US20030064412A1 - 123 human secreted proteins - Google Patents

Abstract

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

Description

FIELD OF THE INVENTION
• This invention relates to newly identified polynucleotides and the polypeptides encoded by these polynucleotides, uses of such polynucleotides and polypeptides, and their production. [0001]
BACKGROUND OF THE INVENTION
• Unlike bacterium, which exist as a single compartment surrounded by a membrane, human cells and other eucaryotes are subdivided by membranes into many functionally distinct compartments. Each membrane-bounded compartment, or organelle, contains different proteins essential for the function of the organelle. The cell uses “sorting signals,” which are amino acid motifs located within the protein, to target proteins to particular cellular organelles. [0002]
• One type of sorting signal, called a signal sequence, a signal peptide, or a leader sequence, directs a class of proteins to an organelle called the endoplasmic reticulum (ER). The ER separates the membrane-bounded proteins from all other types of proteins. Once localized to the ER, both groups of proteins can be further directed to another organelle called the Golgi apparatus. Here, the Golgi distributes the proteins to vesicles, including secretory vesicles, the cell membrane, lysosomes, and the other organelles. [0003]
• Proteins targeted to the ER by a signal sequence can be released into the extracellular space as a secreted protein. For example, vesicles containing secreted proteins can fuse with the cell membrane and release their contents into the extracellular space—a process called exocytosis. Exocytosis can occur constitutively or after receipt of a triggering signal. In the latter case, the proteins are stored in secretory vesicles (or secretory granules) until exocytosis is triggered. Similarly, proteins residing on the cell membrane can also be secreted into the extracellular space by proteolytic cleavage of a “linker” holding the protein to the membrane. [0004]
• Despite the great progress made in recent years, only a small number of genes encoding human secreted proteins have been identified. These secreted proteins include the commercially valuable human insulin, interferon, Factor VIII, human growth hormone, tissue plasminogen activator, and erythropoeitin. Thus, in light of the pervasive role of secreted proteins in human physiology, a need exists for identifying and characterizing novel human secreted proteins and the genes that encode them. This knowledge will allow one to detect, to treat, and to prevent medical disorders by using secreted proteins or the genes that encode them. [0005]
SUMMARY OF THE INVENTION
• The present invention relates to novel polynucleotides and the encoded polypeptides. Moreover, the present invention relates to vectors, host cells, antibodies, and recombinant methods for producing the polypeptides and polynucleotides. Also provided are diagnostic methods for detecting disorders related to the polypeptides, and therapeutic methods for treating such disorders. The invention further relates to screening methods for identifying binding partners of the polypeptides. [0006]
DETAILED DESCRIPTION
• Definitions [0007]
• The following definitions are provided to facilitate understanding of certain terms used throughout this specification. [0008]
• In the present invention, “isolated” refers to material removed from its original environment (e.g., the natural environment if it is naturally occurring), and thus is altered “by the hand of man” from its natural state. For example, an isolated polynucleotide could be part of a vector or a composition of matter, or could be contained within a cell, and still -be “isolated” because that vector, composition of matter, or particular cell is not the original environment of the polynucleotide. [0009]
• In the present invention, a “secreted” protein refers to those proteins capable of being directed to the ER, secretory vesicles, or the extracellular space as a result of a signal sequence, as well as those proteins released into the extracellular space without necessarily containing a signal sequence. If the secreted protein is released into the extracellular space, the secreted protein can undergo extracellular processing to produce a “mature” protein. Release into the extracellular space can occur by many mechanisms, including exocytosis and proteolytic cleavage. [0010]
• As used herein, a “polynucleotide” refers to a molecule having a nucleic acid sequence contained in SEQ ID NO:X or the cDNA contained within the clone deposited with the ATCC. For example, the polynucleotide can contain the nucleotide sequence of the full length cDNA sequence, including the 5′ and 3′ untranslated sequences, the coding region, with or without the signal sequence, the secreted protein coding region, as well as fragments, epitopes, domains, and variants of the nucleic acid sequence. Moreover, as used herein, a “polypeptide” refers to a molecule having the translated amino acid sequence generated from the polynucleotide as broadly defined. [0011]
• In the present invention, the full length sequence identified as SEQ ID NO:X was often generated by overlapping sequences contained in multiple clones (contig analysis). A representative clone containing all or most of the sequence for SEQ ID NO:X was deposited with the American Type Culture Collection (“ATCC”). As shown in Table 1, each clone is identified by a cDNA Clone ID (Identifier) and the ATCC Deposit Number. The ATCC is located at 10801 University Boulevard, Manassas, Va. 20110-2209, USA. The ATCC deposit was made pursuant to the terms of the Budapest Treaty on the international recognition of the deposit of microorganisms for purposes of patent procedure. [0012]
• A “polynucleotide” of the present invention also includes those polynucleotides capable of hybridizing, under stringent hybridization conditions, to sequences contained in SEQ ID NO:X, the complement thereof, or the cDNA within the clone deposited with the ATCC. “Stringent hybridization conditions” refers to an overnight incubation at 42° C. in a solution comprising 50% formamide, 5× SSC (750 mM NaCl, 75 mM sodium citrate), 50 mM sodium phosphate (pH 7.6), 5× Denhardt's solution, 10% dextran sulfate, and 20 μg/ml denatured, sheared salmon sperm DNA, followed by washing the filters in 0.1× SSC at about 65° C. [0013]
• Also contemplated are nucleic acid molecules that hybridize to the polynucleotides of the present invention at lower stringency hybridization conditions. Changes in the stringency of hybridization and signal detection are primarily accomplished through the manipulation of formamide concentration (lower percentages of formamide result in lowered stringency); salt conditions, or temperature. For example, lower stringency conditions include an overnight incubation at 37° C. in a solution comprising 6× SSPE (20× SSPE=3M NaCl; 0.2M NaH[0014] ₂PO₄; 0.02M EDTA, pH 7.4), 0.5% SDS, 30% formamide, 100 ug/ml salmon sperm blocking DNA; followed by washes at 50° C. with 1× SSPE, 0.1% SDS. In addition, to achieve even lower stringency, washes performed following stringent hybridization can be done at higher salt concentrations (e.g. 5× SSC).
• Note that variations in the above conditions may be accomplished through the inclusion and/or substitution of alternate blocking reagents used to suppress background in hybridization experiments. Typical blocking reagents include Denhardt's reagent, BLOTTO, heparin, denatured salmon sperm DNA, and commercially available proprietary formulations. The inclusion of specific blocking reagents may require modification of the hybridization conditions described above, due to problems with compatibility. [0015]
• Of course, a polynucleotide which hybridizes only to polyA+ sequences (such as any 3′ terminal polyA+ tract of a cDNA shown in the sequence listing), or to a complementary stretch of T (or U) residues, would not be included in the definition of “polynucleotide,” since such a polynucleotide would hybridize to any nucleic acid molecule containing a poly (A) stretch or the complement thereof (e.g., practically any double-stranded cDNA clone). [0016]
• The polynucleotide of the present invention can be composed of any polyribonucleotide or polydeoxribonucleotide, which may be unmodified RNA or DNA or modified RNA or DNA. For example, polynucleotides can be composed of single- and double-stranded DNA, DNA that is a mixture of single- and double-stranded regions, single- and double-stranded RNA, and RNA that is mixture of single- and double-stranded regions, hybrid molecules comprising DNA and RNA that may be single-stranded or, more typically, double-stranded or a mixture of single- and double-stranded regions. In addition, the polynucleotide can be composed of triple-stranded regions comprising RNA or DNA or both RNA and DNA. A polynucleotide may also contain one or more modified bases or DNA or RNA backbones modified for stability or for other reasons. “Modified” bases include, for example, tritylated bases and unusual bases such as inosine. A variety of modifications can be made to DNA and RNA; thus, “polynucleotide” embraces chemically, enzymatically, or metabolically modified forms. [0017]
• The polypeptide of the present invention can be composed of amino acids joined to each other by peptide bonds or modified peptide bonds, i.e., peptide isosteres, and may contain amino acids other than the 20 gene-encoded amino acids. The polypeptides may be modified by either natural processes, such as posttranslational processing, or by chemical modification techniques which are well known in the art. Such modifications are well described in basic texts and in more detailed monographs, as well as in a voluminous research literature. Modifications can occur anywhere in a polypeptide, including the peptide backbone, the amino acid side-chains and the amino or carboxyl termini. It will be appreciated that the same type of modification may be present in the same or varying degrees at several sites in a given polypeptide. Also, a given polypeptide may contain many types of modifications. Polypeptides may be branched , for example, as a result of ubiquitination, and they may be cyclic, with or without branching. Cyclic, branched, and branched cyclic polypeptides may result from posttranslation natural processes or may be made by synthetic methods. Modifications include acetylation, acylation, ADP-ribosylation, amidation, covalent attachment of flavin, covalent attachment of a heme moiety, covalent attachment of a nucleotide or nucleotide derivative, covalent attachment of a lipid or lipid derivative, covalent attachment of phosphotidylinositol, cross-linking, cyclization, disulfide bond formation, demethylation, formation of covalent cross-links, formation of cysteine, formation of pyroglutamate, formylation, gamma-carboxylation, glycosylation, GPI anchor formation, hydroxylation, iodination, methylation, myristoylation, oxidation, pegylation, proteolytic processing, phosphorylation, prenylation, racemization, selenoylation, sulfation, transfer-RNA mediated addition of amino acids to proteins such as arginylation, and ubiquitination. (See, for instance, PROTEINS—STRUCTURE AND MOLECULAR PROPERTIES, 2nd Ed., T. E. Creighton, W. H. Freeman and Company, New York (1993); POSTTRANSLATIONAL COVALENT MODIFICATION OF PROTEINS, B. C. Johnson, Ed., Academic Press, New York, pgs. 1-12 (1983); Seifter et al., Meth Enzymol 182:626-646 (1990); Rattan et al., Ann NY Acad Sci 663:48-62 (1992).) [0018]
• “SEQ ID NO:X” refers to a polynucleotide sequence while “SEQ ID NO:Y” refers to a polypeptide sequence, both sequences identified by an integer specified in Table 1. [0019]
• “A polypeptide having biological activity” refers to polypeptides exhibiting activity similar, but not necessarily identical to, an activity of a polypeptide of the present invention, including mature forms, as measured in a particular biological assay, with or without dose dependency. In the case where dose dependency does exist, it need not be identical to that of the polypeptide, but rather substantially similar to the dose-dependence in a given activity as compared to the polypeptide of the present invention (i.e., the candidate polypeptide will exhibit greater activity or not more than about 25-fold less and, preferably, not more than about tenfold less activity, and most preferably, not more than about three-fold less activity relative to the polypeptide of the present invention.) [0020]
• Polynucleotides and Polypeptides of the Invention [0021]
• Features of Protein Encoded by Gene No: 1 [0022]
• This gene is expressed primarily in cerebellum. Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neural disorders, particularly damage to the cerebellum or additional CNS tissues caused by injuries, which include, but are not limited to, trauma or ischemia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system (CNS), expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., neural, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0023]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 150 as residues: Pro-7 to Cys-21, Leu-25 to Ser-30. [0024]
• The tissue distribution in cerebellum indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection, treatment, and/or prevention of neurodegenerative disease states, behavioral disorders, or inflammatory conditions which include, but are not limited to Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, depression, panic disorder, learning disabilities, ALS, psychoses, autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception. [0025]
• In addition, elevated expression of this gene product in regions of the brain indicates it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues. [0026]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:11 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1868 of SEQ ID NO:11, b is an integer of 15 to 1882, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:11, and where b is greater than or equal to a+14. [0027]
• Features of Protein Encoded by Gene No: 2 [0028]
• The translation product of this gene was found to have homology to the human env endogenous retrovirus protein (See Genbank Accession No, gil757872), which is thought to play a contributing role in the events leading up to the onset of cancer or of proliferative disorders in teratocarcinoma cell lines. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0029]

  VDPRVRRFWEDPEYPPVAVMSRLMLRRIPTVMSNTHRTQPSTWEQIKKLSQMVGENLRKAGQPVT	(SEQ ID NO: 289),
  VRRFWEDPEYPPVAVMSRLMLRRIP	(SEQ ID NO: 290),
  SNTHRTQPSTWEQIKKLSQMVGENLRK	(SEQ ID NO: 291),
  SACHSHTVFNWSEQNGQMVQMVRRMARVPIIWNHGSIGAPQPQMIWPIVGA	(SEQ ID NO: 292),
  KHKDLWQLLIALNKIKIWERIKKHLEGHSANLSLDIAKYIYIFKASQAHLT
  LMPELECSKELQTD
  MARVPIIWNHGSIGAPQPQMIWPIV	(SEQ ID NO: 293),
  RIKKHLEGHSANLSL DIAKYIYIFKASQAHLT	(SEQ ID NO: 294),
  VFLQQGLTQRSVILIGHICQFWLAIMPGYNHFMTQLHMLSGLNIYH	(SEQ ID NO: 295),
  NKSAPIIEAYHP QKSICKQN
  IGHICQFWLAIMPGYNHFMTQLHMLSGL	(SEQ ID NO: 296),
  SIPGTPDLNARTGVLEGAADRLAASNPLKWIKTLRSSVISMMIVLLICVVCLYIVCRC	(SEQ ID NO: 297),
  VLEGAADRLAASNPLKWIKTLRSSVIS	(SEQ ID NO: 298),
  LTVTKLPWLFIALQNKRMGTSWEQA	(SEQ ID NO: 299), and/or
  PKSGHKLAPKLVINKISAALSHACDSLTPTLEGCRFTGM RARNNWPTQGG
  MGTSWEQAPKSGHKLAPKLVINKISAALS (SEQ ID NO: 300).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0030]
• This gene is expressed primarily in PHA stimulated T-cells. [0031]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of the following diseases and conditions which include, but are not limited to, immune disorders, particularly autoimmune, inflammatory, or immunodeficiency diseases, in addition to, proliferative conditions such as cancers. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of -the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, hematopoietic, teratocarcinoma, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum; plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0032]
• The tissue distribution in T-cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, and/or prevention of a variety of immune system disorders. The expression of this gene product indicates a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer e.g. by boosting immune responses. Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia. [0033]
• In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. The protein may also show utility in the development of novel inhibitors to viral infections, or the protein may be useful in the development of novel vectors, such as those used in gene therapy, and/or immuno-therapy which could lead to the amelioration of disease of disease states. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues. [0034]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:12 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1576 of SEQ ID NO:12, b is an integer of 15 to 1590, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:12, and where b is greater than or equal to a+14. [0035]
• Features of Protein Encoded by Gene No: 3 [0036]
• The translation product of this gene was shown to have homology to the human retrovirus-related reverse transcriptase pseudogene (See Genbank Accession No. pirlA25313|GNHULL).In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0037]

  STHASVQKKDLTKFSAHSWLKKKKTFRKMIMEEIFLNLIKNIYKSPYSQCNT	(SEQ ID NO: 301),
  VRSEKGFDKIQCPFMVK	(SEQ ID NO: 302),
  FSKPSSYKTYIPKINLHFYILLMNIWETIKIVPLNNCFTKMNYLGI	(SEQ ID NO: 303),
  KKETKLSLFANDMI	(SEQ ID NO: 304), and/or
  SPLLFNILLEVLSSAVRKEKELK	(SEQ ID NO: 305).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0038]
• This gene is expressed primarily in PHA activated T cells. [0039]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions: immune or hematopoietic disorders, particularly inflammation, immunodeficiencies, and autoimmune diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0040]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 152 as residues: Ile-14 to Thr-24. [0041]
• The tissue distribution in T-cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, and/or prevention of a variety of immune system disorders. The expression of this gene product indicates a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer e.g. by boosting immune responses. Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia. [0042]
• In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Alternatively, the homology to a reverse transcriptase human gene may implicate this gene as providing utility in the understanding of host-viral interactions, particularly those involving retroviruses and other integration-dependent viruses. Moreover, the protein may show utility in the development of novel inhibitors to viral infection, and thus to the amelioration of human diseases and conditions. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0043]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:13 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1359 of SEQ ID NO:13, b is an integer of 15 to 1373, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:13, and where b is greater than or equal to a+14. [0044]
• Features of Protein Encoded by Gene No: 4 [0045]
• The translation product of this gene shares sequence homology with npdcf-1 which is thought to be important in promoting the survival of bi-potential glial progenitor cells (See Genbank Accession No. gi|456107). One embodiment of this gene comprises polypeptides of the following amino acid sequence: [0046]

  LRRPSTPLRRPWLHLQLPRISLGDQRLAQSAEMYHYQHQRQQMLSLERHKEPP	(SEQ ID NO: 306),
  KELDTALRMRRMRTETSRCTSARAWPRPGKWRCATICSTTPHCPRPCRPP
  AHRLHCHDLEADRRPLAPR
  RATQGAGHGSSDEENEDG	(SEQ ID NO: 307),
  DFTVYECPGMAPTGEMEVRNHLFD HAALSAPLPAPSSPLALP
  KAEYATAKALATPAATPDLAWGPAPGTERGDVPLPAPTATDVVPGAA	(SEQ ID NO: 308),
  SAEMYHYQHQRQQML	(SEQ ID NO: 309),
  LERHKEPPKEL	(SEQ ID NO: 310),
  AKCPPGAHACGP	(SEQ ID NO: 311),
  PVHMSPLEP	(SEQ ID NO: 312),
  WCRLQREIRLTQ	(SEQ ID NO: 313),
  SSDEENEDGDFTVYECPG	(SEQ ID NO: 314),
  APTGEMEVRN	(SEQ ID NO: 315),
  CPGSLDCALK	(SEQ ID NO: 316),
  RATQGAGHGSSDEENEDGDETVYECPGMAPTGEMEVRNHLFDHAALS	(SEQ ID NO: 317),
  APLPAPSSPLALP
  NEDGDFTVYECPGMAPTGEMEV	(SEQ ID NO: 318),
  RPTRPSSSCVLPRCLRCSRRGARSPRRAPGLAVPCCPGGGAEGWR	(SEQ ID NO: 319),
  RRCLRPPRGTCGCCGCCSPASSSAPPCVEPPPATRNVAACPGSLDCALKKRA
  SVLLVHMPVGLPSALPXGTAKACFAXMRRASXGGRAQPXLEMRLIPGPR
  ELARKGIWTSIPP
  RCLRCSRRGARSPRRAPGLAVPCCP	(SEQ ID NO: 320), and/or
  GSLDCALKKRASVLLVHMPVGLPSALPXGTAKAC	(SEQ ID NO: 321).

• Additional embodiments is the polynucleotides encoding these polypeptides. [0047]
• This gene is expressed primarily in cerebellum, synovial sarcoma, and to a lesser extent, in several other cancer cell lines. [0048]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neural or skeletal disorders, particularly tumors characterized by cells of a relatively undifferentiated state, including neural tumors. Similarly, polypeptides and antibodies directed to those polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the synovial fluid, prostate, breast and uterus, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., neural, skeletal, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0049]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 153 as residues: Pro-6 to Arg-11, Glu-52 to Gly-59. [0050]
• The tissue distribution in the cerebellum, combined with the homology to the human npdcf-1 protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosing and treating tumors that contain relatively high numbers of undifferentiated cells. Moreover, this gene is useful for the detection, treatment, and/or prevention of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception. [0051]
• In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Alternatively, the expression of this gene product in synovium would suggest a role in the detection and treatment of disorders and conditions affecting the skeletal system, in particular osteoporosis, bone cancer, as well as, disorders afflicting connective tissues (e.g., arthritis, trauma, tendonitis, chrondomalacia and inflammation), such as in the diagnosis or treatment of various autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (i.e. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). [0052]
• Moreover, the protein may be useful for inducing astroglial proliferation and promoting neuronal survival, in addition to other highly vascular tissues. The protein can also be used to regulate cellular metabolism (e.g., through the modulation of protein expression). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0053]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:14 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1128 of SEQ ID NO:14, b is an integer of 15 to 1142, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:14, and where b is greater than or equal to a+14. [0054]
• Features of Protein Encoded by Gene No: 5 [0055]
• The translation product of this gene was found to have homology to the RoBo-1 protein from Rattus norvegicus (See Genbank Accession No.gi|2895563 (AF041083)) which is thought to be important as a mediator in bone remodeling. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: DSHQARSRRLEALWSPSLGEVSSST (SEQ ID NO: ). Polynucleotides encoding these polypeptides are also encompassed by the invention. [0056]
• This gene is expressed primarily in colon, pituitary, and to a lesser extent in fetal lung and fibrosarcoma. [0057]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, endocrine, gastrointestinal, pulmonary, skeletal, or developmental and proliferative disorders, particularly those effecting the Gut/pituitary/hypothalamic axis. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the digestive system and regulation of feeding, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., gastrointesinal, endocrine, developmental, skeletal, pulmonary, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, amniotic fluid, pulmonary surfactant or sputum, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0058]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 154 as residues: Asn-26 to Cys-32, Cys-100 to Leu-112, Cys-128 to Ser-135. [0059]
• The tissue distribution in colon and pituitary indicates that polynucleotides and polypeptides corresponding to this gene are useful for treating disorders related to the intake and utilization of food since this gene is expressed in the digestive tract and a CNS site involved in regulation of weight homeostasis. The secreted protein can also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, and as nutritional supplements. It may also have a very wide range of biological activities. Typical of these are cytokine, cell proliferation/differentiation modulating activity or induction of other cytokines; immunostimulating/immunosuppressant activities (e.g., for treating human immunodeficiency virus infection, cancer, autoimmune diseases and allergy); regulation of hematopoiesis (e.g., for treating anemia or as adjunct to chemotherapy); stimulation or growth of bone, cartilage, tendons, ligaments and/or nerves (e.g., for treating wounds, stimulation of follicle stimulating hormone (for control of fertility); chemotactic and chemokinetic activities (e.g., for treating infections, tumors); hemostatic or thrombolytic activity (e.g., for treating hemophilia, cardiac infarction etc.); anti-inflammatory activity (e.g., for treating septic shock, Crohn's disease); as antimicrobials; for treating psoriasis or other hyperproliferative diseases; for regulation of metabolism, and behavior. Also contemplated is the use of the corresponding nucleic acid in gene therapy procedures. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0060]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:15 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1020 of SEQ ID NO:15, b is an integer of 15 to 1034, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 15, and where b is greater than or equal to a+14. [0061]
• Features of Protein Encoded by Gene No: 6 [0062]
• The translation product of this gene shares sequence homology with Cortical granule lectin which is thought to be important in blocking polyspermy (See Genbank Accession No. gnl|PID|e1181610). In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0063]

  	RSCKEIKD	(SEQ ID NO: 323),
  	GGGWTLVASVHEN	(SEQ ID NO: 324),
  	ADYPEGDGNWANYNTFGSA	(SEQ ID NO: 325),
  	ATSDDYKNPGYYDI	(SEQ ID NO: 326),
  	CIGGGGYFPEA	(SEQ ID NO: 327),
  	DSDKIT	(SEQ ID NO: 329),
  	YQTFCDMT	(SEQ ID NO: 330), and/or
  	EITEAAVLLFY	(SEQ ID NO: 328).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0064]
• This gene is expressed primarily in benign and metastatic colon, and to a lesser extent in HEL cells. [0065]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, gastrointestinal, reproductive, or developmental disorders, particularly cancer, or inflammatory conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the digestive system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g., gastrointestinal, reproductive, proliferating, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, seminal fluid, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0066]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 155 as residues: Arg-15 to Ser-33, Pro-35 to Cys-41. [0067]
• The tissue distribution in colon, combined with the homology to cortical granule lectins indicates that polynucleotides and polypeptides corresponding to this gene are useful for treating disorders of the colon. These may include diseases related to damage or chronic inflammation as well as tumors of the colon. The product may also be useful for the identification of colon cancer metastasis and, as a secreted protein, may have diagnostic and prognostic applications. Moreover, the protein is useful in the treatment, detection, and/or prevention of reproductive disorders, particularly normal testicular function, in addition having utility in the development of contraceptives, or in the treatment of polyspermy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues. [0068]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:16 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1184 of SEQ ID NO:16, b is an integer of 15 to 1198, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:16, and where b is greater than or equal to a+14. [0069]
• Features of Protein Encoded by Gene No: 7 [0070]
• This gene is expressed primarily in eight week human embryos. [0071]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, fetal and/or developmental abnormalities. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the developing fetus, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., developing, differentiating, and cancerous and wounded tissues) or bodily fluids (e.g., amniotic fluid, serum, plasma, lymph, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0072]
• The tissue distribution in eight week old tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for detecting embryonic abnormalities, in particular congenital abnormalities, which include, but are not limited to Tay-Sachs disease, phenylkenonuria, galactosemia, hyperlipidemias, porphyrias, and Hurler's syndrome. Expression within embryonic tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis, treatment, and/or prevention of cancer and other proliferative′ disorders. Similarly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0073]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:17 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1433 of SEQ ID NO:17, b is an integer of 15 to 1447, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:17, and where b is greater than or equal to a+14. [0074]
• Features of Protein Encoded by Gene No: 8 [0075]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0076]

  MGKRAHEVRRPPHSRPLHGTPAGWVLDPSGYKDVTQDA	(SEQ ID NO: 331),
  EVMEVLQNLYRTKSFLFVGCGETLRDQIFQALFLYSVPNKVDLEHYMLVLKE
  NEDHFFKHQADMLLHGIKVVSYGDCFDHFPGYVQDLATQICKQQSPGHLYSN
  SWSATPDGRGGP
  VLDPSGYKDVTQDAEVMEVLQNLYRT	(SEQ ID NO: 332),
  YSVPNKVDLEHY MLVLKENEDHFFKII	(SEQ ID NO: 333),
  DLATQICKQQSPGHLYSNSWSATPD	(SEQ ID NO: 334),
  RRMKTISLSIRQICFC	(SEQ ID NO: 335),
  TESKLYPTGTVLTTFQDMCKTLPLRSANSKAQDICTRIHGVPLLMGEEAHDSD
  SHASDRGHHTMLPLPAGSFSESSHQAWEVEMLIAWTAPHYWVMHARTVQRGS
  TESKLYPTGTVLTTFQDMCKTLPLRSA	(SEQ ID NO: 336), and/or
  LMGEEAH DSDSHASDRGHHTMLPLPAG	(SEQ ID NO: 337).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0077]
• This gene is expressed primarily in endothelial cells, and to a lesser extent in lymph node, tonsils, heart and spinal cord. [0078]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, vascular diseases, such as restenosis, including disorders of the integumentary system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the vascular system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., vascular, integumentary, immune, hematopoietic, neural, cardiovascular, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0079]
• The tissue distribution in endothelial cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for treating diseases of the vasculature including problems associated with diabetes and restenosis following angioplasty. Moreover, the protein is useful in the detection, treatment, and/or prevention of a variety of other vascular conditions, which include, but are not limited to, stroke, microvascular disease, aneurysm, vascular leak syndrome, or embolism. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0080]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:18 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1408 of SEQ ID NO:18, b is an integer of 15 to 1422, where both a and b correspond to the-positions of nucleotide residues shown in SEQ ID NO:18, and where b is greater than or equal to a+14. [0081]
• Features of Protein Encoded by Gene No: 9 [0082]
• The translation product of this gene was shown to have homology to the Gcap1 gene product of Mus musculus, which is specifically expressed in cerebellum and appears to be developmentally regulated (See Genbank Accession No. gi|862343). In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0083]

  LCAVEKTRTFTRGDCGPNRHHKHVLKAKDNNHIQRHQFSSTLEFS	(SEQ ID NO:338),
  SNSTDGLKYICVYLYVCTHPCIYIYLSAHTLHMYTHYLCKI
  SST LEFSSNSTDGLKYICVYLYVCTHPCIY	(SEQ ID NO:339),
  STSVCICTCAHTHVYI	(SEQ ID NO:340),
  FIYLHTHYICIHTIYVKYNICIMHINSNKCICVIFKIEQLYLEVVNAENWFYC
  IHTIYVKYNICIMHIN SNKCICVITFKIEQLY	(SEQ ID NO:341), and/or
  NSAVTVQMA	(SEQ ID NO:342).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0084]
• This gene is expressed primarily in fetal lung, endothelial cells and to a lesser extent, in astrocytes and fetal brain. [0085]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, vasdcular, developmental, neural, or proliferative conditions, particularly endothelial cell proliferation, such as occurs in restenosis. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the vascular system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., developmental, neural, vascular, and cancerous and wounded tissues) or bodily fluids (e.g., amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression, level in healthy tissue or bodily fluid from an individual not having the disorder. [0086]
• The tissue distribution in fetal brain, in addition to the homology to a brain-specific regulatory protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection, treatment, or prevention of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism; and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. [0087]
• Alternatively, the tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treating abnormal proliferation of endothelial cells such as occurs upon injury to the lung or arteries. Moreover, this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0088]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:19 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1093 of SEQ ID NO:19, b is an integer of 15 to 1107, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:19, and where b is greater than or equal to a+14. [0089]
• Features of Protein Encoded by Gene No: 10 [0090]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: TKTSTPLR (SEQ ID NO: 343). Polynucleotides encoding these polypeptides are also encompassed by the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 12. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 12. [0091]
• This gene is expressed primarily in infant brain and fetal tissues. [0092]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, developmental abnormalities or neural disorders, particularly gestational conditions, such as spina bifida. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., developing, neural, differentiating, and cancerous and wounded tissues) or bodily fluids (e.g., amniotic fluid, serum, lymph, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0093]
• The tissue distribution in infant brain and fetal tissues suggests that the protein product of this clone is useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses, autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Alternatively, the tissue distribution suggests that the protein product of this clone is useful for the diagnosis, treatment, and/or prevention of cancer and other proliferative disorders Moreover, the expression within fetal tissue and other cellular sources marked by proliferating cells suggests that this protein may play a role in the regulation of cellular division. Similarly, embryonic development also involves decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0094]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:20 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1169 of SEQ ID NO:20, b is an integer of 15 to 1183, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:20, and where b is greater than or equal to a+14. [0095]
• Features of Protein Encoded by Gene No: 11 [0096]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: VCIPGAAGLSVLLG (SEQ ID NO: 344). Polynucleotides encoding these polypeptides are also encompassed by the invention. [0097]
• This gene is expressed primarily in fetal kidney. [0098]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, urogenital, renal, or developmental disorders, particularly renal failure, tumors of the kidney, and/or developmental abnormalities associated with the kidney. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the renal system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., urological, renal, developmental, and cancerous and wounded tissues) or bodily fluids (e.g., amniotic fluid, lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0099]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 160 as residues: Gln-26 to Gln-34. [0100]
• The tissue distribution in fetal kidney indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, and/or prevention of cancer and other proliferative disorders, particularly renal disorders. Expression within embryonic tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division. Similarly, embryonic development also involves decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. [0101]
• Moreover, the protein product of this gene could be used in the treatment and/or detection of kidney diseases including nephritus, renal tubular acidosis, proteinuria, pyuria, edema, pyelonephritis, hydronephritis, nephrotic syndrome, crush syndrome, glomerulonephritis, hematuria, renal colic and kidney stones, in addition to Wilm's Tumor Disease, and congenital kidney abnormalities such as horseshoe kidney, polycystic kidney, and Falconi's syndrome. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0102]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:21 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1406 of SEQ ID NO:21, b is an integer of 15 to 1420, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:21, and where b is greater than or equal to a+14. [0103]
• Features of Protein Encoded by Gene No: 12 [0104]
• The gene encoding the disclosed cDNA is believed to reside on chromosome 17. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 17. [0105]
• This gene is expressed primarily in breast, fetal kidney, and T-cells. [0106]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, reproductive, immune, developmental, or renal disorders, particularly autoimmune diseases, chronic inflammatory conditions, or urogenital disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, reproductive, cancerous and wounded tissues) or bodily fluids (e.g., breast milk, lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0107]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 161 as residues: His-2 to Lys-7, Ser-28 to Glu-35. [0108]
• The tissue distribution in breast and T-cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, and/or prevention of a variety of immune system disorders. Moreover, the expression of this gene product indicates a role in regulating the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer e.g. by boosting immune responses. [0109]
• Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. [0110]
• Alternatively, the expression within fetal tissue indicates this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0111]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:22 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1561 of SEQ ID NO:22, b is an integer of 15 to 1575, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:22, and where b is greater than or equal to a+14. [0112]
• Features of Protein Encoded by Gene No: 13 [0113]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0114]

  SILPVEMAAAVAGMLRGGLLPQAGRLPTLQTVRYGSKAVTRHRRV	(SEQ ID NO: 345), and/or
  AGMLRGGLLPQAGRLPTLQTVRYGSK	(SEQ ID NO: 346).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0115]
• This gene is expressed primarily in the frontal cortex of the brain. [0116]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neural disorders, particularly neurodegenerative disorders, ischemia, Alzheimer's, or Parkinson's. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., neural, and cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0117]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 162 as residues: Glu-31 to Gly-37. [0118]
• The tissue distribution in frontal cortex indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues. [0119]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:23 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 527 of SEQ ID NO:23, b is an integer of 15 to 541, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:23, and where b is greater than or equal to a+14. [0120]
• Features of Protein Encoded by Gene No: 14 [0121]
• The gene encoding the disclosed cDNA is believed to reside on chromosome 1. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 1. [0122]
• This gene is expressed primarily in ovary, and to a lesser extent, in infant brain. [0123]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, reproductive, neural, or developmental disorders, particularly cancers and other diseases of the reproductive system including ovarian cysts and hormonal disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the female reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., reproductive, neural, developmental, and cancerous and wounded tissues) or bodily fluids (e.g., amniotic fluid, lymph, seminal fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0124]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 163 as residues: Ser-32 to Glu-37. [0125]
• The tissue distribution in ovarian tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of ovarian tumors, in addition to other tumors where expression has been indicated. Alternatively, expression within the fetal brain indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo. [0126]
• Moreover, the expression within fetal tissue indicates this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0127]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:24 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 819 of SEQ ID NO:24, b is an integer of 15 to 833, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:24, and where b is greater than or equal to a+14. [0128]
• Features of Protein Encoded by Gene No: 15 [0129]
• The translation product of this gene was shown to have homology to the highly conserved ras gene which is known to be important in the regulation of cell growth, and thus has been shown to serve as an inducible oncogene in eukaryotic tissues (See Genbank Accession No. gb|Z11804|DDRASX). When tested against PC12 (rat pheochromocytoma cells) and NIH3T3 cell lines, supernatants removed from cells containing this gene activated the EGR1 (early growth response gene 1) promoter element. Thus, it is likely that this gene activates sensory neuron cells and fibroblasts, in addition to other tissues or cell types, through the EGR1 signal transduction pathway. The EGR1 (early growth response gene 1) is a separate signal transduction pathway from Jaks-STAT, genes containing the EGR1 promoter are induced in various tissues and cell types upon activation, leading the cells to undergo differentiation and proliferation. [0130]
• Moreover, contact of cells with supernatant expressing the product of this gene has been shown to increase the permeability of the plasma membrane of monocytes to calcium. Thus it is likely that the product of this gene is involved in a signal transduction pathway that is initiated when the product-binds a receptor on the surface of the plasma membrane of monocytes, in addition to other cell-lines or tissue cell types, such as immune or hematopoietic cells. Thus, polynucleotides and polypeptides have uses which include, but are not limited to, activating monocytes. [0131]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: ARAGQMQNLESARAGRSVSTQTGS (SEQ ID NO: 347). Polynucleotides encoding these polypeptides are also encompassed by the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 13. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 13. [0132]
• This gene is expressed primarily in T-cells. [0133]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases involving immune regulation, which include, but are not limited to autoimmune diseases such as rheumatoid arthritis, lupus, and leukemia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., hematopoietic, immune, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0134]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 164 as residues: Ala-28 to His-41, Pro-43 to Gln-64. [0135]
• The tissue distribution in T-cells, combined with the detected EGR1 and calcium flux activities, indicates polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, and/or prevention of a variety of immune system disorders, particularly those dependent upon signalling aberrations. Expression of this gene product in T-cells indicates a role in regulating the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer—particularly considering the homology to a conserved ras gene, and the detected EGR1 biological activity. [0136]
• Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0137]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:25 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1541 of SEQ ID NO:25, b is an integer of 15 to 1555, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:25, and where b is greater than or equal to a+14. [0138]
• Features of Protein Encoded by Gene No: 16 [0139]
• This gene is expressed primarily in kidney cortex. [0140]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases of the kidney including cancer and renal dysfunction, in addition to, endocrine disorders, particularly of the adrenal glands. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the renal system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., urogenital, renal, endocrine, and cancerous and wounded tissues) or bodily fluids (e.g., urine, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0141]
• The tissue distribution in kidney cortex indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment, diagnosis, and/or prevention of diseases of the kidney including renal failure, nephritus, renal tubular acidosis, proteinuria, pyuria, edema, pyelonephritis, hydronephritis, nephrotic syndrome, crush syndrome, glomerulonephritis, hematuria, renal colic and kidney stones, in addition to Wilm's Tumor Disease, and congenital kidney abnormalities such as horseshoe kidney, polycystic kidney, and Falconi's syndrome. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0142]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:26 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1529 of SEQ ID NO:26, b is an integer of 15 to 1543, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:26, and where b is greater than or equal to a+14. [0143]
• Features of Protein Encoded by Gene No: 17 [0144]
• This gene is expressed primarily in T-cell lymphoma, and to a lesser extent, in bone marrow stromal cells. [0145]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune or hematopoietic disorders, particularly cancers, such as lymphomas and leukemias. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0146]
• The tissue distribution in bone marrow stromal cells and T-cell lymphoma indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, and/or prevention of a variety of immune or hematopoietic disorders. Expression of this gene product in T-cells indicates a role in regulating the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g., by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. [0147]
• Expression in bone marrow cells suggest that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoetic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues. [0148]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:27 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1248 of SEQ ID NO:27, b is an integer of 15 to 1262, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:27, and where b is greater than or equal to a+14. [0149]
• Features of Protein Encoded by Gene No: 18 [0150]
• This gene is expressed primarily in medulloblastoma. [0151]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, disorders of the central nervous system, including cancers. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., neural, cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0152]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 167 as residues: Phe-22 to Leu-28. [0153]
• The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection, treatment, and/or prevention of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0154]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:28 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 739 of SEQ ID NO:28, b is an integer of 15 to 753, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:28, and where b is greater than or equal to a+14. [0155]
• Features of Protein Encoded by Gene No: 19 [0156]
• The translation product of this gene was shown to have homology to the mammalian notch I protein which has been shown to be important in the regulation of cell-fate during pattern formation and development (See Genbank Accession No. gi|57635). One embodiment of this gene comprises polypeptides of the following amino acid sequence: [0157]

  KHEXHQVSDGALRCFASLADRFTRRGVDPAPLAKHGLTEE	(SEQ ID NO: 348),
  LLSRMAAAGGTVSGPSSACKPXRSTTGAPSTTADSKLSNQVSTIVSLLSTLCRG
  SPVVTHDLLRSELPDSIESALQGDERCVLDTMRLVDFLLVLLFEGRKALPKSSA
  GSTGRIPGLRRLDSSGERSHRQLIDCIRSKDTDALIDAIDTGAFEVNFMDDVG
  QTLLNWASAFGTQEMVEFLCERGADVNRGQRSSSLHYAACFGRPQVAKT
  LLRHGANPDLRDEDGKTPLDKARERGHSEVVAILQSPGDWMCPVNKGDDK
  PLDKARERGHSEVVAIL	(SEQ ID NO: 349),
  AKTLLRHGANPDLRD	(SEQ ID NO: 350),
  GRGRAWLCRRPVGSWIGAVWNDKPDKETFKKPWQMWTQIHCWNGYRWDXXDXKD	(SEQ ID NO: 351),
  SWIGAVWNDKPDKETFKKPWQMW	(SEQ ID NO: 352),
  KTMADVDPDTLLEWLQMGXGRXKGHATN TP	(SEQ ID NO: 353),
  RGVDPAPLAKHGLTEELLSRMAAAGGTVSGPSSA	(SEQ ID NO: 354),
  RSTTGAPSTTADSKLSNQVSTIVSLLSTLCR	(SEQ ID NO: 355),
  FEVNFMDDVGQTLLNWASAFGTQEMVEFLCERGA	(SEQ ID NO: 356), and/or
  EDGKTPLDKARERGHSEVVAILQSPGDW	(SEQ ID NO: 357).

• An additional embodiment is the polynucleotides encoding these polypeptides. [0158]
• This gene is expressed primarily in endothelial cells. [0159]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, vascular disorders, particularly diseases involving angiogenic abnormalities including diabetic retinopathy, macular degeneration, and other diseases including arterioscerosis, stroke, aneurysm, embolism, and cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the vascular system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., endothelial, vascular, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue from an individual not having the disorder. [0160]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 168 as residues: Asp-17 to Phe-23. [0161]
• The tissue distribution in endothelial cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for treating diseases where an increase or decrease in angiogenesis is indicated and as a factor in the wound healing process. The protein is useful in the treatment of cancer cells and tissues, particularly in inhibiting angiogenesis of the invading tumor. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0162]
• Alternatively, considering the homology to the Notch I protein, this gene may show utility in the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses, autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0163]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:29 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1607 of SEQ ID NO:29, b is an integer of 15 to 1621, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:29, and where b is greater than or equal to a+14. [0164]
• Features of Protein Encoded by Gene No: 20 [0165]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: TRPTMPNFLWFPKCA (SEQ ID NO: 358). Polynucleotides encoding these polypeptides are also encompassed by the invention. [0166]
• This gene is expressed primarily in meningioma tissues. [0167]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neural or central nervous system disorders, particularly cancers of the central nervous system and endothelium. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., neural, endothelial, CNS, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0168]
• The tissue distribution in meningioma tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses, autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. [0169]
• Moreover, the protein is useful in inhibiting or ameliorating infections of the meninges, particular viral infections. In addition, the protein may show utility in the treatment, detection, and/or prevention of such infections and disorders, in addition to degenerative conditions or congenital defects of the meninges. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0170]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:30 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 907 of SEQ ID NO:30, b is an integer of 15 to 921, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:30, and where b is greater than or equal to a+14. [0171]
• Features of Protein Encoded by Gene No: 21 [0172]
• The translation product of this gene was shown to have homology to the retinoic acid receptor gamma-2 which is thought to be important in the development of, and may be a key determinant for, human breast cancer during aberrant activation (See Genbank Accession No. AA176435). In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0173]

  LPPCLAQIFPFFSSGTNLTFCFFVFVFVFVFAELDYRNSYEIEY	(SEQ ID NO: 359).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0174]
• This gene is expressed primarily in ovary, and to a lesser extent, in meningioma. [0175]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, reproductive or neural disorders, particularly ovarian cancer, as well as, other cancers of the reproductive system, meninges, and endothelial tissue in general. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the female reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., ovarian, reproductive, neural, endothelial, endocrine, and cancerous and wounded tissues) or bodily fluids (e.g., amniotic fluid, lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0176]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 170 as residues: Leu-8 to Gln-1 8, Thr-26 to Lys-33, Met-39 to Cys-46, Ala-62 to Pro-69, Pro-83 to Glu-90. [0177]
• The tissue distribution in ovarian tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of tumors within these tissues, in addition to other tumors where expression has been indicated. The protein may also show utility in the treatment, detection, prevention, and/or amelioration of degenerative conditions or congenital disorders of the meninges, and the brain and spinal cord, in general. Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker and/or immunotherapy target for the above listed tumors and tissues. [0178]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:31 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2081 of SEQ ID NO:31, b is an integer of 15 to 2095, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:3 1, and where b is greater than or equal to a+14. [0179]
• Features of Protein Encoded by Gene No: 22 [0180]
• This gene is expressed primarily in the spongy tissue from Alzheimer's brain. [0181]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neural disorders, which include, but are not limited to Alzheimer's disease and other neurodegenerative diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells. particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., neural, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0182]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 171 as residues: Ser-31 to Ala-37, Ala-50 to Tyr-55, Phe-63 to Arg-68, His-83 to Pro-89. [0183]
• The tissue distribution in spongy tissue from Alzheimer's patient indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0184]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:32 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1824 of SEQ ID NO:32, b is an integer of 15 to 1838, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:32, and where b is greater than or equal to a+14. [0185]
• Features of Protein Encoded by Gene No: 23 [0186]
• This gene is expressed primarily in bone marrow cells. [0187]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune or hematological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hematological and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, haematopoeitic, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0188]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 172 as residues: Glu-22 to Ser-33, Leu-47 to Ser-55, Thr-87 to Arg-104. [0189]
• The tissue distribution in bone marrow cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoetic related disorders, which include, but are not limited to anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0190]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:33 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 768 of SEQ ID NO:33, b is an integer of 15 to 782, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:33, and where b is greater than or equal to a+14. [0191]
• Features of Protein Encoded by Gene No: 24 [0192]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: LKCTIYGGA (SEQ ID NO: 360). Polynucleotides encoding these polypeptides are also encompassed by the invention. [0193]
• This gene is expressed primarily in neutrophils. [0194]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases of the immune system, including inflammatory diseases and allergies. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, haematopoeitic, and. cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0195]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 173 as residues: Gln-36 to Lys-41. [0196]
• The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, and/or prevention of a variety of immune system disorders. Expression of this gene product indicates a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. [0197]
• Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic, anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0198]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:34 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1546 of SEQ ID NO:34, b is an integer of 15 to 1560, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:34, and where b is greater than or equal to a+14. [0199]
• Features of Protein Encoded by Gene No: 25 [0200]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0201]

  HVLWSLLSACWTQFLVYFCCLMILQRTFPPRALRTSPWLSNPMGVKGKKKKGTFME	(SEQ ID NO: 361), and/or
  ELVYFCCLMILQRTFPPRALRTSPWLSNPM	(SEQ ID NO: 362).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0202]
• This gene is expressed primarily in neutrophils. [0203]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune or hematopoietic disorders, including inflammatory diseases and allergies. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, haematopoeitic, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0204]
• The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, and/or prevention of a variety of immune system disorders. Expression of this gene product indicates a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). [0205]
• Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0206]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:35 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence-would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1078 of SEQ ID NO:35, b is an integer of 15 to 1092, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:35, and where b is greater than or equal to a+14. [0207]
• Features of Protein Encoded by Gene No: 26 [0208]
• This gene is expressed primarily in neutrophils. [0209]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune or hematopoietic disorders, including inflammatory conditions and allergies. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0210]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 175 as residues: Lys-9 to Leu-16, Ser-33 to Met-43. [0211]
• The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, and/or prevention of a variety of immune system disorders. Expression of this gene product indicates a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). [0212]
• Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0213]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:36 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1139 of SEQ ID NO:36, b is an integer of 15 to 1153, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:36, and where b is greater than or equal to a+14. [0214]
• Features of Protein Encoded by Gene No: 27 [0215]
• The translation product of this gene was shown to have homology to the intrinsic factor-B 12 receptor precursor of Rattus norvegicus which is thought to be important in development (See Genbank Accession No. gi|2961490 (AF022247)). One embodiment of this gene comprises polypeptides of the following amino acid sequence: [0216]

  DCNRDYHKAFGNLRSPGWPDNYDNDXDCXVTLTAPQNHHSGIVENAETISWR	(SEQ ID NO: 363),
  FGNLRSPGWPDNYDN	(SEQ ID NO: 364),
  ASFYRTS	(SEQ ID NO: 366), and/or
  APQNHXLKCRNDFLEV	(SEQ ID NO: 365).

• An additional embodiment is the polynucleotides encoding these polypeptides. [0217]
• This gene is expressed primarily in neutrophils. [0218]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune or hematopoietic disorders, including inflammatory disorders, and allergies. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, haematopoetic, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0219]
• The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, and/or prevention of a variety of immune system disorders. Expression of this gene product indicates a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). [0220]
• Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0221]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:37 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 971 of SEQ ID NO:37, b is an integer of 15 to 985, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:37, and where b is greater than or equal to a+14. [0222]
• Features of Protein Encoded by Gene No: 28 [0223]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0224]

  KADVKWHMCLQSPLCGLFCSIEGVLK	(SEQ ID NO: 367),
  ACMNPAMCFVCACPHTGSTPEKAILQGRLISLGTSLSPASNGSGQQSFSICMI	(SEQ ID NO: 368),
  NPSLPXSTSSHHLFSVLTGDLDSYSQRKLKPTSRKSFLLPKTQTYXVXHPSSP
  PLVLVQHRSPLSTYPKPVPSCCALDLISVIALETFLVYIHLFPSIDLSYWILSMLQ
  PLLLIKQQSTKTLSLNCMLYSSYYLISFLSFKAKVLRRGGNILHHFFTSYSEFNTY
  CPHTGSTPEKAILQGRLISLGTSLSPAS	(SEQ ID NO: 369),
  QHRSPLSTYPKPVPSCCALDLISV	(SEQ ID NO: 370), and/or
  IKQQSTKTLSLNCMLYSSYYLISFLSFKA	(SEQ ID NO: 371).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0225]
• This gene is expressed primarily in neutrophils. [0226]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune and/or haematological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, hematopoietic and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0227]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 177 as residues: Pro-55 to Ser-66. [0228]
• The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, and/or prevention of a variety of immune system disorders. Expression of this gene product indicates a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). [0229]
• Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0230]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:38 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1108 of SEQ ID NO:38, b is an integer of 15 to 1122, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:38, and where b is greater than or equal to a+14. [0231]
• Features of Protein Encoded by Gene No: 29 [0232]
• This gene is expressed primarily in neutrophils. [0233]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune and haematological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0234]
• The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, and/or prevention of a variety of immune system disorders. Expression of this gene product indicates a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). [0235]
• Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0236]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:39 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 584 of SEQ ID NO:39, b is an integer of 15 to 598, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:39, and where b is greater than or equal to a+14. [0237]
• Features of Protein Encoded by Gene No: 30 [0238]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: KYLVSSVLPTISMARSLISALRSG (SEQ ID NO: 372). Polynucleotides encoding these polypeptides are also encompassed by the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 7. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 7. [0239]
• This gene is expressed primarily in ovarian cancer. [0240]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, reproductive disorders, particularly ovarian cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., reproductive, ovarian, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0241]
• The tissue distribution in ovarian tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of ovarian cancer. Moreover, the protein is useful for the treatment, detection, and/or prevention of endocrine disorders, particularly those related to the reproductive system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0242]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:40 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1115 of SEQ ID NO:40, b is an integer of 15 to 1129, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:40, and where b is greater than or equal to a+14. [0243]
• Features of Protein Encoded by Gene No: 31 [0244]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0245]

  	MRTLFGAVRAPFSSLTLLLITPSPSPL	(SEQ ID NO: 373),
  	MAYAFHRTST	(SEQ ID NO: 374),
  	LKSTYTLLSILWFLVLIPVEGN	(SEQ ID NO: 375),
  		and/or
  	GPLLASHATLCFSLGSKF	(SEQ ID NO: 376).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0246]
• This gene is expressed primarily in ovarian cancer. [0247]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, reproductive, or endocrine disorders, particularly proliferative condtions such as ovarian cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., reproductive, endocrine, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0248]
• The tissue distribution in ovarian tumor tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of ovarian cancer. Moreover, the protein is useful for the detection, treatment, and/or prevention of a variety of reproductive disorders such as infertility. In addition, the protein may also be useful in the development of novel or improved contraceptives. The expression within cellular sources marked by proliferating cells indicates this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0249]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:41 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1144 of SEQ ID NO:41, b is an integer of 15 to 1158, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:41, and where b is greater than or equal to a+14. [0250]
• Features of Protein Encoded by Gene No: 32 [0251]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: TVWGILPRKR (SEQ ID NO: 377). Polynucleotides encoding these polypeptides are also encompassed by the invention. [0252]
• This gene is expressed primarily in ovarian tumor. [0253]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, reproductive or endocrine disorders, particularly proliferative conditions such as ovarian cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., reproductive, endocrine, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0254]
• The tissue distribution in ovarian tumor tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of ovarian cancer. Moreover, the protein is useful for the detection, treatment, and/or prevention of a variety of reproductive disorders such as infertility. In addition, the protein may also be useful in the development of novel or improved contraceptives. The expression within cellular sources marked by proliferating cells indicates this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0255]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:42 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1753 of SEQ ID NO:42, b is an integer of 15 to 1767, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:42, and where b is greater than or equal to a+14. [0256]
• Features of Protein Encoded by Gene No: 33 [0257]
• The translation product of this gene shares sequence homology with uroplakin III which is thought to be important in urothelial differentiation (See Accession No. d10226610). In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: ASIDTWPGRRSGGMIVITSI (SEQ ID NO: 378) and/or GSPQAETRWSDPIALHQGKSPASIDTWPGRRSGGMIVITSI (SEQ ID NO: 379). Polynucleotides encoding these polypeptides are also encompassed by the invention. [0258]
• This gene is expressed primarily in ovarian tumor. [0259]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, reproductive or endocrine disorders, particularly proliferative conditions such as ovarian cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., reproductive, endocrine, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0260]
• The tissue distribution in ovarian tumor tissue, combined with the homology to uroplakin III indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of reproductive disorders, urogential condtions, or endocrine disorders. Moreover, the protein is useful for the detection, treatment, and/or prevention of a variety of reproductive disorders such as infertility. In addition, the protein may also be useful in the development of novel or improved contraceptives. The expression within cellular sources marked by proliferating cells indicates this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0261]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:43 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 903 of SEQ ID NO:43, b is an integer of 15 to 917, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:43, and where b is greater than or equal to a+14. [0262]
• Features of Protein Encoded by Gene No: 34 [0263]
• The translation product of this gene shares sequence homology with estrogen-responsive finger protein. which is thought to be important in uterine implantation. (See Accession No. 1088467; and J. Biol. Chem. 270 (41), 24406-24413 (1995), herein incorporated by reference in its entirety.) Moreover, the protein product of this gene was also shown to homology to the human rfp transforming protein (See Genbank Accession No. gil337372) which is thought to play a role in in male germ cell development. Preferred polypeptide fragments comprise the amino acid sequence: [0264]

  VXDITFDPDTAHKYLRLQEENRKVTNTTPWEHPYPDLPSRFLH	(SEQ ID NO: 380);
  LYLHRYYFEVEIFGAGTYV	(SEQ ID NO: 381);
  SCISGNNFSWSLQWNGKEFTAW	(SEQ ID NO: 382);
  TPLKAGPFWSSGSILTS	(SEQ ID NO: 383);
  SVSEVKAVAEMQFGELLAAVRKAQANVMLFLXEKEQAAL	(SEQ ID NO: 384);
  EKSKQELETMAAISNTVQFLEEYCKFKNTEDITFPSVYIGLKD	(SEQ ID NO: 385);
  LENYKKKLQEFSKEEEYDIRTQVSAXVQR	(SEQ ID NO: 386);
  GTVSRERRAG	(SEQ ID NO: 388),
  HGDPTQSWPFLELGVYIDFPGGILSFYGVEYDSM	(SEQ ID NO: 389),
  TLVHKFACKFSEPVYAAFWLSKKENAIRIVDLGEEPEKPAP SLVGTAP
  SFYGVEYDSMTLVHKFACKFSEPVYAAFWL	(SEQ ID NO: 390),
  AELQCTQLDLERKLKLNENAISRLQANQKSVLVSVSEVKAVAEMQFGELLAAV	(SEQ ID NO: 391),
  RKAQANVMLFLXEKEQAALSQANGIKAHLEYKSAEMEKSKQELETMAAISN
  TVQFLEEYCKFKNTEDITFPSVYIGLKDKLSGIRKVITESTVHLIXXLENYKKKL
  QEFSKEEEYDIRTQVSAXVQRKYWTSKPEPSTREQFLQYVXDITFDPDTAHKYL
  RLQEENRKVTNTTPWEHPYPDLPSRFLHWRQVLSQQSLYLHRYYFEVEIFGA
  GTYVGLTCKGIDXKGEERXSCISGNNFSWSLQWNGKEFTAWYSDMETPL
  KAGPFWSSGSILTSQEGSFPSMA
  RTAPYGAKESSWR	(SEQ ID NO: 392), and/or
  MFSFRDPIGFQKPATISSYFCPQITLKCKSHHCSWQRSGIWLLESREQSPPRT
  VLASRVPLPDLQSGWRFPSWKARRQHRLVLKTCRQTCEPESWNHTLRHRR
  KGSLLGSQYRPRAPERASFEWGLHVTVPGRELLPVPLEAPGEVVSGNATXALL
  PFXVDAFAGQANIGACPEDLHLKIVPVQVQTLLGQHLPPVQEPAGEVRVG
  MLPGRGVGDLAVLLLQPEILVCCVRVERDVXHILEELFPGAGLRFGSPIFALN
  NGRHLSSDVILLFLGKLLELFLIVLQXXD
  GVYIDFPGGILSFYGVEYDSMTLVHKFACKFSEPVYAA	(SEQ ID NO: 387).

• Also preferred are polynucleotide fragments encoding these polypeptide fragments. [0265]
• This gene is expressed primarily in ovarian cancer. [0266]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, ovarian cancer and other disorders of the reproductive system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., reproductive, developmental, ovarian, testicular, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, seminal, fluid, amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0267]
• The tissue distribution in ovarian tumors, combined with the homology to estrogen-responsive finger protein, in addition, to the conserved rfp transforming protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of ovarian cancer and other disorders of the reproductive system. Moreover, the expression within cellular sources marked by proliferating cells indicates this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. The protein may also show utility in the development of novel contraceptives. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0268]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:44 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1973 of SEQ ID NO:44, b is an integer of 15 to 1987, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:44, and where b is greater than or equal to a+14. [0269]
• Features of Protein Encoded by Gene No: 35 [0270]
• This gene shows sequence homology to a [0271] Caenorhabditis elegans gene, called D1054.3, in addition, to the Sgt1p protein of Saccharomyces cerevisiae which are thought to play a role in the regulation of cellular division and developmental precesses (See Accession Nos. gn1|PID|e348554 and gi|1870791, respectively) Preferred polypeptide fragments comprise the amino acid sequence:

  SKIKYDWYQTESQVVITLMIKNVQKNDVNVEFSEKELSALVKLPSGEDYNLKL	(SEQ ID NO: 393);
  ELLHPIIPEQSTFKVLSTKIEIKLKKPEAVRWEKLEGQGDVPTPKQFVDVKNLY
  PSSSPTRNWDKLVGEIKEEEKNEKLEGDAALNRLFQQIYSDGSDEVKRAMN
  KSFMESGGTVLSTNWSDVGKRKVEINPPDDMEWKKY
  GDAALNRLFQQIYSDGSDEVKRAMNKSFMESGGTVLSTN	(SEQ ID NO: 394);
  MAAAAAGTXXSQRFFQSFSDALIDEDPQAALEELTKALEQKPDDAQYYCQ	(SEQ ID NO: 396),
  RAYCHILLGNYCVAVADAKKSLELNPNNSTAMLRKGICEYHEKNYAAALETFT
  EGQKLDSADAN FSVWIKRCQEAQNGSESEVVSPKFSFFMFLLF
  LEELTKALEQKPDD AQYYCQRAYCHILLGNYCVAVADA	(SEQ ID NO: 397),
  AMLRKGICEYHEKNYAAALETFTEGQKLDSA	(SEQ ID NO: 398),
  LRLWNRNQMM HSIIVKELIVTFFLGITVLLLLMQRSL	(SEQ ID NO: 399),
  NSIQIIPLLC	(SEQ ID NO: 400),
  YMHFNNTVAKLTCKNLSLSTYQNQSASQWTHQSKIKYDW	(SEQ ID NO: 401),
  YQTESQVVITLMIKNVQKNDVNVEFSEKELSALVKLPSGEDYNLKLELLHPI
  IPEQSTFKVLSTKIEIKLKKPEAVRWEKLEGQGDVPTPKQFVADVKNLYPSSS
  PYTRNWDKLVGEIKEEEKNEKLEGDAALNRLFQQIYSDGSDEVKRAMNKSF
  MESGGTVLSTNWSDVGKRKVEINPPDDMEWKKY
  TCKNLSLSTYQNQSASQWTHQSKIKYDWY	(SEQ ID NO: 402),
  EKELSALVKLPSGEDYNLKLELLH	(SEQ ID NO: 403),
  LHPIIPEQSTFKVLSTKIEIKLKKPEAVR	(SEQ ID NO: 404),
  KQFVADVKNLYPSSSPYTRNWDKL	(SEQ ID NO: 405), and/or
  DWYQTESQVVITLMIKNVQKNDV	(SEQ ID NO: 395).

• Also preferred are polynucleotide fragments encoding these polypeptide fragments. [0272]
• This gene is expressed primarily in osteoclastoma. [0273]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include; but are not limited to, skeletal or developmental disorders, particularly osteoclastoma and other forms of Cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the skeletal system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., skeletal, developmental, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0274]
• The tissue distribution in osteoclastoma, combined with the homology to the D1054.3 and Sgt1p proteins indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of osteoclastoma and other forms of cancers. Moreover, the expression within embryonic tissue and other cellular sources marked by proliferating cells indicates this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein may also play a role as a tumor supressor, or in the development of tumor progression inhibitors. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0275]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:45 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2039 of SEQ ID NO:45, b is an integer of 15 to 2053, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:45, and where b is greater than or equal to a+14. [0276]
• Features of Protein Encoded by Gene No: 36 [0277]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0278]

  GSKGQERKWRVRMGYLN	(SEQ ID NO: 406),
  QRYRLLPLFCYVCSRKIKLNENLFVFSAYSLATLPHTYLFSIVEC SSFCLSGTRN	(SEQ ID NO: 407), and/or
  FSAYSLATLPHTYLFSIVEC SSFCLSG	(SEQ ID NO: 408).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 7. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 7. [0279]
• This gene is expressed primarily in human placenta. [0280]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, developmental, vascular, and/or reproductive disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the embryonic and reproductive systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., developmental, vascular, reproductive, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, amniotic fluid, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0281]
• The tissue distribution in human placenta tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of the disorders of embryonic and reproductive systems. Moreover, the protein is useful for the detection, treatment, and/or prevention of a variety of vascular disorders, which include, but are not limited to, microvascular disease, aneurysm, arteriosclerosis, atherosclerosis, stroke, or embolism. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0282]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:46 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1258 of SEQ ID NO:46, b is an integer of 15 to 1272, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:46, and where b is greater than or equal to a+14. [0283]
• Features of Protein Encoded by Gene No: 37 [0284]
• This gene is expressed primarily in anergic T-cells. [0285]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune or hematopoietic disorders, particularly inflammatory conditions and immunodeficiencies such as AIDS. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0286]
• The tissue distribution in anergic T-cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of T cell related disorders. Moreover, the expression of this gene product indicates a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). [0287]
• Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0288]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:47 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 759 of SEQ ID NO:47, b is an integer of 15 to 773, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:47, and where b is greater than or equal to a+14. [0289]
• Features of Protein Encoded by Gene No: 38 [0290]
• The translation product of this gene shares sequence homology with a murine bone-related sulphatase (See Genbank Accession No. 3046314, and Genseq Accession No. R51355) which is thought to be involved in proteoglycan metabolism. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0291]

  	ASFGSCSLSLPCSARERTPEGGGWPGGRLSEPLPA	(SEQ ID NO: 409),
  	APNVVLV	(SEQ ID NO: 410),
  	DGRLTF	(SEQ ID NO: 411),
  	PGSQVVKLPFINFM	(SEQ ID NO: 412),
  	FLNAYTNSP	(SEQ ID NO: 413),
  	ICCPSRAAMWSGLFTHLTESWNNFKGLDPNYTTWMD	(SEQ ID NO: 414),
  	TQKFGK	(SEQ ID NO: 415),
  	DYTSGHHSI	(SEQ ID NO: 416),
  	SNRVEAWTRDVAFLLRQEGRP	(SEQ ID NO: 417),
  	DWQNTDKA	(SEQ ID NO: 418),
  	YLGLNLPHPYPSPSSGENFGSSTFHTSLYWLEKV	(SEQ ID NO: 419),
  	DAIKIPKW	(SEQ ID NO: 420),
  	YTKNCTG	(SEQ ID NO: 421),
  	NIRAFYYAMCAETDAMLGEIILALH	(SEQ ID NO: 422),
  	LDLLQKTIVIY	(SEQ ID NO: 423),
  	MEHRQFYKMSMYEAS	(SEQ ID NO: 424),
  	HVPLLMMGPGIKA	(SEQ ID NO: 425),
  	VVSLVDIYPTMLDIAGI	(SEQ ID NO: 426),
  	DPDELTN	(SEQ ID NO: 427),
  	WKYIAY	(SEQ ID NO: 428),
  	NFPEITYSLDQKLHSIINYPKVSASVHQYNKEQFIKWKQSIGQNYSNVIANFRWHQDWOKEPRKYENAID	(SEQ ID NO: 429),
  	QWLKTHMNPRAV
  	FPEITYSLDQKL	(SEQ ID NO: 430),
  	NYPKVSASVHQYNKEQFI	(SEQ ID NO: 431),
  	GQNYSNVIA	(SEQ ID NO: 432),
  	RWHQDWQ	(SEQ ID NO: 433), and/or
  	PRKYENAI	(SEQ ID NO: 434).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0292]
• This gene is expressed primarily in retina. [0293]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, visual, skeletal, or metabolic disorders, particularly eye dieases and bone metabolic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the eye, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., visual, skeletal, metabolic, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, vitreous humor, aqueous humor, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0294]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 187 as residues: Ala-21 to Arg-27, Asp-40 to Arg-45, Glu-97 to Thr-110, Glu-117 to Lys-128, Arg-175 to Lys-182, Pro-207 to Gly-220, Val-253 to Ile-272. [0295]
• The tissue distribution in retina, combined with the homology to sulphatases indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of eye disorders. Moreover, this gene may be useful in the detection, treatment, and/or prevention of bone-related disorders, osteoporosis, Paget's disease, osteomalacia, in addition to bone metabolic disorders, particularly those involving proteoglycans. The protein is also useful in the disorders involving aberrant proteoglycan metabolism or related conditions, which may include arthritis, immune cell migration, cellular proliferation, vascular disorders, hematopoietic disorders, in addition to showing utility in the detection, treatment, and/or prevention of the disorders mentioned above. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0296]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:42 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2105 of SEQ ID NO:48, b is an integer of 15 to 2119, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:48, and where b is greater than or equal to a+14. [0297]
• Features of Protein Encoded by Gene No: 39 [0298]
• This gene is expressed primarily in human stomach cancers. [0299]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, gastointestinal disorders, particularly cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the cancer, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., endothelial, gastrointestinal, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, chyme, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0300]
• The tissue distribution in tumors of the stomach indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, and/or prevention of these tumors, in addition to other tumors in other tissues. The protein may also be useful for the treatment and/or prevention of ulcers, in addition to additional gastrointestinal or metabolic conditions. Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker and/or immunotherapy target for the above listed tissues. [0301]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:49 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1174 of SEQ ID NO:49, b is an integer of 15 to 1188, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:49, and where b is greater than or equal to a+14. [0302]
• Features of Protein Encoded by Gene No: 40 [0303]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: RNSLHCYNEQPPNASGLIQWSSD LIPISLQCGCSW (SEQ ID NO: 435). Polynucleotides encoding these polypeptides are also encompassed by the invention. [0304]
• This gene is expressed primarily in human synovial membrane. [0305]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases of synovial membrane, skeletal and/or musculoskeletal disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the synovial membrane system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., skeletal, muscular, rheumatiod, synovial, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0306]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 189 as residues: Pro-10 to Ser-20. [0307]
• The tissue distribution in synovial tissue indicates the product of this gene may play a role in the detection, treatment, and/or prevention of disorders and conditions affecting the skeletal systemskeletal system, in particular osteoporosis, bone cancer, as well as, disorders afflicting connective tissues (e.g. arthritis, trauma, tendonitis, chrondomalacia and inflammation), such as in the diagnosis or treatment of various autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (i.e. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0308]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:50 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 464 of SEQ ID NO:50, b is an integer of 15 to 478, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:50, and where b is greater than or equal to a+14. [0309]
• Features of Protein Encoded by Gene No: 41 [0310]
• The translation product of this gene shares sequence homology with adipose specific collagen-like factor as well as the human adipocyte complement related protein Acrp30, the latter of which is known to be important in energy balance and homeostasis involving food intake, particularly in carbohydrate and lipid catabolism/anabolism (See Genbank Accession Nos.gnl|PID|d1008822 and W09108, respectively). One embodiment of this gene comprises polypeptides of the following amino acid sequence: [0311]

  XLWDPGLPGVCRCGSIVLKSAFSVGITTSYPEXRLPIIFNKVLLPRGXALQPC	(SEQ ID NO: 436),
  HRGSSSVLSQGIYYFSYDITLANKHLAIGLVHNGQYRIKTFDANTGNHDVASG
  STVIYLQPEDEVWLEIFFTDQNGLFSDPGWADSLFSGFLLYVDTDYLDSISEDDEL
  GSIVLKSAFSVGITT	(SEQ ID NO: 437),
  GIYYFSYDITLANK	(SEQ ID NO: 438),
  DSLFSGFLLYVDT	(SEQ ID NO: 439), and/or
  NHDVASGSTVIYL	(SEQ ID NO: 440).

• An additional embodiment is the polynucleotides encoding these polypeptides. [0312]
• This gene is expressed primarily in human schwanoma. [0313]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neural or integumentary disorders, particularly neurofibroma. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the diseases relating to peripheral or sympathetic nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., neural, integumentary, extracellular matrix, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0314]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 190 as residues: Gly-16 to Pro-30, Pro-42 to Gly-56, Gly-62 to Gly-77, Glu-93 to Gly-104, Glu-109 to Glu-114, Pro-121 to Asp-126. [0315]
• The tissue distribution in schwanoma cells combined with the homology to a conserved human adipose specific collagen-like factor as well as to the human adipocyte complement related protein Acrp30, indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioural disorders particularly neuroschwannoma, and including Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. [0316]
• Moreover, polynucleotides and polypeptides corresponding to this gene are useful for the treatment, diagnosis, and/or prevention of various skin disorders including congenital disorders (i.e. nevi, moles, freckles, Mongolian spots, hemangiomas, port-wine syndrome), integumentary tumors (i.e. keratoses, Bowen's disease, basal cell carcinoma, squamous cell carcinoma, malignant melanoma, Paget's disease, mycosis fungoides, and Kaposi's sarcoma), injuries and inflammation of the skin (i.e. wounds, rashes, prickly heat disorder, psoriasis, dermatitis), atherosclerosis, uticaria, eczema, photosensitivity, autoimmune disorders (i.e. lupus erythematosus, vitiligo, dermatomyositis, morphea, scleroderma, pemphigoid, and pemphigus), keloids, striae, erythema, petechiae, purpura, and xanthelasma. In addition, such disorders may predispose increased susceptibility to viral and bacterial infections of the skin (i.e. cold sores, warts, chickenpox, molluscum contagiosum, herpes zoster, boils, cellulitis, erysipelas, impetigo, tinea, althletes foot, and ringworm). Moreover, the protein product of this gene may also be useful for the treatment or diagnosis of various connective tissue disorders such as arthritis, trauma, tendonitis, chrondomalacia and inflammation, autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (i.e. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). [0317]
• Alternatively, considering the homology to a conserved adipose specific collagen-like factor, would suggest that this protein may also be important in the diagnosis or treatment of various autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias ie. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0318]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:51 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1319 of SEQ ID NO:51, b is an integer of 15 to 1333, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:51, and where b is greater than or equal to a+14. [0319]
• Features of Protein Encoded by Gene No: 42 [0320]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: SNSHTHTHVKSFLR (SEQ ID NO: 441). Polynucleotides encoding these polypeptides are also encompassed by the invention. [0321]
• This gene is expressed primarily in human activated T-Cells. [0322]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immunodeficiencies, inflammatory conditions, and other immune or hematopoietic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the disorders of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0323]
• The tissue distribution in T-cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, and/or prevention of a variety of immune system disorders. Expression of this gene product in T-cells indicates a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g., by boosting immune responses). [0324]
• Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0325]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:52 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1241 of SEQ ID NO:52, b is an integer of 15 to 1255, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:52, and where b is greater than or equal to a+14., [0326]
• Features of Protein Encoded by Gene No: 43 [0327]
• The protein product of this gene was found to have homology to the human CD84 protein which, as a novel member of the Ig superfamily, is thought to play an important role in the modulation of the immune response. The present invention appears to encode a novel full-length CD84 homolog and is highly enriched, if not specific, for activated T cells. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0328]

  ITPLGLGAAD	(SEQ ID NO: 442),
  TLRVLGKVPAVCPWCALWRKAGMDMTYSWLSRGDSTYTFHEGPVLSTSWRPGDSALSYTCR	(SEQ ID NO: 443),
  ANNPISNVSSCPIPDGPFYADPNYASEKPSTAFCLLAKGLLIFLLLVILAMGLW
  VIRVQKRHKMPRMKKLMRNRMKLRKEAKPGSSPA
  AVCPWCALWRKAGMDMTYSWL	(SEQ ID NO: 444),
  PGDSALSYTCRANNPISNVSSCPI	(SEQ ID NO: 445),
  YASEKPSTAFCLLAKGLLIFLLLV	(SEQ ID NO: 446), and/or
  QKRHKMPRMKKLMRNRMKLRKEAKPG	(SEQ ID NO: 447).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0329]
• This gene is expressed primarily in human activated T-Cells. [0330]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immunodeficiencies, inflammatory conditions, infections, and other immune or hematopoietic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the disorders of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0331]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 192 as residues: Glu-15 to Arg-23, Asn-79 to Gly-84. [0332]
• The tissue distribution in activated T-cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, and/or prevention of a variety of immune system disorders. Expression of this gene product in T-cells indicates a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g., by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0333]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID. NO:53 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1126 of SEQ ID NO:53, b is an integer of 15 to 1140, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:53, and where b is greater than or equal to a+14. [0334]
• Features of Protein Encoded by Gene No: 44 [0335]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: IAWSGNIPSLLCLFEHDMSFQDE (SEQ ID NO: 448). Polynucleotides encoding these polypeptides are also encompassed by the invention. [0336]
• This gene is expressed primarily in human tonsil. [0337]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, inflammatory conditions, infections, or immunodeficiencies, and immune or hematopoietic diseases and/or disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune diseases, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0338]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 193 as residues: Ile-2 to Lys-9, Gln-43 to Phe-49, Asn-59 to His-69, Gly-87 to Asp-93. [0339]
• The tissue distribution in tonsils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, and/or prevention of a variety of immune system disorders. Expression of this gene product indicates a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g., by boosting immune responses). [0340]
• Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0341]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:54 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1206 of SEQ ID NO:54, b is an integer of 15 to 1220, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:54, and where b is greater than or equal to a+14. [0342]
• Features of Protein Encoded by Gene No: 45 [0343]
• The translation product of this gene shares sequence homology with a novel human G52-24 secreted protein as well as the early lymphocyte activation antigen CD69, the latter of which has been shown to be important in lymphocyte proliferation and functions as a signal trasmitting receptor in lymphocytes, natural killer cells, and platelets (See Genseq and Genbank Accession Nos. W27288 and gi|558352, respectively). Preferred polypeptides comprise the following amino acid sequence: [0344]

  ENFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQLVMKEDGANLYVAKV	(SEQ ID NO: 449),
  SQVPRMNPXLS WVLLCYPGWSAVXTIVAHCSLDFPGSK
  ELTAIKSHQYVLQAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQ	(SEQ ID NO: 450),
  VESFQELVRK
  WIGLSREQGQPWKWING	(SEQ ID NO: 451),
  CPESWIGFQRKC	(SEQ ID NO: 452),
  NFLLRYKGPSDHWIGL	(SEQ ID NO: 453),
  ASHLRLLSSWDYRFPILGAGECAYLNDKGASSARHYTERKWI CSKSDIHV	(SEQ ID NO: 454),
  ENFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQLV	(SEQ ID NO: 455),
  MKEDGANLYVAKVSQVPRMNPXLS WVLLCYPGWSAVXTIVAHCSLDFPGSK
  EQLEELELKKKDFIKILESVQGNWRQNEDSGKGPQRSCL	(SEQ ID NO: 457),
  FWPESKIQPYKDMFSCEII	(SEQ ID NO: 458),
  SWTSSLLNXCLHSKEHSIKATIWRLFFXILTIILCGMVAALSAIRANCHQ EPSVCSSSCMP	(SEQ ID NO: 456),
  RKLDWFSKKVFLFF
  EQLEELELKKKDFIKILESVQGNWRQ	(SEQ ID NO: 459), and/or
  NEDSGKGPQRSCLHSKEHSIKATLIWRLFFLI
  ENFLLRYKGPSDHWIGLXXEQGQPWKWINGTEWTRQ	(SEQ ID NO: 460).

• Also preferred are the polynucleotides encoding these polypeptides. [0345]
• This gene is expressed primarily in human testes. [0346]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, reproductive, endocrine, and/or immune or hematopoietic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the disorders of reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, reproductive, endcrine, cancerous and wounded tissues) or bodily fluids (e.g., lymph, seminal fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0347]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 194 as residues: Asn-20 to Pro-25, Ser-48 to Asp-65. [0348]
• The tissue distribution in human testes indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, and/or prevention of a variety of reproductive disorders, particularly autoimmune disorders, infertility, or the protein may even be useful as a novel contraceptive. Homology of this gene product to the early lymphocyte activation antigen CD69 indicates a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g., by boosting immune responses). [0349]
• Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0350]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:55 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 680 of SEQ ID NO:55, b is an integer of 15 to 694, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:55, and where b is greater than or equal to a+14. [0351]
• Features of Protein Encoded by Gene No: 46 [0352]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: RHEPDPM (SEQ ID NO: 461). Polynucleotides encoding these polypeptides are also encompassed by the invention. [0353]
• This gene is expressed primarily in human testes. [0354]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, male reproductive or endocrine disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., endocrine, reproductive, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, seminal fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0355]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 195 as residues: Pro-20 to Trp-25, Arg-33 to Thr-38, Asn-5 1 to Ile-56, Gly-82 to Ser-91, Lys-151 to Arg-156. [0356]
• The tissue distribution in human testicular tissues and cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection, treatment, and/or prevention of various endocrine disorders and cancers, particularly Addison's disease, Cushing's Syndrome, and disorders and/or cancers of the pancrease (e.g., diabetes mellitus), adrenal cortex, ovaries, pituitary (e.g., hyper-, hypopituitarism), thyroid (e.g., hyper-, hypothyroidism), parathyroid (e.g., hyper-, hypoparathyroidism), hypothallamus, and testes. [0357]
• Alternatively, expression within the human testis may be indicative for a role in normal testicular function, and may implicate this gene product in male fertility, and could even suggest its use as a novel contraceptive. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0358]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:56 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 974 of SEQ ID NO:56, b is an integer of 15 to 988, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:56, and where b is greater than or equal to a+14. [0359]
• Features of Protein Encoded by Gene No: 47 [0360]
• One embodiment of this gene comprises polypeptides of the following amino acid sequence: [0361]

  	LKGREAGAGPGTAGAPGREDANGXXRGRGGXHQLYLWVDNIPLSRPKRNLS (SEQ ID NO:462),
  	RDFSDGVLVAEVIKFYFPKMVEMHYVGTSSLQQKLSNWGHLNRKVLKRL
  	NFSVPDDV
  	WVDNIPLSRPKRNLSRDFSDGVLVA	(SEQ ID NO:463),
  	YVGTSSLQQKLSNWGHLNRKVLKRL	(SEQ ID NO:464),
  	GSAWRRG	(SEQ ID NO:465),
  	RGAGSRAPAPYRSWLPRMAVATWMWVYPRRPEVKVSRTPREGVSSAGTG
  	RRRLGLQRITGRCRATPASSSRSLKRSRSCWPLKRPCRSCR
  	WLPRMAVATWMWVYPRRPEVK	(SEQ ID NO:466),
  	CRATPASSSRSLKRSRSCWPLKR	(SEQ ID NO:467),
  	EHNTDFNGAALSRNLQTFRLSTPCARREGRLLRA	(SEQ ID NO:468);
  	HRRCPPYSWRSHASPLPLQLLRSPSPRWVPGKLPGGAGEPLSGPGQIPPWLRA
  	WGTSLDGDAAVLGAGRGPDSGGVDRAKGPPPKAQRREMQGRAQGVGHCFG
  	GQARSLHVASGLWKAVHSPDPDLRSGRRRLSPGPALLEFLSHLLHAHPSQGRR
  	ALGPQQARESSGLRPPNGLSIGGWVRRGVGALAGTRASPRGPGRRSPLLTXR
  	XLEPPGEVFDPHILELEQVLQAPYLHLQDLHGLLRGQQLLLLFSDLEDEAGVA
  	LQRPVIRWRPRRRRPVPAELTPSLGVRDTFTSGLLGYTHIHVATAILGS   QLL
  	TDFNGAALSRNLQTFRLSTPCARREG	(SEQ ID NO:469),
  	RCPPYSWRSHASPLPLQLLRSPSPR	(SEQ ID NO:470),
  	GAGEPLSGPGQIPPWLRAWGTSLD	(SEQ ID NO:471),
  	LGAGRGPDSGGVDRAKGPPPKAQRREMQGR	(SEQ ID NO:472),
  	QARSLHVASGLWKAVHSPDPDLR	(SEQ ID NO:473),
  	HPSQGRRALGPQQARESSGL	(SEQ ID NO:474),
  	IGGWVRRGVGALAGTRASPRGPGRRSP	(SEQ ID NO: 475),
  	EPPGEVFDPHILELEQVLQAPYLHL	(SEQ ID NO:476), and/or
  	VPAELTPSLGVRDTFTSGLLGYTHIHVA	(SEQ ID NO:477).

• An additional embodiment is the polynucleotides encoding these polypeptides. [0362]
• This gene is expressed primarily in human adult testis. [0363]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, reproductive and/or endocrine disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the disorders of the reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., reproductive, endocrine, cancerous and wounded tissues) or bodily fluids (e.g., lymph, seminal fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0364]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 196 as residues: Gln-21 to Gly-33, Gln-55 to Glu-60. [0365]
• The tissue distribution in testicular tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection, treatment, and/or prevention of reproductive system disorders, and may be indicative of a role for this gene product in normal testicular function, male fertility, and/or as a male contraceptive. Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker and/or immunotherapy target for the above listed tissues. . [0366]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:57 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1486 of SEQ ID NO:57, b is an integer of 15 to 1500, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:57, and where b is greater than or equal to a+14. [0367]
• Features of Protein Encoded by Gene No: 48 [0368]
• The translation product of this gene shares sequence homology with the human M phase phosphoprotein 10 as well as ORF YJR002w of [0369] Saccharomyces cerevisiae (See Genbank Accession No.gnl|PID|e266673) which are thought to play important roles in the regulation of cellular division. Preferred polypeptides comprise the following amino acid sequence:

  AKNSQKEENPEHVEIQKMMDSLFLKLDALSNFHFIPKPPVEIKVVSNLPAI	(SEQ ID NO:478),
  TMEEVAPVSVSDAALLAPEEIKEKNKAGDIKTAAEKTATDKKRERRKKKYQKR
  MKIKEKEKRRKLLEKSSVDQAGKYSKTVASEKLKQLTKTGKASFIKVRTR
  ERKLLKGTFVGEVDSKCWVTGMSEPADSPPVG
  LQDEGKDKALKSSQAFFSKLQDQVKMQINDAKKTEKKKKKRQDISVHKLKL	(SEQ ID NO:479),
  DEGKDKALKSSQAFFSKLQDQVKMQINDA	(SEQ ID NO:480),
  EENPEHVEIQKMMDSLFLKLDALSNFHF	(SEQ ID NO:481),
  SSVDQAGKYSKTVASEKLKQLTKTGKASFIK	(SEQ ID NO:483),
  VSVSDAALLAPEEIKEKNKAGDI	(SEQ ID NO:484),
  VLEVMVTVAPK	(SEQ ID NO:485),
  LQDEGKDKALKSSQAFFSKLQDQVKMQINDAKKTE	(SEQ ID NO:486),

• Also preferred are the polynucleotides encoding these polypeptides. [0370]
• This gene is expressed primarily in human thyroid. -Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, endocrine, proliferative, or developmental disorders, particularly diseases relating to the thyroid gland, particularly hyper- and hypothyroidism. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the disorders of the endocrine system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., endocrine, developmental, metabolic, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e.:, the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0371]
• The tissue distribution in human thyroid indicates that polynucleotides and polypeptides corresponding to this gene are useful for metabolic disorders, particularly hyper-, hypothyroidism, Graves' disease, Hashimoto's thyroiditis, and/or cancer or neoplasias of the thyroid, and/or other endocrine organs and immune system. Moreover, the protein may show utility in the diagnosis, prevention, and/or treatment of developmental disorders. In addition, the homology to an M phase phosphoprotein indicates it may be a key player in the proliferation, maintenance, and/or differentiation of various cell types during development. It may also act as a morphogen to control cell and tissue type specification. Because of potential roles in proliferation and differentiation, this gene product may have applications in the adult for tissue regeneration and the treatment of cancers. Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker and/or immunotherapy target for the above listed tissues. [0372]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:58 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1377 of SEQ ID NO:58, b is an integer of 15 to 1391, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:58, and where b is greater than or equal to a+14. [0373]
• Features of Protein Encoded by Gene No: 49 [0374]
• The translation product of this gene was found to have homology to the cell division control protein 48 (cdc48) of [0375] Methanococcus jannaschii (See Genbank Accession No.gi|1591785) which is thought to play a key role in the regulation of cellular division. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:

  HEAAQGAVCRGQGAPATNPQAPVAAAARVARRVN	(SEQ ID NO:487),
  KIPS	(SEQ ID NO:488),
  ANRRATRCLGCDHQNFVKVRNKHKGKPTFMEEVLEHLPGKTQDEVQQHEKW
  YQKFLALEERKKESIQIWKTKKQQKREEIFKLKEKADNTPVLFHNKQEDNQKQ
  KEEQRKKQKLAVEAWKKQKSIEMSMKCASQLKKKKKKKKKNQKERQRQFK
  LKLLLESYTQQKKEQEEFLRLEKEIREKAEKAEKRKNAADEISRFQERDLHKLE
  LKILDRQAKEDEKSQKQRRLAKLKEKVENNVSRDPSRLYKPTK
  VKVRNKHKGKPTFMEEVLEHLPGK	(SEQ ID NO:489),
  QHEKWYQKFLALEERKKESIQIW	(SEQ ID NO:490),
  FKLKEKADNTPVLFHNKQEDNQKQKEEQRKK	(SEQ ID NO:491),
  FLRLEKIEIREKAEKAEKRKNAADEISRFQERDLHKL	(SEQ ID NO:492), and/or
  KQRRLAKLKEKVENNVSRDPSRLY	(SEQ ID NO:493).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0376]
• This gene is expressed primarily in pancreas, and to a lesser extent in kidney and bone marrow. [0377]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, pancreas, urogenital, developmental, metabolic, immune, and/or hematopoietic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification, of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the pancreas, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., endocrine, developmental, metabolic, immune, hematopoietic, gastrointestinal, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, bile, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0378]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO:198 as residues: Pro-35 to Cys-43, Gln-56 to Lys-67, Thr-73 to Lys-78, Tyr-93 to Asp-98, Ser-116 to Gln-125, Leu-142 to Phe-151, Phe-169 to Arg-174, Ile-181 to Glu-190, Thr-243 to Gly-248. [0379]
• The tissue distribution in pancreas indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection, treatment, and/or prevention of various endocrine disorders and cancers, particularly Addison's disease, Cushing's Syndrome, and disorders and/or cancers of the pancrease (e.g., diabetes mellitus), adrenal cortex, ovaries, pituitary (e.g., hyper-, hypopituitarism), thyroid (e.g., hyper-, hypothyroidism), parathyroid (e.g., hyper-,hypoparathyroidism), hypothallamus, and testes. Alternatively, the expression within bone marrow indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and-diagnosis of hematopoetic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. [0380]
• Moreover, the protein product of this gene could be used in the treatment and/or detection of kidney diseases including renal failure, nephritus, renal tubular acidosis, proteinuria, pyuria, edema, pyelonephritis, hydronephritis, nephrotic syndrome, crush syndrome, glomerulonephritis, hematuria, renal colic and kidney stones, in addition to Wilm's Tumor Disease, and congenital kidney abnormalities such as horseshoe kidney, polycystic kidney, and Falconi's syndrome. Considering the homology to a conserved cell division control protein indicates that the protein may show utility in the diagnosis, prevention, and/or treatment of developmental disorders, and may even serve as a suppressor in tumorigenesis. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0381]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:59 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1565 of SEQ ID NO:59, b is an integer of 15 to 1579, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:59, and where b is greater than or equal to a+14. [0382]
• Features of Protein Encoded by Gene No: 50 [0383]
• The translation product of this gene was shown to have homology to the chicken LRP/alpha-2-macroglobulin receptor which is thought to play a pivitol role on the metabolism of alpha-2-macroglubulins, as well as, complexes between plasminogen activators and their endogenous inhibitors (See Genbank Accession No.gb|X74904|GGLRPA2MR). [0384]
• This gene is expressed primarily in neuronal tissues, and to a lesser extent in uterine cancer. [0385]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neuronal disorders and uterine cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s) For a number of disorders of the above tissues or cells, particularly of the central neuron system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., neural, reproductive, cancerous and wounded tissues) or bodily fluids (e.g., amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0386]
• The tissue distribution in neuronal tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses, autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0387]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:60 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1227 of SEQ ID NO:60, b is an integer of 15 to 1241, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:60, and where b is greater than or equal to a+14. [0388]
• Features of Protein Encoded by Gene No: 51 [0389]
• This gene is expressed primarily in uterine cancer. [0390]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, uterine cancer, and other reproductive disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the uterine cancer, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., reproductive, cancerous and wounded tissues) or bodily fluids (e.g., amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0391]
• The tissue distribution in tumors of the uterus indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of these tumors or proliferative conditions, in addition to other tumors or cell types. Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker and/or immunotherapy target for the above listed tissues. [0392]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:61 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 916 of SEQ ID NO:61, b is an integer of 15 to 930, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:61, and where b is greater than or equal to a+14. [0393]
• Features of Protein Encoded by Gene No: 52 [0394]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: VKPPDQSCNHWRDEQCLV (SEQ ID NO: 494). Polynucleotides encoding these polypeptides are also encompassed by the invention. [0395]
• This gene is expressed primarily in wilm's tumor. [0396]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, Wilm's tumor, and other urogenital disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the Wilm's tumor, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., urogenital, cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0397]
• The tissue distribution in Wilm's tumor indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of Wilm's tumor. Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker and/or immunotherapy target for the above listed tissues. Furthermore, this gene or gene product is useful in the treatment and/or detection of kidney diseases including renal failure, nephritus, renal tubular acidosis, proteinuria, pyuria, edema, pyelonephritis, hydronephritis, nephrotic syndrome, crush syndrome, glomerulonephritis, hematuria, renal colic and kidney stones, in addition to congenital kidney abnormalities such as horseshoe kidney, polycystic kidney, and Falconi's syndrome. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0398]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:62 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 984 of SEQ ID NO:62, b is an integer of 15 to 998, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:62, and where b is greater than or equal to a+14. [0399]
• Features of Protein Encoded by Gene No: 53 [0400]
• The translation product of this gene was shown to have homology to the MEK kinase 3 of Mus musculus, mutations of which and/or aberrant regulation of, may provide a predisposition to cancer. The gene encoding the disclosed cDNA is thought to reside on chromosome 17. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 17. [0401]
• This gene is expressed primarily in pituitary, and to a lesser extent in ulcerative colitis and hematopoietic cells. [0402]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune, gastrointestinal, hematopoietic diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the neuronal and immune tissues, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., neuronal, immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0403]
• The tissue distribution in hematopoietic tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, and/or prevention of a variety of immune system disorders. Expression of this gene product in ulcerative colitis indicates a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g., by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. [0404]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:63 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1179 of SEQ ID NO:63, b is an integer of 15 to 1193, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:63, and where b is greater than or equal to a+14. [0405]
• Features of Protein Encoded by Gene No: 54 [0406]
• When tested against Jurkat T-cell cell lines, supernatants removed from cells containing this gene activated the GAS (gamma activation site) pathway. Thus, it is likely that this gene activates T-cells through the Jaks-STAT signal transduction pathway. GAS (gamma activation site) is a promoter element found upstream in many genes which are involved in the Jaks-STAT pathway. The Jaks-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jaks-STATs pathway, reflected by the binding of the GAS element, can be used to indicate proteins involved in the proliferation and differentiation of cells. [0407]
• This gene is expressed primarily in fetal spleen and adipose tissues. [0408]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune, metabolic, and developmental disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the fetal spleen and adipose tissues, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, developing, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0409]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 203 as residues: Tyr-41 to Phe-47. [0410]
• The tissue distribution in fetal liver/spleen, combined with the detection of GAS promoter activation activity, indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, and/or prevention of a variety of immune system disorders. Expression of this gene product in fetal spleen indicates a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g., by boosting immune responses). [0411]
• Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0412]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:64 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 816 of SEQ ID NO:64, b is an integer of 15 to 830, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:64, and where b is greater than or equal to a+14. [0413]
• Features of Protein Encoded by Gene No: 55 [0414]
• This gene is expressed primarily in IL-1/TNF stimulated synovial and human adipose tissues. [0415]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, rheumatoid arthritis or obessity, and disorders of the musculo-skeletal system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and musculo-skeletal systems, expression of this gene at significantly higher or lower levels may. be routinely detected in certain tissues or cell types and cell types (e.g., synovial and adipose cells and tissues, musculo-skeletal, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0416]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 204 as residues: Leu-37 to Arg-45, Ser-60 to Ser-65. [0417]
• The tissue distribution in synovial tissue and adipose tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis or treatment of rheumatoid arthritis or other immune diseases. In addition, the expression of this gene product in synovium indicates a role in the detection and treatment of disorders and conditions affecting the skeletal system, in particular osteoporosis as well as disorders afflicting connective tissues (e.g. arthritis, trauma, tendonitis, chrondomalacia and inflammation), such as in the diagnosis or treatment of various autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (ie. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). [0418]
• The tissue distribution in adipose tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment of obesity and other metabolic and endocrine conditions or disorders. Furthermore, the protein product of this gene may show utility in ameliorating conditions which occur secondary to aberrant fatty-acid metabolism (e.g. aberrant myelin sheath development), either directly or indirectly. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0419]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:65 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 853 of SEQ ID NO:65, b is an integer of 15 to 867, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:65, and where b is greater than or equal to a+14. [0420]
• Features of Protein Encoded by Gene No: 56 [0421]
• When tested against K562 leukemia cell lines, supernatants removed from cells containing this gene activated the ISRE assay. Thus, it is likely that this gene activates leukemia cells through the Jak-STAT signal transduction pathway. The interferon-sensitive response element is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jak-STAT pathway, reflected by the binding of the ISRE element, can be used to indicate proteins involved in the proliferation and differentiation of cells. [0422]
• This gene is expressed primarily in aortic endothelium, and to a lesser extent in melanocyte. [0423]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, cardiovascular diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the cardiovascular system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., vascular, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0424]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 205 as residues: Met-1 to Trp-12, Arg-33 to Ser-53. [0425]
• The tissue distribution in human aortic endothelial cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection or intervention of cardiovascular diseases, such as hypertension, cadiovascular injuries, congenital heart diseases, ischemic heart diseases, rheumatic and other hypersensitivity diseases, cardiomyopathy, restenosis, atherosclerosis, stoke, angina, thrombosis, and wound healing. Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker and/or immunotherapy target for the above listed tissues. [0426]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:66 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 671 of SEQ ID NO:66, b is an integer of 15 to 685, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:66, and where b is greater than or equal to a+14. [0427]
• Features of Protein Encoded by Gene No: 57 [0428]
• The translation product of this gene shares sequence homology with prostaglandin EP3-9 receptor, which is thought to be important in prostaglandin hormonal reaction. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: MAIPAFSSCQQISSAAALQI (SEQ ID NO: 495), and/or CNGPFKHFSFTVST (SEQ ID NO: 496). Polynucleotides encoding these polypeptides are also encompassed by the invention. [0429]
• This gene is expressed primarily in human retina. [0430]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, glaucoma or other ocular diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the ocular system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., retinal and other optic tissue, tissue of the nervous system, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0431]
• The tissue distribution in retinal tissues and the homology to prostaglandin receptor indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and intervention of ocular diseases like glaucoma. Specifically, the receptor can be used for the identification of agonists or antagonists, anti-inflammatories for the eyes, and vasoconstrictive agents, etc. Furthermore, the tissue distribution in retina indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and/or detection of eye disorders including blindness, color blindness, impaired vision, short and long sightedness, retinitis pigmentosa, retinitis proliferans, and retinoblastoma. [0432]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:67 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 787 of SEQ ID NO:67, b is an integer of 15 to 801, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:67, and where b is greater than or equal to a+14. [0433]
• Features of Protein Encoded by Gene No: 58 [0434]
• The translation product of this gene shares weak sequence homology with Hemophilus influenzae outmembrane protein P6 which is thought to be important in host cell interaction. [0435]
• This gene is expressed primarily in human adrenal gland tumor. [0436]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, adrenal insufficiency or hyperfunction, adrenal gland tumors. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine systems and cancers thereof, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., adrenal gland, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0437]
• The tissue distribution in adrenal gland tumor and homology to Haemophilus influenzae outer membrane protein suggest that polynucleotides and polypeptides corresponding to this gene are useful for adrenal insufficiencies or hyperfunction, because a secretory protein from an endocrine organ may function as a hormone. The protein product of this gene is also useful as a diagnostic and/or treatment for adrenal gland tumors, as well as tumors of other tissues where expression has been observed. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0438]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:68 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 894 of SEQ ID NO:68, b is an integer of 15 to 908, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:68, and where b is greater than or equal to a+14. [0439]
• Features of Protein Encoded by Gene No: 59 [0440]
• When tested against a Jurkat T-cell line, supernatants-removed from cells containing this gene activated the GAS (gamma activation site) pathway. Thus, it is likely that this gene activates T-cells through the Jaks-STAT signal transduction pathway. The GAS is a promoter element found upstream in many genes which are involved in the Jaks-STAT pathway. The Jaks-STAT pathway is a complex, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jaks-STATs pathway, reflected by the binding of the GAS element, can be used to indicate proteins involved in the proliferation and differentiation of cells. [0441]
• This gene is expressed primarily in human kidney pyramid, and to a lesser extent in human brain. [0442]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, nephrotic, nephritic syndromes, renal failure, hypertensive nephrosclerosis. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the renal system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., renal, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0443]
• The tissue distribution in kidney indicates that polynucleotides and polypeptides corresponding to this gene are useful for renal diseases, including renal failure, nephritus, renal tubular acidosis, proteinuria, pyuria, edema, pyelonephritis, hydronephritis, nephrotic syndrome, crush syndrome, glomerulonephritis, hematuria, renal colic and kidney stones, in addition to Wilm's Tumor Disease, and congenital kidney abnormalities such as horseshoe kidney, polycystic kidney, and Falconi's syndrome. Additionally, the gene product may have endocrine functions related to renal function, metabolism and homeostasis. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0444]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:69 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 682 of SEQ ID NO:69, b is an integer of 15 to 696, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:69, and where b is greater than or equal to a+14. [0445]
• Features of Protein Encoded by Gene No: 60 [0446]
• This gene is expressed primarily in both normal or cancerous human breast tissue. [0447]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, Non-neoplastic breast diseases or breast cancers. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the breast, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., mammary tissue, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0448]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 209 as residues: Pro-20 to Ser-28. [0449]
• The tissue distribution in breast indicates that polynucleotides and polypeptides corresponding to this gene are useful for either non-neoplastic breast diseases, such as congentital anomalities, gynecomastia, mastitis and abscess, duct ectasia and fat necrosis, or neoplasia in the breast. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0450]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:70 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 441 of SEQ ID NO:70, b is an integer of 15 to 455, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:70, and where b is greater than or equal to a+14. [0451]
• Features of Protein Encoded by Gene No: 61 [0452]
• When tested against a K562 cell line, supernatants removed from cells containing this gene activated the ISRE (interferon-sensitive responsive element) pathway. Thus, it is likely that this gene activates leukemia cells, or more generally, immunr or hematopoietic cells, or other cells or cell-types, through the Jaks-STAT Signal transduction pathway. The ISRE is a promoter element found upstream in many genes which are involved in the Jaks-STAT pathway. The Jaks-STAT pathway is a complex, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jaks-STATs pathway, reflected by the binding of the ISRE element, can be used to indicate proteins involved in the proliferation and differentiation of cells. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: IRHERLWAELALLTGRNE (SEQ ID NO: 497). Polynucleotides encoding these polypeptides are also encompassed by the invention. The gene encoding the disclosed cDNA is thought to reside on chromosome 3. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 3. [0453]
• This gene is expressed primarily in activated T-cells and osteoarthritis, and to a lesser extent in aortic endothelium and placenta. [0454]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, inflammatory conditions, vascular disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system and vascular tissues, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types and cell types (e.g., T-cells and other cells and tissue of the immune system, bone tissue, endothelium and placenta, vascular tissue, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0455]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 210 as residues: Gln-36 to Glu-49, Glu-51 to Leu-66, Asp-68 to Ser-73. [0456]
• The tissue distribution in activated T-cells and under inflammatory conditions like osteoarthritis suggest that the protein product of this gene is involved in the inflammatory reactions. Therefore it may be useful in the diagnosis or intervention in the inflammatory diseases with the involvement of T-cells, including osteoarthritis. Furthermore, the tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and/or treatment of disorders of the placenta. Specific expression within the placenta indicates that this gene product may play a role in the proper establishment and maintenance of placental function. [0457]
• Alternately, this gene product may be produced by the placenta and then transported to the embryo, where it may play a crucial role in the development and/or survival of the developing embryo or fetus. Expression of this gene product in a vascular-rich tissue such as the placenta also indicates that this gene product may be produced more generally in endothelial cells or within the circulation. In such instances, it may play more generalized roles in vascular function, such as in angiogenesis. It may also be produced in the vasculature and have effects on other cells within the circulation, such as hematopoietic cells. It may serve to promote the proliferation, survival, activation, and/or differentiation of hematopoietic cells, as well as other cells throughout the body. [0458]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:71 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 399 of SEQ ID NO:71, b is an integer of 15 to 413, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:71, and where b is greater than or equal to a+14. [0459]
• Features of Protein Encoded by Gene No: 62 [0460]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0461]

