide to a compound, and b) detecting altered expression of the target polynucleotide.

28. A method for assessing toxicity of a test compound, said method comprising:
a) treating a biological sample containing nucleic acids with the test compound;

b) hybridizing the nucleic acids of the treated biological sample with a probe comprising at least 20 contiguous nucleotides of a polynucleotide of claim 11 under conditions whereby a specific hybridization complex is formed between said probe and a target polynucleotide in the biological sample, said target polynucleotide comprising a polynucleotide sequence of a polynucleotide of claim 11 or fragment thereof;

c) quantifying the amount of hybridization complex; and d) comparing the amount of hybridization complex in the treated biological sample with the amount of hybridization complex in an untreated biological sample, wherein a difference in the amount of hybridization complex in the treated biological sample is indicative of toxicity of the test compound.