  GTESPMVMCCREVSQSENCLFLDTTFRFIFGKTFTNHDYISIHFYFLKAFLFSFFYSNV (SEQ ID NO:498).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0462]
• This gene is expressed primarily in breast lymph nodes, B-cell lymphoma, and to a lesser extent in neutrophils and bone marrow cells. [0463]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, inflammation, immunodeficiency, allergy. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may-be routinely detected in certain tissues or cell types and cell types (e.g., blood cells, hematopoietic cells, and cells and tissue of the immune system, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0464]
• The tissue distribution in the cells of immunological functions indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis or intervention of immunologically mediated disorders, such as allergy, immunodeficiency, immune surveillance, etc. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0465]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:72 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 835 of SEQ ID NO:72, b is an integer of 15 to 849, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:72, and where b is greater than or equal to a+14. [0466]
• Features of Protein Encoded by Gene No: 63 [0467]
• The translation product of this gene shares weak sequence homology with Interferon induced 1-8 gene encoded polypeptide, which is thought to be important in retroviral REV responsive element binding and thus viral replication. [0468]
• This gene is expressed primarily in B-cell lymphoma. [0469]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune response to viral infections and other immunologically related disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types and cell types (e.g., T-cells and other cells and tissue of the immune system, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0470]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 212 as residues: Pro-47 to Asn-53. [0471]
• The tissue distribution in B-cell lymphoma and homology to interferon induced 1-8 gene indicates that polynucleotides and polypeptides corresponding to this gene are useful for the intervention of viral infection and other immunologically related disorders. The homology with interferon induced 1-8 REV response element binding gene indicates the gene product may bind to viral components to interfere with the entry, packaging, replication, or induce the host cell anti-viral response by intereferon mediated pathways. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0472]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:73 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between I to 491 of SEQ ID NO:73, b is an integer of 15 to 505, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:73, and where b is greater than or equal to a+14. [0473]
• Features of Protein Encoded by Gene No: 64 [0474]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: IRHEEKGGKAQRWAE (SEQ ID NO: 499). Polynucleotides encoding these polypeptides are also encompassed by the invention. [0475]
• This gene is expressed primarily in bone marrow. [0476]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, hemapoiesis disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hemapoietic system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., bone marrow, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0477]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 23 as residues: Thr-45 to Tyr-50. [0478]
• The tissue distribution in bone marrow indicates that polynucleotides and polypeptides corresponding to this gene are useful for hemapoiesis disorders. The gene product may function as a growth factor or mobilization agent for the cells of myeloid or lymphoid lineages. Furthermore, the polypeptides or polynucleotides are also useful to enhance or protect proliferation, differentiation, and functional activation of hematopoietic progenitor cells (e.g., bone marrow cells), useful in treating cancer patients undergoing chemotherapy or patients undergoing bone marrow transplantation. Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker and/or immunotherapy target for the above listed tissues. [0479]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:74 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 705 of SEQ ID NO:74, b is an integer of 15 to 719, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:74, and where b is greater than or equal to a+14. [0480]
• Features of Protein Encoded by Gene No: 65 [0481]
• The translation product of this gene shares sequence homology familial adenomatous polyposis gene which is thought to be important in the tumorigenesis of colon cancer (see, e.g., Fulton, Nature 368, 32-38 (1994); accession no. U28412; Joslyn et al., Cell 66 (3), 601-613 (1991); accession no. M73547; and Spirio et al., Nucleic Acids Res. 19 (22), 6348 (1991)). In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0482]

  CRWRPESAAPC	(SEQ ID NO:500),
  TRPGRGAQAPVK	(SEQ ID NO:501),
  MVSWMISRAVVLVFGMLYPAY	(SEQ ID NO:502),
  GMLYPAYYSYKAVKTKN	(SEQ ID NO:503),
  EYVRWMMYWIVFALYTV	(SEQ ID NO:504),
  YPAYYSYKAVKTKNVKE	(SEQ ID NO:505),
  VAWFPLYYELKIA	(SEQ ID NO:506), and/or
  MVSWMISRAVVLVFGMLYPAYYSYK	(SEQ ID NO:507).
  AVKTKNVKEYVRWMMYWIVFALYTVIETVADQTVAWFPLYYELKIAFVIWLLS
  PYTKGASLIYRKFLHPLLSSKEREIDDYIVQAKERGYETMVNFGRQGLNLAATA
  AVTAAVKSQGAITERLRSFSMHDLTTIQGDEPVGQRPYQPLPEAKKKSXQPPVN
  QXVMEFHXKTXMXKQXKKQRGHIQLMRC

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0483]
• This gene is expressed primarily in osteoclastoma, prostate, bone marrow and to a lesser extent in testes and dendritic cells. Northern data has demonstrated that an abundant 1.3 kb band is seen in testes tissues. [0484]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, colon cancer and cancers of various origin, including osteoclastoma and prostate cancer, as well as reproductive disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the tumorigenesis and reproductive disorders, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types and cell types (e.g., bone, prostate, reproductive, bone marrow, colon and other gastrointestinal tissue, tissue of the nervous system, and testis and other reproductive tissue, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0485]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 214 as residues: Ser-59 to Ile-64, Ala-71 to Tyr-76, Pro-125 to Ser-141. [0486]
• The tissue distribution in osteoclastoma, prostate, bone marrow and homology to familial adenomatous polyposis gene indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of tumors of various origins, including colon cancer, osteoclastoma and prostate cancer. Alternatively, the Northern data demonstrating expression in testes tissues indicates that the translation product of this gene is useful for the diagnosis and/or treatment of reproductive disorders and conditions concerning proper testicular function (e.g., endocrine function, sperm maturation), as well as cancer. Therefore, this gene product is useful in the treatment of male infertility and/or impotence. [0487]
• This gene product is also useful in assays designed to identify binding agents, as such agents (antagonists) are useful as male contraceptive agents. Similarly, the protein is believed to be useful in the treatment and/or diagnosis of testicular cancer. The testes are also a site of active gene expression of transcripts that may be expressed, particularly at low levels, in other tissues of the body. Therefore, this gene product may be expressed in other specific tissues or organs where it may play related functional roles in other processes, such as hematopoiesis, inflammation, bone formation, and kidney function, to name a few possible target indications. [0488]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:75 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1260 of SEQ ID NO:75, b is an integer of 15 to 1274, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:75, and where the b is greater than or equal to a+14. [0489]
• Features of Protein Encoded by Gene No: 66 [0490]
• The translation product of this gene shares regional and weak sequence homology with neu differentiation factor and a serine protease N-terminal fragment which contains a EGF-like domain and is thought to be important in the growth and differentiation of several cell types, including colon epithelial cells and Schwann cells. [0491]
• This gene is expressed primarily in fetal lung, bone marrow, fetal liver, and to a lesser extent in brain. [0492]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, tissue injuries or diseases in lung, bone marrow, or liver. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the liver and lung, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types and cell types (e.g., lung and pulmonary tissue, bone marrow, hepatic tissue, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0493]
• The tissue distribution in fetal liver, combined with the homology to neu differentiation factor indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis or intervention of liver or lung injuries, including hepatic failure, recovery from hepatitis, cirrhosis, hepatoblastoma, jaundice, liver metabolic diseases and conditions that are attributable to the differentiation of hepatocyte progenitor cells, and complications from liver transplantation. [0494]
• Moreover, the protein product of this clone is useful for the treatment and diagnosis of hematopoietic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages The uses include bone marrow cell ex-vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0495]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:76 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 505 of SEQ ID NO:76, b is an integer of 15 to 519, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:76, and where b is greater than or equal to a+14. [0496]
• Features of Protein Encoded by Gene No: 67 [0497]
• This gene is expressed primarily in activated T-cells. [0498]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, arthritis, asthma, auto-immune and immunodeficiency diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types and cell types (e.g., T-cells and other cells and tissue of the immune system, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0499]
• The expression of this gene in T-cells indicates a potential role in the treament/detection of immune disorders such as arthritis, asthma, hypersensitivity reactions and transplant rejection, and also in immune deficiency diseases such as AIDS, and leukemia. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0500]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:77 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 375 of SEQ ID NO:77, b is an integer of 15 to 389, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:77, and where b is greater than or equal to a+14. [0501]
• Features of Protein Encoded by Gene No: 68 [0502]
• The gene encoding the disclosed cDNA is thought to reside on chromosome 7. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 7. [0503]
• This gene is expressed primarily in brain, and to a lesser extent in breast. [0504]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neurodegenerative conditions and behavioural disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., brain and other tissue of the nervous system, mammary tissue, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0505]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 217 as residues: Leu-40 to His-46. [0506]
• The tissue distribution in brain indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, or sexually-linked disorders. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0507]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:78 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 809 of SEQ ID NO:78, b is an integer of 15 to 823, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:78, and where b is greater than or equal to a+14. [0508]
• Features of Protein Encoded by Gene No: 69 [0509]
• The translation product of this gene shares sequence homology with a rat secretory carrier membrane protein which is believed to play a role in cell surface re-cycling. See e.g., Brand et al., EMBO J 1993 October;12(10):3753-3761. Secretory carrier membrane proteins (SCAMPs) are widely distributed as components of post-Golgi membranes that function as recycling carriers to the cell surface. In fibroblasts, SCAMPs are concentrated in compartments involved in the endocytosis and recycling of cell surface receptors while in neurons and other cell types having regulated transport pathways, SCAMPs are also components of regulated carriers (synaptic vesicles, secretion granules and transporter vesicles). Their presence in multiple pathways distinguishes them from proteins (e.g., recycling cell surface receptors and synaptic vesicle proteins) which are concentrated in selected pathways. The SCAMPs also do not appear to reside beyond the boundaries of these pathways. This distribution indicates that SCAMPs are general markers of membranes that function in cell surface recycling. Accordingly, polpeptides of the invention and antibodies thereto, may be used to identify membranes that function in cell surface recycling. The gene encoding the disclosed cDNA is thought to reside on chromosome 15. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 15. [0510]
• This gene is expressed primarily in hematopoietic cell types. [0511]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune and hematopoetic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and hematopoetic systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types and cell types (e.g., hematopoietic cells, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0512]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 218 as residues: Ser-25 to Gly-31, Gln-149 to Ser-155. [0513]
• The hematopoetic tissue distribution and homology to a cell surface molecule indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and/or treatment of immune or hematopoietic disorders including arthritis, asthma and immunodeficiency diseases. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0514]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:79 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2441 of SEQ ID NO:79, b is an integer of 15 -to 2455, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:79, and where b is greater than or equal to a+14. [0515]
• Features of Protein Encoded by Gene No: 70 [0516]
• The gene encoding the disclosed cDNA is thought to reside on chromosome 4. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 4. When tested against a Jurkat T-cell line, supernatants removed from cells containing this gene activated the GAS (gamma activation site) pathway. Thus, it is likely that this gene activates T-cells through the Jaks-STAT signal transduction pathway. The GAS is a promoter element found upstream in many genes which are involved in the Jaks-STAT pathway. The Jaks-STAT pathway is a complex, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jaks-STATs pathway, reflected by the binding of the GAS element, can be used to indicate proteins involved in the proliferation and differentiation of cells. [0517]
• This gene is expressed primarily in brain. [0518]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neurodegenerative conditions and behavioural disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the brain and central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., brain and other tissues of the nervous system, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0519]
• Preferred epitopes include those comprising a sequence shown in-SEQ ID NO. 219 as residues: Asp-57 to Gly-64. [0520]
• The tissue distribution of this gene primarily in brain indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and/or detection of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, or sexually-linked disorders. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0521]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:80 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 907 of SEQ ID NO:80, b is an integer of 15 to 921, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:80, and where b is greater than or equal to a+14. [0522]
• Features of Protein Encoded by Gene No: 71 [0523]
• This gene is expressed primarily in hematopoietic progenitor cells (CD34+ cells). [0524]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, autoimmune and immunodeficiency disease states. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hematopoietic system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types and cell types (e.g., hematopoietic cells, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0525]
• The tissue distribution of this gene predominantly in hematopoietic progenitor cell types indicates that the gene could be important for the treatment or detection of immune or hematopoietic disorders including arthritis, asthma, immunodeficiency diseases, leukemia, hypersensitivity and transplant rejection. Additionally, expression of this gene product in CD34+ cells indicates a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g., by boosting immune responses). [0526]
• Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0527]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:81 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 664 of SEQ ID NO:81, b is an integer of 15 to 678, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:81, and where b is greater than or equal to a+14. [0528]
• Features of Protein Encoded by Gene No: 72 [0529]
• This gene is expressed primarily in hematopoietic progenitor cells (CD34+ cells). [0530]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, auto-immune and immunodeficiency disease states. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hematopoietic system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types and cell types (e.g., hematopoietic cells, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0531]
• The tissue distribution of this gene predominantly in hematopoietic progenitor cell types indicates that the gene is important for the treatment or detection of immune or hematopoietic disorders including arthritis, asthma, immunodeficiency diseases, leukemia, and transplant rejection. Expression of this gene product in CD34+ cells indicates a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). [0532]
• Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0533]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 82 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 843 of SEQ ID NO:82, b is an integer of 15 to 857, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:82, and where b is greater than or equal to a+14. [0534]
• Features of Protein Encoded by Gene No: 73 [0535]
• The translation product of this gene shares sequence homology with rat synaptogyrin which is thought to be important in membrane trafficking (see e.g., Stenius et al., J. Cell Biol. 131 (6 Pt 2), 1801-1809 (1995)). In specific embdodiments, polypeptides of the invention comprise the following amino acid sequences: [0536]

  QPYQVLPSRQVFALI	(SEQ ID NO:508),
  VFSCIYGEGYSNAHESKQMYCVFN	(SEQ ID NO:509),
  RNEDACRYGSAIGVLAFL	(SEQ ID NO:510),
  LVVDAYFPQISNATDRK	(SEQ ID NO:511), and/or
  SALWTFLWFVGFCFLTNQWAVTNPK	(SEQ ID NO:512).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0537]
• This gene is expressed primarily in breast and ovary, and to a lesser extent in most hematopoietic tissue types. [0538]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, female infertility and female reproductive abnormalities. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., mammary tissue, and ovary and other reproductive tissue, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0539]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 222 as residues: Pro-9 to Trp-18, Thr-20 to Ala-27. [0540]
• The tissue distribution in ovary and breast and homology to a protein involved in membrane trafficking indicates that this protein may play a role in the detection/treatment of female fertility disorders, endocrine disorders, ovarian failure, amenorrhea, ovarian cancer, and also potentially in both non-neoplastic breast diseases such as congenital abnormalities and neoplasia in the breast. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0541]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:83 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1963 of SEQ ID NO:83, b is an integer of 15 to 1977, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:83, and where b is greater than or equal to a+14. [0542]
• Features of Protein Encoded by Gene No: 74 [0543]
• The gene encoding the disclosed cDNA is thought to reside on chromosome 12. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 12. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0544]

  	LNIDSFDYGKFESLLAKQHYKFSFLLPLAAGTERCKWWLKIEEASSDQCGCWFLVKCVPKPPSPCRQPPTQVSKIGHAPFFL (SEQ ID NO:513).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0545]
• This gene is expressed primarily in brain, and to a lesser extent in placenta and spleen. [0546]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, behavioural disorders and neurodegenerative disease states. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly. of the brain and central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., brain and other tissue of the nervous system, spleen and other cells and tissue of the immune system, placenta, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0547]
• The tissue distribution in brain indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, or sexually-linked disorders. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0548]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 84 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1135 of SEQ ID NO:84, b is an integer of 15 to 1149, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:84, and where b is greater than or equal to a+14. [0549]
• Features of Protein Encoded by Gene No: 75 [0550]
• When tested against a K562 cell line, supernatants removed from cells containing this gene activated the ISRE (interferon-sensitive responsive element) pathway. Thus, it is likely that this gene activates leukemia cells, or more generally, in immune or hematopoietic cells, or other cells or cell-types, through the Jaks-STAT signal transduction pathway. The ISRE is a promoter element found upstream in many genes which are involved in the Jaks-STAT pathway. The Jaks-STAT pathway is a complex, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jaks-STATs pathway, reflected by the binding of the GAS element, can be used to indicate proteins involved in the proliferation and differentiation of cells. [0551]
• This gene is expressed primarily in bone marrow and spleen. [0552]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, autoimmune diseases, transplant rejection and immundeficiency disease states. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hematopoietic and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0553]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 224 as residues: Pro-22 to His-33, Ser-42 to Trp-48. [0554]
• The tissue distribution of this gene predominantly in hematopoietic cell types indicates that the gene is important for the treatment or detection of immune or hematopoietic disorders including arthritis, asthma, immunodeficiency diseases, leukemia, and transplant rejection. Furthermore, the polypeptides or polynucleotides are also useful to enhance or protect the proliferation, differentiation, and functional activation of hematopoietic progenitor cells (e.g., bone marrow cells), useful in treating cancer patients undergoing chemotherapy or patients undergoing bone marrow transplantation. The polypeptides or polynucleotides are also useful to increase the proliferation of peripheral blood leukocytes, which can be used in the combat of a range of hematopoietic disorders, including immunodeficiency diseases, leukemia, and septicemia. [0555]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 85 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence. would be cumbersome. [0556]
• Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 753 of SEQ ID NO:85, b is an integer of 15 to 767, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:85, and where b is greater than or equal to a+14. [0557]
• Features of Protein Encoded by Gene No: 76 [0558]
• In specific embodiments, polypeptides of the invention comprise the sequence: [0559]

  SLQYRIRIPGRPT	(SEQ ID NO:514),
  DLVTYTSSLQYRIRIPGRPTRP	(SEQ ID NO:515),
  VKTAECYSIPLGSCPVNIQRVR	(SEQ ID NO:517), and/or
  LGNKKYINIRCLEMQVTLKILCEIEKKERRGTHCLV	(SEQ ID NO:516).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. Contact of cells with supernatant expressing the product of this gene increases the permeability of U937 monocyte cells to calcium. Thus, it is likely that the product of this gene is involved in a signal transduction pathway that is initiated when the product of this gene binds a receptor on the surface of the monocyte cell. Thus, polynucleotides and polypeptides have uses which include, but are not limited to, activating monocyte cells. [0560]
• This gene is expressed in primary dendritic cells. [0561]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, auto-immune disorders such as asthma and arthritis, in transplant rejection, leukemia and immunodeficiency disease states. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types and cell types (e.g., primary dendritic cells and other cells and tissue of the immune system, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0562]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 225 as residues: Gly-2 to Glu-7, Arg-27 to Gly-34. [0563]
• The tissue distribution of this gene predominantly in hematopoietic cell types indicates that the gene is important for the treatment or detection of immune or hematopoietic disorders including arthritis, asthma, immunodeficiency diseases, leukemia, hypersensitivity and graft rejection. Expression of this gene product in primary dendritic cells also strongly indicates a role for this protein in immune function and immune surveillance. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0564]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:86 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 714 of SEQ ID NO:86, b is an integer of 15 to 728, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:86, and where b is greater than or equal to a+14. [0565]
• Features of Protein Encoded by Gene No: 77 [0566]
• This gene is expressed primarily in 12 week old early stage human. [0567]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, developmental abnormalities. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the developmental system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., developing and differentiating tissue, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0568]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 226 as residues: Thr-14 to Thr-19. [0569]
• The expression of this gene primarily in the embryo indicates a key role in embryonic development, and could be used in the treatment and or detection of developmental disorders. Expression within embryonic tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility it the diagnosis and treatment of cancer and other proliferative disorders. Similarly, embryonic development also involves decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0570]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:87 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 721 of SEQ ID NO:87, b is an integer of 15 to 735, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:87, and where b is greater than or equal to a+14. [0571]
• Features of Protein Encoded by Gene No: 78 [0572]
• This gene is expressed primarily in T-cells, and to a lesser extent in cord blood and osteosarcoma. [0573]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, auto-immune diseases, immunodeficiency diseases and host-graft rejection. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., cells and tissues of the immune system, bone, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0574]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 227 as residues: Pro-36 to Ala-41. [0575]
• The expression of this gene in T-cells indicates a potential role in the treament/detection of immune disorders such as arthritis, asthma, immune deficiency diseases such as AIDS, leukemia and transplant rejection. Expression of this gene product in T cells also strongly indicates a role for this protein in immune function and immune surveillance. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0576]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:88 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 875 of SEQ ID NO:88, b is an integer of 15 to 889, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:88, and where b is greater than or equal to a+14. [0577]
• Features of Protein Encoded by Gene No: 79 [0578]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0579]

  LFYLLTCSCAPGHLAFVCSQCLPFDMGKELWPKSPSSCTSTSVAQGWGGRGRPSPYICVV	(SEQ ID NO:518),
  IQGSRLPPLPAPLHPLPLIYLLLGSPAQSWLLVPSWGHPSTLTLTMAAEHQAWPSGFHGDH	(SEQ ID NO:519).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0580]
• This gene is expressed primarily in placenta and 9 week old embryo, and to a lesser extent in fetal spleen. [0581]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, developmental disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the developmental system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., developing and differentiating tissues, and spleen and other cells and tissue of the immune system, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0582]
• The expression of this gene primarily in the embryo indicates a key role in embryonic development, and could be used in the treatment and or detection of developmental disorders. The tissue distribution in placenta also indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and/or treatment of disorders of the placenta. Specific expression within the placenta indicates that this gene product may play a role in the proper establishment and maintenance of placental function. Alternately, this gene product may be produced by the placenta and then transported to the embryo, where it may play a crucial role in the development and/or survival of the developing embryo or fetus. Expression within embryonic tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division. Similarly, embryonic development also involves decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0583]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 89 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 555 of SEQ ID NO:89, b is an integer of 15 to 569, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:89, and where b is greater than or equal to a+14. [0584]
• Features of Protein Encoded by Gene No: 80 [0585]
• This gene is expressed primarily in early stage brain. [0586]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, developmental and neurodegenerative diseases of the brain and nervous system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the brain, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., brain and other tissue of the nervous system, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0587]
• The tissue distribution in brain indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and detection of developmental and neurodegenerative diseases, as well as behavioral or nervous system disorders. [0588]
• Examples of such conditions would include: depression, schizophrenia, mania, dementia, paranoia, addictive behavior and sleep disorders. In addition a brain-specific gene product may be useful in the diagnosis of specific brain tumors. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0589]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:90 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 320 of SEQ ID NO:90, b is an integer of 15 to 334, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:90, and where b is greater than or equal to a+14. [0590]
• Features of Protein Encoded by Gene No: 81 [0591]
• This gene is expressed primarily in synovial tissue. [0592]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, arthritis, tendonitis and chrondomalacia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the synovium, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., synovial tissue, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0593]
• The tissue distribution in synovial tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of connective tissue disorders such as arthritis, tendonitis, chrondomalacia, inflammation and trauma. In addition, the expression of this gene product in synovium indicates a role in the detection and treatment of disorders and conditions affecting the skeletal system, in particular osteoporosis as well as disorders afflicting connective tissues (e.g. arthritis, trauma, tendonitis, chrondomalacia and inflammation), such as in the diagnosis or treatment of various autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (ie. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0594]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:91 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 781 of SEQ ID NO:91, b is an integer of 15 to 795, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:91, and where b is greater than or equal to a+14. [0595]
• Features of Protein Encoded by Gene No: 82 [0596]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: VDPPGCRNSARGCTRLLRGSSKI (SEQ ID NO: 520). Polynucleotides encoding these polypeptides are also encompassed by the invention. [0597]
• This gene is expressed primarily in the frontal cortex of the brain. [0598]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, developmental and neurodegenerative diseases of the brain. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., brain and other tissue of the nervous system, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0599]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 231 as residues: Ser-4 to Tyr-13. [0600]
• The tissue distribution in brain indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of developmental and neurodegenerative diseases of the brain and nervous system, including malignancies as well as behavioral disorders. Examples of such conditions might include: depression, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's disease, mania, dementia, paranoia, addictive behavior and sleep disorders. Furthermore, elevated expression of this gene product within the frontal cortex of the brain indicates that it may be involved in neuronal survival; synapse formation; conductance; neural differentiation, etc. Such involvement may impact many processes, such as learning and cognition. It may also be useful in the treatment of such neurodegenerative disorders as schizophrenia; ALS; or Alzheimer's. [0601]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:92 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one-or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 563 of SEQ ID NO:92, b is an integer of 15 to 577, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:92, and where b is greater than or equal to a+14. [0602]
• Features of Protein Encoded by Gene No: 83 [0603]
• The translation product of this gene shares sequence homology with the L6 cell surface antigen, which is highly expressed in lung, breast, colon, and ovarian carcinomas. See e.g., Marken et al., Proc Natl Acad Sci U S A 1992 April 15;89(8):3503-3507. In specific embodiments, polypeptides of the invention comprise the sequence: ITLCLVCIVANA (SEQ ID NO: 521). Polynucleotides encoding these polypeptides are also encompassed by the invention. This gene was recently cloned and sequenced by another group, which identified the gene as a putative tetraspan transmembrane (TM4) protein L6H from humans. The transmembrane 4 superfamily (TM4SF) or tetraspan superfamily has at least 16 members (including CD9, CD20, CD37, CD53, CD63, CD81, CD82, A15, CO-029, Sm23, RDS, Uro B, Uro A, SAS, Rom-1, PETA3, and YKK8), is the second biggest subfamily among CD antigen superfamilies, and are activation antigens of T-cells. All TM4SF members contain four putative transmembrane domains, two extracellular loops, and two short cytoplasmic tails. They are variously expressed on immature, early, mature, activated lymphocytes, monocytes, macrophages, granulocytes, platelets, eosinophils, basophils, certain leukemic and lymphoma cells, and a variety of other cells and tissues. [0604]
• This gene is expressed primarily in fetal liver/spleen tissues. [0605]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, cancers of the liver, immune system disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hepatic and immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., lung and pulmonary tissue, colon and other gastrointestinal tissue, mammary tissue, ovarian tissue and other tissue of the reproductive system, hepatic tissue, immune system tissues, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0606]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 232 as residues: Asn-32 to Asn-41, Thr-140 to Ala-147, Asp-188 to His-197. [0607]
• The murine monoclonal antibody (mAb) L6 recognizes an integral membrane glycoprotein that is highly expressed in lung, breast, colon, and ovarian carcinomas and is referred to as the L6 antigen. This antigen is an attractive target for therapeutic intervention due to its high level expression on malignant cells. The tissue distribution and homology to L6 antigen indicates that polynucleotides and polypeptides corresponding to this gene are useful for detection and treatment of neoplastic tissues particularly of the liver. The translation product of this gene is a member of the tetraspan transmembrane superfamily, and therefore, antigenic regions of members of this family could be valuable immunogens or targets to implement active and passive immunotherapy in patients with cancer. Moreover, the protein product of this clone is useful for the treatment and diagnosis of hematopoietic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex-vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0608]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:93 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 954 of SEQ ID NO:93, b is an integer of 15 to 968, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:93, and where b is greater than or equal to a+14. [0609]
• Features of Protein Encoded by Gene No: 84 [0610]
• This gene is expressed primarily in glioblastoma. [0611]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, glioblastoma. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., tissue of the nervous system, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0612]
• The tissue distribution in glioblastoma indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of malignancies, as well as developmental and neurodegenerative diseases of the brain and nervous system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0613]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:94 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 539 of SEQ ID NO:94, b is an integer of 15 to 553, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:94, and where b is greater than or equal to a+14. [0614]
• Features of Protein Encoded by Gene No: 85 [0615]
• The translation product of this gene shares sequence homology with Tbx, which is thought to be important in developmental regulation (see e.g., Knezevic et al., Development 124, 411-419 (1997); and accession U80951). In specific embodiments, polypeptides of the invention comprise the sequence: [0616]

  VTAYQNQQITRLKIDRNPFAKGFR	(SEQ ID NO:522),
  GTATVTAYQNQQITRL	(SEQ ID NO:523),
  KIDRNPFAKGFRDSGRNRMGLEAL	(SEQ ID NO:524),
  STLLQVLGMAFLPLTLTFCLA	(SEQ ID NO:525), and/or
  VESYAFWRPSLRTLTFEDIPGIPKQGNASS	(SEQ ID NO:526).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0617]
• This gene is expressed primarily in synovial sarcoma and to a lesser extent in osteoclastoma, osteoblastoma, and hemangiopericytoma. [0618]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, osteosarcoma, osteoclastoma, and chondrosarcoma, and diseases of the skeletal system, such as osteoporosis. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the skeletal system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types and cell types (e.g., bone cells and tissue, synovial cells and tissue, cartilage, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0619]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 234 as residues: Ala-45 to Asp-50, Arg-57 to Pro-63. [0620]
• The tissue distribution in skeletal tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of osteoperosis, fracture, osteosarcoma, osteoclastoma, chondrosarcoma, ossification and osteonecrosis, arthritis, tendonitis, chrondomalacia, and inflammation. Elevated levels of expression of this gene product in osteoclastoma and osteoblastoma indicates that it may play a role in the survival, proliferation, and/or growth of these cells. Therefore, it may be useful in influencing bone mass in such conditions as osteoporosis. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0621]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:95 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 954 of SEQ ID NO:95, b is an integer of 15 to 968, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:95, and where b is greater than or equal to a+14. [0622]
• Features of Protein Encoded by Gene No: 86 [0623]
• The gene encoding the disclosed cDNA is thought to reside on chromosome 19. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 19. The translation product of this gene is a transmembrane protein that forms disulfide-bonded homodimers and contains a motif in its cytoplasmic domain (located at the carboxy terminus of the protein relative to the transmembrane domain) that functions as an adaptor for associating protein complexes involved in triggering cellular activation. The transmembrane domain is predicted to consist of the amino acid sequence: VLAGIVMGDLVLTVLIALAVYFLG.(SEQ ID NO: 528). In specific embodiments, polypeptides of the invention comprise the following amino acid sequences: [0624]

  QAQSDCSCSTVSPG	(SEQ ID NO:527),
  VLAGIVMGDLVLTVLIALAVYFLG	(SEQ ID NO:528),
  VPRGRGAAEATRKQRITETESPYQELQGQRSDVYSDL	(SEQ ID NO:529), and/or
  ETESPYQELQGQRSDVYSDLNT	(SEQ ID NO:530).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0625]
• This gene is expressed primarily in macrophage, and to a lesser extent in primary dendritic cells and neutrophils. [0626]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immunologically mediated disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types and cell types (e.g., blood cells, and cells and tissue of the immune system, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0627]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 235 as residues: Ala-28 to Ser-33, Ala-76 to Lys-111. [0628]
• The tissue distribution in immune tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, and/or prevention of immune disorders including: leukemias, lymphomas, auto-immunities, immunodeficiencies (e.g., AIDS), immuno-supressive conditions (transplantation) and hematopoietic disorders. Furthermore, expression of this gene product in macrophage and primary dendritic cells also strongly indicates a role for this protein in immune function and immune surveillance. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0629]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:96 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 683 of SEQ ID NO:96, b is an integer of 15 to 697, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:96, and where b is greater than or equal to a+14. [0630]
• Features of Protein Encoded by Gene No: 87 [0631]
• This gene is expressed primarily in prostate cancer. [0632]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, prostate cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the prostate, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., prostate, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0633]
• The tissue distribution in prostate cancerous tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of prostate cancer and other prostate disorders, as well as cancers in other tissues where expression has been indicated. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0634]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:97 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 852 of SEQ ID NO:97, b is an integer of 15 to 866, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:97, and where b is greater than or equal to a+14. [0635]
• Features of Protein Encoded by Gene No: 88 [0636]
• The translation product of this gene shares sequence homology with retinal epithelial membrane protein (REMP), which is thought to be important in development and maintenance of normal retinal function (See e.g., Philp et al., Exp. Cell Res. 219 (1), 64-73 (1995); and Genbank Accesion No.U15685). The translation product of this gene also shares homology with monocarboxylate transporter protein (Genbank Accesion no.U87627). Another group recently cloned and sequenced this gene, describing it as a monocarboxylate transporter protein (Genbank Accession No. gi|2463634). In quantitative terms, lactic acid is one of the most important metabolites in the body, substantial amounts being used and/or produced by almost all mammalian cells. As such it must be rapidly transported into and out of cells. Lactic acid transport across the plasma membrane is catalysed by proton-linked monocarboxylate transporters (MCTs), which are also responsible for the transport of pyruvate and the ketone bodies acetoacetate, -hydroxybutyrate and acetate. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0637]

  FLCALSPLGQLLQDRYGWRGGFLILGGL,	(SEQ ID NO:531)
  LLNCCVCAALMRPLVVTAQPGXGPPRP,	(SEQ ID NO:532)
  and/or
  SRRLXDLSVFRDRGFVLYAVAASVM	(SEQ ID NO:533).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. The gene encoding the disclosed cDNA is thought to reside on chromosome 17. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 17. [0638]
• This gene is expressed primarily in neutrophils, and to a lesser extent in a variety of other tissues and cell types, including retina. [0639]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, eye, and metabolic and cellular transport disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly. of the eye and immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types and cell types (e.g., retinal cells, neutrophils and other blood cells, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0640]
• The tissue distribution in retinal tissue and the homology to REMP indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, and/or prevention of eye disorders, including neoplasms, visual impairments and blindness. Alternatively, the homology to monocarboxylate transporter protein indicates that the translation product of this gene is useful for the diagnosis and/or treatment of disorders involving the cellular transport of lactic acid into and out of the cell. [0641]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:98 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1354 of SEQ ID NO:98, b is an integer of 15 to 1368, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:98, and where b is greater than or equal to a+14. [0642]
• Features of Protein Encoded by Gene No: 89 [0643]
• The translation product of this gene shares sequence homology with human squamous cell E48 antigen which is thought to be important in self-recognition and immune function. In specific embodiments, polypeptides of the invention comprise the following amino acid sequences: [0644]

  MMATPSTRPPPPAASTTSATAPALPPRPPWPWPPSSWPPSGVSSKAPEADPLKNKAL	(SEQ ID NO:534);
  LLLTSPLPRCPPACSHDAPAHPDPGGPHGLTSGPGLGLPRVCLQRRQLLQPHALPGYGCLLHDHAHLLHPHQDEGQ	(SEQ ID NO:535); and/or
  WLLQARVHHLLLPVRPLQRHRPCHPGHPGPGPHPPGHPLGSPLKPPRQTHSRTKLS	(SEQ ID NO:536).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. When tested against K562 leukemia cell lines, supernatants removed from cells containing this gene activated the ISRE assay. Thus, it is likely that this gene activates leukemia cells through the Jak-STAT signal transduction pathway. The interferon-sensitive response element is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jak-STAT pathway, reflected by the binding of the ISRE element, can be used to indicate proteins involved in the proliferation and differentiation of cells. [0645]
• This gene is expressed primarily in adult brain, and to a lesser extent in fetal lung. [0646]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, autoimmune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0647]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 238 as residues: Tyr-28 to Phe-34, Thr-54 to Val-60, Tyr-73 to Thr-82. [0648]
• The tissue distribution and homology to human squamous cell E48 antigen indicates that polynucleotides and polypeptides corresponding to this gene are useful for study, diagnosis and treatment of autoimmune diseases and disorders, such as lupus, transplant rejection, allergic reactions, and arthritis. Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker and/or immunotherapy target for the above listed tissues. [0649]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:99 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 599 of SEQ ID NO:99, b is an integer of 15 to 613, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:99, and where b is greater than or equal to a+14. [0650]
• Features of Protein Encoded by Gene No: 90 [0651]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0652]

  QEFQTGLGNMVKPCLYEKYRNISWLWWHTPVVPATWEAEVGGSLEPGRLRLQ	(SEQ ID NO:537), and/or
  ILGGESILIILSWVFSYIFFRIALEITIYILNVSPFCLGRWLMPVIPALWEAEVGGLPELRSSRPA	(SEQ ID NO:538).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0653]
• This gene is expressed primarily in human adult lymph node tissue. [0654]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune disorders and lymphomas. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and metabolic systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, metabolic, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0655]
• The tissue distribution in lymph nodes indicates that polynucleotides and polypeptides corresponding to this gene are useful for the study, diagnosis and treatment of immune and lymph diseases and disorders such as lymphomas. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0656]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:100 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 671 of SEQ ID NO: 100, b is an integer of 15 to 685, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:100, and where b is greater than or equal to a+14. [0657]
• Features of Protein Encoded by Gene No: 91 [0658]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0659]

  MPKQLAQLLYRLPRG,	(SEQ ID NO:539)
  LFQAISVSGSHR,	(SEQ ID NO:540)
  QGSRTWNTLTEGNAEAACTVALQTSKRLILASRW
  TLSFM,	(SEQ ID NO:541)
  NSHCVPIKALFFLSVVSYIFIMPHHIFFTVKILKSCFQVGQLMKL
  and/or
  RPTRPITFSSNISEWVPSTGFQDLEHFNRRKCRSSLHSCFTDFQEA (SEQ ID NO:542)
  DSGFKMEPWSWFFFFFFFFPQRTCGCALCVLFLFSIWGPHGKELLNSFLYELPL
  CSYKGPFLS.

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0660]
• This gene is expressed primarily in placenta and synovium. [0661]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases of the synovium and placenta. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the placenta and synovium, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., placenta, synovium, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0662]
• The tissue distribution in placenta and synovium indicates that polynucleotides and polypeptides corresponding to this gene are useful for the study, diagnosis and treatment of growth and developmental disorders and arthritic and inflammatory conditions. Expression within embryonic tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, embryonic development also involves decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Specific expression within the placenta indicates that this gene product may play a role in the proper establishment and maintenance of placental function. Alternately, this gene product may be produced by the placenta and then transported to the embryo, where it may play a crucial role in the development and/or survival of the developing embryo or fetus. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0663]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:101 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 632 of SEQ ID NO:101, b is an integer of 15 to 646, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 101, and where b is greater than or equal to a+14. [0664]
• Features of Protein Encoded by Gene No: 92 [0665]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0666]

  VDPRVRLPLFWWQPSCAVYLFPRVYNNMCTRVLGTLPHCWDLATLLQPSSRI,	(SEQ ID NO:543)
  WGNVSEAPGM
  VPYHIAGTLPHCCSLPVGYGGMSVRLQ,	(SEQ ID NO:544)
  GCRYVGNVGPQGNMQSGRSWALKMVLLCNSCLGLGVGSVGPSMSSLFGAVL
  SETPGSSVY
  MLDPRATCNLVGVGLSKWCCCVTAAWVLG	(SEQ ID NO:545).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0667]
• This gene is expressed primarily in chronic lymphocytic leukemia. [0668]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases of immune system including cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0669]
• The tissue distribution in chronic lymphocytic leukemia indicates that polynucleotides and polypeptides corresponding to this gene are useful for the study, diagnosis and treatment of disorders of the immune system including cancers. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0670]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:102 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 812 of SEQ ID NO: 102, b is an integer of 15 to 826, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:102, and where b is greater than or equal to a+14. [0671]
• Features of Protein Encoded by Gene No: 93 [0672]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0673]

  HGDWIYVHIVEQLNQANNKSVTSHTYFVVKTCKIHSLSNFQASNTLLXTVVTMLYNRSLELILPV	(SEQ ID NO:546)
  LYNRSLELILPV
  TYSSCLTKILYSLINIYPIPHCSPAXITTILL,	(SEQ ID NO:547)
  SMNLTFFFFRFHICEIAQYLSFCAWLISLNIKSL
  and/or
  MNLTFFFFRFHICEIAQYLSFCAWLISLNIKSL	(SEQ ID NO:548).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0674]
• This gene is expressed primarily in brain medulloblastoma. [0675]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of cancer and disorders of the CNS. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., brain, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0676]
• The tissue distribution in brain indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, and/or prevention of cancers and other disorders and diseases of the CNS. The tissue distribution further indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses, autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and perception. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, or sexually-linked disorders. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0677]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 103 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 572 of SEQ ID NO: 103, b is an integer of 15 to 586, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 103, and where b is greater than or equal to a+14. [0678]
• Features of Protein Encoded by Gene No: 94 [0679]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0680]

  LVCYCSTKKEKKLHEIAIQQGQNWRWLLFYKEISVPGFQSVWCSYKCLCVVW,	(SEQ ID NO:549)
  KAGEGG
  RRSCSGPPLVNTAGKILSSSPAKLACKRTDFHIP,	(SEQ ID NO:550)
  SI
  RASILGIDNERGCHFRHFNPLKEYKRKKKENKSFRIV,	(SEQ ID NO:551)
  SKNKTRGGDWCVTVLRKRRKSFMKSPFSKDRTGDGF,	(SEQ ID NO:552)
  SFTKKSLSQAFSLFGVHTSVCVLCGRRGKAGEGGPVQGPLW
  and/or
  MKSPFSKDRTGDGFSFTKKSLSQAFSLFGVHTSVCVLCGR	(SEQ ID NO:553)
  RGKAGEGGPVQGPLW.

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0681]
• This gene is expressed primarily in meningima and neutrophils and to a lesser extent in anergic T cells and CD34 depleted buffy coat. [0682]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, inflammatory, immune and hemopoietic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hemopoietic, immune and inflammatory systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0683]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 243 as residues: Glu-45 to Asn-50. [0684]
• The tissue distribution in immune tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the study, diagnosis and treatment of various disorders and diseases of the immune, inflammatory, and hemopoietic systems. Furthermore, the tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and/or treatment of hematopoietic disorders. This gene product is primarily expressed in hematopoietic cells and tissues, suggesting that it plays a role in the survival, proliferation, and/or differentiation of hematopoieitic lineages. Expression of this gene product in T cells and neutrophils also strongly indicates a role for this protein in immune function and immune surveillance. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0685]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:104 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 614 of SEQ ID NO:104, b is an integer of 15 to 628, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:104, and where b is greater than or equal to a+14. [0686]
• Features of Protein Encoded by Gene No: 95 [0687]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0688]

  MGESECYRRLSGASCTWTVHVDFA	(SEQ ID NO:554);
  MHCGTRVWKTMKHDYFLLACLSMTSTGGILCTL	9SEQ ID NO:555);
  STLSLI	(SEQ ID NO:556); and/or
  PTSSSLSFWPWCTAIIGSIFTYCVCVCVCFVVMNRTCYLPNSIIYHNSKLATIIDK
  SMTLS
  MWILPKVSLICIVELGYGKP	(SEQ ID NO:557).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0689]
• This gene is expressed primarily in human meningima. [0690]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, meningitis and other inflammatory conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the cerebrospinal membranes, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0691]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 244 as residues: Ser-35 to Phe-41. [0692]
• The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for study, treatment, and diagnosis of disorders of the meningima. The protein is also useful in the development of inhibitors of infections, particularly, though not limited to, the meninges or other neural-associated or neural tissue. In addition, the protein is useful for the treatment of injuries to the meninges, potentially in regeneration, or in congenital disorders, birth defects, etc. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0693]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:105 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 544 of SEQ ID NO: 105, b is an integer of 15 to 558, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 105, and where b is greater than or equal to a+14. [0694]
• Features of Protein Encoded by Gene No: 96 [0695]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0696]

  MSTGDGRDAEKGWPVSEEENQRSVYPGYPECDERQAVPQHCAIASPSSLQSHH,	(SEQ ID NO:558)
  PASACVPRR
  QQMTLGTKIKWGQLQRGQEIPTGDFTVRNFM,	(SEQ ID NO:559)
  RFSIIYC
  and/or
  PFLFCASRIRXQGIGIHGQVACSAVRMYNNR	(SEQ ID NO:560).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. The gene encoding the disclosed cDNA is thought to reside on chromosome 10. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 10. [0697]
• This gene is expressed primarily in neutrophils and activated monocytes. [0698]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune and hematopoietic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and hematopoietic systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0699]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 245 as residues: Met-l to Ser-6, Pro-29 to Ser-34. [0700]
• The tissue distribution in monocytes and neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the study, diagnosis and treatment of diseases of the immune and hematopoietic systems. Expression of this gene product in monocytes and neutrophils also strongly indicates a role for this protein in immune function and immune surveillance. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0701]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 106 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 742 of SEQ ID NO: 106, b is an integer of 15 to 756, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 106, and where b is greater than or equal to a+14. [0702]
• Features of Protein Encoded by Gene No: 97 [0703]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0704]

  VLCEEAGQKVPSTPSWSSWTLQKRLRGSPAEANCSPSFPAPPGKE	(SEQ ID NO:561),
  MSLSALACDFTPIQPWEWEEYEQITLGLTAPSNLLESNYLGQASE	(SEQ ID NO:562),
  CFVRKLVRRFPQLLPGPPGHCRKDLGDPQQRPIALLPSLPHQERNNVHRLEAD
  SEVDL
  CVDFDEYFSSWEPLLKMMFKGVVGGKMKAW	(SEQ ID NO:563), and/or
  RRKKRRKPLPYKIHAD
  MMFKGVVGGKMKAWRR	(SEQ ID NO:564).
  KKRRKPLPYKIHAD

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0705]
• This gene is expressed primarily in bone marrow, and to a lesser extent in testes. [0706]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, hematopoietic and reproductive disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hematopoietic and reproductive systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., reproductive, immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0707]
• The tissue distribution in bone marrow and testes indicates that polynucleotides and polypeptides corresponding to this gene are useful for the study, diagnosis and treatment of various disorders involving the hematopoietic and reproductive systems. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Furthermore, polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of conditions concerning proper testicular function (e.g. endocrine function, sperm maturation), as well as cancer. Therefore, this gene product is useful in the treatment of male infertility and/or impotence. This gene product is also useful in assays designed to identify binding agents, as such agents (antagonists) are useful as male contraceptive agents. [0708]
• Similarly, the protein is believed to be useful in the treatment and/or diagnosis of testicular cancer. The testes are also a site of active gene expression of transcripts that may be expressed, particularly at low levels, in other tissues of the body. Therefore, this gene product may be expressed in other specific tissues or organs where it may play related functional roles in other processes, such as hematopoiesis, inflammation, bone formation, and kidney function, to name a few possible target indications. Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker and/or immunotherapy target for the above listed tissues. [0709]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:107 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1132 of SEQ ID NO:107, b is an integer of 15 to 1146, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:107, and where b is greater than or equal to a+14. [0710]
• Features of Protein Encoded by Gene No: 98 [0711]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0712]

  LISSVNKTKQKRSDATLSHKHDRLLNHFVFFGNSYNY	(SEQ ID NO:565),
  SSK
  FPSDMLLRIQQIIYCHKLTIILTKWRNTARHKSKKKEDELILKHELQLKKWKNR	(SEQ ID NO:566),
  LILKRAAAEESNFPERSSSEVFLVDETLKCDISLLPEXAILQVCMNSVYIIYYNLP
  SVVVHACNPSCLGG
  SLESTNAIKSN (SEQ ID NO:567),
  IRP	(SEQ ID NO:568)
  NKNDQMRHCLINMIDY
  ITLCFLETAITINIYSNLVNFLQICYC	(SEQ ID NO:569), and/or
  GYNRSSIVTS
  ISFRYAIADTTDHLLSQANHYPNKMA	(SEQ ID NO:570).
  EYSKT

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0713]
• This gene is expressed primarily in T-cells, tonsils, and heart tissue. [0714]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of immune system and vascular tissue disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system and vascular tissue, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, vascular, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0715]
• The tissue distribution in T-cells, tonsils and heart indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of disorders of the immune system and vascular tissues. Expression of this gene product in tonsils indicates a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. [0716]
• Expression of this gene product in T cells also strongly indicates a role for this protein in immune function and immune surveillance. The tissue distribution in heart muscle tissue indicates that the protein product of this gene is useful for the diagnosis and treatment of conditions and pathologies of the cardiovascular system, such as heart disease, restenosis, atherosclerosis, stoke, angina, thrombosis, and wound healing. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0717]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:108 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 761 of SEQ ID NO: 108, b is an integer of 15 to 775, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 108, and where b is greater than or equal to a+14. [0718]
• Features of Protein Encoded by Gene No: 99 [0719]
• An embodiment of the invention is directed to polypeptides comprising those which exhibit sequence homology with honeybee venom sacepin. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0720]

  PQIKLLNSDALGMRTTSXDLVPCNQCFIPLPPSCNRIASRKAVNWKQQRLPAVR	(SEQ ID NO:571),
  GLLNNAPHRRPPTPRTPCVFPSEGPKGYGFHV
  EQLAXISCR	(SEQ ID NO:572),
  VINVSFRCLHHVIESLPERQLTGSSRGSQP
  EDCSTMPPIAAP	(SEQ ID NO:573), and/or
  PPLAPLVFSPLRGPRVMAFMSRCGDRGGRGRSXAGRGWPWSESGVINAHPK
  KRPCPGPMLS
  EFGTRRQWGTRCFPPLVGRKQSALR	(SEQ ID NO:574).
  RREGKARAGRCCGKRSVKAGFDA

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0721]
• This gene is expressed primarily in activated and control neutrophils, and to a lesser extent in fetal liver and spleen. [0722]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of disorders of the immune and endocrine systems. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune, inflammatory and hormonal systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0723]
• The tissue distribution in neutrophils and fetal liver and spleen indicates that polynucleotides and polypeptides corresponding to this gene are useful for the study, diagnosis and treatment of inflammation and various disorders of the immune and endocrine systems. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. [0724]
• In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Expression of this gene product in neutrophils also strongly indicates a role for this protein in immune function and immune surveillance. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0725]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:109 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 897 of SEQ ID NO:109, b is an integer of 15 to 911, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:109, and where b is greater than or equal to a+14. [0726]
• Features of Protein Encoded by Gene No: 100 [0727]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0728]

  AFFLLQALEIQSQLATPASSTARNPAPDLHHPHQPTIERFCRHSSSWERIEY (SEQ ID NO:575).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. When tested against Jurkat T-cell lines, supernatants removed from cells containing this gene activated the GAS assay. Thus, it is likely that this gene activates T-cells through the Jak-STAT signal transduction pathway. The gamma activating sequence (GAS) is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS element, can be used to indicate proteins involved in the proliferation and differentiation of cells. Furthermore, contact of cells with supernatant expressing the product of this gene increases the permeability of Brian microvascular pericyte cells to calcium. Thus, it is likely that the product of this gene is involved in a signal transduction pathway that is initiated when the product of this gene binds a receptor on the surface of the pericyte cell. Thus, polynucleotides and polypeptides have uses which include, but are not limited to, activating pericyte (endothelial) cells. [0729]
• This gene is expressed primarily in activated neutrophils. [0730]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune disorders, inflammation. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard-gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0731]
• The tissue distribution in neutrophils and the biological activity data suggest that polynucleotides and polypeptides corresponding to this gene are useful for the study and treatment of inflammatory and immune conditions. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. [0732]
• In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Expression of this gene product in neutrophils also strongly indicates a role for this protein in immune function and immune surveillance. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0733]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:110 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 442 of SEQ ID NO:110, b is an integer of 15 to 456, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:110, and where b is greater than or equal to a+14. [0734]
• Features of Protein Encoded by Gene No: 101 [0735]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0736]

  	ATVPGSIYNYFYHYNAGALKPEHASESPRGLCAQTAGPFPSF	(SEQ ID NO:576),
  	IRHEPPPPRFKRFSCLSLLSSWDYRRAPPHVAIFCTLSRDGVLPHWPGWSQTPDLK	(SEQ ID NO:577),
  	STHLGLPRCWDYRHEPLCLAPFTTISIIIMQGLSNLSMPQNPPEGCAHRLLDLSPASDSVPPEWGSKIAFEV	(SEQ ID NO:578), and/or
  	LRVGGTSENCCRGECCGSVCIPPGRL	(SEQ ID NO:579).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. When tested against Jurkat T-cell lines, supernatants removed from cells containing this gene activated the GAS assay. Thus, it is likely that this gene activates T-cells through the Jak-STAT signal transduction pathway. The gamma activating sequence (GAS) is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS element, can be used to indicate proteins involved in the proliferation and differentiation of cells. [0737]
• This gene is expressed primarily in neutrophils. [0738]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0739]
• The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the study and treatment of immune disorders. Expression of this gene product in neutrophils also strongly indicates a role for this protein in immune function and immune surveillance. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). [0740]
• Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0741]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:111 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 540 of SEQ ID NO:111, b is an integer of 15 to 554, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:111, and where b is greater than or equal to a+14. [0742]
• Features of Protein Encoded by Gene No: 102 [0743]
• This gene is expressed primarily in neutrophils. [0744]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0745]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 251 as residues: Lys-33 to Lys-41. [0746]
• The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for study and treatment of immune disorders. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0747]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 112 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 708 of SEQ ID NO:112, b is an integer of 15 to 722, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:112, and where b is greater than or equal to a+14. [0748]
• Features of Protein Encoded by Gene No: 103 [0749]
• When tested against K562 leukemia cell lines, supernatants removed from cells containing this gene activated the ISRE assay. Thus, it is likely that this gene activates leukemia cells through the Jak-STAT signal transduction pathway. The interferon-sensitive response element is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jak-STAT pathway, reflected by the binding of the ISRE element, can be used to indicate proteins involved in the proliferation and differentiation of cells. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0750]

  MCVTRMHVKCPPPSASVTAVKWPLSWSSSSFCISLHAGRH	(SEQ ID NO:580), and/or
  EERNKNHLSCQGLSTICCSYLSSKGEHLRNLSPYSF	(SEQ ID NO:581).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0751]
• This gene is expressed primarily in neutrophils. [0752]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0753]
• The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the study and treatment of immune disorders. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Expression of this gene product in neutrophils also strongly indicates a role for this protein in immune function and immune surveillance. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0754]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:113 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 917 of SEQ ID NO:113, b is an integer of 15 to 931, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:113, and where b is greater than or equal to a+14. [0755]
• Features of Protein Encoded by Gene No: 104 [0756]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0757]

  GLCMVHSLLTSSLGGRCCNYPYIADKDIETEVKPPSQGHTWHLHCS	(SEQ ID NO:582),
  QLWCITALPSTRHCSKGFAWFTHSLRHPSVAGAVIILILQTRTLRQRSSHLPKGTHGICTAPDRPTERAAVTILK	(SEQ ID NO:583),
  SFDNNNSYGVSQLYQVPDTVLRALHGSLTPYVIPRWQVL	(SEQ ID NO:584), and/or
  DRGQATFPRAHMASALLLTDRQRELLSRSSNELCMSKV	(SEQ ID NO:585).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0758]
• This gene is expressed primarily in neutrophils. [0759]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of immune diseases and disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0760]
• The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the study and treatment of immune disorders. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Expression of this gene product in neutrophils also strongly indicates a role for this protein in immune function and immune surveillance. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0761]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:114 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 574 of SEQ ID NO:114, b is an integer of 15 to 588, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 114, and where b is greater than or equal to a+14. [0762]
• Features of Protein Encoded by Gene No: 105 [0763]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0764]

  LLLILRPFLNSQFKLQLPLVLFHSSCTYICLLYNYELFHIVALTGKLMNLGLHLFAHHLILAVAHXGCSIPIY	(SEQ ID NO:586), and/or
  THNSNYSSLWFSSTAVVLTYVYYIIMNCFILSPLQVN	(SEQ ID NO:587).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0765]
• This gene is expressed primarily in neutrophils. [0766]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of immune disorders and diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0767]
• The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the study and treatment of inflammatory and immune disorders. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Expression of this gene product in neutrophils also strongly indicates a role for this protein in immune function and immune surveillance. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0768]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:115 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 798 of SEQ ID NO:115, b is an integer of 15 to 812, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:115, and where b is greater than or equal to a+14. [0769]
• Features of Protein Encoded by Gene No: 106 [0770]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0771]

  TLVAGSPCSLSRWIMAGFCHGELVQSDMESQEWERGQVVLSHTSLPWCYVSP	(SEQ ID NO:588),
  R
  MAGFCHGELVQSDMESQEWERGQVVLSHTSLPWCYVSP	(SEQ ID NO:589),
  R
  MAVWISGSYSSFCSRSNWDVFSPNIVLASLPFSFRSVSK	(SEQ ID NO:590), and/or
  AAKPWWLALPALFPDGLWLDSAMGSLYSQTWKARNGKEVRWFSPTPHCLGA
  MSHL
  GWLYGSVGLIPHSAAEATG	(SEQ ID NO:591).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0772]
• This gene is expressed primarily in neutrophils. [0773]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of immune disorders and diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0774]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 255 as residues: Pro-54 to Gly-62. [0775]
• The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the study and treatment of immune disorders. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Expression of this gene product in neutrophils also strongly indicates a role for this protein in immune function and immune surveillance. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0776]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:116 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 492 of SEQ ID NO:116, b is an integer of 15 to 506, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:116, and where b is greater than or equal to a+14. [0777]
• Features of Protein Encoded by Gene No: 107 [0778]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0779]

  RSKRQSQGSRCSVPLLAQQSRSPPVPLQAQPAWLLGSETIAWSGGGSGWEGPR	(SEQ ID NO:592),
  DPGTSTAAGNSGPGIGMGHRTPPPSHTGR
  RWDPAWGLDIP	(SEQ ID NO:593),
  ESSCPVTMGELRSGDGIVL
  GALLWDNSMISAPRGSHREA	(SEQ ID NO:594),
  GALFPSWLSNPAVLPSRSRPSQPGCLDPRQ
  NSAREPRRWIR	(SEQ ID NO:595),
  PTRGSGETTAPCCFEPLNGGTLVHAAAMARASEAAGTG
  MARASEAAGTG	(SEQ ID NO:596),
  CFTTAFQKALRDPRPTLPDTHGSLRNAP	(SEQ ID NO:597),
  LKSLTLPAAFVVSFFFLSLLQDGIKERSQTQNATFFFHDRSDIEGLSEEPCSGTTP
  LALQEAVTGKQVLCSPPGSAIPQSSRPAPGPASLAAWIRDN	(SEQ ID NO:598), and/or
  SLVWRRLRVGGTQGPGHQYSSWEFRPRDRDGAQDTTPISHREMKVGSSMGTG
  HP
  MAGRLFTLLLWQELARRLVPGDASPRLSRKR	(SEQ ID NO:599).
  SVTPGPPFPTLTVPSE

• Polynucleotides encoding these polypeptides are also encompassed by the invention. When tested against sensory neuron cell lines, supernatants removed from cells containing this gene activated the EGR1 assay. Thus, it is likely that this gene activates sensory neuron cells through a signal transduction pathway. Early growth response 1 (EGR1) is a promoter associated with certain genes that induces various tissues and cell types upon activation, leading the cells to undergo differentiation and proliferation. [0780]
• This gene is expressed primarily in neutrophils. [0781]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of immune disorders and diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0782]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 256 as residues: Met-25 to Gly-30. [0783]
• The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the study and treatment of immune disorders. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Expression of this gene product in neutrophils also strongly indicates a role for this protein in immune function and immune surveillance. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0784]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:117 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 737 of SEQ ID NO:117, b is an integer of 15 to 751, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:117, and where b is greater than or equal to a+14. [0785]
• Features of Protein Encoded by Gene No: 108 [0786]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0787]

  MFYSKIFYELLLNSDTSNNVTSKTLVSSISSSNNRLAVSIVF	(SEQ ID NO:600),
  SRQKNLLKLHSNPNCDNFCFIFNYKPKYICIFKLICLKILLYIFGSG	(SEQ ID NO:601), and/or
  MLLSLLMVFTSELYVKRHISFKSXDKPHCHKNQDIDVLFRKLLEKHFKVINMICFP	(SEQ ID NO:602).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0788]
• This gene is expressed primarily in fetal liver, and to a lesser extent in bone and breast cancer cell lines. [0789]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, cancer and metabolic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the digestive and skeletal system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., digestive, skeletal, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0790]
• The tissue distribution in fetal liver/spleen, as well as bone and breast cancer, indicates that polynucleotides and polypeptides corresponding to this gene are useful for study and treatment of growth and metabolic disorders and neoplasias (e.g. hepatoblastoma, jaundice, hepatitis, liver metabolic diseases and conditions that are attributable to the differentiation of hepatocyte progenitor cells). Furthermore, the tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and/or treatment of bone and breast cancer, as well as cancers of other tissues where expression has been observed. The expression within fetal tissue and other cellular sources marked by proliferating cells suggests this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. The protein product of this clone is useful for the treatment and diagnosis of hematopoietic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex-vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0791]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:118 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 946 of SEQ ID NO:118, b is an integer of 15 to 960, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:118, and where b is greater than or equal to a+14. [0792]
• Features of Protein Encoded by Gene No: 109 [0793]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0794]

  FREYGFYNLHFC	(SEQ ID NO:603),
  LVTTDYYDGCNEDYEYNWSYMFLNSEQLFIKFYPTEFC	(SEQ ID NO:604), and/or
  NVIAPGLESSCANSLFLLFVCLPVAHHRHNFLFIKHSLYNHLRDYESDFDKI	(SEQ ID NO:605).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0795]
• This gene is expressed primarily in T cells, fetal heart and infant brain, and to a lesser extent in some transformed cell lines. [0796]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of growth and immune disorders and diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and cardiovascular systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, cardiovascular, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine; synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0797]
• The tissue distribution in immune cells, heart tissue, and brain tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the study and treatment of developmental and immune disorders. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Expression of this gene product in T cells also strongly indicates a role for this protein in immune function and immune surveillance. [0798]
• The tissue distribution in heart muscle tissue indicates that the protein product of this gene is useful for the diagnosis and treatment of conditions and pathologies of the cardiovascular system, such as heart disease, restenosis, atherosclerosis, stoke, angina, thrombosis, and wound healing. The tissue distribution in brain tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses, autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and perception. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, or sexually-linked disorders. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0799]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:119 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1428 of SEQ ID NO:119, b is an integer of 15 to 1442, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:1 19, and where b is greater than or equal to a+14. [0800]
• Features of Protein Encoded by Gene No: 110 [0801]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0802]

  PKVLAVLKKKNHVALSIFELLSNDICSFISFFMS	(SEQ ID NO:606),
  EGPDINSNLKELLCLKKKIMWPFQYLNC	(SEQ ID NO:607), and/or
  LLSLILLRIWYDFSKQTVFWFFLNVFNFFSSCNNDGACSYKYRKVQI	(SEQ ID NO:608).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0803]
• This gene is expressed primarily in osteoblasts, and to a lesser extent in bone marrow and bladder. [0804]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, skeletal and hematopoietic diseases and disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the skeletal and vascular systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., skeletal, vascular, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0805]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 259 as residues: Gly-33 to Lys-38. [0806]
• The tissue distribution in bone marrow and osteoblasts indicates that polynucleotides and polypeptides corresponding to this gene are useful for the study, diagnosis, and treatment of bone and hematopoietic disorders. Elevated levels of expression of this gene product in osteoblasts indicates that it may play a role in the survival, proliferation, and/or growth of osteoblasts. Therefore, it may be useful in influencing bone mass in such conditions as osteoporosis. More generally, as evidenced by expression in bone marrow, this gene may play a role in the survival, proliferation, and/or differentiation of hematopoietic cells in general, and may be of use in augmentation of the numbers of stem cells and committed progenitors. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0807]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 120 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 831 of SEQ ID NO: 120, b is an integer of 15 to 845, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 120, and where b is greater than or equal to a+14. [0808]
• Features of Protein Encoded by Gene No: 111 [0809]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0810]

  HTLFISFLWAEG	(SEQ ID NO:609),
  MLPVFVLFFCFTYSARKQSVFKKGNVFE	(SEQ ID NO:610), and/or
  SPCSAAECHNLSLLSSCSLVSSNILFSFPFFGQKARCCLFLFYFSASHIAHESRVYSKKEMCL	(SEQ ID NO:611).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0811]
• This gene is expressed primarily in prostate cancer. [0812]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, prostate and other cancers. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., endocrine, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0813]
• The tissue distribution in prostate cancer indicates that polynucleotides and polypeptides corresponding to this gene are useful for the study and treatment of prostate cancer, as well as cancers of other tissues where expression has been observed. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0814]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:121 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 346 of SEQ ID NO:121, b is an integer of 15 to 360, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:121, and where b is greater than or equal to a+14. [0815]
• Features of Protein Encoded by Gene No: 112 [0816]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0817]

  HKCFQCFILANGFLKVIKPFQRNWSDKTFFLVCLNKAISEALLSKMTFLSFFKT	(SEQ ID NO:612),
  NLLLLETFCTI
  LLGVLKPLYFSVEPVLGERSVAFEEVREKNH	(SEQ ID NO:613),
  GTSGFSLYSLAAIVCGHLMFFHTLLGRGGNDHPGQSPLPGMRPLRGGLAGQ
  APSGHPWMQPLDTCLL
  RPTRPPTRPDRPSLELAPGLCADF	(SEQ ID NO:614), and/or
  LGSSNHCIFLLSLYLGRDQ
  EKRIMVPQGFFPFTRWQP	(SEQ ID NO:615).
  LSVGTSCFSTLYWAVEVTITQASLLCLGCAL

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0818]
• This gene is expressed primarily in haemopoietic and neural tissues, and to a lesser extent in a number of cancers and other tissues. [0819]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases of the haemopoietic and neural systems. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and neural system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, neural, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0820]
• The tissue distribution in immune and neural tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of diseases of the haemopoietic and neural systems, including several cancers. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. [0821]
• In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Furthermore, the tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses, autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and perception. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, or sexually-linked disorders. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0822]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:122 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 930 of SEQ ID NO:122, b is an integer of 15 to 944, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 122, and where b is greater than or equal to a+14. [0823]
• Features of Protein Encoded by Gene No: 113 [0824]
• The translation product of this gene shares sequence homology with intestinal epithelium proliferating cell-associated mRNA sequence, which is thought to be important in the growth and development of epithelial cells. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0825]

  MTLDEWKNLQEQTRPKPEFNIRKPESTVPSKAVVIRESKYRDDMVKDDYEDDS	(SEQ ID NO:616),
  HVFRKPANDITSQLEINFGNLPRPGRGARGGTRGGRGRIRRAENYGPRAEVVM
  QDVAPNPDDPEDFPALS
  CKMLPPTQMTRKISLRCLERAL	(SEQ ID NO:617),
  FPSTAELHCTPVGRLFQLGQGSQTLRTIDVAFPVSCKFVALFWAELLEGLLQRL
  ESRPFPKKMKNGDCVFIEGISNEE
  PPSSWAWSQRRHPG	(SEQ ID NO:618), and/or
  RPGKDQEGRELWTQSRSGDARCCPQPR
  CLKCVY	(SEQ ID NO:619).
  RDSIDSSAEAWRERRL

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0826]
• This gene is expressed primarily in brain and central nervous system tissues, such as the frontal cortex, amygdala, and hypothalmus, and to a lesser extent in testis. [0827]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases of the neural system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the neural and reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., neural, reproductive, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0828]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 262 as residues: Glu-20 to Glu-27, Glu-30 to Trp-44. [0829]
• The tissue distribution and homology to intestinal epithelium proliferating cell-associated mRNA sequence indicates that polynucleotides and polypeptides corresponding to this gene are useful for growth and developmental diseases of the brain, central nervous system and reproductive system. The tissue distribution in neural tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses, autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and perception. [0830]
• In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, or sexually-linked disorders. Elevated expression of this gene product within the frontal cortex of the brain indicates that it may be involved in neuronal survival; synapse formation; conductance; neural differentiation, etc. Such involvement may impact many processes, such as learning and cognition. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0831]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:123 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 900 of SEQ ID NO:123, b is an integer of 15 to 914, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:123, and where b is greater than or equal to a+14. [0832]
• Features of Protein Encoded by Gene No: 114 [0833]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0834]

  LSYSVLLILPLFHSLPTLKDTHTHNKWVE	(SEQ ID NO:620),
  EVNGVGYKHSCFSDISSVLENKDSRMRAPHYASFQHFFSVLLKL	(SEQ ID NO:621),
  SPQACLTESQCIPLTFY
  KTHTHTISGWSKKSTELDISIPAFL	(SEQ ID NO:622), and/or
  TSPVSWRTRILE
  IRHELGSSDPPAEASQIAGTAAVS	(SEQ ID NO:623).
  HHAQP

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0835]
• This gene is expressed primarily in spinal cord. [0836]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, spinal cord injuries and diseases of the neural system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the neural system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., neural, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0837]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 263 as residues: Pro-45 to Gln-52. [0838]
• The tissue distribution in spinal cord indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of spinal cord injuries and diseases of the neural system, such as spinal deformation, spinocerebullar ataxia types I and III, dentatorubropallidoluysian and spinal bulbar muscular atrophy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0839]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:124 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 448 of SEQ ID NO:124, b is an integer of 15 to 462, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:124, and where b is greater than or equal to a+14. [0840]
• Features of Protein Encoded by Gene No: 115 [0841]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0842]

  MLYLILISLSSLSFSFSLPPFSIII	(SEQ ID NO:624),
  SSYFL	(SEQ ID NO:625),
  RHFRIYHTCPKYFSMNIIN
  KLTLTKGNKSWSSTAVAAA	(SEQ ID NO:626), and/or
  LELVDPPGCRNSARDSLPNSTM MFYYACFILYSSLSPLSLSLSPSLLSLL
  QFHTGNSYDHDYAK	(SEQ ID NO:627).

• Polynucleotides encoding these polypeptides are also encompassed by the invention. When tested against U937 Myeloid cell lines, supernatants removed from cells containing this gene activated the GAS assay. Thus, it is likely that this gene activates myeloid cells through the Jak-STAT signal transduction pathway. The gamma activating sequence (GAS) is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS element, can be used to indicate proteins involved in the proliferation and differentiation of cells. [0843]
• This gene is expressed primarily in striatum. [0844]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of a number of diseases of the neural system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the neural diseases, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., striatum, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0845]
• The tissue distribution in striatum indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of diseases of the neural system. Furthermore, the tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses, autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and perception. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, or sexually-linked disorders. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0846]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:125 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 531 of SEQ ID NO:125, b is an integer of 15 to 545, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:125, and where b is greater than or equal to a+14. [0847]
• Features of Protein Encoded by Gene No: 116 [0848]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0849]

  AVCTGGYCESCRCEHCVCVCVDLCVLFSGKELRVR	(SEQ ID NO:628),
  VSFFFVFKWSFAEIKSREEHWASLTPKPTLLSALLTCDVLKS	(SEQ ID NO:629),
  SIIFKCCESTEDKGFDSFFQASKDGSSSRI
  RSWGSQRSLCLL	(SEQ ID NO:630),
  FIPFAAESYSVVWMGHLFVVCLLSSWWTFRPFALAVTVNHVAVNIVCVSAWTC
  VSCSLGRSCGLEGSFLFPLETLWFPHMVVLCLTF
  MGHLFV	(SEQ ID NO:631),
  VCLLSSWWTFRPFALAVTVNHVAVNIVCVSAWTCVSCSLGRSCGLEGSFLFPL
  ETLWFPHMVVLCLTF
  HDVLGARNAACVCCSFLLQQNRILL	(SEQ ID NO:632),
  FGWATCLLSVYSPAGGHLGRLHWRLL
  MLDFKTSQVSKAL	(SEQ ID NO:633), and/or
  KRVGFGVRLAQCSSLDLISAKLHLKTKKKETYITSTVMTAASLFLSYVTSEFTR
  SIMATFYCFVLKLHIGEMGTLQTAGGSKMTWPLQKAIWQFLKRLSIKLPYVET
  RESPGETKNY
  LTRNSFPENRTHKSTQTHTQCSQRHD	(SEQ ID NO:634).
  SQ

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0850]
• This gene is expressed primarily in intestine and cancer cells. [0851]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases of the gastrointestinal tract and cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the digestive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., digestive, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0852]
• The tissue distribution in gastrointestinal tissues and cancerous tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of diseases of the digestive system and cancer. Furthermore, the tissue distribution in gastrointestinal tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, prevention, and/or treatment of various metabolic disorders such as Tay-Sachs disease, phenylkenonuria, galactosemia, porphyrias, and Hurler's syndrome. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0853]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:126 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 898 of SEQ ID NO:126, b is an integer of 15 to 912, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 126, and where b is greater than or equal to a+14. [0854]
• Features of Protein Encoded by Gene No: 117 [0855]
• The translation product of this gene shares sequence homology with a human apoptosis regulating protein which is thought to be important in regulating cell death. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0856]

  IRHEGQSSSRGSSHCDSPSPQEDGQIMFDVEMHTSRDHSSQSEEEVVEGEKEVE	(SEQ ID NO:635),
  ALKKSADWVSDWSSRPENIPPKEFHFRHPKRSVSLS
  GILLTLYPFWPEDILEFPNRVYCCLEICKGFFSANATSRL	(SEQ ID NO:636),
  EFGTRDRVVPEAVLTVTALRHKKMGRSCLMWKCTPAGTIALSQKKKL	(SEQ ID NO:637),
  AHPLPAPTEGKEKPLEMRVTCEVVYCHSSLFELETIVSMTQPT	(SEQ ID NO:638),
  TLFLHIQFQ
  TFCVFKHEEKWSHEERGYFLRRISEGVHSISLP	(SEQ ID NO:639), and/or
  FSCFGFGARHLYWKATEHTLCQHLLRERKSPWKCV
  QSLLLFRNLQGLLFRKCHQQIIILSAMLLSLISATRLDLYHSWYKFYSCNITTISL	(SEQ ID NO:640).
  LKRDQVSK

• Polynucleotides encoding these polypeptides are also encompassed by the invention. When tested against Jurkat cell lines, supernatants removed from cells containing this gene activated the NF-kB transcription factor. Thus, it is likely that this gene activates Jurkat cells by activating a transcriptional factor found within these cells. Nuclear factor kB is a transcription factor activated by a wide variety of agents, leading to cell activation, differentiation, or apoptosis. Reporter constructs utilizing the NF-kB promoter element are used to screen supernatants for such activity. [0857]
• This gene is expressed primarily in muscle, fibroblast cells, haemopoietic cells, and fetal lung. [0858]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases of the haemopoietic, muscular and developing systems. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and muscular system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, muscular, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0859]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 266 as residues: Met-1 to Ala-6. [0860]
• The tissue distribution in muscle and homology to apoptosis regulating protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of diseases of the haemopoietic, muscular and developing systems. Expression within embryonic tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation-of cellular division. Additionally, the expression in hematopoietic cells and tissues indicates that this protein may play a role in the proliferation, differentiation, and/or survival of hematopoietic cell lineages. In such an event, this gene may be useful in the treatment of lymphoproliferative disorders, and in the maintenance and differentiation of various hematopoietic lineages from early hematopoietic stem and committed progenitor cells. Similarly, embryonic development also involves decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0861]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:127 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1034 of SEQ ID NO:127, b is an integer of 15 to 1048, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:127, and where b is greater than or equal to a+14. [0862]
• Features of Protein Encoded by Gene No: 118 [0863]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0864]

  IRHEESFNPLTCGFSLFFSLFS,	(SEQ ID NO: 641)
  METLLLLLFFLSLLIFRFRILVSQCIN,	(SEQ ID NO: 642)
  FLLTTVLLFSSKVRDPRANFDQSLRVLKHAKKVQ	(SEQ ID NO: 643)
  PDVISKTSIMLGLGENDEQVYATMKGKEIEK,
  and/or QQSCCFPVRFVILGPILISPYVY.	(SEQ ID NO: 644)

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0865]
• This gene is expressed primarily in synovium. [0866]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, arthritis and other diseases of the musculo-skeletal system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the musculo-skeletal system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., musculo-skeletal, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0867]
• The tissue distribution in synovium indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of diseases of the muscular-skeletal system. Furthermore, the expression of this gene product in synovium indicates a role in the detection and treatment of disorders and conditions affecting the skeletal system, in particular osteoporosis as well as disorders afflicting connective tissues (e.g. arthritis, trauma, tendonitis, chrondomalacia and inflammation), such as in the diagnosis or treatment of various autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (ie. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0868]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:128 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 708 of SEQ ID NO:128, b is an integer of 15 to 722, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 128, and where b is greater than or equal to a+14. [0869]
• Features of Protein Encoded by Gene No: 119 [0870]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0871]

  VWLLSSILLRVLWNRYTLQELSFWLPWFASRATS	(SEQ ID NO: 645)
  LVLQHGDNYLLFLFCFVCFVLAMPF,
  IRHEVSMAFVFHLAQGTLEPLYIAGA,	(SEQ ID NO: 646)
  NSARGEYGFCLPSCSGYFGTAIHCRSLASGYHGL	(SEQ ID NO: 647)
  LPEQQA,
  and/or HELTVPSRMGSKGKPYPCGFYSSLIP.	(SEQ ID NO: 648)

• Polynucleotides encoding these polypeptides are also encompassed by the invention. When tested against U937 Myeloid cell lines, supernatants removed from cells containing this gene activated the GAS assay. Thus, it is likely that this gene activates myeloid cells through the Jak-STAT signal transduction pathway. The gamma activating sequence (GAS) is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS element, can be used to indicate proteins involved in the proliferation and differentiation of cells. [0872]
• This gene is expressed primarily in rejected kidney, stromal cells, and infant brain. [0873]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases of the renal, central nervous and immune systems. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune, renal and central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, renal, nervous, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0874]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 268 as residues: Ser-6 to Arg-15. [0875]
• The tissue distribution rejected kidney, stromal cells, and infant brain indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of diseases of the renal, central nervous, and immune systems. The tissue distribution in infant brain indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses, autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and perception. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, or sexually-linked disorders. [0876]
• Alternatively, this gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. [0877]
• The tissue distribution in kidney indicates that this gene or gene product is useful in the treatment and/or detection of kidney diseases including renal failure, nephritus, renal tubular acidosis, proteinuria, pyuria, edema, pyelonephritis, hydronephritis, nephrotic syndrome, crush syndrome, glomerulonephritis, hematuria, renal colic and kidney stones, in addition to Wilm's Tumor Disease, and congenital kidney abnormalities such as horseshoe kidney, polycystic kidney, and Falconi's syndrome. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0878]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:129 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 463 of SEQ ID NO:129, b is an integer of 15 to 477, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:129, and where b is greater than or equal to a+14. [0879]
• Features of Protein Encoded by Gene No: 120 [0880]
• The protein of the invention has sequence identity to the [0881] Saccharomyces cerevisiae ankyrin repeat-containing protein (gi|466522). The translation product of this gene also shares homology with C. elegans protein C43H6.7 gene product (Genbank Accession No. gi|1255324). In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:

  KCIYPKPARTHHCSICNRCVLKMDHHCPWLNNC	(SEQ ID NO: 649)
  VGHYNHRYFFSFCFFMTLGCVYCSYGSWDLFREA
  YAAIEKMKQLDKNKLQAVANQTYHQTPPPTFSF
  RER,
  ARGHWNLILIVFHYYQAITTPPGYPPQGRNDIA	(SEQ ID NO: 650)
  TVSIC,
  WQCELDCVSHDSSTHSAPYVISRASKGSFSQNP,	(SEQ ID NO: 651)
  SKRASGPALGYHAGQFKDQPFYHCRRKTQCGEI	(SEQ ID NO: 652)
  LGLTSLYSGKQKFQPQTRGQAASYLPCPVLTRT
  SSRIQHWSWPPPLLLAV,
  ESLQLRLLGQLEGIPGCGYRKALAYSGALTF,	(SEQ ID NO: 653)
  and/or SLAPWEWNELGAPSLGDCSLSLCDGS	(SEQ ID NO: 654)
  VSWTVSATTRALILLPMLFQGPPRAAFLRILDQ
  KEPVGLP.

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0882]
• This gene is expressed primarily in endometrial tumor, colon tumor, prostate cancer, and ovarian cancer. [0883]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of a number of types of cancers, particularly endometrial, prostate, ovarian, and colon cancers. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endometrium, prostate, colon, and ovary, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., prostate, colon, ovary, endometrium, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0884]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 269 as residues: Asn-43 to Arg-49, Phe-57 to Cys-65, Pro-93 to Ser-99. [0885]
• The tissue distribution in prostate cancer, ovarian cancer, colon cancer, and endometrial cancer tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of diseases and cancers of the prostate, ovaries, colon, and endometrium, as well as cancers of other tissues where expression has been observed. Expression within cellular sources marked by proliferating cells suggests this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0886]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:130 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1282 of SEQ ID NO:130, b is an integer of 15 to 1296, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:130, and where b is greater than or equal to a+14. [0887]
• Features of Protein Encoded by Gene No: 121 [0888]
• The translation product of this gene shares sequence homology with adrenalin receptor (Patent serial No. J08126491-A.) In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0889]

  TATLNSFFGGWGLALLLRLECSDTIMDHCSLDLL	(SEQ ID NO: 655)
  GSSNPPASASQVVGTTGARHHAQLIFCFFVQTRS
  HSVA,
  MDHCSLDLLGSSNPPASASQVVGTTGARHHAQLI	(SEQ ID NO: 656)
  FCFFVQTRSHSVA,
  GVLKQSSHLVLSKG,	(SEQ ID NO: 657)
  DYSCESLCPALLSIAPDIVLN,	(SEQ ID NO: 658)
  TTIHKTQLGSYKILWEPKEGYHNSTWI,	(SEQ ID NO: 659)
  IREIFLRRP, and/or	(SEQ ID NO: 660)
  LKFQKPGKIQMRGGGRVFWYKNCK.	(SEQ ID NO: 661)

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0890]
• This gene is expressed primarily in synovial sarcoma. [0891]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, arthritis and other diseases of the synovium including cancers. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and muscular-skeletal system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., immune, musculo-skeletal, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0892]
• The tissue distribution in synovial sarcoma tissue and the homology to adrenalin receptor indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of diseases of the synovium, immune system and musculo-skeletal system including cancers of these tissues and systems. It may also be useful for identifying and therapeutically using antagonists and agonists for this receptor family. In addition, the expression of this gene product in synovium indicates a role in the detection and treatment of disorders and conditions affecting the skeletal system, in particular osteoporosis as well as disorders afflicting connective tissues (e.g. arthritis, trauma, tendonitis, chrondomalacia and inflammation), such as in the diagnosis or treatment of various autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (ie. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0893]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:131 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 724 of SEQ ID NO:131, b is an integer of 15 to 738, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:131, and where b is greater than or equal to a+14. [0894]
• Features of Protein Encoded by Gene No: 122 [0895]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0896]

  NSARVTQKGESVGSVGCMRAIAGFDNYPLF,	(SEQ ID NO: 662)
  GTIGIFWPLPVAILSSGDYLQTQIHRPLLHRGT,	(SEQ ID NO: 663)
  LPLPLSSLLHIATCNPFPKT,	(SEQ ID NO: 664)
  SYFFVYNLILKIIQGDHASIILLATIPIFGDIYY	(SEQ ID NO: 665)
  VKGQLASFGPYL,
  LFYHLEIISRHKSIAHCSIEA,	(SEQ ID NO: 666)
  CSCHCPSRAFST, and/or	(SEQ ID NO: 667)
  PHAIHSQKPSSIFLITDVFPDPPVGIYLL.	(SEQ ID NO: 668)

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0897]
• This gene is expressed primarily in chronic synovitis. [0898]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, inflammatory diseases -and disorders of the musculo-skeletal system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the inflammatory and musculo-skeletal system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., musculo-skeletal, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0899]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 271 as residues: Ser-39 to Pro-44. [0900]
• The tissue distribution in chronic synovitis tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of disorders and diseases of the inflammatory and musculo-skeletal system. In addition, the expression of this gene product in synovium indicates a role in the detection and treatment of disorders and conditions affecting the skeletal system, in particular osteoporosis as well as disorders afflicting connective tissues (e.g. arthritis, trauma, tendonitis, chrondomalacia and inflammation), such as in the diagnosis or treatment of various autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (ie. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0901]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:132 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 428 of SEQ ID NO:132, b is an integer of 15 to 442, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:132, and where b is greater than or equal to a+14. [0902]
• Features of Protein Encoded by Gene No: 123 [0903]
• In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: [0904]

  RKLFHKINSKSFHLSGMHILISVWIVRSRIIKVK	(SEQ ID NO: 669)
  YELLLCFFDVIFYV,
  NSARDVFFTQKILYSQTCIFFPCLVPFSFLFSFF	(SEQ ID NO: 670)
  FFLSFVG,
  MFSSLKKFYILKHVYSFPVLFHFLFFFLFSFSFL	(SEQ ID NO: 671)
  SWAEKGAGKMKLATENCKMVKS, and/or
  IQLLYLKGAAMKYLSYVARLLFLKALDLFAPKMV	(SEQ ID NO: 672)
  QIDSF.

• Polynucleotides encoding these polypeptides are also encompassed by the invention. [0905]
• This gene is expressed primarily in kidney and infant brain. [0906]
• Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases of the renal and central nervous systems. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the neural and renal system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., neural, renal, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. [0907]
• Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 272 as residues: Gly-24 to Lys-31. [0908]
• The tissue distribution in kidney and infant brain tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of diseases of the neural and renal systems. The tissue distribution in infant brain indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses, autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and perception. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, or sexually-linked disorders. [0909]
• The tissue distribution in kidney indicates that this gene or gene product is useful in the treatment and/or detection of kidney diseases including renal failure, nephritus, renal tubular acidosis, proteinuria, pyuria, edema, pyelonephritis, hydronephritis, nephrotic syndrome, crush syndrome, glomerulonephritis, hematuria, renal colic and kidney stones, in addition to Wilm's Tumor Disease, and congenital kidney abnormalities such as horseshoe kidney, polycystic kidney, and Falconi's syndrome. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. [0910]
• Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 133 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 868 of SEQ ID NO:133, b is an integer of 15 to 882, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:133, and where b is greater than or equal to a+14. [0911]

  	5′ NT

  NT

  of

  AA

  First

  Last

  ATCC

  SEQ

  5′ NT

  3′ NT

  5′ NT

  First

  SEQ

  AA

  AA

  First AA

  Last

  Deposit

  ID

  Total

  of

  of

  of

  AA of

  ID

  of

  of

  of

  AA

  Gene

  cDNA

  Nr and

  NO.

  NT

  Clone

  Clone

  Start

  Signal

  NO:

  Sig

  Sig

  Secreted

  of

  No.

  Clone ID

  Date

  Vector

  X

  Seq.

  Seq.

  Seq.

  Condon

  Pep

  Y

  Pep

  Pep

  Portion

  ORF

  1	HCEIA77	209119	Uni-ZAP XR	11	1882	676	1882	785	785	150	1	37	38	53
  		06/12/97
  2	HCFCE10	209119	pSport1	12	1590	18	1590	198	198	151	1	19	20	45
  		06/12/97
  3	HCFNC26	209119	pSport1	13	1373	6	1373	85	85	152	1	18	19	24
  		06/12/97
  4	HCHAA63	209119	pSport1	14	1142	1	1142	130	130	153	1	37	38	264
  		06/12/97
  5	HCNSP40	209119	pBluescript	15	1034	1	1034	106	106	154	1	19	20	237
  		06/12/97
  5	HCNSP40	209119	pBluescript	134	1032	1	1032		111	273	1			14
  		06/12/97
  6	HDAAC10	209119	pSport1	16	1198	1	1198	117	117	155	1	21	22	313
  		06/12/97
  7	HE8CV18	209119	Uni-ZAP XR	17	1447	1	1447	176	176	156	1	29	30	98
  		06/12/97
  8	HELDY05	209119	Uni-ZAP XR	18	1422	1	1375	79	79	157	1	34	35	36
  		06/12/97
  9	HELDZ32	209119	Uni-ZAP XR	19	1107	12	1107	148	148	158	1	15	16	22
  		06/12/97
  10	HFGAL10	209119	Uni-ZAP XR	20	1183	1	1183	179	179	159	1	20	21	96
  		06/12/97
  10	HFGAL10	209119	Uni-ZAP XR	135	1766	3	1765	179	179	274	1	17	18	36
  		06/12/97
  11	HFKEB72	209119	Uni-ZAP XR	21	1420	1	1420	43	43	160	1	29	30	65
  		06/12/97
  12	HFTCU19	209119	Uni-ZAP XR	22	1575	1266	1575	137	137	161	1	30	31	222
  		06/12/97
  12	HFTCU19	209119	Uni-ZAP XR	136	470	1	470	157	157	275	1	24	25	56
  		06/12/97
  13	IIFXHN31	209119	Lambda ZAP	23	541	1	541	172	172	162	1	30	31	91
  		06/12/97	II
  13	HFXHN31	209119	Lambda ZAP	137	1168	1	1168	293	293	276	1	22	23	26
  		06/12/97	II
  14	HGLAM53	209119	Uni-ZAP XR	24	833	219	833	359	359	163	1	27	28	74
  		06/12/97
  14	HGLAM53	209119	Uni-ZAP XR	138	1294	226	1288		369	277	1	26	27	67
  		06/12/97
  15	HJABB94	209119	pBluescript	25	1555	1	1555	74	74	164	1	28	29	77
  		06/12/97	SK-
  16	HKIYO61	209119	pBluescript	26	1543	1	1543	181	181	165	1	19	20	37
  		06/12/97
  17	HLTAI94	209119	Uni-ZAP XR	27	1262	1	1262	47	47	166	1	18	19	44
  		06/12/97
  18	HMDAI51	209119	Uni-ZAP XR	28	753	1	753	12	12	167	1	21	22	38
  		06/12/97
  19	HMELR03	209119	Lambda ZAP	29	1621	8	1535	200	200	168	1	25	26	173
  		06/12/97	II
  20	HMKAH10	209119	pSport1	30	921	1	921	48	48	169	1	463	44	54
  		06/12/97
  21	HMKCW19	209119	pSport1	31	2095	473	1934	529	529	170	1	30	31	344
  		06/12/97
  21	HMKCW19	209119	pSport1	139	1720	103	1692	188	188	278	1	27	28	45
  		06/12/97
  22	HMSJW18	209119	Uni-ZAP XR	32	1838	1	1838	28	28	171	1	23	24	89
  		06/12/97
  23	HMWGY01	209119	Uni-Zap XR	33	782	1	782	423	423	172	1	30	31	104
  		06/12/97
  23	HMWGY01	209119	Uni-Zap XR	140	774	1	774	17	17	279	1	31	32	39
  		06/12/97
  24	HNFID82	209119	pBluescript	34	1560	1	1560	161	161	173	1	17	18	41
  		06/12/97
  25	HNFIG36	209119	pBluescript	35	1092	1	1082	171	171	174	1	18	19	46
  		06/12/97
  26	HNGEV29	209119	Uni-ZAP XR	36	1153	1	1153	173	173	175	1	30	31	73
  		06/12/97
  26	HNGEV29	209119	Uni-ZAP XR	141	1566	1	1566	79	79	280	1			10
  		06/12/97
  27	HNGIK21	209119	Uni-ZAP XR	37	985	1	985	152	152	176	1	25	26	28
  		06/12/97
  28	HNGJJ65	209124	Uni-ZAP XR	38	1122	1	1122	84	84	177	1	22	23	67
  		06/19/97
  29	HNGJU42	209124	Uni-ZAP XR	39	598	6	598	273	273	178	1	17	18	23
  		06/19/97
  30	HODAZ26	209124	Uni-ZAP XR	40	1129	8	1129	133	133	179	1			30
  		06/19/97
  31	HODDB05	209124	Uni-ZAP XR	41	1158	22	1158	244	244	180	1			10
  		06/19/97
  32	HOFAF39	209124	pSport1	42	1767	1	1767	57	57	181	1	22	23	31
  		06/19/97
  33	HOFNY71	209124	pCMVSport	43	917	1	917	114	114	182	1	31	32	35
  		06/19/97	2.0
  34	HORBI81	209124	Uni-ZAP XR	44	1987	8	1965	31	31	183	1	34	35	34
  		06/19/97
  35	HOSCY73	209124	Uni-ZAP XR	45	2053	196	2048	209	209	184	1			28
  		06/19/97
  36	HPMBR15	209124	Uni-ZAP XR	46	1272	25	1272	262	262	185	1			5
  		06/19/97
  37	HSAVD46	209124	Uni-ZAP XR	47	773	2	767	155	155	186	1	20	21	58
  		06/19/97
  38	HSLBF69	209124	Uni-ZAP XR	48	2119	1	2119	107	107	187	1	19	20	405
  		06/19/97
  39	HSOAH66	209124	Uni-ZAP XR	49	1188	7	1188	196	196	188	1	27	28	36
  		06/19/97
  39	HSOAH66	209124	Uni-ZAP XR	143	537	1	537	136	136	282	1	21	22	47
  		06/19/97
  40	HSVBH58	209124	Uni-ZAP XR	50	478	24	155	249	249	189	1	40	41	57
  		06/19/97
  40	HSVBH58	209124	Uni-ZAP XR	144	680	1	680	168	168	283	1	20	21	22
  		06/19/97
  41	HSZAF47	209124	Uni-ZAP XR	51	1333	2	1333	107	107	190	1	18	19	126
  		06/19/97
  42	HTADV27	209124	Uni-ZAP XR	52	1255	14	1255	69	69	191	1	20	21	20
  		06/19/97
  43	HTADX17	209124	Uni-ZAP XR	53	1140	22	1140	84	84	192	1	24	25	142
  		06/19/97
  44	HTDAD22	209124	pSport1	54	1220	1	1220	193	193	193	1	37	38	109
  		06/19/97
  45	HTEDS39	209124	Uni-ZAP XR	55	694	198	694	205	205	194	1	21	22	80
  		06/19/97
  45	HTEDS39	209124	Uni-ZAP XR	145	1048	1	1048		227	284	1			20
  		06/19/97
  46	HTEHH53	209124	Uni-ZAP XR	56	988	1	980	22	22	195	1	24	25	209
  		06/19/97
  47	HTLDP69	209124	Uni-ZAP XR	57	1500	237	1500	330	330	196	1	29	30	148
  		06/19/97
  48	HTNBR95	209124	pBluescript	58	1391	1	1386	70	70	197	1	28	29	35
  		06/19/97	SK-
  49	HTPCS60	209124	Uni-ZAP XR	59	1579	7	1259	105	105	198	1	19	20	257
  		06/19/97
  50	HUKBH05	209124	Lambda ZAP	60	1241	1	1215	151	151	199	1	18	19	33
  		06/19/97	II
  51	HUKEX85	209124	Lambda ZAP	61	930	7	925	35	35	200	1	18	19	33
  		06/19/97	II
  51	HUKEX85	209124	Lambda ZAP	146	930	6	917	83	83	285	1	30	31	122
  		06/19/97	II
  52	HWTBM45	209124	Uni-ZAP XR	62	998	1	998	69	69	201	1	19	20	25
  		06/19/97
  53	HADFF38	209124	pSport1	63	1193	1	1034	64	64	202	1	19	20	33
  		06/19/97
  54	HADFK68	209124	pSport1	64	830	1	830	91	91	203	1	24	25	58
  		06/19/97
  54	HADFK68	209124	pSport1	147	830	1	830	45	45	286	1	26	27	26
  		06/19/97
  55	HADGG19	209125	pSport1	65	867	1	867	262	262	204	1	30	31	75
  		06/19/97
  55	IIADGG19	209125	pSport1	148	865	1	865	281	281	287	1			7
  		06/19/97
  56	HAEAV45	209125	pBluescript	66	685	46	647	487	487	205	1	34	35	66
  		06/19/97	SK-
  56	HAEAV45	209125	pBluescript	149	545	1	545	24	24	288	1	25	26	28
  		06/19/97	SK-
  57	HARAA15	209125	pBluescript	67	801	1	801	185	185	206	1	34	35	43
  		06/19/97	SK-
  58	HATDL27	209125	Uni-ZAP XR	68	908	1	908	82	82	207	1	28	29	31
  		06/19/97
  59	HBAFQ54	209125	pSport1	69	696	209	696	229	229	208	1	20	21	47
  		06/19/97
  60	HBGBA14	209125	Uni-ZAP XR	70	455	1	452	32	32	209	1	24	25	36
  		06/19/97
  61	HBIAS26	209125	Uni-ZAP XR	71	413	1	372	57	57	210	1	27	28	73
  		06/19/97
  62	HBJFU48	209125	Uni-ZAP XR	72	849	1	849	20	20	211	1	39	40	40
  		06/19/97
  63	HBJFV28	209125	Uni-ZAP XR	73	505	1	505	306	306	212	1	21	22	53
  		06/19/97
  64	HBMWB01	209125	Uni-ZAP XR	74	719	1	719	48	48	213	1	17	18	62
  		06/19/97
  65	HBMXN79	209125	Uni-ZAP XR	75	1274	141	974	192	192	214	1	44	45	175
  		06/19/97
  66	HBMXP84	209125	Uni-ZAP XR	76	519	1	519	161	161	215	1	31	32	39
  		06/19/97
  67	HCFMM26	209125	pSport1	77	389	1	389	178	178	216	1	27	28	54
  		06/19/97
  68	HCNAV36	209125	Lambda ZAP	78	823	411	823	505	505	217	1	15	16	46
  		06/19/97	II
  69	HCNSB01	209125	pBluescript	79	2455	533	1308	552	552	218	1	22	23	179
  		06/19/97
  70	HCRBR74	209125	Uni-ZAP XR	80	921	365	911	415	415	219	1	39	40	43
  		06/19/97
  71	HCUBN59	209125	ZAP Express	81	678	1	678	96	96	220	1	39	40	43
  		06/19/97
  72	HCUDB38	209125	ZAP Express	82	857	1	857	221	221	221	1	17	18	41
  		06/19/97
  73	HCUFZ62	209125	ZAP Express	83	1977	28	661	233	233	222	1	28	29	51
  		06/19/97
  74	HDHMB42	209125	pCMVSport	84	1149	427	1149	592	592	223	1	26	27	31
  		06/19/97	2.0
  75	HDPCO25	209125	pCMVSport	85	767	76	767	182	182	224	1	20	21	53
  		06/19/97	3.0
  76	HDPHI51	209125	pCMVSport	86	728	1	728	245	245	225	1	30	31	40
  		06/19/97	3.0
  77	HE2EC79	209125	Uni-ZAP XR	87	735	1	735	151	151	226	1	21	22	30
  		06/19/97
  78	HE9FE83	209125	Uni-ZAP XR	88	889	332	889	351	351	227	1	21	22	59
  		06/19/97
  79	HE9HW52	209125	Uni-ZAP XR	89	569	73	569	122	122	228	1	25	26	34
  		06/19/97
  80	HEBFL88	209125	Uni-ZAP XR	90	334	2	334	76	76	229	1	22	23	38
  		06/19/97
  81	HFIVB57	209125	pSport1	91	795	92	795	286	286	230	1	35	36	38
  		06/19/97
  82	HFPDE69	209125	Uni-ZAP XR	92	577	1	577	72	72	231	1	33	34	61
  		06/19/97
  83	HGBGV89	209125	Uni-ZAP XR	93	968	1	968	55	55	232	1	26	27	197
  		06/19/97
  84	HGLDE38	209125	Uni-ZAP XR	94	553	1	553	31	31	233	1	19	20	61
  		06/19/97
  85	HHGDU58	209125	Lambda ZAP	95	968	70	898	235	235	234	1	46	47	80
  		06/19/97	II
  86	HHTLF25	209125	ZAP Express	96	697	1	661	142	142	235	1	26	27	111
  		06/19/97
  87	HJMAV91	209125	pCMVSport	97	866	74	866	251	251	236	1	16	17	32
  		06/19/97	3.0
  88	HKAFB88	209125	pCMVSport	98	1368	219	795	238	238	237	1	45	46	228
  		06/19/97	2.0
  89	HLHFP03	209126	Uni-ZAP XR	99	613	1	613	224	224	238	1	20	21	116
  		06/19/97
  90	HLNAB07	209126	Lambda ZAP	100	685	1	685	187	187	239	1	32	33	36
  		06/19/97	II
  91	HLWCF05	209126	pCMVSport	101	646	1	646	155	155	240	1	36	37	58
  		06/19/97	3.0
  92	HLYAF80	209126	pSport1	102	826	1	826	222	222	241	1	24	25	47
  		06/19/97
  93	HMDAA66	209126	Uni-ZAP XR	103	586	1	586	106	106	242	1	23	24	31
  		06/19/97
  94	HMKDD07	209126	pSport1	104	628	43	628	267	267	243	1	29	30	63
  		06/19/97
  95	HMKDS08	209126	pSport1	105	558	1	558	230	230	244	1	30	31	67
  		06/19/97
  96	HMSHM14	209126	Uni-ZAP XR	106	756	1	756	103	103	245	1	29	30	45
  		06/19/97
  97	HMWDC28	209126	Uni-Zap XR	107	1146	105	754	124	124	246	1	30	31	42
  		06/19/97
  98	HNDAH54	209126	pCMVSport	108	775	1	775	26	26	247	1	20	21	31
  		06/19/97	2.0
  99	HNFDS53	209126	Uni-ZAP XR	109	911	1	911	200	200	248	1	22	23	23
  		06/19/97
  100	IINFIU96	209126	pBluescript	110	456	1	456	170	170	249	1	33	34	79
  		06/19/97
  101	HNGAC63	209126	Uni-ZAP XR	111	554	1	554	214	214	250	1			15
  		06/19/97
  102	HNGAX58	209126	Uni-ZAP XR	112	722	1	722	100	100	251	1	16	17	46
  		06/19/97
  103	HNGEM24	209126	Uni-ZAP XR	113	931	1	931	239	239	252	1	30	31	31
  		06/19/97
  104	HNGFT78	209126	Uni-ZAP XR	114	588	1	588	20	20	253	1	29	30	35
  		06/19/97
  105	HNHDL85	209126	Uni-ZAP XR	115	812	1	812	194	194	254	1	22	23	50
  		06/19/97
  106	HNHFU59	209126	Uni-ZAP XR	116	506	1	506	278	278	255	1	16	17	76
  		06/19/97
  107	HNHFW22	209126	Uni-ZAP XR	117	751	1	751	228	228	256	1	26	27	60
  		06/19/97
  108	HOAAF80	209126	Uni-ZAP XR	118	960	131	960	303	303	257	1	33	34	36
  		06/19/97
  109	HODCJ90	209126	Uni-ZAP XR	119	1442	326	1133	344	344	258	1	18	19	42
  		06/19/97
  110	HOECO90	209126	Uni-ZAP XR	120	845	215	845	299	299	259	1	24	25	38
  		06/19/97
  111	HPEBT80	209126	Uni-ZAP XR	121	360	1	360	21	21	260	1	40	41	50
  		06/19/97
  112	HSDAG05	209126	Uni-ZAP XR	122	944	231	848	419	419	261	1	37	38	75
  		06/19/97
  113	HSDGR57	209126	Uni-ZAP XR	123	914	115	914	195	195	262	1	21	22	44
  		06/19/97
  114	HSDJJ82	209126	Uni-ZAP XR	124	462	1	462	79	79	263	1	32	33	52
  		06/19/97
  115	HSDZM95	209126	pBluescript	125	545	1	545	223	223	264	1	23	24	42
  		06/19/97
  116	HSIDI15	209126	Uni-ZAP XR	126	912	1	873	273	273	265	1	22	23	74
  		06/19/97
  117	HSKYU29	209126	pBluescript	127	1048	1	1047	290	290	266	1	36	37	51
  		06/19/97
  118	HSNAA55	209126	Uni-ZAP XR	128	722	1	722	35	35	267	1	15	16	40
  		06/19/97
  119	HSQFP66	209126	Uni-ZAP XR	129	477	1	477	96	96	268	1	32	33	78
  		06/19/97
  120	HSRDE35	209126	Uni-ZAP XR	130	1296	232	804	428	428	269	1	21	22	116
  		06/19/97
  121	HSSJN64	209126	Uni-ZAP XR	131	738	1	738	70	70	270	1	33	34	61
  		06/19/97
  122	HSVAQ28	209126	Uni-ZAP XR	132	442	1	442	149	149	271	1	24	25	98
  		06/19/97
  123	HSVAY16	209126	Uni-ZAP XR	133	882	1	790	52	52	272	1	30	31	31
  		06/19/97

• Table 1 summarizes the information corresponding to each “Gene No.” described above. The nucleotide sequence identified as “NT SEQ ID NO:X” was assembled from partially homologous (“overlapping”) sequences obtained from the “cDNA clone ID” identified in Table 1 and, in some cases, from additional related DNA clones. The overlapping sequences were assembled into a single contiguous sequence of high redundancy (usually three to five overlapping sequences at each nucleotide position), resulting in a final sequence identified as SEQ ID NO:X. [0912]
• The cDNA Clone ID was deposited on the date and given the corresponding deposit number listed in “ATCC Deposit No:Z and Date.” Some of the deposits contain multiple different clones corresponding to the same gene. “Vector” refers to the type of vector contained in the cDNA Clone ID. [0913]
• “Total NT Seq.” refers to the total number of nucleotides in the contig identified by “Gene No.” The deposited clone may contain all or most of these sequences, reflected by the nucleotide position indicated as “5′ NT of Clone Seq.” and the “3′ NT of Clone Seq.” of SEQ ID NO:X. The nucleotide position of SEQ ID NO:X of the putative start codon (methionine) is identified as “5′ NT of Start Codon.” Similarly, the nucleotide position of SEQ ID NO:X of the predicted signal sequence is identified as “5′ NT of First AA of Signal Pep.”[0914]
• The translated amino acid sequence, beginning with the methionine, is identified as “AA SEQ ID NO:Y,” although other reading frames can also be easily translated using known molecular biology techniques. The polypeptides produced by these alternative open reading frames are specifically contemplated by the present invention. [0915]
• The first and last amino acid position of SEQ ID NO:Y of the predicted signal peptide is identified as “First AA of Sig Pep” and “Last AA of Sig Pep.” The predicted first amino acid position of SEQ ID NO:Y of the secreted portion is identified as “Predicted First AA of Secreted Portion.” Finally, the amino acid position of SEQ ID NO:Y of the last amino acid in the open reading frame is identified as “Last AA of ORF.”[0916]
• SEQ ID NO:X and the translated SEQ ID NO:Y are sufficiently accurate and otherwise suitable for a variety of uses well known in the art and described further below. For instance, SEQ ID NO:X is useful for designing nucleic acid hybridization probes that will detect nucleic acid sequences contained in SEQ ID NO:X or the cDNA contained in the deposited clone. These probes will also hybridize to nucleic acid molecules in biological samples, thereby enabling a variety of forensic and diagnostic methods of the invention. Similarly, polypeptides identified from SEQ ID NO:Y may be used to generate antibodies which bind specifically to the secreted proteins encoded by the cDNA clones identified in Table 1. [0917]
• Nevertheless, DNA sequences generated by sequencing reactions can contain sequencing errors. The errors exist as misidentified nucleotides, or as insertions or deletions of nucleotides in the generated DNA sequence. The erroneously inserted or deleted nucleotides cause frame shifts in the reading frames of the predicted amino acid sequence. In these cases, the predicted amino acid sequence diverges from the actual amino acid sequence, even though the generated DNA sequence may be greater than 99.9% identical to the actual DNA sequence (for example, one base insertion or deletion in an open reading frame of over 1000 bases). [0918]
• Accordingly, for those applications requiring precision in the nucleotide sequence or the amino acid sequence, the present invention provides not only the generated nucleotide sequence identified as SEQ ID NO:X and the predicted translated amino acid sequence identified as SEQ ID NO:Y, but also a sample of plasmid DNA containing a human cDNA of the invention deposited with the ATCC, as set forth in Table 1. The nucleotide sequence of each deposited clone can readily be determined by sequencing the deposited clone in accordance with known methods. The predicted amino acid sequence can then be verified from such deposits. Moreover, the amino acid sequence of the protein encoded by a particular clone can also be directly determined by peptide sequencing or by expressing the protein in a suitable host cell containing the deposited human cDNA, collecting the protein, and determining its sequence. [0919]
• The present invention also relates to the genes corresponding to SEQ ID NO:X, SEQ ID NO:Y, or the deposited clone. The corresponding gene can be isolated in accordance with known methods using the sequence information disclosed herein. Such methods include preparing probes or primers from the disclosed sequence and identifying or amplifying the corresponding gene from appropriate sources of genomic material. [0920]
• Also provided in the present invention are species homologs. Species homologs may be isolated and identified by making suitable probes or primers from the sequences provided herein and screening a suitable nucleic acid source for the desired homologue. [0921]
• The polypeptides of the invention can be prepared in any suitable manner. Such polypeptides include isolated naturally occurring polypeptides, recombinantly produced polypeptides, synthetically produced polypeptides, or polypeptides produced by a combination of these methods. Means for preparing such polypeptides are well understood in the art. [0922]
• The polypeptides may be in the form of the secreted protein, including the mature form. or may be a part of a larger protein, such as a fusion protein (see below). It is often advantageous to include an additional amino acid sequence which contains secretory or leader sequences, pro-sequences, sequences which aid in purification, such as multiple histidine residues, or an additional sequence for stability during recombinant production. [0923]
• The polypeptides of the present invention are preferably provided in an isolated form, and preferably are substantially purified. A recombinantly produced version of a polypeptide, including the secreted polypeptide, can be substantially purified by the one-step method described in Smith and Johnson, Gene 67:31-40 (1988). Polypeptides of the invention also can be purified from natural or recombinant sources using antibodies of the invention raised against the secreted protein in methods which are well known in the art. [0924]
• Signal Sequences [0925]
• Methods for predicting whether a protein has a signal sequence, as well as the cleavage point for that sequence, are available. For instance, the method of McGeoch, Virus Res. 3:271-286 (1985), uses the information from a short N-terminal charged region and a subsequent uncharged region of the complete (uncleaved) protein. The method of von Heinje, Nucleic Acids Res. 14:4683-4690 (1986) uses the information from the residues surrounding the cleavage site, typically residues -13 to +2, where +1 indicates the amino terminus of the secreted protein. The accuracy of predicting the cleavage points of known mammalian secretory proteins for each of these methods is in the range of 75-80%. (von Heinje, supra.) However, the two methods do not always produce the same predicted cleavage point(s) for a given protein. [0926]
• In the present case, the deduced amino acid sequence of the secreted polypeptide was analyzed by a computer program called SignalP (Henrik Nielsen et al., Protein Engineering 10: 1-6 (1997)), which predicts the cellular location of a protein based on the amino acid sequence. As part of this computational prediction of localization, the methods of McGeoch and von Heinje are incorporated. The analysis of the amino acid sequences of the secreted proteins described herein by this program provided the results shown in Table 1. [0927]
• As one of ordinary skill would appreciate, however, cleavage sites sometimes vary from organism to organism and cannot be predicted with absolute certainty. Accordingly, the present invention provides secreted polypeptides having a sequence shown in SEQ ID NO:Y which have an N-terminus beginning within 5 residues (i.e., +or −5 residues) of the predicted cleavage point. Similarly, it is also recognized that in some cases, cleavage of the signal sequence from a secreted protein is not entirely uniform, resulting in more than one secreted species. These polypeptides, and the polynucleotides encoding such polypeptides, are contemplated by the present invention. [0928]
• Moreover, the signal sequence identified by the above analysis may not necessarily predict the naturally occurring signal sequence For example, the naturally occurring signal sequence may be further upstream from the predicted signal sequence. However, it is likely that the predicted signal sequence will be capable of directing the secreted protein to the ER. These polypeptides, and the polynucleotides encoding such polypeptides, are contemplated by the present invention. [0929]
• Polynucleotide and Polypeptide Variants [0930]
• “Variant” refers to a polynucleotide or polypeptide differing from the polynucleotide or polypeptide of the present invention, but retaining essential properties thereof. Generally, variants are overall closely similar, and, in many regions, identical to the polynucleotide or polypeptide of the present invention. [0931]
• By a polynucleotide having a nucleotide sequence at least, for example, 95% “identical” to a reference nucleotide sequence of the present invention, it is intended that the nucleotide sequence of the polynucleotide is identical to the reference sequence except that the polynucleotide sequence may include up to five point mutations per each 100 nucleotides of the reference nucleotide sequence encoding the polypeptide. In other words, to obtain a polynucleotide having a nucleotide sequence at least 95% identical to a reference nucleotide sequence, up to 5% of the nucleotides in the reference sequence may be deleted or substituted with another nucleotide, or a number of nucleotides up to 5% of the total nucleotides in the reference sequence may be inserted into the reference sequence. The query sequence may be an entire sequence shown in Table 1, the ORF (open reading frame), or any fragement specified as described herein. [0932]
• As a practical matter, whether any particular nucleic acid molecule or polypeptide is at least 90%, 95%, 96%, 97%, 98% or 99% identical to a nucleotide sequence of the presence invention can be determined conventionally using known computer programs. A preferred method for determing the best overall match between a query sequence (a sequence of the present invention) and a subject sequence, also referred to as a global sequence alignment, can be determined using the FASTDB computer program based on the algorithm of Brutlag et al. (Comp. App. Biosci. (1990) 6:237-245). In a sequence alignment the query and subject sequences are both DNA sequences. An RNA sequence can be compared by converting U's to T's. The result of said global sequence alignment is in percent identity. Preferred parameters used in a FASTDB alignment of DNA sequences to calculate percent identify are: Matrix=Unitary, k-tuple=4, Mismatch Penalty=1, Joining Penalty=30, Randomization Group Length=0, Cutoff Score=1, Gap Penalty=5, Gap Size Penalty 0.05, Window Size=500 or the lenght of the subject nucleotide sequence, whichever is shorter. [0933]
• If the subject sequence is shorter than the query sequence because of 5′ or 3′ deletions, not because of internal deletions, a manual correction must be made to the results. This is becuase the FASTDB program does not account for 5′ and 3′ truncations of the subject sequence when calculating percent identity. For subject sequences truncated at the 5′ or 3′ ends, relative to the the query sequence, the percent identity is corrected by calculating the number of bases of the query sequence that are 5′ and 3′ of the subject sequence, which are not matched/aligned, as a percent of the total bases of the query sequence. Whether a nucleotide is matched/aligned is determined by results of the FASTDB sequence alignment. This percentage is then subtracted from the percent identity, calculated by the above FASTDB program using the specified parameters, to arrive at a final percent identity score. This corrected score is what is used for the purposes of the present invention. Only bases outside the 5′ and 3′ bases of the subject sequence, as displayed by the FASTDB alignment, which are not matched/aligned with the query sequence, are calculated for the purposes of manually adjusting the percent identity score. [0934]
• For example, a 90 base subject sequence is aligned to a 100 base query sequence to determine percent identity. The deletions occur at the 5′ end of the subject sequence and therefore, the FASTDB alignment does not show a matched/alignement of the first 10 bases at 5′ end. The 10 unpaired bases represent 10% of the sequence (number of bases at the 5′ and 3′ ends not matched/total number of bases in the query sequence) so 10% is subtracted from the percent identity score calculated by the FASTDB program. If the remaining 90 bases were perfectly matched the final percent identity would be 90%. In another example, a 90 base subject sequence is compared with a 100 base query sequence. This time the deletions are internal deletions so that there are no bases on the 5′ or 3′ of the subject sequence which are not matched/aligned with the query. In this case the percent identity calculated by FASTDB is not manually corrected. Once again, only bases 5′ and 3′ of the subject sequence which are not matched/aligned with the query sequnce are manually corrected for. No other manual corrections are to made for the purposes of the present invention. [0935]
• By a polypeptide having an amino acid sequence at least, for example, 95% “identical” to a query amino acid sequence of the present invention, it is intended that the amino acid sequence of the subject polypeptide is identical to the query sequence except that the subject polypeptide sequence may include up to five amino acid alterations per each 100 amino acids of the query amino acid sequence. In other words, to obtain a polypeptide having an amino acid sequence at least 95% identical to a query amino acid sequence, up to 5% of the amino acid residues in the subject sequence may be inserted, deleted, (indels) or substituted with another amino acid. These alterations of the reference sequence may occur at the amino or carboxy terminal positions of the reference amino acid sequence or anywhere between those terminal positions, interspersed either individually among residues in the reference sequence or in one or more contiguous groups within the reference sequence. [0936]
• As a practical matter, whether any particular polypeptide is at least 90%, 95%, 96%, 97%, 98% or 99% identical to, for instance, the amino acid sequences shown in Table 1 or to the amino acid sequence encoded by deposited DNA clone can be determined conventionally using known computer programs. A preferred method for determing the best overall match between a query sequence (a sequence of the present invention) and a subject sequence, also referred to as a global sequence alignment, can be determined using the FASTDB computer program based on the algorithm of Brutlag et al. (Comp. App. Biosci. (1990) 6:237-245). In a sequence alignment the query and subject sequences are either both nucleotide sequences or both amino acid sequences. The result of said global sequence alignment is in percent identity. Preferred parameters used in a FASTDB amino acid alignment are: Matrix=PAM 0, k-tuple=2, Mismatch Penalty=1, Joining Penalty=20, Randomization Group Length=0, Cutoff Score=1, Window Size=sequence length, Gap Penalty=5, Gap Size Penalty=0.05, Window Size=500 or the length of the subject amino acid sequence, whichever is shorter. [0937]
• If the subject sequence is shorter than the query sequence due to N- or C-terminal deletions, not because of internal deletions, a manual correction must be made to the results. This is becuase the FASTDB program does not account for N- and C-terminal truncations of the subject sequence when calculating global percent identity. For subject sequences truncated at the N- and C-termini, relative to the the query sequence, the percent identity is corrected by calculating the number of residues of the query sequence that are N- and C-terminal of the subject sequence, which are not matched/aligned with a corresponding subject residue, as a percent of the total bases of the query sequence. Whether a residue is matched/aligned is determined by results of the FASTDB sequence alignment. This percentage is then subtracted from the percent identity, calculated by the above FASTDB program using the specified parameters, to arrive at a final percent identity score. This final percent identity score is what is used for the purposes of the present invention. Only residues to the N- and C-termini of the subject sequence, which are not matched/aligned with the query sequence, are considered for the purposes of manually adjusting the percent identity score. That is, only query residue positions outside the farthest N- and C-terminal residues of the subject sequence. [0938]
• For example, a 90 amino acid residue subject sequence is aligned with a 100 residue query sequence to determine percent identity. The deletion occurs at the N-terminus of the subject sequence and therefore, the FASTDB alignment does not show a matching/alignment of the first 10 residues at the N-terminus. The 10 unpaired residues represent 10% of the sequence (number of residues at the N- and C-termini not matched/total number of residues in the query sequence) so 10% is subtracted from the percent identity score calculated by the FASTDB program. If the remaining 90 residues were perfectly matched the final percent identity would be 90%. In another example, a 90 residue subject sequence is compared with a 100 residue query sequence. This time the deletions are internal deletions so there are no residues at the N- or C-termini of the subject sequence which are not matched/aligned with the query. In this case the percent identity calculated by FASTDB is not manually corrected. Once again, only residue positions outside the N- and C-terminal ends of the subject sequence, as displayed in the FASTDB alignment, which are not matched/aligned with the query sequnce are manually corrected for. No other manual corrections are to made for the purposes of the present invention. [0939]
• The variants may contain alterations in the coding regions, non-coding regions, or both. Especially preferred are polynucleotide variants containing alterations which produce silent substitutions, additions, or deletions, but do not alter the properties or activities of the encoded polypeptide. Nucleotide variants produced by silent substitutions due to the degeneracy of the genetic code are preferred. Moreover, variants in which 5-10, 1-5, or 1-2 amino acids are substituted, deleted, or added in any combination are also preferred. Polynucleotide variants can be produced for a variety of reasons, e.g., to optimize codon expression for a particular host (change codons in the human mRNA to those preferred by a bacterial host such as [0940] E. coli).
• Naturally occurring variants are called “allelic variants,” and refer to one of several alternate forms of a gene occupying a given locus on a chromosome of an organism. (Genes II, Lewin, B., ed., John Wiley & Sons, New York (1985).) These allelic variants can vary at either the polynucleotide and/or polypeptide level. Alternatively, non-naturally occurring variants may be produced by mutagenesis techniques or by direct synthesis. [0941]
• Using known methods of protein engineering and recombinant DNA technology, variants may be generated to improve or alter the characteristics of the polypeptides of the present invention. For instance, one or more amino acids can be deleted from the N-terminus or C-terminus of the secreted protein without substantial loss of biological function. The authors of Ron et al., J. Biol. Chem. 268: 2984-2988 (1993), reported variant KGF proteins having heparin binding activity even after deleting 3, 8, or 27 amino-terminal amino acid residues. Similarly, Interferon gamma exhibited up to ten times higher activity after deleting 8-10 amino acid residues from the carboxy terminus of this protein. (Dobeli et al., J. Biotechnology 7:199-216 (1988).) [0942]
• Moreover, ample evidence demonstrates that variants often retain a biological activity similar to that of the naturally occurring protein. For example, Gayle and coworkers (J. Biol. Chem 268:22105-22111 (1993)) conducted extensive mutational analysis of human cytokine IL-1a. They used random mutagenesis to generate over 3,500 individual IL-1a mutants that averaged 2.5 amino acid changes per variant over the entire length of the molecule. Multiple mutations were examined at every possible amino acid position. The investigators found that “[m]ost of the molecule could be altered with little effect on either [binding or biological activity].” (See, Abstract.) In fact, only 23 unique amino acid sequences, out of more than 3,500 nucleotide sequences examined, produced a protein that significantly differed in activity from wild-type. [0943]
• Furthermore, even if deleting one or more amino acids from the N-terminus or C-terminus of a polypeptide results in modification or loss of one or more biological functions, other biological activities may still be retained. For example, the ability of a deletion variant to induce and/or to bind antibodies which recognize the secreted form will likely be retained when less than the majority of the residues of the secreted form are removed from the N-terminus or C-terminus. Whether a particular polypeptide lacking N- or C-terminal residues of a protein retains such immunogenic activities can readily be determined by routine methods described herein and otherwise known in the art. [0944]
• Thus, the invention further includes polypeptide variants which show substantial biological activity. Such variants include deletions, insertions, inversions, repeats, and substitutions selected according to general rules known in the art so as have little effect on activity. For example, guidance concerning how to make phenotypically silent amino acid substitutions is provided in Bowie, J. U. et al., Science 247:1306-1310 (1990), wherein the authors indicate that there are two main strategies for studying the tolerance of an amino acid sequence to change. [0945]
• The first strategy exploits the tolerance of amino acid substitutions by natural selection during the process of evolution. By comparing amino acid sequences in different species, conserved amino acids can be identified. These conserved amino acids are likely important for protein function. In contrast, the amino acid positions where substitutions have been tolerated by natural selection indicates that these positions are not critical for protein function. Thus, positions tolerating amino acid substitution could be modified while still maintaining biological activity of the protein. [0946]
• The second strategy uses genetic engineering to introduce amino acid changes at specific positions of a cloned gene to identify regions critical for protein function. For example, site directed mutagenesis or alanine-scanning mutagenesis (introduction of single alanine mutations at every residue in the molecule) can be used. (Cunningham and Wells, Science 244:1081-1085 (1989).) The resulting mutant molecules can then be tested for biological activity. [0947]
• As the authors state, these two strategies have revealed that proteins are surprisingly tolerant of amino acid substitutions. The authors further indicate which amino acid changes are likely to be permissive at certain amino acid positions in the protein. For example, most buried (within the tertiary structure of the protein) amino acid residues require nonpolar side chains, whereas few features of surface side chains are generally conserved. Moreover, tolerated conservative amino acid substitutions involve replacement of the aliphatic or hydrophobic amino acids Ala, Val, Leu and Ile; replacement of the hydroxyl residues Ser and Thr; replacement of the acidic residues Asp and Glu; replacement of the amide residues Asn and Gln, replacement of the basic residues Lys, Arg, and His; replacement of the aromatic residues Phe, Tyr, and Trp, and replacement of the small-sized amino acids Ala, Ser, Thr, Met, and Gly. [0948]
• Besides conservative amino acid substitution, variants of the present invention include (i) substitutions with one or more of the non-conserved amino acid residues, where the substituted amino acid residues may or may not be one encoded by the genetic code, or (ii) substitution with one or more of amino acid residues having a substituent group, or (iii) fusion of the mature polypeptide with another compound, such as a compound to increase the stability and/or solubility of the polypeptide (for example, polyethylene glycol), or (iv) fusion of the polypeptide with additional amino acids, such as an IgG Fc fusion region peptide, or leader or secretory sequence, or a sequence facilitating purification. Such variant polypeptides are deemed to be within the scope of those skilled in the art from the teachings herein. [0949]
• For example, polypeptide variants containing amino acid substitutions of charged amino acids with other charged or neutral amino acids may produce proteins with improved characteristics, such as less aggregation. Aggregation of pharmaceutical formulations both reduces activity and increases clearance due to the aggregate's immunogenic activity. (Pinckard et al., Clin. Exp. Immunol. 2:331-340 (1967); Robbins et al., Diabetes 36: 838-845 (1987); Cleland et al., Crit. Rev. Therapeutic Drug Carrier Systems 10:307-377 (1993).) [0950]
• Polynucleotide and Polypeptide Fragments [0951]
• In the present invention, a “polynucleotide fragment” refers to a short polynucleotide having a nucleic acid sequence contained in the deposited clone or shown in SEQ ID NO:X. The short nucleotide fragments are preferably at least about 15 nt, and more preferably at least about 20 nt, still more preferably at least about 30 nt, and even more preferably, at least about 40 nt in length. A fragment “at least 20 nt in length,” for example, is intended to include 20 or more contiguous bases from the cDNA sequence contained in the deposited clone or the nucleotide sequence shown in SEQ ID NO:X. These nucleotide fragments are useful as diagnostic probes and primers as discussed herein. Of course, larger fragments (e.g., 50, 150, 500, 600, 2000 nucleotides) are preferred. [0952]
• Moreover, representative examples of polynucleotide fragments of the invention, include, for example, fragments having a sequence from about nucleotide number 1-50, 51-100, 101-150, 151-200, 201-250, 251-300, 301-350, 351-400, 401-450, 451-500, 501-550, 551-600, 651-700, 701-750, 751-800, 800-850, 851-900, 901-950, 951-1000, 1001-1050, 1051-1100, 1101-1150, 1151-1200, 1201-1250, 1251-1300, 1301-1350, 1351-1400, 1401-1450, 1451-1500, 1501-1550, 1551-1600, 1601-1650, 1651-1700, 1701-1750, 1751-1800, 1801-1850, 1851-1900, 1901-1950, 1951-2000, or 2001 to the end of SEQ ID NO:X or the cDNA contained in the deposited clone. In this context “about” includes the particularly recited ranges, larger or smaller by several (5, 4, 3, 2, or 1) nucleotides, at either terminus or at both termini. Preferably, these fragments encode a polypeptide which has biological activity. More preferably, these polynucleotides can be used as probes or primers as discussed herein. [0953]
• In the present invention, a “polypeptide fragment” refers to a short amino acid sequence contained in SEQ ID NO:Y or encoded by the cDNA contained in the deposited clone. Protein fragments may be “free-standing,” or comprised within a larger polypeptide of which the fragment forms a part or region, most preferably as a single continuous region. Representative examples of polypeptide fragments of the invention, include, for example, fragments from about amino acid number 1-20, 21-40, 41-60, 61-80, 81-100, 102-120, 121-140, 141-160, or 161 to the end of the coding region. Moreover, polypeptide fragments can be about 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, or 150 amino acids in length. In this context “about” includes the particularly recited ranges, larger or smaller by several (5, 4, 3, 2, or 1) amino acids, at either extreme or at both extremes. [0954]
• Preferred polypeptide fragments include the secreted protein as well as the mature form. Further preferred polypeptide fragments include the secreted protein or the mature form having a continuous series of deleted residues from the amino or the carboxy terminus, or both. For example, any number of amino acids, ranging from 1-60, can be deleted from the amino terminus of either the secreted polypeptide or the mature form. Similarly, any number of amino acids, ranging from 1-30, can be deleted from the carboxy terminus of the secreted protein or mature form. Furthermore, any combination of the above amino and carboxy terminus deletions are preferred. Similarly, polynucleotide fragments encoding these polypeptide fragments are also preferred. [0955]
• Also preferred are polypeptide and polynucleotide fragments characterized by structural or functional domains, such as fragments that comprise alpha-helix and alpha-helix forming regions, beta-sheet and beta-sheet-forming regions, turn and turn-forming regions, coil and coil-forming regions, hydrophilic regions, hydrophobic regions, alpha amphipathic regions, beta amphipathic regions, flexible regions, surface-forming regions, substrate binding region, and high antigenic index regions. Polypeptide fragments of SEQ ID NO:Y falling within conserved domains are specifically contemplated by the present invention. Moreover, polynucleotide fragments encoding these domains are also contemplated. [0956]
• Other preferred fragments are biologically active fragments. Biologically active fragments are those exhibiting activity similar, but not necessarily identical, to an activity of the polypeptide of the present invention. The biological activity of the fragments may include an improved desired activity, or a decreased undesirable activity. [0957]
• Epitopes & Antibodies [0958]
• In the present invention, “epitopes” refer to polypeptide fragments having antigenic or immunogenic activity in an animal, especially in a human. A preferred embodiment of the present invention relates to a polypeptide fragment comprising an epitope, as well as the polynucleotide encoding this fragment. A region of a protein molecule to which an antibody can bind is defined as an “antigenic epitope.” In contrast, an “immunogenic epitope” is defined as a part of a protein that elicits an antibody response. (See, for instance, Geysen et al., Proc. Natl. Acad. Sci. USA 81:3998-4002 (1983).) [0959]
• Fragments which function as epitopes may be produced by any conventional means. (See, e.g., Houghten, R. A., Proc. Natl. Acad. Sci. USA 82:5131-5135 (1985) further described in U.S. Pat. No. 4,631,211.) [0960]
• In the present invention, antigenic epitopes preferably contain a sequence of at least seven, more preferably at least nine, and most preferably between about 15 to about 30 amino acids. Antigenic epitopes are useful to raise antibodies, including monoclonal antibodies, that specifically bind the epitope. (See, for instance, Wilson et al., Cell 37:767-778 (1984); Sutcliffe, J. G. et al., Science 219:660-666 (1983).) [0961]
• Similarly, immunogenic epitopes can be used to induce antibodies according to methods well known in the art. (See, for instance, Sutcliffe et al., supra; Wilson et al., supra; Chow, M. et al., Proc. Natl. Acad. Sci. USA 82:910-914; and Bittle, F. J. et al., J. Gen. Virol. 66:2347-2354 (1985).) A preferred immunogenic epitope includes the secreted protein. The immunogenic epitopes may be presented together with a carrier protein, such as an albumin, to an animal system (such as rabbit or mouse) or, if it is long enough (at least about 25 amino acids), without a carrier. However, immunogenic epitopes comprising as few as 8 to 10 amino acids have been shown to be sufficient to raise antibodies capable of binding to, at the very least, linear epitopes in a denatured polypeptide (e.g., in Western blotting.) [0962]
• As used herein, the term “antibody” (Ab) or “monoclonal antibody” (Mab) is meant to include intact molecules as well as antibody fragments (such as, for example, Fab and F(ab′)2 fragments) which are capable of specifically binding to protein. Fab and F(ab′)2 fragments lack the Fc fragment of intact antibody, clear more rapidly from the circulation, and may have less non-specific tissue binding than an intact antibody. (Wahl et al., J. Nucl. Med. 24:316-325 (1983).) Thus, these fragments are preferred, as well as the products of a FAB or other immunoglobulin expression library. [0963]
• Moreover, antibodies of the present invention include chimeric, single chain, and humanized antibodies. [0964]
• Fusion Proteins [0965]
• Any polypeptide of the present invention can be used to generate fusion proteins. For example, the polypeptide of the present invention, when fused to a second protein, can be used as an antigenic tag. Antibodies raised against the polypeptide of the present invention can be used to indirectly detect the second protein by binding to the polypeptide. Moreover, because secreted proteins target cellular locations based on trafficking signals, the polypeptides of the present invention can be used as targeting molecules once fused to other proteins. [0966]
• Examples of domains that can be fused to polypeptides of the present invention include not only heterologous signal sequences, but also other heterologous functional regions. The fusion does not necessarily need to be direct, but may occur through linker sequences. [0967]
• Moreover, fusion proteins may also be engineered to improve characteristics of the polypeptide of the present invention. For instance, a region of additional amino acids, particularly charged amino acids, may be added to the N-terminus of the polypeptide to improve stability and persistence during purification from the host cell or subsequent handling and storage. Also, peptide moieties may be added to the polypeptide to facilitate purification. Such regions may be removed prior to final preparation of the polypeptide. The addition of peptide moieties to facilitate handling of polypeptides are familiar and routine techniques in the art. [0968]
• Moreover, polypeptides of the present invention, including fragments, and specifically epitopes, can be combined with parts of the constant domain of immunoglobulins (IgG), resulting in chimeric polypeptides. These fusion proteins facilitate purification and show an increased half-life in vivo. One reported example describes chimeric proteins consisting of the first two domains of the human CD4-polypeptide and various domains of the constant regions of the heavy or light chains of mammalian immunoglobulins. (EP A 394,827; Traunecker et al., Nature 331:84-86 (1988).) Fusion proteins having disulfide-linked dimeric structures (due to the IgG) can also be more efficient in binding and neutralizing other molecules, than the monomeric secreted protein or protein fragment alone. (Fountoulakis et al., J. Biochem. 270:3958-3964 (1995).) [0969]
• Similarly, EP-A-O 464 533 (Canadian counterpart 2045869) discloses fusion proteins comprising various portions of constant region of immunoglobulin molecules together with another human protein or part thereof. In many cases, the Fc part in a fusion protein is beneficial in therapy and diagnosis, and thus can result in, for example, improved pharmacokinetic properties. (EP-A 0232 262.) Alternatively, deleting the Fc part after the fusion protein has been expressed, detected, and purified, would be desired. For example, the Fc portion may hinder therapy and diagnosis if the fusion protein is used as an antigen for immunizations. In drug discovery, for example, human proteins, such as hIL-5, have been fused with Fc portions for the purpose of high-throughput screening assays to identify antagonists of hIL-5. (See, D. Bennett et al., J. Molecular Recognition 8:52-58 (1995); K. Johanson et al., J. Biol. Chem. 270:9459-9471 (1995).) [0970]
• Moreover, the polypeptides of the present invention can be fused to marker sequences, such as a peptide which facilitates purification of the fused polypeptide. In preferred embodiments, the marker amino acid sequence is a hexa-histidine peptide, such as the tag provided in a pQE vector (QIAGEN, Inc., 9259 Eton Avenue, Chatsworth, Calif., 91311), among others, many of which are commercially available. As described in Gentz et al., Proc. Natl. Acad. Sci. USA 86:821-824 (1989), for instance, hexa-histidine provides for convenient purification of the fusion protein. Another peptide tag useful for purification, the “HA” tag, corresponds to an epitope derived from the influenza hemagglutinin protein. (Wilson et al., Cell 37:767 (1984).) [0971]
• Thus, any of these above fusions can be engineered using the polynucleotides or the polypeptides of the present invention. [0972]
• Vectors, Host Cells, and Protein Production [0973]
• The present invention also relates to vectors containing the polynucleotide of the present invention, host cells, and the production of polypeptides by recombinant techniques. The vector may be, for example, a phage, plasmid, viral, or retroviral vector. Retroviral vectors may be replication competent or replication defective. In the latter case, viral propagation generally will occur only in complementing host cells. [0974]
• The polynucleotides may be joined to a vector containing a selectable marker for propagation in a host. Generally, a plasmid vector is introduced in a precipitate, such as a calcium phosphate precipitate, or in a complex with a charged lipid. If the vector is a virus, it may be packaged in vitro using an appropriate packaging cell line and then transduced into host cells. [0975]
• The polynucleotide insert should be operatively linked to an appropriate promoter, such as the phage lambda PL promoter, the [0976] E. coli lac, trp, phoA and tac promoters, the SV40 early and late promoters and promoters of retroviral LTRs, to name a few. Other suitable promoters will be known to the skilled artisan. The expression constructs will further contain sites for transcription initiation, termination, and, in the transcribed region, a ribosome binding site for translation. The coding portion of the transcripts expressed by the constructs will preferably include a translation initiating codon at the beginning and a termination codon (UAA, UGA or UAG) appropriately positioned at the end of the polypeptide to be translated.
• As indicated, the expression vectors will preferably include at least one selectable marker. Such markers include dihydrofolate reductase, G418 or neomycin resistance for eukaryotic cell culture and tetracycline, kanamycin or ampicillin resistance genes for culturing in [0977] E. coli and other bacteria. Representative examples of appropriate hosts include, but are not limited to, bacterial cells, such as E. coli, Streptomyces and Salmonella typhimurium cells; fungal cells, such as yeast cells; insect cells such as Drosophila S2 and Spodoptera Sf9 cells; animal cells such as CHO, COS, 293, and Bowes melanoma cells; and plant cells. Appropriate culture mediums and conditions for the above-described host cells are known in the art.
• Among vectors preferred for use in bacteria include pQE70, pQE60 and pQE-9, available from QIAGEN, Inc.; pBluescript vectors, Phagescript vectors, pNH8A, pNH16a, pNH18A, pNH46A, available from Stratagene Cloning Systems, Inc.; and ptrc99a, pKK223-3, pKK233-3, pDR540, pRIT5 available from Pharmacia Biotech, Inc. Among preferred eukaryotic vectors are pWLNEO, pSV2CAT, pOG44, pXT1 and pSG available from Stratagene; and pSVK3, pBPV, pMSG and pSVL available from Pharmacia. Other suitable vectors will be readily apparent to the skilled artisan. [0978]
• Introduction of the construct into the host cell can be effected by calcium phosphate transfection, DEAE-dextran mediated transfection, cationic lipid-mediated transfection, electroporation, transduction, infection, or other methods. Such methods are described in many standard laboratory manuals, such as Davis et al., Basic Methods In Molecular Biology (1986). It is specifically contemplated that the polypeptides of the present invention may in fact be expressed by a host cell lacking a recombinant vector. [0979]
• A polypeptide of this invention can be recovered and purified from recombinant cell cultures by well-known methods including ammonium sulfate or ethanol precipitation, acid extraction, anion or cation exchange chromatography, phosphocellufose chromatography, hydrophobic interaction chromatography, affinity chromatography, hydroxylapatite chromatography and lectin chromatography. Most preferably, high performance liquid chromatography (“HPLC”) is employed for purification. [0980]
• Polypeptides of the present invention, and preferably the secreted form, can also be recovered from: products purified from natural sources, including bodily fluids, tissues and cells, whether directly isolated or cultured; products of chemical synthetic procedures; and products produced by recombinant techniques from a prokaryotic or eukaryotic host, including, for example, bacterial, yeast, higher plant, insect, and mammalian cells. Depending upon the host employed in a recombinant production procedure, the polypeptides of the present invention may be glycosylated or may be non-glycosylated. In addition, polypeptides of the invention may also include an initial modified methionine residue, in some cases as a result of host-mediated processes. Thus, it is well known in the art that the N-terminal methionine encoded by the translation initiation codon generally is removed with high efficiency from any protein after translation in all eukaryotic cells. While the N-terminal methionine on most proteins also is efficiently removed in most prokaryotes, for some proteins, this prokaryotic removal process is inefficient, depending on the nature of the amino acid to which the N-terminal methionine is covalently linked. [0981]
• Uses of the Polynucleotides [0982]
• Each of the polynucleotides identified herein can be used in numerous ways as reagents. The following description should be considered exemplary and utilizes known techniques. [0983]
• The polynucleotides of the present invention are useful for chromosome identification. There exists an ongoing need to identify new chromosome markers, since few chromosome marking reagents, based on actual sequence data (repeat polymorphisms), are presently available. Each polynucleotide of the present invention can be used as a chromosome marker. [0984]
• Briefly, sequences can be mapped to chromosomes by preparing PCR primers (preferably 15-25 bp) from the sequences shown in SEQ ID NO:X. Primers can be selected using computer analysis so that primers do not span more than one predicted exon in the genomic DNA. These primers are then used for PCR, screening of somatic cell hybrids containing individual human chromosomes. Only those hybrids containing the human gene corresponding to the SEQ ID NO:X will yield an amplified fragment. [0985]
• Similarly, somatic hybrids provide a rapid method of PCR mapping the polynucleotides to particular chromosomes. Three or more clones can be assigned per day using a single thermal cycler. Moreover, sublocalization of the polynucleotides can be achieved with panels of specific chromosome fragments. Other gene mapping-strategies that can be used include in situ hybridization, prescreening with labeled flow-sorted chromosomes, and preselection by hybridization to construct chromosome specific-cDNA libraries. [0986]
• Precise chromosomal location of the polynucleotides can also be achieved using fluorescence in situ hybridization (FISH) of a metaphase chromosomal spread. This technique uses polynucleotides as short as 500 or 600 bases; however, polynucleotides 2,000-4,000 bp are preferred. For a review of this technique, see Verma et al., “Human Chromosomes: a Manual of Basic Techniques,” Pergamon Press, New York (1988). [0987]
• For chromosome mapping, the polynucleotides can be used individually (to mark a single chromosome or a single site on that chromosome) or in panels (for marking multiple sites and/or multiple chromosomes). Preferred polynucleotides correspond to the noncoding regions of the cDNAs because the coding sequences are more likely conserved within gene families, thus increasing the chance of cross hybridization during chromosomal mapping. [0988]
• Once a polynucleotide has been mapped to a precise chromosomal location, the physical position of the polynucleotide can be used in linkage analysis. Linkage analysis establishes coinheritance between a chromosomal location and presentation of a particular disease. (Disease mapping data are found, for example, in V. McKusick, Mendelian Inheritance in Man (available on line through Johns Hopkins University Welch Medical Library).) Assuming 1 megabase mapping resolution and one gene per 20 kb, a cDNA precisely localized to a chromosomal region associated with the disease could be one of 50-500 potential causative genes. [0989]
• Thus, once coinheritance is established, differences in the polynucleotide and the corresponding gene between affected and unaffected individuals can be examined. First, visible structural alterations in the chromosomes, such as deletions or translocations, are examined in chromosome spreads or by PCR. If no structural alterations exist, the presence of point mutations are ascertained. Mutations observed in some or all affected individuals, but not in normal individuals, indicates that the mutation may cause the disease. However, complete sequencing of the polypeptide and the corresponding gene from several normal individuals is required to distinguish the mutation from a polymorphism. If a new polymorphism is identified, this polymorphic polypeptide can be used for further linkage analysis. [0990]
• Furthermore, increased or decreased expression of the gene in affected individuals as compared to unaffected individuals can be assessed using polynucleotides of the present invention. Any of these alterations (altered expression, chromosomal rearrangement, or mutation) can be used as a diagnostic or prognostic marker. [0991]
• In addition to the foregoing, a polynucleotide can be used to control gene expression through triple helix formation or antisense DNA or RNA. Both methods rely on binding of the polynucleotide to DNA or RNA. For these techniques, preferred polynucleotides are usually 20 to 40 bases in length and complementary to either the region of the gene involved in transcription (triple helix—see Lee et al., Nucl. Acids Res. 6:3073 (1979); Cooney et al., Science 241:456 (1988); and Dervan et al., Science 251:1360 (1991) ) or to the mRNA itself (antisense—Okano, J. Neurochem. 56:560 (1991); Oligodeoxy-nucleotides as Antisense Inhibitors of Gene Expression, CRC Press, Boca Raton, Fla. (1988).) Triple helix formation optimally results in a shut-off of RNA transcription from DNA, while antisense RNA hybridization blocks translation of an mRNA molecule into polypeptide. Both techniques are effective in model systems, and the information disclosed herein can be used to design antisense or triple helix polynucleotides in an effort to treat disease. [0992]
• Polynucleotides of the present invention are also useful in gene therapy. One goal of gene therapy is to insert a normal gene into an organism having a defective gene, in an effort to correct the genetic defect. The polynucleotides disclosed in the present invention offer a means of targeting such genetic defects in a highly accurate manner. Another goal is to insert a new gene that was not present in the host genome, thereby producing a new trait in the host cell. [0993]
• The polynucleotides are also useful for identifying individuals from minute biological samples. The United States military, for example, is considering the use of restriction fragment length polymorphism (RFLP) for identification of its personnel. In this technique, an individual's genomic DNA is digested with one or more restriction enzymes, and probed on a Southern blot to yield unique bands for identifying personnel. This method does not suffer from the current limitations of “Dog Tags” which can be lost, switched, or stolen, making positive identification difficult. The polynucleotides of the present invention can be used as additional DNA markers for RFLP. [0994]
• The polynucleotides of the present invention can also be used as an alternative to RFLP, by determining the actual base-by-base DNA sequence of selected portions of an individual's genome. These sequences can be used to prepare PCR primers for amplifying and isolating such selected DNA, which can then be sequenced. Using this technique, individuals can be identified because each individual will have a unique set of DNA sequences. Once an unique ID database is established for an individual, positive identification of that individual, living or dead, can be made from extremely small tissue samples. [0995]
• Forensic biology also benefits from using DNA-based identification techniques as disclosed herein. DNA sequences taken from very small biological samples such as tissues, e.g., hair or skin, or body fluids, e.g., blood, saliva, semen, etc., can be amplified using PCR. In one prior art technique, gene sequences amplified from polymorphic loci, such as DQa class II HLA gene, are used in forensic biology to identify individuals. (Erlich, H., PCR Technology, Freeman and Co. (1992).) Once these specific polymorphic loci are amplified, they are digested with one or more restriction enzymes, yielding an identifying set of bands on a Southern blot probed with DNA corresponding to the DQa class II HLA gene. Similarly, polynucleotides of the present invention can be used as polymorphic markers for forensic purposes. [0996]
• There is also a need for reagents capable of identifying the source of a particular tissue. Such need arises, for example, in forensics when presented with tissue of unknown origin. Appropriate reagents can comprise, for example, DNA probes or primers specific to particular tissue prepared from the sequences of the present invention. Panels of such reagents can identify tissue by species and/or by organ type. In a similar fashion, these reagents can be used to screen tissue cultures for contamination. [0997]
• In the very least, the polynucleotides of the present invention can be used as molecular weight markers on Southern gels, as diagnostic probes for the presence of a specific mRNA in a particular cell type, as a probe to “subtract-out” known sequences in the process of discovering novel polynucleotides, for selecting and making oligomers for attachment to a “gene chip” or other support, to raise anti-DNA antibodies using DNA immunization techniques, and as an antigen to elicit an immune response. [0998]
• Uses of the Polypeptides [0999]
• Each of the polypeptides identified herein can be used in numerous ways. The following description should be considered exemplary and utilizes known techniques. [1000]
• A polypeptide of the present invention can be used to assay protein levels in a biological sample using antibody-based techniques. For example, protein expression in tissues can be studied with classical immunohistological methods. (Jalkanen, M., et al., J. Cell. Biol. 101:976-985 (1985); Jalkanen, M., et al., J. Cell . Biol. 105:3087-3096 (1987).) Other antibody-based methods useful for detecting protein gene expression include immunoassays, such as the enzyme linked immunosorbent assay (ELISA) and the radioimmunoassay (RIA). Suitable antibody assay labels are known in the art and include enzyme labels, such as, glucose oxidase, and radioisotopes, such as iodine (1251, 1211), carbon (14C), sulfur (35S), tritium (3H), indium (112In), and technetium (99 mTc), and fluorescent labels, such as fluorescein and rhodamine, and biotin. [1001]
• In addition to assaying secreted protein levels in a biological sample, proteins can also be detected in vivo by imaging. Antibody labels or markers for in vivo imaging of protein include those detectable by X-radiography, NMR or ESR. For X-radiography, suitable labels include radioisotopes such as barium or cesium, which emit detectable radiation but are not overtly harmful to the subject. Suitable markers for NMR and ESR include those with a detectable characteristic spin, such as deuterium, which may be incorporated into the antibody by labeling of nutrients for the relevant hybridoma. [1002]
• A protein-specific antibody or antibody fragment which has been labeled with an appropriate detectable imaging moiety, such as a radioisotope (for example, 131I, 112In, 99 mTc), a radio-opaque substance, or a material detectable by nuclear magnetic resonance, is introduced (for example, parenterally, subcutaneously, or intraperitoneally) into the mammal. It will be understood in the art that the size of the subject and the imaging system used will determine the quantity of imaging moiety needed to produce diagnostic images. In the case of a radioisotope moiety, for a human subject, the quantity of radioactivity injected will normally range from about 5 to 20 millicuries of 99 mTc. The labeled antibody or antibody fragment will then preferentially accumulate at the location of cells which contain the specific protein. In vivo tumor imaging is described in S. W. Burchiel et al., “Immunopharmacokinetics of Radiolabeled Antibodies and Their Fragments.” (Chapter 13 in Tumor Imaging: The Radiochemical Detection of Cancer, S. W. Burchiel and B. A. Rhodes, eds., Masson Publishing Inc. (1982).) [1003]
• Thus, the invention provides a diagnostic method of a disorder, which involves (a) assaying the expression of a polypeptide of the present invention in cells or body fluid of an individual; (b) comparing the level of gene expression with a standard gene expression level, whereby an increase or decrease in the assayed polypeptide gene expression level compared to the standard expression level is indicative of a disorder. [1004]
• Moreover, polypeptides of the present invention can be used to treat disease. For example, patients can be administered a polypeptide of the present invention in an effort to replace absent or decreased levels of the polypeptide (e.g., insulin), to supplement absent or decreased levels of a different polypeptide (e.g., hemoglobin S for hemoglobin B), to inhibit the activity of a polypeptide (e.g., an oncogene), to activate the activity of a polypeptide (e.g., by binding to a receptor), to reduce the activity of a membrane bound receptor by competing with it for free ligand (e.g., soluble TNF receptors used in reducing inflammation), or to bring about a desired response (e.g., blood vessel growth). [1005]
• Similarly, antibodies directed to a polypeptide of the present invention can also be used to treat disease. For example, administration of an antibody directed to a polypeptide of the present invention can bind and reduce overproduction of the polypeptide. Similarly, administration of an antibody can activate the polypeptide, such as by binding to a polypeptide bound to a membrane (receptor). [1006]
• At the very least, the polypeptides of the present invention can be used as molecular weight markers on SDS-PAGE gels or on molecular sieve gel filtration columns using methods well known to those of skill in the art. Polypeptides can also be used to raise antibodies, which in turn are used to measure protein expression from a recombinant cell, as a way of assessing transformation of the host cell. Moreover, the polypeptides of the present invention can be used to test the following biological activities. [1007]
• Biological Activities [1008]
• The polynucleotides and polypeptides of the present invention can be used in assays to test for one or more biological activities. If these polynucleotides and polypeptides do exhibit activity in a particular assay, it is likely that these molecules may be involved in the diseases associated with the biological activity. Thus, the polynucleotides and polypeptides could be used to treat the associated disease. [1009]
• Immune Activity [1010]
• A polypeptide or polynucleotide of the present invention may be useful in treating deficiencies or disorders of the immune system, by activating or inhibiting the proliferation, differentiation, or mobilization (chemotaxis) of immune cells. Immune cells develop through a process called hematopoiesis, producing myeloid (platelets, red blood cells, neutrophils, and macrophages) and lymphoid (B and T lymphocytes) cells from pluripotent stem cells. The etiology of these immune deficiencies or disorders may be genetic, somatic, such as cancer or some autoimmune disorders, acquired (e.g., by chemotherapy or toxins), or infectious. Moreover, a polynucleotide or polypeptide of the present invention can be used as a marker or detector of a particular immune system disease or disorder. [1011]
• A polynucleotide or polypeptide of the present invention may be useful in treating or detecting deficiencies or disorders of hematopoietic cells. A polypeptide or polynucleotide of the present invention could be used to increase differentiation and proliferation of hematopoietic cells, including the pluripotent.stem cells, in an effort to treat those disorders associated with a decrease in certain (or many) types hematopoietic cells. Examples of immunologic deficiency syndromes include, but are not limited to: blood protein disorders (e.g. agammaglobulinemia, dysgammaglobulinemia), ataxia telangiectasia, common variable immunodeficiency, Digeorge Syndrome, HIV infection, HTLV-BLV infection, leukocyte adhesion deficiency syndrome, lymphopenia, phagocyte bactericidal dysfunction, severe combined immunodeficiency (SCIDs), Wiskott-Aldrich Disorder, anemia, thrombocytopenia, or hemoglobinuria. [1012]
• Moreover, a polypeptide or polynucleotide of the present invention could also be used to modulate hemostatic (the stopping of bleeding) or thrombolytic activity (clot formation). For example, by increasing hemostatic or thrombolytic activity, a polynucleotide or polypeptide of the present invention could be used to treat blood coagulation disorders (e.g., afibrinogenemia, factor deficiencies), blood platelet disorders (e.g. thrombocytopenia), or wounds resulting from trauma, surgery, or other causes. Alternatively, a polynucleotide or polypeptide of the present invention that can decrease hemostatic or thrombolytic activity could be used to inhibit or dissolve clotting. These molecules could be important in the treatment of heart attacks (infarction), strokes, or scarring. [1013]
• A polynucleotide or polypeptide of the present invention may also be useful in treating or detecting autoimmune disorders. Many autoimmune disorders result from inappropriate recognition of self as foreign material by immune cells. This inappropriate recognition results in an immune response leading to the destruction of the host tissue. Therefore, the administration of a polypeptide or polynucleotide of the present invention that inhibits an immune response, particularly the proliferation, differentiation, or chemotaxis of T-cells, may be an effective therapy in preventing autoimmune disorders. [1014]
• Examples of autoimmune disorders that can be treated or detected by the present invention include, but are not limited to: Addison's Disease, hemolytic anemia, antiphospholipid syndrome, rheumatoid arthritis, dermatitis, allergic encephalomyelitis, glomerulonephritis, Goodpasture's Syndrome, Graves' Disease, Multiple Sclerosis, Myasthenia Gravis, Neuritis, Ophthalmia, Bullous Pemphigoid, Pemphigus, Polyendocrinopathies, Purpura, Reiter's Disease, Stiff-Man Syndrome, Autoimmune Thyroiditis, Systemic Lupus Erythematosus, Autoimmune Pulmonary Inflammation, Guillain-Barre Syndrome, insulin dependent diabetes mellitis, and autoimmune inflammatory eye disease. [1015]
• Similarly, allergic reactions and conditions, such as asthma (particularly allergic asthma) or other respiratory problems, may also be treated by a polypeptide or polynucleotide of the present invention. Moreover, these molecules can be used to treat anaphylaxis, hypersensitivity to an antigenic molecule, or blood group incompatibility. [1016]
• A polynucleotide or polypeptide of the present invention may also be used to treat and/or prevent organ rejection or graft-versus-host disease (GVHD). Organ rejection occurs by host immune cell destruction of the transplanted tissue through an immune response. Similarly, an immune response is also involved in GVHD, but, in this case, the foreign transplanted immune cells destroy the host tissues. The administration of a polypeptide or polynucleotide of the present invention that inhibits an immune response, particularly the proliferation, differentiation, or chemotaxis of T-cells, may be an effective therapy in preventing organ rejection or GVHD. [1017]
• Similarly, a polypeptide, or polynucleotide of the present invention may also be used to modulate inflammation. For example, the polypeptide or polynucleotide may inhibit the proliferation and differentiation of cells involved in an inflammatory response. These molecules can be used to treat inflammatory conditions, both chronic and acute conditions, including inflammation associated with infection (e.g., septic shock, sepsis, or systemic inflammatory response syndrome (SIRS)), ischemia-reperfusion injury, endotoxin lethality, arthritis, complement-mediated hyperacute rejection, nephritis, cytokine or chemokine induced lung injury, inflammatory bowel disease, Crohn's disease, or resulting from over production of cytokines (e.g., TNF or IL-1.) [1018]
• Hyperproliferative Disorders [1019]
• A polypeptide or polynucleotide can be used to treat or detect hyperproliferative disorders, including neoplasms. A polypeptide or polynucleotide of the present invention may inhibit the proliferation of the disorder through direct or indirect interactions. Alternatively, a polypeptide or polynucleotide of the present invention may proliferate other cells which can inhibit the hyperproliferative disorder. [1020]
• For example, by increasing an immune response, particularly increasing antigenic qualities of the hyperproliferative disorder or by proliferating, differentiating, or mobilizing T-cells, hyperproliferative disorders can be treated. This immune response may be increased by either enhancing an existing immune response, or by initiating a new immune response. Alternatively, decreasing an immune response may also be a method of treating hyperproliferative disorders, such as a chemotherapeutic agent. [1021]
• Examples of hyperproliferative disorders that can be treated or detected by a polynucleotide or polypeptide of the present invention include, but are not limited to neoplasms located in the: abdomen, bone, breast, digestive system, liver, pancreas, peritoneum, endocrine glands (adrenal, parathyroid, pituitary, testicles, ovary, thymus, thyroid), eye, head and neck, nervous (central and peripheral), lymphatic system, pelvic, skin, soft tissue, spleen, thoracic, and urogenital. [1022]
• Similarly, other hyperproliferative disorders can also be treated or detected by a polynucleotide or polypeptide of the present invention. Examples of such hyperproliferative disorders include, but are not limited to: hypergammaglobulinemia, lymphoproliferative disorders, paraproteinemias, purpura, sarcoidosis, Sezary Syndrome, Waldenstron's Macroglobulinemia, Gaucher's Disease, histiocytosis, and any other hyperproliferative disease, besides neoplasia, located in an organ system listed above. [1023]
• Infectious Disease [1024]
• A polypeptide or polynucleotide of the present invention can be used to treat or detect infectious agents. For example, by increasing the immune response, particularly increasing the proliferation and differentiation of B and/or T cells, infectious diseases may be treated. The immune response may be increased by either enhancing an existing immune response, or by initiating a new immune response. Alternatively, the polypeptide or polynucleotide of the present invention may also directly inhibit the infectious agent, without necessarily eliciting an immune response. [1025]
• Viruses are one example of an infectious agent that can cause disease or symptoms that can be treated or detected by a polynucleotide or polypeptide of the present invention. Examples of viruses, include, but are not limited to the following DNA and RNA viral families: Arbovirus, Adenoviridae, Arenaviridae, Arterivirus, Birnaviridae, Bunyaviridae, Caliciviridae, Circoviridae, Coronaviridae, Flaviviridae, Hepadnaviridae (Hepatitis), Herpesviridae (such as, Cytomegalovirus, Herpes Simplex, Herpes Zoster), Mononegavirus (e.g., Paramyxoviridae, Morbillivirus, Rhabdoviridae), Orthomyxoviridae (e.g., Influenza), Papovaviridae, Parvoviridae, Picomaviridae, Poxviridae (such as Smallpox or Vaccinia), Reoviridae (e.g., Rotavirus), Retroviridae (HTLV-I, HTLV-II, Lentivirus), and Togaviridae (e.g., Rubivirus). Viruses falling within these families can cause a variety of diseases or symptoms, including, but not limited to: arthritis, bronchiollitis, encephalitis, eye infections (e.g., conjunctivitis, keratitis), chronic fatigue syndrome, hepatitis (A, B, C, E, Chronic Active, Delta), meningitis, opportunistic infections (e.g., AIDS), pneumonia, Burkitt's Lymphoma, chickenpox, hemorrhagic fever, Measles, Mumps, Parainfluenza, Rabies, the common cold, Polio, leukemia, Rubella, sexually transmitted-diseases, skin diseases (e.g.; Kaposi's, warts), and viremia. A polypeptide or polynucleotide of the present invention can be used to treat or detect any of these symptoms or diseases. [1026]
• Similarly, bacterial or fungal agents that can cause disease or symptoms and that can be treated or detected by a polynucleotide or polypeptide of the present invention include, but not limited to, the following Gram-Negative and Gram-positive bacterial families and fungi: Actinomycetales (e.g., Corynebacterium, Mycobacterium, Norcardia), Aspergillosis, Bacillaceae (e.g., Anthrax, Clostridium), Bacteroidaceae, Blastomycosis, Bordetella, Borrelia, Brucellosis, Candidiasis, Campylobacter, Coccidioidomycosis, Cryptococcosis, Dermatocycoses, Enterobacteriaceae (Kiebsiella, Salmonella, Serratia, Yersinia), Erysipelothrix, Helicobacter, Legionellosis, Leptospirosis, Listeria, Mycoplasmatales, Neisseriaceae (e.g., Acinetobacter, Gonorrhea, Menigococcal), Pasteurellacea Infections (e.g., Actinobacillus, Heamophilus, Pasteurella), Pseudomonas, Rickettsiaceae. Chlamydiaceae, Syphilis, and Staphylococcal. These bacterial or fungal families can cause the following diseases or symptoms, including, but not limited to: bacteremia, endocarditis, eye infections (conjunctivitis, tuberculosis, uveitis), gingivitis, opportunistic infections (e.g., AIDS related infections), paronychia, prosthesis-related infections, Reiter's Disease, respiratory tract infections, such as Whooping Cough or Empyema, sepsis, Lyme Disease, Cat-Scratch Disease, Dysentery, Paratyphoid Fever, food poisoning, Typhoid, pneumonia, Gonorrhea, meningitis, Chlamydia, Syphilis, Diphtheria, Leprosy, Paratuberculosis, Tuberculosis, Lupus, Botulism, gangrene, tetanus, impetigo, Rheumatic Fever, Scarlet Fever, sexually transmitted diseases, skin diseases (e.g., cellulitis, dermatocycoses), toxemia, urinary tract infections, wound infections. A polypeptide or polynucleotide of the present invention can be used to treat or detect any of these symptoms or diseases. [1027]
• Moreover, parasitic agents causing disease or symptoms that can be treated or detected by a polynucleotide or polypeptide of the present invention include, but not limited to, the following families: Amebiasis, Babesiosis, Coccidiosis, Cryptosporidiosis, Dientamoebiasis, Dourine, Ectoparasitic, Giardiasis, Helminthiasis, Leishmaniasis, Theileriasis, Toxoplasmosis, Trypanosomiasis, and Trichomonas. These parasites can cause a variety of diseases or symptoms, including, but not limited to: Scabies, Trombiculiasis, eye infections, intestinal disease (e.g., dysentery, giardiasis), liver disease, lung disease, opportunistic infections (e.g., AIDS related), Malaria, pregnancy complications, and toxoplasmosis. A polypeptide or polynucleotide of the present invention can be used to treat or detect any of these symptoms or diseases. [1028]
• Preferably, treatment using a polypeptide or polynucleotide of the present invention could either be by administering an effective amount of a polypeptide to the patient, or by removing cells from the patient, supplying the cells with a polynucleotide of the present invention, and returning the engineered cells to the patient (ex vivo therapy). Moreover, the polypeptide or polynucleotide of the present invention can be used as an antigen in a vaccine to raise an immune response against infectious disease. [1029]
• Regeneration [1030]
• A polynucleotide or polypeptide of the present invention can be used to differentiate, proliferate, and attract cells, leading to the regeneration of tissues. (See, Science 276:59-87 (1997).) The regeneration of tissues could be used to repair, replace, or protect tissue damaged by congenital defects, trauma (wounds, burns, incisions, or ulcers), age, disease (e.g. osteoporosis, osteocarthritis, periodontal disease, liver failure), surgery, including cosmetic plastic surgery, fibrosis, reperfusion injury, or systemic cytokine damage. [1031]
• Tissues that could be regenerated using the present invention include organs (e.g., pancreas, liver, intestine, kidney, skin, endothelium), muscle (smooth, skeletal or cardiac), vascular (including vascular endothelium), nervous, hematopoietic, and skeletal (bone, cartilage, tendon, and ligament) tissue. Preferably, regeneration occurs without or decreased scarring. Regeneration also may include angiogenesis. [1032]
• Moreover, a polynucleotide or polypeptide of the present invention may increase regeneration of tissues difficult to heal. For example, increased tendon/ligament regeneration would quicken recovery time after damage. A polynucleotide or polypeptide of the present invention could also be used prophylactically in an effort to avoid damage. Specific diseases that could be treated include of tendinitis, carpal tunnel syndrome, and other tendon or ligament defects. A further example of tissue regeneration of non-healing wounds includes pressure ulcers, ulcers associated with vascular insufficiency, surgical, and traumatic wounds. [1033]
• Similarly, nerve and brain tissue could also be regenerated by using a polynucleotide or polypeptide of the present invention to proliferate and differentiate nerve cells. Diseases that could be treated using this method include central and peripheral nervous system diseases, neuropathies, or mechanical and traumatic disorders (e.g., spinal cord disorders, head trauma, cerebrovascular disease, and stoke). Specifically, diseases associated with peripheral nerve injuries, peripheral neuropathy (e.g., resulting from chemotherapy or other medical therapies), localized neuropathies, and central nervous system diseases (e.g., Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and Shy-Drager syndrome), could all be treated using the polynucleotide or polypeptide of the present invention. [1034]
• Chemotaxis [1035]
• A polynucleotide or polypeptide of the present invention may have chemotaxis activity. A chemotaxic molecule attracts or mobilizes cells (e.g., monocytes, fibroblasts, neutrophils, T-cells, mast cells, eosinophils, epithelial and/or endothelial cells) to a particular site in the body, such as inflammation, infection, or site of hyperproliferation. The mobilized cells can then fight off and/or heal the particular trauma or abnormality. [1036]
• A polynucleotide or polypeptide of the present invention may increase chemotaxic activity of particular cells. These chemotactic molecules can then be used to treat inflammation, infection, hyperproliferative disorders, or any immune system disorder by increasing the number of cells targeted to a particular location in the body. For example, chemotaxic molecules can be used to treat wounds and other trauma to tissues by attracting immune cells to the injured location. Chemotactic molecules of the present invention can also attract fibroblasts, which can be used to treat wounds. [1037]
• It is also contemplated that a polynucleotide or polypeptide of the present invention may inhibit chemotactic activity. These molecules could also be used to treat disorders. Thus, a polynucleotide or polypeptide of the present invention could be used as an inhibitor of chemotaxis. [1038]
• Binding Activity [1039]
• A polypeptide of the present invention may be used to screen for molecules that bind to the polypeptide or for molecules to which the polypeptide binds. The binding of the polypeptide and the molecule may activate (agonist), increase, inhibit (antagonist), or decrease activity of the polypeptide or the molecule bound. Examples of such molecules include antibodies, oligonucleotides, proteins (e.g., receptors),or small molecules. [1040]
• Preferably, the molecule is closely related to the natural ligand of the polypeptide, e.g., a fragment of the ligand, or a natural substrate, a ligand, a structural or functional mimetic. (See, Coligan et al., Current Protocols in Immunology 1(2):Chapter 5 (1991).) Similarly, the molecule can be closely related to the natural receptor to which the polypeptide binds, or at least, a fragment of the receptor capable of being bound by the polypeptide (e.g., active site). In either case, the molecule can be rationally designed using known techniques. [1041]
• Preferably, the screening for these molecules involves producing appropriate cells which express the polypeptide, either as a secreted protein or on the cell membrane. Preferred cells include cells from mammals, yeast, Drosophila, or [1042] E. coli. Cells expressing the polypeptide (or cell membrane containing the expressed polypeptide) are then preferably contacted with a test compound potentially containing the molecule to observe binding, stimulation, or inhibition of activity of either the polypeptide or the molecule.
• The assay may simply test binding of a candidate compound to the polypeptide, wherein binding is detected by a label, or in an assay involving competition with a labeled competitor. Further, the assay may test whether the candidate compound results in a signal generated by binding to the polypeptide. [1043]
• Alternatively, the assay can be carried out using cell-free preparations, polypeptide/molecule affixed to a solid support, chemical libraries, or natural product mixtures. The assay may also simply comprise the steps of mixing a candidate compound with a solution containing a polypeptide, measuring polypeptide/molecule activity or binding, and comparing the polypeptide/molecule activity or binding to a standard. [1044]
• Preferably, an ELISA assay can measure polypeptide level or activity in a sample (e.g., biological sample) using a monoclonal or polyclonal antibody. The antibody can measure polypeptide level or activity by either binding, directly or indirectly, to the polypeptide or by competing with the polypeptide for a substrate. [1045]
• All of these above assays can be used as diagnostic or prognostic markers. The molecules discovered using these assays can be used to treat disease or to bring about a particular result in a patient (e.g., blood vessel growth) by activating or inhibiting the polypeptide/molecule. Moreover, the assays can discover agents which may inhibit or enhance the production of the polypeptide from suitably manipulated cells or tissues. [1046]
• Therefore, the invention includes a method of identifying compounds which bind to a polypeptide of the invention comprising the steps of: (a) incubating a candidate binding compound with a polypeptide of the invention; and (b) determining if binding has occurred. Moreover, the invention includes a method of identifying agonists/antagonists comprising the steps of: (a) incubating a candidate compound with a polypeptide of the invention, (b) assaying a biological activity, and (b) determining if a biological activity of the polypeptide has been altered. [1047]
• Other Activities [1048]
• A polypeptide or polynucleotide of the present invention may also increase or decrease the differentiation or proliferation of embryonic stem cells, besides, as discussed above, hematopoietic lineage. [1049]
• A polypeptide or polynucleotide of the present invention may also be used to modulate mammalian characteristics, such as body height, weight, hair color, eye color, skin, percentage of adipose tissue, pigmentation, size, and shape (e.g., cosmetic surgery). Similarly, a polypeptide or polynucleotide of the present invention may be used to modulate mammalian metabolism affecting catabolism, anabolism, processing, utilization, and storage of energy. [1050]
• A polypeptide or polynucleotide of the present invention may be used to change a mammal's mental state or physical state by influencing biorhythms, caricadic rhythms, depression (including depressive disorders), tendency for violence, tolerance for pain, reproductive capabilities (preferably by Activin or Inhibin-like activity), hormonal or endocrine levels, appetite, libido, memory, stress, or other cognitive qualities. [1051]
• A polypeptide or polynucleotide of the present invention may also be used as a food additive or preservative, such as to increase or decrease storage capabilities, fat content, lipid, protein, carbohydrate, vitamins, minerals, cofactors or other nutritional components. [1052]
• Other Preferred Embodiments [1053]
• Other preferred embodiments of the claimed invention include an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to a sequence of at least about 50 contiguous nucleotides in the nucleotide sequence of SEQ ID NO:X wherein X is any integer as defined in Table 1. [1054]
• Also preferred is a nucleic acid molecule wherein said sequence of contiguous nucleotides is included in the nucleotide sequence of SEQ ID NO:X in the range of positions beginning with the nucleotide at about the position of the 5′ Nucleotide of the Clone Sequence and ending with the nucleotide at about the position of the 3′ Nucleotide of the Clone Sequence as defined for SEQ ID NO:X in Table 1. [1055]
• Also preferred is a nucleic acid molecule wherein said sequence of contiguous nucleotides is included in the nucleotide sequence of SEQ ID NO:X in the range of positions beginning with the nucleotide at about the position of the 5′ Nucleotide of the Start Codon and ending with the nucleotide at about the position of the 3′ Nucleotide of the Clone Sequence as defined for SEQ ID NO:X in Table 1. [1056]
• Similarly preferred is a nucleic acid molecule wherein said sequence of contiguous nucleotides is included in the nucleotide sequence of SEQ ID NO:X in the range of positions beginning with the nucleotide at about the position of the 5′ Nucleotide of the First Amino Acid of the Signal Peptide and ending with the nucleotide at about the position of the 3′ Nucleotide of the Clone Sequence as defined for SEQ ID NO:X in Table 1. [1057]
• Also preferred is an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to a sequence of at least about 150 contiguous nucleotides in the nucleotide sequence of SEQ ID NO:X. [1058]
• Further preferred is an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to a sequence of at least about 500 contiguous nucleotides in the nucleotide sequence of SEQ ID NO:X. [1059]
• A further preferred embodiment is a nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to the nucleotide sequence of SEQ ID NO:X beginning with the nucleotide at about the position of the 5′ Nucleotide of the First Amino Acid of the Signal Peptide and ending with the nucleotide at about the position of the 3′ Nucleotide of the Clone Sequence as defined for SEQ ID NO:X in Table 1. [1060]
• A further preferred embodiment is an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to the complete nucleotide sequence of SEQ ID NO:X. [1061]
• Also preferred is an isolated nucleic acid molecule which hybridizes under stringent hybridization conditions to a nucleic acid molecule, wherein said nucleic acid molecule which hybridizes does not hybridize under stringent hybridization conditions to a nucleic acid molecule having a nucleotide sequence consisting of only A residues or of only T residues. [1062]
• Also preferred is a composition of matter comprising a DNA molecule which comprises a human cDNA clone identified by a cDNA Clone Identifier in Table 1, which DNA molecule is contained in the material deposited with the American Type Culture Collection and given the ATCC Deposit Number shown in Table 1 for said cDNA Clone Identifier. [1063]
• Also preferred is an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to a sequence of at least 50 contiguous nucleotides in the nucleotide sequence of a human cDNA clone identified by a cDNA Clone Identifier in Table 1, which DNA molecule is contained in the deposit given the ATCC Deposit Number shown in Table 1. [1064]
• Also preferred is an isolated nucleic acid molecule, wherein said sequence of at least 50 contiguous nucleotides is included in the nucleotide sequence of the complete open reading frame sequence encoded by said human cDNA clone. [1065]
• Also preferred is an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to sequence of at least 150 contiguous nucleotides in the nucleotide sequence encoded by said human cDNA clone. [1066]
• A further preferred embodiment is an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to sequence of at least 500 contiguous nucleotides in the nucleotide sequence encoded by said human cDNA clone. [1067]
• A further preferred embodiment is an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to the complete nucleotide sequence encoded by said human cDNA clone. [1068]
• A further preferred embodiment is a method for detecting in a biological sample a nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to a sequence of at least 50 contiguous nucleotides in a sequence selected from the group consisting of: a nucleotide sequence of SEQ ID NO:X wherein X is any integer as defined in Table 1; and a nucleotide sequence encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1; which method comprises a step of comparing a nucleotide sequence of at least one nucleic acid molecule in said sample with a sequence selected from said group and determining whether the sequence of said nucleic acid molecule in said sample is at least 95% identical to said selected sequence. [1069]
• Also preferred is the above method wherein said step of comparing sequences comprises determining the extent of nucleic acid hybridization between nucleic acid molecules in said sample and a nucleic acid molecule comprising said sequence selected from said group. Similarly, also preferred is the above method wherein said step of comparing sequences is performed by comparing the nucleotide sequence determined from a nucleic acid molecule in said sample with said sequence selected from said group. The nucleic acid molecules can comprise DNA molecules or RNA molecules. [1070]
• A further preferred embodiment is a method for identifying the species, tissue or cell type of a biological sample which method comprises a step of detecting nucleic acid molecules in said sample, if any, comprising a nucleotide sequence that is at least 95% identical to a sequence of at least 50 contiguous nucleotides in a sequence selected from the group consisting of: a nucleotide sequence of SEQ ID NO:X wherein X is any integer as defined in Table 1; and a nucleotide sequence encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1. [1071]
• The method for identifying the species, tissue or cell type of a biological sample can comprise a step of detecting nucleic acid molecules comprising a nucleotide sequence in a panel of at least two nucleotide sequences, wherein at least one sequence in said panel is at least 95% identical to a sequence of at least 50 contiguous nucleotides in a sequence selected from said group. [1072]
• Also preferred is a method for diagnosing in a subject a pathological condition associated with abnormal structure or expression of a gene encoding a secreted protein identified in Table 1, which method comprises a step of detecting in a biological sample obtained from said subject nucleic acid molecules, if any, comprising a nucleotide sequence that is at least 95% identical to a sequence of at least 50 contiguous nucleotides in a sequence selected from the group consisting of: a nucleotide sequence of SEQ ID NO:X wherein X is any integer as defined in Table 1; and a nucleotide sequence encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1. [1073]
• The method for diagnosing a pathological condition can comprise a step of detecting nucleic acid molecules comprising a nucleotide sequence in a panel of at least two nucleotide sequences, wherein at least one sequence in said panel is at least 95% identical to a sequence of at least 50 contiguous nucleotides in a sequence selected from said group. [1074]
• Also preferred is a composition of matter comprising isolated nucleic acid molecules wherein the nucleotide sequences of said nucleic acid molecules comprise a panel of at least two nucleotide sequences, wherein at least one sequence in said panel is at least 95% identical to a sequence of at least 50 contiguous nucleotides in a sequence selected from the group consisting of: a nucleotide sequence of SEQ ID NO:X wherein X is any integer as defined in Table 1; and a nucleotide sequence encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1. The nucleic acid molecules can comprise DNA molecules or RNA molecules. [1075]
• Also preferred is an isolated polypeptide comprising an amino acid sequence at least 90% identical to a sequence of at least about 10 contiguous amino acids in the amino acid sequence of SEQ ID NO:Y wherein Y is any integer as defined in Table 1. [1076]
• Also preferred is a polypeptide, wherein said sequence of contiguous amino acids is included in the amino acid sequence of SEQ ID NO:Y in the range of positions beginning with the residue at about the position of the First Amino Acid of the Secreted Portion and ending with the residue at about the Last Amino Acid of the Open Reading Frame as set forth for SEQ ID NO:Y in Table 1. [1077]
• Also preferred is an isolated polypeptide comprising an amino acid sequence at least 95% identical to a sequence of at least about 30 contiguous amino acids in the amino acid sequence of SEQ ID NO:Y. [1078]
• Further preferred is an isolated polypeptide comprising an amino acid sequence at least 95% identical to a sequence of at least about 100 contiguous amino acids in the amino acid sequence of SEQ ID NO:Y. [1079]
• Further preferred is an isolated polypeptide comprising an amino acid sequence at least 95% identical to the complete amino acid sequence of SEQ ID NO:Y. [1080]
• Further preferred is an isolated polypeptide comprising an amino acid sequence at least 90% identical to a sequence of at least about 10 contiguous amino acids in the complete amino acid sequence of a secreted protein encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1. [1081]
• Also preferred is a polypeptide wherein said sequence of contiguous amino acids is included in the amino acid sequence of a secreted portion of the secreted protein encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1. [1082]
• Also preferred is an isolated polypeptide comprising an amino acid sequence at least 95% identical to a sequence of at least about 30 contiguous amino acids in the amino acid sequence of the secreted portion of the protein encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1. [1083]
• Also preferred is an isolated polypeptide comprising an amino acid sequence at least 95% identical to a sequence of at least about 100 contiguous amino acids in the amino acid sequence of the secreted portion of the protein encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1. [1084]
• Also preferred is an isolated polypeptide comprising an amino acid sequence at least 95% identical to the amino acid sequence of the secreted portion of the protein encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1. [1085]
• Further preferred is an isolated antibody which binds specifically to a polypeptide comprising an amino acid sequence that is at least 90% identical to a sequence of at least 10 contiguous amino acids in a sequence selected from the group consisting of: an amino acid sequence of SEQ ID NO:Y wherein Y is any integer as defined in Table 1; and a complete amino acid sequence of a protein encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1. [1086]
• Further preferred is a method for detecting in a biological sample a polypeptide comprising an amino acid sequence which is at least 90% identical to a sequence of at least 10 contiguous amino acids in a sequence selected from the group consisting of: an amino acid sequence of SEQ ID NO:Y wherein Y is any integer as defined in Table 1; and a complete amino acid sequence of a protein encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1; which method comprises a step of comparing an amino acid sequence of at least one polypeptide molecule in said sample with a sequence selected from said group and determining whether the sequence of said polypeptide molecule in said sample is at least 90% identical to said sequence of at least 10 contiguous amino acids. [1087]
• Also preferred is the above method wherein said step of comparing an amino acid sequence of at least one polypeptide molecule in said sample with a sequence selected from said group comprises determining the extent of specific binding of polypeptides in said sample to an antibody which binds specifically to a polypeptide comprising an amino acid sequence that is at least 90% identical to a sequence of at least 10 contiguous amino acids in a sequence selected from the group consisting of: an amino acid sequence of SEQ ID NO:Y wherein Y is any integer as defined in Table 1; and a complete amino acid sequence of a protein encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1. [1088]
• Also preferred is the above method wherein said step of comparing sequences is performed by comparing the amino acid sequence determined from a polypeptide molecule in said sample with said sequence selected from said group. [1089]
• Also preferred is a method for identifying the species, tissue or cell type of a biological sample which method comprises a step of detecting polypeptide molecules in said sample, if any, comprising an amino acid sequence that is at least 90% identical to a sequence of at least 10 contiguous amino acids in a sequence selected from the group consisting of: an amino acid sequence of SEQ ID NO:Y wherein Y is any integer as defined in Table 1; and a complete amino acid sequence of a secreted protein encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1. [1090]
• Also preferred is the above method for identifying the species, tissue or cell type of a biological sample, which method comprises a step of detecting polypeptide molecules comprising an amino acid sequence in a panel of at least two amino acid sequences, wherein at least one sequence in said panel is at least 90% identical to a sequence of at least 10 contiguous amino acids in a sequence selected from the above group. [1091]
• Also preferred is a method for diagnosing in a subject a pathological condition associated with abnormal structure or expression of a gene encoding a secreted protein identified in Table 1, which method comprises a step of detecting in a biological sample obtained from said subject polypeptide molecules comprising an amino acid sequence in a panel of at least two amino acid sequences, wherein at least one sequence in said panel is at least 90% identical to a sequence of at least 10 contiguous amino acids in a sequence selected from the group consisting of: an amino acid sequence of SEQ ID NO:Y wherein Y is any integer as defined in Table 1; and a complete amino acid sequence of a secreted protein encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1. [1092]
• In any of these methods, the step of detecting said polypeptide molecules includes using an antibody. [1093]
• Also preferred is an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to a nucleotide sequence encoding a polypeptide wherein said polypeptide comprises an amino acid sequence that is at least 90% identical to a sequence of at least 10 contiguous amino acids in a sequence selected from the group consisting of: an amino acid sequence of SEQ ID NO:Y wherein Y is any integer as defined in Table 1; and a complete amino acid sequence of a secreted protein encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1. [1094]
• Also preferred is an isolated nucleic acid molecule, wherein said nucleotide sequence encoding a polypeptide has been optimized for expression of said polypeptide in a prokaryotic host. [1095]
• Also preferred is an isolated nucleic acid molecule, wherein said polypeptide comprises an amino acid sequence selected from the group consisting of: an amino acid sequence of SEQ ID NO:Y wherein Y is any integer as defined in Table 1; and a complete amino acid sequence of a secreted protein encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1. [1096]
• Further preferred is a method of making a recombinant vector comprising inserting any of the above isolated nucleic acid molecule into a vector. Also preferred is the recombinant vector produced by this method. Also preferred is a method of making a recombinant host cell comprising introducing the vector into a host cell, as well as the recombinant host cell produced by this method. [1097]
• Also preferred is a method of making an isolated polypeptide comprising culturing this recombinant host cell under conditions such that said polypeptide is expressed and recovering said polypeptide. Also preferred is this method of making an isolated polypeptide, wherein said recombinant host cell is a eukaryotic cell and said polypeptide is a secreted portion of a human secreted protein comprising an amino acid sequence selected from the group consisting of: an amino acid sequence of SEQ ID NO:Y beginning with the residue at the position of the First Amino Acid of the Secreted Portion of SEQ ID NO:Y wherein Y is an integer set forth in Table 1 and said position of the First Amino Acid of the Secreted Portion of SEQ ID NO:Y is defined in Table 1; and an amino acid sequence of a secreted portion of a protein encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1. The isolated polypeptide produced by this method is also preferred. [1098]
• Also preferred is a method of treatment of an individual in need of an increased level of a secreted protein activity, which method comprises administering to such an individual a pharmaceutical composition comprising an amount of an isolated polypeptide, polynucleotide, or antibody of the claimed invention effective to increase the level of said protein activity in said individual. [1099]
• Having generally described the invention, the same will be more readily understood by reference to the following examples, which are provided by way of illustration and are not intended as limiting. [1100]
EXAMPLES Example 1 Isolation of a Selected cDNA Clone From the Deposited Sample
• Each cDNA clone in a cited ATCC deposit is contained in a plasmid vector. Table 1 identifies the vectors used to construct the cDNA library from which each clone was isolated. In many cases, the vector used to construct the library is a phage vector from which a plasmid has been excised. The table immediately below correlates the related plasmid for each phage vector used in constructing the cDNA library. For example, where a particular clone is identified in Table 1 as being isolated in the vector “Lambda Zap,” the corresponding deposited clone is in “pBluescript.” [1101]

  Vector Used to Construct Library	Corresponding Deposited Plasmid
  Lambda Zap	pBluescript (pBS)
  Uni-Zap XR	pBluescript (pBS)
  Zap Express	pBK
  lafmid BA	plafmid BA
  pSport1	pSport1
  pCMVSport 2.0	pCMVSport 2.0
  pCMVSport 3.0	pCMVSport 3.0
  pCR ®2.1	pCR ®2.1

• Vectors Lambda Zap (U.S. Pat. Nos. 5,128,256 and 5,286,636), Uni-Zap XR (U.S. Pat. Nos. 5,128, 256 and 5,286,636), Zap Express (U.S. Pat. Nos. 5,128,256 and 5,286,636), pBluescript (pBS) (Short, J. M. et al., Nucleic Acids Res. 16:7583-7600 (1988); Alting-Mees, M. A. and Short, J. M., Nucleic Acids Res. 17:9494 (1989)) and pBK (Alting-Mees, M. A. et al., Strategies 5:58-61 (1992)) are commercially available from Stratagene Cloning Systems, Inc., 11011 N. Torrey Pines Road, La Jolla, Calif., 92037. pBS contains an ampicillin resistance gene and pBK contains a neomycin resistance gene. Both can be transformed into [1102] E. coli strain XL-1 Blue, also available from Stratagene. pBS comes in 4 forms SK+, SK−, KS+ and KS. The S and K refers to the orientation of the polylinker to the T7 and T3 primer sequences which flank the polylinker region (“S” is for SacI and “K” is for KpnI which are the first sites on each respective end of the linker). “+” or “−” refer to the orientation of the f1 origin of replication (“ori”), such that in one orientation, single stranded rescue initiated from the f1 ori generates sense strand DNA and in the other, antisense.
• Vectors pSport1, pCMVSport 2.0 and pCMVSport 3.0, were obtained from Life Technologies, Inc., P. O. Box 6009, Gaithersburg, Md. 20897. All Sport vectors contain an ampicillin resistance gene and may be transformed into [1103] E. coli strain DH10B, also available from Life Technologies. (See, for instance, Gruber, C. E., et al., Focus 15:59 (1993).) Vector lafmid BA (Bento Soares, Columbia University, NY) contains an ampicillin resistance gene and can be transformed into E. coli strain XL-1 Blue. Vector pCR®2. 1, which is available from Invitrogen, 1600 Faraday Avenue, Carlsbad, Calif. 92008, contains an ampicillin resistance gene and may be transformed into E. coli strain DH10B, available from Life Technologies. (See, for instance, Clark, J. M., Nuc. Acids Res. 16:9677-9686 (1988) and Mead, D. et al., Bio/Technology 9: (1991).) Preferably, a polynucleotide of the present invention does not comprise the phage vector sequences identified for the particular clone in Table 1, as well as the corresponding plasmid vector sequences designated above.
• The deposited material in the sample assigned the ATCC Deposit Number cited in Table 1 for any given cDNA clone also may contain one or more additional plasmids, each comprising a cDNA clone different from that given clone. Thus, deposits sharing the same ATCC Deposit Number contain at least a plasmid for each cDNA clone identified in Table 1. Typically, each ATCC deposit sample cited in Table 1- comprises a mixture of approximately equal amounts (by weight) of about 50 plasmid DNAs, each containing a different cDNA clone; but such a deposit sample may include plasmids for more or less than 50 cDNA clones, up to about 500 cDNA clones. [1104]
• Two approaches can be used to isolate a particular clone from the deposited sample of plasmid DNAs cited for that clone in Table 1. First, a plasmid is directly isolated by screening the clones using a polynucleotide probe corresponding to SEQ ID NO:X. [1105]
• Particularly, a specific polynucleotide with 30-40 nucleotides is synthesized using an Applied Biosystems DNA synthesizer according to the sequence reported. The oligonucleotide is labeled, for instance, with [1106] ³²P-γ-ATP using T4 polynucleotide kinase and purified according to routine methods. (E.g., Maniatis et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Press, Cold Spring, N.Y. (1982).) The plasmid mixture is transformed into a suitable host, as indicated above (such as XL-1 Blue (Stratagene)) using techniques known to those of skill in the art, such as those provided by the vector supplier or in related publications or patents cited above. The transformants are plated on 1.5% agar plates (containing the appropriate selection agent, e.g., ampicillin) to a density of about 150 transformants (colonies) per plate. These plates are screened using Nylon membranes according to routine methods for bacterial colony screening (e.g., Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd Edit., (1989), Cold Spring Harbor Laboratory Press, pages 1.93 to 1.104), or other techniques known to those of skill in the art.
• Alternatively, two primers of 17-20 nucleotides derived from both ends of the SEQ ID NO:X (i.e., within the region of SEQ ID NO:X bounded by the 5′ NT and the 3′ NT of the clone defined in Table 1) are synthesized and used to amplify the desired cDNA using the deposited cDNA plasmid as a template. The polymerase chain reaction is carried out under routine conditions, for instance, in 25 μl of reaction mixture with 0.5 ug of the above cDNA template. A convenient reaction mixture is 1.5-5 mM MgCl[1107] ₂, 0.01% (w/v) gelatin, 20 μM each of dATP, dCTP, dGTP, dTTP, 25 pmol of each primer and 0.25 Unit of Taq polymerase. Thirty five cycles of PCR (denaturation at 94° C. for 1 min; annealing at 55° C. for 1 min; elongation at 72° C. for 1 min) are performed with a Perkin-Elmer Cetus automated thermal cycler. The amplified product is analyzed by agarose gel electrophoresis and the DNA band with expected molecular weight is excised and purified. The PCR product is verified to be the selected sequence by subcloning and sequencing the DNA product.
• Several methods are available for the identification of the 5′ or 3′ non-coding portions of a gene which may not be present in the deposited clone. These methods include but are not limited to, filter probing, clone enrichment using specific probes, and protocols similar or identical to 5′ and 3′ “RACE” protocols which are well known in the art. For instance, a method similar to 5′ RACE is available for generating the missing 5′ end of a desired full-length transcript. (Fromont-Racine et al., Nucleic Acids Res. 21(7):1683-1684 (1993).) [1108]
• Briefly, a specific RNA oligonucleotide is ligated to the 5′ ends of a population of RNA presumably containing full-length gene RNA transcripts. A primer set containing a primer specific to the ligated RNA oligonucleotide and a primer specific to a known sequence of the gene of interest is used to PCR amplify the 5′ portion of the desired full-length gene. This amplified product may then be sequenced and used to generate the full length gene. [1109]
• This above method starts with total RNA isolated from the desired source, although poly-A+ RNA can be used. The RNA preparation can then be treated with phosphatase if necessary to eliminate 5′ phosphate groups on degraded or damaged RNA which may interfere with the later RNA ligase step. The phosphatase should then be inactivated and the RNA treated with tobacco acid pyrophosphatase in order to remove the cap structure present at the 5′ ends of messenger RNAs. This reaction leaves a 5′ phosphate group at the 5′ end of the cap cleaved RNA which can then be ligated to an RNA oligonucleotide using T4 RNA ligase. [1110]
• This modified RNA preparation is used as a template for first strand cDNA synthesis using a gene specific oligonucleotide. The first strand synthesis reaction is used as a template for PCR amplification of the desired 5′ end using a primer specific to the ligated RNA oligonucleotide and a primer specific to the known sequence of the gene of interest. The resultant product is then sequenced and analyzed to confirm that the 5′ end sequence belongs to the desired gene. [1111]
Example 2 Isolation of Genomic Clones Corresponding to a Polynucleotide
• A human genomic P1 library (Genomic Systems, Inc.) is screened by PCR using primers selected for the cDNA sequence corresponding to SEQ ID NO:X., according to the method described in Example 1. (See also, Sambrook.) [1112]
Example 3 Tissue Distribution of Polypeptide
• Tissue distribution of mRNA expression of polynucleotides of the present invention is determined using protocols for Northern blot analysis, described by, among others, Sambrook et al. For example, a cDNA probe produced by the method described in Example 1 is labeled with P[1113] ³² using the rediprime™ DNA labeling system (Amersham Life Science), according to manufacturer's instructions. After labeling, the probe is purified using CHROMA SPIN-100™ column (Clontech Laboratories, Inc.), according to manufacturer's protocol number PT1200-1. The purified labeled probe is then used to examine various human tissues for mRNA expression.
• Multiple Tissue Northern (MTN) blots containing various human tissues (H) or human immune system tissues (IM) (Clontech) are examined with the labeled probe using ExpressHyb™ hybridization solution (Clontech) according to manufacturer's protocol number PT1190-1. Following hybridization and washing, the blots are mounted and exposed to film at −70° C. overnight, and the films developed according to standard procedures. [1114]
Example 4 Chromosomal Mapping of the Polynucleotides
• An oligonucleotide primer set is designed according to the sequence at the 5′ end of SEQ ID NO:X. This primer preferably spans about 100 nucleotides. This primer set is then used in a polymerase chain reaction under the following set of conditions: 30 seconds, 95° C.; 1 minute, 56° C.; 1 minute, 70° C. This cycle is repeated 32 times followed by one 5 minute cycle at 70° C. Human, mouse, and hamster DNA is used as template in addition to a somatic cell hybrid panel containing individual chromosomes or chromosome fragments (Bios, Inc). The reactions is analyzed on either 8% polyacrylamide gels or 3.5% agarose gels. Chromosome mapping is determined by the presence of an approximately 100 bp PCR fragment in the particular somatic cell hybrid. [1115]
Example 5 Bacterial Expression of a Polypeptide
• A polynucleotide encoding a polypeptide of the present invention is amplified using PCR oligonucleotide primers corresponding to the 5′ and 3′ ends of the DNA sequence, as outlined in Example 1, to synthesize insertion fragments. The primers used to amplify the cDNA insert should preferably contain restriction sites, such as BamHI and XbaI, at the 5′ end of the primers in order to clone the amplified product into the expression vector. For example, BamHI and XbaI correspond to the restriction enzyme sites on the bacterial expression vector pQE-9. (Qiagen, Inc., Chatsworth, Calif.). This plasmid vector encodes antibiotic resistance (Amp[1116] ^r), a bacterial origin of replication (ori), an IPTG-regulatable promoter/operator (P/O), a ribosome binding site (RBS), a 6-histidine tag (6-His), and restriction enzyme cloning sites.
• The pQE-9 vector is digested with BamHI and XbaI and the amplified fragment is ligated into the pQE-9 vector maintaining the reading frame initiated at the bacterial RBS. The ligation mixture is then used to transform the [1117] E. coli strain M15/rep4 (Qiagen, Inc.) which contains multiple copies of the plasmid pREP4, which expresses the lacI repressor and also confers kanamycin resistance (Kan^r). Transformants are identified by their ability to grow on LB plates and ampicillin/kanamycin resistant colonies are selected. Plasmid DNA is isolated and confirmed by restriction analysis.
• Clones containing the desired constructs are grown overnight (O/N) in liquid culture in LB media supplemented with both Amp (100 ug/ml) and Kan (25 ug/ml). The O/N culture is used to inoculate a large culture at a ratio of 1:100 to 1:250. The cells are grown to an optical density 600 (O.D.[1118] ⁶⁰⁰) of between 0.4 and 0.6. IPTG (Isopropyl-B-D-thiogalacto pyranoside) is then added to a final concentration of 1 mM. IPTG induces by inactivating the lacI repressor, clearing the P/O leading to increased gene expression.
• Cells are grown for an extra 3 to 4 hours. Cells are then harvested by centrifugation (20 mins at 6000× g). The cell pellet is solubilized in the chaotropic agent 6 Molar Guanidine HCl by stirring for 3-4 hours at 4° C. The cell debris is removed by centrifugation, and the supernatant containing the polypeptide is loaded onto a nickel-nitrilo-tri-acetic acid (“Ni-NTA”) affinity resin column (available from QIAGEN, Inc., supra). Proteins with a 6× His tag bind to the Ni-NTA resin with high affinity and can be purified in a simple one-step procedure (for details see: The QIAexpressionist (1995) QIAGEN, Inc., supra). [1119]
• Briefly, the supernatant is loaded onto the column in 6 M guanidine-HCl, pH 8, the column is first washed with 10 volumes of 6 M guanidine-HCl, pH 8, then washed with 10 volumes of 6 M guanidine-HCl pH 6, and finally the polypeptide is eluted with 6 M guanidine-HCl, pH 5. [1120]
• The purified protein is then renatured by dialyzing it against phosphate-buffered saline (PBS) or 50 mM Na-acetate, pH 6 buffer plus 200 mM NaCl. Alternatively, the protein can be successfully refolded while immobilized on the Ni-NTA column. The recommended conditions are as follows: renature using a linear 6M-1M urea gradient in 500 mM NaCl, 20% glycerol, 20 mM Tris/HCl pH 7.4, containing protease inhibitors. The renaturation should be performed over a period of 1.5 hours or more. After renaturation the proteins are eluted by the addition of 250 mM immidazole. Immidazole is removed by a final dialyzing step against PBS or 50 mM sodium acetate pH 6 buffer plus 200 mM NaCl. The purified protein is stored at 4° C. or frozen at −80° C. [1121]
• In addition to the above expression vector, the present invention further includes an expression vector comprising phage operator and promoter elements operatively linked to a polynucleotide of the present invention, called pHE4a. (ATCC Accession Number 209645, deposited on February 25, 1998.) This vector contains: 1) a neomycinphosphotransferase gene as a selection marker, 2) an [1122] E. coli origin of replication, 3) a T5 phage promoter sequence, 4) two lac operator sequences, 5) a Shine-Delgarno sequence, and 6) the lactose operon repressor gene (lacIq). The origin of replication (oriC) is derived from pUC19 (LTI, Gaithersburg, Md.). The promoter sequence and operator sequences are made synthetically.
• DNA can be inserted into the pHEa by restricting the vector with NdeI and XbaI, BamHI, XhoI, or Asp718, running the restricted product on a gel, and isolating the larger fragment (the stuffer fragment should be about 310 base pairs). The DNA insert is generated according to the PCR protocol described in Example 1, using PCR primers having restriction sites for NdeI (5′ primer) and XbaI, BamHI, XhoI, or Asp718 (3′ primer). The PCR insert is gel purified and restricted with compatible enzymes. The insert and vector are ligated according to standard protocols. [1123]
• The engineered vector could easily be substituted in the above protocol to express protein in a bacterial system. [1124]
Example 6 Purification of a Polypeptide from an Inclusion Body
• The following alternative method can be used to purify a polypeptide expressed in [1125] E coli when it is present in the form of inclusion bodies. Unless otherwise specified, all of the following steps are conducted at 4-10° C.
• Upon completion of the production phase of the [1126] E. coli fermentation, the cell culture is cooled to 4-10° C. and the cells harvested by continuous centrifugation at 15,000 rpm (Heraeus Sepatech). On the basis of the expected yield of protein per unit weight of cell paste and the amount of purified protein required, an appropriate amount of cell paste, by weight, is suspended in a buffer solution containing 100 mM Tris, 50 mM EDTA, pH 7.4. The cells are dispersed to a homogeneous suspension using a high shear mixer.
• The cells are then lysed by passing the solution through a microfluidizer (Microfuidics, Corp. or APV Gaulin, Inc.) twice at 4000-6000 psi. The homogenate is then mixed with NaCl'solution to a final concentration of 0.5 M NaCl, followed by centrifugation at 7000× g for 15 min. The resultant pellet is washed again using 0.5M NaCl, 100 mM Tris, 50 mM EDTA, pH 7.4. [1127]
• The resulting washed inclusion bodies are solubilized with 1.5 M guanidine hydrochloride (GuHCl) for 2-4 hours. After 7000× g centrifugation for 15 min., the pellet is discarded and the polypeptide containing supernatant is incubated at 4° C. overnight to allow further GuHCl extraction. [1128]
• Following high speed centrifugation (30,000× g) to remove insoluble particles, the GuHCl solubilized protein is refolded by quickly mixing the GuHCl extract with 20 volumes of buffer containing 50 mM sodium, pH 4.5, 150 mM NaCl, 2 mM EDTA by vigorous stirring. The refolded diluted protein solution is kept at 4° C. without mixing for 12 hours prior to further purification steps. [1129]
• To clarify the refolded polypeptide solution, a previously prepared tangential filtration unit equipped with 0.16 μm membrane filter with appropriate surface area (e.g., Filtron), equilibrated with 40 mM sodium acetate, pH 6.0 is employed. The filtered sample is loaded onto a cation exchange resin (e.g., Poros HS-50, Perseptive Biosystems). The column is washed with 40 mM sodium acetate, pH 6.0 and eluted with 250 mM, 500 mM, 1000 mM, and 1500 mM NaCl in the same buffer, in a stepwise manner. The absorbance at 280 nm of the effluent is continuously monitored. Fractions are collected and further analyzed by SDS-PAGE. [1130]
• Fractions containing the polypeptide are then pooled and mixed with 4 volumes of water. The diluted sample is then loaded onto a previously prepared set of tandem columns of strong anion (Poros HQ-50, Perseptive Biosystems) and weak anion (Poros CM-20, Perseptive Biosystems) exchange resins. The columns are equilibrated with 40 mM sodium acetate, pH 6.0. Both columns are washed with 40 MM sodium acetate, pH 6.0, 20.0 mM NaCl. The CM-20 column is then eluted using a 10 column volume linear gradient ranging from 0.2 M NaCl, 50 mM sodium acetate, pH 6.0 to 1.0 M NaCl, 50 mM sodium acetate, pH 6.5. Fractions are collected under constant A[1131] ₂₈₀ monitoring of the effluent. Fractions containing the polypeptide (determined, for instance, by 16% SDS-PAGE) are then pooled.
• The resultant polypeptide should exhibit greater than 95% purity after the above refolding and purification steps. No major contaminant bands should be observed from Commassie blue stained 16% SDS-PAGE gel when 5 μg of purified protein is loaded. The purified protein can also be tested for endotoxinlLPS contamination, and typically the LPS content is less than 0.1 ng/ml according to LAL assays. [1132]
Example 7 Cloning and Expression of a Polypeptide in a Baculovirus Expression System
• In this example, the plasmid shuttle vector pA2 is used to insert a polynucleotide into a baculovirus to express a polypeptide. This expression vector contains the strong polyhedrin promoter of the [1133] Autographa californica nuclear polyhedrosis virus (AcMNPV) followed by convenient restriction sites such as BamHI, XbaI and Asp718. The polyadenylation site of the simian virus 40 (“SV40”) is used for efficient polyadenylation. For easy selection of recombinant virus, the plasmid contains the beta-galactosidase gene from E. coli under control of a weak Drosophila promoter in the same orientation, followed by the polyadenylation signal of the polyhedrin gene. The inserted genes are flanked on both sides by viral sequences for cell-mediated homologous recombination with wild-type viral DNA to generate a viable virus that express the cloned polynucleotide.
• Many other baculovirus vectors can be used in place of the vector above, such as pAc373, pVL941, and pAcIM1, as one skilled in the art would readily appreciate, as long as the construct provides appropriately located signals for transcription, translation, secretion and the like, including a signal peptide and an in-frame AUG as required. Such vectors are described, for instance, in Luckow et al., Virology 170:31-39 (1989). [1134]
• Specifically, the cDNA sequence contained in the deposited clone, including the AUG initiation codon and the naturally associated leader sequence identified in Table 1, is amplified using the PCR protocol described in Example 1. If the naturally occurring signal sequence is used to produce the secreted protein, the pA2 vector does not need a second signal peptide. Alternatively, the vector can be modified (pA2 GP) to include a baculovirus leader sequence, using the standard methods described in Summers et al., “A Manual of Methods for Baculovirus Vectors and Insect Cell Culture Procedures,” Texas Agricultural Experimental Station Bulletin No. 1555 (1987). [1135]
• The amplified fragment is isolated from a 1% agarose gel using a commercially available kit (“Geneclean,” BIO 101 Inc., La Jolla, Calif.). The fragment then is digested with appropriate restriction enzymes and again purified on a 1% agarose gel. [1136]
• The plasmid is digested with the corresponding restriction enzymes and optionally, can be dephosphorylated using calf intestinal phosphatase, using routine procedures known in the art. The DNA is then isolated from a 1% agarose gel using a commercially available kit (“Geneclean” BIO 101 Inc., La Jolla, Calif.). [1137]
• The fragment and the dephosphorylated plasmid are ligated together with T4 DNA ligase. [1138] E. coli HB 101 or other suitable E. coli hosts such as XL-1 Blue (Stratagene Cloning Systems, La Jolla, Calif.) cells are transformed with the ligation mixture and spread on culture plates. Bacteria containing the plasmid are identified by digesting DNA from individual colonies and analyzing the digestion product by gel electrophoresis. The sequence of the cloned fragment is confirmed by DNA sequencing.
• Five μg of a plasmid containing the polynucleotide is co-transfected with 1.0 μg of a commercially available linearized baculovirus DNA (“BaculoGold™ baculovirus DNA”, Pharmingen, San Diego, Calif.), using the lipofection method described by Felgner et al., Proc. Natl. Acad. Sci. USA 84:7413-7417 (1987). One μg of BaculoGold™ virus DNA and 5 μg of the plasmid are mixed in a sterile well of a microtiter plate containing 50 μl of serum-free Grace's medium (Life Technologies Inc., Gaithersburg, Md.). Afterwards, 10 μl Lipofectin plus 90 μl Grace's medium are added, mixed and incubated for 15 minutes at room temperature. Then the transfection mixture is added drop-wise to Sf9 insect cells (ATCC CRL 1711) seeded in a 35 mm tissue culture plate with 1 ml Grace's medium without serum. The plate is then incubated for 5 hours at 27° C. The transfection solution is then removed from the plate and 1 ml of Grace's insect medium supplemented with 10% fetal calf serum is added. Cultivation is then continued at 27° C. for four days. [1139]
• After four days the supernatant is collected and a plaque assay is performed, as described by Summers and Smith, supra. An agarose gel with “Blue Gal” (Life Technologies Inc., Gaithersburg) is used to allow easy identification and isolation of gal-expressing clones, which produce blue-stained plaques. (A detailed description of a “plaque assay” of this type can also be found in the user's guide for insect cell culture and baculovirology distributed by Life Technologies Inc., Gaithersburg, page 9-10.) After appropriate incubation, blue stained plaques are picked with the tip of a micropipettor (e.g., Eppendorf). The agar containing the recombinant viruses is then resuspended in a microcentrifuge tube containing 200 μl of Grace's medium and the suspension containing the recombinant baculovirus is used to infect Sf9 cells seeded in 35 mm dishes. Four days later the supernatants of these culture dishes are harvested and then they are stored at 4° C. [1140]
• To verify the expression of the polypeptide, Sf9 cells are grown in Grace's medium supplemented with 10% heat-inactivated FBS. The cells are infected with the recombinant baculovirus containing the polynucleotide at a multiplicity of infection (“MOI”) of about 2. If radiolabeled proteins are desired, 6 hours later the medium is removed and is replaced with SF900 II medium minus methionine and cysteine (available from Life Technologies Inc., Rockville, Md.). After 42 hours, 5 μCi of [1141] ³⁵S-methionine and 5 μCi ³⁵S-cysteine (available from Amersham) are added. The cells are further incubated for 16 hours and then are harvested by centrifugation. The proteins in the supernatant as well as the intracellular proteins are analyzed by SDS-PAGE followed by autoradiography (if radiolabeled).
• Microsequencing of the amino acid sequence of the amino terminus of purified protein may be used to determine the amino terminal sequence of the produced protein. [1142]
Example 8 Expression of a Polypeptide in Mammalian Cells
• The polypeptide of the present invention can be expressed in a mammalian cell. A typical mammalian expression vector contains a promoter element, which mediates the initiation of transcription of mRNA, a protein coding sequence, and signals required for the termination of transcription and polyadenylation of the transcript. Additional elements include enhancers, Kozak sequences and intervening sequences flanked by donor and acceptor sites for RNA splicing. Highly efficient transcription is achieved with the early and late promoters from SV40, the long terminal repeats (LTRs) from Retroviruses, e.g., RSV, HTLVI, HIVI and the early promoter of the cytomegalovirus (CMV). However, cellular elements can also be used (e.g., the human actin promoter). [1143]
• Suitable expression vectors for use in practicing the present invention include, for example, vectors such as pSVL and pMSG (Pharmacia, Uppsala, Sweden), pRSVcat (ATCC 37152), pSV2dhfr (ATCC 37146), pBC12MI (ATCC 67109), pCMVSport 2.0, and pCMVSport 3.0. Mammalian host cells that could be used include, human Hela, 293, H9 and Jurkat cells, mouse NIH3T3 and C127 cells, Cos 1, Cos 7 and CV1, quail QC1-3 cells, mouse L cells and Chinese hamster ovary (CHO) cells. [1144]
• Alternatively, the polypeptide can be expressed in stable cell lines containing the polynucleotide integrated into a chromosome. The co-transfection with a selectable marker such as dhfr, gpt, neomycin, hygromycin allows the identification and isolation of the transfected cells. [1145]
• The transfected gene can also be amplified to express large amounts of the encoded protein. The DHFR (dihydrofolate reductase) marker is useful in developing cell lines that carry several hundred or even several thousand copies of the gene of interest. (See, e.g., Alt, F. W., et al., J. Biol. Chem. 253:1357-1370 (1978); Hamlin, J. L. and Ma, C., Biochem. et Biophys. Acta, 1097:107-143 (1990); Page, M. J. and Sydenham, M. A., Biotechnology 9:64-68 (1991).) Another useful selection marker is the enzyme glutamine synthase (GS) (Murphy et al., Biochem J. 227:277-279 (1991); Bebbington et al., Bio/Technology 10:169-175 (1992). Using these markers, the mammalian cells are grown in selective medium and the cells with the highest resistance are selected. These cell lines contain the amplified gene(s) integrated into a chromosome. Chinese hamster ovary (CHO) and NSO cells are often used for the production of proteins. [1146]
• Derivatives of the plasmid pSV2-dhfr (ATCC Accession No. 37146), the expression vectors pC4 (ATCC Accession No. 209646) and pC6 (ATCC Accession No.209647) contain the strong promoter (LTR) of the Rous Sarcoma Virus (Cullen et al., Molecular and Cellular Biology, 438-447 (March, 1985)) plus a fragment of the CMV-enhancer (Boshart et al., Cell 41:521-530 (1985).) Multiple cloning sites, e.g., with the restriction enzyme cleavage sites BamHI, XbaI and Asp718, facilitate the cloning of the gene of interest. The vectors also contain the 3′ intron, the polyadenylation and termination signal of the rat preproinsulin gene, and the mouse DHFR gene under control of the SV40 early promoter. [1147]
• Specifically, the plasmid pC6, for example, is digested with appropriate restriction enzymes and then dephosphorylated using calf intestinal phosphates by procedures known in the art. The vector is then isolated from a 1% agarose gel. [1148]
• A polynucleotide of the present invention is amplified according to the protocol outlined in Example 1. If the naturally occurring signal sequence is used to produce the secreted protein, the vector does not need a second signal peptide. Alternatively, if the naturally occurring signal sequence is not used, the vector can be modified to include a heterologous signal sequence. (See, e.g., WO 96/34891.) [1149]
• The amplified fragment is isolated from a 1% agarose gel using a commercially available kit (“Geneclean,” BIO 101 Inc., La Jolla, Calif.). The fragment then is digested with appropriate restriction enzymes and again purified on a 1% agarose gel. [1150]
• The amplified fragment is then digested with the same restriction enzyme and purified on a 1% agarose gel. The isolated fragment and the dephosphorylated vector are then ligated with T4 DNA ligase. [1151] E. coli HB 101 or XL-1 Blue cells are then transformed and bacteria are identified that contain the fragment inserted into plasmid pC6 using, for instance, restriction enzyme analysis.
• Chinese hamster ovary cells lacking an active DHFR gene is used for transfection. Five μg of the expression plasmid pC6 is cotransfected with 0.5 μg of the plasmid pSVneo using lipofectin (Felgner et al., supra). The plasmid pSV2-neo contains a dominant selectable marker, the neo gene from Tn5 encoding an enzyme that confers resistance to a group of antibiotics including G418. The cells are seeded in alpha minus MEM supplemented with 1 mg/ml G418. After 2 days, the cells are trypsinized and seeded in hybridoma cloning plates (Greiner, Germany) in alpha minus MEM supplemented with 10, 25, or 50 ng/ml of metothrexate plus 1 mg/ml G418. After about 10-14 days single clones are trypsinized and then seeded in 6-well petri dishes or 10 ml flasks using different concentrations of methotrexate (50 nM, 100 nM, 200 nM, 400 nM, 800 nM). Clones growing at the highest concentrations of methotrexate are then transferred to new 6-well plates containing even higher concentrations of methotrexate (1 μM, 2 μM, 5 μM, 10 mM, 20 mM). The same procedure is repeated until clones are obtained which grow at a concentration of 100-200 μM. Expression of the desired gene product is analyzed, for instance, by SDS-PAGE and Western blot or by reversed phase HPLC analysis. [1152]
Example 9 Protein Fusions
• The polypeptides of the present invention are preferably fused to other proteins. These fusion proteins can be used for a variety of applications. For example, fusion of the present polypeptides to His-tag, HA-tag, protein A, IgG domains, and maltose binding protein facilitates purification. (See Example 5; see also EP A 394,827; Traunecker, et al., Nature 331:84-86 (1988).) Similarly, fusion to IgG-1, IgG-3, and albumin increases the halflife time in vivo. Nuclear localization signals fused to the polypeptides of the present invention can target the protein to a specific subcellular localization, while covalent heterodimer or homodimers can increase or decrease the activity of a fusion protein. Fusion proteins can also create chimeric molecules having more than one function. Finally, fusion proteins can increase solubility and/or stability of the fused protein compared to the non-fused protein. All of the types of fusion proteins described above can be made by modifying the following protocol, which outlines the fusion of a polypeptide to an IgG molecule, or the protocol described in Example 5. [1153]
• Briefly, the human Fc portion of the IgG molecule can be PCR amplified, using primers that span the 5′ and 3′ ends of the sequence described below. These primers also should have convenient restriction enzyme sites that will facilitate cloning into an expression vector, preferably a mammalian expression vector. [1154]
• For example, if pC4 (Accession No. 209646) is used, the human Fc portion can be ligated into the BamHI cloning site. Note that the 3′ BamHI site should be destroyed. Next, the vector containing the human Fc portion is re-restricted with BamHI, linearizing the vector, and a polynucleotide of the present invention, isolated by the PCR protocol described in Example 1, is ligated into this BamHI site. Note that the polynucleotide is cloned without a stop codon, otherwise a fusion protein will not be produced. [1155]
• If the naturally occurring signal sequence is used to produce the secreted protein, pC4 does not need a second signal peptide. Alternatively, if the naturally occurring signal sequence is not used, the vector can be modified to include a heterologous signal sequence. (See, e.g., WO 96/34891.) [1156]
• Human IgG Fc Region: [1157]

  GGGATCCGGAGCCCAAATCTTCTGACAAAACTCACA	(SEQ ID NO: 1)
  CATGCCCACCGTGCCCAGCACCTGAATTCGAGGGTG
  CACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGG
  ACACCCTCATGATCTCCCGGACTCCTGAGGTCACAT
  GCGTGGTGGTGGACGTAAGCCACGAAGACCCTGAGG
  TCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGC
  ATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACA
  ACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCC
  TGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGT
  GCAAGGTCTCCAACAAAGCCCTCCCAACCCCCATCG
  AGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAG
  AACCACAGGTGTACACCCTGCCCCCATCCCGGGATG
  AGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGG
  TCAAAGGCTTCTATCCAAGCGACATCGCCGTGGAGT
  GGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGA
  CCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCT
  TCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGT
  GGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGC
  ATGAGGCTCTGCACAACCACTACACGCAGAAGAGCC
  TCTCCCTGTCTCCGGGTAAATGAGTGCGACGGCCGC
  GACTCTAGAGGAT

Example 10 Production of an Antibody from a Polypeptide
• The antibodies of the present invention can be prepared by a variety of methods. (See, Current Protocols, Chapter 2.) For example, cells expressing a polypeptide of the present invention is administered to an animal to induce the production of sera containing polyclonal antibodies. In a preferred method, a preparation of the secreted protein is prepared and purified to render it substantially free of natural contaminants. Such a preparation is then introduced into an animal in order to produce polyclonal antisera of greater specific activity. [1158]
• In the most preferred method, the antibodies of the present invention are monoclonal antibodies (or protein binding fragments thereof). Such monoclonal antibodies can be prepared using hybridoma technology. (Köhler et al., Nature 256:495 (1975); Köhler et al., Eur. J. Immunol. 6:511 (1976); Köhler et al., Eur. J. Immunol. 6:292 (1976); Hammerling et al., in: Monoclonal Antibodies and T-Cell Hybridomas, Elsevier, N.Y., pp. 563-681 (1981).) In general, such procedures involve immunizing an animal (preferably a mouse) with polypeptide or, more preferably, with a secreted polypeptide-expressing cell. Such cells may be cultured in any suitable tissue culture medium; however, it is preferable to culture cells in Earle's modified Eagle's medium supplemented with 10% fetal bovine serum (inactivated at about 56° C.), and supplemented with about 10 g/l of nonessential amino acids, about 1,000 U/ml of penicillin, and about 100 μg/ml of streptomycin. [1159]
• The splenocytes of such mice are extracted and fused with a suitable myeloma cell line. Any suitable myeloma cell line may be employed in accordance with the present invention; however, it is preferable to employ the parent myeloma cell line (SP20), available from the ATCC. After fusion, the resulting hybridoma cells are selectively maintained in HAT medium, and then cloned by limiting dilution as described by Wands et al. (Gastroenterology 80:225-232 (1981).) The hybridoma cells obtained through such a selection are then assayed to identify clones which secrete antibodies capable of binding the polypeptide. [1160]
• Alternatively, additional antibodies capable of binding to the polypeptide can be produced in a two-step procedure using anti-idiotypic antibodies. Such a method makes use of the fact that antibodies are themselves antigens, and therefore, it is possible to obtain an antibody which binds to a second antibody. In accordance with this method, protein specific antibodies are used to immunize an animal, preferably a mouse. The splenocytes of such an animal are then used to produce hybridoma cells, and the hybridoma cells are screened to identify clones which produce an antibody whose ability to bind to the protein-specific antibody can be blocked by the polypeptide. Such antibodies comprise anti-idiotypic antibodies to the protein-specific antibody and can be used to immunize an animal to induce formation of further protein-specific antibodies. [1161]
• It will be appreciated that Fab and F(ab′)2 and other fragments of the antibodies of the present invention may be used according to the methods disclosed herein. Such fragments are typically produced by proteolytic cleavage, using enzymes such as papain (to produce Fab fragments) or pepsin (to produce F(ab′)2 fragments). Alternatively, secreted protein-binding fragments can be produced through the application of recombinant DNA technology or through synthetic chemistry. [1162]
• For in vivo use of antibodies in humans, it may be preferable to use “humanized” chimeric monoclonal antibodies. Such antibodies can be produced using genetic constructs derived from hybridoma cells producing the monoclonal antibodies described above. Methods for producing chimeric antibodies are known in the art. (See, for review, Morrison, Science 229:1202 (1985); Oi et al., BioTechniques 4:214 (1986); Cabilly et al., U.S. Pat. No. 4,816,567; Taniguchi et al., EP 171496; Morrison et al., EP 173494; Neuberger et al., WO 8601533; Robinson et al., WO 8702671; Boulianne et al., Nature 312:643 (1984); Neubergeret al., Nature 314:268 (1985).) [1163]
Example 11 Production Of Secreted Protein For High-throughput Screening Assays
• The following protocol produces a supernatant containing a polypeptide to be tested. This supernatant can then be used in the Screening Assays described in Examples 13-20. [1164]
• First, dilute Poly-D-Lysine (644 587 Boehringer-Mannheim) stock solution (1 mg/ml in PBS) 1:20 in PBS (w/o calcium or magnesium 17-516F Biowhittaker) for a working solution of 50 ug/ml. Add 200 ul of this solution to each well (24 well plates) and incubate at RT for 20 minutes. Be sure to distribute the solution over each well (note: a 12-channel pipetter may be used with tips on every other channel). Aspirate off the Poly-D-Lysine solution and rinse with 1 ml PBS (Phosphate Buffered Saline). The PBS should remain in the well until just prior to plating the cells and plates may be poly-lysine coated in advance for up to two weeks. [1165]
• Plate 293T cells (do not carry cells past P+20) at 2×10[1166] ⁵ cells/well in 0.5 ml DMEM(Dulbecco's Modified Eagle Medium)(with 4.5 G/L glucose and L-glutamine (12-604F Biowhittaker))/10% heat inactivated FBS(14-503F Biowhittaker)/1× Penstrep(17-602E Biowhittaker). Let the cells grow overnight.
• The next day, mix together in a sterile solution basin: 300 ul Lipofectamine (18324-012 Gibco/BRL) and 5 ml Optimem I (31985070 Gibco/BRL)/96-well plate. With a small volume multi-channel pipetter, aliquot approximately 2 ug of an expression vector containing a polynucleotide insert, produced by the methods described in Examples 8 or 9, into an appropriately labeled 96-well round bottom plate. With a multi-channel pipetter, add 50 ul of the Lipofectamine/Optimem I mixture to each well. Pipette up and down gently to mix. Incubate at RT 15-45 minutes. After about 20 minutes, use a multi-channel pipetter to add 150 ul Optimem I to each well. As a control, one plate of vector DNA lacking an insert should be transfected with each set of transfections. [1167]
• Preferably, the transfection should be performed by tag-teaming the following tasks. By tag-teaming, hands on time is cut in half, and the cells do not spend too much time on PBS. First, person A aspirates off the media from four 24-well plates of cells, and then person B rinses each well with 0.5-1 ml PBS. Person A then aspirates off PBS rinse, and person B, using a 12-channel pipetter with tips on every other channel, adds the 200 ul of DNA/Lipofectamine/Optimem I complex to the odd wells first, then to the even wells, to each row on the 24-well plates. Incubate at 37° C. for 6 hours. [1168]
• While cells are incubating, prepare appropriate media, either 1%BSA in DMEM with 1× penstrep, or CHO-5 media (116.6 mg/L of CaCl2 (anhyd); 0.00130 mg/L CuSO[1169] ₄-5H₂O; 0.050 mg/L of Fe(NO₃)₃-9H₂O; 0.417 mg/L of FeSO₄-7H₂O; 311.80 mg/L of Kcl; 28.64 mg/L of MgCl₂; 48.84 mg/L of MgSO₄; 6995.50 mg/L of NaCl; 2400.0 mg/L of NaHCO₃; 62.50 mg/L of NaH₂PO₄—H₂O; 71.02 mg/L of NaHPO4; 0.4320 mg/L of ZnSO₄-7H₂O; 0.002 mg/L of Arachidonic Acid; 1.022 mg/L of Cholesterol; 0.070 mg/L of DL-alpha-Tocopherol-Acetate; 0.0520 mg/L of Linoleic Acid; 0.010 mg/L of Linolenic Acid; 0.010 mg/L of Myristic Acid; 0.010 mg/L of Oleic Acid; 0.010 mg/L of Palmitric Acid; 0.010 mg/L of Palmitic Acid; 100 mg/L of Pluronic F-68; 0.010 mg/L of Stearic Acid; 2.20 mg/L of Tween 80; 4551 mg/L of D-Glucose; 130.85 mg/ml of L-Alanine; 147.50 mg/ml of L-Arginine-HCL; 7.50 mg/ml of L-Asparagine-H₂O; 6.65 mg/ml of L-Aspartic Acid; 29.56 mg/ml of L-Cystine-2HCL-H₂O; 31.29 mg/ml of L-Cystine-2HCL; 7.35 mg/ml of L-Glutamic Acid; 365.0 mg/ml of L-Glutamine; 18.75 mg/ml of Glycine; 52.48 mg/ml of L-Histidine-HCL-H₂O; 106.97 mg/ml of L-Isoleucine; 111.45 mg/ml of L-Leucine; 163.75 mg/ml of L-Lysine HCL; 32.34 mg/ml of L-Methionine; 68.48 mg/ml of L-Phenylalamine; 40.0 mg/ml of L-Proline; 26.25 mg/ml of L-Serine; 101.05 mg/ml of L-Threonine; 19.22 mg/ml of L-Tryptophan; 91.79 mg/ml of L-Tryrosine-2Na-2H₂O; 99.65 mg/ml of L-Valine; 0.0035 mg/L of Biotin; 3.24 mg/L of D-Ca Pantothenate; 11.78 mg/L of Choline Chloride; 4.65 mg/L of Folic Acid; 15.60 mg/L of i-Inositol; 3.02 mg/L of Niacinamide; 3.00 mg/L of Pyridoxal HCL; 0.031 mg/L of Pyridoxine HCL; 0.319 mg/L of Riboflavin; 3.17 mg/L of Thiamine HCL; 0.365 mg/L of Thymidine; and 0.680 mg/L of Vitamin B₁₂; 25 mM of HEPES Buffer; 2.39 mg/L of Na Hypoxanthine; 0.105 mg/L of Lipoic Acid; 0.081 mg/L of Sodium Putrescine-2HCL; 55.0 mg/L of Sodium Pyruvate; 0.0067 mg/L of Sodium Selenite; 20 uM of Ethanolamine; 0.122 mg/L of Ferric Citrate; 41.70 mg,/L of Methyl-B-Cyclodextrin complexed with Linoleic Acid; 33.33 mg/L of Methyl-B-Cyclodextrin complexed with Oleic Acid; and 10 mg/L of Methyl-B-Cyclodextrin complexed with Retinal) with 2 mm glutamine and 1× penstrep. (BSA (81-068-3 Bayer) 100 μm dissolved in 1 L DMEM for a 10% BSA stock solution). Filter the media and collect 50 ul for endotoxin assay in 15 ml polystyrene conical.
• The transfection reaction is terminated, preferably by tag-teaming, at the end of the incubation period. Person A aspirates off the transfection media, while person B adds 1.5 ml appropriate media to each well. Incubate at 37° C. for 45 or 72 hours depending on the media used: 1%BSA for 45 hours or CHO-5 for 72 hours. [1170]
• On day four, using a 300 ul multichannel pipetter, aliquot 600 ul in one 1 ml deep well plate and the remaining supernatant into a 2 ml deep well. The supernatants from each well can then be used in the assays described in Examples 13-20. [1171]
• It is specifically understood that when activity is obtained in any of the assays described below using a supernatant, the activity originates from either the polypeptide directly (e.g., as a secreted protein) or by the polypeptide inducing expression of other proteins, which are then secreted into the supernatant. Thus, the invention further provides a method of identifying the protein in the supernatant characterized by an activity in a particular assay. [1172]
Example 12 Construction of GAS Reporter Construct
• One signal transduction pathway involved in the differentiation and proliferation of cells is called the Jaks-STATs pathway. Activated proteins in the Jaks-STATs pathway bind to gamma activation site “GAS” elements or interferon-sensitive responsive element (“ISRE”), located in the promoter of many genes. The binding of a protein to these elements alter the expression of the associated gene. [1173]
• GAS and ISRE elements are recognized by a class of transcription factors called Signal Transducers and Activators of Transcription, or “STATs.” There are six members of the STATs family. Stat1 and Stat3 are present in many cell types, as is Stat2 (as response to IFN-alpha is widespread). Stat4 is more restricted and is not in many cell types though it has been found in T helper class I, cells after treatment with IL-12. Stat5 was originally called mammary growth factor, but has been found at higher concentrations in other cells including myeloid cells. It can be activated in tissue culture cells by many cytokines. [1174]
• The STATs are activated to translocate from the cytoplasm to the nucleus upon tyrosine phosphorylation by a set of kinases known as the Janus Kinase (“Jaks”) family. Jaks represent a distinct family of soluble tyrosine kinases and include Tyk2, Jak1, Jak2, and Jak3. These kinases display significant sequence similarity and are generally catalytically inactive in resting cells. [1175]
• The Jaks are activated by a wide range of receptors summarized in the Table below. (Adapted from review by Schidler and Darnell, Ann. Rev. Biochem. 64:621-51 (1995).) A cytokine receptor family, capable of activating Jaks, is divided into two groups: (a) Class 1 includes receptors for IL-2, IL-3, IL-4, IL-6, IL-7, IL-9, IL-11, IL-12, IL-15, Epo, PRL, GH, G-CSF, GM-CSF, LIF, CNTF, and thrombopoietin; and [1176]
• (b) Class 2 includes IFN-a, IFN-g, and IL-10. The Class 1 receptors share a conserved cysteine motif (a set of four conserved cysteines and one tryptophan) and a WSXWS motif (a membrane proximal region encoding Trp-Ser-Xxx-Trp-Ser (SEQ ID NO:2)). [1177]
• Thus, on binding of a ligand to a receptor, Jaks are activated, which in turn activate STATs, which then translocate and bind to GAS elements. This entire process is encompassed in the Jaks-STATs signal transduction pathway. [1178]
• Therefore, activation of the Jaks-STATs pathway, reflected by the binding of the GAS or the ISRE element, can be used to indicate proteins involved in the proliferation and differentiation of cells. For example, growth factors and cytokines are known to activate the Jaks-STATs pathway. (See Table below.) Thus, by using GAS elements linked to reporter molecules, activators of the Jaks-STATs pathway can be identified. [1179]

  	JAKs

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

  IFN family

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

• To construct a synthetic GAS containing promoter element, which is used in the Biological Assays described in Examples 13-14, a PCR based strategy is employed to generate a GAS-SV40 promoter sequence. The 5′ primer contains four tandem copies of the GAS binding site found in the IRF1 promoter and previously demonstrated to bind STATs upon induction with a range of cytokines (Rothman et al., Immunity 1:457-468 (1994).), although other GAS or ISRE elements can be used instead. The 5′ primer also contains 18bp of sequence complementary to the SV40 early promoter sequence and is flanked with an XhoI site. The sequence of the 5′ primer is: [1180]

  5′:GCGCCTCGAGATTTCCCCGAAATCTAGATTTCC	(SEQ ID NO: 3)
  CCGAAATGATTTCCCCGAAATGATTTCCCCGAAATA
  TCTGCCATCTCAATTAG:3′

• The downstream primer is complementary to the SV40 promoter and is flanked with a Hind III site: 5′:GCGGCAAGCTTTTTGCAAAGCCTAGGC:3′ (SEQ ID NO:4) [1181]
• PCR amplification is performed using the SV40 promoter template present in the B-gal:promoter plasmid obtained from Clontech. The resulting PCR fragment is digested with XhoI/Hind III and subcloned into BLSK2-. (Stratagene.) Sequencing with forward and reverse primers confirms that the insert contains the following sequence: [1182]

  5′:CTCGAGATTTCCCCGAAATCTAGATTTCCCCGA	(SEQ ID NO: 5)
  AATGATTTCCCCGAAATGATTTCCCCGAAATATCTG
  CCATCTCAATTAGTCAGCAACCATAGTCCCGCCCCT
  AACTCCGCCCATCCCGCCCCTAACTCCGCCCAGTTC
  CGCCCATTCTCCGCCCCATGGCTGACTAATTTTTTT
  TATTTATGCAGAGGCCGAGGCCGCCTCGGCCTCTGA
  GCTATTCCAGAAGTAGTGAGGAGGCTTTTTTGGAGG
  CCTAGGCTTTTGCAAAAAGCTT:3′

• With this GAS promoter element linked to the SV40 promoter, a GAS:SEAP2 reporter construct is next engineered. Here, the reporter molecule is a secreted alkaline phosphatase, or “SEAP.” Clearly, however, any reporter molecule can be instead of SEAP, in this or in any of the other Examples. Well known reporter molecules that can be used instead of SEAP include chloramphenicol acetyltransferase (CAT), luciferase, alkaline phosphatase, B-galactosidase, green fluorescent protein (GFP), or any protein detectable by an antibody. [1183]
• The above sequence confirmed synthetic GAS-SV40 promoter element is subcloned into the pSEAP-Promoter vector obtained from Clontech using HindIII and XhoI, effectively replacing the SV40 promoter with the amplified GAS:SV40 promoter element, to create the GAS-SEAP vector. However, this vector does not contain a neomycin resistance gene, and therefore, is not preferred for mammalian expression systems. [1184]
• Thus, in order to generate mammalian stable cell lines expressing the GAS-SEAP reporter, the GAS-SEAP cassette is removed from the GAS-SEAP vector using SalI and NotI, and inserted into a backbone vector containing the neomycin resistance gene, such as pGFP-1 (Clontech), using these restriction sites in the multiple cloning site, to create the GAS-SEAP/Neo vector. Once this vector is transfected into mammalian cells, this vector can then be used as a reporter molecule for GAS binding as described in Examples 13-14. [1185]
• Other constructs can be made using the above description and replacing GAS with a different promoter sequence. For example, construction of reporter molecules containing NFK-B and EGR promoter sequences are described in Examples 15 and 16. However, many other promoters can be substituted using the protocols described in these Examples. For instance, SRE, IL-2, NFAT, or Osteocalcin promoters can be substituted, alone or in combination (e.g., GAS/NF-KB/EGR, GAS/NF-KB, I1-2/NFAT, or NF-KB/GAS). Similarly, other cell lines can be used to test reporter construct activity, such as HELA (epithelial), HUVEC (endothelial), Reh (B-cell), Saos-2 (osteoblast), HUVAC (aortic), or Cardiomyocyte. [1186]
Example 13 High-throughput Screening Assay for T-cell Activity
• The following protocol is used to assess T-cell activity by identifying factors, such as growth factors and cytokines, that may proliferate or differentiate T-cells. T-cell activity is assessed using the GAS/SEAP/Neo construct produced in Example 12. Thus, factors that increase SEAP activity indicate the ability to activate the Jaks-STATS signal transduction pathway. The T-cell used in this assay is Jurkat T-cells (ATCC Accession No. TIB-152), although Molt-3 cells (ATCC Accession No. CRL-1552) and Molt-4 cells (ATCC Accession No. CRL-1582) cells can also be used. [1187]
• Jurkat T-cells are lymphoblastic CD4+ Th1 helper cells. In order to generate stable cell lines, approximately 2 million Jurkat cells are transfected with the GAS-SEAP/neo vector using DMRIE-C (Life Technologies)(transfection procedure described below). The transfected cells are seeded to a density of approximately 20,000 cells per well and transfectants resistant to 1 mg/ml genticin selected. Resistant colonies are expanded and then tested for their response to increasing concentrations of interferon gamma. The dose response of a selected clone is demonstrated. [1188]
• Specifically, the following protocol will yield sufficient cells for 75 wells containing 200 ul of cells. Thus, it is either scaled up, or performed in multiple to generate sufficient cells for multiple 96 well plates. Jurkat cells are maintained in RPMI+10% serum with 1%Pen-Strep. Combine 2.5 mls of OPTI-MEM (Life Technologies) with 10 ug of plasmid DNA in a T25 flask. Add 2.5 ml OPTI-MEM containing 50 ul of DMRIE-C and incubate at room temperature for 1545 mins. [1189]
• During the incubation period, count cell concentration, spin down the required number of cells (10[1190] ⁷ per transfection), and resuspend in OPTI-MEM to a final concentration of 10⁷ cells/ml. Then add 1 ml of 1×10⁷ cells in OPTI-MEM to T25 flask and incubate at 37° C. for 6 hrs. After the incubation, add 10 ml of RPMI+15% serum.
• The Jurkat:GAS-SEAP stable reporter lines are maintained in RPMI+10% serum, 1 mg/ml Genticin, and 1% Pen-Strep. These cells are treated with supernatants containing a polypeptide as produced by the protocol described in Example 11. [1191]
• On the day of treatment with the supernatant, the cells should be washed and resuspended in fresh RPMI+10% serum to a density of 500,000 cells per ml. The exact number of cells required will depend on the number of supernatants being screened. For one 96 well plate, approximately 10 million cells (for 10 plates, 100 million cells) are required. [1192]
• Transfer the cells to a triangular reservoir boat, in order to dispense the cells into a 96 well dish, using a 12 channel pipette. Using a 12 channel pipette, transfer 200 ul of cells into each well (therefore adding 100, 000 cells per well). [1193]
• After all the plates have been seeded, 50 ul of the supernatants are transferred directly from the 96 well plate containing the supernatants into each well using a 12 channel pipette. In addition, a dose of exogenous interferon gamma (0.1, 1.0, 10 ng) is added to wells H9, H10, and H11 to serve as additional positive controls for the assay. [1194]
• The 96 well dishes containing Jurkat cells treated with supernatants are placed in an incubator for 48 hrs (note: this time is variable between 48-72 hrs). 35 ul samples from each well are then transferred to an opaque 96 well plate using a 12 channel pipette. The opaque plates should be covered (using sellophene covers) and stored at −20° C. until SEAP assays are performed according to Example 17. The plates containing the remaining treated cells are placed at 4° C. and serve as a source of material for repeating the assay on a specific well if desired. [1195]
• As a positive control, 100 Unit/ml interferon gamma can be used which is known to activate Jurkat T cells. Over 30 fold induction is typically observed in the positive control wells. [1196]
• The above protocol may be used in the generation of both transient, as well as, stable transfected cells, which would be apparent to those of skill in the art. [1197]
Example 14 High-throughput Screening Assay Identifying Myeloid Activity
• The following protocol is used to assess myeloid activity by identifying factors, such as growth factors and cytokines, that may proliferate or differentiate myeloid cells. Myeloid cell activity is assessed using the GAS/SEAP/Neo construct produced in Example 12. Thus, factors that increase SEAP activity indicate the ability to activate the Jaks-STATS signal transduction pathway. The myeloid cell used in this assay is U937, a pre-monocyte cell line, although TF-1, HL60, or KG1 can be used. [1198]
• To transiently transfect U937 cells with the GAS/SEAP/Neo construct produced in Example 12, a DEAE-Dextran method (Kharbanda et. al., 1994, Cell Growth & Differentiation, 5:259-265) is used. First, harvest 2×10e[1199] ⁷ U937 cells and wash with PBS. The U937 cells are usually grown in RPMI 1640 medium containing 10% heat-inactivated fetal bovine serum (FBS) supplemented with 100 units/ml penicillin and 100 mg/ml streptomycin.
• Next, suspend the cells in 1 ml of 20 mM Tris-HCl (pH 7.4) buffer containing 0.5 mg/ml DEAE-Dextran, 8 ug GAS-SEAP2 plasmid DNA, 140 mM NaCl, 5 mM KCl, 375 uM Na[1200] ₂HPO₄.7H₂O, 1 mM MgCl₂, and 675 uM CaCl₂. Incubate at 37° C. for 45 min.
• Wash the cells with RPMI 1640 medium containing 10% FBS and then resuspend in 10 ml complete medium and incubate at 37° C. for 36 hr. [1201]
• The GAS-SEAP/U937 stable cells are obtained by growing the cells in 400 ug/ml G418. The G418-free medium is used for routine growth but every one to two months, the cells should be re-grown in 400 ug/ml G418 for couple of passages. [1202]
• These cells are tested by harvesting 1×10[1203] ⁸ cells (this is enough for ten 96-well plates assay) and wash with PBS. Suspend the cells in 200 ml above described growth medium, with a final density of 5×10⁵ cells/ml. Plate 200 ul cells per well in the 96-well plate (or 1×10⁵ cells/well).
• Add 50 ul of the supernatant prepared by the protocol described in Example 11. Incubate at 37° C. for 48 to 72 hr. As a positive control, 100 Unit/ml interferon gamma can be used which is known to activate U937 cells. Over 30 fold induction is typically observed in the positive control wells. SEAP assay the supernatant according to the protocol described in Example 17. [1204]
Example 15 High-throughput Screening Assay Identifying Neuronal Activity
• When cells undergo differentiation and proliferation, a group of genes are activated through many different signal transduction pathways. One of these genes, EGR1 (early growth response gene 1), is induced in various tissues and cell types upon activation. The promoter of EGR1 is responsible for such induction. Using the EGR1 promoter linked to reporter molecules, activation of cells can be assessed. [1205]
• Particularly, the following protocol is used to assess neuronal activity in PC12 cell lines. PC12 cells (rat phenochromocytoma cells) are known to proliferate and/or differentiate by activation with a number of mitogens, such as TPA (tetradecanoyl phorbol acetate), NGF (nerve growth factor), and EGF (epidermal growth factor). The EGRI gene expression is activated during this treatment. Thus, by stably transfecting PC12 cells with a construct containing an EGR promoter linked to SEAP reporter, activation of PC12 cells can be assessed. [1206]
• The EGR/SEAP reporter construct can be assembled by the following protocol. The EGR-1 promoter sequence (−633 to +l) (Sakamoto K et al., Oncogene 6:867-871 (1991)) can be PCR amplified from human genomic DNA using the following primers: [1207]

  (SEQ ID NO: 6)

  5′ GCGCTCGAGGGATGACAGCGATAGAACCCCGG-3′

  (SEQ ID NO: 7)

  5′ GCGAAGCTTCGCGACTCCCCGGATCCGCCTC-3′

• Using the GAS:SEAP/Neo vector produced in Example 12, EGR1 amplified product can then be inserted into this vector. Linearize the GAS:SEAP/Neo vector using restriction enzymes XhoI/HindIII, removing the GAS/SV40 stuffer. Restrict the EGRI amplified product with these same enzymes. Ligate the vector and the EGR1 promoter. [1208]
• To prepare 96 well-plates for cell culture, two mls of a coating solution (1:30 dilution of collagen type I (Upstate Biotech Inc. Cat#08-115) in 30% ethanol (filter sterilized)) is added per one 10 cm plate or 50 ml per well of the 96-well plate, and allowed to air dry for 2 hr. [1209]
• PC12 cells are routinely grown in RPMI-1640 medium (Bio Whittaker) containing 10% horse serum (JRH BIOSCIENCES, Cat. # 12449-78P), 5% heat-inactivated fetal bovine serum (FBS) supplemented with 100 units/mil penicillin and 100 ug/ml streptomycin on a precoated 10 cm tissue culture dish. One to four split is done every three to four days. Cells are removed from the plates by scraping and resuspended with pipetting up and down for more than 15 times. [1210]
• Transfect the EGR/SEAP/Neo construct into PC12 using the Lipofectamine protocol described in Example 11. EGR-SEAP/PC 12 stable cells are obtained by growing the cells in 300 ug/ml G418. The G418-free medium is used for routine growth but every one to two months, the cells should be re-grown in 300 ug/ml G418 for couple of passages. [1211]
• To assay for neuronal activity, a 10 cm plate with cells around 70 to 80% confluent is screened by removing the old medium. Wash the cells once with PBS (Phosphate buffered saline). Then starve the cells in low serum medium (RPMI-1640 containing 1% horse serum and 0.5% FBS with antibiotics) overnight. [1212]
• The next morning, remove the medium and wash the cells with PBS. Scrape off the cells from the plate, suspend the cells well in 2 ml low serum medium. Count the cell number and add more low serum medium to reach final cell density as 5×10[1213] ⁵ cells/ml.
• Add 200 ul of the cell suspension to each well of 96-well plate (equivalent to 1×10[1214] ⁵ cells/well). Add 50 ul supernatant produced by Example 11, 37° C. for 48 to 72 hr. As a positive control, a growth factor known to activate PC12 cells through EGR can be used, such as 50 ng/ul of Neuronal Growth Factor (NGF). Over fifty-fold induction of SEAP is typically seen in the positive control wells. SEAP assay the supernatant according to Example 17.
Example 16 High-throughput Screening Assay for T-cell Activity
• NF-κB (Nuclear Factor κB) is a transcription factor activated by a wide variety of agents including the inflammatory cytokines IL-1 and TNF, CD30 and CD40, lymphotoxin-alpha and lymphotoxin-beta, by exposure to LPS or thrombin, and by expression of certain viral gene products. As a transcription factor, NF-κB regulates the expression of genes involved in immune cell activation, control of apoptosis (NF-κB appears to shield cells from apoptosis), B and T-cell development, anti-viral and antimicrobial responses, and multiple stress responses. [1215]
• In non-stimulated conditions, NF-κB is retained in the cytoplasm with I-KB (inhibitor KB). However, upon stimulation, I-κB is phosphorylated and degraded, causing NF-κB to shuttle to the nucleus, thereby activating transcription of target genes. Target genes activated by NF-κB include IL-2, IL-6, GM-CSF, ICAM-1 and class 1 MHC. [1216]
• Due to its central role and ability to respond to a range of stimuli, reporter constructs utilizing the NF-κB promoter element are used to screen the supernatants produced in Example 11. Activators or inhibitors of NF-KB would be useful in treating diseases. For example, inhibitors of NF-κB could be used to treat those diseases related to the acute or chronic activation of NF-KB, such as rheumatoid arthritis. [1217]
• To construct a vector containing the NF-κB promoter element, a PCR based strategy is employed. The upstream primer contains four tandem copies of the NF-κB binding site (GGGGACTTTCCC) (SEQ ID NO:8), 18 bp of sequence complementary to the 5′ end of the SV40 early promoter sequence, and is flanked with an XhoI site: [1218]

  5′:GCGGCCTCGAGGGGACTTTCCCGGGGACTTTCCG	(SEQ ID NO:9)
  GGGACTTTCCGGGACTTTCCATCCTGCCATCTCAATT
  AG:3′

• The downstream primer is complementary to the 3′ end of the SV40 promoter and is flanked with a Hind III site: [1219]

  	5′:GCGGCAAGCTTTTTGCAAAGCCTAGGC:3′ (SEQ ID NO:4)

• PCR amplification is performed using the SV40 promoter template present in the pB-gal:promoter plasmid obtained from Clontech. The resulting PCR fragment is digested with XhoI and Hind III and subcloned into BLSK2-. (Stratagene) Sequencing with the T7 and T3 primers confirms the insert contains the following sequence: [1220]

  5′:CTCGAGGGGACTTTCCCGGGGACTTTCCGGGGAC	(SEQ ID NO:10)
  TTTCCGGGACTTTCCATCTGCCATCTCAATTAGTCAG
  CAACCATAGTCCCGCCCCTAACTCCGCCCATCCCGCC
  CCTAACTCCGCCCAGTTCCGCCCATTCTCCGCCCCAT
  GGCTGACTAATTTTTTTTATTTATGCAGAGGCCGAGG
  CCGCCTCGGCCTCTGAGCTATTCCAGAAGTAGTGAGG
  AGGCTTTTTTGGAGGCCTAGGCTTTTGCAAAAAGCT
  T:3′

• Next, replace the SV40 minimal promoter element present in the pSEAP2-promoter plasmid (Clontech) with this NF-κB/SV40 fragment using XhoI and HindIII. However, this vector does not contain a neomycin resistance gene, and therefore, is not preferred for mammalian expression systems. [1221]
• In order to generate stable mammalian cell lines, the NF-KB/SV40/SEAP cassette is removed from the above NF-κB/SEAP vector using restriction enzymes SalI and NotI, and inserted into a vector containing neomycin resistance. Particularly, the NF-κB/SV40/SEAP cassette was inserted into pGFP-1 (Clontech), replacing the GFP gene, after restricting pGFP-1 with SalI and NotI. [1222]
• Once NF-κB/SV40/SEAP/Neo vector is created, stable Jurkat T-cells are created and maintained according to the protocol described in Example 13. Similarly, the method for assaying supernatants with these stable Jurkat T-cells is also described in Example 13. As a positive control, exogenous TNF alpha (0.1, 1, 10 ng) is added to wells H9, H10, and H11, with a 5-10 fold activation typically observed. [1223]
Example 17 Assay for SEAP Activity
• As a reporter molecule for the assays described in Examples 13-16, SEAP activity is assayed using the Tropix Phospho-light Kit (Cat. BP-400) according to the following general procedure. The Tropix Phospho-light Kit supplies the Dilution, Assay, and Reaction Buffers used below. [1224]
• Prime a dispenser with the 2.5× Dilution Buffer and dispense 15 μl of 2.5× dilution buffer into Optiplates containing 35 μl of a supernatant. Seal the plates with a plastic sealer and incubate at 65° C. for 30 min. Separate the Optiplates to avoid uneven heating. [1225]
• Cool the samples to room temperature for 15 minutes. Empty the dispenser and prime with the Assay Buffer. Add 50 μl Assay Buffer and incubate at room temperature 5 min. Empty the dispenser and prime with the Reaction Buffer (see the table below). Add 50 μl Reaction Buffer and incubate at room temperature for 20 minutes. Since the intensity of the chemiluminescent signal is time dependent, and it takes about 10 minutes to read 5 plates on luminometer, one should treat 5 plates at each time and start the second set 10 minutes later. [1226]
• Read the relative light unit in the luminometer. Set H12 as blank, and print the results. An increase in chemiluminescence indicates reporter activity. [1227]

  Reaction Buffer Formulation:

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

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

Example 18 High-throughput Screening Assay Identifying Changes in Small Molecule Concentration and Membrane Permeability
• Binding of a ligand to a receptor is known to alter intracellular levels of small molecules, such as calcium, potassium, sodium, and pH, as well as alter membrane potential. These alterations can be measured in an assay to identify supernatants which bind to receptors of a particular cell. Although the following protocol describes an assay for calcium, this protocol can easily be modified to detect changes in potassium, sodium, pH, membrane potential, or any other small molecule which is detectable by a fluorescent probe. [1228]
• The following assay uses Fluorometric Imaging Plate Reader (“FLIPR”) to measure changes in fluorescent molecules (Molecular Probes) that bind small molecules. Clearly, any fluorescent molecule detecting a small molecule can be used instead of the calcium fluorescent molecule, fluo-4 (Molecular Probes, Inc.; catalog no. F-14202),used here. [1229]
• For adherent cells, seed the cells at 10,000 -20,000 cells/well in a Co-star black 96-well plate with clear bottom. The plate is incubated in a CO[1230] ₂ incubator for 20 hours. The adherent cells are washed two times in Biotek washer with 200 ul of HBSS (Hank's Balanced Salt Solution) leaving 100 ul of buffer after the final wash.
• A stock solution of 1 mg/ml fluo-4 is made in 10% pluronic acid DMSO. To load the cells with fluo-4, 50 ul of 12 ug/ml fluo-4 is added to each well. The plate is incubated at 37° C. in a CO[1231] ₂ incubator for 60 min. The plate is washed four times in the Biotek washer with HBSS leaving 100 ul of buffer.
• For non-adherent cells, the cells are spun down from culture media. Cells are re-suspended to 2-5×10[1232] ⁶ cells/ml with HBSS in a 50-ml conical tube. 4 ul of 1 mg/ml fluo-4 solution in 10% pluronic acid DMSO is added to each ml of cell suspension. The tube is then placed in a 37° C. water bath for 30-60 min. The cells are washed twice with HBSS, resuspended to 1×10⁶ cells/ml, and dispensed into a microplate, 100 ul/well. The plate is centrifuged at 1000 rpm for 5 min. The plate is then washed once in Denley CellWash with 200 ul, followed by an aspiration step to 100 ul final volume.
• For a non-cell based assay, each well contains a fluorescent molecule, such as fluo-4. The supernatant is added to the well, and a change in fluorescence is detected. [1233]
• To measure the fluorescence of intracellular calcium, the FLIPR is set for the following parameters: (1) System gain is 300-800 mW; (2) Exposure time is 0.4 second; (3) Camera F/stop is F/2; (4) Excitation is 488 nm; (5) Emission is 530 nm; and (6) Sample addition is 50 ul. Increased emission at 530 nm indicates an extracellular signaling event which has resulted in an increase in the intracellular Ca[1234] ⁺⁺ concentration.
Example 19 High-throughput Screening Assay Identifying Tyrosine Kinase Activity
• The Protein Tyrosine Kinases (PTK) represent a diverse group of transmembrane and cytoplasmic kinases. Within the Receptor Protein Tyrosine Kinase RPTK) group are receptors for a range of mitogenic and metabolic growth factors including the PDGF, FGF, EGF, NGF, HGF and Insulin receptor subfamilies. In addition there are a large family of RPTKs for which the corresponding ligand is unknown. Ligands for RPTKs include mainly secreted small proteins, but also membrane-bound and extracellular matrix proteins. [1235]
• Activation of RPTK by ligands involves ligand-mediated receptor dimerization, resulting in transphosphorylation of the receptor subunits and activation of the cytoplasmic tyrosine kinases. The cytoplasmic tyrosine kinases include receptor associated tyrosine kinases of the src-family (e.g., src, yes, Ick, lyn, fyn) and non-receptor linked and cytosolic protein tyrosine kinases, such as the Jak family, members of which mediate signal transduction triggered by the cytokine superfamily of receptors (e.g., the Interleukins, Interferons, GM-CSF, and Leptin). [1236]
• Because of the wide range of known factors capable of stimulating tyrosine kinase activity, the identification of novel human secreted proteins capable of activating tyrosine kinase signal transduction pathways are of interest. Therefore, the following protocol is designed to identify those novel human secreted proteins capable of activating the tyrosine kinase signal transduction pathways. [1237]
• Seed target cells (e.g., primary keratinocytes) at a density of approximately 25,000 cells per well in a 96 well Loprodyne Silent Screen Plates purchased from Nalge Nunc (Naperville, Ill.). The plates are sterilized with two 30 minute rinses with 100% ethanol, rinsed with water and dried overnight. Some plates are coated for 2 hr with 100 ml of cell culture grade type I collagen (50 mg/ml), gelatin (2%) or polylysine (50 mg/ml), all of which can be purchased from Sigma Chemicals (St. Louis, Mo.) or 10% Matrigel purchased from Becton Dickinson (Bedford, Mass.), or calf serum, rinsed with PBS and stored at 4° C. Cell growth on these plates is assayed by seeding 5,000 cells/well in growth medium and indirect quantitation of cell number through use of alamarBlue as described by the manufacturer Alamar Biosciences, Inc. (Sacramento, Calif.) after 48 hr. Falcon plate covers #3071 from Becton Dickinson (Bedford, Mass.) are used to cover the Loprodyne Silent Screen Plates. Falcon Microtest III cell culture plates can also be used in some proliferation experiments. [1238]
• To prepare extracts, A431 cells are seeded onto the nylon membranes of Loprodyne plates (20,000/200ml/well) and cultured overnight in complete medium. Cells are quiesced by incubation in serum-free basal medium for 24 hr. After 5-20 minutes treatment with EGF (60 ng/ml) or 50 ul of the supernatant produced in Example 11, the medium was removed and 100 ml of extraction buffer ((20 mM HEPES pH 7.5, 0.15 M NaCl, 1% Triton X-100, 0.1% SDS, 2 mM Na3VO4, 2 mM Na4P2O7 and a cocktail of protease inhibitors (# 1836170) obtained from Boeheringer Mannheim (Indianapolis, Ind.) is added to each well and the plate is shaken on a rotating shaker for 5 minutes at 4° C. The plate is then placed in a vacuum transfer manifold and the extract filtered through the 0.45 mm membrane bottoms of each well using house vacuum. Extracts are collected in a 96-well catch/assay plate in the bottom of the vacuum manifold and immediately placed on ice. To obtain extracts clarified by centrifugation, the content of each well, after detergent solubilization for 5 minutes, is removed and centrifuged for 15 minutes at 4° C. at 16,000× g. [1239]
• Test the filtered extracts for levels of tyrosine kinase activity. Although many methods of detecting tyrosine kinase activity are known, one method is described here. [1240]
• Generally, the tyrosine kinase activity of a supernatant is evaluated by determining its ability to phosphorylate a tyrosine residue on a specific substrate (a biotinylated peptide). Biotinylated peptides that can be used for this purpose include PSK1 (corresponding to amino acids 6-20 of the cell division kinase cdc2-p34) and PSK2 (corresponding to amino acids 1-17 of gastrin). Both peptides are substrates for a range of tyrosine kinases and are available from Boehringer Mannheim. [1241]
• The tyrosine kinase reaction is set up by adding the following components in order. First, add 10 ul of 5 uM Biotinylated Peptide, then 10 ul ATP/Mg[1242] ₂₊ (5 mM ATP/50 mM MgCl₂), then 10 ul of 5× Assay Buffer (40 mM imidazole hydrochloride, pH 7.3, 40 mM beta-glycerophosphate, 1 mM EGTA, 100 mM MgCl₂, 5 mM MnCl₂, 0.5 mg/ml BSA), then 5 ul of Sodium Vanadate (1 mM), and then 5 ul of water. Mix the components gently and preincubate the reaction mix at 30° C. for 2 min. Initial the reaction by adding 10 ul of the control enzyme or the filtered supernatant.
• The tyrosine kinase assay reaction is then terminated by adding 10 ul of 120 mm EDTA and place the reactions on ice. [1243]
• Tyrosine kinase activity is determined by transferring 50 ul aliquot of reaction mixture to a microtiter plate (MTP) module and incubating at 37° C. for 20 min. This allows the streptavadin coated 96 well plate to associate with the biotinylated peptide. Wash the MTP module with 300 ul/well of PBS four times. Next add 75 ul of anti-phospotyrosine antibody conjugated to horse radish peroxidase(anti-P-Tyr-POD(0.5u/ml)) to each well and incubate at 37° C. for one hour. Wash the well as above. [1244]
• Next add 100 ul of peroxidase substrate solution (Boehringer Mannheim) and incubate at room temperature for at least 5 mins (up to 30 min). Measure the absorbance of the sample at 405 nm by using ELISA reader. The level of bound peroxidase activity is quantitated using an ELISA reader and reflects the level of tyrosine kinase activity. [1245]
Example 20 High-throughput Screening Assay Identifying Phosphorylation Activity
• As a potential alternative and/or compliment to the assay of protein tyrosine kinase activity described in Example 19, an assay which detects activation (phosphorylation) of major intracellular signal transduction intermediates can also be used. For example, as described below one particular assay can detect tyrosine phosphorylation of the Erk-1 and Erk-2 kinases. However, phosphorylation of other molecules, such as Raf, JNK, p38 MAP, Map kinase kinase (MEK), MEK kinase, Src, Muscle specific kinase (MuSK), IRAK, Tec, and Janus, as well as any other phosphoserine, phosphotyrosine, or phosphothreonine molecule, can be detected by substituting these molecules for Erk-1 or Erk-2 in the following assay. [1246]
• Specifically, assay plates are made by coating the wells of a 96-well ELISA plate with 0.1 ml of protein G (1 ug/ml) for 2 hr at room temp, (RT). The plates are then rinsed with PBS and blocked with 3% BSA/PBS for 1 hr at RT. The protein G plates are then treated with 2 commercial monoclonal antibodies (100 ng/well) against Erk-1 and Erk-2 (1 hr at RT) (Santa Cruz Biotechnology). (To detect other molecules, this step can easily be modified by substituting a monoclonal antibody detecting any of the above described molecules.) After 3-5 rinses with PBS, the plates are stored at 4° C. until use. [1247]
• A431 cells are seeded at 20,000/well in a 96-well Loprodyne filterplate and cultured overnight in growth medium. The cells are then starved for 48 hr in basal medium (DMEM) and then treated with EGF (6ng/well) or 50 ul of the supernatants obtained in Example 11 for 5-20 minutes. The cells are then solubilized and extracts filtered directly into the assay plate. [1248]
• After incubation with the extract for 1 hr at RT, the wells are again rinsed. As a positive control, a commercial preparation of MAP kinase (10 ng/well) is used in place of A43 1 extract. Plates are then treated with a commercial polyclonal (rabbit) antibody (1 ug/mil) which specifically recognizes the phosphorylated epitope of the Erk-1 and Erk-2 kinases (1 hr at RT). This antibody is biotinylated by standard procedures. The bound polyclonal antibody is then quantitated by successive incubations with Europium-streptavidin and Europium fluorescence enhancing reagent in the Wallac DELFIA instrument (time-resolved fluorescence). An increased fluorescent signal over background indicates a phosphorylation. [1249]
Example 21 Method of Determining Alterations in a Gene Corresponding to a Polynucleotide
• RNA isolated from entire families or individual patients presenting with a phenotype of interest (such as a disease) is be isolated. cDNA is then generated from these RNA samples using protocols known in the art. (See, Sambrook.) The cDNA is then used as a template for PCR, employing primers surrounding regions of interest in SEQ ID NO:X. Suggested PCR conditions consist of 35 cycles at 95° C. for 30 seconds; 60-120 seconds at 52-58° C.; and 60-120 seconds at 70° C., using buffer solutions described in Sidransky, D., et al., Science 252:706 (1991). [1250]
• PCR products are then sequenced using primers labeled at their 5′ end with T4 polynucleotide kinase, employing SequiTherm Polymerase. (Epicentre Technologies). The intron-exon borders of selected exons is also determined and genomic PCR products analyzed to confirm the results. PCR products harboring suspected mutations is then cloned and sequenced to validate the results of the direct sequencing. [1251]
• PCR products is cloned into T-tailed vectors as described in Holton, T. A. and Graham, M. W., Nucleic Acids Research, 19:1156 (1991) and sequenced with T7 polymerase (United States Biochemical). Affected individuals are identified by mutations not present in unaffected individuals. [1252]
• Genomic rearrangements are also observed as a method of determining alterations in a gene corresponding to a polynucleotide. Genomic clones isolated according to Example 2 are nick-translated with digoxigenindeoxy-uridine 5′-triphosphate (Boehringer Manheim), and FISH performed as described in Johnson, Cg. et al., Methods Cell Biol. 35:73-99 (1991). Hybridization with the labeled probe is carried out using a vast excess of human cot-1 DNA for specific hybridization to the corresponding genomic locus. [1253]
• Chromosomes are counterstained with 4,6-diamino-2-phenylidole and propidium iodide, producing a combination of C- and R-bands. Aligned images for precise mapping are obtained using a triple-band filter set (Chroma Technology, Brattleboro, Vt.) in combination with a cooled charge-coupled device camera (Photometrics, Tucson, Ariz.) and variable excitation wavelength filters. (Johnson, Cv. et al., Genet. Anal. Tech. Appl., 8:75 (1991).) Image collection, analysis and chromosomal fractional length measurements are performed using the ISee Graphical Program System. (Inovision Corporation, Durham, N.C.) Chromosome alterations of the genomic region hybridized by the probe are identified as insertions, deletions, and translocations. These alterations are used as a diagnostic marker for an associated disease. [1254]
Example 22 Method of Detecting Abnormal Levels of a Polypeptide in a Biological Sample
• A polypeptide of the present invention can be detected in a biological sample, and if an increased or decreased level of the polypeptide is detected, this polypeptide is a marker for a particular phenotype. Methods of detection are numerous, and thus, it is understood that one skilled in the art can modify the following assay to fit their particular needs. [1255]
• For example, antibody-sandwich ELISAs are used to detect polypeptides in a sample, preferably a biological sample. Wells of a microtiter plate are coated with specific antibodies, at a final concentration of 0.2 to 10 ug/ml. The antibodies are either monoclonal or polyclonal and are produced by the method described in Example 10. The wells are blocked so that non-specific binding of the polypeptide to the well is reduced. [1256]
• The coated wells are then incubated for >2 hours at RT with a sample containing the polypeptide. Preferably, serial dilutions of the sample should be used to validate results. The plates are then washed three times with deionized or distilled water to remove unbounded polypeptide. [1257]
• Next, 50 ul of specific antibody-alkaline phosphatase conjugate, at a concentration of 25-400 ng, is added and incubated for 2 hours at room temperature. The plates are again washed three times with deionized or distilled water to remove unbounded conjugate. [1258]
• Add 75 ul of 4-methylumbelliferyl phosphate (MUP) or p-nitrophenyl phosphate (NPP) substrate solution to each well and incubate 1 hour at room temperature. Measure the reaction by a microtiter plate reader. Prepare a standard curve, using serial dilutions of a control sample, and plot polypeptide concentration on the X-axis (log scale) and fluorescence or absorbance of the Y-axis (linear scale). Interpolate the concentration of the polypeptide in the sample using the standard curve. [1259]
Example 23 Formulating a Polypeptide
• The secreted polypeptide composition will be formulated and dosed in a fashion consistent with good medical practice, taking into account the clinical condition of the individual patient (especially the side effects of treatment with the secreted polypeptide alone), the site of delivery, the method of administration, the scheduling of administration, and other factors known to practitioners. The “effective amount” for purposes herein is thus determined by such considerations. [1260]
• As a general proposition, the total pharmaceutically effective amount of secreted polypeptide administered parenterally per dose will be in the range of about 1 μg/kg/day to 10 mg/kg/day of patient body weight, although, as noted above, this will be subject to therapeutic discretion. More preferably, this dose is at least 0.01 mg/kg/day, and most preferably for humans between about 0.01 and 1 mg/kg/day for the hormone. If given continuously, the secreted polypeptide is typically administered at a dose rate of about 1 μg/kg/hour to about 50 μg/kg/hour, either by 1-4 injections per day or by continuous subcutaneous infusions, for example, using a mini-pump. An intravenous bag solution may also be employed. The length of treatment needed to observe changes and the interval following treatment for responses to occur appears to vary depending on the desired effect. [1261]
• Pharmaceutical compositions containing the secreted protein of the invention are administered orally, rectally, parenterally, intracistemally, intravaginally, intraperitoneally, topically (as by powders, ointments, gels, drops or transdermal patch), bucally, or as an oral or nasal spray. “Pharmaceutically acceptable carrier” refers to a non-toxic solid, semisolid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type. The term “parenteral” as used herein refers to modes of administration which include intravenous, intramuscular, intraperitoneal, intrasternal, subcutaneous and intraarticular injection and infusion. [1262]
• The secreted polypeptide is also suitably administered by sustained-release systems. Suitable examples of sustained-release compositions include semi-permeable polymer matrices in the form of shaped articles, e.g., films, or mirocapsules. Sustained-release matrices include polylactides (U.S. Pat. No. 3,773,919, EP 58,481), copolymers of L-glutamic acid and gamma-ethyl-L-glutamate (Sidman, U. et al., Biopolymers 22:547-556 (1983)), poly (2-hydroxyethyl methacrylate) (R. Langer et al., J. Biomed. Mater. Res. 15:167-277 (1981), and R. Langer, Chem. Tech. 12:98-105 (1982)), ethylene vinyl acetate (R. Langer et al.) or poly-D-(−)-3-hydroxybutyric acid (EP 133,988). Sustained-release compositions also include liposomally entrapped polypeptides. Liposomes containing the secreted polypeptide are prepared by methods known per se: DE 3,218,121; Epstein et al., Proc. Natl. Acad. Sci. USA 82:3688-3692 (1985); Hwang et al., Proc. Natl. Acad. Sci. USA 77:4030-4034 (1980); EP 52,322; EP 36,676; EP 88,046; EP 143,949; EP 142,641; Japanese Pat. Appl. 83-118008; U.S. Pat. Nos. 4,485,045 and 4,544,545; and EP 102,324. Ordinarily, the liposomes are of the small (about 200-800 Angstroms) unilamellar type in which the lipid content is greater than about 30 mol. percent cholesterol, the selected proportion being adjusted for the optimal secreted polypeptide therapy. [1263]
• For parenteral administration, in one embodiment, the secreted polypeptide is formulated generally by mixing it at the desired degree of purity, in a unit dosage injectable form (solution, suspension, or emulsion), with a pharmaceutically acceptable carrier, i.e., one that is non-toxic to recipients at the dosages and concentrations employed and is compatible with other ingredients of the formulation. For example, the formulation preferably does not include oxidizing agents and other compounds that are known to be deleterious to polypeptides. [1264]
• Generally, the formulations are prepared by contacting the polypeptide uniformly and intimately with liquid carriers or finely divided solid carriers or both. Then, if necessary, the product is shaped into the desired formulation. Preferably the carrier is a parenteral carrier, more preferably a solution that is isotonic with the blood of the recipient. Examples of such carrier vehicles include water, saline, Ringer's solution, and dextrose solution. Non-aqueous vehicles such as fixed oils and ethyl oleate are also useful herein, as well as liposomes. [1265]
• The carrier suitably contains minor amounts of additives such as substances that enhance isotonicity and chemical stability. Such materials are non-toxic to recipients at the dosages and concentrations employed, and include buffers such as phosphate, citrate, succinate, acetic acid, and other organic acids or their salts; antioxidants such as ascorbic acid; low molecular weight (less than about ten residues) polypeptides, e.g., polyarginine or tripeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids, such as glycine, glutamic acid, aspartic acid, or arginine; monosaccharides, disaccharides, and other carbohydrates including cellulose or its derivatives, glucose, manose, or dextrins; chelating agents such as EDTA; sugar alcohols such as mannitol or sorbitol; counterions such as sodium; and/or nonionic surfactants such as polysorbates, poloxamers, or PEG. [1266]
• The secreted polypeptide is typically formulated in such vehicles at a concentration of about 0.1 mg/ml to 100 mg/ml, preferably 1-10 mg/mil, at a pH of about 3 to 8. It will be understood that the use of certain of the foregoing excipients, carriers, or stabilizers will result in the formation of polypeptide salts. [1267]
• Any polypeptide to be used for therapeutic administration can be sterile. Sterility is readily accomplished by filtration through sterile filtration membranes (e.g., 0.2 micron membranes). Therapeutic polypeptide compositions generally are placed into a container having a sterile access port, for example, an intravenous solution bag or vial having a stopper pierceable by a hypodermic injection needle. [1268]
• Polypeptides ordinarily will be stored in unit or multi-dose containers, for example, sealed ampoules or vials; as an aqueous solution or as a lyophilized formulation for reconstitution. As an example of a lyophilized formulation, 10-ml vials are filled with 5 ml of sterile-filtered 1% (w/v) aqueous polypeptide solution, and the resulting mixture is lyophilized. The infusion solution is prepared by reconstituting the lyophilized polypeptide using bacteriostatic Water-for-Injection. [1269]
• The invention also provides a pharmaceutical pack or kit comprising one or more containers filled with one or more of the ingredients of the pharmaceutical compositions of the invention. Associated with such container(s) can be a notice in the form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals or biological products, which notice reflects approval by the agency of manufacture, use or sale for human administration. In addition, the polypeptides of the present invention may be employed in conjunction with other therapeutic compounds. [1270]
Example 24 Method of Treating Decreased Levels of the Polypeptide
• It will be appreciated that conditions caused by a decrease in the standard or normal expression level of a secreted protein in an individual can be treated by administering the polypeptide of the present invention, preferably in the secreted form. Thus, the invention also provides a method of treatment of an individual in need of an increased level of the polypeptide comprising administering to such an individual a pharmaceutical composition comprising an amount of the polypeptide to increase the activity level of the polypeptide in such an individual. [1271]
• For example, a patient with decreased levels of a polypeptide receives a daily dose 0.1-100 ug/kg of the polypeptide for six consecutive days. Preferably, the polypeptide is in the secreted form. The exact details of the dosing scheme, based on administration and formulation, are provided in Example 23. [1272]
Example 25 Method of Treating Increased Levels of the Polypeptide
• Antisense technology is used to inhibit production of a polypeptide of the present invention. This technology is one example of a method of decreasing levels of a polypeptide, preferably a secreted form, due to a variety of etiologies, such as cancer. [1273]
• For example, a patient diagnosed with abnormally increased levels of a polypeptide is administered intravenously antisense polynucleotides at 0.5, 1.0, 1.5, 2.0 and 3.0 mg/kg day for 21 days. This treatment is repeated after a 7-day rest period if the treatment was well tolerated. The formulation of the antisense polynucleotide is provided in Example 23. [1274]
Example 26 Method of Treatment Using Gene Therapy
• One method of gene therapy transplants fibroblasts, which are capable of expressing a polypeptide, onto a patient. Generally, fibroblasts are obtained from a subject by skin biopsy. The resulting tissue is placed in tissue-culture medium and separated into small pieces. Small chunks of the tissue are placed on a wet surface of a tissue culture flask, approximately ten pieces are placed in each flask. The flask is turned upside down, closed tight and left at room temperature over night. After 24 hours at room temperature, the flask is inverted and the chunks of tissue remain fixed to the bottom of the flask and fresh media (e.g., Ham's F12 media, with 10% FBS, penicillin and streptomycin) is added. The flasks are then incubated at 37° C. for approximately one week. [1275]
• At this time, fresh media is added and subsequently changed every several days. After an additional two weeks in culture, a monolayer of fibroblasts emerge. The monolayer is trypsinized and scaled into larger flasks. [1276]
• pMV-7 (Kirschmeier, P. T. et al., DNA, 7:219-25 (1988)), flanked by the long terminal repeats of the Moloney murine sarcoma virus, is digested with EcoRI and HindIII and subsequently treated with calf intestinal phosphatase. The linear vector is fractionated on agarose gel and purified, using glass beads. [1277]
• The cDNA encoding a polypeptide of the present invention can be amplified using PCR primers which correspond to the 5′ and 3′ end sequences respectively as set forth in Example 1. Preferably, the 5′ primer contains an EcoRI site and the 3′ primer includes a HindIII site. Equal quantities of the Moloney murine sarcoma virus linear backbone and the amplified EcoRI and HindIII fragment are added together, in the presence of T4 DNA ligase. The resulting mixture is maintained under conditions appropriate for ligation of the two fragments. The ligation mixture is then used to transform bacteria HB 101, which are then plated onto agar containing kanamycin for the purpose of confirming that the vector has the gene of interest properly inserted. [1278]
• The amphotropic pA317 or GP+am12 packaging cells are grown in tissue culture to confluent density in Dulbecco's Modified Eagles Medium (DMEM) with 10% calf serum (CS), penicillin and streptomycin. The MSV vector containing the gene is then added to the media and the packaging cells transduced with the vector. The packaging cells now produce infectious viral particles containing the gene (the packaging cells are now referred to as producer cells). [1279]
• Fresh media is added to the transduced producer cells, and subsequently, the media is harvested from a 10 cm plate of confluent producer cells. The spent media, containing the infectious viral particles, is filtered through a millipore filter to remove detached producer cells and this media is then used to infect fibroblast cells. Media is removed from a sub-confluent plate of fibroblasts and quickly replaced with the media from the producer cells. This media is removed and replaced with fresh media. If the titer of virus is high, then virtually all fibroblasts will be infected and no selection is required. If the titer is very low, then it is necessary to use a retroviral vector that has a selectable marker, such as neo or his. Once the fibroblasts have been efficiently infected, the fibroblasts are analyzed to determine whether protein is produced. [1280]
• The engineered fibroblasts are then transplanted onto the host, either alone or after having been grown to confluence on cytodex 3 microcarrier beads. [1281]
• It will be clear that the invention may be practiced otherwise than as particularly described in the foregoing description and examples. Numerous modifications and variations of the present invention are possible in light of the above teachings and, therefore, are within the scope of the appended claims. [1282]
• The entire disclosure of each document cited (including patents, patent applications, journal articles, abstracts, laboratory manuals, books, or other disclosures) in the Background of the Invention, Detailed Description, and Examples is hereby incorporated herein by reference. Further, the hard copy of the sequence listing submitted herewith and the corresponding computer readable form are both incorporated herein by reference in their entireties. [1283]
• 0

  SEQUENCE LISTING

  <160> NUMBER OF SEQ ID NOS: 672

  <210> SEQ ID NO 1

  <211> LENGTH: 733

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 1

  gggatccgga gcccaaatct tctgacaaaa ctcacacatg cccaccgtgc ccagcacctg 60

  aattcgaggg tgcaccgtca gtcttcctct tccccccaaa acccaaggac accctcatga 120

  tctcccggac tcctgaggtc acatgcgtgg tggtggacgt aagccacgaa gaccctgagg 180

  tcaagttcaa ctggtacgtg gacggcgtgg aggtgcataa tgccaagaca aagccgcggg 240

  aggagcagta caacagcacg taccgtgtgg tcagcgtcct caccgtcctg caccaggact 300

  ggctgaatgg caaggagtac aagtgcaagg tctccaacaa agccctccca acccccatcg 360

  agaaaaccat ctccaaagcc aaagggcagc cccgagaacc acaggtgtac accctgcccc 420

  catcccggga tgagctgacc aagaaccagg tcagcctgac ctgcctggtc aaaggcttct 480

  atccaagcga catcgccgtg gagtgggaga gcaatgggca gccggagaac aactacaaga 540

  ccacgcctcc cgtgctggac tccgacggct ccttcttcct ctacagcaag ctcaccgtgg 600

  acaagagcag gtggcagcag gggaacgtct tctcatgctc cgtgatgcat gaggctctgc 660

  acaaccacta cacgcagaag agcctctccc tgtctccggg taaatgagtg cgacggccgc 720

  gactctagag gat 733

  <210> SEQ ID NO 2

  <211> LENGTH: 5

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: Site

  <222> LOCATION: (3)

  <223> OTHER INFORMATION: Xaa equals any of the twenty naturally ocurring

  L-amino acids

  <400> SEQUENCE: 2

  Trp Ser Xaa Trp Ser

  1 5

  <210> SEQ ID NO 3

  <211> LENGTH: 86

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 3

  gcgcctcgag atttccccga aatctagatt tccccgaaat gatttccccg aaatgatttc 60

  cccgaaatat ctgccatctc aattag 86

  <210> SEQ ID NO 4

  <211> LENGTH: 27

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 4

  gcggcaagct ttttgcaaag cctaggc 27

  <210> SEQ ID NO 5

  <211> LENGTH: 271

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 5

  ctcgagattt ccccgaaatc tagatttccc cgaaatgatt tccccgaaat gatttccccg 60

  aaatatctgc catctcaatt agtcagcaac catagtcccg cccctaactc cgcccatccc 120

  gcccctaact ccgcccagtt ccgcccattc tccgccccat ggctgactaa ttttttttat 180

  ttatgcagag gccgaggccg cctcggcctc tgagctattc cagaagtagt gaggaggctt 240

  ttttggaggc ctaggctttt gcaaaaagct t 271

  <210> SEQ ID NO 6

  <211> LENGTH: 32

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 6

  gcgctcgagg gatgacagcg atagaacccc gg 32

  <210> SEQ ID NO 7

  <211> LENGTH: 31

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 7

  gcgaagcttc gcgactcccc ggatccgcct c 31

  <210> SEQ ID NO 8

  <211> LENGTH: 12

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 8

  ggggactttc cc 12

  <210> SEQ ID NO 9

  <211> LENGTH: 73

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 9

  gcggcctcga ggggactttc ccggggactt tccggggact ttccgggact ttccatcctg 60

  ccatctcaat tag 73

  <210> SEQ ID NO 10

  <211> LENGTH: 256

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 10

  ctcgagggga ctttcccggg gactttccgg ggactttccg ggactttcca tctgccatct 60

  caattagtca gcaaccatag tcccgcccct aactccgccc atcccgcccc taactccgcc 120

  cagttccgcc cattctccgc cccatggctg actaattttt tttatttatg cagaggccga 180

  ggccgcctcg gcctctgagc tattccagaa gtagtgagga ggcttttttg gaggcctagg 240

  cttttgcaaa aagctt 256

  <210> SEQ ID NO 11

  <211> LENGTH: 1882

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (12)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (565)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 11

  ttcggcacgg anactggaag gaaagaaaga aaggtcagct ttggcccaga tgtggttacc 60

  ccttggtctc ctgtctttat gtctttctcc tcttcctatt ctgtcatctc cctcacttaa 120

  gtctcaggcc tgtcagcagc tcctgtggac attgccatcc cctctggtag ccttcagagc 180

  aaacaggaca acctatgtta tggatgtttc caccaaccag ggtagtggca tggagcaccg 240

  taaccatctg tgcttctgtg atctctatga cagagccact tctccacctc tgaaatgttc 300

  cctgctctga aatctggcat gagatggcac aggtgaccac gcagaagcca ccagaatytt 360

  gcctgcccta ttcctcctcc caagtctgtt ctcttattgt caacctcagc acaacaggct 420

  ggcgccaatg gcattacaga gaaagcaatc tgtgtggcta gtgggcagat taccatgcaa 480

  gccccaggag aaatggagga gctttgtagc cacctccctg tcasccagta ttaacatgtc 540

  cccttccccc tgccccgccg taganttcag gacattcgcc cctgtgtgcc accaaaccag 600

  ggactttccc cttsssttgg gttggcatcc ctgggctctc tcctggtacc cagcaagacg 660

  tctgttccag ggcagggcac gagctttcaa gctccgttac tatggcgatg gccatgatgt 720

  tacaatccca cttgcctgaa taatcaagtg ggaasgggaa gcasagggaa atggggccat 780

  gtgaatgcag ctgctctgtt ctccctaccc tgaggaaaaa ccaaagggaa gcaacaggaa 840

  cttctgcaac tggtttttat cggaaagatc atcctgcctg cagatgctgt tgaaggggca 900

  caagaaattg gagctggaga agattgatga aagtgcaggt gtgtaaggaa atagaacagt 960

  ctgctgggag tcagacctgg aattctgatt ccaaactctt tattactttg ggaagtcact 1020

  cagcctcccc gtagccatct ccagggtgac ggaacccagt gtattacctg ctggaaccaa 1080

  ggaaactaac aatgtaggtt actagtgaat accccaatgg tttctccaat tatgcccatg 1140

  ccaccaaaac aataaaacaa aattctctaa cactgcaaag agtgagccat gcctgttaac 1200

  actgtaaaga atgtaacatg tgggggacac acaggggcag atgggatggt ttagtttagg 1260

  attttattag tgcatgccct accctctggg cgaacgtccc ctctgaggtt ttcttctcgg 1320

  tggggggatt taacttctgt cctagggaaa acagtgtctg atgaggagtg tttccaacac 1380

  aggctacatg aattccccta taccagtgcg aaagcagcca ggagtccccg ttggaaaaga 1440

  acaatgccac tctcttttat gtatcttggt tctgcaactc atttgttgta agtagggtta 1500

  atcgagtatc aggttcacag tatcctgccc ttattatttt atgattcact gactcaagtt 1560

  ccacgaagtc cttagaaatg gacctcttca tgtaaaatat cttgagaata ataaatgtga 1620

  gggaataaga aaggcaagct ttggacacag atatgatagg tgcatcagct tcggaagaga 1680

  agaatgatgt gcagagtgtt aggaagacat ccgggctgct gagactcggg attagaagaa 1740

  agagaggtaa ataaagtggg tcctggaatc ttttaggact tctgctgtag gacaaacagc 1800

  tgcctttggt gttttaatgt ctcccaaagt acccttcagc caataaatac catctgttgg 1860

  tgcaaaaaaa aaaaaaaaaa aa 1882

  <210> SEQ ID NO 12

  <211> LENGTH: 1590

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (1374)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1397)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1516)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 12

  gggtcgaccc acgcgtccgg agattctggg aggatcccga gtacccccca gttgcagtca 60

  tgtcaagact gatgctcagg aggatcccaa ctgtcatgag caacacccat cgaacacagc 120

  catccacctg ggaacagatc aagaagctgt cacagatggt gggagaaaac ctgaggaaag 180

  cgggacaacc agtcacaatg agtaatttaa tggtagctat gatagcagtg atcaccattg 240

  ccgtgagtat tccttcaaca agggctgaca cagagatcag ttatacttat tgggcatatt 300

  tgtcaatttt ggctggcaat aatgcctgga tataatcact ttatgacaca gttacacatg 360

  ctttctggtc tcaatattta ccataataag tctgctccta taattgaggc ataccaccct 420

  caaaaatcta tttgtaaaca aaattgaacc tggccagaaa aaatgaatgt acttttttag 480

  gaaggttgca ttgcagaaca ggcagaggtg ctgcacaacg attcctatgg aatcattatt 540

  gattggtccc ctaaggggat gtttagcttg aattgcacct cttagtctgc atgtcacagc 600

  cacactgtgt tcaactggtc tgaacagaat ggtcagatgg tacaaatggt aagacgtatg 660

  gcaagagttc ctattatctg gaaccatggc agtatagggg cacctcaacc tcaaatgata 720

  tggcccattg taggagctaa acataaggat ttgtggcaac tgttaatagc tcttaataag 780

  atcaaaattt gggaaagaat aaaaaagcat ctagaaggac actctgcaaa cttgtctttg 840

  gatattgcaa aatatatata tatatttaaa gcatcccagg cacacctgac cttaatgcca 900

  gaactggagt gctcgaagga gctgcagaca gattagcagc tagtaaccca ttaaaatgga 960

  taaaaacact tagaagctct gtgatttcaa tgatgattgt gcttttaatc tgtgttgttt 1020

  gtctttatat agtctgcaga tgctgatctt gactcctgtg agaagtagct caccgtgaca 1080

  aagctgcctt ggctttttat cgctttgcaa aacaagagaa tggggacaag ttgggaacag 1140

  gccccaaaat ctggccataa actggcccct aaactggtca taaacaaaat ctctgcagca 1200

  ctgtcacatg cttgtgatag cctgacgccc acgttggaag gctgtcggtt taccggaatg 1260

  agggcaagga acaactggcc cactcagggc ggataaccac ttaaggcatt cttaaaccac 1320

  aaacaatagc atgagctatc tgtgccttaa ggacatgttc atgctgcaga taantagcca 1380

  gagcccatcc ctttacntcg gcccatccct ttatttccca taaggaatac ttatagttaa 1440

  tctatagaaa caatgcttat cactggcttg ctgtcaataa atatgtgggt aaatctctgt 1500

  tcaaggctct cagctntgaa ggctgtgaga cccctgattt cccactccac aatctaaaaa 1560

  aaaaataaaa acaaaaaaaa aaaaaaaaaa 1590

  <210> SEQ ID NO 13

  <211> LENGTH: 1373

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 13

  tcgacccacg cgtccgttca gaaaaaggat ttgacaaaat tcagtgccca ttcatggtta 60

  aaaaaaaaaa aaactttcag aaaaatgata atggaggaga tctttctcaa cttgataaag 120

  aacatctaca aaagccccta cagccaatgt aacacataat agtaaaagac taattgcttt 180

  tctccaatat cagggatatt agggacagag atgtctgtcc tcaccactct tattcaacat 240

  attgctggaa gttctgtcta gtgcagtgag gaaagaaaag gaattaaaaa gcatgcagac 300

  aaaaagaagg aaacaaaact gtctctattt gcaaatgaca tgattctcta aataaaaaat 360

  cccaaggaat ctacaaaaaa aactagagct aggtggggtg tggtggctca tgcctgtaat 420

  cccagcactt tgggaggctg aattaagagg attacctaaa ccaagaagtt caagaccagc 480

  ctgcgcaaca tagtaagacc cccatctcta caaaaaattg aaaaattagc tggatgtatt 540

  agctactcag ggagctgagc tgggagggat tgtttgagcc agagaggtca gggctctggt 600

  gatccatgat cacatcacca tactccagcc tgggcaaccg agtgagacct gtccttaaaa 660

  aacaaacaaa aacaaactag atctagtgag agttcagcaa gccctcaagc tacaagacct 720

  atataccaaa aatcaacttg catttctata tactattaat gaacatatgg gaaacctaaa 780

  tttaaaagat agtaccactt aacaattgtt tcacaaaaat gaattacctg ggcataaatt 840

  aaataaacat atacaggatc tgtatgctaa aaattgcaaa atactgataa aagaaatcaa 900

  agcaaaccca aagaagtgga gacacatacc gtgttcatgt actggaaggc tcagcagaga 960

  cgtgggttcc ctccagactg atgtacaggt ttgatgtact tgctagcaaa aatcccagca 1020

  aggtattttt ttgtagatgc gcaagattat tctaaaattt gtatggaagg gcagtgaaac 1080

  taaaagtcac gaaaataatc ttgaaaaaga aaaagaaaat gggcagaatc actgtatttg 1140

  ataacatacc ttgttatata actgcagtaa tcaagacagt atagtgttgg tgaagggaca 1200

  gacacaaggt caatgaaaca gaatagagaa cccagacata gacccacaca agtaccacca 1260

  gtggatttgg acaaggtgca aaagcaactc attggaggaa ggcagcctat ttagccaatg 1320

  tgactggagc actggatacc cataagccaa aaaaagaaaa aaaaaaaaaa agg 1373

  <210> SEQ ID NO 14

  <211> LENGTH: 1142

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (341)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (369)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (386)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (408)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (412)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (526)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (598)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (676)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (739)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 14

  tcgacccacg cgtccgtctt cctcctgcgt cctcccccgc tgcctccgct gctcccgacg 60

  cggagcccgg agcccgcgcc gagcccctgg cctcgcggtg ccatgctgcc ccggcggcgg 120

  cgctgaagga tggcgacgcc gctgcctccg ccctccccgc ggcacctgcg gctgctgcgg 180

  ctgctgctct ccggcctcgt cctcggcgcc gccctgcgtg gagccgccgc cggccacccg 240

  gaatgttgcc gcctgtcccg ggagcctgga ctgtgccctg aagaagcggg caagtgtcct 300

  cctggtgcac atgcctgtgg gcctgccttc agcccttcca naaggaacag caaaggcttg 360

  ttttgccang atgcgccggg cttcangcgg gggccgggcc caacccanac tngaaatgag 420

  attgattcct ggcccaaggg agcttgcccg gaaaggaatt tggacatcaa ttccgcccta 480

  acccaaggac ggacagcggt tcccggagct tgccaccttg ggattntcgg cacgggggca 540

  ggggctggag ctgggcttcc cttccactcc aggaaccccc acgcccacgc cccacacnta 600

  ccatgggtta cccctgtgtc atccgacccg gtgcacatgt cgcccctgga gccccgggga 660

  gggcaaggcg acggcntcgc ccttgtgctg atcctggcgt tctgtgtggc cggtgcagcc 720

  gccctctccg tagcctccnt ctgctggtgc aggctgcagc gtgagatccg cctgactcag 780

  aaggccgagt acgccactgc gaaggccctg gctacacctg cagctacccc ggatctcgct 840

  tggggaccag cgcctggcac agagcgcgga gatgtaccac taccagcacc aacggcaaca 900

  gatgttgtcc ctggagcggc ataaagagcc acccaaggag ctggacacgg ctcttcggat 960

  gaggagaatg aggacggaga cttcacggtg tacgagtgcc cgggcatggc cccgaccggg 1020

  gaaatggagg tgcgcaacca tctgttcgac cacgccgcac tgtccgcgcc cctgccggcc 1080

  cccagctcac cgcttgcact gccatgacct ggaggcagac agacgcccac ttgctccccg 1140

  ac 1142

  <210> SEQ ID NO 15

  <211> LENGTH: 1034

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 15

  aattcggca cgaggaacca ccttctgtag gacagtcacc aggccagatc cagaaggctt 60

  aggccctgt ggtccccatc cttgggagaa gtcagctcca gcaccatgaa gggcatcctc 120

  ttgctggta tcactgcagt gcttgttgca gctgtagaat ctctgagctg cgtgcagtgt 180

  attcatggg aaaaatcctg tgtcaacagc attgcctctg aatgtccctc acatgccaac 240

  ccagctgta tcagctcctc agccagctcc tctctagaga caccagtcag attataccag 300

  atatgttct gctcagcgga gaactgcagt gaggagacac acattacagc cttcactgtc 360

  acgtgtctg ctgaagaaca ctttcatttt gtaagccagt gctgccaagg aaaggaatgc 420

  gcaacacca gcgatgccct ggaccctccc ctgaagaacg tgtccagcaa cgcagagtgc 480

  ctgcttgtt atgaatctaa tggaacttcc tgtcrtggga agccctggaa atgctatgaa 540

  aagaacagt gtgtcyttct agttgcagaa cttaagaatg acattgagtc taagagtctc 600

  tgctgaaag gctgttccaa cgtcagtaac gccacctgtc agttcctgtc tggtgaaaac 660

  agactcttg gaggagtcat ctttcgaaag tttgagtgtg caaatgtaaa cagcttaacc 720

  ccacgtctg caccaaccac ttcccacaac gtgggctcca aagcttccct ctacctcttg 780

  cccttgcca gcctccttct tcggggactg ctgccctgag gtcctggggc tgcactttgc 840

  cagcacccc atttctgctt ctctgaggtc cagagcatcc cctgcggtgc tgacaccctc 900

  ttccctgct ctgccccgtt taactgccca gtaagtggga gtcacaggtc tccaggcaat 960

  ccgacagct gccttgttct tcattattaa agcactggtt cattcactga aaaaaaaaaa 1020

  aaaaaaaac tcga 1034

  <210> SEQ ID NO 16

  <211> LENGTH: 1198

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 16

  cccacgcgtc cgggagaaag ctgcactctg ttgagctcca gggcgcagtg gagggaggga 60

  gtgaaggagc tctctgtacc caaggaaagt gcagctgaga ctcagacaag attacaatga 120

  accaactcag cttcctgctg tttctcatag cgaccaccag aggatggagt acagatgagg 180

  ctaatactta cttcaaggaa tggacctgtt cttcgtctcc atctctgccc agaagctgca 240

  aggaaatcaa agacgaatgt cytagtgcat ttgatggcct gtattttctc cgcactgaga 300

  atggtgttat ctaccagacc ttctgtgaca tgacctctgg gggtggcggc tggaccctgg 360

  tggccagcgt gcatgagaat gacatgcgtg ggaagtgcac ggtgggcgat cgctggtcca 420

  gtcagcaggg cagcaaagca gactacccag agggggacgg caactgggcc aactacaaca 480

  cctttggatc tgcagaggcg gccacgagcg atgactacaa gaaccctggc tactacgaca 540

  tccaggccaa ggacctgggc atctggcacg tgcccaataa gtcccccatg cagcactgga 600

  gaaacagctc cctgmtgagg taccgcacgg acactggctt cctccagaca ctgggacata 660

  atctgtttgg catctaccag aaatatccag tgaaatatgg agaaggraag tgttggactg 720

  acaacggccc ggtgatccct gtggtctatg attttggcga cgcccagaaa acagcatctt 780

  attactcacc ctatggccag cgggaattca ctgcgggatt tgttcagttc agggtattta 840

  ataacgagag agcagccaac gccttgtgtg ctggaatgag ggtcaccgga tgtaacactg 900

  agcaccactg cattggtgga ggaggatact ttccagaggc cagtccccag cagtgtggag 960

  atttttctgg ttttgattgg agtggatatg gaactcatgt tggttacagc agcagccgtg 1020

  agataactga ggcagctgtg cttctattct atcgttgaga gttttgtggg agggaaccca 1080

  gacctctcct cccaaccatg agatcccaag gatggagaac aacttaccca gtagctagaa 1140

  tgttaatggc agaagagaaa acaataaatc atattgactc aaaaaaaaaa aaaaaaaa 1198

  <210> SEQ ID NO 17

  <211> LENGTH: 1447

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (1420)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1432)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1436)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 17

  caagcgcgca agggcgcggg cgagcaggcc tgtgaattcg caggatcatt tcagacccgc 60

  acttcggcag ccaactcgaa agcaggcggt tgtgtgcggc agcagttggc gtttgctttg 120

  cacttcggaa cctgttgcgt tttgacccac ggaggtggag gagtaacttt ttgacatgtt 180

  ggcctttcca gttttgttgg aagtttcatg gtcggttttg tttygtttct cattcttctc 240

  tccksgcccc tcagcccccc aacccccaac cccctcccgg tccgtgttgc atgcacgctg 300

  ttcaaatgtg aggtctgaaa tggctggcac acgggaaaag ctgcttgtgt cattcgtttc 360

  tgggagtggg atggctctga gcagcctcgc ctccctgttt gtactatttg aactttgcag 420

  atctctgttc tctcaagcag aactcccaac cagatccatt cttgaccagt gaccggctcg 480

  gaatctggcc ttttgtgtga gatgatcacg gtttcttttg tttatcacgc catttgcaaa 540

  tcagagcaag agctctttct caagggcaag aaacgcaaac aagaaatatt tgtgagatga 600

  aagttgtcaa ttggattttc ttcctaaaca aacaacaaca acaaactact agaagtctcc 660

  ctgagtccac tcgcttggat ttctgacaca gtttacaaaa aaggaaaaag gcactgctcc 720

  tattttccct tatggctgag ttcaccttaa gattgtaaat gtgtatatgt cagtgaaaac 780

  attgaggctt ggaaaatgtg ttattttcgt tgccctaagt ttgagtcgac tttagactca 840

  aaaacatttt gagcgaatat caaagttaac ttttaaaaat tgcgaaacta tttcagaatc 900

  gcaattttat cgaagattaa atcagacttt tttgtctggt aattatatat ttattattta 960

  gcaaaactga agaaaaaaag cacagaattg tttcaacaga tgtctctcat tttcagctag 1020

  catttctctc ccaagttgag ctggtttaat gtgttttgga tttccctcct caattggctt 1080

  attttttaga tcacctgcaa ttcatttgca aattgcaata aaacacattt tagaaaaaag 1140

  gaaccttcaa ttattagctt tgtttctttt taaatgtata taaaaagact aatgtttgtg 1200

  aatgaagttg gctaacatgt atttagtttc attttggctt tatgtaatat aaagttttta 1260

  aaattttaaa tatggtttta acctttatgt gtaaatgatt ttctagtgtg accttctaat 1320

  ttaatattag acgtctaagg tatatctgta aattagaatc cgactatcac tctgttcatt 1380

  ttttttgaac aaagagttta aataaagcct gaaccagggn acagataaag anaatnaaaa 1440

  aaaaaaa 1447

  <210> SEQ ID NO 18

  <211> LENGTH: 1422

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (1397)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 18

  gtttctctta ggttttgaag gtataagtgt aaagtgaagc atctctcgat gattctttcc 60

  aagataggtt taaaaactat gaatccattt tcagtattty cttctctctg tttgaaacag 120

  tttgaggatg tgtytctttt tcttggcttg atgtttggta sgtccttgaa tgggcaagag 180

  ggcacatgaa gtacggcgtc ctccacattc acggcctcta cacgggaccc ctgcggggtg 240

  ggtgctggac ccatcggggt ataaagacgt cactcaagac gcagaagtca tggaagtcct 300

  ccagaactta taccgcacca agtcctttct gtttgtgggc tgtggggaga cccttcgtga 360

  tcagatattc caggccctct ttctttactc cgtgccgaat aaggtggatt tggagcacta 420

  catgcttgtg ctgaaggaga atgaagacca tttctttaag catcaggcag atatgcttct 480

  gcacggaatc aaagttgtat cctacgggga ctgttttgac cactttccag gatatgtgca 540

  agaccttgcc actcagatct gcaaacagca aagcccagga catttgtact cgaattcatg 600

  gagtgccact cctgatggga gaggaggccc atgacagtga cagtcatgct agtgatcgcg 660

  gacaccacac catgctgcct ttgccagctg gctccttcag cgagtcctcg caccaagcct 720

  gggaggtaga gatgctgatc gcgtggacag caccacatta ttgggtaatg catgccagga 780

  ctgtgcaaag aggaagttag aagagaatgg aattgaagtt tcaaaaaaac gcacacaatc 840

  agatactggt gtctgtgcca tcctcatgct cgcgggagtt ttggcatggg attctccgtt 900

  gtgattcccc cggactccac tgtctgaaga ccaggtttcc tatgaagagg gtctgatggg 960

  aacctgttcc cagtgatttg aagatgatgc tggagggtct tgaaatcttt acagtaaaac 1020

  ctgcaacttg aaaactagcc tttctgtaac cacagtgccc aaacgaagag gaatgtatgg 1080

  agaactccac gtggatctct gattgggaaa ccgtcacata caccaagaga gccacatggg 1140

  catgtggccc tcaaggctgg gtgagagggc tcccctgtgt gttgaactat gcaggagggt 1200

  gacgcggaca catttcaggt ggactttgca aggactgatg gatagctacc tcagggacca 1260

  gaatccgtgg gaagggatgg acctggtgtt cccgttccca tctgacaggc tctcttttgt 1320

  ccaaggtggt atttttcgta ataaaagggg aagagtaaar amwrwmmaar maamagtagc 1380

  tgccaaagag aaaatangaa atagacactt tttttttttg gg 1422

  <210> SEQ ID NO 19

  <211> LENGTH: 1107

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 19

  taaactatt tagttcaaaa gtaacccaac taattaaagt gaaaaaaaat tgttgaatca 60

  aatgaacaa acataaaaca atacttaaat gagaattctg tgtctttttt ggttttatct 120

  tgatttatt ttgtccagta ttaaggaatg gttatcttta tcattcttct aacatgtttt 180

  gtttctcta atggttcatt ttcctttagc ttgtgaaaat tagggcagtt tgtccagagc 240

  ttactcgca ggagacacca gacccaaccc atgcttagat ttctgttaat aaaagggaga 300

  gggtatttg aataggtagt aaaggcaggt acaagtttaa gggagcaggg ctatcatatg 360

  actaggtga gattactata aatgtctgaa aagttacatg catagtcatt ggctcaggta 420

  tttctctga atttgaactt atttgattta tttaaccaag ttattataat atgcagttct 480

  tttaatcaa tcttctatta ttcaatcatc tatccattta ttaattcaac aaatatttat 540

  aaagtgcct accatgatta tgtgctgtag aaaagacaag gacatttact aggggggatt 600

  tgggcccaa tcggcatcat aagcatgttc tgaaagccaa agacaataat cacatccaac 660

  gcaccagtt cagctcaact ttagaattca gcagtaacag tacagatggc ctaaagtaca 720

  ctgtgtgta tctgtacgtg tgcacacacc catgtatata tatttatcta tctgcacaca 780

  actacatat gtatacacac tatctatgta aaatataata tatgtataat gcatataaat 840

  ctaacaagt gtatttgtgt tatctttaaa atagaacaat tgtatcttga agtggtaaat 900

  cagagaatt ggttttattg ttgatctgtg gatttaatga tttctaggtg aaaaggacgt 960

  taagtgtac aatttctttt cttaatttaa tatatttatg taaatgcatg cctgaaattt 1020

  gttagattg gctgtgtttt gtgtctttta acatgatcaa atgattaaac tttatgctta 1080

  gacttgaaa aaaaaaaaaa aaaaaaa 1107

  <210> SEQ ID NO 20

  <211> LENGTH: 1183

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (266)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (426)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1170)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1178)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 20

  gtgattcaaa gccatcacaa aacactataa gactgaccaa aatttagata acctttgaac 60

  cacgattttt ttccacatct gtytgtgaga cacagcgcaa tgctactgcc cttccagaaa 120

  ctgtgctaaa aagagaaagt ccaaaagact ctaaacaaaa acctcgacgc cgttgaggat 180

  gtgtttcatt ctggtggtct gttttgcaag cttgataaca gaatgtccgt gccattgtaa 240

  atgttgtaga gatgtgggcc gtggcncaac cgtcctatat gwgtgtagca tggtacagaa 300

  caaactgctt acacaggtct cactagttag aaacctgtgg gccatggagg tcagacatcc 360

  atcttgtmcm tctataggca agaagtgttt ccagatcctt tggaaaggtg ggcatggggc 420

  aggtsnttgg agagtggcgt ttgagcagag cgaccccatt tccgtgtgaa ccataggcac 480

  aacccaggaa gtttccccac ttgtaggagt gtgggtattc cagagcaaga ctgtggccac 540

  catcttcccc tcttggtgtt ttccgaaagt gacagtgttg gtcatcccat gaccactgaa 600

  gcttagtaac cagcgccaaa aagtagattc atcaaactag agaccccagc tccccttctc 660

  gccatcttct ttctcaagtt gaccgtggtg ctgtttctgg aaggcatctg caactccaag 720

  tccatgcaga actctggaag gccaagttca tcgcagcatg ttcaccatat cccagcctcc 780

  aaatctatcc tcctaccttc caacgcatga cctgttgggg agcagagact taacccccaa 840

  ctcagaggaa cccttcctcc agcgtctttg gcatggtttc tagggtgaga gttcccaatt 900

  tggatagaac ggccaccata ttggttactg aatctctctc ccttgttttt attacgtttc 960

  ctttttcaaa ctgtccatgg gaaggctgaa ttgagtgact ccccagaatg aagatgagaa 1020

  ggtgaatata atcaatgcca atgtaatgcc agcgggtgar gatggccgat ggraggtttt 1080

  caaagatgta gctagcattt tggaaaccat atgggcaaaa cccgggcaac cagagggggg 1140

  aacaggttaa gggaccgttt cccaggaaan tccccaantt ttt 1183

  <210> SEQ ID NO 21

  <211> LENGTH: 1420

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (524)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (585)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (596)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1042)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1062)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1144)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1171)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1286)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1350)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 21

  gtctgcatcc cgggcgcggc tgggttgagt gttctcttag gaatggtgga gaactgggtc 60

  cttgaggagt caccggggag actgctcgca ctgtttgtgg tgcgacgggc actggcccag 120

  ggacagaggg aagagaaggg ccagccagcg gcagtggagt cggcaggctg gctgcccact 180

  cgctttctct cctcacaaga ctcgcttccc ctgtcttcga ggatctcgaa cggactatag 240

  tctggactcg ctgggctgga ggaaacttgg ccgctggcca cccggaggag actgaaaatc 300

  ctttggtcaa cagggcgcct ttccttgaac caaaacaaaa ctttccgaag ccggaaagga 360

  aacgcccagt gtcgcctgag agccctggag ctgcgcgaga cccaggcact gagtgcggcc 420

  tcggcctctg acctctaaca cgccgggaac aaaccatctg gggcggcccg caggcctgcg 480

  ggagcggaat gtgacccgaa accgaccgac ttcctgaccc atantccata gttctcttca 540

  gcaacttgaa cattttggaa aaagaaacaa tcttaacatg ccacnaccta atgganaaac 600

  taaatcccct tcctacacct tgctttccaa aagttaaaaa aaaatagtta aacgctatta 660

  gaggtctcaa gttcactgtc accagatcag ctaggtccag aatcttcagt tcttgaagcc 720

  aagccctaca aatagattta ttgtagcata tcacacctct tcaggtgact taaaacaatg 780

  agaattcatg agaaattatc ttcatcctca agtaaaaatc atgaggtgcc tttcacatgg 840

  atgaaattgt aagtgcttgt tgaacaagga ataattggat aatggtattg tggtcatact 900

  ttttaagaat atctgttaga aagatatagg atgcagaaca tctaggattt gctgaaagtc 960

  atttattatg gatagggggt atgagtaagt tcatagatga aaagggatga aacaagattg 1020

  gccatagttg ctctattttt gngtatcttg tttctttatt tngtttcttt aaaaagtcct 1080

  catatcactg acatttacac ttagttttag ggaaagtcaa atttagaaat aagctacagc 1140

  tctntaagct atcggtctaa ctggattttt ntcgatgctg aagaactttt taaaaaattc 1200

  agccatttag gtcacacagc aaatacattt ggcattaaat tcctagtatc actaaagtac 1260

  tccctcccac cgccgcgccc cccccnttcc ccccgcaccc ttagacctgg gcaagagaga 1320

  cttctatcct ggactccatg ctttaaaggn acttacatat cacacacaca cattaattta 1380

  aaaaggaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1420

  <210> SEQ ID NO 22

  <211> LENGTH: 1575

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 22

  gtccattctt ccggtggaga tggctgcggc cgtggcgggg atgctgcgag ggggtctcct 60

  gccccaggcg ggccggctgc ctaccctcca gactgtccgc tatggctcca aggctgttac 120

  ccgccaccgt cgtgtgatgc actttcagcg gcagaagctg atggctgtga ctgaatatat 180

  ccccccgaaa ccagccatcc acccatcatg cctgccatct cctcccagcc ccccacagga 240

  ggagataggc ctcatcaggc ttctccgccg ggagatagca gcagttttcc aggacaaccg 300

  aatgatagcc gtctgccaga atgtggctct gagtgcagag gacaagcttc ttatgcgaca 360

  ccagctgcgg aaacacaaga tcctgatgaa grtcttcccc aaccaggtcc tgaagccctt 420

  cctggaggat tccaagtacc aaaatctgct gccccttttt gtggggcaca acatgctgct 480

  ggtcagtgaa gagcccaagg tcaaggagat ggtacggatc ttaaggactg tgccattcct 540

  gccgctgcta ggtggctgca ttgatgacac catcctcagc aggcagggct ttatcaacta 600

  ctccaagctc cccagcctgc ccctggtgca gggggagctt gtaggaggcc tcacctgcct 660

  cacagcccag acccactccc tgctccagca ccagcccctc cagctgacca ccctgttgga 720

  ccagtacatc agagagcaac gcgagaagga ttctgtcatg tcggccaatg ggaagccaga 780

  tcctgacact gttccggact cgtagccagc ctgtttagcc agccctgcgc ataaatacac 840

  tctgcgttat tggctgtgct ctcctcaatg ggacatgtgg aagaacttgg ggtcggggag 900

  tgtgtttgtc acttggtttt cactagtaat gatattgtca ggtatagggc cacttggaga 960

  tgcagaggat tccatttcag atgtcagtca ccggcttcgt ccttagtttt cccaacttgg 1020

  gacgtgatag gagcaaagtc tctccattct ccaggtccaa ggcagagatc ctgaaaagat 1080

  agggctattg tcccctgcct ccttggtcac tgcctcttgc tgcacgggct cctgagccca 1140

  cccccttggg gcacaacctg ccactgccac agtagctcaa ccaagcagtt gtgctgagaa 1200

  tggcacctgg tgagagcctg ctgtgtgcca ggctttgtgc tgagtgctgt acatgtatta 1260

  gttcctttac tgctgaccac attgtaccca tttcacagag aaggagcaga gaaattaagt 1320

  ggcttgctca aggtcatgca gttagtaagt ggcagaacag ggacttgaac caagccctct 1380

  gctctgaaga ccgcgtcctg aatttcttca ctagagcttc ctcatcaggt tacccagaag 1440

  tgggtcccat ccaccatcca ggtgtgcttg gatgttagtt ctccaccctc gaggtgtacg 1500

  ctgtgaaaag tttgggagca ctgctttata ataaaatgaa atatattcta maaaaaaaaa 1560

  aaaaaaaaaa ykcga 1575

  <210> SEQ ID NO 23

  <211> LENGTH: 541

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 23

  caggagcaag gctttgtgct atatctacat aatcttagac cctgttcctt ccaattccag 60

  ggatatgctc ttaaccactg cagtataagc ctccccgcya cactctgagt ggagcagagg 120

  aaggtgtttt tgtctttgag aaaggcaagg atgaagggca agatttgagc catggtggta 180

  gatcagaaag aagatctgat aacaggctta gggatcaaaa tggtaaggaa atggcttcag 240

  gggagtcagg cctggcccct ggagagggag gagagggaag ggctaggctc tttatgtaca 300

  tgctgtccat ggggcctggt aagattcmtg gaatcactaa cccatttcac aggtgaggca 360

  attgagcctc tcagagctga agtaactgac ccaaagcatc cgtgctcttg tgtggcagag 420

  ccagaagtca aatccaggtc tctgtgamct caaggggcac caaartgagt atcaaaaagg 480

  cagaaaggga cttatccctt cactcactca gcaaaagcat agtaagcagg tggcgtgcct 540

  t 541

  <210> SEQ ID NO 24

  <211> LENGTH: 833

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 24

  gatcttgtcc aagcagtcgg ggctacttcc aagaatgtca gctcctgtta gcaaccagtg 60

  gagtctggcc ttgggctcta agttgacctc tctatagctc caaatcctac caatctcaga 120

  aaactgtaag aggcacagat gactccacca gctgcagagt gactctgaag agagtcttca 180

  cttactgcac aggcaaagaa aggcacagga atatttccta cctctccctc ctgtgagtcc 240

  cacctccccc cacccccatc tccaggaggc aggtagagca gttctraccg agaggataga 300

  ctgctgttgc tgtctttccc cagctctgaa ctagttttaa ggtagcttag gatgaaaaat 360

  ggagaatgat tgggggttcc aaaccacttt yttctccctt ggcttatatc tcttcaccat 420

  ttggtggtca actgtgggsc taccctggac ctcatctact cagcgagaat tggacatgaa 480

  gctagaggca gctgccttgg aagggaagtm aggctcactt ggacagccca ggccatggca 540

  ggaagaatcc cttcctcttg gggtccttga tgggcatgtg tgatggggaa ggagcagtct 600

  cccagccctg ggtctgctcc ccacatctct cctaattcca cttcaccttt tgccaccccc 660

  tccccaccag aggcctagcc cttttgtcac cgaaggcccc cagagtgttt ctgtgtgaaa 720

  ccctctcatt tacactgtgg catcaaaatc cacaaaagat ggattaattg cactctggtt 780

  aatagcagca gcacaatgat taaaatctat attcctaaaa aaaaaaaaaa aaa 833

  <210> SEQ ID NO 25

  <211> LENGTH: 1555

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (1248)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1389)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1391)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1393)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1396)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1551)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 25

  ggcacgagct gggcagatgc aaaatctgga gagcgcgagg gccgggcggt cagtcagcac 60

  ccagactggc agcatgaccg gtcagatacc aaggctttct aaagtcaacc ttttcactct 120

  gctcagcctc tggatggagc tctttccagc agaagcccag cggcaaaaat ctcagaaaaa 180

  tgaagaggga aagcatggac ccttaggaga taatgaagag aggaccagag tatctactga 240

  caaaagacag gattactggg agcagctaag atgcctarat gaaaggttta ccatcactgc 300

  tggttaggaa atggattatg agaactcgaa cagagggaag gtgaaatgca accggaggaa 360

  acactctgat atgaggtttg aggccttcaa aattgctttg cagcataagc cacagtgagt 420

  caggagtacc agggagtgga tagaatgttt atttgtttaa ctgagacttt ttagttcatc 480

  aattattttg aagggtagaa cactctgtgg gctctctttc tatttccttc tgggtacaat 540

  cacaaaaaaa aaatctctcc tagctgaaat tacatgcagt actagcaaag ggtctctttg 600

  ttataaactg ttcattaatt gacgaacatt tgtgtactta actatgtata aggcatctca 660

  tcgttcaatt tcaaatacaa attaaaatat tttttcacat ttgttatcct gttatgtttt 720

  ctcttttaca aattgtctgt tcgtatcttt ttgtctctct ttaggcctta ttcttgtcaa 780

  ttcatatgtg ctctaatgaa ttgaaatatt ttctgtatat taaacattac taacctttcc 840

  tctgtcacac tgattgaaaa atgatctatt tagtttgttg ttttgtcttt aattttgtaa 900

  gctttaaaaa gttaatattg cccttcagac accatcccaa catcacataa gaattttttc 960

  atgttataaa ttctttgtgg acatatttga taactgtttt attatgagga ggaccataat 1020

  taattcaacc attcccctat tttggtcatt taggtttttg ggtttgggtt ttttgtttgt 1080

  ttaacgtctt tgcttgctat tttaaagaat gctgcactaa atgtgaatgc ttgagatttc 1140

  ttctctgtat ttagaatatt ttcctagaat ggattctcag aagaattctc agtctgtgga 1200

  gaggaacatt tttaatgcat ggaagagctg gagtgaaccg aatttcanac tgccctgctg 1260

  atccagaaat aagtttgctt acggaggctt ctagttctga agatgcaaag ttagatgcca 1320

  aagcagtgga aagattgaag tcaaacagtc gggcccatgt gtgtgtctta cttcaacctt 1380

  tggtgtgtna nanggngcag tttgtagagg agacctctta caaatgtgac tttattcaaa 1440

  aaattacaaa aacattgccg gatgctaaca ctgactttta ttatgaatgt aaacaagaaa 1500

  gaataaaaga atatgaaatg ttaaaaaaaa aaaaaaaaaa aaaaaaaaaa naaaa 1555

  <210> SEQ ID NO 26

  <211> LENGTH: 1543

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (69)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (717)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (899)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 26

  gagcgggata acaatttcac acagggaaca agctatgacc atggattacg ccaagcttgg 60

  aattaaccnt cactaaaggg aacaaaagct gggagctccc accgcggtgg cggccgttct 120

  agaactagtg gatcccccgg gctgcaggaa ttcggcacga gccgaacagt aggacatgtc 180

  atggcatttt tgctcaccct tgttccactc ctccccagcc gttgtcttgg tttggaggag 240

  atggcagttc ctaattccac ctgtattagt ccattctcat gctgctatgg ataaatatct 300

  aagactgggt aatttataaa ggaaagaggt ttagttgact cacagttctg catagctgag 360

  gagacctcag gaaccttata atcatggcaa aaggcaaagg agaagcagac aggacagagt 420

  gaatgccagc aggagaaatg ccagacgctt ataaaaccat caaatcttgt gagaactctt 480

  cactatcata agaacggcat ggggaaaact gcccccatga ttcagttacc tccacctggt 540

  cccacccttg acatgtggga attattacaa ttcaaggtga gatttgggtg gggacacaca 600

  gccaaatcat atcaccatcc cttgaaccaa aacgaacaag gctgacctta tttgcaacat 660

  tctaacttgt ctaaaggctg cctgaagaat tgatccctga ttcacctaac tcagatntct 720

  gctaggagac aagcatggcc ttaatctcag atgaggagaa gcagtagtca tggctcagaa 780

  agctgcagag agaccctaca gattcctggg gcaaaagatt ataggtggag acatatgaca 840

  gaccatcaag accccacaaa gatctcttgg gaaatttaag acaattaaaa gcagccatnt 900

  atacagagat tcaaaaaacc acaaacaggt ccaggcaagg atgcatgctc agtaaagacc 960

  tgagaagacc tttagctttc tctttgatgt gatctcaaaa ttcagaagca aggccaagat 1020

  aattaggaaa ggacttccat ggcaaagagc cagtctacag agaatgggag aagtagctgt 1080

  ttttcttttt gttttcaaat ccccaacata actattgtga atttaaaatc ccaaaatcac 1140

  aatgcataaa aagaaacgga aacatggacc attcaataat aataataaat tggcagaaac 1200

  tatccctgaa aaaatacagg tatcagactt actagaaaaa gattttcaaa caatgtttta 1260

  aatatgttca aacagtaaag aacaacatgg acagagacct aaaggaaatc aggtaaatta 1320

  tatgaacaaa ggggaatttc aacagagata gacattatta aaagaaccaa ccagaaattc 1380

  tggaaatgaa aaatataatg ggcacactgg ggatagtcaa acttaaaaat tcactagagg 1440

  gattcaatag cagacttgga cagaagaaag aataaacaag cttaaagata acttatttga 1500

  aattatctag tatgaggtac aaaaaaaaaa aaaaaaaaaa aaa 1543

  <210> SEQ ID NO 27

  <211> LENGTH: 1262

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (621)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (641)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (722)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (723)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (726)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (730)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1259)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1261)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 27

  ggcaccagaa aaaaaaaaga taatccaaag aatttaaatt gtaatcatgt ttcatgtatt 60

  tgttttatta cttactttta tagcacttag tcccagtggt attagactgc tatttggttt 120

  catacaaaaa ggattaaatt taaattcatt catgtttaga cttgagttat tacattttta 180

  aaactatcat cttgccttta atgtttgtgg tcctacacaa actattagta catttcagta 240

  tcctcttacc cctttgtttt taagtttttg attgctaaag caagactttt ttcttctaga 300

  atttaagtca accaagtgtt atctatgttg taaaaatgga taatagtaga ttttaggtga 360

  taaaacaact tgttagtaag acatttccta gcttaaaaaa aaaaatcaaa aattccatga 420

  tagaaatgca gacctgtgag ggaaactcct gaaaagcata agaagcatcc cagagagcca 480

  tgggttttct agaccagaga atttagaggg agattgtgga actgaggctt aggtggtcag 540

  atcgtttccc ttatcactgt aatattttct gggggaaaaa tgctttctga gttgtttaaa 600

  caagcatcct tacatttttt ntttaattaa aacagcctgt ntagggcttg ggattcccta 660

  atactacagt agcagtatat gaatatgatt ttgtgattgt gttttttaaa agataagtaa 720

  tnngangaan tgttcttttg cagtcagaaa acactcacaa aaagacaaaa aaagttccac 780

  agtattatat ttcatgtcag ttcaggccta aaatcctttg caaataagat gtttataggc 840

  tggtcacaat taacaatgtt attattggca gcacttcttg gatggatacc ttttgggacc 900

  tttcattaga aagagggaaa gaatggggtg gttttgtatg ggctcctgtt tggggtaaaa 960

  atagcagagt cagttgctga ggaccaatga cctttcctta taaacattta gtttcatacc 1020

  catattaggt cttgtcttga ggacccttta tatgtgcttg tttactagtg gccttccagc 1080

  catagcattc ttaccttttt ttcctattct aagaattaaa aaaaaaaatt atagagccag 1140

  caagggagga ggcaggaaac agaaatcgaa tttcatcatt ccagtatagt tgtccctttt 1200

  tttgtatttc tgacttggtt ttataattat atttacttac taaaaaaaaa aaaaagggna 1260

  na 1262

  <210> SEQ ID NO 28

  <211> LENGTH: 753

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 28

  ggcacgaggt gatgacttca ctcccaattc tggcatttgg ggctgtctat tggccagacc 60

  ttgcttcaca tagtttctca ccctcaagga gtctagccca gactccccat atgtcagtct 120

  cagggtagca tttcaagagg gataaggtag acgtttctgg cctgttgtgg tgtaggctgt 180

  gaattaccat aacatcactt ctttgagatt ttcttggtca aggcaaatca catgacaagg 240

  actcaagagg gtagagaaat aggttctact atttagtgga aaggacagca aagtgacatc 300

  acaaagagga atgcatatag agatgggggg aatatgtgac caactttagt aatcactgta 360

  attctgaatt gactcacaaa cactatcaag acggatcatt gtcataccct agttcaaaaa 420

  gcagtccttg cagcaataca gaacagatag aagtgaagag aatgtgattt tgctaaaaat 480

  gacatattta catgaccagt gatgggtgag acctatgaaa aatccccaga gattctcaag 540

  aactcataaa gtgcatttcc atatttatgt agaatatcaa tctcctgctg tctttgactt 600

  cacctagtat attcctaggt atgtgtatct aagcccaagt tggtctcacg tttttgccta 660

  cttccgagtc aatatgtgac atgccatccc acctttttgt gttaccacat tattataaca 720

  taaggggtgg ttatgtttcc tggatatctt gag 753

  <210> SEQ ID NO 29

  <211> LENGTH: 1621

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (527)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (542)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (553)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (701)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (731)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (906)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 29

  ggcacaggcg cggcctgcgg cttcttggga actctagggc cgcggccggg cctggctctg 60

  ccggcggcct gttgggagct ggatcggagc ggtttggaac gacaagcccg acaaagagac 120

  ttttaaaaaa ccatggcaga tgtggaccca gatacattgc tggaatggct acagatggga 180

  casggragat saaaaggaca tgcaactaat accccttgaa cagctatgca tgctgctttt 240

  gatgtctgac aacgtggatc gttgttttga aacatgtcct cctcgcactt tcttaccagc 300

  cctttgcaaa atttttcttg atgaaagtgc tccagacaat gtattagagg tgacagcccg 360

  tgccataaca tactacctgg atgtatctgc ggaatgtacc cgaaggattg ttggggtaga 420

  tggagctata aaagcacttt gtaatcsttt ggttgtagtt gaacttaaca acaggactag 480

  cagagactta gctgaacagt gtgtaaaggt attagaactg atatgtnctc ctgagtccgg 540

  ancagtcttt gangctggtg gtttgaatcg tgttgcttac cttccaagcg tgaacagtgg 600

  acatctagtt cataaagaca ccttgcactc tgctatggct gtggtatcaa gactctgtgg 660

  caaaatggag cctcaagatt cttctttaga aatttgtgta naatctctgt ctagtttatg 720

  aaagcatgaa natcatcagg tttcagatgg agctctgcga tgctttgcat cactggctga 780

  ccgatttacc cgtcgtggtg ttgacccagc tccattagcc aagcatggat taactgagga 840

  gctgttatct cgaatggctg ctgctggtgg tactgtttca ggaccatcat cagcatgcaa 900

  accagntcgc agcaccacag gagctccatc caccactgca gattccaaat tgagtaatca 960

  ggtgtcaaca attgtaagtc tgctctcaac actttgcaga ggctctccgg tagtaacaca 1020

  tgatcttctg aggtcggagc ttccagattc aattgaaagt gcattgcagg gtgatgaaag 1080

  atgtgtgctt gatactatgc gtttggttga ctttctcttg gtgctattat ttgaaggacg 1140

  aaaagctttg ccaaagtcta gtgctggatc tacaggcaga atcccaggac tccggagatt 1200

  agatagttct ggggagcgct cacatcggca gcttatagat tgtattcgaa gtaaagatac 1260

  cgatgcactt atagatgcaa ttgacacagg agcctttgaa gtaaatttta tggatgatgt 1320

  aggtcagact ctattaaact gggcctctgc ttttggaact caggaaatgg tagaatttct 1380

  ttgtgagaga ggtgcagatg ttaatagagg tcaaaggtca tcatcattac attatgctgc 1440

  atgttttgga agacctcaag tagcaaagac tctgttacgg catggtgcaa atccagatct 1500

  gagagatgaa gatgggaaaa ctccattaga taaagctcga gaaaggggcc atagtgaagt 1560

  ggtagctatt cttcagtctc caggtgattg gatgtgtcca gttaataaag gagatgataa 1620

  g 1621

  <210> SEQ ID NO 30

  <211> LENGTH: 921

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 30

  ccacgcgtcc gaccatgcca aatttcttgt ggttccctaa atgcgccatg tttgaagata 60

  ctctgaggac attgtatata cttttgttct acctgagata catttgctta ctttctccac 120

  atattgccct catgacactt atccttattg atggatttct tcaatgctac tattgtgcct 180

  tacatgtgcc ttgtattata gcatttttat agcatttctc acccaattgt ggctatttgt 240

  ttacatgtct gtctccttgg tggaactgtg aactctgtca taacagatgc cattttatgt 300

  cagttagact tctttggttg ccagtaagag aagctgactc taatctaaac caaaaggaat 360

  tcattggacg gatgtgggtt ggctcacaaa atcaaaggga caactgcgga ccgatcttgg 420

  aatgatgctc tgacaccaga acagctctgt gaattcagat aggggtagtg aattgaccat 480

  ttcatcaaat gctgcagcaa gctaggtggt ttccccaaag gaaattgagg agtgttacaa 540

  gaagaccatt aggggaacgg ttatctggtg gctgataata acaaatttcc atggcagtct 600

  ctttgctctc tgttggaaga ggtactccac catgggcctt gagcatctct acacatcctt 660

  gctaagcgtg tcaaatttca agtcctaact gtcctctgtc tctggaggag gagacaggtt 720

  tggttactgt ttgttgtaaa aattactgag cccttcacca tgggtgcctc agctgtatgc 780

  aaagcccctt gtattgctgg gggacagagc aactggtact gccatgctgg tgctctggct 840

  gtttgctgtt ggcaataaac tattctgttt tggttcaaaa aaaaaaaaaa aaaaaaaaaa 900

  aaaaaaaaaa aaaaaaaaaa a 921

  <210> SEQ ID NO 31

  <211> LENGTH: 2095

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (14)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 31

  cccacgcggt ccgnatcgtc cttccctcac ttcagagggt ggccagagct gaatacccag 60

  agagggacaa gtaagggtcc agttccaaaa catcatgagg atgtatcatc ccacgtgtct 120

  cacctgacag ttacagagga aacccgcacc cagaatgcac gtgctgtctt atgggaacac 180

  tcagcgcaga gtgctcaggt ccggccacac tcgggctgtg cttggtcgtg ccatggaatt 240

  cctcaggact ttctcagcct ccctaatggc agaagcccct ttacagcaag acatttaccg 300

  tttgtctgaa aatagccgaa ctgagccttt tcttcaggct atatgagaag tctctagaca 360

  gtgggcaccg tcagaaagcc cagagccttg tgatagctcc caccctgcct ggctcagatc 420

  ttcccatttt tttcctctgg cactaacctc accttttgtt tttttgtgtt tgtgtttgtt 480

  tttgtttttg cagagttgga ttacagaaac tcctatgaaa ttgaatatat ggagaaaatt 540

  ggctcctcct tacctcagga cgacgatgcc ccgaagaagc aggccttgta ccttatgttt 600

  gacacttctc aggagagccc tgtcaagtca tctcccgtcc gcatgtcaga gtccccgacg 660

  ccgtgttcag ggtcaagttt tgaagagact gaagcccttg tgaacactgc tgcgaaaaac 720

  cagcatcctg tcccacgagg actggcccct aaccaagagt cacacttgca ggtgccagag 780

  aaatcctccc agaaggagct ggaggccatg ggcttgggca ccccttcaga agcgattgaa 840

  attagagagg ctgctcaccc aacagacgtc tccatctcca aaacagcctt gtactcccgc 900

  atcrggaccr ctgaggtgga gaaacctgca ggccttctgt tccagcagcc cgacctggac 960

  tctgccctcc agatcgccag agcagagatc ataaccaagg agagagaggt ctcagaatgg 1020

  aaagataaat atgaagaaag caggcgggaa gtgatggaaa tgaggaaaat agtggccgag 1080

  tatgagaaga ccatcgctca gatgatagag gacgaacaga gagagaagtc agtctcccac 1140

  cagacggtgc agcagctggt tctggagaag gagcaagccc tggccgacct gaactccgtg 1200

  gagaagtctc tggccgacct cttcagaaga tatgagaaga tgaaggaggt cctagaaggc 1260

  ttccgcaaga atgaagaggt gttgaagaga tgtgcgcagg agtacctgtc ccgggtgaag 1320

  aaggaggagc agaggtacca ggccctgaag gtgcacgcgg aggagaaact ggacagggcc 1380

  aatgctgaga ttgctcaggt tcgaggcaag gcccagcagg agcaagccgc ccaccaggcc 1440

  agcctgcgga aggagcagct gcgagtggac gccctggaaa ggacgctgga gcagaagaat 1500

  aaagaaatag aagaactcac caagatttgt gacgaactga ttgccaaaat ggggaaaagc 1560

  taactctgaa ccgaatgttt tggacttaac tgttgcgtgc aatatgaccg tcggcacact 1620

  gctgttcctc cagttccatg gacaggttct gttttcactt tttygtatgc actactgtat 1680

  ttcctttcta aataaaattg atttgattgt atgcagtact aaggagacta tcagaatttc 1740

  ttgctattgg tttgcatttt cctagtataa ttcatagcaa gttgacctca gagttcctgt 1800

  atcagggaga ttgtctgatt ctctaataaa agacacattg ctgaccttgg ccttgccctt 1860

  tgtacacaag ttcccagggt gagcagcttt tggatttaat atgaacatgt acagcgtgca 1920

  tagggactct tgccttaagg agtgtaaact tgatctgcat ttgctgattt gtttttaaaa 1980

  aaacaagaaa tgcatgtttc aaataaaatt ctctattgta aataaaattt tttctttgga 2040

  tcttggcaaw aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aattc 2095

  <210> SEQ ID NO 32

  <211> LENGTH: 1838

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (1076)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 32

  tgttcaccag tagctgggat tacaggcatg tatcactatg cctggctaat ttttgtattt 60

  ttagtagaaa tggggttttg ccatgttggc caggctggtc tcaaacttct gacctcaagt 120

  gatccacctg cctcggcctc ccaaagtgct gggattacag gtgtgagcca ccatgcctgg 180

  ggcaaaagat attttcaaaa cattgtmaat aacttctccc ccaaacccag acagggtctc 240

  attctgttgc ccaggctgga gtggcagggg caccatcgta gctcactgca gccttgaaca 300

  ccggggctca agcaatcctc ccgcctcagc ctgccaaagt gctgggatta cacacgtaag 360

  ccagtgcact cagtcctaag taacttttta aataccaaag gtagaaaagg aagaagaggg 420

  aaaaaaaaaa taagcccata tatggaaaag gaaaagacag cagataaata taggcaaata 480

  gaggtggaaa atataatcac gtagaattta gtatagtaaa ggattatctc tgaaaaacaa 540

  aaacagaaaa ctatcagagc caaataaaga aaaatggaaa tgactgggga aaaccactca 600

  ctaatgagtt gaatgttcaa gagaaactga gaaagagtac tgcttatata aaaattatgt 660

  gaaattaaac aaaaatgtag tttagtaatg aatggtgttt aagcacttat ggaatataaa 720

  attatcacct gttaaataag aatgcatagt aaatggaatg gacaaagaat atgagtgaca 780

  gataaaatca gtttttaaaa aattttatta aagttgatta agcctattag tgaaagaaag 840

  caggccaggc acaatggctt gctcctgtaa tgccaatact ctgggaggtc aaggcaggaa 900

  gatcacctga gcccaggagt ttgagataag cctgggtaac acagtgagac tccatctcta 960

  aaaaaattaa aaagtaaaaa aaaattagct ggtcatggtg acacacacct gtsgkccyas 1020

  skmctwkgga ggctgaggca agaggattac ataagcccag gaagatgaag ctgcantgac 1080

  ccatgattgt gccactgcac tccggcttgg gtaacaaagt gagatcctat tttccatccc 1140

  caaccagtcc ccccagaaaa ggccaggtgt ggtagctcat gcctgtaatc ccagcacttt 1200

  gggaggccga ggtgggagga ttgcttgagc ccaggrgcyy ysagtascag tttaggcaac 1260

  aaagtgaaac cctgtcttta caaaaggcaa tacagtgaaa ccttgtcttt acaaaaagtg 1320

  caaaaataag ctgggcatgt gtgccacaac acctgtaatt gcagctactc aggaggcaga 1380

  gacaggagga ttgcttgagc ccagaggtca agactgtaat gaaccatgat tgtgccattg 1440

  cactccagtt taactgacag agtgagactc tgtcttaaaa aaaaaattat tttgatatta 1500

  agtgataagt ggctatttgc ctagtagctt cctaaaataa actagcataa aatgaaactt 1560

  attttccaac ctatccctaa gcccttggaa tttcagttct aataactaga atagttacat 1620

  aaaaccagta aaaagttgtt taataagaat gtacacattt cccctactaa aatttattgc 1680

  ttgtagtttc aaaataaaat cataaagtta tctcaaagcc aagcaaaaaa attatttggt 1740

  acaaagtagc aaactcgctg cattagaaga aaaggccatt tcttcacata tttgaataca 1800

  ggcaccaaca catagttcca catgaaatta tatttcgg 1838

  <210> SEQ ID NO 33

  <211> LENGTH: 782

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 33

  tacgagtttt tttttttttt ttttgagaag gagtctcggg ctctgtcacc caggctggag 60

  tgcagtggcg agactccgtt tcaaaacaaa aacaaagcat caattcctga tcatgaccca 120

  ctgtaacttc aagcaagcta caagaatcta tactagggtt cagacctttg aggctgacag 180

  cgagctttga gtttgatgac agtacctaaa atatattaag tgtactcagg aactggccaa 240

  gcatggggtg gggcttgtca ggaaactggt atttctttct tctatttgta gtgaataaga 300

  tgctcaatag acgactttta ctcctcgtca atggtcgcat aactgtctct ttttagacac 360

  ttatgaaatt gtctgaactt cctcctctac ttctccaact cccagaagag tgaaggtaac 420

  aaatgttatg tccaaaccac ggtttgttcc cagaccctgg tttccaatgc ccacctcttt 480

  tccaagaagt ccaaagagac gcccctcatc gcaaaggaag tgctaccgtg ctgcctcgat 540

  gtcccccttg ggtgccatcc ctgaaacatc gaacctccca tacctcttct ccagccgtcc 600

  ccctcatcct cgttccccgc ctaccctctc ttcaacttca ttcattcatc caacattcgc 660

  tgggggattt ctacattgac acgccccgga cagaagcctg gggtaaagat gatcaggaac 720

  acgttccctc ccgctaagcg gcttggcaga gtaagaggca tcccaaaact cgtgccgaat 780

  tc 782

  <210> SEQ ID NO 34

  <211> LENGTH: 1560

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (461)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (497)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (499)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (595)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (621)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (622)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 34

  ggctttttct gacattggtg aaccccctag actacaatta atccctttgc tacagacacc 60

  tgtagccctt gctgcctcct ttttgttaag aggtcttata attttatgtt tgatgtccat 120

  cttccccact tgattgaaat gcactattta tggaggagct atgtctgtat tgtttgttgc 180

  tgtatcccta ttgtctagca tagtgcctga catacagtac aggctcaaga catatttgca 240

  cattgattta tggaaaactg atactcaggt tctgaagaat aaataaatgc acctgaactg 300

  tcaaagtgct aaaagcaggc aatccagaaa tgtctggagg taggaatcac agctgcaaga 360

  ggcacttcct ggttaacctc gccctccgac ctctagttgg agccacccct ttggatccta 420

  cttcagcctt tctggagtca gtggctcaca ggtttcctga nacaaagaga agaggcttga 480

  gactattatt acatatnant cttctttaga agcaaagttg gttcgtggat tgaattttca 540

  accttacagt accaattata aatcctgagg cattctatca gttaagacaa cttanaatat 600

  ttgatcccat tcagaacttt nncatttgtt ttaaagcagg aaaagtaaar gmagtcaatg 660

  twmtaacyct tcttctttaa aatgtggatc atagtcctct tggggatgtt tgttcattta 720

  atattaacat tttttaagct tgscatgtwt cgtgggtgta tctgtttggt ttcctttggt 780

  aactgcattt tgccatgacc cttgatacca gctctactgc tacagcccta ggctaggcca 840

  ccgtcatctg tggcctggac cctttcagtc ctaactggtt gccgtgtctc ctttcttagg 900

  ccccccaaca gttcatcttc catatccaca cacagtagcc cttaatgatg tttttaaagg 960

  aatgagctat attaggatga tttctttgcc caaaaactcc ttcaatggtt ttccacttac 1020

  tccagagacc caaaaatcta aggcattttc cctatgggcc ctggatggcc ccacattccc 1080

  cctgaccccc gtctccagtg ctgtcccctc ctgcttgctg tgcttccagc ccacactggc 1140

  ttccttcctt accctcaggg ttccaccaat ctggatcttg tctcataaac tttgttcctc 1200

  tgacttcttc tttttgaatg ttcttttccc agaccttcac atggctcttt gctctcccct 1260

  tctgagtctg aacacaaagg tcactgactt aaagaggctt tttcccacca tccagttgaa 1320

  atcagcaccc tctctgtaac tgtgtaccac attgtcttat tctttctcat aggtctgaaa 1380

  ttgtcgtatt catttttaat gtattttttg cctttttgtc cctgctaaca tataagcttt 1440

  ttgaggtcag agactttctt ttcactgtag tattcccagt tcctaaaaca gggccctaca 1500

  catattggat gtttaataaa catttattga ctaatacaaa tgaaaaaaaa aaaaaaaaaa 1560

  <210> SEQ ID NO 35

  <211> LENGTH: 1092

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 35

  ggcacgtgtt gtggagtctc ctaagtgctt gctggacaca atttcttgtc tatttttgct 60

  gccttatgat tctccaaagg acatttcccc cacgggctct gaggacatct ccgtggcttt 120

  ccaaccccat gggggttaaa gggaaaaaaa aaaaaggaac gtttatggaa atgatgctag 180

  ggttgttctc tcctctttgc cttgtcactg gaattgctga aggcagggct gaagatgctt 240

  ctctacatga catctgcacc acccaacaca cacttacctt cacaccttca taccctgttg 300

  gagggtcctg atgactacag ggcagtaaat tcagccccac aggagggcca cagcagcccc 360

  cagcctctag cctcctaccc tccttcttag gcaaccttga caggaaattt tccctctgcc 420

  ttctccttga tcccaacggt agctgcataa tagctgagct cacataatcc ctgtcgccag 480

  tgctagagtg cccttagatg gaggtagccc aggtttgact tcctgaatcc ccagcagcag 540

  gccttttctt tctagagctc tttgcaggaa gagaaagctt tggaccagct catgctgggt 600

  gtaatccttt gtggaagcct ccctgtttcc cttctctgat ctgccccgga gattcctgtg 660

  tgtcccagtc tctagggagg gaggcttagc tggagaggtt caagggcagg agaaagcagg 720

  agaatgcaga ggccgcgggg agaggacaga aagtatatca tttataacta acctttagcc 780

  tttagccact caaaaatatt tcctaatagc ctaagggttc ttggcaggtc tttccccaca 840

  tcagcaagaa atcttgggag ttgggaagag tcagaccttg ttccctgaac aagctttctg 900

  ctttggccaa gagttgttag gagattaatg cctgtccctg aaaggcacag gttggagtgt 960

  ttacttcttc ctctcctttc ctctctcccc ccttagagat cgtgaccctt cctgcttgcc 1020

  tccctggtgg gctctttcag gctggacaca gggtttaaaa aaaaaaaaaa aaaaaaaaaa 1080

  aaaaaaactc ga 1092

  <210> SEQ ID NO 36

  <211> LENGTH: 1153

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (409)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (511)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1001)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1089)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1113)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 36

  agactatcct caaggagctt acatatcagt aaataaatta ttaaaggtgg aaaatgtggt 60

  aaaagagaca taatgtctcg gagagagaac aaatttctgc tttaggagtg ttcttagtta 120

  aggtaacatt agcttctata atacgcacac tcccaaatct cagtatttca acatgagttt 180

  ctctcttgct catgtaaaga ctggtcaggg acccaggttg acagaggctc ttcagtacat 240

  agcttccaag attgctgtgg gtgtgacatc cagccagaaa tctggtgaag agagagcaat 300

  grttacacag gaacttttaa tggaccaggc ctgggacagc gtatgtcact tccaccaaca 360

  tcccactcac cagaatttsg tcacagggcc atagctatct gcagagaang ctgggaaatg 420

  gaacttagct atgtgctcaa gaggaaaagt aaaacagtta ttgaataatt agtaataatt 480

  agcaagtaac tacctagggg tcacagagga nctctcaggt agaatttaga cttaaagatg 540

  atgggggagt gtgtggaaga gtggtgcaga atagggaaag gggggattga aggaagaaca 600

  agctctagct tcacctgcat gggtagagcc cacagtgttg gtagggacat gttagctttc 660

  aacatcagct tcttaacagt attattcttt catcggagga aattagtcta tttctgagga 720

  aaaaaaaatc tgcaatacgt agcaatttac ttacttggat attgaatgtt aaagcagaga 780

  gagactttgt cctcaaaacc ctcccatttc agaagtgagg agcctgggga ggtcatgctc 840

  tctggatgtc acacagtgag tcactgtcaa agccagaata gaacccagac ctctcagttt 900

  cccatwccag tgctctttct atgaggaaag tataagtttg agcattttta aaccttaatt 960

  atgtagaaat aaccatgata ttttatcgta aattatttca ntcatctcat tttaaatttt 1020

  actccaaact aaaggaaaac ggtactgatt taaaacatct atcataattc aatatagccc 1080

  atatttctnc tttaggaaaa attttttttt gtnttttatc ctgaagaccc gtgccctctt 1140

  cctgtgtctc atg 1153

  <210> SEQ ID NO 37

  <211> LENGTH: 985

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (633)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (642)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 37

  ggcacgagca cacccccctg agaccaggga gcatttattc aaggaaacac ttgtctttag 60

  aggatgttga cgatgcccca aacttactgt agctgtcagg aaaattaggt gagctattta 120

  gtatcattga gcttcatttt acagaaccag catgttgtcc ttagacttcc ctctgatcct 180

  tttaggtctc aacttacata ttgccctctt gagccttcta gttcccagac tgagttagga 240

  accccaaccc atgctggact cagttagtcc tttccacatt gtgctgtaat tggctatacc 300

  ccatctgtcc ttcctgccag actaggagtc tcctgcgggc cctaacgttc ccaatttccg 360

  gtgtttggac tggtgctctg tagatgttta gggaatgaaa gggtaatgaa taaattaatg 420

  aaacaaataa gaatcatata gtattagcag cactagataa aaggtgtaaa atcttaagtg 480

  atccaccatc ttttaaataa ttcattcaaa cgatatttca aatgcatatc acctccaaga 540

  aatcgtttct gcatttcrrs tgasttctac gatgccwwrt gaatgarraa rsrrgracak 600

  ggyrtggttc tggggggctg tgagagtaac ggngcaatcc tngtcattgt cgtagttatc 660

  tggccatcca gggcttctca ggttgccaaa tgccttgtga tagtctctgt tgcaatctta 720

  gaggaaaaat aggcataatt aatgtacgca ttccaatatt tagtgctctt tcaacttaca 780

  caggaatcat tcaaaaagat cattgcattt gataaacttt agaaaaaagt aatccagctt 840

  cttcgtttac ctttgagata attgagaccc tgagcagtga agtgaattgc tcaagcagca 900

  cacacaggtg caacgcaaca gctcgttcac acaaacacgc ctacaggaag catgacacag 960

  gaggcttctc ctttaaagac gaata 985

  <210> SEQ ID NO 38

  <211> LENGTH: 1122

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (380)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (381)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (402)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (499)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (505)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 38

  agtgaaaagc agatgttaag tggcatatgt gtcttcagtc acctctgtgt gggttgttct 60

  gtagtataga gggtgttcta aaaatgatct ttaggaatgg agtgaggctt gtttttgttt 120

  ttgttttgtt ttacacttcc acacaatccc ttttcaattc cttgcaaact gctgagtatg 180

  tactattttg ccagcaaagg ctgagcctgt atgaacccag ccatgtgctt tgtctgtgca 240

  tgtccccaca caggaagcac accagagaaa gcgatacttc agggtagatt gatttcatta 300

  ggaacttcat tatcaccagc ctcaaatggt tctggccagc agtctttttc tatctgtatg 360

  attaaccctt ctctgccgcn nagcacctcc tcccaccacc tnttctcagt gttaacaggt 420

  gatctagact cctactctca gagaaaattg aagccaacaa gtagaaagtc ttttttgcta 480

  ccaaagacac aaacctatnt tgttntgcat ccatcctcac ccccgctggt gcttgttcaa 540

  cacaggagtc ctctctccac ctacccaaag cctgtcccct cctgctgtgc cctggatctt 600

  atctctgtca ttgccttaga aacctttctt gtatatattc atctttttcc ttcaatagat 660

  ctttcttatt ggattttaag catgttgcag cctcttctgt taataaaaca acaatcaaca 720

  aaaacactct cccttaactg catgctttat tccagctact accttatatc attcctttcc 780

  ttcaaggcca aagtcctcag aagaggtggc aatatcctcc atcatttctt cacttcatac 840

  tcattcttca acacatacta atctagtctc ttaccccata attcattaaa acacttattc 900

  ttgggtcatg ggtgacttct gtatagctaa atccagtgga tatttttcag gcctcctctt 960

  ccttacattt tagtatttca ccctattggc cattcttttc ttcttgaaat actctctcct 1020

  ttagctttta tgacactgta ctcctggttt ttctcccatt tcttgtctgc tcctgcttag 1080

  ttccctctgt aaacttggcc tctttcacaa ggccagtaaa ca 1122

  <210> SEQ ID NO 39

  <211> LENGTH: 598

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 39

  gaattcggca cgagctggct gcaaggtctg ttgggggagg gtcctcactt gacccttact 60

  ggggtcagtg tgggtcaagg gttaagtgtc accctcggcc cttgggagcc tcattgctga 120

  gggtctcagc gcttaccact ggtcctggcg tcacggactg tggagctggg ggcagcccgt 180

  ggtgggtttt atagcaagtg gtgagatgtg ggcgctgtgc tccaaaccag accccgttaa 240

  gtgccacatg gtcaacagtt tagtgtgcag aaatgaattt ccttctctta atttttcctt 300

  atttttccag cctgttgggg gaggtggagg tggtgaaatg ttagcagtga ccagttcatc 360

  ctgatctgct tgggaccttc cagttttagc actgaaagcc ccacagccca agaatccctt 420

  ggatatcaac cacggttcct ccttccagaa tgtcccaaga gccttagggc ctggagacac 480

  acaggtgggg gcctgagccc ctgtccccct cctccagatg gagcaggcag ggccccaggg 540

  ccccagggct cacggtgttc tggggtccac agtgtgctgt gcggccaggc tggtcttc 598

  <210> SEQ ID NO 40

  <211> LENGTH: 1129

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (1053)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 40

  ggcacgagct tatttatttc tgctgtcctt tttcttatta ttctgcctat attatcctga 60

  aaatatttag tcagttctgt tttgcccaca attagcatgg ctaggtcatt gatttcagca 120

  ctcaggtcag gtatgtcccc aggaagggtc tcagtggttt ctttgcaggg atcacagcta 180

  tgtcttttgg tatctattgc aatcatgggt ttgcttctat tttgaatttg tctgtcttat 240

  ctcttggaca tcaaaagtgc ccttcagggt aggcatgcta cttgttttat atctgccacc 300

  caatttcaac tgtaaaatcc taatcacaag tggcaactag ataggttaaa atgatttctg 360

  gaactttcct tctggacatg taagatccta aaatcttacg agaatttcag tgagttgatt 420

  ttgtctttaa tattttttct taggaaaaag aagacccatt ttgaatctgt tcaactgaaa 480

  acctcaagat ccccaaatat atgaagagac agtgctgtag cccttgagac taatgaacaa 540

  agaaacctgc tctagtttta caggaccata ttttagggtc tgtcctcata cctgtcacat 600

  tggtgatctc acagaggagg gccatgccgc tgaaaaggga aggagattga aacatttgat 660

  tgccttatca catggtcaag taccttgcca aataaaggaa agcaaatgat ttgggtctca 720

  actgaagatg aagctcaact caggaagaga tttatctgta tatacacata actgaaaacc 780

  aagtttaagc ccaccaatgc actgctgatg catgccatat aattaatggg taactttgat 840

  tctttatgac gtctacataa caagtgtgat ttggaaggca catgtgagca tatgcattat 900

  gatccaattt atgttttttc tttgtttata ttttggggaa aattaaaatt tttttaaggt 960

  atatttttcc cattatttat tttcctgacc ttaaaacagc ttttctacta aaaaatggtg 1020

  agcaatgaag acaataaatt tttcattttt ccnaaaaaaa aaaaaaaaaa aaaaaaaaaa 1080

  aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaccc 1129

  <210> SEQ ID NO 41

  <211> LENGTH: 1158

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 41

  ttaacccaaa tgggttggga tggcacgagg ggaaatggga ggggaagaga acagctgaca 60

  tcttgaggaa agctttgggg tagtggagag gtaagggggt catggtcagt ctgaactcaa 120

  caatagggct gaatgaattt accaaaggaa gctgccttat attatatgcc aggctgctgg 180

  ggaaagcctc aggtcctggc cagcccctgt tctcacaaga acatgcaggt taccacataa 240

  ataatggcat atgccttcca taggacgtca acctgactta aatctaccta taccctactc 300

  tctattcttt ggtttttggt tctcatccct gtggaaggaa atgggcctct tctggcatct 360

  catgctactc tgtgcttttc cttgggctcc aaattctagc tcataaagat gcaagttttg 420

  caatttccta taaatggtta agaaaagagc aagctgtcca gagagtgaga agtttgaaaa 480

  gagaggtgca taagagagaa atgatgtcca tttgagcccc accacggagg ttatgtggtc 540

  ccaaaaggaa tgatggccaa gcaattaatt tttcctccta gttcttagct tgcttctgca 600

  ttgattggct ttacacaact ggcatttagt ctgcattaca caaatagaca ctaatttatt 660

  tggaacaagc agcaaaatga gaactttatt tggtgcagtc agggctccat ttagttccct 720

  cactctgctt ctaatcaccc cttctcccag ccctcttcta tttgatagag gtctgtccct 780

  cagatcagca atgtcttagc ccctctcctc tcttccattc cttcctgttg gtactcattt 840

  cttctaactt ttaataaaca tttaggtata atacattaca gtaagtgcta tttagataca 900

  aacttaaaac atactatata ttttaaggat ctaagaatcc tttagagaag gcacatgact 960

  gaagtacctc agctgcgcag cctgtagcca gtttttttaa tgtaaaagta agaatgccag 1020

  ccttaaccta gccctgcaga taaaagctaa cttttattaa taccagccct gaataatggc 1080

  actaatccac actcttcctt agagtgatgc tggaaaaata aaatcagggg cttcaggatt 1140

  aaaaaaaaaa aaaaaaaa 1158

  <210> SEQ ID NO 42

  <211> LENGTH: 1767

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (765)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1130)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1545)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1658)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1744)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1748)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 42

  ccgggtcgac ccacgcgtcc gattgaacgg tttggggcat ccttcctagg aaaagaatgt 60

  cagttaaggt ggggtctctt ctggttttgg tgtattttac cctgggccca gttgttgcag 120

  aactggaggt gaccctgcct tctcattcct aacatttttc tctactacca cccggatttt 180

  gaggcagacc cccaactcgt catggctcca gctgaagttt gaaatataac gtcccggact 240

  tctagcctgt aggagctgca gatgtagtgg ggcagacatg gggagggtca gtggtgagcc 300

  tatagaaaca tctctttccg caggaaaaga taaaggatgt gatgtgtgta gctcacctcc 360

  aggctgaaat gcagactttc ctcatcttcc acagtaagca ggattccctt ctgataacct 420

  tgtcagaaat gttgtttttc aaagggcatg tatggtatct gtcactttca gtgatgattg 480

  tgtcgtcagt tgatgtctct tgacctgaac tgagtatgcc tgtggaaggt cctcttagcc 540

  ccctcacaga aataggaggg ggtgtcctcg ggctgtagct gtgcttcctc tgaaggtcac 600

  tggggaaaag ggataccaag ggccgttgtc cagcttatta tcccagctgc tgcacaaagt 660

  gtccaggaac tggtccttag agcttttgag ttttatcaga tcagtttgtt ccttgggttg 720

  gccatcaaga tgggtctcaa tataaatgaa ggaatctgaa tagantccag ttttatgtgt 780

  ttctagagaa aatgctcaag tgttcttatg caagtcatgt tagatttata tgatgtgtga 840

  aatctgctta caaggaaatt ttcatgattt gtgttagatt agcatttaat tgtctgcttt 900

  aacagatact taatttattt caaaaataag gaaaaataga ggaatcggtg tgaatgtttt 960

  aagactgaga gatgatgatc ctttactttt cctgtaaaga agataatttt taaatctttc 1020

  atatcctgta gagaaaacca acttttcctc tgtgatatag tacattatgt ttgcactact 1080

  ataatgtcaa gactgaaagt ataaaaaatg tacatataag attaattttn atatcttttt 1140

  ttttaaaggg gtttgaggtg cctgcctggc tcattcagta aaacatacaa ctctcgatct 1200

  tgggatcatg agttcaagcc ccacgttagg ggtagagttt actttaaaaa taaataaaag 1260

  gggttgagtc tattgcacta agctctacat gactaattta aagtggagag atgttgtgct 1320

  agatttaaaa aaaataacta gttttcttaa tgtgtctttg tatgatcaac agcatgccat 1380

  aagcaataca aaacaccaag ccttatactt acaagaaaaa aggttaacat actggtaaag 1440

  ttctaaacat atcaaatgta cataagtgac aaaggtagga ttttaaggaa atgtcagtat 1500

  atagagaagc tcagtactgc attaaggaac ttcttcagaa ctagngaagt attcctgtgt 1560

  ttgaggagaa aacttagggg tttgagaagt tatatttttc tatttaaaag ggttaaatta 1620

  ttgcataatt tggaaaaggt tgctttgaat gtaggacnaa actgtttcaa agatttttgt 1680

  ttgaaaagtt tatgtatttt tgtgccttaa tatttgttct gacttttaat aaaatgcttt 1740

  ctgnaaanaa aaaaaaaaaa aaaaaaa 1767

  <210> SEQ ID NO 43

  <211> LENGTH: 917

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 43

  ccacgcgtcc gggctcaccc caggccgaga ccaggtggtc cgaccccatc gctcttcacc 60

  aagggaagtc gccagcctcc atcgacacgt ggccagggcg acgcagtggt ggtatgatcg 120

  tcatcacctc tatcctctcc tccctggcca gcctcctgct cctggccttc ctggcagcgt 180

  ccaccgcacg cttgagccct cagtcacttc cagagacctg ataccggggt tagtcagggc 240

  aaccacctgg aggaagtggg ccaggagctg cttctagaag gaaggaaagg gagagactgc 300

  aggaggaccg gggacccagt gctgcctcct ctccccatcc agctccagcc tgtggtggcc 360

  ggaggaggcc ccggagcagc tgagaattgg ctccttcatg gggaagcgct acatgaccca 420

  ccacatccca cccagcgaag ccgccaccct gcccgtgggc tgtgagcctg gcctggaccc 480

  cctccccagc ctcagcccct agcctggccc ttgtggctgg ggcgtgtgtg gctgtggcca 540

  gtgtgggggc aaggacgtgg tagttattcc cagcccctgc accctcctcc tcacccctgc 600

  caaagtccca ctgatgtagg acagatgtca gggttctaga cgtctttggt gcaaaaaggg 660

  ggttttattc aagcacaggg acaggaccca tgggcaggga gagcggcacc ggggtggtga 720

  ggagtggccc gttatatata ctttcgagtt gggagggctt agagagagcg taagtctcta 780

  aggaattttg gaagcaaggt ctccagggtc ctgagggggc tagctgttgt taggaaaagg 840

  tcatttatta ctgtttagta aaaactttca ccagaaaaaa aaaaaaaaaa aaaaaaaaaa 900

  aaaaaaaaaa aaaaaaa 917

  <210> SEQ ID NO 44

  <211> LENGTH: 1987

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (1554)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 44

  ggcacagttt ccagggaaag aagggcgggg atgtcagggc tggagagtgc ccgtgtcctt 60

  ctgtgtgcat tgggctcctt cctccttaat tctctgcttt ccacttttag gctgaactcc 120

  agtgcaccca gttagacttg gagcggaaac tcaagttgaa tgaaaatgcc atctccaggc 180

  tccaggctaa ccaaaagtct gttctggtgt cggtgtcaga ggtcaaagca gtggctgaaa 240

  tgcagtttgg ggaactcctt gctgctgtga ggaaggccca ggccaatgtg atgctcttct 300

  takakgagaa ggagcaagct gcgctgagcc aggccaacgg tatcaaggcc cacctggagt 360

  acaagagtgc cgagatggag aagagtaagc aggagctgga gacgatggcg gccatcagca 420

  acactgtcca gttcttggag gagtactgca agtttaagaa cactgaagac atcaccttcc 480

  ctagtgttta catagggctg aaggataaac tctcgggcat ccgcaaagtt atcacggaat 540

  ccactgtaca cttaatccak ttkytggaga actataagaa aaagctccag gagttttcca 600

  aggaagagga gtatgacatc agaactcaag tgtctgccrt tgttcagcgc aaatattgga 660

  cttccaaacc tgagcccagc accagggaac agttcctcca atatgtgyat gacatcacgt 720

  tcgacccgga cacagcacac aagtatctcc ggctgcagga ggagaaccgc aaggtcacca 780

  acaccacgcc ctgggagcat ccctacccgg acctccccag caggttcctg cactggcggc 840

  aggtgctgtc ccagcagagt ctgtacctgc acaggtacta ttttgaggtg gagatcttcg 900

  gggcaggcac ctatgttggc ctgacctgca aaggcatcga ccrgaaaggg gaggagcgca 960

  rcagttgcat ttccggaaac aacttctcct ggagcctcca atggaacggg aaggagttca 1020

  cggcctggta cagtgacatg gagaccccac tcaaagctgg ccctttctgg agctcggggt 1080

  ctatattgac ttcccaggag ggatcctttc cttctatggc gtagagtatg attccatgac 1140

  tctggttcac aagtttgcct gcaagttttc agaaccagtc tatgctgcct tctggctttc 1200

  caagaaggaa aacgccatcc ggattgtaga tctgggagag gaacccgaga agccagcacc 1260

  gtccttggtg gggactgctc cctagactcc aggagccata tcccagacct ttgccagcta 1320

  cagtgatggg atttgcattt tagggtgatt tgggggcaaa aataactgct gatggtagct 1380

  ggcttttgaa atcctatggg gtctctgaat gaaaacattc tccagctgct ctcttttgct 1440

  ccatatggtg ctgttctcta tgtgtttggc agtaattctt tttttttttt tttttttgag 1500

  acggagtctc gcactgttgc ccaggctgga gtgcagtggc gcgaatcttg gctncactgc 1560

  caagtccgcc tcccgagttc caagccaatt ctcctgcctc agcctcccga gtagctggga 1620

  ttacaggtgc ctgccaccac acccagctaa cgttttgtat ttttagtaga gatggggttt 1680

  caccatgttg gccaggcaga tctcaaactt ctgacctcgt gatgcactca cctcggcctc 1740

  ccaaagtgct gggattacag gcgtgagcca ctgcgccctg cctgtttgta gtaattttta 1800

  ggcaccaaat ctccctcatc ttctagtgcc attctcctct ctgttcaggt aaatgtcaca 1860

  ctgtgcccag aatggatgac caggaacctt caagagtggc tgaaaagatt gcagagttat 1920

  cataataaat tgctaacttg cgtatwaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1980

  aaaaaaa 1987

  <210> SEQ ID NO 45

  <211> LENGTH: 2053

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 45

  acgctgggac ttgggcggtg gtggaggtgg taaccgtgat agtagcagct ccggcgrcag 60

  caacagcgac tacgagggat ggcggcggct gcagcaggaa ctgmarcatc ccagaggttt 120

  ttccagagct tctcggatgc cctaatcgac gaggaccccc aggcggcgtt agargagctg 180

  actaaggctt tggaacagaa accagatgat gcacagtatt attgtcaaag agcttattgt 240

  cacattcttc ttgggaatta ctgtgttgct gttgctgatg caaagaagtc tctagaactc 300

  aatccaaata attccactgc tatgctgaga aaaggaatat gtgaatacca tgaaaaaaac 360

  tatgctgctg ccctagaaac ttttacagaa ggacaaaaat tagatagtgc agatgctaat 420

  ttcagtgtct ggattaaaag gtgtcaagaa gctcagaatg gctcagaatc tgaggtggta 480

  agtccaaagt tttcattctt catgttttta ttattttaaa tttcagctac caaatatatt 540

  tgagacaaga ctcaggatga gctgtctgat atttaaatat taagcaattc catttaagtg 600

  ctggttcctc taggcactga aataaaatca ttttttgata aatatagaag tttccagtca 660

  tgaaaattat tggcctattt taatgaattt agtgtgtggt taaagttgat ttcgtgtgtt 720

  ttaatatggt catgatgatc atttatcttt tccgttacta aaaccttatt gcatttattt 780

  aggttcaaca gtttgaatca cttgtagggc tttttatgat aggctaagac aaaagttaaa 840

  gaaaattgga aattgacagg gtcttgctct gtcatgcagg ctggagtgca gtggtgccat 900

  catagtgcac ttgagcttca aactcctggg ctcaagcaat cttcccacct cagccttcca 960

  agtagctggg actacaggtg tacaccacca agcctggcta attactctgt ttctttaaaa 1020

  cgatttttaa aacaatgtta ttttagttta ggaagttgct gaatcttaga actggccatt 1080

  ttatataagc aaccttttct aatcatgcct ttagaagttt tctgttattt aaagttctgt 1140

  tattttagag caaaaatctt ttatgaaatt caatctaaga ttttttaaat gctgagcatt 1200

  ctaatttttt tccgaaaact agtggtattt aacaattaca gttactatgt ctttggaagg 1260

  aaaattttca tgtagttatt ttatatcaaa ataactgcag tgttgggtaa attaataata 1320

  catgcatttt aataatacag ttgctaaact gacttgtaaa aatctttctc tttcaactta 1380

  ccaaaatcaa tctgcatccc agtggactca tcagtcaaaa atcaagtatg actggtatca 1440

  aacagaatct caagtagtca ttacacttat gatcaagaat gttcagaaga atgatgtaaa 1500

  tgtggaattt tcagaaaaag agttgtctgc tttggttaaa cttccttctg gagaggatta 1560

  caatttgaaa ctggaacttc ttcatcctat aataccagaa cagagcacgt ttaaagtact 1620

  ttcaacaaag attgaaatta aactgaaaaa gccagaggct gtgagatggg aaaagctaga 1680

  ggggcaagga gatgtgccta cgccaaaaca attcgtagca gatgtaaaga acctatatcc 1740

  atcatcatct ccttatacaa gaaattggga taaattggtt ggtgagatca aagaagaaga 1800

  aaagaatgaa aagttggagg gagatgcagc tttaaacaga ttatttcagc agatctattc 1860

  agatggttct gatgaagtga aacgtgccat gaacaaatcc tttatggagt cgggtggtac 1920

  agttttgagt accaactggt ctgatgtagg taaaaggaaa gttgaaatca atcctcctga 1980

  tgatatggaa tggaaaaagt actaaataaa ttaatttgct ctcaaaaaaa aaaaaaaaaa 2040

  aaaaaaaact cga 2053

  <210> SEQ ID NO 46

  <211> LENGTH: 1272

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (1264)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 46

  aggctgctac actaatagga tgtagcaaag ggcggaggag gagatccaga agcaaacaca 60

  agcaatgcaa gaactccaca gagtggagct ggagagagag aaagcgcgga taagagagga 120

  gtatgaagag aaaatcagaa agctggaaga taaagtggag caggaaaaga gaaagaagca 180

  aatggagaaa gaaactagca gaacaggagg ctcactatgc tgtaaggcag caaagggcaa 240

  gaacggaagt ggagagtaag gatgggatac ttgaattaat catgacagcg ttacagattg 300

  cttcctttat tttgttacgt ctgttcgcgg aagattaaac ttaatgaaaa tctgtttgta 360

  ttttctgcat attctctggc aaccttgccc catacttact tatttagcat agtcgagtgc 420

  tctagtttct gtctctcagg cactcgtaac taaggaccac cattggccat tggtagatgt 480

  ttgattgact taacaagaga gggacaaatt ttcaatttgt gaaactccaa agcagaaagt 540

  attggtgctt gctaccttgt gaattcttcc ttagacatgc agagaaaatg tatgcaagag 600

  accaaaaaga tggctccaag ctatgtcatg ttacctgtaa taaaatcttt tcttctagat 660

  tctttctatg ttggcagata atctcccctt gtagcttcca ctcacttatt cttgcattca 720

  gagtcacaat gatcatctta cccatgtggt ttttgagaaa gaaagatcaa ttctttgttt 780

  gcagtaggta atcttagaga tggagatgat tgtagaatta ttcctagatg agtgtcaatt 840

  tatttaattc cattgtcata taaggagtca aattgtttct tatcatttgt tcattgaaga 900

  acagagacct gtctggaaaa tcgatctcta caaattcaat taaataatga tccccaaatg 960

  sykmaaaagt gaaatacagc aattcaacag ataatagagc aatgtttagt atattcagct 1020

  gtatctgtag aaactctttg acgaacctca atttaaccaa tttgatgaat acccagttct 1080

  cttcttttct agagaaagat agttgcaacc tcacctccct cactcaacac tttgaatact 1140

  tattgtttgg caggtcatcc acacacttct gcccccactg cattgaattt tttgcttatg 1200

  ttgtttataa taaaactttt caattatctc ataaaaaaaa aaaaaaaaaa agggggggcc 1260

  cggnacccaa tt 1272

  <210> SEQ ID NO 47

  <211> LENGTH: 773

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (459)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (503)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 47

  cggcacgagc ttttgcccat aggataagta caaactagat ctggttactg cctgccccac 60

  cagcctcagt atctctcaca actaggacta actttttctt ctgacaacta taaaatattt 120

  cccttgcctt ctcaagtttg ctcaaggtca agttatgcct tttgcctgga atgacttgac 180

  ttctcttttg ttttacttag ctggctgctt ttcatcttgt aggttaggtc aagggactcc 240

  aggaagtctt ccctggacaa gtaatgaaga gggcataatc caagggccaa ctcccatgtt 300

  ttggaacctg actccatttt caggcacgta atattgtcaa attcctttta aaagcacctg 360

  tctgtctgtt aacgttggtg cagatactgc tattcccctc ctccatacca ttgctgatgg 420

  ttactgaggg tatgggaagg gccgactagt ccagctgtnc acaaacagcc cttaatgtca 480

  aactgaatac tgccaacgta gtnccagttt ctgtatctaa agactcagct tggagtcact 540

  tgtctggact aaaaaagtac ccctccttgt ctggtttgtg actttctgta ctctgatgcc 600

  cccagctttc tgccttctag aaatttgtca gaatttccaa aattcttggg ccttccttct 660

  tgctctatat atggttttgg attcattcct tttaaaaaat atttactgtc atttcagtag 720

  aattttgaca caataaatat aagcacatca aaaaaaaaaa aaaaaaactc gga 773

  <210> SEQ ID NO 48

  <211> LENGTH: 2119

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (1424)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1438)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 48

  wgcaagcttt gggagttgtt cgctgtccct gccctgctct gctagggaga gaacgccaga 60

  gggaggcggc tggcccggcg gcaggctctc agaaccgcta ccggcgatgc tactgctgtg 120

  ggtgtcggtg gtcgcagcct tggcgctggc ggtactggcc cccggagcag gggagcagag 180

  gcggagagca gccaaagcgc ccaatgtggt gctggtcgtg agcgactcct acgatggaag 240

  gttaacattt catccaggaa gtcaggtagt gaaacttcct tttatcaact ttatgaagac 300

  acgtgggact tcctttctga atgcctacac aaactctcca atttgttgcc catcacgcgc 360

  agcaatgtgg agtggcctct tcactcactt aacagaatct tggaataatt ttaagggtct 420

  agatccaaat tatacaacat ggatggatgt catggagagg catggctacc gaacacaaaa 480

  atttgggaaa ctggactata cttcaggaca tcactccatt agtaatcgtg tggaagcgtg 540

  gacaagagat gttgctttct tactcagaca agaaggcagg cccatggtta atcttatccg 600

  taacaggact aaagtcagag tgatggaaag ggattggcag aatacagaca aagcagtaaa 660

  ctggttaaga aaggaagcaa ttaattacac tgaaccattt gttatttact tgggattaaa 720

  tttaccacac ccttaccctt caccatcttc tggagaaaat tttggatctt caacatttca 780

  cacatctctt tattggcttg aaaaagtgtc tcatgatgcc atcaaaatcc caaagtggtc 840

  acctttgtca gaaatgcacc ctgtagatta ttactcttct tatacaaaaa actgcactgg 900

  aagatttacw aaaaaagaaa ttaakaatat tagagcattt tattatgcta tgtgtgctga 960

  gacagatgcc atgcttggtg aaattatttt ggcccttcat caattagatc ttcttcagaa 1020

  aactattgtc atatactcct cagaccatgg agagctggcc atggaacatc gacagtttta 1080

  taaaatgagc atgtacgagg ctagtgcaca tgttccgctt ttgatgatgg gaccaggaat 1140

  taaagccggc ctacaagtat caaatgtggt ttctcttgtg gatatttacc ctaccatgct 1200

  tgatattgct ggaattcctc tgcctcagaa cctgagtgga tactcttcgt tgccgttatc 1260

  atcagaaaca tttaagaatg aacataaagt caaaaacctg catccaccct ggattactga 1320

  gtgaattacc atggatgtaa tgtgaatgcc tccacctaca tgcttcgaac taaccacttg 1380

  gaaatatata gcctattcgg atgttgcatc aatgttgcct caantctttg atctttcntc 1440

  ggatccagat gaattaacaa atgttgctgt aaaatttccc agaaattact tattctttgg 1500

  atcagaagct tcattccatt ataaactacc ctaaagtttc tgcttctgtc caccagtata 1560

  ataaagagca gtttatcaag tggaaacaaa gtataggaca gaattattca aacgttatag 1620

  caaattttag gtggcaccaa gactggcaga aggaaccaag gaagtatgaa aatgcaattg 1680

  atcagtggct taaaacccat atgaatccaa gagcagtttg aacaaaaagt ttaaaaatag 1740

  tgttctagag atacatataa atatattaca agatcataat tatgtatttt aaatgaaaca 1800

  gttttaataa ttaccaagtt ttggccgggc acagtggctc acacctgtaa tcccaggact 1860

  ttgggaggct gaggaaagca gatcacaagg tcaagagatt gagaccatcc tggccaacat 1920

  ggtgaaaccc tgtctctact aaaaatacaa aaattagctg ggcgcggtgg tgcacaccta 1980

  tagtctcagc tactcagagg ctgaggcagg aggatcgctt gaacccggga ggcagcagtt 2040

  gcagtgagct gagattgcgc cactgtactc cagcctggca acagagtgag actgtgtcgc 2100

  aaaaaaaaaa aaaaaaaaa 2119

  <210> SEQ ID NO 49

  <211> LENGTH: 1188

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (577)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1022)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1052)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 49

  gaattcggca cgagtaattt tgtattttta gtagagacag ggtttctccg tgttggtcag 60

  actggtctcg aactcccgac ctcaggtgat ctgcccacct cggcctccca aagtgctggg 120

  attacaggcg tgagccaccg agcctagccc tgtttaggct ttttatagcc tatgttctta 180

  tgagcagtaa acattatgaa tggtttagtt agacctgttg aattgaattc acttcttctg 240

  cctgtggtca ggtatcaggt agcacagcca cagaagttac tgaatgtctt tgttggtgga 300

  ctttaggaaa gtggtttaat ttatgtggta ttcctatctg ggaattgcaa cagtattgtt 360

  agattgcatt ttgtcacagg gaggaaatta cctggtaact ccctgattag gaacaaaatg 420

  aagcttcccc tttttacaaa tcctggctaa cattccattt ggatctcttc tgttgaacac 480

  ctctctctct cccctccctc ctcactccat tttctcagtt attttattgt ttactattgg 540

  aagtcacctc ccaactcagg atacttgtta gtccatntta ggaaaaatat caccattctt 600

  tcactattat tctctgttga agttgaagaa cagaatatta ctttttttct ttccattatt 660

  ggttacacca gctagttaga gacttggggt aatactgtgg gcatgggttg gatcctgata 720

  tctgtgtcag ttagtgagag ttggttctat gaccctagag ctctttgtgt ccttcaaacg 780

  agggtgctga aacaagacga acatagaact gtctatacca agcaaaaaac tcctgaaagc 840

  acatgcccac tgcaggtgaa ttggtagcat agtgtggaga taagtgggca gtgcttggtc 900

  ctgtttctgc ctcctagaga gtacctctca gcatccaggg atgctttagt aactcttagt 960

  taaaacgaaa tgaactataa ttaattacct tttttttggg ggggacacag agagtttcca 1020

  cngcatttac catgcttttt tttttttttt gnaaaggaaa tatgatagga tattaagatt 1080

  gacagagctg gggatgggtt ggaggctgaa ttatgatgtg tgtatttctt tatgcttgga 1140

  ttatttcata attaaaaacc aaacatataa aaaaaaaaaa gaaaaaaa 1188

  <210> SEQ ID NO 50

  <211> LENGTH: 478

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 50

  ttttttagca tttcacgcta tttattcccc aaaaccttct gccatagaag acagccacca 60

  tacagattgg aaaatgtgga cgaggagaaa aggggtgtat ggtaagcaaa ataaattgta 120

  ttttccatcc ttggggagga taaaggaact ctttgcactg ctataatgaa cagcccccaa 180

  atgccagtgg tttaattcag tggagttcag acctcattcc tatatcattg cagtgtggat 240

  gctcctggat gaaggctctt gtaggtaact ctcctccagt cggtgattca gggacccagc 300

  ctccttctgc cttgcggctt tgccttttaa aggtcctcag ggtgctctcc atgtatcttg 360

  ccaatgggga acgagtgtgg aggactcaca agcgggtcyc acatcacgtc ctccggggct 420

  aatacacatc ccttctcccc acactctgtt ggtcagaagt cactgcttgg cgccctgc 478

  <210> SEQ ID NO 51

  <211> LENGTH: 1333

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (485)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (486)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (493)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (496)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (587)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (633)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1330)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 51

  agctggtacc aaagcaagtt tttcactgag ctctcatgaa agatcctcag tctcttgtgg 60

  atttagaatc ctgcagcagc ccaccatcta agagcaagar ccaaagatgt ttgtcttgct 120

  ctatgttaca agttttgcca tttgtgccag tggacaaccc cggggtaatc agttgaaagg 180

  agagaactac tcccccaggt atatctgcag cattcctggc ttgcctggac ctccagggcc 240

  ccctggagca aatggttccc ctgggcccca tggtcgcatc ggccttccag gaagagatgg 300

  tagagacggc aggaaaggag agaaaggtga aaagggaact gcaggtttga gaggtaagac 360

  tggaccgcta ggtcttgccg gtgagaaagg ggaccaagga gagactggga agaaaggacc 420

  cataggacca gagggagaga aaggagaagt aggtccaatt ggtcctcctg gaccaaaggg 480

  agacnnatga tanctntggg acccggggct gcctggagtt tgcagatgtg gaagcatcgt 540

  gctcaaatcc gccttttctg ttggcatcac aaccagctac ccagaanaaa gactacctat 600

  tatatttaac aaggtcctcc ttccacgagg ganagcacta caaccctgcc acaggggaag 660

  ttcatctgtg ctttcccagg ggatctatta cttttcttat gatatcacat tggctaataa 720

  gcatctggca atcggactgg tacacaatgg gcaataccgg ataaagacct tcgacgccaa 780

  cacaggaaac catgatgtgg cttcggggtc cacagtcatc tatctgcagc cagaagatga 840

  agtctggctg gagattttct tcacagacca gaatggcctc ttctcagacc caggttgggc 900

  agacagctta ttctccgggt ttctcttata cgttgacaca gattacctag attccatatc 960

  agaagatgat gaattgtgat caggaccaag atccctgtgg taaacactct gattgaatct 1020

  ggggttccag aaggtggaac aagcaggaat gggatccaaa gagactccca ctcagattct 1080

  aaagcattta aagacaattc tagcagaatt tatcaaaaca agatgaaaca cagaaaagtt 1140

  gaaaccacaa caaaatgaat tctattaaag aatagcccca gatataaatt ctcttgaaag 1200

  caatgttcat aaatatttaa gcaaattaaa gacaatgtta acaaattttc tattaaatgc 1260

  cctgagtgat aaaaccagtt ggcaataata ttgccttatt aaatcttcaa aaaataaaaa 1320

  aaattaaaan aaa 1333

  <210> SEQ ID NO 52

  <211> LENGTH: 1255

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (541)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (542)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1156)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1162)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1223)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 52

  gaattcggca cgagcacatt taataatcta attcacacac acacacacac gtgaaatcat 60

  tcttgagaat gaaatttatc atgcttttac ttcttccttc aatcttccca actactgttg 120

  aaatgatctg agattttaga tctacattat tgttactttt taacattatg tatcttctgt 180

  ttcaagaagg cttttgatgt ttgagttaag tttcataagc ttttaaacaa gcatttagac 240

  atttacacct gcttaactga tttcattgat cacttttatt tcatttgcac tgtatatccc 300

  cattatttca actcatttca cagttgtctt tggtacttct tttagtactt ttttaaggaa 360

  cagatgggtg atacagtatt atatgttctt gccttcctga agatacttgt gttcaataga 420

  gcgtaacatt tttttcccac agtgactttt ccctcagaat actaaagtca cagaaagtta 480

  tcacatcaac ttaatgttgc ccaagagaag tccaaactct ttgcgcttct tttgtaggtt 540

  nntttgggtt atctccccac aatgatgttt atagattctt tattctttct tcttggaaca 600

  aagaaatttc attgggatat gtttttaaaa atagatctct ttttattatt tttgcatggt 660

  actagatgag acattttagt gcatagatgc aagtcttttt tcaactctgg gaattttact 720

  tctatggaat ttttttttct ttccctaata ttttttcact ctttttctta tcctttagaa 780

  atttttatgt tgatccccta gatctgctct ctgttctgac tagtttttgc tcattatatc 840

  tttttatcct tttcccttag aatcagtact tcttgaaata aactgcttct atgattctga 900

  ggtatagcca aattggggaa gccctcttgt gaagggtcag cagtgtttac ctggaagaag 960

  aacccatttc agttgtgctt cttgctgttt ggctgcctga ttcaatcagt ggcagaaaat 1020

  catattaaat atatttagag tactcccttt aaaagratta cctctctttg aaattcagta 1080

  aatttacatt gagratattt gacaaatttg tatatacatt tgcaggcaat aatttttatg 1140

  agctgatctg ccatgnttaa angttttcct ttgtaaacca tttggtgtgg gtatttttta 1200

  aatttcctca gtatgatccc agngggcatt aactgtccaa aaaaaaaaaa aaaaa 1255

  <210> SEQ ID NO 53

  <211> LENGTH: 1140

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 53

  ctaggagcct cctaatgcag tgttctgcac agtcctgggg actgactgac tgaatcacac 60

  ctctggggct gggggctgct gacatgtgtg cctttccttg gctgcttctt ctcctgctgc 120

  tccaggargg cagccaaagg agactctgga gatggtgtgg atccgaggaa gtggttgcgg 180

  tccttcagga gtccatcagc ctccccctgg aaataccacc agatgaagag gttgagaaca 240

  tcatctggtc ctctcacaaa agtcttgcca ctgtggtgcc agggaaagag ggacatccag 300

  ctaccatcat ggtgaccaat ccacactacc agggccaagt gagcttcctg gaccccarct 360

  attccctgca tatcagcaat ctgagctggg aggattcagg gctttaccaa gctcaagtca 420

  acctgagaac atcccagatc tctaccatgc agcagtacaa tctatgtgtc taccgatggc 480

  tgtcagagdc cccasatcac tgtgaacttt gagagttctg gggaaggtgc ctgcagtatg 540

  tccctggtgt gctctgtgga graaggcagg catggatatg acctacagct ggctctcccg 600

  gggggatagc acttatacat tccatgaagg ccctgtcctc agcacatcct ggaggccggg 660

  ggacagtgcc ctctcctaca cctgcagagc caacaacccc atcagcaacg tcagttcttg 720

  ccccatccct gatgggccct tctatgcaga tcctaactat gcttctgaga agccttcaac 780

  agccttctgc ctcctggcca agggattgct catcttcttg ctcttggtaa ttctggccat 840

  gggactctgg gtcatccgag tccagaaaag acacaaaatg ccaaggatga agaaactcat 900

  gagaaacaga atgaaattga ggaaggaggc aaagcctggc tccagccctg cctgactgct 960

  ccttgggaac cccagtcctg agcttggttt cttcccagca cccagagaat ccttcctcag 1020

  ctctcttctt tccaggggaa ggaggtgctc aggggtgggt atccagagag ccatacttct 1080

  gagggaagac tggctggcaa taaagtcaaa ttaagtgacc accaaaaaaa aaaaaaaaaa 1140

  <210> SEQ ID NO 54

  <211> LENGTH: 1220

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (1197)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1208)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1209)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 54

  ccacgcgtcc gcaaataggt acctaaggca tgtgatttta tttttaaata acaaaaaata 60

  acccaagttt cttgcttctc caaagtattc ttctcatagc ttataaaaga aagtccacat 120

  tgaatagcat ggtctgggaa cattccttct ttattgtgtt tatttgaaca tgatatgagt 180

  ttccaagatg aaatgatcaa aaaagataag taccacaaga aagttttttt gtttggttgg 240

  tttttttgtt tgtttgtttt tttcttgaga ctgagtctct ccctgttgcc caagttggag 300

  tgcaatcttg gctcactgca gcctccacct ccccggttcc agcgattctc ctgcctcagc 360

  ctcttgaata gctgggatta caggcgcccg ccaccacacc tggctaattt ttgtgttgtt 420

  agtagaggcg gggtttcatc atgttggcca ggctggtctc gaactcctga tctcatgatc 480

  cgtctgcctc ggcctcccag agtgctggga ttacaggcat gagccactgc gcccggccaa 540

  gaaagtatgt ttttagaggt gtgtgtaagt gcatttgtat tacctatgaa caaaattacc 600

  tgactcttgt cccaggaaag ctgtttcgca ttttcgcttt ttgattggta ttatccagtt 660

  ctatgtagtt catattattg ttctgtctga ctctcagaaa ttacttcttc acgccagtgt 720

  cttgttgcat gactttgatg tcacctatag gaatacacct cactgcacgt aagtgggtat 780

  cttactgtat aaaaggtcta catggcttta ggttttagga caaatgtgta gatttataga 840

  ccatttctgt tggccaggac acagattttg agagctgtgt gtatatatat ataatcatgt 900

  ttgtattttt ttcctgaaag ttatcaattg cttttgttta aaacagtttg ttttagaggt 960

  ggggtgggga tgtatataac gaggaaaagt tatatgtact ttaaagtatg tcaagttctt 1020

  actagtttcc tgtactgaag gttcaatttt ttttatataa gtttactttt cacctgctct 1080

  attctttgtg gggaaaaaat gcatctagaa aaacatagtt taaatactgt atataagata 1140

  atgaaagtta gtaatgtcca ttatttaata aagtttgtaa agtacaaggt aaaaaanaaa 1200

  aaaaaaanna aaaaaaaagg 1220

  <210> SEQ ID NO 55

  <211> LENGTH: 694

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (621)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (651)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 55

  ataactggag agacatcaaa ctcatgctga gaacaactag aagagttaga attgaagaaa 60

  aaggatttca ttaagatatt agagagtgtt caaggcaact ggaggcagaa cgargattct 120

  ggaaaggggc cacagagaag ttgtctgcat tcaaaagagc attctattaa agctacctta 180

  atttggcgct tatttttctt aatcatgttt ctgacaatca tagtgtgtgg aatggttgct 240

  gctttaagyg caataagagc taactgccat caagagccat cagtatgtct tcaagctgca 300

  tgcccagaaa gctggattgg ttttcaaaga aagtgtttct atttttctga tgacaccaag 360

  aactggacat caagtcagag gttttgtgac tcacaagatg ctgatcttgc tcaggttgaa 420

  agmttccagg aactgktaag aaaatagttc tggccagaat caaagattca gccctacaag 480

  gatatgtttt cctgtgaaat tatctaagag aatttcctgt tgagatataa aggcccatct 540

  gatcactgga ttgggctgas caragaacaa ggccaaccat ggaaatggat aaatggtact 600

  gaatggacaa gacagtaagt nctaaaaatc tggcagtaat atttgtattt naatttactt 660

  tgcattaaat ctgaagtgtt ctctagttac atgc 694

  <210> SEQ ID NO 56

  <211> LENGTH: 988

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 56

  cggcacgagc cagaccctat gatgtgtcca ctctggaggc tcctcatctt cctcgggttg 60

  ctggccttgc ccttggcacc acacaagcag ccttggcctg gcctggccca agcccacaga 120

  gacaacaaat ccaccctggc aagaattatt gctcagggcc tcataaagca caacgcagaa 180

  agccgaattc agaacatcca ctttggggac agactgaatg cctcagcaca agtggcccca 240

  gggctggtgg gctggctaat cagcggcagg aaacaccagc agcagcaaga gagcagcatc 300

  aacatcacca acattcagct ggactgtggt gggatccaga tatcattcca taaggagtgg 360

  ttctcggcaa atatctcact tgaatttgac cttgaattga gaccgtcctt cgataacaac 420

  atcataaaga tgtgtgcaca tatgagcatc gttgtggagt tctggctgga gaaagacgag 480

  tttggccgga gggatctggt gataggcaaa tgcgatgcag agcccagcag tgtccatgtg 540

  gccatcctca ctgaggctat cccaccaaag atgaatcagt ttctctacaa cctcaaagag 600

  aatctgcaaa aagttctccc acacatggta gaaagtcagc ccctggcctg atccttctct 660

  ctgtgctgat ggtccaggta tgtcctctga tcggtgaaat cctcgggcag ctggatgtga 720

  aactgttgaa aagcctcata gaacaggagg ctgctcatga accaacccac catgaaacca 780

  gccaaccctc tgcatgccag gctggagagt cccccagctg acttctgctg atcagaagga 840

  aagtccacat cttgcaacct taagtctccc ttagagtggg gcttctgcta ccctaaaaac 900

  tttaccccag gctctgtgga cataccatcc tctcctacaa taaactctag ctctgaaggg 960

  tgaaaaaaaa aaaaaaaaaa cggcacga 988

  <210> SEQ ID NO 57

  <211> LENGTH: 1500

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (71)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (73)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (755)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 57

  gcctgaaggg tcgtgaggct ggggcgggac ccggcaccgc tggggcgcca ggccgtgagg 60

  acgccaatgg nangcakcgt ggacgaggag gcrctcacca gctgtacctg tgggtagaca 120

  acatccctct gtcccggccc aagcgaaacc tctcccggga ctttagcgat ggagtccttg 180

  ttgcagaggt catcaagttt tacttcccca agatggtgga gatgcacaat tatgtcggca 240

  cgagctctct ccagcagaag ctcagcaact ggggtcatct gaacaggaag gtactgaaga 300

  ggctgaactt ttcagtaccg gatgacgtga tgcgcaagat cgcgcagtgc gccccaggcg 360

  tggtggagct ggtgctcatc ccgctgaggc agcgcctgga ggagaggcag aggcgcagga 420

  agcagggcgc cggctcctta caggagctgg ctccccagga tggcagtggc tacatggatg 480

  tgggtgtatc ccagaaggcc cgaggtgaar gtgtcccgga cccccaggga gggggtcagc 540

  tcagctggga ccggccgccg gcgcctcggc ctccagcgta taaccgggcg ttgcagggcg 600

  accccagctt cgtcctccag atcgctgaaa aggagcagga gctgttggcc tctcaagaga 660

  ccgtgcaggt cctgcagatg aaggtaaggc gcctggagca cctgctccag ctcaagaatg 720

  tgcggatcga aaacctctcc cggcggctcc agcangcgga rcgtaagcag cggtgagcgg 780

  cggcccgggc cgcgcgggga cgcccgggta cccgccagag ccccgacgcc gcgccggacc 840

  cacccaccga tggatagacc attgggaggg cggagcccgc tgctctcacg agcctgctgg 900

  ggcccgagtg ccctccttcc ttgggatggg tgagcgtgga ggagatggga caggaactct 960

  aggagcgcag gcccgggact gagccgcctc ctaccactcc ggagatccgg gtcaggagaa 1020

  tggaccgctt tccagagccc agaagccacg tgcagagacc tagcctgtcc cccaaagcag 1080

  tgtccaacac cttgggcccg gccttgcatc tcccggcgct gggccttggg gggcggtccc 1140

  ttggctctgt ccacaccccc agaatcaggt ccccgcccag ctccgaggac ggcggcgtct 1200

  ccatccaggc tagttcccca tgccctcagc catgggggaa tctgtcccgg gccgctgagg 1260

  ggctcccctg cccctcctgg gagcttacct gggacccacc tcggcgacgg agaccgcagc 1320

  agctggagag gaaggggtga ggcgtgggat cgccaggagt agggaggaca tcgacgatgt 1380

  gcccgtagca gtcgcccctc cctcctcgcg cacggggtac tgaggcggaa ggtttgaagg 1440

  ttacggctca gggctgcccc attaaagtca gtgttgtgtt ctaaaaaaaa aaaaaaaaaa 1500

  <210> SEQ ID NO 58

  <211> LENGTH: 1391

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 58

  ggtaaatacc aaggtaatta aatttttaag ttctgagtat tagaggtaat ggttactgta 60

  gctcctaaaa tgcacatcac atctctggta ggtgctggaa ccctcatggt actgctgctt 120

  ttaattttgc ttttggaatg tttctttgta gctgaagctt tagtgatgag aagttagaaa 180

  tactctcatt gacctttagt gttttgtcct gttgatatat atcaagttcg cttagtttga 240

  cattgtttga acttatttcc ctaagcaaaa aacagccaga aagaagaaaa tccagaacat 300

  gtagaaattc agaagatgat ggattccctc ttcttaaaat tggatgccct ctcaaacttc 360

  cactttatcc ctaaaccgcc tgtaccagag attaaagttg tgtcaaatct gccagccata 420

  accatggagg aagtagcccc agtgagtgtt agtgatgcag ctctcctggc cccagaggag 480

  atcaaggaga aaaataaagc tggagatata aaaacagctg ctgaaaaaac agctacagac 540

  aagaaacgag agcgaaggaa aaagaaatat caaaagcgta tgaaaataaa agagaaggag 600

  aagcggagaa aactgcttga aaagagcagt gtagatcaag cagggaaata cagcaaaaca 660

  gtagcttcgg agaagttaaa acagctgacc aaaactggca aagcttcctt cataaaggta 720

  aggacaaggg aaagaaaact gctcaagggg acctttgtgg gggaagtgga tagcaagtgc 780

  tgggtgactg gaatgtctga gccagctgac agcccacctg tgggatagag atgcatgatg 840

  ctgactggct ggaatcgcaa cctttaatgt tctagaattt ttcacgtagg gtcctcacaa 900

  taacctgggt cctggcagca gcttgtcttc cactcctttc tctcttagat tataagaaca 960

  ttgtagcagt gcagaatacg tctatgctaa ctgattccag ttttctgtaa ttctagtccc 1020

  tttttcatat ttatggttgc atacattgtt gtaatggtga tgtactattt ttggcttttt 1080

  tcacttataa gtacatttta cagcataagc atgtggtgtt tttaattgca ggatgaaggt 1140

  aaagacaagg ccttaaagtc ctctcaagca ttcttttcta aattacaaga tcaagtaaaa 1200

  atgcaaatca atgatgcaaa gaaaacagaa aagaaaaaga agaaaagaca ggatatttct 1260

  gttcataaat taaagctgta atatattttg aatataatgt aaatattaat gtgtaagctt 1320

  atattgtgtc attgttctgt tttataataa aattcttgag aaccttcaaa aaaaaaaaaa 1380

  aaaaaactcg a 1391

  <210> SEQ ID NO 59

  <211> LENGTH: 1579

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 59

  ggcacgaggc agcgcaggga gctgtctgca gaggccaggg tgcgcctgcc acgaatcccc 60

  aggcaccggt ggccgccgcg gcccgagtag ctcggcgggt aaacatggcc gcactgacga 120

  cggttgtggt agcggctgcg gccaccgcgg tagccggggc tgtggcaggg gcgggcgcgg 180

  ccaccgggac cggcgtggga gcgacgccag cgcctcaaca gagtgatggc tgttttagta 240

  cttcaggtgg aattcgtcct tttcatcttc agaactggaa gcagaaagtt aatcagacta 300

  agaaagcaga atttgtacgc acagcagaaa aatttaaaaa tcaagtaatt aacatggaaa 360

  aagataaaca cagtcatttc tacaaccaaa aaagtgactt cagatttgag catagtatgc 420

  tagaagaatt ggaaaataaa ttgattcaca gcaggaaaac agaaagagca aaattccagc 480

  aacaattggc caaaatacat aataatgtaa agaaacttca gcatcaatta aaagatgtga 540

  agcctacacc tgattttgtt gagaagctca gagaaatgat ggaagaaatt gaaaatgcaa 600

  ttaacacttt taaagaagag cagaggttga tatatgaaga gctaattaaa gaagagaaga 660

  caactaataa tgagttgagt gccatatcaa gaaaaattga cacatgggct ttgggtaatt 720

  cagaaacaga gaaagctttc agagcaatct caagcaaagt tcctgtagac aaagtaacac 780

  caagtactct tccagaagag gtactagatt ttgaaaaatt ccttcagcaa acaggagggc 840

  gacaaggtgc ctgggatgtg atcaccagaa ctttgtaaag gtgagaaaca aacataaagg 900

  gaagccaaca tttatggaag aagttctaga acaccttcct ggaaaaacac aagatgaagt 960

  tcaacagcat gaaaaatggt atcaaaagtt tctggctcta gaagaaagaa aaaaagagtc 1020

  aattcagatt tggaaaacta aaaagcagca aaaaagggag gaaattttca agttaaagga 1080

  aaaggcagac aacacacctg tgctttttca taataaacaa gaggataatc aaaagcaaaa 1140

  agaggaacaa agaaagaaac agaaattggc agttgaagct tggaagaaac agaaaagtat 1200

  agaaatgtca atgaaatgtg cttcccagtt aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1260

  tcagaaagaa cgccagcgcc agtttaagtt aaaattacta ctagaaagtt atacccagca 1320

  gaagaaagaa caggaagaat ttttgaggct tgaaaaggag ataagggaaa aggcagaaaa 1380

  ggcagaaaaa aggaaaaatg ctgctgatga aatttccaga tttcaagaaa gagatttaca 1440

  taaacttgaa ctgaaaattc tagatagaca ggcaaaggaa gatgaaaagt cacaaaaaca 1500

  aagaagactg gcaaaattaa aagaaaaggt tgaaaacaat gttagtagag atccctctag 1560

  gctttacaaa cccaccaaa 1579

  <210> SEQ ID NO 60

  <211> LENGTH: 1241

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (8)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (59)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (78)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (84)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (86)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (104)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (128)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 60

  ggcacganct gttatcctac ttcctgctgg ctgcctttaa acatggagct gctacacana 60

  caggtcctgg ctctgcanac acananggtc ctgctggaga agangcggaa ggcttcagcc 120

  tgggaacnga acctgggcta ccccctggct atgctgtgct tgctggtgct gacsggcctg 180

  tytgtgctca ttgtgggcat ccacatcctg gagctgctca tcgatgaggc tgccatgccc 240

  cgaggcatgc agggtacctc cttaggccag gtctccttct ccaagctggg ctcctttgcc 300

  tcttcagcct ccctttctgc aagatagggg caagggcggc tagatggatg tgtctgctgg 360

  gcaagtcata taacatttct gatcctcagt ttcatcctac aaaatgggcg taacaatgtc 420

  tacctactcc attgtgtgga ccaaaggaga tggttaatgt gaaagccctt tgtgaacctg 480

  aagtgagcaa ctgctggatg aatgtcatta cgggcacagg ctctgtgtca tctcctctcc 540

  tagtgcttcc acagccagga ccagagacct ccctgatgac tggggaacct ggtgatggtg 600

  gcctttctct ttatggggag cctgagtatg ctcagatcgc agctttcctt ccctagacat 660

  tgtgtaattg ggggtggggg cacacttgcc ccacwkccta gctccagcct ttcctcctct 720

  taggatggct caggatgagt cccccctcaa caaggcagct acccaagagt aattcccctg 780

  gggactttct gtgtgaatct ccccttcccc ctcctctctt ttccctttcc tggacccagc 840

  cactgatgta accaacctca cagactagtt gtttattata ttaatagttt gagcatataa 900

  agaggaactt gtgatgggag agatctaggg aggagtaaag aagtatagga atgtctggcc 960

  tgtattctct tcacctggga ccactgattt ttaagctgcc acattggctg gagaacaggc 1020

  tatggagttc ataatgtgtg gtctcctgga gctcctgttc agctctgcct tctttgaggg 1080

  ggcagggatg gggcagggag cacatygtaa tactaacggc ctcagagmtg ccccctgatg 1140

  tcctcctgcc tgttaccccg tgcctctgtc tcttaacagt gggatgatga agatgccacc 1200

  gtcaacaagr ktgcgctcga gctgtgcamc tttaacctgg g 1241

  <210> SEQ ID NO 61

  <211> LENGTH: 930

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 61

  gaattcggca cgagctaagt cctgatatcc catgatgttt tttgttttac tttgtttttg 60

  gctatttcct ttttctaaaa atagccctct ctggggaatg ctgagatctt cattctttat 120

  tagtatcaat ttataattat ctacatctgt aagcagttat tcgaaagtct ccagatctta 180

  ttctatcctg gcacccatgg tgactaaaaa aatcaaagac gttaaatctt tgaaagcagc 240

  cttcaaacca catactccaa ccaacttacc ttatatgtcg gggagttatg gagcaaatac 300

  attaattaac ttgacagaag ttgcacactt tctgtacttc tgaaccaaaa tttggatgca 360

  tgtttttctt tatcatgagt cacacctgat taggatttcc ttagcttttg ttggggtcag 420

  acaggattgt gaccaaaggc aagatttctc tgtcatctct tttgacagaa tttccacaat 480

  catggatttt gtaatagtcc tggacattca tcagaaagta acctgtagtg gggctgccta 540

  cataggattc ttcctttgaa aagccttaaa catttttcta atggttggtc tctcttaact 600

  aacaataaaa aacagcaaca atgcasctgg gcacagtggc ttttgcctgt aatcccagca 660

  ctttgggagg cccaggcagg tggatcaact gaggtcagga gtttaagacc agcctggcca 720

  acatgtgaaa ccctgtctct acgaaaaata caaaaattag ccggatgttg tgttgcacac 780

  ccgtagtccc acctactggg gaggctgagg caggagaatt gcttaaaccc aggaggcaga 840

  gcttgcattg agctgaaatc gtaccacagc actccagcct gggcaacaga gtgagactcc 900

  atatccaaaa aaaaaaaaaa aaaaactcga 930

  <210> SEQ ID NO 62

  <211> LENGTH: 998

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 62

  ggcacgaggc ttaagtcaag ccacctgatc agtcttgtaa ccactggaga gatgagcagt 60

  gtttagtcat gtccctaata ctgttattgt cagtcaccct tttacatctg tctttttctg 120

  ttggcttctt tctttttagg ttgtagggga gacccattgt ctagagagaa tatacgcttt 180

  gacttgatga aatcccagtt taatctagaa aggtccattt tgaggttaag aacatttcgg 240

  agatgtggag gtgaagatat aaagtaggtc tcagctttgg ctggccaata tgggatccta 300

  cttatctcct caggggactg gacaattcgt gtcaagactc tgtgcttcag gagcctctgc 360

  ttcttcctcc ttcatggtcc aactttcctg ccccttcttc atctcattag cttaaccctc 420

  agttgcctga cccaagtcaa ggtgtgtgac ctggtcctga tcaccacctc tttttggggg 480

  cttctgcaac tgtgctctgt cctggcaacc tgcttctgta atctgtttat ccccaaattt 540

  gaatgagtaa taggaattgc ctaaattttg gataaattat cctacaaaat aaaagcattc 600

  tcacattgcc ctctcaaatc acatgatctt tgtagaaaat ggccggtccc tatgaagcta 660

  attgatcttt ggcatcaata gggaaattca gctgggcgca gtggctcaca cctgtaatcc 720

  cagcactttg ggaggccgag gtgggagggt catttgaggt caagcattca agaccagcct 780

  ggccaacgtg gtgaaacccc gcctctacta aaaatacaaa aaaattagct gggcgtggtg 840

  gtgtgtgcct gtaatcccag ctactcagga ggctgaggca ggagaattgc ttgaaccagg 900

  gagatggagc ttgcagtgag ccgggattgc gccactgcac tacagccagg atgacagagt 960

  gaggctccat ctcaaaaaaa aaaaaaaaaa aaaaaaaa 998

  <210> SEQ ID NO 63

  <211> LENGTH: 1193

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (1080)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1186)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 63

  ggtcgaccca cgcgtccgca ccgaagccca gagggtctgg gggcacaaga ctgacgccag 60

  ggtatgaaga gtgttatttt cattcaaagt gttattttgt ttttccttcc aatgtctgga 120

  gaccaccagg gcatctctgg gctggatgag ctcccacaag cctgagggaa aggccagcac 180

  tcgctagcag tggcaggcag aggcccaggc tgccgtcccc tagagtccca ggttggctct 240

  gccagtgcct gtcctttacc aaagatgaat gaagcaaatg tcatgctgcc ttattcaggg 300

  aaggaggagc ctgtcctgcc tgtggccatg accctgcctc tcccaggcag gggcccgcga 360

  tgtggaactg ctgccactga ggggggatcc agttttgtca atgcagttgt ctctgtttta 420

  caagttggag tcactcttat gctgtaccca gtttctaaac tggagactgt gtgtgccctc 480

  tggctctgag tacccctgct ttgggcttgg gcctaggctg cattgaaaag agctgaaggt 540

  tgtggccttt gcgctcctgg cccagccttt gttccccact ggagcagaag gggagatgga 600

  cgacacggts ggggcatctg gcctggccag tgccctgatc ccagagagcc cgaggaggtg 660

  tctcaggctg cctgagtcgt gacctgctag gccagagccc actccatctg gtagaaggga 720

  aagcccatat gctaccacca gctgtgtcca aaaccgccag ctctgttctt cctcagccag 780

  cctcgcccat ccccttgagg tctcagcccc tttcccttgt agctcctccc ctggaggggg 840

  aatggcagca ggggttgggg aaacagcatc tccaagcagc ttagagttgg ccatatttac 900

  ctcagcctgg gcgctggtcc tttcttccgg cccctcccct ccaaaatgtg cctattgcta 960

  gagctcctcc ctctcaacac ccagtttcct tgggagttgt cattaaagga aaaaaaaaaa 1020

  aaaaaaaaag ccagtgccca gggatgggca tctccaggga gctggggatt agtgccaggn 1080

  agccctgcca gccatgccta catccccatg ggcacagaac aagccaaagc cttcgttgta 1140

  tgttgacgat gcacttttat gaaatgtagt ttctatcgct gttttnagcc ttt 1193

  <210> SEQ ID NO 64

  <211> LENGTH: 830

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 64

  ggtcgaccca cgcgtccgct gaaaggaaaa gcactgtttg gagaatgatc cacctttcaa 60

  gattttactt attgttgata atgctcccac atgtcctctt ttttacgggt gatcttcatt 120

  cctaatatca aagtgatatt tcttcctcca ggcaccacct ctttgatcca cacaatggat 180

  caaggagtta tagcagcttt taagttctac tacctgagaa gggaggactt ttgcccagtc 240

  ccatactgca gtggaggaag acactgagaa gactctgatg aaattctgaa cagcatcaag 300

  aaccttgttt aggcttggat tatgtcgcta aggactgtag gaatggcacc tggaagaaga 360

  cacgcaagag gtttgtcaat aayttcaaag gatttgccaa ggatgasgaa gttgcaaaaa 420

  tcaagaargc tgtggttgag atggcaaaca actttaacct gggtgtggat gtggatgaca 480

  ttgagtaatt cctagagggg gttcctgagg aattgactaa tgggttgctg ttggaactgg 540

  aataggagtg catagctgaa gaagaggtaa agaaaaagaa agtgcaggag aagggaaaaa 600

  agaactccca agaatactca cagtgatggg tttagcagaa gcttcttcag actccaacaa 660

  gctccttaag aagtctgaaa acatggaccc caaaactgaa aggttttcac taatagagag 720

  gaaagttcat ggtgcattat ctgcctacaa gcaaaaccag gattcaaaaa accctttgag 780

  ctggagcttc aaagcacaaa aaaaaaaaaa aaaaaaaaaa aagggcggcc 830

  <210> SEQ ID NO 65

  <211> LENGTH: 867

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (457)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 65

  ggccgccctt tttttttttt tttttttttt ttttttattg gttaaagtgc tgatgccaga 60

  tgacccttga gatcccttat tagtgaaatg ttctgataat aaagaagagt ttggctcacc 120

  tgctggtctc caccacacag gtttataacc aagagcccta cagctcttgt cccaccctga 180

  gggcctgact gacctgtgga gggccccacc tttcgcctcc attcactcac ccctgttccc 240

  aagaaccact gacttcttta catgaagcct actttgagta agtttttagg tacagatgct 300

  gaattaccca agctgtatcc accctcactc caggcacccc gaggagagac tcaactgctt 360

  ggcccagggt tagagaggcc cacacgggaa ggcagagtgg agcagatgtt atttaaccaa 420

  aagtctgtat cctggggctc ccagctacca cagtcangaa acacattttt aaaaaatcma 480

  gacccttgaa ctagcagcag tagtcaccca taccgtatac gataaataaa agtaagccaa 540

  tgtttattct tctttgcata aaatcaccta taccaacact tatacattac agcatcattc 600

  agttaattca agtctgaatc ccagaaactc tcctgaaatc aagccacagt tcagccctat 660

  tcttcctagt ttttcctgac atacttttgc ttactctata aatccacgga tattcttctt 720

  gcctactccc accaaagccc aaatacacgt gaaaaaagtt aatcatgaag tttttcttat 780

  tcccttacat ttagaaaatc agcatctact ctcatagact acttgtaaga agacaaattt 840

  ctgctactcc ggacgcgtgg gtcgacc 867

  <210> SEQ ID NO 66

  <211> LENGTH: 685

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (7)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 66

  gggcccnttt gggggccccc cctttttttt tttttttttt tttttttttt tttttttttt 60

  tttttttttt tttggacagg aagtagaatt tattggtgag tattaagagg ggggcagcac 120

  attggaagcc ctcatgagtg cagggcccgc cacttgtcca gagggccacg actggggatg 180

  tacttgaccc cacagccatc tgggatgagc cgcttttcag ccaccatgtc ttcaaattca 240

  tcagcattga acttggtgaa gccccacttc tttgagatgt ggatcttctg gcggccagga 300

  aacttgaact tggccctgcg cagggcctca atcacatgct ccttgttctg cagcttggtg 360

  cggatggaca tgataacttg gccaatgtga accctggcca cagtgccctg gggctttcca 420

  aaggcacctc gcatgcctgt ttggagcctg tcagccccag cacaggacaa catcttgttg 480

  atgcggatga cgtggaaggg gtggagccgc acccggatat ggaagccatc tttgccacaa 540

  ctttttacca tgtacttatt ggcacaaatt cgggcagcct ccagggcttc agaggacagc 600

  tgctcatatt catctgacac catgtggcca caaagcggaa actcatccac ttttgccttt 660

  ttccgcccca ggtyaaaaat gcgaa 685

  <210> SEQ ID NO 67

  <211> LENGTH: 801

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 67

  gaattcggca cgagtggaga tgcactgacc ttccttgcaa gagcctttcc ctgaagttgg 60

  gctcctgaga gaagttctga acatggctat ccctgccttt tcatcttgtc agcagatttc 120

  ttcagcagct gctctacaaa tatgcaatgg accctttaag catttctcct ttacagtgag 180

  cacaatgcta agctttgtca gcagatgcca ctggagcagc attgcagaag aaagcgagtt 240

  tctcttcctg attttggtgt gctacttttc ttcttcttgc tccagctgca ttatccatca 300

  gtggtactat gtataagacc atcccgctgt gccctgccct accacctgcc cagaggcaca 360

  tccctcactg actatttggc ctgattctga gcctgtggcc accttctcac agccctgcaa 420

  cacaggcact gtgtgctcca ggcctcacgt ccccagcagt ggcctgactg tgcacttagc 480

  cacagcctca gtttgcctgt gctccaagaa attgcatcct atttgcccag cagctatgga 540

  ccagctctct ggtcctggaa aacagcaggc ttctctgaca tctagtggac tgcaaacaca 600

  ccttctccaa caaggcctga ccccagcctt aaggagagaa ccgtctttcc gagttgtctt 660

  tccttgggta ctctccctca atcctcggat acccttgaaa gttctcttta cattgttata 720

  gttattcttc tatcactgtc gaataatttt ttatattaaa cttctcttgc tttacattaa 780

  aaaaaaaaaa aaaaaactcg a 801

  <210> SEQ ID NO 68

  <211> LENGTH: 908

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 68

  gaattcggca cgagatttta ttaaaaataa gtgcttttct ctgcttacct tttactatga 60

  tctaactatg atactttcaa tatgctgcag actctcattc ttatctttct tttgttgtta 120

  ccttgttacc tagaactctt atgtttcagc ctaatttctt catctgcaaa gacctaatag 180

  gaagaaattt ttactttggt ttagtgtgta taaaatctgg gaacagctaa atttcagttt 240

  taatataaaa ttttgacttt tatatattac ccaatattgt taaaaggaga attctatgta 300

  tacctatctc ttaaaaatat tgctctatat attacccgct taaaacaaca acagcaacaa 360

  caaaaactta gaaggtaaac aaaaagtaat ctcataaaac atagaagggg aatacacctt 420

  ggtttcagat atgcacagaa agtatgtaag ctgtacccca gaagcatcct tataaatttt 480

  gcagtcagtt tctctgacct ttctttacac aggagggatt tgttgtayca atctttaatc 540

  taagtgtgat acaccaactt cctattgaat tgccttagag cagaagaaaa ggtataaaga 600

  tgatgcatct tacttagaaa tgaaaatata acaaaacaag tcatgttaaa caaggaaaga 660

  tatggatctt taatcacgaa cccaaaccaa gttggtggct gaacagagaa gaactgtggg 720

  agccaggcca gttggcatga cagtatgtgt tcagctggtg tggagtaagc ccctggactg 780

  agggtgttca gtgtggcttc agccagggga ttcagtggtg aagaaccctc ttgctactgt 840

  actctttgtc tttattacaa tactagtcaa gaaaaaattc tttctaaaaa gaaaaaaaaa 900

  aaactcga 908

  <210> SEQ ID NO 69

  <211> LENGTH: 696

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (605)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (648)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (655)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 69

  ggaaaatttt taaaaaatag attataatga tacatattgg tatcattaag acaacagatt 60

  tgagcaaata caattaaggt gtcttatttt ttgcatcaag taattattgc tgtggtcttt 120

  ctactccaca aaataatttt ttctttttgc agttgaaaat taactgcatt attaactaat 180

  taataaaata aatcaagtgg tataagggat tagtttaccc tcaagccgat gactccatgg 240

  ctactgatat tagttagttt wggattttta aaaagcatat cagaccccca gtttcaggaa 300

  ttgagtataa atattgcttc ttgtcaccct gggacagtaa tgccttatag tggcactagt 360

  caccttaagt agattacaca tggttgaggt gaataaagct gcatgggaat ttgctttcgt 420

  gatatatttc atttgcaaac ttctacataa tcaagtttta tgtttaaaac catcggttct 480

  atatatctag ctttaggaag ttgcccttac aggtgggacc ttttgtgtta atctgttttc 540

  tccccagtca tcttattggc tatgttaaaa aaaaaaaaaa aaaaaagggs ggccgctcta 600

  kaggntccaa gcttacgtac gcgtgcatgc gacgtcatag ctcttctnta agggncacct 660

  aaattcaatt cactgggcgg ccgtttacaa cgtcgg 696

  <210> SEQ ID NO 70

  <211> LENGTH: 455

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (431)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (432)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 70

  gtgctcaggg agctgaatac acggctgcgg gatgacaggg acgcctgcct gggcccacct 60

  gctgctgctg ctgttgctgg gctcggcccc ccagacgcgg ctctggccac cttcccagtg 120

  cccggtgacc agccccgagt gactcacgga ccatgagcta gaagctgccc ttgcaggagg 180

  cttgtcatgg gtcggggrtg cccactcagg atgcaggctc tccccagggg gccccaggct 240

  cgcctgactg aagacatgaa ggacctagcc taggagtggt cagggtcccg ggagtggcca 300

  gggtcccgtg tgtkccctct gccagtcttc gctctgtccc cgttcaatca accccatctc 360

  agttcagcag aaaaccccct cgtcaaataa aacccactga ctgcaaaaaa aaaaaaaaaa 420

  aaaaaaactc nngggggggc ccggtaccca atttg 455

  <210> SEQ ID NO 71

  <211> LENGTH: 413

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (343)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (385)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (410)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 71

  gaattcggca cgagcggctt tgggcggaac tggctttgtt gaccgggaga aacgagatgg 60

  gggtgaagct ggagatattt cggatgataa tctacctcac tttccctgtg gctatgttct 120

  gggtttccaa tcaggccgag tggtttgagg acgatgtcat acagcgcaag agggagctgt 180

  ggccacctga gaagcttcaa gagatagagg aattcaaaga gaggttacgg aagcggcggg 240

  aggagaagct ccttcgcgac gcccagcaga actcctgagg cctccaagtg ggagtcctag 300

  cccctcccct gatgaaatat acatatactc agttccttgt tanaaaaaaa aaaaaaaaaa 360

  aaaaaaaaaa aaaaaaaaaa aaaanaaaaa aaaaaaaaaa aaaaaaaaan aaa 413

  <210> SEQ ID NO 72

  <211> LENGTH: 849

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 72

  gaattcggca cgaggtataa tgccattctc ttcctctgtg aagtgcctgt tcggggtgtt 60

  gctacgtttt tgttttgttg tgttttctgt tgtagtgttt acatttttct tgtcgattcc 120

  taagaggact ttagggtact gagtcaccca tggtcatgtg ttgcagagaa gtgtcacaga 180

  gtgaaaactg tcttttcctt gatactacct ttagattcat atttgggaag accttcacta 240

  atcatgacta cataagtatt cacttttact ttcttaaggc ctttttgttt tcattctttt 300

  atagtaatgt ctaagccatc tggaattagt ttgttgatta tgcaagaaag ggatcgaagt 360

  gctttttctg agtcattatc cacatgccga aacatttatt gaatagccct ttccttattg 420

  atctgaaaac accttcttat aaaaccttgc attggttttt ggacttgctg tgctttcagg 480

  agtcagaaga acattctttt gattatkgta gctttacatw aataatacat ttkggccggg 540

  tgcggtggct cacgtatgta atcctagcat tttgggagac tgaggcaggc ggaacacctg 600

  aggtcagggg ttcaagacca gactggccaa catggcaaaa ccccgtctct acaaaaaaaa 660

  aaaaaaaaaa aattagctgg gcatggtggt gcctgcctga aatcccagct actttgggag 720

  gctgaggcag gagaacctct tgagcctggg aggtagaggc tgcagtgagc cgagcttgca 780

  ccactgcact ccaacttggg taacagagtg agactccatc tcaaaaaaaa aaaaaaaaaa 840

  aaaactcga 849

  <210> SEQ ID NO 73

  <211> LENGTH: 505

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (12)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (501)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 73

  gctccaccgc gntggcggcc cctctagaac tagtggatcc cccgggttgc caggaattcg 60

  gcacgagttc atctattgaa gggtgtttga gttttttcac tttttggctt ttgtaagtga 120

  tatagtttgg atctgggtcc ccattcaaat ctcatgtcaa gttgcagtcc ctagtgttgg 180

  aggtgggcct ggtgggaggt gatgggatgg tagggttggc ttctcatgaa tggttaacac 240

  catccccttt ggtactgtct ttggcatagt gagtttgttc tcctgagatc tcatttttta 300

  aaagcatgtg gcacctctcc tttcactgtc tcttgctcct gctcccacta tgtgaggtga 360

  ctcactcttt gtttgctttc taccataatt ggaagctttt tgaggcctct ctagaaacag 420

  aagctgctat gcttcctgta cagcctgcag aaccacgagc caattaaacc tttttctaaa 480

  aaaaaaaaaa aaaaactcga ngggg 505

  <210> SEQ ID NO 74

  <211> LENGTH: 719

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 74

  gaattcggca cgaggagaaa ggagggaagg cacagcgctg ggcagagatg ccagaaaacc 60

  tagttctaat cttggccttg ctgctgtcag tgtgtggcct taagcaagtc atttttctct 120

  cggcctcaat ttactctaaa atgtgtaccc tcatagctac taagaaagtt gttgcaaaaa 180

  ctagaaatga tgcttactgg tatttaatta gtctcaaaca catagtaggc ttttaacaat 240

  tagtggctgt cattttcatt attattaggc gcttcaattt ttacatgttg gcaatctcaa 300

  acataccatt ttcttttttt taaaaccctt ttttttkttt ttttttttga gacagaatct 360

  ccagcctggg agacagagca agaccgtgtc tcagaaaaaa gtggggccgg gtgcagtggc 420

  tcatgcctgt aatcccagca ctttgggagg ccagggcggg cggatcacaa gatcaggaga 480

  tcgagaccat cctggctaat gcggtgaaaa catgtctcta ctaaaaatac aaaaaattgg 540

  ctgggcttgg tggtgggcgc ctgtagtccc agctactcag gaggctgagg caggagaatg 600

  gcgtgagccc gggaggcgga gcttgcagtg agcagaaatt gcgccactgc actccagcct 660

  gggcaacaga gcgagactct gtctccaaaa aaaaaaaaaa aaaaaaaaaa aaaactcga 719

  <210> SEQ ID NO 75

  <211> LENGTH: 1274

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (1243)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1270)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 75

  cctgccgttg gcggcctgag tccgcagcgc cctgckccac ccgccccgga cgtggggccc 60

  aagcccccgt gaagatggtg tcctggatga tctccagagc cgtggtgctg gtgtttggaa 120

  tgctttatcc tgcatattat tcatacaaag ctgtgaaaac aaaaaacgtg aaggaatatg 180

  ttcgatggat gatgtactgg attgtttttg ctctctatac tgtgattgaa acagtagccg 240

  atcaaacagt tgcttggttt cccctgtact atgagctgaa gattgctttt gtcatatggc 300

  tgctttctcc ctataccaaa ggagcaagtt taatatatag aaaattcctt catccacttc 360

  tttcttcaaa ggaaagggag attgatgatt atattgtaca agcaaaggaa cgaggctatg 420

  aaaccatggt aaactttgga cggcaaggtt taaaccttgc agckactgct gctgttactg 480

  cagcagtaaa gagccaagga gcaataactg aacgtttaag aagcttcagt atgcatgatt 540

  taacaactat ccaaggtgat gagcctgtgg gacaaagacc ataccaacct ctaccagaag 600

  cmaaaaagaa aagtarccag cccccagtga atcagcmggt tatggaattc cactgraaga 660

  cggrgatgwg raaacagatk aagaagcaga ggggccatat tcagataatg agatgttaac 720

  acacaaaggg cttcgaagat cgcaaagcat gaaatctgtg aaaaccacca aaggccgcaa 780

  agaggtgcgg tacgggtcac taaaatacaa agtgaagaaa cgaccacaag tgtattttta 840

  gtcatctaca cgtcaaatat cccaagacag attatgctaa atacatcgac ttcatcttct 900

  aacatgatat attcaggatt tacacattaa aatgattatt taaattgtgg cagtgatggg 960

  gtttactttc atgaatttaa attgttttta tttcctgtaa caattgcttc caaatattga 1020

  ctactaaagg cagttctgca agatgtacta aatatgtata ttagaaatta tagaaaatca 1080

  tgttgtccgt tttcaaattc atcaacagcc tagagtgcct gagatataag atgaaacaca 1140

  aatccacagt atacttgaaa ggagcctttt tacggttcag gataaatcag cctttgtgat 1200

  gtactgtgtt tacctccttt tgtgttgtat ctggtaatta aantagggcc cagattcagc 1260

  aagtgacatn acaa 1274

  <210> SEQ ID NO 76

  <211> LENGTH: 519

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (13)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (24)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (35)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (44)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 76

  accaaaagct ggnagctccc accncggttg gccgnccgct ctangaacta gtggaatccc 60

  cccggggctg caggaattcg gcacgaggtt ttgttttgtt tttttctaat cctgctttca 120

  tactagccag tgtggggaaa aggtacaata tgtcaaagag atgagagagt gttatttctt 180

  gggcaatttt ctattagtgt ttcttatttt ggccagttct tttatttatg tccttgtgac 240

  ccaggtactt ggggggccag ctacccttct ggccttttag cgtctttgaa ggagaccaga 300

  catgagtgaa tacctaggag agtgtcagca tgtttctgga aaattggcag agaccaagcc 360

  ctgctgcaga ttcgtcaggc caggtgaaag ggccaggcag ttgcagctga tgatgtaaat 420

  attttgtaca gtagataaat aaatgtttaa aaaaaaaaaa aaaaaaaaaa aaaaraaaaa 480

  aaarwaaaaa aaaactcgag ggggggcccg gtacccaat 519

  <210> SEQ ID NO 77

  <211> LENGTH: 389

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 77

  ggtcgaccca cgcgtccggt ttgccatata atgagcattt tgtatacata aatttatagt 60

  ttaattaaat taggacattt gtaaaaaatt ggatacaatt ttattttcaa ataccttttt 120

  ttagctacac tcaaacactt attgaattga aattatgcac atgtttgatt tagtgatatg 180

  gtattacaaa acaccaatac cctgttaatt gtttctgcct ttcttctttc catgctgttt 240

  ttcaaatttt ctattgctat atttctagtc actaatctgt cttttgaaag gtctaatctg 300

  ttgttagggc catccagtga tttgttttta aattttaagt aatttatctc tataagttct 360

  agatcgcgag cggccgctct agagggatc 389

  <210> SEQ ID NO 78

  <211> LENGTH: 823

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 78

  cccacgcgtc cgcccacgcg tccggtaact ttatgaatat aaatttacag tttgatacag 60

  gaattattag gagtaattct tttctgtttc tgtttataat gtagctacag tgttcttcat 120

  tttcagaagt taacatcaag ccatcaaacc tgggtatagt gcagaaaacg tggcacacac 180

  tgaccacaca ttaggctgtg tcaccattgt gtggtgtacc tgctggaaga attctagcat 240

  gctacttggg gacataattt cagtgggaaa tatgccactg accgattttt tttttttcct 300

  ctttgcagtg gggctaggac agttgattca acaaagtatt tttttctttt ttctcagtcc 360

  taatttgaac aggtcaaaga tgtgttcagg cattccaggt aacaggtgtg tatgtaaagt 420

  taaaaatagg ctttttagga actcactctt tagatattta catccagctt ctcatgttaa 480

  atatttgtcc ttaaagggtt tgagatgtac atctttcatt tcgtatttct cataggctat 540

  gccatgtgcg gaattcaagt taccaatgta acactggcca gcgggcccag caatctccat 600

  gtgtacttat tacagtctta tttaaccagg ggtcctaacc actaacattg tgactttgct 660

  ttgagacctt tcctctcctg ggtactgagg tgctatgaag ccaactgaca aagatgcatc 720

  acgtgtctta ggctgatgcc actacccgat ttgtttattt gcaatttgag ccatttaaag 780

  accaataaac ttcctttttt aaaaaaaaaa aaaaaaaact cga 823

  <210> SEQ ID NO 79

  <211> LENGTH: 2455

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (2277)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 79

  ggcctcgctc ccggaagtgg agggtctaca cgaagcgccg ctgggtctgg gtgcccggag 60

  gcagcagcgt tcgcggagtt cgcccgctgg cccccgatca ccatgtcggc tttcgacacc 120

  aaccccttcg cggacccagt ggatgtaaac cccttccagg atccctctgt gacccagctg 180

  accaacgccc cgcagsggcc ctggcggaat tcaacccctt ctcagagaca aatgcagcga 240

  caacagttcc tgtcacccaa ctccctgggt cctcacagcc agcggttctc cagccatcag 300

  tggaaccaac ccagccgacc ccccaggccg tggtgtctgc agcccaggca ggcctgctcc 360

  ggcagcagga agaactggac aggaaagctg ccgagctgga acgcaaggag cgggagctgc 420

  agaacactgt agccaacttg catgtgagac agaacaactg gccccctctg ccctcgtggt 480

  gccctgtgaa gccctgcttc tatcaggatt tctccacaga gatccctgcc gactaccagc 540

  ggatatgcaa gatgctctac tatctgtgga tgttgcattc agtgactctg tttctgaacc 600

  tgcttgcctg cctggcctgg ttctcgggca acagctccaa gggagtggac tttggcctct 660

  ccatcctgtg gtttctgatc ttcactccct gtgccttcct ttgttggtac cgacccatct 720

  ataaggcctt taggtccgac aactctttca gcttctttgt gttcttcttt gtattttttt 780

  gtcaaatagg gatctacatc atccagttgg ttggcatccc tggcctgggg gacagcggtt 840

  ggattgcagc cctgtctaca ctggataatc attccctggc catatcagtc atcatgatgg 900

  tggtggctgg cttcttcacc ctctgtgccg tgctctcagt cttcctcctg cagcgggtgc 960

  actccctcta ccgacggaca ggggccagct tccagcaggc ccaggaggag ttttcccagg 1020

  gcatcttcag cagcagaacc ttccacagag ctgcttcatc tgctgcccaa ggagccttcc 1080

  aggggaatta gtcctcctct cttctctccc cctcagcctt tctctcgcct gccttctgag 1140

  ctgcactttc cgtgggtgcc ttatgtggtg gtggttgtgc ccagcacaga cctggcaggg 1200

  ttcttgccgt ggctcttcct cctccctcag cgaccagctc tccctggaac gggagggaca 1260

  gggaattttt tccccctcta tgtacaaaaa aaaacaaagc tctctttcct tctctggtga 1320

  tggtttggta ggattctttt gtctctggaa gcagtgggac tgaagttctc ttcgtcctgt 1380

  gcacacacag acacccccac acagttggga tcacaggctg acctgggccc atcccagctg 1440

  gagctttctg ccagggtcct gggccttgac tcccccaccc tgcaggcctg gcctgaatct 1500

  ggcttcttag acacagccca gtccttcctg cctgggctgg gaataagcct ctcacaggtt 1560

  ctggtggaca gatctgttcc ccaggtcact ccagtggtct ccaggcttcc agagaaggct 1620

  ggttgcctca agctcttctc tgcctcataa acggatccag agaaggctgg ttgccttaag 1680

  ctcttccctg cctcgtgttc ctgagaaacg gattaatagc cctttatccc cctgcaccct 1740

  cctgcagggg atggcacttt gagccctctg gagccctccc cttgctgagc cttactctct 1800

  tcagactttc tgaatgtaca gtgccgttgg ttgggatttg gggactggaa gggaccaagg 1860

  acactgaccc caagctgtcc tgcctagcgt ccagcgtctt ctaggagggt ggggtctgcc 1920

  tgtcctggtg tggttggttt ggccctgttt gctgtgacta cccccccccc tccccgaacc 1980

  gagggacggc tgcctttgtc tctgcctcag atgccacctg ccccgcccat gctccccatc 2040

  agcagcatcc agactttcag gaagggcagg gccagccagt ccagaaccgc atccctcagc 2100

  agggactgat aagccatctc tcggagggcc ccctaatacc cagtggagtc tggtttcama 2160

  ccctgggggg tgtgtcactg tgatgggaca cgtaggagtc cacccttaaa accagcaccc 2220

  tgtccctcga ggctgccgag tgggtgtgtg gactcggggg ccttcccaca aaaactnstc 2280

  cggctctggg cccgagacag ccgcaggccc cagccactga atgatactgg cagcggctgg 2340

  ggttttatga actcctttct ggtatttttt cccctctatg tacaaatgta tatgttacgt 2400

  ctcaattttt gtgcttaagt aaaaataaaa acattttcag acaaaaaaaa aaaaa 2455

  <210> SEQ ID NO 80

  <211> LENGTH: 921

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (111)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 80

  ttttcttaag ggaaaaatca cgctgtgttc ttttaaaatc cctcaggttt tatgttttat 60

  tgctaccaga gtctgcctcc ctgaggttct tgtatagact agttatttcc ntctgtaaag 120

  aagctgttct attcgttctc gcctggtttg gaacaaactg aacacttcca aaggaggcag 180

  tccttgcagc cttgtctcct tccactcccc tcctccccac agtcctgggc tggagcagcg 240

  agtctgtcga tcccagggcc agagacaagg cagacaaagg ttcatttgta aagaagctcc 300

  ttccagcacc tcctctcttc tccttttgcc caaactcacc cagtgagtgt gagcatttaa 360

  gaagcatcct ctgccaagac caaaaggaaa gaagaaaaag ggccaaaagc caaaatgaaa 420

  ctgatggtac ttgttttcac cattgggcta actttgctgc taggagttca agccatgcct 480

  gcaaatcgcc tctcttgcta cagaaagata ctaaaagatc acaactgtca caaccttccg 540

  gaaggagtag ctgacctgac acagattgat gtcaatgtcc aggatcattt ctgggatggg 600

  aagggatgtg agatgatctg ttactgcaac ttcagcgaat tgctctgctg cccaaaagac 660

  gttttctttg gaccaaagat ctctttcgtg attccttgca acaatcaatg agaatcttca 720

  tgtattctgg agaacaccat tcctgatttc ccacaaactg cactacatca gtataactgc 780

  atttctagtt tctatatagt gcaatagagc atagattcta taaattctta cttgtctaag 840

  acaagtaaat ctgtgttaaa caagtagtaa taaaagttaa ttcaatctaa tttttctctg 900

  tggaaaaaaa aaaaaaaaaa t 921

  <210> SEQ ID NO 81

  <211> LENGTH: 678

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 81

  gaattcggca cgctcttggg ggtagtggat gcgggttgag gggtttcagg tgccctgggc 60

  tgtcactttg taaaggcttg ccaacctaga ttgagatggg tggtaaagga atcaattaca 120

  caatgccaca catttgcttg cttctgctga atgccttagt agtttcatgt ttattgctgg 180

  aagccattct cttacagcat ctagtgctgt gtaacgagct accttaaaat gtaaaggctt 240

  aaaacagcca tctttgatgt ctttgcaggt ctagaagtca ggaagggtaa ttattcagct 300

  ccaagtggca ttggctctag ttactacctg atattccagg gtggtagctg gagtggtctc 360

  aagggtccaa gctgacctca cttacaagct gggtgccttg gcagggacag ttaggaggct 420

  gtgtgtagca gagcctcact cggtctttgt attctccagg cctcttcagt ggtttctttg 480

  gcacttctta aatgatgtca gggttccagg agttaatgtt ccaagagaca ggaagtggat 540

  gctgcccatc tctttttttt tgtttgtttg tttgtttgtt tttttgagat ggagtcttac 600

  tctgtcacca ctgcactcca gcctgggcaa cagagcgaga ctctgtctca aaaaaaaaaa 660

  aaaaaaaaaa aaactcga 678

  <210> SEQ ID NO 82

  <211> LENGTH: 857

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (493)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (562)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 82

  gaattcggca cgaggggaaa taatgtttgt ggaaaattgc ttagaggaaa tggagtatat 60

  tactggtata ggtactctaa aatgtctttt gaattaagtc agagttagag ggttgtgtct 120

  ctaaaccgca tcttactggt attatgctat cagcctgtat tgagagactt tataggtaaa 180

  gtccaattta ggctgtttgg tattatctat taaaattaga atgttcatgc tctgtaacct 240

  gctacttcca cttctagaat ttatctttgg aagcacatat ctgtccacag acctatattt 300

  acacacatgt atgaagaatg tkttccttca cattcattca ttttaacaaa tgttttgatg 360

  tgtagggcct aagctgattt gaatgcagct gaaatgcaca tatctggttg agtcmtggga 420

  actgatttgc atgtgtcttt ctcttttatg gcttgaagag gagagaaatt tgtgcttagc 480

  acattgaagg gcntacgaga tacaaggagt ctgtccttag ctctgccctt tggactgttg 540

  tctgaaggct aaagaagaga gnacaaagaa agcttgcatt gggaggctga ggtgggagga 600

  tcacttgagc ttaggagttt gagaccagcc tgggcaacat agggagactg cacctctata 660

  agaaatttta aaaattagcc gggttggcag cgtgctcttg tggtcccagc cgcttgaaaa 720

  gctgaggtgg gagaatcgcg tgagcctggg aggtcgaggc tgcagtgcac cgtgattatg 780

  ccactgcact ccagcttggc aacattgact gtctcaaaaa gattatatat ctctaaaaaa 840

  aaaaaaaaaa aactcga 857

  <210> SEQ ID NO 83

  <211> LENGTH: 1977

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (664)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (716)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1319)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 83

  gcaaaaaccc aaaaggggac agcagtagtg ggagaggcca gcatctgtac accccatcag 60

  ggtccccgct gtgtgtgccc ctcaggcggc caccagccct accaggtcct cccctcccgg 120

  caggtcttcg ccttgatcgt gttctcctgc atctatggtg agggctacag caatgcccac 180

  gagtctaagc agatgtactg cgtgttcaac cgcaacgagg atgcctgccg ctatggcagt 240

  gccatcgggg tgctggcctt cctggcctcg gccttcttct tggtggtcga cgcgtatttc 300

  ccccagatca gcaacgccac tgaccgcaag tacctggtca ttggtgacct gctcttctca 360

  ggtatctgcc tgtggcacct ccatttgatc ttgggggagg cattaactct agggttccgc 420

  agctgggagg gtctcggcct ctctgggagg ggcagggagc agctcactcc tccagggcat 480

  ttttaggaaa gggttttcag ctagtgtttt tccgtgcttg aatggcacca gccctgcctg 540

  gggtagctag aagctgagtg gacctgcagc acacccgagc agatgggctt tgcctctgcc 600

  ccttttgtcc cctaggctgt ctgctgtggc ccaccctgcc aaggcccgag tgtgggggac 660

  tttngaggtg gctcccggcc cggcttccaa gtcctcccct ccatagtgtg gaagcntccc 720

  ccgggaggtc cctgccctac ctgcccgcgt cccctcccag agtcctggaa agcccctccc 780

  tttccatgga actgacgctt cacccgtcct cttctcagct ctctggacct tcctgtggtt 840

  tgttggtttc tgcttcctca ccaaccagtg ggcagtcacc aacccgaaga cgtgctggtg 900

  ggggccgact ctgtgagggc agccatcacc ttcagcttct tttccatctt ctcctggcgc 960

  tacaaggctg gcgtggacga cttcatccag aattacgttg accccactcc ggaccccaac 1020

  actgcctacg cctcctaccc aggtgcatct gtggacaact accaacagcc acccttcacc 1080

  cagaacgcgg agaccaccga gggctaccag ccgccccctg tgtactgagc ggcggttagc 1140

  gtgggaaggg ggacagagag ggccctcccc tctgccctgg actttcccat gagcctcctg 1200

  gaactgccag cccctctctt tcacctgttc catcctgtgc agctgacaca cagctaagga 1260

  gcctcatagc ctggcggggg ctggcagagc cacaccccaa gtgcctgtgc ccagagggnt 1320

  tcagtcagcy gctcactcct ccagggcact tttaggaaag ggtttttagc tagtgttttt 1380

  cctcgctttt aatgacctca gccccgcctg cagtggctag aagccagcag gtgcccatgt 1440

  gctactgaca agtgcctcag cttccccccg gcccgggtca ggccgtggga gccgctatta 1500

  tctgcgttct ctgccaaaga ctcgtggggg ccatcacacc tgccctgtgc agcggagccg 1560

  gaccaggctc ttgtgtcctc actcaggttt gcttcccctg tgcccactgc tgtatgatct 1620

  gggggccacc accctgtgcc ggtggcctct gggctgcctc ccgtggtgtg agggcggggc 1680

  tggtgctcat ggcacttcct ccttgctccc acccctggca gcagggaagg ctttgcctga 1740

  caacacccag ctttatgtaa atattctgca gttgttactt aggaagcctg gggagggcag 1800

  gggtgcccca tggctcccag actctgtctg tgccgagtgt attataaaat cgtgggggag 1860

  atgcccggcc tgggatgctg tttggagacg gaataaatgt tttctcattc aaaaaaaaaa 1920

  aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaagggcggc cgctcgcgat ctagaac 1977

  <210> SEQ ID NO 84

  <211> LENGTH: 1149

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (837)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 84

  acccactgac aggcattatg acctaacagg aggttggtag cagtagatcc aagcatgcat 60

  gttgcctggc ctgtagattg gccttatcag gtttctgggt gcctctgcct taagatcctg 120

  aaggmaaatt ttgtttcaac agtttggaag tcatctgtgg gtccagcttg actttggagg 180

  aataagaaga tacttctaga gtatgggaat gattccagat aatttctggg atttgaatct 240

  acttgagttt aagggcctgg gacctaattt ggtttagtat agaatttgaa gaattaattt 300

  ataggcagct gaatacccaa aacttgggtg gtggtcctgt ggtttggctg agctgtccgg 360

  gcataacctg gttctctgtt atgttaaggc tttctgggaa gccagccact ctgcgcagga 420

  gtgaaacatg aagttgtttt ctgaggacct gttttggtgg gattgtttgg gcagaggact 480

  gtgtttatgc agggcaaatc ccagaaagat aagaggaagc tagagaaact taatgtacct 540

  gaattcttca tggtgtattt gcaaactaac ttaacataga ttcttttgac tatggtaagt 600

  ttgaatctct ccttgccaaa caacattata agtttagttt tcttcttcct cttgcagccg 660

  gtacagaaag gtgtaagtgg tggctgaaaa ttgaggaagc ttcatctgac caatgtgggt 720

  gctggtttct tgtgaaatgt gtccctaagc ctccttctcc ttgcaggcag ccacccaccc 780

  aggtgtctaa gataggacat gctcctttct ttctctaatc csatcctgag gttgccngca 840

  aagccaatat gaccactact gagaaatagt aatgacttct acaaatgcaa gggtcttacc 900

  ctcctctttc ccttaaamac cctccctttt ccttagaccc cgtttttgcc atcccccaaa 960

  tgtgtggtat ggtgaaacta atcccctgaa tgtgaattgc tatccttatt gccctattaa 1020

  agaagagcca gctggtatat tgtcaggaag cactatttaa aatgtgaact gttatagagt 1080

  aaataaataa atactctaca ggaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1140

  agggcggcc 1149

  <210> SEQ ID NO 85

  <211> LENGTH: 767

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 85

  catgaaaaca cattctctta tagtttttaa attcatcatc caagagttcc tgctctttga 60

  tgatgagaca tacctggtag actccaaaac agagagcaga cgcctagtat ctttgttctg 120

  gggtgtgcat taagagtaca ttgacctgtc tgtctccagt cttgactctt ttggaagaga 180

  gatgctagta ctgatgacaa cctgcattct ggctgcggtg tgygtccaca ctgcacagtg 240

  tgcaccagac tctcgtatgg acaatgactg tccctcacat caggcgcaga tccattttag 300

  agcctcagaa gtcaggagag ggtggacttt caaccacgac tgaaaacact gtctttctta 360

  ggacatgctg tgtgtatgac acacttacag atgtctgtgc tcactgatgc ttgttgatgt 420

  gtcatcgcac atcagtgaca aacatttgtc atgtttttgc ctttggtgga acttctttat 480

  tatactcact ttcctcccaa accatttttc tcaacttcat catgaagcaa atgtcatgtg 540

  gtcattctgt gatggggctc agggctaggt taggtgatga tttctgaaag ctcagagacg 600

  tgaaggaaaa aggacatcag tgcttggatc ttagctctta taagcctcac gtgcaacaat 660

  aaacccgagt tcaagaatca gattcttaga tagattggtt tggtagcaaa tgacaaaaaa 720

  ccaacgtaaa tatgcttcgg caaaaaaaaa aaaaaaaaag ggcggcc 767

  <210> SEQ ID NO 86

  <211> LENGTH: 728

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 86

  aaatgattta gtgacctata caagtagcct gcagtaccgg atccgaattc ccggtcgacc 60

  cacgcgtccg gtgaaaacag cagagtgcta ctccatacca ctgggatctt gtccagtaaa 120

  catccagaga gtgaggttag gaaataaaaa gtatataaat attagatgcc tagaaatgca 180

  agtcacttta aagattttat gtgaaataga aaaaaaagag aggagaggga ctcattgtct 240

  tgtaatgggt ccttcccaga gagaggtgac tgtccagtgg caccgggccc ttttcctcct 300

  tcccctttta ctcttatcaa ctaggacaga aactaagaat tttggcttca agtggctaaa 360

  agactgatgg gggaaaaaag aaaatagaaa aaaataacag agagactgac gctctaggca 420

  gttacaagtc caagaaaaaa gacagaaact tttaagtatt gagccaaaac caggtctagc 480

  aamcataatg ctggccctag attatttatt aatttatgaa gaaacttcta gatatggggg 540

  tgacaaaagg aaattaaatc cattatatat gcatatattt taatgtaaat atataataga 600

  taaattatgt atacataata tataaccaaa ttgaaacagt tttacaattt ggtttgactg 660

  gaaattcaaa atccatatat taatttttgt agtaaaagtt tatgtaaaaa aaaaaaaaaa 720

  gggcggcc 728

  <210> SEQ ID NO 87

  <211> LENGTH: 735

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (376)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 87

  gaattcggca cgagtagcag cttgattttc tgttagccta tgaaatgtta ttgtcctata 60

  aaaataactt taaactgatt taatatttca tatttacatt atatgaaaat caattacatt 120

  ataaaaggaa tccctaatgc agaaacaaag atgcaacttt caaaattctt attattccta 180

  tttgtatata cacgagagaa cccaaccagt gcctgtgttt ggggggaaaa gtcaacagtg 240

  tagttctaaa ccttatccca aacagaaaat gtggktaatg atgtcacttt ccttgctggk 300

  catcattagg cttaaattaa atgctgaagc tgtcatcaaa gagtttacac taaaatcttc 360

  agggctttaa ataaanggtt aagtccagct tccaaacaca attttccaca ttagcagctc 420

  caatcttctt aaataaagct ctgttttcct atatttttat gactgctgag accccacagg 480

  gaccaatatt tgtattcaaa ttacatttca tggtttccca ttgtttcaca atgagttcta 540

  ataaatggga tttactataa taatccaagt atgacatagc cggtatgctt tcatgaatgt 600

  ttttatgtag attttcctcc catgaacatg agtaaataaa tctgtttcct gaatggattg 660

  tggttgcatt taaagctctg taataattct aataaattta ctctatagaa aaaaaaaaaa 720

  aaaaaaaaaa ctcga 735

  <210> SEQ ID NO 88

  <211> LENGTH: 889

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (117)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (292)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (341)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 88

  tgttaggtta attattgctt cacatgtggt cacggtttga aaacttattt tggggggagt 60

  ataaagtaga atacagagat tccttgctca tagctcctac tgctatcggg gaacaancct 120

  tgagggtgag aacgtggatt gattcttgat tgatagtggg gattccatta tctgtatttg 180

  gcagttatgg cctgctgcgg tgtatagaag cttctttcca ttcattttcc cgaattttca 240

  tactgctcaa ggaacagttg ggggggaatg ggcagaaggt tgggcacttg angtatttga 300

  gctatcggta ataactgact ttttagggcg cacagatttg nagtagagcc atggtagtag 360

  ttagtaccaa tgggtttttg ctgcttctac tctttcttaa cagaaaaagt ggattgtgtt 420

  catataggaa agcagttcac agactgtctt cctgcccctc ccgccaccaa gctggaccta 480

  gaatcaagtg tgactttaaa tggggaaagc tgtgttacag ttgtgcttaa gccactgctg 540

  tggcttaacc tcacctatgc ataagaattt gctcgtggct ggccgggcgc ggtggctcga 600

  gcctgtaatc ccagcacttt gggaggctga ggcgggcgga tcacgaggtc aggagattgg 660

  gaccatcgtg gctaacacgg tgaagccccg tctctactaa aaatacaaaa aaaattagcc 720

  gggcgtggtg gcgggcgccg ctagtcccac tactgagtcc caggctgaag caggagaatg 780

  gtgtgaaccc aggaggcgga sttgcarcga gccgagatcc tgtcactgca ctccagcctg 840

  ggcgaagcga gactctgtct caaaaaaaaa aaaaaaaaaa aaaactcga 889

  <210> SEQ ID NO 89

  <211> LENGTH: 569

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (1)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 89

  ntaaggtgtt gattctggat cacgggatac cattcctgtc macaccccga ccaggggcta 60

  gaaaatttgt ttgagatttt tatatcatct tgtcaaattg cttcagttgt aaatgtgaaa 120

  aatgggctgg ggaaaggagg tggtgtccct aattgtttta cttgttaact tgttcttgtg 180

  cccctgggca cttggccttt gtctgctctc agtgtcttcc ctttgacatg ggaaaggagt 240

  tgtggccaaa atccccatct tcttgcacct caacgtctgt ggctcagggc tggggtggca 300

  gagggaggcc ttcaccttat atctgtgttg ttatccaggg ctccagactt cctcctctgc 360

  ctgccccact gcaccctctc ccccttatct atctccttct cggctcccca gcccagtctt 420

  ggcttcttgt cccctcctgg ggtcatccct ccactctgac tctgactatg gcagcagaac 480

  accaggcctg gcccagtgga tttcatggtg atcattaaaa aagaaaaatc gcaaccaaaa 540

  aaaaaaaaaa aaaaaaaaaa aaaactcga 569

  <210> SEQ ID NO 90

  <211> LENGTH: 334

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (321)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 90

  agaaaatgaa caaactagtg agaaacattg taaacatata gtgtagatga taactctgaa 60

  cttaagtaca agataatgat gaatattctg ctgcttaagt atatcttaga aatattaatt 120

  cttagtgaaa atcttaacct attcaacatc acttatggta agtataactt atttttccta 180

  tacaggtatt aaatatataa tttatatgcc agtcacattt cctcacacta aataaggcag 240

  cagacacata tatttaatat catgggtatg cattttaggt tctaaaacct aaggtatgtg 300

  gatttcttaa agccatatct naaatatttt cacc 334

  <210> SEQ ID NO 91

  <211> LENGTH: 795

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (3)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 91

  cgnaccattt tttttttttt gaatatcatc agcttacttg actggcaagg gcagaagctg 60

  gggttggcct gaactctgcc aaacaaatat caaagtgtat ttaatagtta aatttgtgcc 120

  ctttcccttc ttgctgcacc catgttgtca cttaaccccc aggagttatt tattatcttt 180

  ttgttaaagt caggctcatt tggggtaatg tgatgactgt ttaggtttac atgaccctcc 240

  tctcctttcc ctacccccaa atatgtatat atacatatat aaaatatgta tatattttac 300

  ctatataaaa tatatatata tacacatata tgtatctata ttcctttgtt tctttgcctg 360

  cttatactgg ccataaaaga gggagctgcc ttcaatgtat aaagtataag aagagtgcca 420

  gggaatgcca taatggaggc ttttggatct gaatttggac catttcacta aagagaacat 480

  gagtttgctc agccctttcc tcacaagagg gagggccccg gttccccaga cttctccacg 540

  cgctggctcc ataaaggcca gctttggccr ggctgccaca ggggcctgag gagctcactc 600

  tgggcctacc tggtttcagt tagagggtcc tcctgttatt tttccattta aaaagtatgt 660

  cctcagaaaa ctgtactgga aggatgggtg gcaggaactt gtatagttca gcttccaaca 720

  ctttggaaca gattaaaaag ggaatctttt aaataaaaac gtataaaaat aaaaaaaaaa 780

  aaaaaaaggg cggcc 795

  <210> SEQ ID NO 92

  <211> LENGTH: 577

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 92

  tagtggatcc cccgggctgc aggaattcgg cacgaggctg cacgaggttg ttgagaggat 60

  caagtaagat aatgaatgaa agtgtctatg acgacagtac tagttcttac acaccatccc 120

  tccacatttt gggatgtctg ttgctgctct tccttggggt ggaaagagca ctggagccct 180

  tctctggtct ttgtgcttct ttacatgatg tgagacctat agtaaacccc ttaacctcct 240

  tcagcctcat ttattagaga gagagagaaa aaaaaaggtg attttaaaaa aatctgtttt 300

  cggccaggtg cagtggctca tgcctgtaat cccagcactt tgggaggccg aggcaggtgg 360

  atcacctgag gtcaggagtt cgagaccagt ctggctaaca tggtgaaacc ctgtcactac 420

  taaaaatacm aaaaaatcag ctactcggga ggctgaggca ggagaatcct atgaaaacgg 480

  gaggcagagg ttgcagtgag ccgagatcgt gccattgcac tctagcctgg gcaatgagca 540

  aaactttgtc tcaaaaaaaa aaaaaaaaaa actcgta 577

  <210> SEQ ID NO 93

  <211> LENGTH: 968

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (904)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (907)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 93

  gaattcggca cgagcttact ttcactcacc gcctgtcctt cctgacacct caccatgtgt 60

  acgggaaaat gtgcccgctg tgtggggctc tccctcatta ccctctgcct cgtctgcatt 120

  gtggccaacg ccctcctgct ggtacctaat ggggagacct cctggaccaa caccaaccat 180

  ctcagcttgc aagtctggct catgggcggc ttcattggcg ggggcctaat ggtactgtgt 240

  ccagggattg cagccgttcg ggcagggggc aagggctgct gtggtgctgg gtgctgtgga 300

  aaccgctgca ggatgctgcg ctcggtcttc tcctcggcgt tcggggtgct tggtgccatc 360

  tactgcctct cggtgtctgg agctgggctc cgaaatggac ccagatgctt aatgaacggc 420

  gagtggggct accacttcga agacaccgcg ggagcttact tgctcaaccg cactctatgg 480

  gatcggtgcg aggcgccccc tcgcgtggtc ccctggaatg tgacgctctt ctcgctgctg 540

  gtggccgcct cctgcctgga gatagtactg tgtgggatcc agctggtgaa cgcgaccatt 600

  ggtgtcttct gcggcgattg caggaaaaaa caggacacac ctcactgagg ctccactgac 660

  cgccgggtta cacctgctcc ttcctggacg ctcactccct tgctcgctag aataaactgc 720

  tttgcgctct caaaaaaaaa aaaaaaaaac tcgagggggg gcccggtacc caattcgccc 780

  tatagtgagt cgtattacaa ttcactggcc gtcgttttac aacgtcgtga ctgggaaaac 840

  cctggcgtta cccaacttaa tcgccttgca gcacatcccc ctttcgccag ctggcgtaat 900

  aacnaanaag cccgcaccga tcgcccttcc caacagttgc gcagcctgaa tggcgaatgg 960

  caaattgt 968

  <210> SEQ ID NO 94

  <211> LENGTH: 553

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 94

  gaattcggca cgagtcccta aacagttaaa atgtcacagc tgtttcttat aatgcttaca 60

  ttcatatttc taaataacat gtttataatg catctaactt ccttccatgg aaaaagagta 120

  tttggctttt taaaccaatc gagtcacatg catgctttcc cccttccacg ttggactaca 180

  tcaatattta gtgttagtat ttttataaat agataaatat tgttcgcaaa ttttatttgc 240

  tgtctattgc tgtgtaacaa attcctccaa aattattggc tttaaacaac atttattatc 300

  ccatagtttc tatgagttga gaatctaagc aggcttagct gggtccacta gctcggggtc 360

  tctcacaagg ccacagatca aggtgttggt cagtggtttg tgcccttagt cccagctact 420

  tgggaggctg aggcaggagg atcacttgaa cccagtagtt caaggctgca gtgagcwakg 480

  gttacaccac tgcactccar cctgggtgac agagcaagat gccatctctt aaaaaaaaaa 540

  aaaaaaaact cga 553

  <210> SEQ ID NO 95

  <211> LENGTH: 968

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 95

  ggcacagcaa ccgtcactgc ctatcagaat cagcagatta ctcgcctgaa gatagatagg 60

  aatccatttg ctaaaggctt ccgagactcc gggcgcaaca gaatgggttt ggaagccttg 120

  gtggaatcat atgcattctg gcgaccatca ctacggactc tgacctttga agatatccct 180

  ggaattccca agcaaggcaa tgcaagttcc tccaccttgc tccaagtact gggaatggcg 240

  ttcctgccac tcaccctcac cttttgtctg gctcctcttg ctcctctcct gccttccatc 300

  tggggcccaa caccagccag ctgtgtagtc tggcccctgc tgactattct gcctgtgccc 360

  gctcaggcct caccctcaac cgatacagca catctttggc agagacctac aacaggctca 420

  ccaaccaggc tggtgagacc tttgccccgc ccaggactcc ctcctatgtg ggcgtgagca 480

  gcagcacctc cgtgaacatg tccatgggtg gcactgatgg ggacaccttc agctgcccam 540

  agaccagctt atccatgcag atttcgggaa tgtcccccca gctccagtat atcatgccat 600

  caccctccag caatgccttc gccactaacc agacccatca gggttcctat aatactttta 660

  gattacacag cccctgtgca ctatatggat ataacttctc cacatcyccc aaactggctg 720

  ccagtcctga gaaaattgtt tcttcccaag gaagtttctt ggggtcctca ccgagtggga 780

  ccatgacgga tcggcagatg ttgccccctg tggaaggagt gcacctgctt agcatggggg 840

  tcagcagagt ttctttgact ctaggaccct aggaagctta actctgtcat catctcaagt 900

  atctgcacat atggtctgat gaagccttta aagttaaatg aacatttggg atctgtctaa 960

  acatattt 968

  <210> SEQ ID NO 96

  <211> LENGTH: 697

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (19)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (50)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (57)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (662)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (680)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (690)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 96

  aagaaaatta ccctcactna aaaaaaacaa aaactaaaag ctcgcacgcn tgcaggnacg 60

  acactagtgg atccaaagaa ttcggcacga ggccacatcc caccggccct tacactgtgg 120

  tgtccagcag catccggctt catgggggga cttgaaccct gcagcaggct cctgctcctg 180

  cctctcctgc tggctgtagg tctccgtcct gtccaggccc aggcccagag cgattgcagt 240

  tgctctacgg tgagcccggg cgtgctggca gggatcgtga tgggagacct ggtgctgaca 300

  gtgctcattg ccctggccgt gtacttcctg ggccggctgg tccctcgggg gcgaggggct 360

  gcggaggcga cccggaaaca gcgtatcact gagaccgagt cgccttatca ggagctccag 420

  ggtcagaggt cggatgtcta cagcgacctc aacacacaga ggccgtatta caaatgagcc 480

  cgaatcatga cagtcagcaa catgatacct ggatccagcc attcctgaag cccaccctgc 540

  acctcattcc aactcctacc gcgatacaga cccacagagt gccatccctg agagaccaga 600

  ccgctcccca atactctcct aaaataaaca tgaagcacaa aaaaaaaaaa aaaaaaaact 660

  cngggggggg gcccggttan ccaatttggn cctaaag 697

  <210> SEQ ID NO 97

  <211> LENGTH: 866

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 97

  ttttagttca ttattctctt ctattaagag aaattcactg ttaaaaaatt gtttcccatt 60

  tccgtatctg aaataatgac tgtagttgag gtgatcttgc cctgggtctg aaatcatact 120

  tccaaaccaa aaaggacttt gaatacaaaa cttttaagaa atcttgtatg aatacaagct 180

  atatctgaaa aattgtgttt tataatattg atgcctagtt ttgccccagg ccatctgcag 240

  tgtggttact atgcaaagaa tgctggtgtt gctgtttttt tttttttctt tgttggctat 300

  taacccagcg gagacaatat gtggctatgg tagtacttgg aagttctagc attacacaga 360

  ctagcttcca tttctctcat agaggtcatt ttggcattta aaacacatac ttttagaaaa 420

  cagatttgga tgtatgtaaa cacagggtta atccaccaca ctctggatgc tagagctgtt 480

  gacaaagtca tgctttgcag attttaaaat aaactttttg ttactcttac agcttggtat 540

  tttcccctcc tatttttttt acctcctcta aataaacctc tttgttaaat aattgatgtt 600

  tctggatcat agaaaatagt aagtttaaaa tacagaatat ttccaagcta actacaaatc 660

  tgatgacagt tttttgagtg tgcacttttc cttttatttc ttaggtcctt tttggtcctt 720

  tgcaaacata gtaagattcc atatttgtgt cccaactgtg gtaatattgc tgacttctta 780

  ctggaaaaca gtcagctcta ggtagcattt cttctgtgtg gtatttaagt taaattatta 840

  ccaaaaaaaa aaaaaaaagg gcggcc 866

  <210> SEQ ID NO 98

  <211> LENGTH: 1368

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (637)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1140)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1170)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1286)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 98

  ttcctgtgtg ccctgagccc gctggggcag ctgctgcagg accgctacgg ctggcggggc 60

  ggcttcctca tcctgggcgg cctgctgctc aactgctgcg tgtgtgccgc actcatgagg 120

  cccctggtgg tcacggccca gccgggcycg gggccgccgc gaccctcccg gcgcctgcwa 180

  gacctgagcg tcttccggga ccgcggcttt gtgctttacg ccgtggccgc ctcggtcatg 240

  gtgctggggc tcttcgtccc gcccgtgttc gtggtgagct acgccaagga cctgggcgtg 300

  cccgacacca aggccgcctt cctgctcacc atcctgggct tcattgacat cttcgcgcgg 360

  ccggccgcgg gcttcgtggc ggggcttggg aaggtgcggc cctactccgt ctacctcttc 420

  agcttctcca tgttcttcaa cggcctcgcg gacctggcgg gctctacggc gggcgactac 480

  ggcggcctcg tggtcttctg catcttcttt ggcatctcct acggcatggt gggggccctg 540

  cagttcgagg tgctcatggc catcgtgggc acccacaagt tctccagtgc cattggcctg 600

  gtgctgctga tggaggcggt ggccgtgctc gtcgggnccc cttcgggagg caaactcctg 660

  gatgcgaccc acgtctacat gtacgtgttc atcctggcgg gggccgaggt gctcacctcc 720

  tccctgattt tgctgctggg caacttcttc tgcattagga agaagcccaa agagccacag 780

  cctgaggtgg cggccgcgga ggaggagaag ctccacaagc ctcctgcaga ctcgggggtg 840

  gacttgcggg aggtggagca tttcctgaag gctgagcctg agaaaaacgg ggaggtggtt 900

  cacaccccgg aaacaagtgt ctgagtggct gggcggggcc ggcagcacag gggaggaggt 960

  acagaagccg gcaacgcttg ctatttattt tacaaactgg actggctcag gcagggccac 1020

  ggctgggctc cagctgccgg cccagcggat cgtcgcccga tcagtgtttt gagggggaag 1080

  gtggcggggt gggaaccgtg tcattccaga gtggatctgc ggtgaagcca agccgcaagn 1140

  ttacaaggca tcctcaccag gggccccgcn tgctgctccc aggtggcctg cgcatggctt 1200

  atgctcaagg acctggaaac ccatgcttcg agacaacgtg actttaatgg gaagggtggg 1260

  tgggccgcag acaggctggc agggcnggtg ctgcgtgggg ccctctccag cccgtcctac 1320

  cctgggctca catggggcct gtgcccaccc ctcttgagtg tcttgggg 1368

  <210> SEQ ID NO 99

  <211> LENGTH: 613

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (25)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 99

  gaattcggca cgagcgggac gcggntgaag atagcctgcg gagtgtccgg gcggaacacg 60

  gttgcagcac tcccagtaga ccaggagctc cgggaggcag ggccggcccc acgtcctctg 120

  cgcaccaccc tgagttggat cctctgtgcg ccacccctga gttggatcca gggctagctg 180

  ctgttgacct ccccactccc acgctgccct cctgcctgca gccatgacgc ccctgctcac 240

  cctgatcctg gtggtcctca tgggcttacc tctggcccag gccttggact gccacgtgtg 300

  tgcctacaac ggagacaact gcttcaaccc catgcgctgc ccggctatgg ttgcctactg 360

  catgaccacg cgcacctact acacccccac caggatgaag gtcagtaagt cctgcgtgcc 420

  ccgctgcttc gagactgtgt atgatggcta ctccaagcac gcgtccacca cctcctgctg 480

  ccagtacgac ctctgcaacg gcaccggcct tgccaccccg gccaccctgg ccctggcccc 540

  catcctcctg gccaccctct ggggtctcct ctaaagcccc cgaggcagac ccactcaaga 600

  acaaagctct cga 613

  <210> SEQ ID NO 100

  <211> LENGTH: 685

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 100

  gaattcggca cgagcctcag ccaccccagt agctaggact atagacacaa gctagccttt 60

  ttatacttac tgttttcatc aaatgtcttt ttccaactag tttccaacct gtctttgtat 120

  ttgaagtgca tctattgtag atagttcagt gttgctttta aagtgcttac tccatttgtg 180

  tttagtatgt tgacatggtt ggatttagat ctactatttt gctttctgtt tttattcctg 240

  tttatccttt tttacttctt acagcttaat gaattttggg gggggaatcc attttaattc 300

  tctcttgggt ttttagctac atcttcttta ggattgcact agagattaca atatacattc 360

  ttaacgtctc acccttttgc ctggggcggt ggctcatgcc tgtaatccca gcactttggg 420

  aggctgaggt gggtggattg cctgagctca ggagttccag accggcttag gcaacatggt 480

  gaaaccctgt ctctatgaaa aatacagaaa cattagctgg ttgtggtggc acacacctgt 540

  agtcccagct acttgggagg ctgaggtggg aggatccctt gagcctggga ggttgaggct 600

  gcagtgagct gagatcatac cactgcattc tagcctgggt gacagagtga gatgctgtct 660

  ccaaaaaaaa aaaaaaaaaa ctcga 685

  <210> SEQ ID NO 101

  <211> LENGTH: 646

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 101

  tcgacccacg cgtccgataa ctttttcaag caatatcagt gagtgggtcc catcgacagg 60

  gttccaggac ctggaacact ttaacagaag gaaatgccga agcagcttgc acagttgctt 120

  tacagacttc caagaggctg attctggctt caagatggag ccttggagtt ggtttttttt 180

  tttttttttt ttcttccctc aaagaacctg cggttgcgct ttgtgtgttt tgtttttgtt 240

  ttccatttgg gggccccatg ggaaagagct tctgaactct ttcctttatg aactcccact 300

  gtgttcctat aaaggccctt ttctttctta gtgttgtaag ttacattttc attatgcccc 360

  atcacatctt ctttactgta aaaatattaa aaagctgttt ccaagtggga cagctaatga 420

  agctctaatt attgcagaca tatttttgag atgtaaaaaa aaaaatttaa agttaaatga 480

  taagtcttag aggcgagtga ggaataaaat ggatgtaaac atttacatgg gatgcattag 540

  aattctgctg tgtgtactgt cttttggttg aaacaaatta tgaacagtga ctaataataa 600

  aaagtcaata cccaawraaa aaaaaaaaaa aaaaaaaagg gcggcc 646

  <210> SEQ ID NO 102

  <211> LENGTH: 826

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (726)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 102

  ggtcgaccca cgcgtccggc tccctttgtt ttggtggcag ccttcttgtg ctgtatactt 60

  gttccctagg gtgtataata atatgtgcac tagagtgcta ggtaccctac cacattgctg 120

  ggaccttgcc acactgctgc agccttccag taggatatgg gggaatgtca gtgaggctcc 180

  agggatgtag atatgtaggg aatgttggac cccagggcaa catgcaatct ggtaggagtt 240

  gggctctcaa aatggtgctg ctgtgtaaca gctgcttggg tcttggggta gggagtgtag 300

  gacccagcat gagctccctc tttggagcag tgctgtctga gactccaggc agctccgtgt 360

  attagtctca ggacctgcaa aggcctaggg gctctttttg ggtaggactg caggagtctc 420

  catggtggga atgtgaacca ctggaaatct ctcatttacc atttccctgt actggagatg 480

  ctttctgggc tcccagatga tactarctgg gctggttgcc tcamttcctt ctccctctgt 540

  gcataaggca ttttctgtca cttctctgct gaactctagt gttctttctt agaggctgta 600

  ctcaaagttt cattatccat tcagtatttt tattcttctt tgtggaggtg gcaagtgcta 660

  ggtgcctcta gtcaatcatc ttgaagcccc ctgttatgtt aaagtcttta atggaaaaag 720

  aagacnacat gcatgaccag gcagatactt tgagcagagt cataggaact gctaaaaaaa 780

  aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaagg gcggcc 826

  <210> SEQ ID NO 103

  <211> LENGTH: 586

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 103

  gaattcggca cgaggtggct atcagatttg gggttctact ctatgagact tttaagtcat 60

  tatgcaattt ctttattttw atttttttga caagaagtct ggagcatgat tacattatgc 120

  attttcttac tctttaaagt atttgtgggg ataatccttc attatttgat tggcaaaaat 180

  atatatgttt atagtgtgta acatggtgat tggatatatg tacacattgt ggaacagcta 240

  aatcaagcta ataacaaatc agttacctca catacttatt ttgtggtgaa aacatgtaaa 300

  atccactctc ttagcaattt tcaagcatcc aatacattgt tawtaactgt agtcaccatg 360

  ttatacaata gatctcttga acttattctt cctgtctaac taaaattttg tattccttga 420

  tcaacatcta cccaatccct cactgttctc cagcctkgat aactaccatt ctactctctg 480

  cttctatgaa tttgactttt ttttttttta gattccacat atgtgagatc gcgcagtatt 540

  tgtctttctg tgcctggctt atttcactta atataaagtc cctcga 586

  <210> SEQ ID NO 104

  <211> LENGTH: 628

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 104

  tacagcagtt taaaaagcag tgtctttctt tgagagacag gaagtctagt gaagagccag 60

  tattttaggg atagataatg aaagaggctg tcatttcaga cattttaatc ctctgaaaga 120

  atacaaaaga aaaaaaaaag aaaacaaatc tttcagaatt gtttgaagta agaacaagac 180

  aagaggaggt gattggtgtg ttactgttct acgaaaaagg agaaaaagct tcatgaaatc 240

  gccattcagc aaggacagaa ctggagatgg cttctctttt acaaagaaat ctctgtccca 300

  ggctttcagt ctgtttggtg ttcatacaag tgtttgtgtg ttgtgtggaa ggcgggggaa 360

  ggcgggtgaa ggcggtcctg ttcagggccc cctttggtga acacagcagg caaaatactc 420

  tcgtcatccc cagccaaact ggcctgcaag cgcactgact tccacatccc tagcatttag 480

  gcctttgaat agaagctgac acgtagcagc cagctgaaca agtatttaat gaggagcaac 540

  acaactccaa gaagggctcc ttagtgtatt gtcaagttgc tgcagccttg tgagatggaa 600

  aaaaaaaaaa aaaaaaaaaa gggcggcc 628

  <210> SEQ ID NO 105

  <211> LENGTH: 558

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 105

  agctctaata ttactcactw tgaaggsaaa gctggatacg cctggcaggt accggttccg 60

  ggrattcccg ggccccatca caccctatgg gggagagcga atgttacagg aggctttctg 120

  gtgcctcgtg cacatggact gtgcatgtgg attttgccta aggtcagcct tatatgcatt 180

  gtggaactag ggtatggaaa accatgaaac atgattattt tcttctagca tgcctgtcta 240

  tgacttcaac tggtggtatt ctttgtactt tataatctac attatcatta atacctacat 300

  cttcaagtct gtctttctgg ccatggtgta cagcaattat aggaagcatt ttcacatact 360

  gtgtgtgtgt gtgtgtgtgt tttgtagtga tgaacagaac ttgttattta cccaattcta 420

  ttatctatca taatagtaaa ttagctacta taatagacaa aagtatgact ctcagttaaa 480

  taagagattt tttaaaaact tgttacaaaa aaaaaaaaaa aaararaaar aaaaaaaaaa 540

  aaaaaaaaaa gggcggcc 558

  <210> SEQ ID NO 106

  <211> LENGTH: 756

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (230)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (755)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 106

  gaattccaat gtccacaggt gatgggagag atgctgagaa agggtggcca gtgagtgagg 60

  aggaaaacca gaggagtgtg tatcctgggt accctgaatg tgatgagcga caagctgtcc 120

  cccagcactg tgccattgct tctcccagtt ctcttcaaag tcaccatcct gcttcagcgt 180

  gtgtgcccag aagatagccc ttcctcttct gtgcttccag aatccgtagn cagggaatag 240

  gaatacatgg acaagtagca tgcagtgcag tgagaatgta taacaacaga tgactctggg 300

  gaccaaaatc aaatggggcc agctacaaag agggcaggaa atccccacag gtgattttac 360

  tgtgaggaat tttatgaggt tcagcatcat atattgttag gagaaaatgc tgttttgata 420

  agcagagata tgagaaaagt aaacgggaac tatgatttag agatctcatc tgrttacttt 480

  gtcctattcy cagtttwatt actaaagagc agtaaagcca aggagaaagt agtaaagatt 540

  agatgaatgg ttagcatgtg aaacctgaaa ggaaccagag tgatttccct cgaggaacaa 600

  atgcacttct cttacatatg aaagatgatg tgttctgtgt tcccatagaa tctagggaaa 660

  gaaaaagtga gcagatactc tgatatgagc aatataactt aggtgtaaaa aaaaaaggaa 720

  ttcgatatca agcttatcga taccgtcgac ctcgna 756

  <210> SEQ ID NO 107

  <211> LENGTH: 1146

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 107

  cccgtccaca atgcagcaga ctcttcccaa ggccacctag caagcaaggt tgatcggatc 60

  atctaaactg gccgcctcct gaatatttca ctgaatcctg gcgttcatgt tgaagcagac 120

  aaaatgagaa aggaggaggg cattgctcac ctctcaatag cttttttcgt tcaagttcta 180

  tgtctttatc agctcttgcc tgtgatttta ccccaattca accttgggag tgggaagaat 240

  atgaacagat aacccttggc ctaacagctc catcaaacct ccttgagagc aactacctag 300

  gccaggctag tgagtgcttt gtgaggaagc tggtcagaag gttccctcaa ctccttcctg 360

  gtcctcctgg acactgcaga aaagacttag gggatcccca gcagaggcca attgctctcc 420

  ttccttccct gccccaccag gaaaggaata acgtccacag acttgaagca gatagtgaag 480

  tagatctgtg agaggttcta ggtacttagt gtgtagactt tgacgaatat ttctcaagtt 540

  gggagccctt gttaaaaatg atgtttaagg gagtggttgg ggggaagatg aaggcatgga 600

  ggaggaagaa gagaaggaag cccttgccat ataaaattca tgcagactaa acagtttccc 660

  tgacagaata aataaagtgg atgctacccc actccagaat caaaagcaat ttaattaaag 720

  tctcttaagt tgtaaagagt tttaaatgat ccgtgttgaa ggcgaatsct gcyaaatgca 780

  gtgggtctga cgtcagctgc cgggcctggg ctgggaggcc atttgctatt ctgtttaagg 840

  caggctggat tgtcttattt tggaaccagc ttggtggggg gtttgctttg ctactgcttc 900

  tgagccctga gcttcaaagg ctgaaattaa tggtgaacaa aattgtgcgg ctctggccat 960

  cccatgcggg caagcccatt gagggttatc attaagtaaa gaaataaaga gggggaaaaa 1020

  agcctgcctg ttccaaaaac ctcatcagat aatgacctca gtgattgggt tttcattacc 1080

  aaacagcatc cagagattat caacccatag aagaagggag gggaaaaaaa aaaaaaaaaa 1140

  aaattc 1146

  <210> SEQ ID NO 108

  <211> LENGTH: 775

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 108

  tcgacccacg cgtccgaaaa aggaaatgat acatgtcttg acatttctat tgcagtwtta 60

  catcttaatt tctaagggca aaggtgatgt ttcccagttc gtaaagtctc gagagtacta 120

  atgctatcaa aagtaattaa tttcaagtgt aaataagacc aaacaaaaac gatcagatgc 180

  gacattgtct cataaacatg atagactatt aaatcacttt gtgttttttg gaaacagcta 240

  taactattaa tatatacagt aatctagtaa atttccttca gatatgctat tgcggataca 300

  acagatcatc tattgtcaca agctaaccat tatcctaaca aaatggcgga atacagcaag 360

  acataagagt aaaaagaaag aagatgagct gatattaaaa catgaacttc aattgaaaaa 420

  atggaaaaat aggttaatac tcaaaagagc tgctgcagaa gaatccaatt ttcctgaacg 480

  aagttcttct gaagtctttc ttgtagatga gactctaaaa tgtgacattt cactgttacc 540

  kgaargrgca atattacagg tttgtatgaa ttcagtatac attatatact ataatctgcc 600

  aagtgtggtg gtgcatgcct gtaatcccag ctgcttggga ggctgagaca ggagaattgc 660

  ttgaacccag gaggcagagg ttgcagtgag ccgagatcac accattgcac tccagcctgg 720

  gcgacaatag caaaactcca tctcaaaaaa aaaaaaaaaa aaaaaaaggg cggcc 775

  <210> SEQ ID NO 109

  <211> LENGTH: 911

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 109

  gaattcggca cgagacgaca atggggaacg cggtgtttcc cacctcttgt gggtagaaag 60

  cagtctgctt tgaggaggcg agaaggcaaa gccagggcag ggcgttgctg tgggaagcgt 120

  tcggtgaaag crggtttcga cgcttaggag ggccgaggga gaagattcca ccagcattgt 180

  ccttgcttca agttttagga tgtctgaact ttcagctttc atgttttcaa ccatcatttt 240

  tttaatggca caacctacat cttgttttta aaagaagtag cctcaaatta aactcctaaa 300

  ctctgatgcc ctggggatga gaacaactag ctkggatctc gtgccgtgta atcaatgttt 360

  cattccgctg cctccatcat gtaatagaat cgcttccaga aaggcagtta actggaagca 420

  gcagaggctc ccagccgtga gaggactgct caacaatgcc ccccatcgcc gcccccccac 480

  ccctcgcacc ccttgtgttt tcccctctga ggggcccaag ggttatggct ttcatgtcta 540

  ggtgtgggga cagaggaggg agaggcagat ccygggccgg gagaggatgg ccctggtctg 600

  aatctggagt aattaatgcc cacccaaaga aaaggccctg cccaggtcca atgttgtctt 660

  agatctgatg atgctgctat ttacaaaaca ctgatcgtcc gaaagcttga atctgttcct 720

  cctcgaatga ccctgtagat gcctgacctc caccgtacct ccacatcact attcatgtcc 780

  ttctaggaaa atgtgcacat gcctcacgca ctatgtggga agggcgtgtt tttaaattaa 840

  taaagtgtgt caccattagc catamraaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 900

  aaaactcgta g 911

  <210> SEQ ID NO 110

  <211> LENGTH: 456

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (456)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 110

  gaattcggca tgagctttct ttctcctgca ggcattggaa atacagtccc agctggcaac 60

  accagccagc agcacagccc ggaatcctgc tcctgacctg caccatcccc accagcccac 120

  gatagaacgt ttttgtaggc attcctcctc atgggagagg atagagtaca tgcgagtttt 180

  tgctctcctc ccaccctttc acaagagcac tgtgctttct tttcttctct ttttcctttc 240

  tttttttttt tttaggcagg gtcttgctgt gtcasccagg ctggaatgca gtggtgcaat 300

  catagctcac tgcagccttg acctcctgga ctcaagcaat cctcctgcct taacctccca 360

  gctactcagg agaccgagac aggaggacca cttgagccca ggaggttgag gctgcagtga 420

  gccgagattg caccactgsa mtccagcctg gggaan 456

  <210> SEQ ID NO 111

  <211> LENGTH: 554

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 111

  gaattcggca cgagcctcca cctcccaggt tcaagagatt ctcctgcctc agcctcctga 60

  gtagctggga ttacaggcgt gcaccaccac acgttgctat tttttgtact ttaagtagag 120

  acggagtttt gccacattgg ccaggctggt ctcaaactcc tgacctcaag tgatccaccc 180

  accttggcct cccaaggtgc tgggattaca ggcatgagcc actgtgcctg gctccattta 240

  caactatttc tatcattata atgcaggggc tctcaaacct gagcatgcct cagaatcccc 300

  cagagggctg tgcgcacaga ctgctggacc tttccccagc ttctgattcc gtccctccag 360

  agtggggctc gaagattgcc tttgaggtga rgctgcgggt cgggggcacg tctgagaact 420

  gctgcagagg tgartgctgt ggctctgtct gcattccccc tggaagactg argcaccagg 480

  tgtgctggtg ctaacagacc acaagtccct cctggacact gcccttctct gaagggagct 540

  gcctcctcac tcga 554

  <210> SEQ ID NO 112

  <211> LENGTH: 722

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (2)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 112

  gnaattcggc acgagaaaaa tttacgggta acactgaggg gtggggtgga aagttttgat 60

  cataaagtgg tcaccaacaa gggcacttct gaggtgctaa tgatgttctg ttttctgatc 120

  tgggtcgtgg tgacattcac atattcatta aattgtacat ttgttttaca taagtttatt 180

  atatttccta attttaaaaa agttaaaagg aggaggaaaa agttggttat gaaagtgtaa 240

  ccattcttcc aaaatatcaa ttaaaacaca tctgaattaa gaggtaaaat atatcaaaga 300

  ttgacagaaa acaaaagctc tgaaatgata tttccagcct aagaacagtc gttgcttttg 360

  ttggtttagg aagttttgtt ctcctgaact aatgttcaaa atgaaaaaaa gtcacctggg 420

  ccaggagcag aggcccacac ctgtaatccc agcactttgg gaggccgarg tgggtggatc 480

  acaaggtcag gagatcgaga ccatcctggt taacgtggtg aaaccccatc tctacaaaaa 540

  tacaaaaaat tagctgggct tagcggtggg catctgtagc cccagctact cgggagattg 600

  aggcaggaga atggcatgaa cctgggaggt agagcttgca gtgagccgag attgcgccac 660

  tgtaccagcc taggtgacag agcgagactc cgtctcaaaa aaaaaaaaaa aaaaaaactc 720

  ga 722

  <210> SEQ ID NO 113

  <211> LENGTH: 931

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (930)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 113

  gaattcggca cgagaaccag atgtttttcc acacagaatg ctagttcttt aagacacagg 60

  ctgggtgaca tgtttcctta gagtgacaat atttccttat agtgacattt tccttgactg 120

  gctccatgca gaataggagg atatagaata ggaggagaag gtttctgctg tggcacctgg 180

  agtggtactt ggtgcacgcc aggtgctaga caatgtgtgt gacaaggatg cacgtgaaat 240

  gccccccccc gagtgcctca gtgactgcag taaagtggcc cttgtcatgg tcctcttcct 300

  ctttctgcat cagtcttcat gctgggcggc atgaagagag aaacaaaaac cacctttctt 360

  gccagggtct tagtaccatt tgctgctctt atctttcaag taagggagaa catctaagaa 420

  acttatcacc gtattcattc tagactgtta gggrtttaac tcttcaccta cttccctgag 480

  tggtctgggc tggargttca gagctaartg ggctgggtgt aaatcaggat tccgtccctc 540

  amtagctgtg aggctgtggg taattcactt catctctctg agccttcatt ttctcacctg 600

  aaaattgggc atgctaatac ttttccatct ccttcccagg gttcacagga ttaaatgaaa 660

  ttattaacac aaagttcttg gcctggtagg gggcatgtac gtggccaccg tcctggtgct 720

  ggacactggg gtaagagttt ggaagctatt ggctgggcaa ggtggctcac gcctgtaatc 780

  ctagcacttt gggaggctga ggcaggtgga tcacgaggtc aggagattga gaccatcttg 840

  gctaacacgg tgaaacaccg tctctactaa aaatacaaaa aaaaatttag ctgggcgtgg 900

  tggcatgcgc ctgtagtccc atctactcgn a 931

  <210> SEQ ID NO 114

  <211> LENGTH: 588

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 114

  gattcggcac gagatcaaaa tggccagttc tgtgacagta aaagaggttt gtgtcttatt 60

  taatcttttg ataataataa cagctatggt gtatcacagc tttaccaagt accagacact 120

  gttctaaggg ctttgcatgg ttcactcact ccttacgtca tccctcggtg gcaggtgctg 180

  taattatcct tatattgcag acaaggacat tgagacagag gtcaagccac cttcccaagg 240

  gcacacatgg catctgcact gctcctgacc gaccgacaga gagagctgct gtcacgatcc 300

  tcaaatgagc tatgcatgtc aaaagtttaa aaataaaaaa gataaaaaca tgcacaaaat 360

  ttaaaaagta aaccatttca agctggacag actaaaactg agagatggcc agagaagagt 420

  atgaaagata aatctatgga cagagtaaac cctgactggc ttgaaattag ggcccttact 480

  cctccacact cctgacgggt tggttcaaga ccargaawta gaagcmcmtt gtgagttcta 540

  cgstgctgcc ctgggaaaca cacaggctaa acacacccac aggctcga 588

  <210> SEQ ID NO 115

  <211> LENGTH: 812

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (443)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 115

  gaattcggca cgagtatggc ccttctttgg cttctgggta tttaaaaaga gctcttggga 60

  ctcttctgag gtcttcctgg gagcagaaca gtacacatgg tctggaattg ggttgcatgg 120

  aataactttc aaggaaagcc actgaataaa gtgccctgca ttcctgtcca ttggatactg 180

  ataatgctat aagatgatct ttctcttctt tattttgttt gagattattg tgactctctg 240

  gctaactcct acttatcctc aggccttttc tgaactcaca attcaaatta cagctccctt 300

  tggttctctt ccacagcagt tgtacttaca tatgtctatt atataattat gaattgtttc 360

  atattgtcgc ccttacaggt aaactaatga atttggggct ccatctgttt gctcaccact 420

  tgatcctggc agtagcacac aanggctgct caatacctat ttactgaatg agcaaakgga 480

  ctggaccact tttagagact ggagtatttc cttawaccak gtgagattga wttttgagga 540

  cagtttacca ctggaagctt ttgcagaact aaggtcattt ttacagtata cataacctct 600

  gctgtgtttg ttgatactgt aagtttacat tttcttatga ctctttttaa gtagagcacc 660

  cctgtgttta ggaaagctag agctattgtg atgcctttga gtttgcttgg ctgattgctg 720

  ggacttgaac tactgagctt atctaaaagc ctcagaggcc ttgtagcctc tgtcttttag 780

  agagtgtagg taaaggcttg ttttccctca aa 812

  <210> SEQ ID NO 116

  <211> LENGTH: 506

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (13)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 116

  gaccatgatt acnccaagct cgaattaccc ctcactaaag ggaacaaaac tggactccaa 60

  cgcgttggcg gccgctctag aactagtgga tcccccgggc tgcaggaatt cggcacgagc 120

  acctcctgag gaatatggtg taggaaagcc acccgcgtgc tttctggctg ggatggctct 180

  cttccttggc tgctggaggc actggagaga ggtctgataa ggatggctgt atggatcagt 240

  gggtcttatt cctcattctg cagcagaagc aactgggatg ttttttctcc taatattgtg 300

  ctggcttctc tgcctttctc tttccggtct gtatccaagg ctgctaaacc ctggtggctg 360

  gctctccctg ctctctttcc agatggatta tggctggatt ctgccatggg gagcttgtac 420

  agtcagacat ggaaagccag gaatgggaaa gaggtcaggt ggttctctcc cacacctcac 480

  tgccttggtg ctatgtctca cctcga 506

  <210> SEQ ID NO 117

  <211> LENGTH: 751

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 117

  gaattcggca cgagagcctc gcaggtggat tagacccacc cgaggctcgg gagaaaccac 60

  ggcaccttgt tgttttgagc cactaaatgg cgggacgctt gttcacgctg ctgctatggc 120

  aagagctagc gaggcggctg gtaccgggtg atgcttcacc acggctttcc agaaagcgct 180

  ccgtgacccc aggcccaccc ttcccgacac tcacggttcc ctcagaaatg ctcctctcaa 240

  atctctcact ctccctgcag cctttgttgt ttcttttttc tttctttctc ttttgcaaga 300

  tgggatcaag gaaaggtctc agacacaaaa cgcaacattt ttcttccatg acagatcaga 360

  tattgaaggg ctcagtgagg agccctgctc tgggacaact ccatgattag cgctccaaga 420

  ggcagtcaca gggaagcagg tgctctgttc ccctcctggc tcagcaatcc cgcagtcctc 480

  ccgtcccgct ccaggcccag ccagcctggc tgcttggatc cgagacaata gcttggtctg 540

  gaggcggctc agggtgggag ggacccaggg acccgggcac cagtacagca gctgggaatt 600

  caggcccagg gatagggatg gggcacagga caccaccccc atctcacaca gggagatgaa 660

  ggtgggatcc agcatgggga ctggacatcc ctgagtccag ctgccccgtt acaatggggg 720

  aactgagatc cggggatggg atagttctcg a 751

  <210> SEQ ID NO 118

  <211> LENGTH: 960

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (460)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 118

  ttttgtctag tacatatatg taaatatatt aatgttgttt ttgtgtttgt gatgtagtaa 60

  ggagatgtac atagaaattc attgaggtat atagatactc atctgtctag gcagttccca 120

  attttctgaa gaatgtttta cagcaaaatt ttctattttc ttttattaaa tagtgacacg 180

  tcaaacaatg tcacatccaa aacactagtt tcatcaattt ctagcagtaa taatagactt 240

  gctgtaagta ttgttttctg atgccatacc cttgtcatac atattattaa atgaccaata 300

  ttatgtatga agtagacaaa aaaatttact caaacttcat tcaaatccta attgtgataa 360

  tttttgtttt atatttaatt ataaaccaaa atacatttgc atttttaagc taatttgtct 420

  caaaattttg ctttatattt ttggatcagg ttaaagtccn gtggatcccc tgaatgttat 480

  tgtccctctt gatggttttt acttctgagc tatacgtcaa aagacacata agcttcaaaa 540

  gtcmagacaa acctcattgc cataaaaatc aagatataga tgttctgttc cgtaaactcc 600

  ttgaaaaaca ttttaaagtc atcaatatga tctgtttccc atgaaactta agttagcttt 660

  cttattggag twattycttt tctgtaagtc tgaaaagtag agattttgtt ttacgcattt 720

  tagtaacctg caacaaccaa ctctaaaaaa gatttggctt gtaatgacgg tctctgcttt 780

  tttgggtttg gagtacacaa ttgtaatatt tacttagtta tttgtgtttt tctttgttca 840

  aggtattgac tagtttcata aattttttgm aagtttttct ttcattggtt ggaaagcaga 900

  ttacattttg cactattaaa ataagtttat tactttaaaa aaaaaaaaaa aaaaactcga 960

  <210> SEQ ID NO 119

  <211> LENGTH: 1442

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (1377)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1419)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 119

  cttctatatt agatggacag atttatatac ttttccatgg aggattaagt aaactgaaac 60

  ctaagacaca cgaagaaatt ctaagtggaa aggccactta ttagttagtt tacagcagta 120

  tcgtaagtga caggatgata ggagtgtggt aagtgatcag gataataatc tgcttagtaa 180

  gagaaacaat ttgaatttta gaaggaaatt gccttaccat ttgcaaatta aggtaattaa 240

  aatacagtga atttcaaaat gcctttttaa tgacaatgtg tgaacttaat ttgttttaat 300

  aaaccaaaat trttgttatt gtgttaaggc tattttacat tgaatgtgta tcttgccact 360

  gatgttaact tatcccatct tacccaaggt tgtaggtaac aatatactat tgggtgacag 420

  tggactaaca tctctagtga tccctttgtc agtggtcttt aacttaaaat aatttagaga 480

  atatggtttc tacaacttac atttttgttt wcttgtaact acagattatt atgatggttg 540

  taatgaagat tatgagtata attggagcta tatgtttctg aattctgaac aactatttat 600

  aaaattttat cctacttttt tctgttgaac atatgacttc tctggtctgc taaacacata 660

  cagaccttta gttttggttt acatggattt aaatatatag atatatcact gtaaaataaa 720

  cttcaggtgt aacagattta tagagaaagt aatcatattt gtttatggtt gtgtacctac 780

  tttgagaaga aaagaaaaat attagaatga acagataatt ttacaagtgt tgatcactta 840

  ccagcaaacc agaaacttca gagattttga aagcaaatct attttctctg ctgtgtatta 900

  aattcattta tctaaaatgt tattgctcct ggcttagaat catcttgtgc aaattctctt 960

  tttttgttgt ttgtctgttt gcctgttgct caccatagac ataattttct tttcataaaa 1020

  cattctttgt ataatcacct cagagattat gaaagtgact ttgataaaat ttaatggtgt 1080

  tcacaaaata attttcacgt gagtaatttc acagtgcgtg tattgtatgt tatttagtgt 1140

  attttatatt ttgtttcaat tagagaatgc tattgaatcc agtttttgtt tagttactgt 1200

  tcattttact ttataaaatt gacataattg agtttattaa atttattggg ccaatttaag 1260

  taaacagttg aacgtttcat aagtcatgag gtctttttgg gcatatacat gaagtaaaca 1320

  aagacaatac taggctatgt aataggragg ctaccttaat taggaggtaa atattcnttt 1380

  tggaaattgg gcccgtgggc ctcgggtgga aaatggggna atatccctag gtaaaaaaat 1440

  gg 1442

  <210> SEQ ID NO 120

  <211> LENGTH: 845

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 120

  gattttacac agaacatatt ctctgcatga tttcagaaaa gaaaatctaa aaaggtaata 60

  cgggtatttc aaataaaatc ctttctggta tgaaaggctc cattgatttt attaagcctt 120

  cctttacctt gtagtacaag gtgctttaat gggatagaac taagcatatc aatatctata 180

  actgcatttt gtgctagaca attactgttc ttttctctaa aatgtatatg tcaatttaca 240

  aggccaggga tagaaaacac tccataattg ctttccttga ttttgctgag gatttggtat 300

  gattttagta agcaaactgt tttttggttt ttccttaatg tttttaattt tttttcctct 360

  tgcaacaatg acggtgcatg ttcttataaa tataggaagg tccagatata aatagtaacc 420

  taaagttctt gctgtgctta aaaaaaaaaa tcatgtggcc ctttcaatat ttgaactgct 480

  aagcaatgac atctgtagtt ttatctcctt ttttatgtca tagaaattaa tatgatactt 540

  taaatatgta aatataatac attaggtaat gctattattt atatctgtct taacataatt 600

  taagttgtag ctgtgtcttg gaaatatttt taaggtaatc tatattcaca ttgcctgtgt 660

  taatgctttt taaagtttgt atacatcaga tgtatatttt tggtttggca taagctacga 720

  ttgtaatttt tcttggcttt ttgttcataa agaatttttt gaaggaatgg taacaaatgg 780

  taatttacaa atggttgtga ataaacacat ttttacactt aaaggwaaaa aaaaaaaaaa 840

  ctcga 845

  <210> SEQ ID NO 121

  <211> LENGTH: 360

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (340)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 121

  gaattcggca gagaatcagc atgtctatca cctcaaatac ttatttcttt ttattgggag 60

  cattcaaaat cctctcttct agctattgga aaatacacac taaattactg ttaactatag 120

  tccccctgca gtgctgcgga atgccacaac ttatccctcc tctccagctg tagtttagta 180

  tccagtaaca tactcttttc atttcctttc tttgggcaga aggctagatg ttgcctgttt 240

  ttgttttatt tttctgcttc acatatagcg cacgaaagca gagtgtattc aaaaaaggaa 300

  atgtgtttga aaaaaaaaaa aaaaaaactc gagggggggn ccggtaccca attcgcccta 360

  <210> SEQ ID NO 122

  <211> LENGTH: 944

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (932)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (942)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (944)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 122

  tcgacccacg cgtccgccca cgcgtccgga cagacccagc ctggagctgg cccctggcct 60

  gtgtgctgac ttcttggggt cctcaaacca ctgtattttt ctgttgagcc tgtacttggg 120

  gagagatcag tagcatttga ggaagtaaga gaaaagaatc atggtacctc agggtttctt 180

  tccctttact cgctggcagc cattgtctgt gggcacctca tgtttttcca cactctactg 240

  ggccgtggag gtaacgatca cccaggccag tctcctctgc ctgggatgcg ccctctgaga 300

  ggaggcctag cagggcaggc tccctctggg catccctgga tgcagcctct ggacacatgc 360

  ctcctttaaa gtgtccgggt gcagctcagg ttgagtggag gtagaaggag aaacagacat 420

  gtttaccacg cgttttccaa agctcctgat ctttcccaag attgtaactg aaaactgctg 480

  tctcttgttt tgttcgtttt gggggtggtg gtgctggctg ggccatgctt gtgaagtgat 540

  gtgtgtctct gatttaacgg attcactgtt ttctctgcta attgagagag cgttatttac 600

  attatttatt tgttttgaca caagtgcttt cagtgtttta tcctagctaa tggcttctta 660

  aaggtaataa aacccttcca acgtaattgg tcagataaaa ctttttttct tgtatgctta 720

  aataaagcaa ttagtgaagc acttctatcc aaaatgactt ttttgtcctt ttttaaaacc 780

  aatttactgt tactggaaac tttttgtaca ataawgcaat cacgcagatt aaagaaaaaa 840

  aaaaaaaaaa aaaaaaaaaa aagggcggcc gctctagagg atccaagctt acgtacgcgt 900

  gcatgcgacg tcatagctct tctactacgt gnaccctaac tncn 944

  <210> SEQ ID NO 123

  <211> LENGTH: 914

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (909)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 123

  ggcagagcaa gagatgactt tagatgagtg gaaaaatctt caagaacaga ccagaccaaa 60

  gcctgagttt aacatccgga aaccagaatc cactgttcct tccaaagccg tggtgattcg 120

  agagtcaaaa tacagagatg atatggtaaa agatgactat gaggacgatt cccatgtttt 180

  ccggaaaccc gccaatgaca tcacatccca gctggagatt aattttggta acctccctcg 240

  tcctgggcgt ggagccagag gaggcacccg gggaggccgg ggaaggatca ggagggcaga 300

  gaactatgga cccagagcag aagtggtgat gcaagatgtt gcccccaacc cagatgaccc 360

  ggaagatttc cctgcgctgt cttgaaagag ccctgtttcc cagcaccgcg gagctgcact 420

  gcacacctgt ggggagactt ttccagctgg gccaagggag tcagactcta agaacaatag 480

  atgttgcttt tcccgtgtca tgtaaatttg ttgcactttt ttgggctgag ctgttagagg 540

  ggcttctcca gaggctcgag agcaggccat ttcccaagaa gatgaagaat ggtgactgtg 600

  tttttattga aggaatttca aatgaagaat aatgtttaaa atgtgtatat agagatagta 660

  tagactcctc cgcggaagca tggagggaaa ggaggttgta aaatagactc catggagact 720

  cttaggaagc agtagattcc cgggggctgt gcctttagcg ttagaggaaa cacatagagc 780

  tggaactgtt aatggaaagc agtcacagct gagttttcgg agaccaagaa attaaaatac 840

  aattgcactt acaaaaaaaa aaaaaaaaaa aaaaactcga gggggggccc gtacccaatc 900

  gccttgtgnt gcat 914

  <210> SEQ ID NO 124

  <211> LENGTH: 462

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 124

  gaattcggca cgagctgggc tcaagtgatc ctcctgccga ggcctcccaa attgctggga 60

  ctgcagctgt gagccaccat gcccagcctt aacttggttt taagacctct gatttgcctt 120

  gcctcaatta cctcctttct tattttcttt cctttgttga ctctcatact ctgttctcct 180

  aattctcccc cttttccact ccctgcccac cctgaaagac acacacacac acaataagtg 240

  ggtggagtaa gaagtcaacg gagttggata taagcattcc tgcttttctg acatctccag 300

  tgtcttggag aacaaggatt ctagaatgag ggctcctcat tatgcttcct ttcaacattt 360

  tttctctgtg ttacttaagc tttcacccca agcatgtttg acagagagcc agtgcattcc 420

  ccttactttt tacaaaaata aaaaaaaaaa aaaaaaactc ga 462

  <210> SEQ ID NO 125

  <211> LENGTH: 545

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (7)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (16)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (41)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (42)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (87)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 125

  tcacttncgg ttccgntcga tgtggtgtgg attgtgagcg nntacaattt cacacaggaa 60

  acagctatga ccatgattac gccaagncga aattaaccct cactaaaggg aacaaaagct 120

  ggagctccac cgcggtggcg gccgctctag aactagtgga tcccccgggc tgcaggaatt 180

  cggcacgaga ttcgctgcct aattccacca tgatgtttta ctatgcatgc tttatcttat 240

  actcatctct ctctcctctc tctctttctc tttctccctc cctcctttct ctattataat 300

  ttagtcatct tattttttga ggcatttcag aatatatcac acttgtccta aatacttcag 360

  tatgaacatc attaactaga atttattctt tgttttactt ctgatgtgaa ayttatataa 420

  atacaacatg ctatgaattt gttttccmaa aaaccaatca acaatttawt aagcatggka 480

  acaaaaaacc tgaaggcttt atcttttaga gtagtagttt ttaaaaaaaa aaaaaaaaac 540

  tcgta 545

  <210> SEQ ID NO 126

  <211> LENGTH: 912

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (906)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 126

  gaattcggca cagagaaaca tttcatcccc agtaagattc ctcatcgtca ttcacaggtg 60

  atctctgttc ccaccctagc cttggacaat tctgcatcta ctttgtagct ctataaattt 120

  gccttttctg gacatttcat gtaagtcgat cacacagtat gtgttccttt gtgactggct 180

  gcttttgctt agcatgacgt tcttggggct cgcaacgcag cttgtgtctg ttgttcattc 240

  cttttgcagc agaatcgtat tctgttgttt ggatgggcca cctgtttgtt gtctgtttac 300

  tctccagctg gtggacattt aggccgtttg cactggcggt tactgtgaat catgtcgctg 360

  tgaacattgt gtgtgtgtct gcgtggactt gtgtgtcctg ttctctggga aggagttgcg 420

  ggttagargg tagttttttg tttcccctgg agactctctg gtttccacat atggtagttt 480

  tatgcttaac cttttgagaa attgccaaat ggctttctga agtggccacg tcattttgct 540

  ccctccagcc gtttgtaatg ttcccatttc tcctatgtgt aattttaata caaagcagta 600

  aaaagttgcc attatggacc tagtaaattc tgaggtaaca taagagagaa ataatgatgc 660

  agccgtcatt actgtgctgg taatgtaagt ttcctttttt tttgttttta aatggagctt 720

  tgcagagatc aagtcgagag aagaacactg ggccagcctg actccaaagc ctactctctt 780

  aagcgctttg ctgacttgtg atgttttaaa atctagcatt attttcaaat gctgtgagag 840

  cactgaagat aaaggatttg attctttttt tcaggcatcc aaggatggtt catcatcaag 900

  aatcanttta at 912

  <210> SEQ ID NO 127

  <211> LENGTH: 1048

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (13)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (16)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (17)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 127

  gatcccccgg gcncgnngaa ttcggcacga gggacagagt agttccagag gcagttctca 60

  ctgtgacagc ccttcgccac aagaagatgg gcagatcatg tttgatgtgg aaatgcacac 120

  cagcagggac catagctctc agtcagaaga agaagttgta gaaggagaga aggaagtcga 180

  ggctttgaag aaaagtgcgg actgggtatc agactggtcc agtagacccg aaaacattcc 240

  acccaaggag ttccacttca gacaccctaa acgttctgtg tctttaagca tgaggaaaag 300

  tggagccatg aagaaagggg gtattttctc cgcagaattt ctgaaggtgt tcattccatc 360

  tctcttcctt tctcatgttt tggctttggg gctaggcatc tatattggaa agcgactgag 420

  cacaccctct gccagcacct actgagggaa aggaaaagcc cctggaaatg cgtgtgacct 480

  gtgaagtggt gtattgtcac agtagcttat ttgaacttga gaccattgta agcatgaccc 540

  aacctaccac cctgttttta catatccaat tccagtaact ctcaaattca atattttatt 600

  caaactctgt tgaggcattt tactaacctt ataccctttt tggcctgaag acattttaga 660

  atttcctaac agagtttact gttgtttaga aatttgcaag ggcttctttt ccgcaaatgc 720

  caccagcaga ttataatttt gtcagcaatg ctattatctc taattagtgc caccagacta 780

  gacctgtatc attcatggta taaattttac tcttgcaaca taactaccat ctctctctta 840

  aaacgagatc aggttagcaa atgatgtaaa agaagcttta ttgtctagtt gttttttttc 900

  ccccaagaca aaggcaagtt tccctaagtt tgagttgata gttattaaaa agaaaacaaa 960

  acaaaaaaaa aaggcaaggc acaacaaaaa aatatcctgg gcaataaaaa aaatatttta 1020

  aaccaaaaaa aaaaaaaaaa aagggggt 1048

  <210> SEQ ID NO 128

  <211> LENGTH: 722

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (251)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 128

  gaattcggca cgaggaaagt ttcaaccctc tgacatgtgg gttcagctta tttttttctt 60

  tgttcagtat ggagactctc ttacttctgc tttttttcct ttctcttcta atttttcgct 120

  tcagaattct ggtttctcaa tgcataaact gaagtaattt cttccattct acttttctct 180

  gccccaggct tgagatagaa ctagggagcc cagtgaggcc ttttctttcc taaattaaca 240

  ggcatctgtg ncataaatgc tacctttgaa ctatgtgatt taagataatg tgcagaagta 300

  cttctctggt ctttcaggtt gcytgcataa ctawgtactt ggttgaactt gtaattcttg 360

  ctgacaacag tcctgctgtt ttccagtaag gttcgtgatc ctcgggccaa ttttgatcag 420

  tccctacgtg tactgaaaca tgccaagaag gttcagcctg atgttatttc taaaacatct 480

  ataatgttgg gtttaggcga gaatgatgag caagtatatg caacaatgaa aggtaaagaa 540

  attgaaaaat gaaaaatctt tcccatgtaa tttgagtaat agccaggaac ccactcactt 600

  tgaaggccct tctaagaaca aagaaaagta tatggttata gatggcagca tgaaaaggaa 660

  accaacttgc acatgcaccc tcaaatctaa aatacaagtt aaaaaaaaaa aaaaaaactc 720

  ga 722

  <210> SEQ ID NO 129

  <211> LENGTH: 477

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 129

  gaattcggca cgaggtgagt atggcttttg tcttccatct tgctcagggt actttggaac 60

  cgctatacat tgcaggagct tagcttctgg ttaccatggt ttgcttccag agcaacaagc 120

  ctagtacttc aacatggaga caattatctt ttgtttttgt tttgttttgt ttgttttgtc 180

  ttggccatgc ctttttgagt ttaccttttt atattttgtc catcattgcc atgtgtttgg 240

  agcagtgggc gttccataac atgaactcac tgtaccatca cgaatgggaa gtaaggggaa 300

  accttatcca tgtggatttt actcttccct gattccctaa attgggtttg caaaatacta 360

  ctgtgcactt tcttgatgat tcgggcttat ctttatgact gtctgtkttt gtgtcagact 420

  gtaaagaagt ataaaagtct ttagcttgaa aaaaaaaaaa aaaaaaaaaa aactcga 477

  <210> SEQ ID NO 130

  <211> LENGTH: 1296

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 130

  ggcacgaggc cactggaatc tgatcctgat tgtcttccac tactaccagg ccatcaccac 60

  tccgcctggg tacccacccc agggcaggaa tgatatcgcc accgtctcca tctgtragaa 120

  gtgcatttac cccaagccag cccgaacaca ccactgcagc atctgcaaca ggtgtgtgct 180

  gaagatggat caccactgcc cctggctaaa caattgtgtg ggccactata accatcggta 240

  cttcttctct ttctgctttt tcatgactct gggctgtgtc tactgcagct atggaagttg 300

  ggaccttttc cgggaggctt atgctgccat tgagaaaatg aaacagctcg acaagaacaa 360

  actacaggcg gttgccaacc agacttatca ccagacccca ccacccacct tctcctttcg 420

  agaaaggatg actcacaaga gtcttgtcta cctctggttc ctgtgcagtt ctgtggcact 480

  tgccctgggt gccctaactg tatggcatgc tgttctcatc agtcgaggtg agactagcat 540

  cgaaaggcac atcaacaaga aggagagacg tcggctacag gccaagggca gagtatttag 600

  gaatccttac aactacggct gcttggacaa ctggaaggta ttcctgggtg tggatacagg 660

  aaggcactgg cttactcggg tgctcttacc ttctagtcac ttgccccatg ggaatggaat 720

  gagctgggag ccccctccct gggtgactgc tcactcagcc tctgtgatgg cagtgtgagc 780

  tggactgtgt cagccacgac tcgagcactc attctgctcc ctatgttatt tcaagggcct 840

  ccaagggcag cttttctcag aatccttgat caaaaagagc cagtgggcct gccttagggt 900

  accatgcagg acaattcaag gaccagcctt tttaccactg cagaagaaag acacaatgtg 960

  gagaaatctt aggactgaca tccctttact caggcaaaca gaagttccaa ccccagacta 1020

  ggggtcaggc agctagctac ctaccttgcc cagtgctgac ccggacctcc tccaggatac 1080

  agcactggag ttggccacca cctcttctac ttgctgtctg aaaaaacacc tgactagtac 1140

  agctgagatc ttggcttctc aacagggcaa agataccagg cctgctgctg aggtcactgc 1200

  cacttctcac atgctgctta agggagcaca aataaaggta ttcgattttt aaagataaaa 1260

  aaaaaaaaaa aaaatttggg ggggggggcc ccgtta 1296

  <210> SEQ ID NO 131

  <211> LENGTH: 738

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 131

  gaattcggca cgagtgacaa gaaagacggt gtcagatgca cattaatctt tagcctgatg 60

  tccttcatga tgtccaacct ccagtttcat ctcctgccac actcatcccc catacttcca 120

  ctcttcacac tggccttact caaaatgcag attccaggac tcaggctatc tcactgcctt 180

  cttacttaca attcttatac cagaacaccc ttcctcctcc cctcatctga atcttacctg 240

  gtttttgaaa tttaagtcag ggccttctta ggaagatttc cctgattcag atccaagttg 300

  aattatgata accctccttt ggctcccata aaatcttata acttcctaac tgtgttttat 360

  gaatagttgt ctagtttagc actatgtcag gagctattga cagcagggct gggcacagtg 420

  actcacagct gtaatcctag ccctttgaga ggacaaggtg ggaggactgt ttgaggacac 480

  ctcaagccca tccagcctag gcaacagaat gagatcttgt ctgtacaaaa aaacaaaaga 540

  ttaattgggc gtggtgacgt gcacctgtag tcccaactac ttgagaggct gaggcaggag 600

  gattgcttga ccccaggaga tcgaggctgc agtgatccat gatggtgtca ctgcactcca 660

  gtctgagcaa cagagcaaga ccccaccccc caaaaaagct attgagggta gcagtttact 720

  ttcattgctc tacctcga 738

  <210> SEQ ID NO 132

  <211> LENGTH: 442

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (306)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 132

  gaattcggca cgagtgaccc agaagggtga gtcagttggt agtgtggggt gcatgagggc 60

  cattgcaggt tttgataatt accctttatt ttaatttgat catacttttt tgtttataac 120

  cttattctaa aaataattca aggtgaccat gcttccatta tacttcttgc aaccatacct 180

  atctttggtg atatttatta tgttaaggga caattggcat cttttggccc ttacctgtag 240

  ctattctatc atctggagat tatctccaga cacaaatcca tcgcccattg ctccatcgag 300

  gcacantcag ctckttgtag ttgccattgc ccctctcgag ccttctccac atagccacat 360

  gcaatccatt cccaaaaacc tagctcaatt ttcctcatca cagatgtttt ccctgaccct 420

  ccagttggta tatatctcct cc 442

  <210> SEQ ID NO 133

  <211> LENGTH: 882

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (881)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 133

  gaattcggca cgagatgttt tcttcactca aaaaatttta tattctcaaa catgtatatt 60

  ctttccctgt cttgttccat tttcttttct tttttctttt ttctttttcc tttctttcgt 120

  gggctgagaa aggggcaggc aaaatgaagc tggccactga aaactgtaag atggtcaaaa 180

  gctgacagcc tgtgtatgtg aaaagggaat tgtaaatgga ctgcaatgta atgtacactg 240

  taatttgaat acaattactg tatctaaaag gagctgctat gaagtacctt tcttatgttg 300

  ctaggctact gtttctgaaa gccctggatc tctttgcacc aaaaatggtc cagatagact 360

  ctttttaagg atcttggctg ctttttacta gaaggttgct tttatgagca tatttatact 420

  gctgaaggat gagtgttaat tttaattaac tttgccgttt tgtagagaaa actattccac 480

  aagataaatt ccaagtcttt tcacctgtca ggcatgcata ttttaatatc tgtttggata 540

  gtcagaagta gaatcataaa ggtaaaatat gagttgttac tttgtttctt cgatgtcata 600

  ttttatgtgt aatatatatg taaagggcca ttcttaagtt ctctccttaa acttaatgct 660

  gtcaagtgtt agatgtgtgc atgtgaactt gttgcactgc agaaacatat tcagagttta 720

  tctatgtaac ttattcactc tgtaaataca tttaaagttt ttgtgatgta agcttaattg 780

  atattctgtt cagaacttty tttagwctaa araaagttct gaacagaata tcaattaagc 840

  ttacattgat attctgttca gaactttctt tagctagaaa na 882

  <210> SEQ ID NO 134

  <211> LENGTH: 1032

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (5)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (593)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 134

  ggcanaggga accaccttct gtagaacatt caaccaggcc cagatccaga aggcttgagg 60

  ccctgtggtc cccatccttg gggagaagtc agctccagca ccmatgaagg gcatcctcgt 120

  tgctggtatc actgcagtgc ttgttgcagc tgtagaatyt ytgagctgcg tgcagtgtaa 180

  ttcatgggaa aaatcctgtg tcaacagcat tgcctctgaa tgtccctcac atgccaacac 240

  cagctgtatc agctcctcag ccagctcctc tctagagaca ccagtcagat tataccagaa 300

  tatgttctgc tcagcggaga actgcagtga ggagacacac attacagcct tcactgtcca 360

  cgtgtctgct gaagaacact ttcattttgt aagccagtgc tgccaaggaa aggaatgcag 420

  caacaccagc gatgccctgg accctccccc tgaagaacgt gtccagcaac gcagagtgcc 480

  ctgcttgtta tgaatctaat ggaactttcc tgtcatggga agccctggaa atgctatgaa 540

  gaagaacagt gtgtccttcy tagttgcaga acttaagaat gacattgagt ctnaagagtc 600

  tcgtgctgaa aggctgttcc caacgtcagt aacgccacct gtcagttcct gtctggtgaa 660

  aacaagactc ttggaggagt catctttcga aagtttgagt gtgcaaatgt aaacagctta 720

  acccccacgt ctgcaccaac cacttcccac aacgtgggct ccaaagcttc cctctacctc 780

  ttggcccttg ccagcctcct tcttcgggga ctgctgccct gaggtcctgg ggctgcactt 840

  tgcccagcac cccatttctg cttctctgag gtccagagca tcccctgcgg tgctgacacc 900

  ctctttccct gctctgcccc gtttaactgc ccagtaagtg ggagtcacag gtctccaggc 960

  aatgccgaca gctgccttgt tcttcattat taaagcactg gttcattcac tgaaaaaaaa 1020

  aaaaaaaaaa aa 1032

  <210> SEQ ID NO 135

  <211> LENGTH: 1766

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 135

  gtkattcaaa gccatcacaa aacactataa gactgaccaa aatttagata acctttgaac 60

  cacgattttt ttccacatct gtctgtgaga cacagcgcaa tgctactgcc cttccagaaa 120

  ctgtgctaaa aagagaaagt ccaaaagact ctaaacaaaa acctcgacgc cgttgaggat 180

  gtgtttcatt ctggtggtct gttttgcaag cttgataaca gaatgtccgt gccattgtaa 240

  atgttgtaga gatgtgggcc gtggcccaac cgtcctatat gagatgtagc atggtacaga 300

  acaaactgct tacacaggtc tcactagtta gaaacctgtg ggccatggag gtcagacatc 360

  catcttgtcc atctataggc aagaagtgtt tccagatcct ttggaaaggt gggcatgggg 420

  caggtgcttg gagagtggcg tttgagccag agcgacccca tttcccgtgt gaaccatagg 480

  cacaacccag gaagtttccc cacttgtagg agtgtgggta ttccagagca agactgtggc 540

  caccatcttc ccctcttggt gttttccgaa agtgacagtg ttggtcatcc catgaccact 600

  gaagcttagt aaccagcgcc aaaaagtaga ttcatcaaac tagagacccc agctcccctt 660

  ctcgccatct tctttctcaa gttgaccgtg gtgctgtttc tggaaggcat ctgcaactcc 720

  aagtccatgc agaactctgg aaggccaagt tcatcgcagc atgttcacca tatcccagcc 780

  tccaaatcta tcctcctacc ttccaacgca tgacctgttg gggagcagag acttaacccc 840

  caactcagag gaacccttcc tccagcgtct ttggcatggt ttctagggtg agagttccca 900

  atttggatag aacggccacc atattggtta ctgaatctct ctcccttgtt tttattacgt 960

  ttcctttttc aaactgtcca tgggaaggct gaattgagtg actccccaga atgaagatga 1020

  gaaggtgaat ataatcaatg ccaatgtaat gccagcgggg tgagatgccc gatggagrtt 1080

  tcaaagatgt agctagcatt ttgaaaccat atgggcaaaa cccggcaacc agaaggggac 1140

  agataaggac cgttccagaa atcccaactc tcacacccag cccaggctgc agtctccaca 1200

  ccaaacagtc aacaaaacac aaaccctgaa ggaaaacctt ttccatacac ccaggctatg 1260

  cattgaagag ttttccactg tatacatttt tatccagatg aaggtatttt tatattttga 1320

  caataggaaa cagtgaccat tttcagagta atcaaatctg gaacaaatga aacatctttt 1380

  agccaccacc accctgttgc aattaagaca accgtggggg aacacaccac tttttactgt 1440

  tgaaaccaac acaacgttga aatccaggct tatacgcaga ctccgattcc ctagagaact 1500

  aaatttggct ttagtgtgac gggatttgat taagcactta gtatagtctt ttgaacacgg 1560

  aaatcctgtt gtacttaaag ctagcggacc cgtgaacaac tttgtcaggt tcacgtccta 1620

  taacggttma aaracacaca cacacataca caaaccgttt ctatgagaga ttgatgaact 1680

  ttgtttaaaa ttttaaaaaa aggaacacgt tctgtaaacg agtcgctaaa tacagaattg 1740

  tataataaaa aaaaaaaaaa aaaawt 1766

  <210> SEQ ID NO 136

  <211> LENGTH: 470

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (315)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 136

  ccgccgccgc cgctacagcg accctgaccg ccgtccgagc cgccagacac ccagagagac 60

  gccagaggcc gcggaggggc gaagacccgg agtaactctc ccttccaccc caacccggat 120

  cgccagccct cgagagctct gtgctccacg ccgaggatgc accgtctctg gattggtccg 180

  gccttcttcc taatgacatc gctcagcgtc tctggagccg tcatcccgcg gaatgggggc 240

  ccagggggtg tcagytcggg gccttgcctc ttgcagctac tctgtggtca ggccgggtcc 300

  tccaccatca ggaanatccc atcctgagct ctgtctcctg cccctcctgc tgtgggatgc 360

  tgagcacaga gcccacagcc catctgcctc ttcacctccc tgaatccgtg tccatctgca 420

  ataaacgaca gcctcggctg cctcgtgctg aaaaaaaaaa aaaaaaaaaa 470

  <210> SEQ ID NO 137

  <211> LENGTH: 1168

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (1163)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 137

  ctggatctat agactcttct tgccctaaag aatggcatgt ttgcactcct tcccccaaca 60

  tgtacagatg cctgtcactc ttggtgactt tgctgggctt ctagtccctg cagatgttta 120

  agggagcaat gaatggggag tgtggatgca aactacggcc tccttggcac tgtttcagat 180

  gggggatttc ccttctctag gagaacctgt gctggaaaag gtgtggcacc cacactgaaa 240

  tggggcaagc tcttcccagc tttgtggggg cccttggaaa acatccactg agatggaggc 300

  agtcttcttc ctcttcttcc tcctgctcct cttgacctgg accagcaaga tagcaccaat 360

  ccttttctcc tgatggcagt atctgaatga ctttcacagc tgaaggccag agaccagcct 420

  acagctggga ttcaggcttc aaagctttgg tgaggatgac tccagaacca ggcaggtagt 480

  ccccctccag gatgccatgg cctaaagcat ttcactcctc agtcactagg ctgtgaactc 540

  attgtggctg acacttttat tcgctgctat gttttttagc aatgcccggc acacagacct 600

  gcttactatg cttttgctga gtgagtgaag ggataagtcc ctttctgcct ttttgatact 660

  cactttggtg ccccttgagg tcacagagac ctggatttga cttctggctc tgccacacaa 720

  gagcacggat gctttgggtc agttacttca gctctgagag gctcaattgc ctcacctgtg 780

  aaatgggtta gtgattccag gaatcttacc aggccccatg gacagcatgt acataaagag 840

  cctagccctt ccctctcctc cctctccagg ggccaggcct gactcccctg aagccatttc 900

  cttaccattt tgatccctaa gcctgttatc agatcttctt tctgatctac caccatggct 960

  caaatcttgc ccttcatcct tgcctttctc aaagacaaaa acacccttcc tctgctccac 1020

  tcagagtgta gcggggaggc ttatactgca gtggttaaga gcatatccct ggaattggaa 1080

  ggaacagggt ctaagattat gtagatatag cacaaagcct tgctcctgct cgtgccgaat 1140

  tcgatatcaa gcttatcgat acngtcga 1168

  <210> SEQ ID NO 138

  <211> LENGTH: 1294

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 138

  gatcttgtcc aagcagtcgg ggctacttcc aagaatgtca gctcctgtta gcaaccagtg 60

  gagtctggcc ttgggctcta agttgacctc tctatagctc caaatcctac caatctcaga 120

  aaactgtaag aggcacagat gactccacca gctgcagagt gactctgaag agagtcttca 180

  cttactgcac aggcaaagaa aggcacagga atatttccta cctctggcac gaggtgagtc 240

  ccacctcccc ccacccccat ctccaggagg caggtagagc agttctgacc gagaggatag 300

  actgctgttg ctgtctttcc ccagctctga actagtttta aggtagctta ggatgaaaaa 360

  tggagaatga ttgggggttc caaaccactt tcttctccct tggcttatat ctcttcacca 420

  tttggtggtc aactgtgggc ctaccctgga cctcatctac tcagcgagaa ttggacatga 480

  agctagaggc agctgccttg gaagggaart tcaggctcac ttggacagcc caggccatgg 540

  caggaagaat cccttcctct tggggtcctt gatgggcatg tgtgatgggg aaggagcagt 600

  ctcccagccc tgggtctgct ccccacatct ctcctaattc cacttcacct tttgccaccc 660

  cctccccacc agaggcctag cccttttgtc accgaaggcc cccagagtgt ttctgtgtga 720

  aaccctctca tttacactgt ggcmwcaaaa atccacaaaa gatggattaa ttgcactctg 780

  gttaatagca gcagcacaat gattaaaatc tatattccta tcttctctag caccctggtg 840

  tggggatggg gcggaagggt gtcttgaggg gcagggagga ccccataaaa caatccctcc 900

  tgcattctca ggctaaatag ggcccccagt gactacctgt tcttggctgt cccctctgaa 960

  gagctctgcc ttctcacagc caccaccagt tgccccactc ccaggaaaac agcacatgtt 1020

  cttcttctcc tgccttgaga ctgcgtgtta gtcttccatt cataactcat cagcagctca 1080

  gtccttctta tgtctagtct cagttcattc agccaaagct catttttgtc ctatccaaag 1140

  tagaaagggt tcttttagaa aacttgaaga atgtgcctcc tcttagcatc tgtttctgac 1200

  tcccagttat ttttaaaata aatgatgaat aaaatgcctg ccctgaaggg ttctggagga 1260

  aaaaaaaaaa aaaaaaaaaa aaaaaaaact cgta 1294

  <210> SEQ ID NO 139

  <211> LENGTH: 1720

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 139

  aaccagaagt ggacgtgcat gacagtggac ctagaggctg acaaacagga ctacccgcag 60

  ccctcggacc tgtccacctt tgtaaacgag accaaattca gttcacccac tgaggagttg 120

  gattacagaa actcctatga aattgaatat atggagaaaa ttggctcctc cttacctcag 180

  gacgacgatg ccccgaagaa gcaggccttg taccttatgt ttgacacttc tcaggagagc 240

  cctgtcaagt catctcccgt ccgcatgtca gagtccccga cgccgtgttc agggtcaagt 300

  tttgaagaga ctgaagccct tgtgaacact gctgcgaaaa accagcatcc tgtcccacga 360

  ggactggccc ctacccaaga gtcacacttg caggtgccag agaaatcctc ccagaaggag 420

  ctggaggcca tgggcttggg caccccttca gaagcgattg aaattagaga ggctgctcac 480

  ccaacagacg tctccatctc caaaacagcc ttgtwctccc gcatcaggac cactgaggtg 540

  gagaaacctg caggccttct gttccagcag cccgaacttg gactctgccc tccagatcgc 600

  cagagcagag atcataacca aggasagaga ggtctcagaa tggaaagata aatatgaaga 660

  aagcaggcgg gaagtgatgg aaatgaggaa aatcagtggc cgagtatgag aagaccatcg 720

  ctcagatgat agaggacgaa cagagagaga agtcagtctc ccaccagacg gtgcagcagc 780

  tggttctgga gaaggagcaa gccctggccg acctgaactc cgtggagaag tctctggccg 840

  acctcttcag aagatatgag aagatgaagg aggtcctaga aggcttccgc aagaatgaag 900

  aggtgttgaa gagatgtgcg caggagtacc tgtcccgggt gaagaaggag gagcagaggt 960

  accaggccct gaaggtgcac gcggaggaga aactggacag ggccaatgct gagattgctc 1020

  aggttcgagg caaggcccag caggagcaag ccgcccacca ggccagcctg cggaaggagc 1080

  agctgcgagt ggagcgccct ggaaaggacg ctggagcaga agaataaaga aatagaagaa 1140

  ctcaccaaga tttgtgacga actgattgcc aaaatgggga aaagctaact ctgaaccgaa 1200

  tgttttggac ttaactgttg cgtgcaatat gaccgtcggc acactgctgt tcctccagtt 1260

  ccatggacag gttctgtttt cacttttttg tatgcactac tgtatttcct ttctaaataa 1320

  aattgatttg attgtatgca gtactaagga gactatcaga atttcttgct attggtttgc 1380

  attttcctag tataattcat agcaagttga cctcagagtt cctgtatcag ggagattgtc 1440

  tgattctcta ataaaagaca cattgctgac cttggccttg ccctttgtac acaagttccc 1500

  cagggtgagc agcttttgga tttaatatga acatgtacag cgtgcatagg gactcttgcc 1560

  ttaaggagtg taaacttgat ctgcatttgc tgatttgttt ttaaaaaaac aagaaatgca 1620

  tgtttcaaat aaaattctct attgtaaata aaattttttc tttggatctt ggcaaaaaaa 1680

  aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaattc 1720

  <210> SEQ ID NO 140

  <211> LENGTH: 774

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (697)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (709)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (716)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (733)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 140

  cggcacgagt tttgggatgc ctcttactct gccaagccgc ttagcgggag ggaacgtgtt 60

  cctgatcatc tttaccccag gcttctgtcc ggggcgtgtc aatgtagaaa tcccccagcg 120

  aatgttggat gaatgaatga agttgaagag agggtaggcg gggaacgagg atgaggggga 180

  cggctggaga agaggtatgg gaggttcgat gtttcaggga tggcacccaa ggggggacat 240

  tcgaggcagc accggtagca cttcctttgc gatgaggggc gtctctttgg acttcttgga 300

  aaagaggtgg gcattggaaa ccagggtctg ggaacaaacc gtggtttgga cataacattt 360

  gttaccttca cttttctggg agttggagaa gtagaggagg aagttcagac aatttcataa 420

  gtgtctaaaa agagacagtt atgcgaccat tgacgaggag taaaagtcgt ctattgagca 480

  tcttattcac tacaaataga agaaagaaat accagtttcc tgacaagccc caccccatgc 540

  ttggccagtt cctgagtaca cttaatatat tttaggtact gtcatcaaac tcaaagctcg 600

  ctgtcagcct caaaggtctg aaccctagta tagattcttg tagcttgctt gaagttacag 660

  tgggtcatga tcaggaattg atgctttgtt tttgttntga aacggagtnt cgccantgca 720

  ctccagcctg ggngacagag cccgagactc cttctcaaaa aaaaaaaaaa aaaa 774

  <210> SEQ ID NO 141

  <211> LENGTH: 1566

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (415)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (718)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1116)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1122)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1127)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1312)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1373)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1455)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1456)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (1540)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 141

  ggcacgagac tatcctcaag gagcttacat atcagtaaat aaattattaa aggtggaaaa 60

  tgtggtaaaa gagacataat gtctcggaga gagaacaaat ttctgcttta ggagtgttct 120

  tagttaaggt aacattagct tctataatac gcacactccc aaatctcagt atttcaacat 180

  gagtttctct cttgctcatg taaagactgg tcagggaccc aggttgacag aggctcttca 240

  gtacatagct tccaagattg ctgtgggtgt gacatccagc cagaaatctg gtgaagagag 300

  agcaatgatt acacaggaac ttttaatgga ccaggcctgg gacagcgtat gtcacttcca 360

  ccaacatccc actcaccaga atttggtcac agggccatag ctatctgcag agaangctgg 420

  gaaatggaac ttagctatgt gctcaagagg aaaagtaaaa cagttattga ataattagta 480

  ataattagca agtaactacc taggggtcac agaggacctc tcaggtagaa tttagactta 540

  aagatgatgg gggagtgtgt ggaagatggg tgcagaatag ggaaaggggg gattgaagga 600

  agaacaagct ctagcttcac ctgcatgggt agagcccaca gtgttggtag ggacatgtta 660

  gctttcaaca tcagcttctt aacagtatta ttctttcatc ggaggaaatt agtctatntc 720

  tgaggaaaaa aaaatctgca atacgtagca atttacttac ttggatattg aatgttaaag 780

  cagagagaga ctttgtcctc aaaaccctcc catttcagaa gtgaggagcc tggggaggtc 840

  atgctctctg gatgtcacac agtgagtcac tgtcaaagcc agaatagaac ccagacctct 900

  cagtttccca ttccagtgct ctttctatga ggaaagtata agtttgagca tttttaaacc 960

  ttaattatgt agaaataacc atgatatttt atcgtaaatt atttcagtca tctcatttta 1020

  aattttactc caaactaaag gaaaacggta ctgatttaaa acatctatca taattcaata 1080

  tagcccatat ttcttcttta ggaaaaattt tttttngttt tntatcntga agacccgtgc 1140

  cctcttcctg tgtctcatgt agacatttca cagtccaaat atacagagca agaatagatg 1200

  aaatcaacat gtttaccatt attctatcta aattttcaaa gaaaaaggga acaaaaggtg 1260

  agtgatgact gagttgcatg gctataattg agtttttgtt gcttttattt tnataatatt 1320

  ttaattgaca tagatgctta aatgtatatc aaaatgcatg tcacagctct tgnacaaaga 1380

  taaatttgac tctagagcac attttcttta gtgagaatga taaattatct cagagcttgt 1440

  gattctctac ttttnnaaat cataaggtca gttctttaat taaaagataa agaaaagtag 1500

  gcattgtcca tgtagtgaaa tcacttttat caggataatn tagtaaccaa aaaaaaaaaa 1560

  aaaaaa 1566

  <210> SEQ ID NO 142

  <211> LENGTH: 1384

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 142

  tcgacccacg cgtccggccg gactaaccag ctcctccagg cgctgggggc gggtgtggca 60

  ggaggaagcc cgatcagccc caggctgtgg atgtgggaga agggcgagct cagggggcca 120

  tcatggggtt cccccagagg caacctggcc tatcagggct gctcctcctc gtgtgggcac 180

  tggcctggcc cctgccttgt atgagcttgg agctgatccc ctacacacca cagataacag 240

  cttgggacct agaagggaag gtcacagcca ccacgttctc cctggagcag cctcgctgtg 300

  tcctggacgg gcttgmcggc gttgccagca ccatctggct ggtggtggcc ttcagcaacg 360

  cctccagaga cttccagaac ccacagacgc gagctgagat cccagccttc ccacggctgc 420

  tgacggaggg gcactatatg acactgcccc tgtccctgga ccagctgccc tgtcaggacc 480

  ccgcaggcgg cggcagggac gtccccttgc tgcgggtggg caatgacccc ggctgccttg 540

  ctgacctcct ccagccgccc tactgcaaca gccccctccc cagccccgga ccttacaggg 600

  tgaagttcct cctgatggac gccaggggct caccccaggc cgagaccagg tggtccgacc 660

  ccatcgctct tcaccaaggg aagtcgccag cctccatcga cacgtggcca gggcgamgca 720

  gtggtggtat gatcgtcatc acctctatcc tctcctccct ggccagcctc ctgctcctgg 780

  ccttcctggc agcgtccacc scacgcttct ccagcctgtg gtggccggag gargccccgg 840

  agcagctgag aattggctcc ttcatgggga agcgctacat gacccaccac atcccaccca 900

  gcgaagccgc caccctgccc gtgggctgtg agcctggcyt ggaccccytc cccagcctca 960

  gcccctagcc tggcccttgt ggctggggcg tgtgtggctg tggccagtgt gggggcaagg 1020

  acgtggtagt tattcccagc ccctgcaccc tcctcctcac ccctgccama gtcccactga 1080

  tgtaggacag atgtcagggt tctagacgtc tttggtgcaa aaagggggtt ttattcaagc 1140

  acagggacag gacccatggg cagggagagc ggcaccgggg tggtgaggag tggcccgtta 1200

  tatatacttt cgagttggga gggcttagag agagcgtaag tctctaagga attttggaag 1260

  caaggtctcc agggtcctga gggggctagc tgttgttagg aaaaggtcat ttattactgt 1320

  ttagtaaaaa ctttcacgag aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaagggc 1380

  ggcc 1384

  <210> SEQ ID NO 143

  <211> LENGTH: 537

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (429)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (502)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (520)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 143

  gccccccaaa aagaaaggta attaattata gttcatttcg ttttaactaa gagttactaa 60

  agcatccctg gatgctgaga ggtactctct aggaggcaga aacaggacca agcactgccc 120

  acttatctcc acactatgct accaattcac ctgcagtggg catgtgcttt caggagtttt 180

  ttgcttggta tagacagttc tatgttcgtc ttgtttcagc accctcgttt gaaggacaca 240

  aagagctcta gggtcataga accaactctc actaactgac acagatatca ggatccaacc 300

  catgcccaca gtattacccc aagtctctaa ctagctggtg taaccaataa tggaaagaaa 360

  aaaagtaata ttctgttctt caacttcaac agagaataat agtgaaagaa tggtgatatt 420

  tttcctaana tggactaaca agtatcctga gttgggaggt gacttccaat agtaaacaat 480

  aaaataactg agaaaatgga gngaggaggg aggggagagn gagagtgggc acagaag 537

  <210> SEQ ID NO 144

  <211> LENGTH: 680

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 144

  aattttttgt attttttagt agagacaggg tttcaccatg ttagccagga tggtctcgat 60

  ctcctgacct cgtgatccac ctgccttggg ctcccaaagt gctgggatta caggcgtgag 120

  cmaccacacc cggccaatca tattttttct tgttactaat tagaatcatg attctcctgg 180

  cattcttcat tttgttatac ctcacttcct tttccttagc aagatctttg ccatagagta 240

  tggaaaccag gttccttgcc agttaatctg tattgtgctt tgtcatgtat tgttactaaa 300

  cagctcaaga tcaaggggaa gaaatgtata tgaggctcag ttcatgttca gttttttttt 360

  tttcagcatt gcaacattgc cactcatcat catgagtgta gccctgtgtc aggtactgaa 420

  ggtaatggaa aaggtatata aggttgatcc ctgtactctt gttgggaact tgagtggtat 480

  gaatagagaa ggtgagttct tggggacaga ggctacagtt tagcaagctt tcctatgcgg 540

  accttggtaa tttctttaca ttttatagac caaagaacaa tcttaacttg cccttttttc 600

  taaaggcatt gtttaaaaac tgtcatcaaa tcattgcagt ttatggcaaa tggccttttt 660

  ttaaaaaaaa aaaaaaaaaa 680

  <210> SEQ ID NO 145

  <211> LENGTH: 1048

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (79)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (117)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (138)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (144)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (147)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (625)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 145

  ggcacgagag aaagtgggcc cttaccaggc accaaatctg ccagcactct gatcttggac 60

  ttccagcctc ctgaactgnt gtctgcattc aaaagaacat tctattaaag ctacctnaat 120

  ttggcgctta tttttctnaa tcangtntct gacaatcata ttgtgtggaa tggttgctgc 180

  tttaagtgca ataagagcta actgccatca agagccatca gtatgttctt caagctgcat 240

  gcccagaaag ctggattggt tttcaaagaa agtgtttcta tttttctgat gacaccaaga 300

  actggacatc aagtcagagg ttttgtgact cacaagatgc tgatcttgct caggttgaaa 360

  gcttccagga actggtaaga aaatagttct ggccagaatc aaagattcag ccctacaagg 420

  atatgttttc ctgtgaaatt atctaagaga atttcctgtt gagatataaa ggcccatctg 480

  atcactggat tgggctgagc agagaacaag gccaaccatg gaaatggata aatggtactg 540

  aatggacaag acagttagtc atgaaagaag atggtgccaa cttgtatgtt gcaaaggttt 600

  cacaagttcc tcgaatgaat ccaanactgt catgggtctt actctgttac ccaggctgga 660

  gtgcagtart taccatcgtg gctcactgca gccttgactt ccctggctcc aagtgagcct 720

  cccatctcag gctcctgagt agctgggact acaggtttcc tatcctggga gcaggagagt 780

  gtgcctattt gaatgacaaa ggtgccagta gtgccaggca ctacacagag aggaagtgga 840

  tttgttccaa atcagatata catgtctaga tgttacagca aagccccaac taatctttag 900

  aagcatattg gaactgataa ctccatttta aaatgagcaa agaatttatt tcttatacca 960

  acaggtatat gaaaatatgc tcaatatcac taataactgg gaaaatacaa atcaaaatca 1020

  tagtaaaata aaaaaaaaaa aaaaaaaa 1048

  <210> SEQ ID NO 146

  <211> LENGTH: 930

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 146

  tcgagttttt tttttttttt ttttggatat ggagtctcac tctgttgccc aggctggagt 60

  gctgtggtac gatttcagct caatgcaagc tctgcctcct gggtttaagc aattctcctg 120

  cctcagcctc cccagtaggt gggactacgg gtgtgcaaca caacatccgg ctaatttttg 180

  tatttttcgt agagacaggg tttcacatgt tggccaggct ggtcttaaac tcctgacctc 240

  agttgatcca cctgcctggg cctcccaaag tgctgggatt acaggcaaaa gccactgtgc 300

  ccagctgcat tgttgctgtt ttttattgtt agttaagaga gaccaaccat tagaaaaatg 360

  tttaaggctt ttcaaaggaa gaatcctatg taggcagccc cactacaggt tactttctga 420

  tgaatgtcca ggactattac aaaatccatg attgtggaaa ttctgtcaaa agagatgaca 480

  gagaaatctt gcctttggtc acaatcctgt ctgaccccaa caaaagctaa ggaaatccta 540

  atcaggtgtg actcatgata aagaaaaaca tgcatccaaa ttttggttca gaagtacaga 600

  aagtgtgcaa cttctgtcaa gttaattaat gtatttgctc cataactccc cgacatataa 660

  ggtaagttgg ttggagtatg tggtttgaag gctgctttca aagatttaac gtctttgatt 720

  tttttagtca ccatgggtgc caggatagaa taagatctgg agactttcga ataactgctt 780

  acagatgtag ataattataa attgatacta ataaagaatg aagatctcag cattccccag 840

  agagggctat ttttagaaaa aggaaatagc caaaaacaaa gtaaaacaaa aaacatcatg 900

  ggatatcagg acttagctcg tgccgaattc 930

  <210> SEQ ID NO 147

  <211> LENGTH: 830

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 147

  ggtcgaccca cgcgtccgct gaaaggaaaa gcactgtttg gagaatgatc cacctttcaa 60

  gattttactt attgttgata atgctcccac atgtcctctt ttttacgggt gatcttcatt 120

  cctaatatca aagtgatatt tcttcctcca ggcaccacct ctttgatcca cacaatggat 180

  caaggagtta tagcagcttt taagttctac tacctgagaa gggaggactt ttgcccagtc 240

  ccatactgca gtggaggaag acactgagaa gactctgatg aaattctgaa cagcatcaag 300

  aaccttgttt aggcttggat tatgtcgcta aggactgtag gaatggcacc tggaagaaga 360

  cacgcaagag gtttgtcaat aacttcaaag gatttgccaa ggatgaggaa gttgcaaaaa 420

  tcaagaaggc tgtggttgag atggcaaaca actttaacct gggtgtggat gtggatgaca 480

  ttgagtaatt cctagagggg gttcctgagg aattgactaa tgggttgctg ttggaactgg 540

  aataggagtg catagctgaa gaagaggtaa agaaaaagaa agtgcaggag aagggaaaaa 600

  agaactccca agaatactca cagtgatggg tttagcagaa gcttcttcag actccaacaa 660

  gctccttaag aagtctgaaa acatggaccc caaaactgaa aggttttcac taatagagag 720

  gaaagttcat ggtgcattat ctgcctacaa gcaaaaccag gattcaaaaa accctttgag 780

  ctggagcttc aaagcacaaa aaaaaaaaaa aaaaaaaaaa aagggcggcc 830

  <210> SEQ ID NO 148

  <211> LENGTH: 865

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (321)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <221> NAME/KEY: SITE

  <222> LOCATION: (409)

  <223> OTHER INFORMATION: n equals a,t,g, or c

  <400> SEQUENCE: 148

  ggtcgaccca cgcgtccgga gtagcagaaa tttgtcttct tacaagtagt ctatgagagt 60

  agatgctgat tttctaaatg taagggaata agaaaaactt catgattaac ttttttcacg 120

  tgtatttggg ctttggtggg agtaggcaag aagaatatcc gtggatttat agagtaagca 180

  aaagtatgtc aggaaaaact aggaagaata gggctgaact gtggcttgat ttcaggagag 240

  tttctgggat tcagacttga attaactgaa tgatgctgta atgtataagt gttggtatag 300

  gtgattttat gcaaagaaga ntaaacattg gcttactttt attatcgtat acggtatggg 360

  tgactactgc tgctagttca aggtctkgat tttttaaaaa tgtgtttcnt gactgtggta 420

  gctgggagcc ccaggataca gacttttggt taaataacat ctgctccact ctgccttccc 480

  gtgtgggcct ctctaaccct gggccaagca gttgagtctc tcctcggggt gcctggagtg 540

  agggtggata cagcttgggt aattcagcat ctgtacctaa aaacttactc aaagtaggct 600

  tcatgtaaag aagtcagtgg ttcttgggaa caggggtgag tgaatggagg cgaaaggtgg 660

  ggccctccac aggtcagtca ggccctcagg gtgggacaag agctgtaggg ctcttggtta 720

  taaacctgtg tggtggagac cagcaggtga gccaaactct tctttattat cagaacattt 780

  cactaataag ggatctcaag ggtcatctgg catcagcact ttaaccaata aaaaaaaaaa 840

  aaaaaaaaaa aaaaaaaggg cggcc 865

  <210> SEQ ID NO 149

  <211> LENGTH: 545

  <212> TYPE: DNA

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 149

  agccagggtt ctagtcattt aagatgyacc tgaataaaac aaagagcctt actctcctag 60

  aacttgtgtt tctacctggg gagactgtca gtaaaccatc cacaaaataa atacagcaga 120

  tgctgttaga agatgatggt gctatggtgt gctgtggaaa atagagaaag tagagggaag 180

  tgagagggat tgcgtacact aggattgtga ctttacacag aagggtcagt ggtgccattt 240

  tagcaaagat ctgagagagg taaaggaata agctttgcag aagtgtggga gacaaatgtt 300

  ccaggtacag gaaatgacca acgccaagac cctagggtgg caatgtgtct gcttkgagtt 360

  ctagagaarg ggtatattat acatcgcttt ttgtgactca ctttttggca aacattatgc 420

  tctaaaatga acctgtattt tggaatawat ckgtggttca ttaattctca tctttgtaca 480

  gtattctatt atataaatac accatgattt atttagtcaa ttaaaaaaaa aaaaaaaaaa 540

  ctcga 545

  <210> SEQ ID NO 150

  <211> LENGTH: 54

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (54)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 150

  Met Gln Leu Leu Cys Ser Pro Tyr Pro Glu Glu Lys Pro Lys Gly Ser

  1 5 10 15

  Asn Arg Asn Phe Cys Asn Trp Phe Leu Ser Glu Arg Ser Ser Cys Leu

  20 25 30

  Gln Met Leu Leu Lys Gly His Lys Lys Leu Glu Leu Glu Lys Ile Asp

  35 40 45

  Glu Ser Ala Gly Val Xaa

  50

  <210> SEQ ID NO 151

  <211> LENGTH: 46

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (46)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 151

  Met Ser Asn Leu Met Val Ala Met Ile Ala Val Ile Thr Ile Ala Val

  1 5 10 15

  Ser Ile Pro Ser Thr Arg Ala Asp Thr Glu Ile Ser Tyr Thr Tyr Trp

  20 25 30

  Ala Tyr Leu Ser Ile Leu Ala Gly Asn Asn Ala Trp Ile Xaa

  35 40 45

  <210> SEQ ID NO 152

  <211> LENGTH: 25

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (25)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 152

  Met Ile Met Glu Glu Ile Phe Leu Asn Leu Ile Lys Asn Ile Tyr Lys

  1 5 10 15

  Ser Pro Tyr Ser Gln Cys Asn Thr Xaa

  20 25

  <210> SEQ ID NO 153

  <211> LENGTH: 265

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (71)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (80)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (86)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (93)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (95)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (133)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (157)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (183)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (204)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (265)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 153

  Met Ala Thr Pro Leu Pro Pro Pro Ser Pro Arg His Leu Arg Leu Leu

  1 5 10 15

  Arg Leu Leu Leu Ser Gly Leu Val Leu Gly Ala Ala Leu Arg Gly Ala

  20 25 30

  Ala Ala Gly His Pro Glu Cys Cys Arg Leu Ser Arg Glu Pro Gly Leu

  35 40 45

  Cys Pro Glu Glu Ala Gly Lys Cys Pro Pro Gly Ala His Ala Cys Gly

  50 55 60

  Pro Ala Phe Ser Pro Ser Xaa Arg Asn Ser Lys Gly Leu Phe Cys Xaa

  65 70 75 80

  Asp Ala Pro Gly Phe Xaa Arg Gly Pro Gly Pro Thr Xaa Thr Xaa Asn

  85 90 95

  Glu Ile Asp Ser Trp Pro Lys Gly Ala Cys Pro Glu Arg Asn Leu Asp

  100 105 110

  Ile Asn Ser Ala Leu Thr Gln Gly Arg Thr Ala Val Pro Gly Ala Cys

  115 120 125

  His Leu Gly Ile Xaa Gly Thr Gly Ala Gly Ala Gly Ala Gly Leu Pro

  130 135 140

  Phe His Ser Arg Asn Pro His Ala His Ala Pro His Xaa Pro Trp Val

  145 150 155 160

  Thr Pro Val Ser Ser Asp Pro Val His Met Ser Pro Leu Glu Pro Arg

  165 170 175

  Gly Gly Gln Gly Asp Gly Xaa Ala Leu Val Leu Ile Leu Ala Phe Cys

  180 185 190

  Val Ala Gly Ala Ala Ala Leu Ser Val Ala Ser Xaa Cys Trp Cys Arg

  195 200 205

  Leu Gln Arg Glu Ile Arg Leu Thr Gln Lys Ala Glu Tyr Ala Thr Ala

  210 215 220

  Lys Ala Leu Ala Thr Pro Ala Ala Thr Pro Asp Leu Ala Trp Gly Pro

  225 230 235 240

  Ala Pro Gly Thr Glu Arg Gly Asp Val Pro Leu Pro Ala Pro Thr Ala

  245 250 255

  Thr Asp Val Val Pro Gly Ala Ala Xaa

  260 265

  <210> SEQ ID NO 154

  <211> LENGTH: 237

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (137)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (151)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 154

  Met Lys Gly Ile Leu Val Ala Gly Ile Thr Ala Val Leu Val Ala Ala

  1 5 10 15

  Val Glu Ser Leu Ser Cys Val Gln Cys Asn Ser Trp Glu Lys Ser Cys

  20 25 30

  Val Asn Ser Ile Ala Ser Glu Cys Pro Ser His Ala Asn Thr Ser Cys

  35 40 45

  Ile Ser Ser Ser Ala Ser Ser Ser Leu Glu Thr Pro Val Arg Leu Tyr

  50 55 60

  Gln Asn Met Phe Cys Ser Ala Glu Asn Cys Ser Glu Glu Thr His Ile

  65 70 75 80

  Thr Ala Phe Thr Val His Val Ser Ala Glu Glu His Phe His Phe Val

  85 90 95

  Ser Gln Cys Cys Gln Gly Lys Glu Cys Ser Asn Thr Ser Asp Ala Leu

  100 105 110

  Asp Pro Pro Leu Lys Asn Val Ser Ser Asn Ala Glu Cys Pro Ala Cys

  115 120 125

  Tyr Glu Ser Asn Gly Thr Ser Cys Xaa Gly Lys Pro Trp Lys Cys Tyr

  130 135 140

  Glu Glu Glu Gln Cys Val Xaa Leu Val Ala Glu Leu Lys Asn Asp Ile

  145 150 155 160

  Glu Ser Lys Ser Leu Val Leu Lys Gly Cys Ser Asn Val Ser Asn Ala

  165 170 175

  Thr Cys Gln Phe Leu Ser Gly Glu Asn Lys Thr Leu Gly Gly Val Ile

  180 185 190

  Phe Arg Lys Phe Glu Cys Ala Asn Val Asn Ser Leu Thr Pro Thr Ser

  195 200 205

  Ala Pro Thr Thr Ser His Asn Val Gly Ser Lys Ala Ser Leu Tyr Leu

  210 215 220

  Leu Ala Leu Ala Ser Leu Leu Leu Arg Gly Leu Leu Pro

  225 230 235

  <210> SEQ ID NO 155

  <211> LENGTH: 314

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (49)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (167)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (314)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 155

  Met Asn Gln Leu Ser Phe Leu Leu Phe Leu Ile Ala Thr Thr Arg Gly

  1 5 10 15

  Trp Ser Thr Asp Glu Ala Asn Thr Tyr Phe Lys Glu Trp Thr Cys Ser

  20 25 30

  Ser Ser Pro Ser Leu Pro Arg Ser Cys Lys Glu Ile Lys Asp Glu Cys

  35 40 45

  Xaa Ser Ala Phe Asp Gly Leu Tyr Phe Leu Arg Thr Glu Asn Gly Val

  50 55 60

  Ile Tyr Gln Thr Phe Cys Asp Met Thr Ser Gly Gly Gly Gly Trp Thr

  65 70 75 80

  Leu Val Ala Ser Val His Glu Asn Asp Met Arg Gly Lys Cys Thr Val

  85 90 95

  Gly Asp Arg Trp Ser Ser Gln Gln Gly Ser Lys Ala Asp Tyr Pro Glu

  100 105 110

  Gly Asp Gly Asn Trp Ala Asn Tyr Asn Thr Phe Gly Ser Ala Glu Ala

  115 120 125

  Ala Thr Ser Asp Asp Tyr Lys Asn Pro Gly Tyr Tyr Asp Ile Gln Ala

  130 135 140

  Lys Asp Leu Gly Ile Trp His Val Pro Asn Lys Ser Pro Met Gln His

  145 150 155 160

  Trp Arg Asn Ser Ser Leu Xaa Arg Tyr Arg Thr Asp Thr Gly Phe Leu

  165 170 175

  Gln Thr Leu Gly His Asn Leu Phe Gly Ile Tyr Gln Lys Tyr Pro Val

  180 185 190

  Lys Tyr Gly Glu Gly Lys Cys Trp Thr Asp Asn Gly Pro Val Ile Pro

  195 200 205

  Val Val Tyr Asp Phe Gly Asp Ala Gln Lys Thr Ala Ser Tyr Tyr Ser

  210 215 220

  Pro Tyr Gly Gln Arg Glu Phe Thr Ala Gly Phe Val Gln Phe Arg Val

  225 230 235 240

  Phe Asn Asn Glu Arg Ala Ala Asn Ala Leu Cys Ala Gly Met Arg Val

  245 250 255

  Thr Gly Cys Asn Thr Glu His His Cys Ile Gly Gly Gly Gly Tyr Phe

  260 265 270

  Pro Glu Ala Ser Pro Gln Gln Cys Gly Asp Phe Ser Gly Phe Asp Trp

  275 280 285

  Ser Gly Tyr Gly Thr His Val Gly Tyr Ser Ser Ser Arg Glu Ile Thr

  290 295 300

  Glu Ala Ala Val Leu Leu Phe Tyr Arg Xaa

  305 310

  <210> SEQ ID NO 156

  <211> LENGTH: 99

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (17)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (24)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (99)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 156

  Met Leu Ala Phe Pro Val Leu Leu Glu Val Ser Trp Ser Val Leu Phe

  1 5 10 15

  Xaa Phe Ser Phe Phe Ser Pro Xaa Pro Ser Ala Pro Gln Pro Pro Thr

  20 25 30

  Pro Ser Arg Ser Val Leu His Ala Arg Cys Ser Asn Val Arg Ser Glu

  35 40 45

  Met Ala Gly Thr Arg Glu Lys Leu Leu Val Ser Phe Val Ser Gly Ser

  50 55 60

  Gly Met Ala Leu Ser Ser Leu Ala Ser Leu Phe Val Leu Phe Glu Leu

  65 70 75 80

  Cys Arg Ser Leu Phe Ser Gln Ala Glu Leu Pro Thr Arg Ser Ile Leu

  85 90 95

  Asp Gln Xaa

  <210> SEQ ID NO 157

  <211> LENGTH: 37

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (8)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (19)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (28)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (37)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 157

  Met Asn Pro Phe Ser Val Phe Xaa Ser Leu Cys Leu Lys Gln Phe Glu

  1 5 10 15

  Asp Val Xaa Leu Phe Leu Gly Leu Met Phe Gly Xaa Ser Leu Asn Gly

  20 25 30

  Gln Glu Gly Thr Xaa

  35

  <210> SEQ ID NO 158

  <211> LENGTH: 23

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (23)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 158

  Met Val Ile Phe Ile Ile Leu Leu Thr Cys Phe Gly Phe Ser Asn Gly

  1 5 10 15

  Ser Phe Ser Phe Ser Leu Xaa

  20

  <210> SEQ ID NO 159

  <211> LENGTH: 96

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (30)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (35)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (64)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (83)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 159

  Met Cys Phe Ile Leu Val Val Cys Phe Ala Ser Leu Ile Thr Glu Cys

  1 5 10 15

  Pro Cys His Cys Lys Cys Cys Arg Asp Val Gly Arg Gly Xaa Thr Val

  20 25 30

  Leu Tyr Xaa Cys Ser Met Val Gln Asn Lys Leu Leu Thr Gln Val Ser

  35 40 45

  Leu Val Arg Asn Leu Trp Ala Met Glu Val Arg His Pro Ser Cys Xaa

  50 55 60

  Ser Ile Gly Lys Lys Cys Phe Gln Ile Leu Trp Lys Gly Gly His Gly

  65 70 75 80

  Ala Gly Xaa Trp Arg Val Ala Phe Glu Gln Ser Asp Pro Ile Ser Val

  85 90 95

  <210> SEQ ID NO 160

  <211> LENGTH: 66

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (66)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 160

  Met Val Glu Asn Trp Val Leu Glu Glu Ser Pro Gly Arg Leu Leu Ala

  1 5 10 15

  Leu Phe Val Val Arg Arg Ala Leu Ala Gln Gly Gln Arg Glu Glu Lys

  20 25 30

  Gly Gln Pro Ala Ala Val Glu Ser Ala Gly Trp Leu Pro Thr Arg Phe

  35 40 45

  Leu Ser Ser Gln Asp Ser Leu Pro Leu Ser Ser Arg Ile Ser Asn Gly

  50 55 60

  Leu Xaa

  65

  <210> SEQ ID NO 161

  <211> LENGTH: 222

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (86)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 161

  Met His Phe Gln Arg Gln Lys Leu Met Ala Val Thr Glu Tyr Ile Pro

  1 5 10 15

  Pro Lys Pro Ala Ile His Pro Ser Cys Leu Pro Ser Pro Pro Ser Pro

  20 25 30

  Pro Gln Glu Glu Ile Gly Leu Ile Arg Leu Leu Arg Arg Glu Ile Ala

  35 40 45

  Ala Val Phe Gln Asp Asn Arg Met Ile Ala Val Cys Gln Asn Val Ala

  50 55 60

  Leu Ser Ala Glu Asp Lys Leu Leu Met Arg His Gln Leu Arg Lys His

  65 70 75 80

  Lys Ile Leu Met Lys Xaa Phe Pro Asn Gln Val Leu Lys Pro Phe Leu

  85 90 95

  Glu Asp Ser Lys Tyr Gln Asn Leu Leu Pro Leu Phe Val Gly His Asn

  100 105 110

  Met Leu Leu Val Ser Glu Glu Pro Lys Val Lys Glu Met Val Arg Ile

  115 120 125

  Leu Arg Thr Val Pro Phe Leu Pro Leu Leu Gly Gly Cys Ile Asp Asp

  130 135 140

  Thr Ile Leu Ser Arg Gln Gly Phe Ile Asn Tyr Ser Lys Leu Pro Ser

  145 150 155 160

  Leu Pro Leu Val Gln Gly Glu Leu Val Gly Gly Leu Thr Cys Leu Thr

  165 170 175

  Ala Gln Thr His Ser Leu Leu Gln His Gln Pro Leu Gln Leu Thr Thr

  180 185 190

  Leu Leu Asp Gln Tyr Ile Arg Glu Gln Arg Glu Lys Asp Ser Val Met

  195 200 205

  Ser Ala Asn Gly Lys Pro Asp Pro Asp Thr Val Pro Asp Ser

  210 215 220

  <210> SEQ ID NO 162

  <211> LENGTH: 91

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (53)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 162

  Met Val Val Asp Gln Lys Glu Asp Leu Ile Thr Gly Leu Gly Ile Lys

  1 5 10 15

  Met Val Arg Lys Trp Leu Gln Gly Ser Gln Ala Trp Pro Leu Glu Arg

  20 25 30

  Glu Glu Arg Glu Gly Leu Gly Ser Leu Cys Thr Cys Cys Pro Trp Gly

  35 40 45

  Leu Val Arg Phe Xaa Glu Ser Leu Thr His Phe Thr Gly Glu Ala Ile

  50 55 60

  Glu Pro Leu Arg Ala Glu Val Thr Asp Pro Lys His Pro Cys Ser Cys

  65 70 75 80

  Val Ala Glu Pro Glu Val Lys Ser Arg Ser Leu

  85 90

  <210> SEQ ID NO 163

  <211> LENGTH: 74

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (51)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 163

  Met Glu Asn Asp Trp Gly Phe Gln Thr Thr Phe Phe Ser Leu Gly Leu

  1 5 10 15

  Tyr Leu Phe Thr Ile Trp Trp Ser Thr Val Gly Leu Pro Trp Thr Ser

  20 25 30

  Ser Thr Gln Arg Glu Leu Asp Met Lys Leu Glu Ala Ala Ala Leu Glu

  35 40 45

  Gly Lys Xaa Gly Ser Leu Gly Gln Pro Arg Pro Trp Gln Glu Glu Ser

  50 55 60

  Leu Pro Leu Gly Val Leu Asp Gly His Val

  65 70

  <210> SEQ ID NO 164

  <211> LENGTH: 78

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (69)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (78)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 164

  Met Thr Gly Gln Ile Pro Arg Leu Ser Lys Val Asn Leu Phe Thr Leu

  1 5 10 15

  Leu Ser Leu Trp Met Glu Leu Phe Pro Ala Glu Ala Gln Arg Gln Lys

  20 25 30

  Ser Gln Lys Asn Glu Glu Gly Lys His Gly Pro Leu Gly Asp Asn Glu

  35 40 45

  Glu Arg Thr Arg Val Ser Thr Asp Lys Arg Gln Asp Tyr Trp Glu Gln

  50 55 60

  Leu Arg Cys Leu Xaa Glu Arg Phe Thr Ile Thr Ala Gly Xaa

  65 70 75

  <210> SEQ ID NO 165

  <211> LENGTH: 38

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (38)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 165

  Met Ala Phe Leu Leu Thr Leu Val Pro Leu Leu Pro Ser Arg Cys Leu

  1 5 10 15

  Gly Leu Glu Glu Met Ala Val Pro Asn Ser Thr Cys Ile Ser Pro Phe

  20 25 30

  Ser Cys Cys Tyr Gly Xaa

  35

  <210> SEQ ID NO 166

  <211> LENGTH: 45

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (45)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 166

  Met Phe His Val Phe Val Leu Leu Leu Thr Phe Ile Ala Leu Ser Pro

  1 5 10 15

  Ser Gly Ile Arg Leu Leu Phe Gly Phe Ile Gln Lys Gly Leu Asn Leu

  20 25 30

  Asn Ser Phe Met Phe Arg Leu Glu Leu Leu His Phe Xaa

  35 40 45

  <210> SEQ ID NO 167

  <211> LENGTH: 39

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (39)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 167

  Met Thr Ser Leu Pro Ile Leu Ala Phe Gly Ala Val Tyr Trp Pro Asp

  1 5 10 15

  Leu Ala Ser His Ser Phe Ser Pro Ser Arg Ser Leu Ala Gln Thr Pro

  20 25 30

  His Met Ser Val Ser Gly Xaa

  35

  <210> SEQ ID NO 168

  <211> LENGTH: 174

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (83)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (110)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (115)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (118)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (168)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (174)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 168

  Met Gln Leu Ile Pro Leu Glu Gln Leu Cys Met Leu Leu Leu Met Ser

  1 5 10 15

  Asp Asn Val Asp Arg Cys Phe Glu Thr Cys Pro Pro Arg Thr Phe Leu

  20 25 30

  Pro Ala Leu Cys Lys Ile Phe Leu Asp Glu Ser Ala Pro Asp Asn Val

  35 40 45

  Leu Glu Val Thr Ala Arg Ala Ile Thr Tyr Tyr Leu Asp Val Ser Ala

  50 55 60

  Glu Cys Thr Arg Arg Ile Val Gly Val Asp Gly Ala Ile Lys Ala Leu

  65 70 75 80

  Cys Asn Xaa Leu Val Val Val Glu Leu Asn Asn Arg Thr Ser Arg Asp

  85 90 95

  Leu Ala Glu Gln Cys Val Lys Val Leu Glu Leu Ile Cys Xaa Pro Glu

  100 105 110

  Ser Gly Xaa Val Phe Xaa Ala Gly Gly Leu Asn Arg Val Ala Tyr Leu

  115 120 125

  Pro Ser Val Asn Ser Gly His Leu Val His Lys Asp Thr Leu His Ser

  130 135 140

  Ala Met Ala Val Val Ser Arg Leu Cys Gly Lys Met Glu Pro Gln Asp

  145 150 155 160

  Ser Ser Leu Glu Ile Cys Val Xaa Ser Leu Ser Ser Leu Xaa

  165 170

  <210> SEQ ID NO 169

  <211> LENGTH: 55

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (55)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 169

  Met Phe Glu Asp Thr Leu Arg Thr Leu Tyr Ile Leu Leu Phe Tyr Leu

  1 5 10 15

  Arg Tyr Ile Cys Leu Leu Ser Pro His Ile Ala Leu Met Thr Leu Ile

  20 25 30

  Leu Ile Asp Gly Phe Leu Gln Cys Tyr Tyr Cys Ala Leu His Val Pro

  35 40 45

  Cys Ile Ile Ala Phe Leu Xaa

  50 55

  <210> SEQ ID NO 170

  <211> LENGTH: 344

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (126)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (128)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 170

  Met Glu Lys Ile Gly Ser Ser Leu Pro Gln Asp Asp Asp Ala Pro Lys

  1 5 10 15

  Lys Gln Ala Leu Tyr Leu Met Phe Asp Thr Ser Gln Glu Ser Pro Val

  20 25 30

  Lys Ser Ser Pro Val Arg Met Ser Glu Ser Pro Thr Pro Cys Ser Gly

  35 40 45

  Ser Ser Phe Glu Glu Thr Glu Ala Leu Val Asn Thr Ala Ala Lys Asn

  50 55 60

  Gln His Pro Val Pro Arg Gly Leu Ala Pro Asn Gln Glu Ser His Leu

  65 70 75 80

  Gln Val Pro Glu Lys Ser Ser Gln Lys Glu Leu Glu Ala Met Gly Leu

  85 90 95

  Gly Thr Pro Ser Glu Ala Ile Glu Ile Arg Glu Ala Ala His Pro Thr

  100 105 110

  Asp Val Ser Ile Ser Lys Thr Ala Leu Tyr Ser Arg Ile Xaa Thr Xaa

  115 120 125

  Glu Val Glu Lys Pro Ala Gly Leu Leu Phe Gln Gln Pro Asp Leu Asp

  130 135 140

  Ser Ala Leu Gln Ile Ala Arg Ala Glu Ile Ile Thr Lys Glu Arg Glu

  145 150 155 160

  Val Ser Glu Trp Lys Asp Lys Tyr Glu Glu Ser Arg Arg Glu Val Met

  165 170 175

  Glu Met Arg Lys Ile Val Ala Glu Tyr Glu Lys Thr Ile Ala Gln Met

  180 185 190

  Ile Glu Asp Glu Gln Arg Glu Lys Ser Val Ser His Gln Thr Val Gln

  195 200 205

  Gln Leu Val Leu Glu Lys Glu Gln Ala Leu Ala Asp Leu Asn Ser Val

  210 215 220

  Glu Lys Ser Leu Ala Asp Leu Phe Arg Arg Tyr Glu Lys Met Lys Glu

  225 230 235 240

  Val Leu Glu Gly Phe Arg Lys Asn Glu Glu Val Leu Lys Arg Cys Ala

  245 250 255

  Gln Glu Tyr Leu Ser Arg Val Lys Lys Glu Glu Gln Arg Tyr Gln Ala

  260 265 270

  Leu Lys Val His Ala Glu Glu Lys Leu Asp Arg Ala Asn Ala Glu Ile

  275 280 285

  Ala Gln Val Arg Gly Lys Ala Gln Gln Glu Gln Ala Ala His Gln Ala

  290 295 300

  Ser Leu Arg Lys Glu Gln Leu Arg Val Asp Ala Leu Glu Arg Thr Leu

  305 310 315 320

  Glu Gln Lys Asn Lys Glu Ile Glu Glu Leu Thr Lys Ile Cys Asp Glu

  325 330 335

  Leu Ile Ala Lys Met Gly Lys Ser

  340

  <210> SEQ ID NO 171

  <211> LENGTH: 90

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (90)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 171

  Met Tyr His Tyr Ala Trp Leu Ile Phe Val Phe Leu Val Glu Met Gly

  1 5 10 15

  Phe Cys His Val Gly Gln Ala Gly Leu Lys Leu Leu Thr Ser Ser Asp

  20 25 30

  Pro Pro Ala Ser Ala Ser Gln Ser Ala Gly Ile Thr Gly Val Ser His

  35 40 45

  His Ala Trp Gly Lys Arg Tyr Phe Gln Asn Ile Val Asn Asn Phe Ser

  50 55 60

  Pro Lys Pro Arg Gln Gly Leu Ile Leu Leu Pro Arg Leu Glu Trp Gln

  65 70 75 80

  Gly His His Arg Ser Ser Leu Gln Pro Xaa

  85 90

  <210> SEQ ID NO 172

  <211> LENGTH: 104

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 172

  Met Leu Cys Pro Asn His Gly Leu Phe Pro Asp Pro Gly Phe Gln Cys

  1 5 10 15

  Pro Pro Leu Phe Gln Glu Val Gln Arg Asp Ala Pro His Arg Lys Gly

  20 25 30

  Ser Ala Thr Val Leu Pro Arg Cys Pro Pro Trp Val Pro Ser Leu Lys

  35 40 45

  His Arg Thr Ser His Thr Ser Ser Pro Ala Val Pro Leu Ile Leu Val

  50 55 60

  Pro Arg Leu Pro Ser Leu Gln Leu His Ser Phe Ile Gln His Ser Leu

  65 70 75 80

  Gly Asp Phe Tyr Ile Asp Thr Pro Arg Thr Glu Ala Trp Gly Lys Asp

  85 90 95

  Asp Gln Glu His Val Pro Ser Arg

  100

  <210> SEQ ID NO 173

  <211> LENGTH: 42

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (42)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 173

  Met Ser Val Leu Phe Val Ala Val Ser Leu Leu Ser Ser Ile Val Pro

  1 5 10 15

  Asp Ile Gln Tyr Arg Leu Lys Thr Tyr Leu His Ile Asp Leu Trp Lys

  20 25 30

  Thr Asp Thr Gln Val Leu Lys Asn Lys Xaa

  35 40

  <210> SEQ ID NO 174

  <211> LENGTH: 47

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (47)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 174

  Met Met Leu Gly Leu Phe Ser Pro Leu Cys Leu Val Thr Gly Ile Ala

  1 5 10 15

  Glu Gly Arg Ala Glu Asp Ala Ser Leu His Asp Ile Cys Thr Thr Gln

  20 25 30

  His Thr Leu Thr Phe Thr Pro Ser Tyr Pro Val Gly Gly Ser Xaa

  35 40 45

  <210> SEQ ID NO 175

  <211> LENGTH: 73

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (44)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (69)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 175

  Met Ser Phe Ser Leu Ala His Val Lys Thr Gly Gln Gly Pro Arg Leu

  1 5 10 15

  Thr Glu Ala Leu Gln Tyr Ile Ala Ser Lys Ile Ala Val Gly Val Thr

  20 25 30

  Ser Ser Gln Lys Ser Gly Glu Glu Arg Ala Met Xaa Thr Gln Glu Leu

  35 40 45

  Leu Met Asp Gln Ala Trp Asp Ser Val Cys His Phe His Gln His Pro

  50 55 60

  Thr His Gln Asn Xaa Val Thr Gly Pro

  65 70

  <210> SEQ ID NO 176

  <211> LENGTH: 29

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (29)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 176

  Met Leu Ser Leu Asp Phe Pro Leu Ile Leu Leu Gly Leu Asn Leu His

  1 5 10 15

  Ile Ala Leu Leu Ser Leu Leu Val Pro Arg Leu Ser Xaa

  20 25

  <210> SEQ ID NO 177

  <211> LENGTH: 67

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 177

  Met Ile Phe Arg Asn Gly Val Arg Leu Val Phe Val Phe Val Leu Phe

  1 5 10 15

  Tyr Thr Ser Thr Gln Ser Leu Phe Asn Ser Leu Gln Thr Ala Glu Tyr

  20 25 30

  Val Leu Phe Cys Gln Gln Arg Leu Ser Leu Tyr Glu Pro Ser His Val

  35 40 45

  Leu Cys Leu Cys Met Ser Pro His Arg Lys His Thr Arg Glu Ser Asp

  50 55 60

  Thr Ser Gly

  65

  <210> SEQ ID NO 178

  <211> LENGTH: 24

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (24)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 178

  Met Asn Phe Leu Leu Leu Ile Phe Pro Tyr Phe Ser Ser Leu Leu Gly

  1 5 10 15

  Glu Val Glu Val Val Lys Cys Xaa

  20

  <210> SEQ ID NO 179

  <211> LENGTH: 31

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (31)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 179

  Met Ser Pro Gly Arg Val Ser Val Val Ser Leu Gln Gly Ser Gln Leu

  1 5 10 15

  Cys Leu Leu Val Ser Ile Ala Ile Met Gly Leu Leu Leu Phe Xaa

  20 25 30

  <210> SEQ ID NO 180

  <211> LENGTH: 11

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (11)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 180

  Met Ala Tyr Ala Phe His Arg Thr Ser Thr Xaa

  1 5 10

  <210> SEQ ID NO 181

  <211> LENGTH: 32

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (32)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 181

  Met Ser Val Lys Val Gly Ser Leu Leu Val Leu Val Tyr Phe Thr Leu

  1 5 10 15

  Gly Pro Val Val Ala Glu Leu Glu Val Thr Leu Pro Ser His Ser Xaa

  20 25 30

  <210> SEQ ID NO 182

  <211> LENGTH: 36

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (36)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 182

  Met Ile Val Ile Thr Ser Ile Leu Ser Ser Leu Ala Ser Leu Leu Leu

  1 5 10 15

  Leu Ala Phe Leu Ala Ala Ser Thr Ala Arg Leu Ser Pro Gln Ser Leu

  20 25 30

  Pro Glu Thr Xaa

  35

  <210> SEQ ID NO 183

  <211> LENGTH: 35

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (35)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 183

  Met Ser Gly Leu Glu Ser Ala Arg Val Leu Leu Cys Ala Leu Gly Ser

  1 5 10 15

  Phe Leu Leu Asn Ser Leu Leu Ser Thr Phe Arg Leu Asn Ser Ser Ala

  20 25 30

  Pro Ser Xaa

  35

  <210> SEQ ID NO 184

  <211> LENGTH: 29

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (29)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 184

  Met His Ser Ile Ile Val Lys Glu Leu Ile Val Thr Phe Phe Leu Gly

  1 5 10 15

  Ile Thr Val Leu Leu Leu Leu Met Gln Arg Ser Leu Xaa

  20 25

  <210> SEQ ID NO 185

  <211> LENGTH: 6

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (6)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 185

  Met Gly Tyr Leu Asn Xaa

  1 5

  <210> SEQ ID NO 186

  <211> LENGTH: 58

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 186

  Met Pro Phe Ala Trp Asn Asp Leu Thr Ser Leu Leu Phe Tyr Leu Ala

  1 5 10 15

  Gly Cys Phe Ser Ser Cys Arg Leu Gly Gln Gly Thr Pro Gly Ser Leu

  20 25 30

  Pro Trp Thr Ser Asn Glu Glu Gly Ile Ile Gln Gly Pro Thr Pro Met

  35 40 45

  Phe Trp Asn Leu Thr Pro Phe Ser Gly Thr

  50 55

  <210> SEQ ID NO 187

  <211> LENGTH: 406

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (273)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (406)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 187

  Met Leu Leu Leu Trp Val Ser Val Val Ala Ala Leu Ala Leu Ala Val

  1 5 10 15

  Leu Ala Pro Gly Ala Gly Glu Gln Arg Arg Arg Ala Ala Lys Ala Pro

  20 25 30

  Asn Val Val Leu Val Val Ser Asp Ser Tyr Asp Gly Arg Leu Thr Phe

  35 40 45

  His Pro Gly Ser Gln Val Val Lys Leu Pro Phe Ile Asn Phe Met Lys

  50 55 60

  Thr Arg Gly Thr Ser Phe Leu Asn Ala Tyr Thr Asn Ser Pro Ile Cys

  65 70 75 80

  Cys Pro Ser Arg Ala Ala Met Trp Ser Gly Leu Phe Thr His Leu Thr

  85 90 95

  Glu Ser Trp Asn Asn Phe Lys Gly Leu Asp Pro Asn Tyr Thr Thr Trp

  100 105 110

  Met Asp Val Met Glu Arg His Gly Tyr Arg Thr Gln Lys Phe Gly Lys

  115 120 125

  Leu Asp Tyr Thr Ser Gly His His Ser Ile Ser Asn Arg Val Glu Ala

  130 135 140

  Trp Thr Arg Asp Val Ala Phe Leu Leu Arg Gln Glu Gly Arg Pro Met

  145 150 155 160

  Val Asn Leu Ile Arg Asn Arg Thr Lys Val Arg Val Met Glu Arg Asp

  165 170 175

  Trp Gln Asn Thr Asp Lys Ala Val Asn Trp Leu Arg Lys Glu Ala Ile

  180 185 190

  Asn Tyr Thr Glu Pro Phe Val Ile Tyr Leu Gly Leu Asn Leu Pro His

  195 200 205

  Pro Tyr Pro Ser Pro Ser Ser Gly Glu Asn Phe Gly Ser Ser Thr Phe

  210 215 220

  His Thr Ser Leu Tyr Trp Leu Glu Lys Val Ser His Asp Ala Ile Lys

  225 230 235 240

  Ile Pro Lys Trp Ser Pro Leu Ser Glu Met His Pro Val Asp Tyr Tyr

  245 250 255

  Ser Ser Tyr Thr Lys Asn Cys Thr Gly Arg Phe Thr Lys Lys Glu Ile

  260 265 270

  Xaa Asn Ile Arg Ala Phe Tyr Tyr Ala Met Cys Ala Glu Thr Asp Ala

  275 280 285

  Met Leu Gly Glu Ile Ile Leu Ala Leu His Gln Leu Asp Leu Leu Gln

  290 295 300

  Lys Thr Ile Val Ile Tyr Ser Ser Asp His Gly Glu Leu Ala Met Glu

  305 310 315 320

  His Arg Gln Phe Tyr Lys Met Ser Met Tyr Glu Ala Ser Ala His Val

  325 330 335

  Pro Leu Leu Met Met Gly Pro Gly Ile Lys Ala Gly Leu Gln Val Ser

  340 345 350

  Asn Val Val Ser Leu Val Asp Ile Tyr Pro Thr Met Leu Asp Ile Ala

  355 360 365

  Gly Ile Pro Leu Pro Gln Asn Leu Ser Gly Tyr Ser Ser Leu Pro Leu

  370 375 380

  Ser Ser Glu Thr Phe Lys Asn Glu His Lys Val Lys Asn Leu His Pro

  385 390 395 400

  Pro Trp Ile Thr Glu Xaa

  405

  <210> SEQ ID NO 188

  <211> LENGTH: 37

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (37)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 188

  Met Asn Gly Leu Val Arg Pro Val Glu Leu Asn Ser Leu Leu Leu Pro

  1 5 10 15

  Val Val Arg Tyr Gln Val Ala Gln Pro Gln Lys Leu Leu Asn Val Phe

  20 25 30

  Val Gly Gly Leu Xaa

  35

  <210> SEQ ID NO 189

  <211> LENGTH: 57

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (51)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 189

  Met Lys Ala Leu Val Gly Asn Ser Pro Pro Val Gly Asp Ser Gly Thr

  1 5 10 15

  Gln Pro Pro Ser Ala Leu Arg Leu Cys Leu Leu Lys Val Leu Arg Val

  20 25 30

  Leu Ser Met Tyr Leu Ala Asn Gly Glu Arg Val Trp Arg Thr His Lys

  35 40 45

  Arg Val Xaa His His Val Leu Arg Gly

  50 55

  <210> SEQ ID NO 190

  <211> LENGTH: 128

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (127)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (128)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 190

  Met Phe Val Leu Leu Tyr Val Thr Ser Phe Ala Ile Cys Ala Ser Gly

  1 5 10 15

  Gln Pro Arg Gly Asn Gln Leu Lys Gly Glu Asn Tyr Ser Pro Arg Tyr

  20 25 30

  Ile Cys Ser Ile Pro Gly Leu Pro Gly Pro Pro Gly Pro Pro Gly Ala

  35 40 45

  Asn Gly Ser Pro Gly Pro His Gly Arg Ile Gly Leu Pro Gly Arg Asp

  50 55 60

  Gly Arg Asp Gly Arg Lys Gly Glu Lys Gly Glu Lys Gly Thr Ala Gly

  65 70 75 80

  Leu Arg Gly Lys Thr Gly Pro Leu Gly Leu Ala Gly Glu Lys Gly Asp

  85 90 95

  Gln Gly Glu Thr Gly Lys Lys Gly Pro Ile Gly Pro Glu Gly Glu Lys

  100 105 110

  Gly Glu Val Gly Pro Ile Gly Pro Pro Gly Pro Lys Gly Asp Xaa Xaa

  115 120 125

  <210> SEQ ID NO 191

  <211> LENGTH: 21

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (21)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 191

  Met Lys Phe Ile Met Leu Leu Leu Leu Pro Ser Ile Phe Pro Thr Thr

  1 5 10 15

  Val Glu Met Ile Xaa

  20

  <210> SEQ ID NO 192

  <211> LENGTH: 143

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (92)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (136)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (138)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (143)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 192

  Met Cys Ala Phe Pro Trp Leu Leu Leu Leu Leu Leu Leu Gln Glu Gly

  1 5 10 15

  Ser Gln Arg Arg Leu Trp Arg Trp Cys Gly Ser Glu Glu Val Val Ala

  20 25 30

  Val Leu Gln Glu Ser Ile Ser Leu Pro Leu Glu Ile Pro Pro Asp Glu

  35 40 45

  Glu Val Glu Asn Ile Ile Trp Ser Ser His Lys Ser Leu Ala Thr Val

  50 55 60

  Val Pro Gly Lys Glu Gly His Pro Ala Thr Ile Met Val Thr Asn Pro

  65 70 75 80

  His Tyr Gln Gly Gln Val Ser Phe Leu Asp Pro Xaa Tyr Ser Leu His

  85 90 95

  Ile Ser Asn Leu Ser Trp Glu Asp Ser Gly Leu Tyr Gln Ala Gln Val

  100 105 110

  Asn Leu Arg Thr Ser Gln Ile Ser Thr Met Gln Gln Tyr Asn Leu Cys

  115 120 125

  Val Tyr Arg Trp Leu Ser Glu Xaa Pro Xaa His Cys Glu Leu Xaa

  130 135 140

  <210> SEQ ID NO 193

  <211> LENGTH: 110

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (110)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 193

  Met Ile Lys Lys Asp Lys Tyr His Lys Lys Val Phe Leu Phe Gly Trp

  1 5 10 15

  Phe Phe Cys Leu Phe Val Phe Phe Leu Arg Leu Ser Leu Ser Leu Leu

  20 25 30

  Pro Lys Leu Glu Cys Asn Leu Gly Ser Leu Gln Pro Pro Pro Pro Arg

  35 40 45

  Phe Gln Arg Phe Ser Cys Leu Ser Leu Leu Asn Ser Trp Asp Tyr Arg

  50 55 60

  Arg Pro Pro Pro His Leu Ala Asn Phe Cys Val Val Ser Arg Gly Gly

  65 70 75 80

  Val Ser Ser Cys Trp Pro Gly Trp Ser Arg Thr Pro Asp Leu Met Ile

  85 90 95

  Arg Leu Pro Arg Pro Pro Arg Val Leu Gly Leu Gln Ala Xaa

  100 105 110

  <210> SEQ ID NO 194

  <211> LENGTH: 80

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (73)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (78)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 194

  Met Phe Leu Thr Ile Ile Val Cys Gly Met Val Ala Ala Leu Ser Ala

  1 5 10 15

  Ile Arg Ala Asn Cys His Gln Glu Pro Ser Val Cys Leu Gln Ala Ala

  20 25 30

  Cys Pro Glu Ser Trp Ile Gly Phe Gln Arg Lys Cys Phe Tyr Phe Ser

  35 40 45

  Asp Asp Thr Lys Asn Trp Thr Ser Ser Gln Arg Phe Cys Asp Ser Gln

  50 55 60

  Asp Ala Asp Leu Ala Gln Val Glu Xaa Phe Gln Glu Leu Xaa Arg Lys

  65 70 75 80

  <210> SEQ ID NO 195

  <211> LENGTH: 210

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (210)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 195

  Met Cys Pro Leu Trp Arg Leu Leu Ile Phe Leu Gly Leu Leu Ala Leu

  1 5 10 15

  Pro Leu Ala Pro His Lys Gln Pro Trp Pro Gly Leu Ala Gln Ala His

  20 25 30

  Arg Asp Asn Lys Ser Thr Leu Ala Arg Ile Ile Ala Gln Gly Leu Ile

  35 40 45

  Lys His Asn Ala Glu Ser Arg Ile Gln Asn Ile His Phe Gly Asp Arg

  50 55 60

  Leu Asn Ala Ser Ala Gln Val Ala Pro Gly Leu Val Gly Trp Leu Ile

  65 70 75 80

  Ser Gly Arg Lys His Gln Gln Gln Gln Glu Ser Ser Ile Asn Ile Thr

  85 90 95

  Asn Ile Gln Leu Asp Cys Gly Gly Ile Gln Ile Ser Phe His Lys Glu

  100 105 110

  Trp Phe Ser Ala Asn Ile Ser Leu Glu Phe Asp Leu Glu Leu Arg Pro

  115 120 125

  Ser Phe Asp Asn Asn Ile Ile Lys Met Cys Ala His Met Ser Ile Val

  130 135 140

  Val Glu Phe Trp Leu Glu Lys Asp Glu Phe Gly Arg Arg Asp Leu Val

  145 150 155 160

  Ile Gly Lys Cys Asp Ala Glu Pro Ser Ser Val His Val Ala Ile Leu

  165 170 175

  Thr Glu Ala Ile Pro Pro Lys Met Asn Gln Phe Leu Tyr Asn Leu Lys

  180 185 190

  Glu Asn Leu Gln Lys Val Leu Pro His Met Val Glu Ser Gln Pro Leu

  195 200 205

  Ala Xaa

  210

  <210> SEQ ID NO 196

  <211> LENGTH: 149

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (61)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (142)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (149)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 196

  Met Arg Lys Ile Ala Gln Cys Ala Pro Gly Val Val Glu Leu Val Leu

  1 5 10 15

  Ile Pro Leu Arg Gln Arg Leu Glu Glu Arg Gln Arg Arg Arg Lys Gln

  20 25 30

  Gly Ala Gly Ser Leu Gln Glu Leu Ala Pro Gln Asp Gly Ser Gly Tyr

  35 40 45

  Met Asp Val Gly Val Ser Gln Lys Ala Arg Gly Glu Xaa Val Pro Asp

  50 55 60

  Pro Gln Gly Gly Gly Gln Leu Ser Trp Asp Arg Pro Pro Ala Pro Arg

  65 70 75 80

  Pro Pro Ala Tyr Asn Arg Ala Leu Gln Gly Asp Pro Ser Phe Val Leu

  85 90 95

  Gln Ile Ala Glu Lys Glu Gln Glu Leu Leu Ala Ser Gln Glu Thr Val

  100 105 110

  Gln Val Leu Gln Met Lys Val Arg Arg Leu Glu His Leu Leu Gln Leu

  115 120 125

  Lys Asn Val Arg Ile Glu Asn Leu Ser Arg Arg Leu Gln Xaa Ala Glu

  130 135 140

  Arg Lys Gln Arg Xaa

  145

  <210> SEQ ID NO 197

  <211> LENGTH: 36

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (36)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 197

  Met His Ile Thr Ser Leu Val Gly Ala Gly Thr Leu Met Val Leu Leu

  1 5 10 15

  Leu Leu Ile Leu Leu Leu Glu Cys Phe Phe Val Ala Glu Ala Leu Val

  20 25 30

  Met Arg Ser Xaa

  35

  <210> SEQ ID NO 198

  <211> LENGTH: 258

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (258)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 198

  Met Ala Ala Leu Thr Thr Val Val Val Ala Ala Ala Ala Thr Ala Val

  1 5 10 15

  Ala Gly Ala Val Ala Gly Ala Gly Ala Ala Thr Gly Thr Gly Val Gly

  20 25 30

  Ala Thr Pro Ala Pro Gln Gln Ser Asp Gly Cys Phe Ser Thr Ser Gly

  35 40 45

  Gly Ile Arg Pro Phe His Leu Gln Asn Trp Lys Gln Lys Val Asn Gln

  50 55 60

  Thr Lys Lys Ala Glu Phe Val Arg Thr Ala Glu Lys Phe Lys Asn Gln

  65 70 75 80

  Val Ile Asn Met Glu Lys Asp Lys His Ser His Phe Tyr Asn Gln Lys

  85 90 95

  Ser Asp Phe Arg Phe Glu His Ser Met Leu Glu Glu Leu Glu Asn Lys

  100 105 110

  Leu Ile His Ser Arg Lys Thr Glu Arg Ala Lys Phe Gln Gln Gln Leu

  115 120 125

  Ala Lys Ile His Asn Asn Val Lys Lys Leu Gln His Gln Leu Lys Asp

  130 135 140

  Val Lys Pro Thr Pro Asp Phe Val Glu Lys Leu Arg Glu Met Met Glu

  145 150 155 160

  Glu Ile Glu Asn Ala Ile Asn Thr Phe Lys Glu Glu Gln Arg Leu Ile

  165 170 175

  Tyr Glu Glu Leu Ile Lys Glu Glu Lys Thr Thr Asn Asn Glu Leu Ser

  180 185 190

  Ala Ile Ser Arg Lys Ile Asp Thr Trp Ala Leu Gly Asn Ser Glu Thr

  195 200 205

  Glu Lys Ala Phe Arg Ala Ile Ser Ser Lys Val Pro Val Asp Lys Val

  210 215 220

  Thr Pro Ser Thr Leu Pro Glu Glu Val Leu Asp Phe Glu Lys Phe Leu

  225 230 235 240

  Gln Gln Thr Gly Gly Arg Gln Gly Ala Trp Asp Val Ile Thr Arg Thr

  245 250 255

  Leu Xaa

  <210> SEQ ID NO 199

  <211> LENGTH: 59

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (11)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (59)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 199

  Met Leu Cys Leu Leu Val Leu Thr Gly Leu Xaa Val Leu Ile Val Gly

  1 5 10 15

  Ile His Ile Leu Glu Leu Leu Ile Asp Glu Ala Ala Met Pro Arg Gly

  20 25 30

  Met Gln Gly Thr Ser Leu Gly Gln Val Ser Phe Ser Lys Leu Gly Ser

  35 40 45

  Phe Ala Ser Ser Ala Ser Leu Ser Ala Arg Xaa

  50 55

  <210> SEQ ID NO 200

  <211> LENGTH: 34

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (34)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 200

  Met Phe Phe Val Leu Leu Cys Phe Trp Leu Phe Pro Phe Ser Lys Asn

  1 5 10 15

  Ser Pro Leu Trp Gly Met Leu Arg Ser Ser Phe Phe Ile Ser Ile Asn

  20 25 30

  Leu Xaa

  <210> SEQ ID NO 201

  <211> LENGTH: 26

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (26)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 201

  Met Ser Leu Ile Leu Leu Leu Ser Val Thr Leu Leu His Leu Ser Phe

  1 5 10 15

  Ser Val Gly Phe Phe Leu Phe Arg Leu Xaa

  20 25

  <210> SEQ ID NO 202

  <211> LENGTH: 34

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (34)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 202

  Met Lys Ser Val Ile Phe Ile Gln Ser Val Ile Leu Phe Phe Leu Pro

  1 5 10 15

  Met Ser Gly Asp His Gln Gly Ile Ser Gly Leu Asp Glu Leu Pro Gln

  20 25 30

  Ala Xaa

  <210> SEQ ID NO 203

  <211> LENGTH: 58

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 203

  Met Ser Ser Phe Leu Arg Val Ile Phe Ile Pro Asn Ile Lys Val Ile

  1 5 10 15

  Phe Leu Pro Pro Gly Thr Thr Ser Leu Ile His Thr Met Asp Gln Gly

  20 25 30

  Val Ile Ala Ala Phe Lys Phe Tyr Tyr Leu Arg Arg Glu Asp Phe Cys

  35 40 45

  Pro Val Pro Tyr Cys Ser Gly Gly Arg His

  50 55

  <210> SEQ ID NO 204

  <211> LENGTH: 75

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (66)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (73)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 204

  Met Lys Pro Thr Leu Ser Lys Phe Leu Gly Thr Asp Ala Glu Leu Pro

  1 5 10 15

  Lys Leu Tyr Pro Pro Ser Leu Gln Ala Pro Arg Gly Glu Thr Gln Leu

  20 25 30

  Leu Gly Pro Gly Leu Glu Arg Pro Thr Arg Glu Gly Arg Val Glu Gln

  35 40 45

  Met Leu Phe Asn Gln Lys Ser Val Ser Trp Gly Ser Gln Leu Pro Gln

  50 55 60

  Ser Xaa Asn Thr Phe Leu Lys Asn Xaa Asp Pro

  65 70 75

  <210> SEQ ID NO 205

  <211> LENGTH: 66

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (63)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 205

  Met Thr Trp Lys Gly Trp Ser Arg Thr Arg Ile Trp Lys Pro Ser Leu

  1 5 10 15

  Pro Gln Leu Phe Thr Met Tyr Leu Leu Ala Gln Ile Arg Ala Ala Ser

  20 25 30

  Arg Ala Ser Glu Asp Ser Cys Ser Tyr Ser Ser Asp Thr Met Trp Pro

  35 40 45

  Gln Ser Gly Asn Ser Ser Thr Phe Ala Phe Phe Arg Pro Arg Xaa Lys

  50 55 60

  Met Arg

  65

  <210> SEQ ID NO 206

  <211> LENGTH: 44

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (44)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 206

  Met Leu Ser Phe Val Ser Arg Cys His Trp Ser Ser Ile Ala Glu Glu

  1 5 10 15

  Ser Glu Phe Leu Phe Leu Ile Leu Val Cys Tyr Phe Ser Ser Ser Cys

  20 25 30

  Ser Ser Cys Ile Ile His Gln Trp Tyr Tyr Val Xaa

  35 40

  <210> SEQ ID NO 207

  <211> LENGTH: 32

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (32)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 207

  Met Leu Gln Thr Leu Ile Leu Ile Phe Leu Leu Leu Leu Pro Cys Tyr

  1 5 10 15

  Leu Glu Leu Leu Cys Phe Ser Leu Ile Ser Ser Ser Ala Lys Thr Xaa

  20 25 30

  <210> SEQ ID NO 208

  <211> LENGTH: 48

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (11)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (48)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 208

  Met Thr Pro Trp Leu Leu Ile Leu Val Ser Xaa Gly Phe Leu Lys Ser

  1 5 10 15

  Ile Ser Asp Pro Gln Phe Gln Glu Leu Ser Ile Asn Ile Ala Ser Cys

  20 25 30

  His Pro Gly Thr Val Met Pro Tyr Ser Gly Thr Ser His Leu Lys Xaa

  35 40 45

  <210> SEQ ID NO 209

  <211> LENGTH: 37

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (37)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 209

  Met Thr Gly Thr Pro Ala Trp Ala His Leu Leu Leu Leu Leu Leu Leu

  1 5 10 15

  Gly Ser Ala Pro Gln Thr Arg Leu Trp Pro Pro Ser Gln Cys Pro Val

  20 25 30

  Thr Ser Pro Glu Xaa

  35

  <210> SEQ ID NO 210

  <211> LENGTH: 74

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (74)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 210

  Met Gly Val Lys Leu Glu Ile Phe Arg Met Ile Ile Tyr Leu Thr Phe

  1 5 10 15

  Pro Val Ala Met Phe Trp Val Ser Asn Gln Ala Glu Trp Phe Glu Asp

  20 25 30

  Asp Val Ile Gln Arg Lys Arg Glu Leu Trp Pro Pro Glu Lys Leu Gln

  35 40 45

  Glu Ile Glu Glu Phe Lys Glu Arg Leu Arg Lys Arg Arg Glu Glu Lys

  50 55 60

  Leu Leu Arg Asp Ala Gln Gln Asn Ser Xaa

  65 70

  <210> SEQ ID NO 211

  <211> LENGTH: 41

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (41)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 211

  Met Pro Phe Ser Ser Ser Val Lys Cys Leu Phe Gly Val Leu Leu Arg

  1 5 10 15

  Phe Cys Phe Val Val Phe Ser Val Val Val Phe Thr Phe Phe Leu Ser

  20 25 30

  Ile Pro Lys Arg Thr Leu Gly Tyr Xaa

  35 40

  <210> SEQ ID NO 212

  <211> LENGTH: 54

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (54)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 212

  Met Trp His Leu Ser Phe His Cys Leu Leu Leu Leu Leu Pro Leu Cys

  1 5 10 15

  Glu Val Thr His Ser Leu Phe Ala Phe Tyr His Asn Trp Lys Leu Phe

  20 25 30

  Glu Ala Ser Leu Glu Thr Glu Ala Ala Met Leu Pro Val Gln Pro Ala

  35 40 45

  Glu Pro Arg Ala Asn Xaa

  50

  <210> SEQ ID NO 213

  <211> LENGTH: 63

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (63)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 213

  Met Pro Glu Asn Leu Val Leu Ile Leu Ala Leu Leu Leu Ser Val Cys

  1 5 10 15

  Gly Leu Lys Gln Val Ile Phe Leu Ser Ala Ser Ile Tyr Ser Lys Met

  20 25 30

  Cys Thr Leu Ile Ala Thr Lys Lys Val Val Ala Lys Thr Arg Asn Asp

  35 40 45

  Ala Tyr Trp Tyr Leu Ile Ser Leu Lys His Ile Val Gly Phe Xaa

  50 55 60

  <210> SEQ ID NO 214

  <211> LENGTH: 176

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (142)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (149)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (155)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (158)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (160)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (163)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (176)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 214

  Met Tyr Trp Ile Val Phe Ala Leu Tyr Thr Val Ile Glu Thr Val Ala

  1 5 10 15

  Asp Gln Thr Val Ala Trp Phe Pro Leu Tyr Tyr Glu Leu Lys Ile Ala

  20 25 30

  Phe Val Ile Trp Leu Leu Ser Pro Tyr Thr Lys Gly Ala Ser Leu Ile

  35 40 45

  Tyr Arg Lys Phe Leu His Pro Leu Leu Ser Ser Lys Glu Arg Glu Ile

  50 55 60

  Asp Asp Tyr Ile Val Gln Ala Lys Glu Arg Gly Tyr Glu Thr Met Val

  65 70 75 80

  Asn Phe Gly Arg Gln Gly Leu Asn Leu Ala Ala Thr Ala Ala Val Thr

  85 90 95

  Ala Ala Val Lys Ser Gln Gly Ala Ile Thr Glu Arg Leu Arg Ser Phe

  100 105 110

  Ser Met His Asp Leu Thr Thr Ile Gln Gly Asp Glu Pro Val Gly Gln

  115 120 125

  Arg Pro Tyr Gln Pro Leu Pro Glu Ala Lys Lys Lys Ser Xaa Gln Pro

  130 135 140

  Pro Val Asn Gln Xaa Val Met Glu Phe His Xaa Lys Thr Xaa Met Xaa

  145 150 155 160

  Lys Gln Xaa Lys Lys Gln Arg Gly His Ile Gln Ile Met Arg Cys Xaa

  165 170 175

  <210> SEQ ID NO 215

  <211> LENGTH: 40

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (40)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 215

  Met Arg Glu Cys Tyr Phe Leu Gly Asn Phe Leu Leu Val Phe Leu Ile

  1 5 10 15

  Leu Ala Ser Ser Phe Ile Tyr Val Leu Val Thr Gln Val Leu Gly Gly

  20 25 30

  Pro Ala Thr Leu Leu Ala Phe Xaa

  35 40

  <210> SEQ ID NO 216

  <211> LENGTH: 55

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (55)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 216

  Met Val Leu Gln Asn Thr Asn Thr Leu Leu Ile Val Ser Ala Phe Leu

  1 5 10 15

  Leu Ser Met Leu Phe Phe Lys Phe Ser Ile Ala Ile Phe Leu Val Thr

  20 25 30

  Asn Leu Ser Phe Glu Arg Ser Asn Leu Leu Leu Gly Pro Ser Ser Asp

  35 40 45

  Leu Phe Leu Asn Phe Lys Xaa

  50 55

  <210> SEQ ID NO 217

  <211> LENGTH: 47

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (47)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 217

  Met Tyr Ile Phe His Phe Val Phe Leu Ile Gly Tyr Ala Met Cys Gly

  1 5 10 15

  Ile Gln Val Thr Asn Val Thr Leu Ala Ser Gly Pro Ser Asn Leu His

  20 25 30

  Val Tyr Leu Leu Gln Ser Tyr Leu Thr Arg Gly Pro Asn His Xaa

  35 40 45

  <210> SEQ ID NO 218

  <211> LENGTH: 180

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (180)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 218

  Met Leu Tyr Tyr Leu Trp Met Leu His Ser Val Thr Leu Phe Leu Asn

  1 5 10 15

  Leu Leu Ala Cys Leu Ala Trp Phe Ser Gly Asn Ser Ser Lys Gly Val

  20 25 30

  Asp Phe Gly Leu Ser Ile Leu Trp Phe Leu Ile Phe Thr Pro Cys Ala

  35 40 45

  Phe Leu Cys Trp Tyr Arg Pro Ile Tyr Lys Ala Phe Arg Ser Asp Asn

  50 55 60

  Ser Phe Ser Phe Phe Val Phe Phe Phe Val Phe Phe Cys Gln Ile Gly

  65 70 75 80

  Ile Tyr Ile Ile Gln Leu Val Gly Ile Pro Gly Leu Gly Asp Ser Gly

  85 90 95

  Trp Ile Ala Ala Leu Ser Thr Leu Asp Asn His Ser Leu Ala Ile Ser

  100 105 110

  Val Ile Met Met Val Val Ala Gly Phe Phe Thr Leu Cys Ala Val Leu

  115 120 125

  Ser Val Phe Leu Leu Gln Arg Val His Ser Leu Tyr Arg Arg Thr Gly

  130 135 140

  Ala Ser Phe Gln Gln Ala Gln Glu Glu Phe Ser Gln Gly Ile Phe Ser

  145 150 155 160

  Ser Arg Thr Phe His Arg Ala Ala Ser Ser Ala Ala Gln Gly Ala Phe

  165 170 175

  Gln Gly Asn Xaa

  180

  <210> SEQ ID NO 219

  <211> LENGTH: 99

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (99)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 219

  Met Lys Leu Met Val Leu Val Phe Thr Ile Gly Leu Thr Leu Leu Leu

  1 5 10 15

  Gly Val Gln Ala Met Pro Ala Asn Arg Leu Ser Cys Tyr Arg Lys Ile

  20 25 30

  Leu Lys Asp His Asn Cys His Asn Leu Pro Glu Gly Val Ala Asp Leu

  35 40 45

  Thr Gln Ile Asp Val Asn Val Gln Asp His Phe Trp Asp Gly Lys Gly

  50 55 60

  Cys Glu Met Ile Cys Tyr Cys Asn Phe Ser Glu Leu Leu Cys Cys Pro

  65 70 75 80

  Lys Asp Val Phe Phe Gly Pro Lys Ile Ser Phe Val Ile Pro Cys Asn

  85 90 95

  Asn Gln Xaa

  <210> SEQ ID NO 220

  <211> LENGTH: 44

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (44)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 220

  Met Gly Gly Lys Gly Ile Asn Tyr Thr Met Pro His Ile Cys Leu Leu

  1 5 10 15

  Leu Leu Asn Ala Leu Val Val Ser Cys Leu Leu Leu Glu Ala Ile Leu

  20 25 30

  Leu Gln His Leu Val Leu Cys Asn Glu Leu Pro Xaa

  35 40

  <210> SEQ ID NO 221

  <211> LENGTH: 42

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (42)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 221

  Met Phe Met Leu Cys Asn Leu Leu Leu Pro Leu Leu Glu Phe Ile Phe

  1 5 10 15

  Gly Ser Thr Tyr Leu Ser Thr Asp Leu Tyr Leu His Thr Cys Met Lys

  20 25 30

  Asn Val Phe Leu His Ile His Ser Phe Xaa

  35 40

  <210> SEQ ID NO 222

  <211> LENGTH: 52

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (52)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 222

  Met Ala Val Pro Ser Gly Cys Trp Pro Ser Trp Pro Arg Pro Ser Ser

  1 5 10 15

  Trp Trp Ser Thr Arg Ile Ser Pro Arg Ser Ala Thr Pro Leu Thr Ala

  20 25 30

  Ser Thr Trp Ser Leu Val Thr Cys Ser Ser Gln Val Ser Ala Cys Gly

  35 40 45

  Thr Ser Ile Xaa

  50

  <210> SEQ ID NO 223

  <211> LENGTH: 32

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (32)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 223

  Met Val Ser Leu Asn Leu Ser Leu Pro Asn Asn Ile Ile Ser Leu Val

  1 5 10 15

  Phe Phe Phe Leu Leu Gln Pro Val Gln Lys Gly Val Ser Gly Gly Xaa

  20 25 30

  <210> SEQ ID NO 224

  <211> LENGTH: 54

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (54)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 224

  Met Leu Val Leu Met Thr Thr Cys Ile Leu Ala Ala Val Cys Val His

  1 5 10 15

  Thr Ala Gln Cys Ala Pro Asp Ser Arg Met Asp Asn Asp Cys Pro Ser

  20 25 30

  His Gln Ala Gln Ile His Phe Arg Ala Ser Glu Val Arg Arg Gly Trp

  35 40 45

  Thr Phe Asn His Asp Xaa

  50

  <210> SEQ ID NO 225

  <211> LENGTH: 41

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (41)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 225

  Met Gly Pro Ser Gln Arg Glu Val Thr Val Gln Trp His Arg Ala Leu

  1 5 10 15

  Phe Leu Leu Pro Leu Leu Leu Leu Ser Thr Arg Thr Glu Thr Lys Asn

  20 25 30

  Phe Gly Phe Lys Trp Leu Lys Asp Xaa

  35 40

  <210> SEQ ID NO 226

  <211> LENGTH: 31

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (31)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 226

  Met Gln Leu Ser Lys Phe Leu Leu Phe Leu Phe Val Tyr Thr Arg Glu

  1 5 10 15

  Asn Pro Thr Ser Ala Cys Val Trp Gly Glu Lys Ser Thr Val Xaa

  20 25 30

  <210> SEQ ID NO 227

  <211> LENGTH: 60

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (60)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 227

  Met Val Val Val Ser Thr Asn Gly Phe Leu Leu Leu Leu Leu Phe Leu

  1 5 10 15

  Asn Arg Lys Ser Gly Leu Cys Ser Tyr Arg Lys Ala Val His Arg Leu

  20 25 30

  Ser Ser Cys Pro Ser Arg His Gln Ala Gly Pro Arg Ile Lys Cys Asp

  35 40 45

  Phe Lys Trp Gly Lys Leu Cys Tyr Ser Cys Ala Xaa

  50 55 60

  <210> SEQ ID NO 228

  <211> LENGTH: 35

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (35)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 228

  Met Gly Trp Gly Lys Glu Val Val Ser Leu Ile Val Leu Leu Val Asn

  1 5 10 15

  Leu Phe Leu Cys Pro Trp Ala Leu Gly Leu Cys Leu Leu Ser Val Ser

  20 25 30

  Ser Leu Xaa

  35

  <210> SEQ ID NO 229

  <211> LENGTH: 39

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (39)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 229

  Met Met Asn Ile Leu Leu Leu Lys Tyr Ile Leu Glu Ile Leu Ile Leu

  1 5 10 15

  Ser Glu Asn Leu Asn Leu Phe Asn Ile Thr Tyr Gly Lys Tyr Asn Leu

  20 25 30

  Phe Phe Leu Tyr Arg Tyr Xaa

  35

  <210> SEQ ID NO 230

  <211> LENGTH: 39

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (39)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 230

  Met Tyr Ile Phe Tyr Leu Tyr Lys Ile Tyr Ile Tyr Thr His Ile Cys

  1 5 10 15

  Ile Tyr Ile Pro Leu Phe Leu Cys Leu Leu Ile Leu Ala Ile Lys Glu

  20 25 30

  Gly Ala Ala Phe Asn Val Xaa

  35

  <210> SEQ ID NO 231

  <211> LENGTH: 62

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (62)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 231

  Met Asn Glu Ser Val Tyr Asp Asp Ser Thr Ser Ser Tyr Thr Pro Ser

  1 5 10 15

  Leu His Ile Leu Gly Cys Leu Leu Leu Leu Phe Leu Gly Val Glu Arg

  20 25 30

  Ala Leu Glu Pro Phe Ser Gly Leu Cys Ala Ser Leu His Asp Val Arg

  35 40 45

  Pro Ile Val Asn Pro Leu Thr Ser Phe Ser Leu Ile Tyr Xaa

  50 55 60

  <210> SEQ ID NO 232

  <211> LENGTH: 198

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (198)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 232

  Met Cys Thr Gly Lys Cys Ala Arg Cys Val Gly Leu Ser Leu Ile Thr

  1 5 10 15

  Leu Cys Leu Val Cys Ile Val Ala Asn Ala Leu Leu Leu Val Pro Asn

  20 25 30

  Gly Glu Thr Ser Trp Thr Asn Thr Asn His Leu Ser Leu Gln Val Trp

  35 40 45

  Leu Met Gly Gly Phe Ile Gly Gly Gly Leu Met Val Leu Cys Pro Gly

  50 55 60

  Ile Ala Ala Val Arg Ala Gly Gly Lys Gly Cys Cys Gly Ala Gly Cys

  65 70 75 80

  Cys Gly Asn Arg Cys Arg Met Leu Arg Ser Val Phe Ser Ser Ala Phe

  85 90 95

  Gly Val Leu Gly Ala Ile Tyr Cys Leu Ser Val Ser Gly Ala Gly Leu

  100 105 110

  Arg Asn Gly Pro Arg Cys Leu Met Asn Gly Glu Trp Gly Tyr His Phe

  115 120 125

  Glu Asp Thr Ala Gly Ala Tyr Leu Leu Asn Arg Thr Leu Trp Asp Arg

  130 135 140

  Cys Glu Ala Pro Pro Arg Val Val Pro Trp Asn Val Thr Leu Phe Ser

  145 150 155 160

  Leu Leu Val Ala Ala Ser Cys Leu Glu Ile Val Leu Cys Gly Ile Gln

  165 170 175

  Leu Val Asn Ala Thr Ile Gly Val Phe Cys Gly Asp Cys Arg Lys Lys

  180 185 190

  Gln Asp Thr Pro His Xaa

  195

  <210> SEQ ID NO 233

  <211> LENGTH: 62

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (62)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 233

  Met Ser Gln Leu Phe Leu Ile Met Leu Thr Phe Ile Phe Leu Asn Asn

  1 5 10 15

  Met Phe Ile Met His Leu Thr Ser Phe His Gly Lys Arg Val Phe Gly

  20 25 30

  Phe Leu Asn Gln Ser Ser His Met His Ala Phe Pro Leu Pro Arg Trp

  35 40 45

  Thr Thr Ser Ile Phe Ser Val Ser Ile Phe Ile Asn Arg Xaa

  50 55 60

  <210> SEQ ID NO 234

  <211> LENGTH: 81

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (81)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 234

  Met Ala Phe Leu Pro Leu Thr Leu Thr Phe Cys Leu Ala Pro Leu Ala

  1 5 10 15

  Pro Leu Leu Pro Ser Ile Trp Gly Pro Thr Pro Ala Ser Cys Val Val

  20 25 30

  Trp Pro Leu Leu Thr Ile Leu Pro Val Pro Ala Gln Ala Ser Pro Ser

  35 40 45

  Thr Asp Thr Ala His Leu Trp Gln Arg Pro Thr Thr Gly Ser Pro Thr

  50 55 60

  Arg Leu Val Arg Pro Leu Pro Arg Pro Gly Leu Pro Pro Met Trp Ala

  65 70 75 80

  Xaa

  <210> SEQ ID NO 235

  <211> LENGTH: 111

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 235

  Met Gly Gly Leu Glu Pro Cys Ser Arg Leu Leu Leu Leu Pro Leu Leu

  1 5 10 15

  Leu Ala Val Gly Leu Arg Pro Val Gln Ala Gln Ala Gln Ser Asp Cys

  20 25 30

  Ser Cys Ser Thr Val Ser Pro Gly Val Leu Ala Gly Ile Val Met Gly

  35 40 45

  Asp Leu Val Leu Thr Val Leu Ile Ala Leu Ala Val Tyr Phe Leu Gly

  50 55 60

  Arg Leu Val Pro Arg Gly Arg Gly Ala Ala Glu Ala Thr Arg Lys Gln

  65 70 75 80

  Arg Ile Thr Glu Thr Glu Ser Pro Tyr Gln Glu Leu Gln Gly Gln Arg

  85 90 95

  Ser Asp Val Tyr Ser Asp Leu Asn Thr Gln Arg Pro Tyr Tyr Lys

  100 105 110

  <210> SEQ ID NO 236

  <211> LENGTH: 33

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (33)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 236

  Met Gln Arg Met Leu Val Leu Leu Phe Phe Phe Phe Ser Leu Leu Ala

  1 5 10 15

  Ile Asn Pro Ala Glu Thr Ile Cys Gly Tyr Gly Ser Thr Trp Lys Phe

  20 25 30

  Xaa

  <210> SEQ ID NO 237

  <211> LENGTH: 229

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (134)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (229)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 237

  Met Val Leu Gly Leu Phe Val Pro Pro Val Phe Val Val Ser Tyr Ala

  1 5 10 15

  Lys Asp Leu Gly Val Pro Asp Thr Lys Ala Ala Phe Leu Leu Thr Ile

  20 25 30

  Leu Gly Phe Ile Asp Ile Phe Ala Arg Pro Ala Ala Gly Phe Val Ala

  35 40 45

  Gly Leu Gly Lys Val Arg Pro Tyr Ser Val Tyr Leu Phe Ser Phe Ser

  50 55 60

  Met Phe Phe Asn Gly Leu Ala Asp Leu Ala Gly Ser Thr Ala Gly Asp

  65 70 75 80

  Tyr Gly Gly Leu Val Val Phe Cys Ile Phe Phe Gly Ile Ser Tyr Gly

  85 90 95

  Met Val Gly Ala Leu Gln Phe Glu Val Leu Met Ala Ile Val Gly Thr

  100 105 110

  His Lys Phe Ser Ser Ala Ile Gly Leu Val Leu Leu Met Glu Ala Val

  115 120 125

  Ala Val Leu Val Gly Xaa Pro Ser Gly Gly Lys Leu Leu Asp Ala Thr

  130 135 140

  His Val Tyr Met Tyr Val Phe Ile Leu Ala Gly Ala Glu Val Leu Thr

  145 150 155 160

  Ser Ser Leu Ile Leu Leu Leu Gly Asn Phe Phe Cys Ile Arg Lys Lys

  165 170 175

  Pro Lys Glu Pro Gln Pro Glu Val Ala Ala Ala Glu Glu Glu Lys Leu

  180 185 190

  His Lys Pro Pro Ala Asp Ser Gly Val Asp Leu Arg Glu Val Glu His

  195 200 205

  Phe Leu Lys Ala Glu Pro Glu Lys Asn Gly Glu Val Val His Thr Pro

  210 215 220

  Glu Thr Ser Val Xaa

  225

  <210> SEQ ID NO 238

  <211> LENGTH: 117

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (117)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 238

  Met Thr Pro Leu Leu Thr Leu Ile Leu Val Val Leu Met Gly Leu Pro

  1 5 10 15

  Leu Ala Gln Ala Leu Asp Cys His Val Cys Ala Tyr Asn Gly Asp Asn

  20 25 30

  Cys Phe Asn Pro Met Arg Cys Pro Ala Met Val Ala Tyr Cys Met Thr

  35 40 45

  Thr Arg Thr Tyr Tyr Thr Pro Thr Arg Met Lys Val Ser Lys Ser Cys

  50 55 60

  Val Pro Arg Cys Phe Glu Thr Val Tyr Asp Gly Tyr Ser Lys His Ala

  65 70 75 80

  Ser Thr Thr Ser Cys Cys Gln Tyr Asp Leu Cys Asn Gly Thr Gly Leu

  85 90 95

  Ala Thr Pro Ala Thr Leu Ala Leu Ala Pro Ile Leu Leu Ala Thr Leu

  100 105 110

  Trp Gly Leu Leu Xaa

  115

  <210> SEQ ID NO 239

  <211> LENGTH: 37

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (37)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 239

  Met Leu Thr Trp Leu Asp Leu Asp Leu Leu Phe Cys Phe Leu Phe Leu

  1 5 10 15

  Phe Leu Phe Ile Leu Phe Tyr Phe Leu Gln Leu Asn Glu Phe Trp Gly

  20 25 30

  Gly Asn Pro Phe Xaa

  35

  <210> SEQ ID NO 240

  <211> LENGTH: 58

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 240

  Met Glu Pro Trp Ser Trp Phe Phe Phe Phe Phe Phe Phe Phe Pro Gln

  1 5 10 15

  Arg Thr Cys Gly Cys Ala Leu Cys Val Leu Phe Leu Phe Ser Ile Trp

  20 25 30

  Gly Pro His Gly Lys Glu Leu Leu Asn Ser Phe Leu Tyr Glu Leu Pro

  35 40 45

  Leu Cys Ser Tyr Lys Gly Pro Phe Leu Ser

  50 55

  <210> SEQ ID NO 241

  <211> LENGTH: 48

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (48)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 241

  Met Gln Ser Gly Arg Ser Trp Ala Leu Lys Met Val Leu Leu Cys Asn

  1 5 10 15

  Ser Cys Leu Gly Leu Gly Val Gly Ser Val Gly Pro Ser Met Ser Ser

  20 25 30

  Leu Phe Gly Ala Val Leu Ser Glu Thr Pro Gly Ser Ser Val Tyr Xaa

  35 40 45

  <210> SEQ ID NO 242

  <211> LENGTH: 32

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (32)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 242

  Met Ile Thr Leu Cys Ile Phe Leu Leu Phe Lys Val Phe Val Gly Ile

  1 5 10 15

  Ile Leu His Tyr Leu Ile Gly Lys Asn Ile Tyr Val Tyr Ser Val Xaa

  20 25 30

  <210> SEQ ID NO 243

  <211> LENGTH: 64

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (64)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 243

  Met Ala Ser Leu Leu Gln Arg Asn Leu Cys Pro Arg Leu Ser Val Cys

  1 5 10 15

  Leu Val Phe Ile Gln Val Phe Val Cys Cys Val Glu Gly Gly Gly Arg

  20 25 30

  Arg Val Lys Ala Val Leu Phe Arg Ala Pro Phe Gly Glu His Ser Arg

  35 40 45

  Gln Asn Thr Leu Val Ile Pro Ser Gln Thr Gly Leu Gln Ala His Xaa

  50 55 60

  <210> SEQ ID NO 244

  <211> LENGTH: 68

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (68)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 244

  Met Pro Val Tyr Asp Phe Asn Trp Trp Tyr Ser Leu Tyr Phe Ile Ile

  1 5 10 15

  Tyr Ile Ile Ile Asn Thr Tyr Ile Phe Lys Ser Val Phe Leu Ala Met

  20 25 30

  Val Tyr Ser Asn Tyr Arg Lys His Phe His Ile Leu Cys Val Cys Val

  35 40 45

  Cys Val Phe Cys Ser Asp Glu Gln Asn Leu Leu Phe Thr Gln Phe Tyr

  50 55 60

  Tyr Leu Ser Xaa

  65

  <210> SEQ ID NO 245

  <211> LENGTH: 46

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (43)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (46)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 245

  Met Ser Asp Lys Leu Ser Pro Ser Thr Val Pro Leu Leu Leu Pro Val

  1 5 10 15

  Leu Phe Lys Val Thr Ile Leu Leu Gln Arg Val Cys Pro Glu Asp Ser

  20 25 30

  Pro Ser Ser Ser Val Leu Pro Glu Ser Val Xaa Arg Glu Xaa

  35 40 45

  <210> SEQ ID NO 246

  <211> LENGTH: 43

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (43)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 246

  Met Arg Lys Glu Glu Gly Ile Ala His Leu Ser Ile Ala Phe Phe Val

  1 5 10 15

  Gln Val Leu Cys Leu Tyr Gln Leu Leu Pro Val Ile Leu Pro Gln Phe

  20 25 30

  Asn Leu Gly Ser Gly Lys Asn Met Asn Arg Xaa

  35 40

  <210> SEQ ID NO 247

  <211> LENGTH: 32

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (11)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (32)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 247

  Met Ile His Val Leu Thr Phe Leu Leu Gln Xaa Tyr Ile Leu Ile Ser

  1 5 10 15

  Lys Gly Lys Gly Asp Val Ser Gln Phe Val Lys Ser Arg Glu Tyr Xaa

  20 25 30

  <210> SEQ ID NO 248

  <211> LENGTH: 24

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (24)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 248

  Met Ser Glu Leu Ser Ala Phe Met Phe Ser Thr Ile Ile Phe Leu Met

  1 5 10 15

  Ala Gln Pro Thr Ser Cys Phe Xaa

  20

  <210> SEQ ID NO 249

  <211> LENGTH: 80

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (36)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (80)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 249

  Met Arg Val Phe Ala Leu Leu Pro Pro Phe His Lys Ser Thr Val Leu

  1 5 10 15

  Ser Phe Leu Leu Phe Phe Leu Ser Phe Phe Phe Phe Arg Gln Gly Leu

  20 25 30

  Ala Val Ser Xaa Arg Leu Glu Cys Ser Gly Ala Ile Ile Ala His Cys

  35 40 45

  Ser Leu Asp Leu Leu Asp Ser Ser Asn Pro Pro Ala Leu Thr Ser Gln

  50 55 60

  Leu Leu Arg Arg Pro Arg Gln Glu Asp His Leu Ser Pro Gly Gly Xaa

  65 70 75 80

  <210> SEQ ID NO 250

  <211> LENGTH: 16

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (16)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 250

  Met Ser His Cys Ala Trp Leu His Leu Gln Leu Phe Leu Ser Leu Xaa

  1 5 10 15

  <210> SEQ ID NO 251

  <211> LENGTH: 47

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (47)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 251

  Met Met Phe Cys Phe Leu Ile Trp Val Val Val Thr Phe Thr Tyr Ser

  1 5 10 15

  Leu Asn Cys Thr Phe Val Leu His Lys Phe Ile Ile Phe Pro Asn Phe

  20 25 30

  Lys Lys Val Lys Arg Arg Arg Lys Lys Leu Val Met Lys Val Xaa

  35 40 45

  <210> SEQ ID NO 252

  <211> LENGTH: 32

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (32)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 252

  Met Pro Pro Pro Glu Cys Leu Ser Asp Cys Ser Lys Val Ala Leu Val

  1 5 10 15

  Met Val Leu Phe Leu Phe Leu His Gln Ser Ser Cys Trp Ala Ala Xaa

  20 25 30

  <210> SEQ ID NO 253

  <211> LENGTH: 36

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (36)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 253

  Met Ala Ser Ser Val Thr Val Lys Glu Val Cys Val Leu Phe Asn Leu

  1 5 10 15

  Leu Ile Ile Ile Thr Ala Met Val Tyr His Ser Phe Thr Lys Tyr Gln

  20 25 30

  Thr Leu Phe Xaa

  35

  <210> SEQ ID NO 254

  <211> LENGTH: 51

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (51)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 254

  Met Ile Phe Leu Phe Phe Ile Leu Phe Glu Ile Ile Val Thr Leu Trp

  1 5 10 15

  Leu Thr Pro Thr Tyr Pro Gln Ala Phe Ser Glu Leu Thr Ile Gln Ile

  20 25 30

  Thr Ala Pro Phe Gly Ser Leu Pro Gln Gln Leu Tyr Leu His Met Ser

  35 40 45

  Ile Ile Xaa

  50

  <210> SEQ ID NO 255

  <211> LENGTH: 76

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 255

  Met Phe Phe Leu Leu Ile Leu Cys Trp Leu Leu Cys Leu Ser Leu Ser

  1 5 10 15

  Gly Leu Tyr Pro Arg Leu Leu Asn Pro Gly Gly Trp Leu Ser Leu Leu

  20 25 30

  Ser Phe Gln Met Asp Tyr Gly Trp Ile Leu Pro Trp Gly Ala Cys Thr

  35 40 45

  Val Arg His Gly Lys Pro Gly Met Gly Lys Arg Ser Gly Gly Ser Leu

  50 55 60

  Pro His Leu Thr Ala Leu Val Leu Cys Leu Thr Ser

  65 70 75

  <210> SEQ ID NO 256

  <211> LENGTH: 61

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (61)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 256

  Met Leu Leu Ser Asn Leu Ser Leu Ser Leu Gln Pro Leu Leu Phe Leu

  1 5 10 15

  Phe Ser Phe Phe Leu Phe Cys Lys Met Gly Ser Arg Lys Gly Leu Arg

  20 25 30

  His Lys Thr Gln His Phe Ser Ser Met Thr Asp Gln Ile Leu Lys Gly

  35 40 45

  Ser Val Arg Ser Pro Ala Leu Gly Gln Leu His Asp Xaa

  50 55 60

  <210> SEQ ID NO 257

  <211> LENGTH: 37

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (37)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 257

  Met Tyr Glu Val Asp Lys Lys Ile Tyr Ser Asn Phe Ile Gln Ile Leu

  1 5 10 15

  Ile Val Ile Ile Phe Val Leu Tyr Leu Ile Ile Asn Gln Asn Thr Phe

  20 25 30

  Ala Phe Leu Ser Xaa

  35

  <210> SEQ ID NO 258

  <211> LENGTH: 43

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (43)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 258

  Met Cys Ile Leu Pro Leu Met Leu Thr Tyr Pro Ile Leu Pro Lys Val

  1 5 10 15

  Val Gly Asn Asn Ile Leu Leu Gly Asp Ser Gly Leu Thr Ser Leu Val

  20 25 30

  Ile Pro Leu Ser Val Val Phe Asn Leu Lys Xaa

  35 40

  <210> SEQ ID NO 259

  <211> LENGTH: 39

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (39)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 259

  Met Ile Leu Val Ser Lys Leu Phe Phe Gly Phe Ser Leu Met Phe Leu

  1 5 10 15

  Ile Phe Phe Pro Leu Ala Thr Met Thr Val His Val Leu Ile Asn Ile

  20 25 30

  Gly Arg Ser Arg Tyr Lys Xaa

  35

  <210> SEQ ID NO 260

  <211> LENGTH: 51

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (51)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 260

  Met Ser Ile Thr Ser Asn Thr Tyr Phe Phe Leu Leu Gly Ala Phe Lys

  1 5 10 15

  Ile Leu Ser Ser Ser Tyr Trp Lys Ile His Thr Lys Leu Leu Leu Thr

  20 25 30

  Ile Val Pro Leu Gln Cys Cys Gly Met Pro Gln Leu Ile Pro Pro Leu

  35 40 45

  Gln Leu Xaa

  50

  <210> SEQ ID NO 261

  <211> LENGTH: 76

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (76)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 261

  Met Phe Thr Thr Arg Phe Pro Lys Leu Leu Ile Phe Pro Lys Ile Val

  1 5 10 15

  Thr Glu Asn Cys Cys Leu Leu Phe Cys Ser Phe Trp Gly Trp Trp Cys

  20 25 30

  Trp Leu Gly His Ala Cys Glu Val Met Cys Val Ser Asp Leu Thr Asp

  35 40 45

  Ser Leu Phe Ser Leu Leu Ile Glu Arg Ala Leu Phe Thr Leu Phe Ile

  50 55 60

  Cys Phe Asp Thr Ser Ala Phe Ser Val Leu Ser Xaa

  65 70 75

  <210> SEQ ID NO 262

  <211> LENGTH: 45

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (45)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 262

  Met Thr Ser His Pro Ser Trp Arg Leu Ile Leu Val Thr Ser Leu Val

  1 5 10 15

  Leu Gly Val Glu Pro Glu Glu Ala Pro Gly Glu Ala Gly Glu Gly Ser

  20 25 30

  Gly Gly Gln Arg Thr Met Asp Pro Glu Gln Lys Trp Xaa

  35 40 45

  <210> SEQ ID NO 263

  <211> LENGTH: 53

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (53)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 263

  Met Pro Ser Leu Asn Leu Val Leu Arg Pro Leu Ile Cys Leu Ala Ser

  1 5 10 15

  Ile Thr Ser Phe Leu Ile Phe Phe Pro Leu Leu Thr Leu Ile Leu Cys

  20 25 30

  Ser Pro Asn Ser Pro Pro Phe Pro Leu Pro Ala His Pro Glu Arg His

  35 40 45

  Thr His Thr Gln Xaa

  50

  <210> SEQ ID NO 264

  <211> LENGTH: 43

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (43)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 264

  Met His Ala Leu Ser Tyr Thr His Leu Ser Leu Leu Ser Leu Phe Leu

  1 5 10 15

  Phe Leu Pro Pro Ser Phe Leu Tyr Tyr Asn Leu Val Ile Leu Phe Phe

  20 25 30

  Glu Ala Phe Gln Asn Ile Ser His Leu Ser Xaa

  35 40

  <210> SEQ ID NO 265

  <211> LENGTH: 74

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 265

  Met Gly His Leu Phe Val Val Cys Leu Leu Ser Ser Trp Trp Thr Phe

  1 5 10 15

  Arg Pro Phe Ala Leu Ala Val Thr Val Asn His Val Ala Val Asn Ile

  20 25 30

  Val Cys Val Ser Ala Trp Thr Cys Val Ser Cys Ser Leu Gly Arg Ser

  35 40 45

  Cys Gly Leu Glu Gly Ser Phe Leu Phe Pro Leu Glu Thr Leu Trp Phe

  50 55 60

  Pro His Met Val Val Leu Cys Leu Thr Phe

  65 70

  <210> SEQ ID NO 266

  <211> LENGTH: 52

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (52)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 266

  Met Arg Lys Ser Gly Ala Met Lys Lys Gly Gly Ile Phe Ser Ala Glu

  1 5 10 15

  Phe Leu Lys Val Phe Ile Pro Ser Leu Phe Leu Ser His Val Leu Ala

  20 25 30

  Leu Gly Leu Gly Ile Tyr Ile Gly Lys Arg Leu Ser Thr Pro Ser Ala

  35 40 45

  Ser Thr Tyr Xaa

  50

  <210> SEQ ID NO 267

  <211> LENGTH: 41

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (41)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 267

  Met Trp Val Gln Leu Ile Phe Phe Phe Val Gln Tyr Gly Asp Ser Leu

  1 5 10 15

  Thr Ser Ala Phe Phe Pro Phe Ser Ser Asn Phe Ser Leu Gln Asn Ser

  20 25 30

  Gly Phe Ser Met His Lys Leu Lys Xaa

  35 40

  <210> SEQ ID NO 268

  <211> LENGTH: 79

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (79)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 268

  Met Val Cys Phe Gln Ser Asn Lys Pro Ser Thr Ser Thr Trp Arg Gln

  1 5 10 15

  Leu Ser Phe Val Phe Val Leu Phe Cys Leu Phe Cys Leu Gly His Ala

  20 25 30

  Phe Leu Ser Leu Pro Phe Tyr Ile Leu Ser Ile Ile Ala Met Cys Leu

  35 40 45

  Glu Gln Trp Ala Phe His Asn Met Asn Ser Leu Tyr His His Glu Trp

  50 55 60

  Glu Val Arg Gly Asn Leu Ile His Val Asp Phe Thr Leu Pro Xaa

  65 70 75

  <210> SEQ ID NO 269

  <211> LENGTH: 117

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (117)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 269

  Met Thr His Lys Ser Leu Val Tyr Leu Trp Phe Leu Cys Ser Ser Val

  1 5 10 15

  Ala Leu Ala Leu Gly Ala Leu Thr Val Trp His Ala Val Leu Ile Ser

  20 25 30

  Arg Gly Glu Thr Ser Ile Glu Arg His Ile Asn Lys Lys Glu Arg Arg

  35 40 45

  Arg Leu Gln Ala Lys Gly Arg Val Phe Arg Asn Pro Tyr Asn Tyr Gly

  50 55 60

  Cys Leu Asp Asn Trp Lys Val Phe Leu Gly Val Asp Thr Gly Arg His

  65 70 75 80

  Trp Leu Thr Arg Val Leu Leu Pro Ser Ser His Leu Pro His Gly Asn

  85 90 95

  Gly Met Ser Trp Glu Pro Pro Pro Trp Val Thr Ala His Ser Ala Ser

  100 105 110

  Val Met Ala Val Xaa

  115

  <210> SEQ ID NO 270

  <211> LENGTH: 62

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (62)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 270

  Met Ser Asn Leu Gln Phe His Leu Leu Pro His Ser Ser Pro Ile Leu

  1 5 10 15

  Pro Leu Phe Thr Leu Ala Leu Leu Lys Met Gln Ile Pro Gly Leu Arg

  20 25 30

  Leu Ser His Cys Leu Leu Thr Tyr Asn Ser Tyr Thr Arg Thr Pro Phe

  35 40 45

  Leu Leu Pro Ser Ser Glu Ser Tyr Leu Val Phe Glu Ile Xaa

  50 55 60

  <210> SEQ ID NO 271

  <211> LENGTH: 98

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (53)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (56)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 271

  Met Leu Pro Leu Tyr Phe Leu Gln Pro Tyr Leu Ser Leu Val Ile Phe

  1 5 10 15

  Ile Met Leu Arg Asp Asn Trp His Leu Leu Ala Leu Thr Cys Ser Tyr

  20 25 30

  Ser Ile Ile Trp Arg Leu Ser Pro Asp Thr Asn Pro Ser Pro Ile Ala

  35 40 45

  Pro Ser Arg His Xaa Gln Leu Xaa Val Val Ala Ile Ala Pro Leu Glu

  50 55 60

  Pro Ser Pro His Ser His Met Gln Ser Ile Pro Lys Asn Leu Ala Gln

  65 70 75 80

  Phe Ser Ser Ser Gln Met Phe Ser Leu Thr Leu Gln Leu Val Tyr Ile

  85 90 95

  Ser Ser

  <210> SEQ ID NO 272

  <211> LENGTH: 32

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (32)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 272

  Met Tyr Ile Leu Ser Leu Ser Cys Ser Ile Phe Phe Ser Phe Phe Phe

  1 5 10 15

  Phe Leu Phe Pro Phe Phe Arg Gly Leu Arg Lys Gly Gln Ala Lys Xaa

  20 25 30

  <210> SEQ ID NO 273

  <211> LENGTH: 15

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (15)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 273

  Ala Ser Ser Leu Leu Val Ser Leu Gln Cys Leu Leu Gln Leu Xaa

  1 5 10 15

  <210> SEQ ID NO 274

  <211> LENGTH: 37

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (37)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 274

  Met Cys Phe Ile Leu Val Val Cys Phe Ala Ser Leu Ile Thr Glu Cys

  1 5 10 15

  Pro Cys His Cys Lys Cys Cys Arg Asp Val Gly Arg Gly Pro Thr Val

  20 25 30

  Leu Tyr Glu Met Xaa

  35

  <210> SEQ ID NO 275

  <211> LENGTH: 57

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (53)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (57)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 275

  Met His Arg Leu Trp Ile Gly Pro Ala Phe Phe Leu Met Thr Ser Leu

  1 5 10 15

  Ser Val Ser Gly Ala Val Ile Pro Arg Asn Gly Gly Pro Gly Gly Val

  20 25 30

  Ser Ser Gly Pro Cys Leu Leu Gln Leu Leu Cys Gly Gln Ala Gly Ser

  35 40 45

  Ser Thr Ile Arg Xaa Ile Pro Ser Xaa

  50 55

  <210> SEQ ID NO 276

  <211> LENGTH: 27

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (27)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 276

  Met Glu Ala Val Phe Phe Leu Phe Phe Leu Leu Leu Leu Leu Thr Trp

  1 5 10 15

  Thr Ser Lys Ile Ala Pro Ile Leu Phe Ser Xaa

  20 25

  <210> SEQ ID NO 277

  <211> LENGTH: 68

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (68)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 277

  Asp Trp Gly Phe Gln Thr Thr Phe Phe Ser Leu Gly Leu Tyr Leu Phe

  1 5 10 15

  Thr Ile Trp Trp Ser Thr Val Gly Leu Pro Trp Thr Ser Ser Thr Gln

  20 25 30

  Arg Glu Leu Asp Met Lys Leu Glu Ala Ala Ala Leu Glu Gly Lys Phe

  35 40 45

  Arg Leu Thr Trp Thr Ala Gln Ala Met Ala Gly Arg Ile Pro Ser Ser

  50 55 60

  Trp Gly Pro Xaa

  65

  <210> SEQ ID NO 278

  <211> LENGTH: 46

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (46)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 278

  Met Pro Arg Arg Ser Arg Pro Cys Thr Leu Cys Leu Thr Leu Leu Arg

  1 5 10 15

  Arg Ala Leu Ser Ser His Leu Pro Ser Ala Cys Gln Ser Pro Arg Arg

  20 25 30

  Arg Val Gln Gly Gln Val Leu Lys Arg Leu Lys Pro Leu Xaa

  35 40 45

  <210> SEQ ID NO 279

  <211> LENGTH: 40

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (40)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 279

  Met Pro Leu Thr Leu Pro Ser Arg Leu Ala Gly Gly Asn Val Phe Leu

  1 5 10 15

  Ile Ile Phe Thr Pro Gly Phe Cys Pro Gly Arg Val Asn Val Glu Ile

  20 25 30

  Pro Gln Arg Met Leu Asp Glu Xaa

  35 40

  <210> SEQ ID NO 280

  <211> LENGTH: 11

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (11)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 280

  Met Ser Arg Arg Glu Asn Lys Phe Leu Leu Xaa

  1 5 10

  <210> SEQ ID NO 281

  <211> LENGTH: 11

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (11)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 281

  Met Ser Arg Arg Glu Asn Lys Phe Leu Leu Xaa

  1 5 10

  <210> SEQ ID NO 282

  <211> LENGTH: 47

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 282

  Met Leu Pro Ile His Leu Gln Trp Ala Cys Ala Phe Arg Ser Phe Leu

  1 5 10 15

  Leu Gly Ile Asp Ser Ser Met Phe Val Leu Phe Gln His Pro Arg Leu

  20 25 30

  Lys Asp Thr Lys Ser Ser Arg Val Ile Glu Pro Thr Leu Thr Asn

  35 40 45

  <210> SEQ ID NO 283

  <211> LENGTH: 23

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (23)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 283

  Met Ile Leu Leu Ala Phe Phe Ile Leu Leu Tyr Leu Thr Ser Phe Ser

  1 5 10 15

  Leu Ala Arg Ser Leu Pro Xaa

  20

  <210> SEQ ID NO 284

  <211> LENGTH: 21

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (21)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 284

  Ser Ser Ser Cys Met Pro Arg Lys Leu Asp Trp Phe Ser Lys Lys Val

  1 5 10 15

  Phe Leu Phe Phe Xaa

  20

  <210> SEQ ID NO 285

  <211> LENGTH: 122

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 285

  Met Gln Ala Leu Pro Pro Gly Phe Lys Gln Phe Ser Cys Leu Ser Leu

  1 5 10 15

  Pro Ser Arg Trp Asp Tyr Gly Cys Ala Thr Gln His Pro Ala Asn Phe

  20 25 30

  Cys Ile Phe Arg Arg Asp Arg Val Ser His Val Gly Gln Ala Gly Leu

  35 40 45

  Lys Leu Leu Thr Ser Val Asp Pro Pro Ala Trp Ala Ser Gln Ser Ala

  50 55 60

  Gly Ile Thr Gly Lys Ser His Cys Ala Gln Leu His Cys Cys Cys Phe

  65 70 75 80

  Leu Leu Leu Val Lys Arg Asp Gln Pro Leu Glu Lys Cys Leu Arg Leu

  85 90 95

  Phe Lys Gly Arg Ile Leu Cys Arg Gln Pro His Tyr Arg Leu Leu Ser

  100 105 110

  Asp Glu Cys Pro Gly Leu Leu Gln Asn Pro

  115 120

  <210> SEQ ID NO 286

  <211> LENGTH: 27

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (27)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 286

  Met Ile His Leu Ser Arg Phe Tyr Leu Leu Leu Ile Met Leu Pro His

  1 5 10 15

  Val Leu Phe Phe Thr Gly Asp Leu His Ser Xaa

  20 25

  <210> SEQ ID NO 287

  <211> LENGTH: 8

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (8)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 287

  Met Tyr Lys Cys Trp Tyr Arg Xaa

  1 5

  <210> SEQ ID NO 288

  <211> LENGTH: 29

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (2)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (29)

  <223> OTHER INFORMATION: Xaa equals stop translation

  <400> SEQUENCE: 288

  Met Xaa Leu Asn Lys Thr Lys Ser Leu Thr Leu Leu Glu Leu Val Phe

  1 5 10 15

  Leu Pro Gly Glu Thr Val Ser Lys Pro Ser Thr Lys Xaa

  20 25

  <210> SEQ ID NO 289

  <211> LENGTH: 65

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 289

  Val Asp Pro Arg Val Arg Arg Phe Trp Glu Asp Pro Glu Tyr Pro Pro

  1 5 10 15

  Val Ala Val Met Ser Arg Leu Met Leu Arg Arg Ile Pro Thr Val Met

  20 25 30

  Ser Asn Thr His Arg Thr Gln Pro Ser Thr Trp Glu Gln Ile Lys Lys

  35 40 45

  Leu Ser Gln Met Val Gly Glu Asn Leu Arg Lys Ala Gly Gln Pro Val

  50 55 60

  Thr

  65

  <210> SEQ ID NO 290

  <211> LENGTH: 25

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 290

  Val Arg Arg Phe Trp Glu Asp Pro Glu Tyr Pro Pro Val Ala Val Met

  1 5 10 15

  Ser Arg Leu Met Leu Arg Arg Ile Pro

  20 25

  <210> SEQ ID NO 291

  <211> LENGTH: 27

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 291

  Ser Asn Thr His Arg Thr Gln Pro Ser Thr Trp Glu Gln Ile Lys Lys

  1 5 10 15

  Leu Ser Gln Met Val Gly Glu Asn Leu Arg Lys

  20 25

  <210> SEQ ID NO 292

  <211> LENGTH: 116

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 292

  Ser Ala Cys His Ser His Thr Val Phe Asn Trp Ser Glu Gln Asn Gly

  1 5 10 15

  Gln Met Val Gln Met Val Arg Arg Met Ala Arg Val Pro Ile Ile Trp

  20 25 30

  Asn His Gly Ser Ile Gly Ala Pro Gln Pro Gln Met Ile Trp Pro Ile

  35 40 45

  Val Gly Ala Lys His Lys Asp Leu Trp Gln Leu Leu Ile Ala Leu Asn

  50 55 60

  Lys Ile Lys Ile Trp Glu Arg Ile Lys Lys His Leu Glu Gly His Ser

  65 70 75 80

  Ala Asn Leu Ser Leu Asp Ile Ala Lys Tyr Ile Tyr Ile Phe Lys Ala

  85 90 95

  Ser Gln Ala His Leu Thr Leu Met Pro Glu Leu Glu Cys Ser Lys Glu

  100 105 110

  Leu Gln Thr Asp

  115

  <210> SEQ ID NO 293

  <211> LENGTH: 25

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 293

  Met Ala Arg Val Pro Ile Ile Trp Asn His Gly Ser Ile Gly Ala Pro

  1 5 10 15

  Gln Pro Gln Met Ile Trp Pro Ile Val

  20 25

  <210> SEQ ID NO 294

  <211> LENGTH: 32

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 294

  Arg Ile Lys Lys His Leu Glu Gly His Ser Ala Asn Leu Ser Leu Asp

  1 5 10 15

  Ile Ala Lys Tyr Ile Tyr Ile Phe Lys Ala Ser Gln Ala His Leu Thr

  20 25 30

  <210> SEQ ID NO 295

  <211> LENGTH: 66

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 295

  Val Phe Leu Gln Gln Gly Leu Thr Gln Arg Ser Val Ile Leu Ile Gly

  1 5 10 15

  His Ile Cys Gln Phe Trp Leu Ala Ile Met Pro Gly Tyr Asn His Phe

  20 25 30

  Met Thr Gln Leu His Met Leu Ser Gly Leu Asn Ile Tyr His Asn Lys

  35 40 45

  Ser Ala Pro Ile Ile Glu Ala Tyr His Pro Gln Lys Ser Ile Cys Lys

  50 55 60

  Gln Asn

  65

  <210> SEQ ID NO 296

  <211> LENGTH: 28

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 296

  Ile Gly His Ile Cys Gln Phe Trp Leu Ala Ile Met Pro Gly Tyr Asn

  1 5 10 15

  His Phe Met Thr Gln Leu His Met Leu Ser Gly Leu

  20 25

  <210> SEQ ID NO 297

  <211> LENGTH: 58

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 297

  Ser Ile Pro Gly Thr Pro Asp Leu Asn Ala Arg Thr Gly Val Leu Glu

  1 5 10 15

  Gly Ala Ala Asp Arg Leu Ala Ala Ser Asn Pro Leu Lys Trp Ile Lys

  20 25 30

  Thr Leu Arg Ser Ser Val Ile Ser Met Met Ile Val Leu Leu Ile Cys

  35 40 45

  Val Val Cys Leu Tyr Ile Val Cys Arg Cys

  50 55

  <210> SEQ ID NO 298

  <211> LENGTH: 27

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 298

  Val Leu Glu Gly Ala Ala Asp Arg Leu Ala Ala Ser Asn Pro Leu Lys

  1 5 10 15

  Trp Ile Lys Thr Leu Arg Ser Ser Val Ile Ser

  20 25

  <210> SEQ ID NO 299

  <211> LENGTH: 75

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 299

  Leu Thr Val Thr Lys Leu Pro Trp Leu Phe Ile Ala Leu Gln Asn Lys

  1 5 10 15

  Arg Met Gly Thr Ser Trp Glu Gln Ala Pro Lys Ser Gly His Lys Leu

  20 25 30

  Ala Pro Lys Leu Val Ile Asn Lys Ile Ser Ala Ala Leu Ser His Ala

  35 40 45

  Cys Asp Ser Leu Thr Pro Thr Leu Glu Gly Cys Arg Phe Thr Gly Met

  50 55 60

  Arg Ala Arg Asn Asn Trp Pro Thr Gln Gly Gly

  65 70 75

  <210> SEQ ID NO 300

  <211> LENGTH: 29

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 300

  Met Gly Thr Ser Trp Glu Gln Ala Pro Lys Ser Gly His Lys Leu Ala

  1 5 10 15

  Pro Lys Leu Val Ile Asn Lys Ile Ser Ala Ala Leu Ser

  20 25

  <210> SEQ ID NO 301

  <211> LENGTH: 52

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 301

  Ser Thr His Ala Ser Val Gln Lys Lys Asp Leu Thr Lys Phe Ser Ala

  1 5 10 15

  His Ser Trp Leu Lys Lys Lys Lys Thr Phe Arg Lys Met Ile Met Glu

  20 25 30

  Glu Ile Phe Leu Asn Leu Ile Lys Asn Ile Tyr Lys Ser Pro Tyr Ser

  35 40 45

  Gln Cys Asn Thr

  50

  <210> SEQ ID NO 302

  <211> LENGTH: 17

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 302

  Val Arg Ser Glu Lys Gly Phe Asp Lys Ile Gln Cys Pro Phe Met Val

  1 5 10 15

  Lys

  <210> SEQ ID NO 303

  <211> LENGTH: 46

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 303

  Phe Ser Lys Pro Ser Ser Tyr Lys Thr Tyr Ile Pro Lys Ile Asn Leu

  1 5 10 15

  His Phe Tyr Ile Leu Leu Met Asn Ile Trp Glu Thr Ile Lys Ile Val

  20 25 30

  Pro Leu Asn Asn Cys Phe Thr Lys Met Asn Tyr Leu Gly Ile

  35 40 45

  <210> SEQ ID NO 304

  <211> LENGTH: 14

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 304

  Lys Lys Glu Thr Lys Leu Ser Leu Phe Ala Asn Asp Met Ile

  1 5 10

  <210> SEQ ID NO 305

  <211> LENGTH: 23

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 305

  Ser Pro Leu Leu Phe Asn Ile Leu Leu Glu Val Leu Ser Ser Ala Val

  1 5 10 15

  Arg Lys Glu Lys Glu Leu Lys

  20

  <210> SEQ ID NO 306

  <211> LENGTH: 122

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 306

  Leu Arg Arg Pro Ser Thr Pro Leu Arg Arg Pro Trp Leu His Leu Gln

  1 5 10 15

  Leu Pro Arg Ile Ser Leu Gly Asp Gln Arg Leu Ala Gln Ser Ala Glu

  20 25 30

  Met Tyr His Tyr Gln His Gln Arg Gln Gln Met Leu Ser Leu Glu Arg

  35 40 45

  His Lys Glu Pro Pro Lys Glu Leu Asp Thr Ala Leu Arg Met Arg Arg

  50 55 60

  Met Arg Thr Glu Thr Ser Arg Cys Thr Ser Ala Arg Ala Trp Pro Arg

  65 70 75 80

  Pro Gly Lys Trp Arg Cys Ala Thr Ile Cys Ser Thr Thr Pro His Cys

  85 90 95

  Pro Arg Pro Cys Arg Pro Pro Ala His Arg Leu His Cys His Asp Leu

  100 105 110

  Glu Ala Asp Arg Arg Pro Leu Ala Pro Arg

  115 120

  <210> SEQ ID NO 307

  <211> LENGTH: 60

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 307

  Arg Ala Thr Gln Gly Ala Gly His Gly Ser Ser Asp Glu Glu Asn Glu

  1 5 10 15

  Asp Gly Asp Phe Thr Val Tyr Glu Cys Pro Gly Met Ala Pro Thr Gly

  20 25 30

  Glu Met Glu Val Arg Asn His Leu Phe Asp His Ala Ala Leu Ser Ala

  35 40 45

  Pro Leu Pro Ala Pro Ser Ser Pro Leu Ala Leu Pro

  50 55 60

  <210> SEQ ID NO 308

  <211> LENGTH: 47

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 308

  Lys Ala Glu Tyr Ala Thr Ala Lys Ala Leu Ala Thr Pro Ala Ala Thr

  1 5 10 15

  Pro Asp Leu Ala Trp Gly Pro Ala Pro Gly Thr Glu Arg Gly Asp Val

  20 25 30

  Pro Leu Pro Ala Pro Thr Ala Thr Asp Val Val Pro Gly Ala Ala

  35 40 45

  <210> SEQ ID NO 309

  <211> LENGTH: 15

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 309

  Ser Ala Glu Met Tyr His Tyr Gln His Gln Arg Gln Gln Met Leu

  1 5 10 15

  <210> SEQ ID NO 310

  <211> LENGTH: 11

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 310

  Leu Glu Arg His Lys Glu Pro Pro Lys Glu Leu

  1 5 10

  <210> SEQ ID NO 311

  <211> LENGTH: 12

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 311

  Ala Lys Cys Pro Pro Gly Ala His Ala Cys Gly Pro

  1 5 10

  <210> SEQ ID NO 312

  <211> LENGTH: 9

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 312

  Pro Val His Met Ser Pro Leu Glu Pro

  1 5

  <210> SEQ ID NO 313

  <211> LENGTH: 12

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 313

  Trp Cys Arg Leu Gln Arg Glu Ile Arg Leu Thr Gln

  1 5 10

  <210> SEQ ID NO 314

  <211> LENGTH: 18

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 314

  Ser Ser Asp Glu Glu Asn Glu Asp Gly Asp Phe Thr Val Tyr Glu Cys

  1 5 10 15

  Pro Gly

  <210> SEQ ID NO 315

  <211> LENGTH: 10

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 315

  Ala Pro Thr Gly Glu Met Glu Val Arg Asn

  1 5 10

  <210> SEQ ID NO 316

  <211> LENGTH: 10

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 316

  Cys Pro Gly Ser Leu Asp Cys Ala Leu Lys

  1 5 10

  <210> SEQ ID NO 317

  <211> LENGTH: 60

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 317

  Arg Ala Thr Gln Gly Ala Gly His Gly Ser Ser Asp Glu Glu Asn Glu

  1 5 10 15

  Asp Gly Asp Phe Thr Val Tyr Glu Cys Pro Gly Met Ala Pro Thr Gly

  20 25 30

  Glu Met Glu Val Arg Asn His Leu Phe Asp His Ala Ala Leu Ser Ala

  35 40 45

  Pro Leu Pro Ala Pro Ser Ser Pro Leu Ala Leu Pro

  50 55 60

  <210> SEQ ID NO 318

  <211> LENGTH: 22

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 318

  Asn Glu Asp Gly Asp Phe Thr Val Tyr Glu Cys Pro Gly Met Ala Pro

  1 5 10 15

  Thr Gly Glu Met Glu Val

  20

  <210> SEQ ID NO 319

  <211> LENGTH: 159

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (114)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (123)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (129)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (136)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 319

  Arg Pro Thr Arg Pro Ser Ser Ser Cys Val Leu Pro Arg Cys Leu Arg

  1 5 10 15

  Cys Ser Arg Arg Gly Ala Arg Ser Pro Arg Arg Ala Pro Gly Leu Ala

  20 25 30

  Val Pro Cys Cys Pro Gly Gly Gly Ala Glu Gly Trp Arg Arg Arg Cys

  35 40 45

  Leu Arg Pro Pro Arg Gly Thr Cys Gly Cys Cys Gly Cys Cys Ser Pro

  50 55 60

  Ala Ser Ser Ser Ala Pro Pro Cys Val Glu Pro Pro Pro Ala Thr Arg

  65 70 75 80

  Asn Val Ala Ala Cys Pro Gly Ser Leu Asp Cys Ala Leu Lys Lys Arg

  85 90 95

  Ala Ser Val Leu Leu Val His Met Pro Val Gly Leu Pro Ser Ala Leu

  100 105 110

  Pro Xaa Gly Thr Ala Lys Ala Cys Phe Ala Xaa Met Arg Arg Ala Ser

  115 120 125

  Xaa Gly Gly Arg Ala Gln Pro Xaa Leu Glu Met Arg Leu Ile Pro Gly

  130 135 140

  Pro Arg Glu Leu Ala Arg Lys Gly Ile Trp Thr Ser Ile Pro Pro

  145 150 155

  <210> SEQ ID NO 320

  <211> LENGTH: 25

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 320

  Arg Cys Leu Arg Cys Ser Arg Arg Gly Ala Arg Ser Pro Arg Arg Ala

  1 5 10 15

  Pro Gly Leu Ala Val Pro Cys Cys Pro

  20 25

  <210> SEQ ID NO 321

  <211> LENGTH: 34

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (28)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 321

  Gly Ser Leu Asp Cys Ala Leu Lys Lys Arg Ala Ser Val Leu Leu Val

  1 5 10 15

  His Met Pro Val Gly Leu Pro Ser Ala Leu Pro Xaa Gly Thr Ala Lys

  20 25 30

  Ala Cys

  <210> SEQ ID NO 322

  <211> LENGTH: 25

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 322

  Asp Ser His Gln Ala Arg Ser Arg Arg Leu Glu Ala Leu Trp Ser Pro

  1 5 10 15

  Ser Leu Gly Glu Val Ser Ser Ser Thr

  20 25

  <210> SEQ ID NO 323

  <211> LENGTH: 8

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 323

  Arg Ser Cys Lys Glu Ile Lys Asp

  1 5

  <210> SEQ ID NO 324

  <211> LENGTH: 13

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 324

  Gly Gly Gly Trp Thr Leu Val Ala Ser Val His Glu Asn

  1 5 10

  <210> SEQ ID NO 325

  <211> LENGTH: 19

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 325

  Ala Asp Tyr Pro Glu Gly Asp Gly Asn Trp Ala Asn Tyr Asn Thr Phe

  1 5 10 15

  Gly Ser Ala

  <210> SEQ ID NO 326

  <211> LENGTH: 14

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 326

  Ala Thr Ser Asp Asp Tyr Lys Asn Pro Gly Tyr Tyr Asp Ile

  1 5 10

  <210> SEQ ID NO 327

  <211> LENGTH: 11

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 327

  Cys Ile Gly Gly Gly Gly Tyr Phe Pro Glu Ala

  1 5 10

  <210> SEQ ID NO 328

  <211> LENGTH: 11

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 328

  Glu Ile Thr Glu Ala Ala Val Leu Leu Phe Tyr

  1 5 10

  <210> SEQ ID NO 329

  <211> LENGTH: 6

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 329

  Asp Ser Asp Lys Ile Thr

  1 5

  <210> SEQ ID NO 330

  <211> LENGTH: 8

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 330

  Tyr Gln Thr Phe Cys Asp Met Thr

  1 5

  <210> SEQ ID NO 331

  <211> LENGTH: 154

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 331

  Met Gly Lys Arg Ala His Glu Val Arg Arg Pro Pro His Ser Arg Pro

  1 5 10 15

  Leu His Gly Thr Pro Ala Gly Trp Val Leu Asp Pro Ser Gly Tyr Lys

  20 25 30

  Asp Val Thr Gln Asp Ala Glu Val Met Glu Val Leu Gln Asn Leu Tyr

  35 40 45

  Arg Thr Lys Ser Phe Leu Phe Val Gly Cys Gly Glu Thr Leu Arg Asp

  50 55 60

  Gln Ile Phe Gln Ala Leu Phe Leu Tyr Ser Val Pro Asn Lys Val Asp

  65 70 75 80

  Leu Glu His Tyr Met Leu Val Leu Lys Glu Asn Glu Asp His Phe Phe

  85 90 95

  Lys His Gln Ala Asp Met Leu Leu His Gly Ile Lys Val Val Ser Tyr

  100 105 110

  Gly Asp Cys Phe Asp His Phe Pro Gly Tyr Val Gln Asp Leu Ala Thr

  115 120 125

  Gln Ile Cys Lys Gln Gln Ser Pro Gly His Leu Tyr Ser Asn Ser Trp

  130 135 140

  Ser Ala Thr Pro Asp Gly Arg Gly Gly Pro

  145 150

  <210> SEQ ID NO 332

  <211> LENGTH: 26

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 332

  Val Leu Asp Pro Ser Gly Tyr Lys Asp Val Thr Gln Asp Ala Glu Val

  1 5 10 15

  Met Glu Val Leu Gln Asn Leu Tyr Arg Thr

  20 25

  <210> SEQ ID NO 333

  <211> LENGTH: 26

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 333

  Tyr Ser Val Pro Asn Lys Val Asp Leu Glu His Tyr Met Leu Val Leu

  1 5 10 15

  Lys Glu Asn Glu Asp His Phe Phe Lys His

  20 25

  <210> SEQ ID NO 334

  <211> LENGTH: 25

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 334

  Asp Leu Ala Thr Gln Ile Cys Lys Gln Gln Ser Pro Gly His Leu Tyr

  1 5 10 15

  Ser Asn Ser Trp Ser Ala Thr Pro Asp

  20 25

  <210> SEQ ID NO 335

  <211> LENGTH: 121

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 335

  Arg Arg Met Lys Thr Ile Ser Leu Ser Ile Arg Gln Ile Cys Phe Cys

  1 5 10 15

  Thr Glu Ser Lys Leu Tyr Pro Thr Gly Thr Val Leu Thr Thr Phe Gln

  20 25 30

  Asp Met Cys Lys Thr Leu Pro Leu Arg Ser Ala Asn Ser Lys Ala Gln

  35 40 45

  Asp Ile Cys Thr Arg Ile His Gly Val Pro Leu Leu Met Gly Glu Glu

  50 55 60

  Ala His Asp Ser Asp Ser His Ala Ser Asp Arg Gly His His Thr Met

  65 70 75 80

  Leu Pro Leu Pro Ala Gly Ser Phe Ser Glu Ser Ser His Gln Ala Trp

  85 90 95

  Glu Val Glu Met Leu Ile Ala Trp Thr Ala Pro His Tyr Trp Val Met

  100 105 110

  His Ala Arg Thr Val Gln Arg Gly Ser

  115 120

  <210> SEQ ID NO 336

  <211> LENGTH: 27

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 336

  Thr Glu Ser Lys Leu Tyr Pro Thr Gly Thr Val Leu Thr Thr Phe Gln

  1 5 10 15

  Asp Met Cys Lys Thr Leu Pro Leu Arg Ser Ala

  20 25

  <210> SEQ ID NO 337

  <211> LENGTH: 27

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 337

  Leu Met Gly Glu Glu Ala His Asp Ser Asp Ser His Ala Ser Asp Arg

  1 5 10 15

  Gly His His Thr Met Leu Pro Leu Pro Ala Gly

  20 25

  <210> SEQ ID NO 338

  <211> LENGTH: 86

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 338

  Leu Cys Ala Val Glu Lys Thr Arg Thr Phe Thr Arg Gly Asp Cys Gly

  1 5 10 15

  Pro Asn Arg His His Lys His Val Leu Lys Ala Lys Asp Asn Asn His

  20 25 30

  Ile Gln Arg His Gln Phe Ser Ser Thr Leu Glu Phe Ser Ser Asn Ser

  35 40 45

  Thr Asp Gly Leu Lys Tyr Ile Cys Val Tyr Leu Tyr Val Cys Thr His

  50 55 60

  Pro Cys Ile Tyr Ile Tyr Leu Ser Ala His Thr Leu His Met Tyr Thr

  65 70 75 80

  His Tyr Leu Cys Lys Ile

  85

  <210> SEQ ID NO 339

  <211> LENGTH: 30

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 339

  Ser Ser Thr Leu Glu Phe Ser Ser Asn Ser Thr Asp Gly Leu Lys Tyr

  1 5 10 15

  Ile Cys Val Tyr Leu Tyr Val Cys Thr His Pro Cys Ile Tyr

  20 25 30

  <210> SEQ ID NO 340

  <211> LENGTH: 69

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 340

  Ser Thr Ser Val Cys Ile Cys Thr Cys Ala His Thr His Val Tyr Ile

  1 5 10 15

  Phe Ile Tyr Leu His Thr His Tyr Ile Cys Ile His Thr Ile Tyr Val

  20 25 30

  Lys Tyr Asn Ile Cys Ile Met His Ile Asn Ser Asn Lys Cys Ile Cys

  35 40 45

  Val Ile Phe Lys Ile Glu Gln Leu Tyr Leu Glu Val Val Asn Ala Glu

  50 55 60

  Asn Trp Phe Tyr Cys

  65

  <210> SEQ ID NO 341

  <211> LENGTH: 31

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 341

  Ile His Thr Ile Tyr Val Lys Tyr Asn Ile Cys Ile Met His Ile Asn

  1 5 10 15

  Ser Asn Lys Cys Ile Cys Val Ile Phe Lys Ile Glu Gln Leu Tyr

  20 25 30

  <210> SEQ ID NO 342

  <211> LENGTH: 9

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 342

  Asn Ser Ala Val Thr Val Gln Met Ala

  1 5

  <210> SEQ ID NO 343

  <211> LENGTH: 8

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 343

  Thr Lys Thr Ser Thr Pro Leu Arg

  1 5

  <210> SEQ ID NO 344

  <211> LENGTH: 14

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 344

  Val Cys Ile Pro Gly Ala Ala Gly Leu Ser Val Leu Leu Gly

  1 5 10

  <210> SEQ ID NO 345

  <211> LENGTH: 45

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 345

  Ser Ile Leu Pro Val Glu Met Ala Ala Ala Val Ala Gly Met Leu Arg

  1 5 10 15

  Gly Gly Leu Leu Pro Gln Ala Gly Arg Leu Pro Thr Leu Gln Thr Val

  20 25 30

  Arg Tyr Gly Ser Lys Ala Val Thr Arg His Arg Arg Val

  35 40 45

  <210> SEQ ID NO 346

  <211> LENGTH: 26

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 346

  Ala Gly Met Leu Arg Gly Gly Leu Leu Pro Gln Ala Gly Arg Leu Pro

  1 5 10 15

  Thr Leu Gln Thr Val Arg Tyr Gly Ser Lys

  20 25

  <210> SEQ ID NO 347

  <211> LENGTH: 24

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 347

  Ala Arg Ala Gly Gln Met Gln Asn Leu Glu Ser Ala Arg Ala Gly Arg

  1 5 10 15

  Ser Val Ser Thr Gln Thr Gly Ser

  20

  <210> SEQ ID NO 348

  <211> LENGTH: 300

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (4)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (62)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 348

  Lys His Glu Xaa His Gln Val Ser Asp Gly Ala Leu Arg Cys Phe Ala

  1 5 10 15

  Ser Leu Ala Asp Arg Phe Thr Arg Arg Gly Val Asp Pro Ala Pro Leu

  20 25 30

  Ala Lys His Gly Leu Thr Glu Glu Leu Leu Ser Arg Met Ala Ala Ala

  35 40 45

  Gly Gly Thr Val Ser Gly Pro Ser Ser Ala Cys Lys Pro Xaa Arg Ser

  50 55 60

  Thr Thr Gly Ala Pro Ser Thr Thr Ala Asp Ser Lys Leu Ser Asn Gln

  65 70 75 80

  Val Ser Thr Ile Val Ser Leu Leu Ser Thr Leu Cys Arg Gly Ser Pro

  85 90 95

  Val Val Thr His Asp Leu Leu Arg Ser Glu Leu Pro Asp Ser Ile Glu

  100 105 110

  Ser Ala Leu Gln Gly Asp Glu Arg Cys Val Leu Asp Thr Met Arg Leu

  115 120 125

  Val Asp Phe Leu Leu Val Leu Leu Phe Glu Gly Arg Lys Ala Leu Pro

  130 135 140

  Lys Ser Ser Ala Gly Ser Thr Gly Arg Ile Pro Gly Leu Arg Arg Leu

  145 150 155 160

  Asp Ser Ser Gly Glu Arg Ser His Arg Gln Leu Ile Asp Cys Ile Arg

  165 170 175

  Ser Lys Asp Thr Asp Ala Leu Ile Asp Ala Ile Asp Thr Gly Ala Phe

  180 185 190

  Glu Val Asn Phe Met Asp Asp Val Gly Gln Thr Leu Leu Asn Trp Ala

  195 200 205

  Ser Ala Phe Gly Thr Gln Glu Met Val Glu Phe Leu Cys Glu Arg Gly

  210 215 220

  Ala Asp Val Asn Arg Gly Gln Arg Ser Ser Ser Leu His Tyr Ala Ala

  225 230 235 240

  Cys Phe Gly Arg Pro Gln Val Ala Lys Thr Leu Leu Arg His Gly Ala

  245 250 255

  Asn Pro Asp Leu Arg Asp Glu Asp Gly Lys Thr Pro Leu Asp Lys Ala

  260 265 270

  Arg Glu Arg Gly His Ser Glu Val Val Ala Ile Leu Gln Ser Pro Gly

  275 280 285

  Asp Trp Met Cys Pro Val Asn Lys Gly Asp Asp Lys

  290 295 300

  <210> SEQ ID NO 349

  <211> LENGTH: 17

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 349

  Pro Leu Asp Lys Ala Arg Glu Arg Gly His Ser Glu Val Val Ala Ile

  1 5 10 15

  Leu

  <210> SEQ ID NO 350

  <211> LENGTH: 15

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 350

  Ala Lys Thr Leu Leu Arg His Gly Ala Asn Pro Asp Leu Arg Asp

  1 5 10 15

  <210> SEQ ID NO 351

  <211> LENGTH: 54

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (49)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (50)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (52)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 351

  Gly Arg Gly Arg Ala Trp Leu Cys Arg Arg Pro Val Gly Ser Trp Ile

  1 5 10 15

  Gly Ala Val Trp Asn Asp Lys Pro Asp Lys Glu Thr Phe Lys Lys Pro

  20 25 30

  Trp Gln Met Trp Thr Gln Ile His Cys Trp Asn Gly Tyr Arg Trp Asp

  35 40 45

  Xaa Xaa Asp Xaa Lys Asp

  50

  <210> SEQ ID NO 352

  <211> LENGTH: 23

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 352

  Ser Trp Ile Gly Ala Val Trp Asn Asp Lys Pro Asp Lys Glu Thr Phe

  1 5 10 15

  Lys Lys Pro Trp Gln Met Trp

  20

  <210> SEQ ID NO 353

  <211> LENGTH: 30

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (19)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (22)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 353

  Lys Thr Met Ala Asp Val Asp Pro Asp Thr Leu Leu Glu Trp Leu Gln

  1 5 10 15

  Met Gly Xaa Gly Arg Xaa Lys Gly His Ala Thr Asn Thr Pro

  20 25 30

  <210> SEQ ID NO 354

  <211> LENGTH: 34

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 354

  Arg Gly Val Asp Pro Ala Pro Leu Ala Lys His Gly Leu Thr Glu Glu

  1 5 10 15

  Leu Leu Ser Arg Met Ala Ala Ala Gly Gly Thr Val Ser Gly Pro Ser

  20 25 30

  Ser Ala

  <210> SEQ ID NO 355

  <211> LENGTH: 31

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 355

  Arg Ser Thr Thr Gly Ala Pro Ser Thr Thr Ala Asp Ser Lys Leu Ser

  1 5 10 15

  Asn Gln Val Ser Thr Ile Val Ser Leu Leu Ser Thr Leu Cys Arg

  20 25 30

  <210> SEQ ID NO 356

  <211> LENGTH: 34

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 356

  Phe Glu Val Asn Phe Met Asp Asp Val Gly Gln Thr Leu Leu Asn Trp

  1 5 10 15

  Ala Ser Ala Phe Gly Thr Gln Glu Met Val Glu Phe Leu Cys Glu Arg

  20 25 30

  Gly Ala

  <210> SEQ ID NO 357

  <211> LENGTH: 28

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 357

  Glu Asp Gly Lys Thr Pro Leu Asp Lys Ala Arg Glu Arg Gly His Ser

  1 5 10 15

  Glu Val Val Ala Ile Leu Gln Ser Pro Gly Asp Trp

  20 25

  <210> SEQ ID NO 358

  <211> LENGTH: 15

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 358

  Thr Arg Pro Thr Met Pro Asn Phe Leu Trp Phe Pro Lys Cys Ala

  1 5 10 15

  <210> SEQ ID NO 359

  <211> LENGTH: 44

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 359

  Leu Pro Pro Cys Leu Ala Gln Ile Phe Pro Phe Phe Ser Ser Gly Thr

  1 5 10 15

  Asn Leu Thr Phe Cys Phe Phe Val Phe Val Phe Val Phe Val Phe Ala

  20 25 30

  Glu Leu Asp Tyr Arg Asn Ser Tyr Glu Ile Glu Tyr

  35 40

  <210> SEQ ID NO 360

  <211> LENGTH: 9

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 360

  Leu Lys Cys Thr Ile Tyr Gly Gly Ala

  1 5

  <210> SEQ ID NO 361

  <211> LENGTH: 56

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 361

  His Val Leu Trp Ser Leu Leu Ser Ala Cys Trp Thr Gln Phe Leu Val

  1 5 10 15

  Tyr Phe Cys Cys Leu Met Ile Leu Gln Arg Thr Phe Pro Pro Arg Ala

  20 25 30

  Leu Arg Thr Ser Pro Trp Leu Ser Asn Pro Met Gly Val Lys Gly Lys

  35 40 45

  Lys Lys Lys Gly Thr Phe Met Glu

  50 55

  <210> SEQ ID NO 362

  <211> LENGTH: 30

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 362

  Phe Leu Val Tyr Phe Cys Cys Leu Met Ile Leu Gln Arg Thr Phe Pro

  1 5 10 15

  Pro Arg Ala Leu Arg Thr Ser Pro Trp Leu Ser Asn Pro Met

  20 25 30

  <210> SEQ ID NO 363

  <211> LENGTH: 52

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (26)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (29)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 363

  Asp Cys Asn Arg Asp Tyr His Lys Ala Phe Gly Asn Leu Arg Ser Pro

  1 5 10 15

  Gly Trp Pro Asp Asn Tyr Asp Asn Asp Xaa Asp Cys Xaa Val Thr Leu

  20 25 30

  Thr Ala Pro Gln Asn His His Ser Gly Ile Val Glu Asn Ala Glu Thr

  35 40 45

  Ile Ser Trp Arg

  50

  <210> SEQ ID NO 364

  <211> LENGTH: 15

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 364

  Phe Gly Asn Leu Arg Ser Pro Gly Trp Pro Asp Asn Tyr Asp Asn

  1 5 10 15

  <210> SEQ ID NO 365

  <211> LENGTH: 16

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (6)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 365

  Ala Pro Gln Asn His Xaa Leu Lys Cys Arg Asn Asp Phe Leu Glu Val

  1 5 10 15

  <210> SEQ ID NO 366

  <211> LENGTH: 7

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 366

  Ala Ser Phe Tyr Arg Thr Ser

  1 5

  <210> SEQ ID NO 367

  <211> LENGTH: 26

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 367

  Lys Ala Asp Val Lys Trp His Met Cys Leu Gln Ser Pro Leu Cys Gly

  1 5 10 15

  Leu Phe Cys Ser Ile Glu Gly Val Leu Lys

  20 25

  <210> SEQ ID NO 368

  <211> LENGTH: 218

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (59)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (99)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (101)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 368

  Ala Cys Met Asn Pro Ala Met Cys Phe Val Cys Ala Cys Pro His Thr

  1 5 10 15

  Gly Ser Thr Pro Glu Lys Ala Ile Leu Gln Gly Arg Leu Ile Ser Leu

  20 25 30

  Gly Thr Ser Leu Ser Pro Ala Ser Asn Gly Ser Gly Gln Gln Ser Phe

  35 40 45

  Ser Ile Cys Met Ile Asn Pro Ser Leu Pro Xaa Ser Thr Ser Ser His

  50 55 60

  His Leu Phe Ser Val Leu Thr Gly Asp Leu Asp Ser Tyr Ser Gln Arg

  65 70 75 80

  Lys Leu Lys Pro Thr Ser Arg Lys Ser Phe Leu Leu Pro Lys Thr Gln

  85 90 95

  Thr Tyr Xaa Val Xaa His Pro Ser Ser Pro Pro Leu Val Leu Val Gln

  100 105 110

  His Arg Ser Pro Leu Ser Thr Tyr Pro Lys Pro Val Pro Ser Cys Cys

  115 120 125

  Ala Leu Asp Leu Ile Ser Val Ile Ala Leu Glu Thr Phe Leu Val Tyr

  130 135 140

  Ile His Leu Phe Pro Ser Ile Asp Leu Ser Tyr Trp Ile Leu Ser Met

  145 150 155 160

  Leu Gln Pro Leu Leu Leu Ile Lys Gln Gln Ser Thr Lys Thr Leu Ser

  165 170 175

  Leu Asn Cys Met Leu Tyr Ser Ser Tyr Tyr Leu Ile Ser Phe Leu Ser

  180 185 190

  Phe Lys Ala Lys Val Leu Arg Arg Gly Gly Asn Ile Leu His His Phe

  195 200 205

  Phe Thr Ser Tyr Ser Phe Phe Asn Thr Tyr

  210 215

  <210> SEQ ID NO 369

  <211> LENGTH: 28

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 369

  Cys Pro His Thr Gly Ser Thr Pro Glu Lys Ala Ile Leu Gln Gly Arg

  1 5 10 15

  Leu Ile Ser Leu Gly Thr Ser Leu Ser Pro Ala Ser

  20 25

  <210> SEQ ID NO 370

  <211> LENGTH: 24

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 370

  Gln His Arg Ser Pro Leu Ser Thr Tyr Pro Lys Pro Val Pro Ser Cys

  1 5 10 15

  Cys Ala Leu Asp Leu Ile Ser Val

  20

  <210> SEQ ID NO 371

  <211> LENGTH: 29

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 371

  Ile Lys Gln Gln Ser Thr Lys Thr Leu Ser Leu Asn Cys Met Leu Tyr

  1 5 10 15

  Ser Ser Tyr Tyr Leu Ile Ser Phe Leu Ser Phe Lys Ala

  20 25

  <210> SEQ ID NO 372

  <211> LENGTH: 24

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 372

  Lys Tyr Leu Val Ser Ser Val Leu Pro Thr Ile Ser Met Ala Arg Ser

  1 5 10 15

  Leu Ile Ser Ala Leu Arg Ser Gly

  20

  <210> SEQ ID NO 373

  <211> LENGTH: 27

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 373

  Met Arg Thr Leu Phe Gly Ala Val Arg Ala Pro Phe Ser Ser Leu Thr

  1 5 10 15

  Leu Leu Leu Ile Thr Pro Ser Pro Ser Pro Leu

  20 25

  <210> SEQ ID NO 374

  <211> LENGTH: 10

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 374

  Met Ala Tyr Ala Phe His Arg Thr Ser Thr

  1 5 10

  <210> SEQ ID NO 375

  <211> LENGTH: 22

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 375

  Leu Lys Ser Thr Tyr Thr Leu Leu Ser Ile Leu Trp Phe Leu Val Leu

  1 5 10 15

  Ile Pro Val Glu Gly Asn

  20

  <210> SEQ ID NO 376

  <211> LENGTH: 18

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 376

  Gly Pro Leu Leu Ala Ser His Ala Thr Leu Cys Phe Ser Leu Gly Ser

  1 5 10 15

  Lys Phe

  <210> SEQ ID NO 377

  <211> LENGTH: 10

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 377

  Thr Val Trp Gly Ile Leu Pro Arg Lys Arg

  1 5 10

  <210> SEQ ID NO 378

  <211> LENGTH: 20

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 378

  Ala Ser Ile Asp Thr Trp Pro Gly Arg Arg Ser Gly Gly Met Ile Val

  1 5 10 15

  Ile Thr Ser Ile

  20

  <210> SEQ ID NO 379

  <211> LENGTH: 41

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 379

  Gly Ser Pro Gln Ala Glu Thr Arg Trp Ser Asp Pro Ile Ala Leu His

  1 5 10 15

  Gln Gly Lys Ser Pro Ala Ser Ile Asp Thr Trp Pro Gly Arg Arg Ser

  20 25 30

  Gly Gly Met Ile Val Ile Thr Ser Ile

  35 40

  <210> SEQ ID NO 380

  <211> LENGTH: 43

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (2)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 380

  Val Xaa Asp Ile Thr Phe Asp Pro Asp Thr Ala His Lys Tyr Leu Arg

  1 5 10 15

  Leu Gln Glu Glu Asn Arg Lys Val Thr Asn Thr Thr Pro Trp Glu His

  20 25 30

  Pro Tyr Pro Asp Leu Pro Ser Arg Phe Leu His

  35 40

  <210> SEQ ID NO 381

  <211> LENGTH: 19

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 381

  Leu Tyr Leu His Arg Tyr Tyr Phe Glu Val Glu Ile Phe Gly Ala Gly

  1 5 10 15

  Thr Tyr Val

  <210> SEQ ID NO 382

  <211> LENGTH: 22

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 382

  Ser Cys Ile Ser Gly Asn Asn Phe Ser Trp Ser Leu Gln Trp Asn Gly

  1 5 10 15

  Lys Glu Phe Thr Ala Trp

  20

  <210> SEQ ID NO 383

  <211> LENGTH: 17

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 383

  Thr Pro Leu Lys Ala Gly Pro Phe Trp Ser Ser Gly Ser Ile Leu Thr

  1 5 10 15

  Ser

  <210> SEQ ID NO 384

  <211> LENGTH: 39

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (32)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 384

  Ser Val Ser Glu Val Lys Ala Val Ala Glu Met Gln Phe Gly Glu Leu

  1 5 10 15

  Leu Ala Ala Val Arg Lys Ala Gln Ala Asn Val Met Leu Phe Leu Xaa

  20 25 30

  Glu Lys Glu Gln Ala Ala Leu

  35

  <210> SEQ ID NO 385

  <211> LENGTH: 43

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 385

  Glu Lys Ser Lys Gln Glu Leu Glu Thr Met Ala Ala Ile Ser Asn Thr

  1 5 10 15

  Val Gln Phe Leu Glu Glu Tyr Cys Lys Phe Lys Asn Thr Glu Asp Ile

  20 25 30

  Thr Phe Pro Ser Val Tyr Ile Gly Leu Lys Asp

  35 40

  <210> SEQ ID NO 386

  <211> LENGTH: 29

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (26)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 386

  Leu Glu Asn Tyr Lys Lys Lys Leu Gln Glu Phe Ser Lys Glu Glu Glu

  1 5 10 15

  Tyr Asp Ile Arg Thr Gln Val Ser Ala Xaa Val Gln Arg

  20 25

  <210> SEQ ID NO 387

  <211> LENGTH: 38

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 387

  Gly Val Tyr Ile Asp Phe Pro Gly Gly Ile Leu Ser Phe Tyr Gly Val

  1 5 10 15

  Glu Tyr Asp Ser Met Thr Leu Val His Lys Phe Ala Cys Lys Phe Ser

  20 25 30

  Glu Pro Val Tyr Ala Ala

  35

  <210> SEQ ID NO 388

  <211> LENGTH: 10

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 388

  Gly Thr Val Ser Arg Glu Arg Arg Ala Gly

  1 5 10

  <210> SEQ ID NO 389

  <211> LENGTH: 82

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 389

  His Gly Asp Pro Thr Gln Ser Trp Pro Phe Leu Glu Leu Gly Val Tyr

  1 5 10 15

  Ile Asp Phe Pro Gly Gly Ile Leu Ser Phe Tyr Gly Val Glu Tyr Asp

  20 25 30

  Ser Met Thr Leu Val His Lys Phe Ala Cys Lys Phe Ser Glu Pro Val

  35 40 45

  Tyr Ala Ala Phe Trp Leu Ser Lys Lys Glu Asn Ala Ile Arg Ile Val

  50 55 60

  Asp Leu Gly Glu Glu Pro Glu Lys Pro Ala Pro Ser Leu Val Gly Thr

  65 70 75 80

  Ala Pro

  <210> SEQ ID NO 390

  <211> LENGTH: 30

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 390

  Ser Phe Tyr Gly Val Glu Tyr Asp Ser Met Thr Leu Val His Lys Phe

  1 5 10 15

  Ala Cys Lys Phe Ser Glu Pro Val Tyr Ala Ala Phe Trp Leu

  20 25 30

  <210> SEQ ID NO 391

  <211> LENGTH: 337

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (65)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (150)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (151)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (177)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (200)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (278)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (284)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 391

  Ala Glu Leu Gln Cys Thr Gln Leu Asp Leu Glu Arg Lys Leu Lys Leu

  1 5 10 15

  Asn Glu Asn Ala Ile Ser Arg Leu Gln Ala Asn Gln Lys Ser Val Leu

  20 25 30

  Val Ser Val Ser Glu Val Lys Ala Val Ala Glu Met Gln Phe Gly Glu

  35 40 45

  Leu Leu Ala Ala Val Arg Lys Ala Gln Ala Asn Val Met Leu Phe Leu

  50 55 60

  Xaa Glu Lys Glu Gln Ala Ala Leu Ser Gln Ala Asn Gly Ile Lys Ala

  65 70 75 80

  His Leu Glu Tyr Lys Ser Ala Glu Met Glu Lys Ser Lys Gln Glu Leu

  85 90 95

  Glu Thr Met Ala Ala Ile Ser Asn Thr Val Gln Phe Leu Glu Glu Tyr

  100 105 110

  Cys Lys Phe Lys Asn Thr Glu Asp Ile Thr Phe Pro Ser Val Tyr Ile

  115 120 125

  Gly Leu Lys Asp Lys Leu Ser Gly Ile Arg Lys Val Ile Thr Glu Ser

  130 135 140

  Thr Val His Leu Ile Xaa Xaa Leu Glu Asn Tyr Lys Lys Lys Leu Gln

  145 150 155 160

  Glu Phe Ser Lys Glu Glu Glu Tyr Asp Ile Arg Thr Gln Val Ser Ala

  165 170 175

  Xaa Val Gln Arg Lys Tyr Trp Thr Ser Lys Pro Glu Pro Ser Thr Arg

  180 185 190

  Glu Gln Phe Leu Gln Tyr Val Xaa Asp Ile Thr Phe Asp Pro Asp Thr

  195 200 205

  Ala His Lys Tyr Leu Arg Leu Gln Glu Glu Asn Arg Lys Val Thr Asn

  210 215 220

  Thr Thr Pro Trp Glu His Pro Tyr Pro Asp Leu Pro Ser Arg Phe Leu

  225 230 235 240

  His Trp Arg Gln Val Leu Ser Gln Gln Ser Leu Tyr Leu His Arg Tyr

  245 250 255

  Tyr Phe Glu Val Glu Ile Phe Gly Ala Gly Thr Tyr Val Gly Leu Thr

  260 265 270

  Cys Lys Gly Ile Asp Xaa Lys Gly Glu Glu Arg Xaa Ser Cys Ile Ser

  275 280 285

  Gly Asn Asn Phe Ser Trp Ser Leu Gln Trp Asn Gly Lys Glu Phe Thr

  290 295 300

  Ala Trp Tyr Ser Asp Met Glu Thr Pro Leu Lys Ala Gly Pro Phe Trp

  305 310 315 320

  Ser Ser Gly Ser Ile Leu Thr Ser Gln Glu Gly Ser Phe Pro Ser Met

  325 330 335

  Ala

  <210> SEQ ID NO 392

  <211> LENGTH: 301

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (166)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (172)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (250)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (299)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (300)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 392

  Arg Thr Ala Pro Tyr Gly Ala Lys Glu Ser Ser Trp Arg Met Phe Ser

  1 5 10 15

  Phe Arg Asp Pro Ile Gly Phe Gln Lys Pro Ala Thr Ile Ser Ser Tyr

  20 25 30

  Phe Cys Pro Gln Ile Thr Leu Lys Cys Lys Ser His His Cys Ser Trp

  35 40 45

  Gln Arg Ser Gly Ile Trp Leu Leu Glu Ser Arg Glu Gln Ser Pro Pro

  50 55 60

  Arg Thr Val Leu Ala Ser Arg Val Pro Leu Pro Asp Leu Gln Ser Gly

  65 70 75 80

  Trp Arg Phe Pro Ser Trp Lys Ala Arg Arg Gln His Arg Leu Val Leu

  85 90 95

  Lys Thr Cys Arg Gln Thr Cys Glu Pro Glu Ser Trp Asn His Thr Leu

  100 105 110

  Arg His Arg Arg Lys Gly Ser Leu Leu Gly Ser Gln Tyr Arg Pro Arg

  115 120 125

  Ala Pro Glu Arg Ala Ser Phe Glu Trp Gly Leu His Val Thr Val Pro

  130 135 140

  Gly Arg Glu Leu Leu Pro Val Pro Leu Glu Ala Pro Gly Glu Val Val

  145 150 155 160

  Ser Gly Asn Ala Thr Xaa Ala Leu Leu Pro Phe Xaa Val Asp Ala Phe

  165 170 175

  Ala Gly Gln Ala Asn Ile Gly Ala Cys Pro Glu Asp Leu His Leu Lys

  180 185 190

  Ile Val Pro Val Gln Val Gln Thr Leu Leu Gly Gln His Leu Pro Pro

  195 200 205

  Val Gln Glu Pro Ala Gly Glu Val Arg Val Gly Met Leu Pro Gly Arg

  210 215 220

  Gly Val Gly Asp Leu Ala Val Leu Leu Leu Gln Pro Glu Ile Leu Val

  225 230 235 240

  Cys Cys Val Arg Val Glu Arg Asp Val Xaa His Ile Leu Glu Glu Leu

  245 250 255

  Phe Pro Gly Ala Gly Leu Arg Phe Gly Ser Pro Ile Phe Ala Leu Asn

  260 265 270

  Asn Gly Arg His Leu Ser Ser Asp Val Ile Leu Leu Phe Leu Gly Lys

  275 280 285

  Leu Leu Glu Leu Phe Leu Ile Val Leu Gln Xaa Xaa Asp

  290 295 300

  <210> SEQ ID NO 393

  <211> LENGTH: 196

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 393

  Ser Lys Ile Lys Tyr Asp Trp Tyr Gln Thr Glu Ser Gln Val Val Ile

  1 5 10 15

  Thr Leu Met Ile Lys Asn Val Gln Lys Asn Asp Val Asn Val Glu Phe

  20 25 30

  Ser Glu Lys Glu Leu Ser Ala Leu Val Lys Leu Pro Ser Gly Glu Asp

  35 40 45

  Tyr Asn Leu Lys Leu Glu Leu Leu His Pro Ile Ile Pro Glu Gln Ser

  50 55 60

  Thr Phe Lys Val Leu Ser Thr Lys Ile Glu Ile Lys Leu Lys Lys Pro

  65 70 75 80

  Glu Ala Val Arg Trp Glu Lys Leu Glu Gly Gln Gly Asp Val Pro Thr

  85 90 95

  Pro Lys Gln Phe Val Ala Asp Val Lys Asn Leu Tyr Pro Ser Ser Ser

  100 105 110

  Pro Tyr Thr Arg Asn Trp Asp Lys Leu Val Gly Glu Ile Lys Glu Glu

  115 120 125

  Glu Lys Asn Glu Lys Leu Glu Gly Asp Ala Ala Leu Asn Arg Leu Phe

  130 135 140

  Gln Gln Ile Tyr Ser Asp Gly Ser Asp Glu Val Lys Arg Ala Met Asn

  145 150 155 160

  Lys Ser Phe Met Glu Ser Gly Gly Thr Val Leu Ser Thr Asn Trp Ser

  165 170 175

  Asp Val Gly Lys Arg Lys Val Glu Ile Asn Pro Pro Asp Asp Met Glu

  180 185 190

  Trp Lys Lys Tyr

  195

  <210> SEQ ID NO 394

  <211> LENGTH: 39

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 394

  Gly Asp Ala Ala Leu Asn Arg Leu Phe Gln Gln Ile Tyr Ser Asp Gly

  1 5 10 15

  Ser Asp Glu Val Lys Arg Ala Met Asn Lys Ser Phe Met Glu Ser Gly

  20 25 30

  Gly Thr Val Leu Ser Thr Asn

  35

  <210> SEQ ID NO 395

  <211> LENGTH: 23

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 395

  Asp Trp Tyr Gln Thr Glu Ser Gln Val Val Ile Thr Leu Met Ile Lys

  1 5 10 15

  Asn Val Gln Lys Asn Asp Val

  20

  <210> SEQ ID NO 396

  <211> LENGTH: 146

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (9)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (10)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 396

  Met Ala Ala Ala Ala Ala Gly Thr Xaa Xaa Ser Gln Arg Phe Phe Gln

  1 5 10 15

  Ser Phe Ser Asp Ala Leu Ile Asp Glu Asp Pro Gln Ala Ala Leu Glu

  20 25 30

  Glu Leu Thr Lys Ala Leu Glu Gln Lys Pro Asp Asp Ala Gln Tyr Tyr

  35 40 45

  Cys Gln Arg Ala Tyr Cys His Ile Leu Leu Gly Asn Tyr Cys Val Ala

  50 55 60

  Val Ala Asp Ala Lys Lys Ser Leu Glu Leu Asn Pro Asn Asn Ser Thr

  65 70 75 80

  Ala Met Leu Arg Lys Gly Ile Cys Glu Tyr His Glu Lys Asn Tyr Ala

  85 90 95

  Ala Ala Leu Glu Thr Phe Thr Glu Gly Gln Lys Leu Asp Ser Ala Asp

  100 105 110

  Ala Asn Phe Ser Val Trp Ile Lys Arg Cys Gln Glu Ala Gln Asn Gly

  115 120 125

  Ser Glu Ser Glu Val Val Ser Pro Lys Phe Ser Phe Phe Met Phe Leu

  130 135 140

  Leu Phe

  145

  <210> SEQ ID NO 397

  <211> LENGTH: 38

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 397

  Leu Glu Glu Leu Thr Lys Ala Leu Glu Gln Lys Pro Asp Asp Ala Gln

  1 5 10 15

  Tyr Tyr Cys Gln Arg Ala Tyr Cys His Ile Leu Leu Gly Asn Tyr Cys

  20 25 30

  Val Ala Val Ala Asp Ala

  35

  <210> SEQ ID NO 398

  <211> LENGTH: 31

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 398

  Ala Met Leu Arg Lys Gly Ile Cys Glu Tyr His Glu Lys Asn Tyr Ala

  1 5 10 15

  Ala Ala Leu Glu Thr Phe Thr Glu Gly Gln Lys Leu Asp Ser Ala

  20 25 30

  <210> SEQ ID NO 399

  <211> LENGTH: 37

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 399

  Leu Arg Leu Trp Asn Arg Asn Gln Met Met His Ser Ile Ile Val Lys

  1 5 10 15

  Glu Leu Ile Val Thr Phe Phe Leu Gly Ile Thr Val Leu Leu Leu Leu

  20 25 30

  Met Gln Arg Ser Leu

  35

  <210> SEQ ID NO 400

  <211> LENGTH: 10

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 400

  Asn Ser Ile Gln Ile Ile Pro Leu Leu Cys

  1 5 10

  <210> SEQ ID NO 401

  <211> LENGTH: 228

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 401

  Tyr Met His Phe Asn Asn Thr Val Ala Lys Leu Thr Cys Lys Asn Leu

  1 5 10 15

  Ser Leu Ser Thr Tyr Gln Asn Gln Ser Ala Ser Gln Trp Thr His Gln

  20 25 30

  Ser Lys Ile Lys Tyr Asp Trp Tyr Gln Thr Glu Ser Gln Val Val Ile

  35 40 45

  Thr Leu Met Ile Lys Asn Val Gln Lys Asn Asp Val Asn Val Glu Phe

  50 55 60

  Ser Glu Lys Glu Leu Ser Ala Leu Val Lys Leu Pro Ser Gly Glu Asp

  65 70 75 80

  Tyr Asn Leu Lys Leu Glu Leu Leu His Pro Ile Ile Pro Glu Gln Ser

  85 90 95

  Thr Phe Lys Val Leu Ser Thr Lys Ile Glu Ile Lys Leu Lys Lys Pro

  100 105 110

  Glu Ala Val Arg Trp Glu Lys Leu Glu Gly Gln Gly Asp Val Pro Thr

  115 120 125

  Pro Lys Gln Phe Val Ala Asp Val Lys Asn Leu Tyr Pro Ser Ser Ser

  130 135 140

  Pro Tyr Thr Arg Asn Trp Asp Lys Leu Val Gly Glu Ile Lys Glu Glu

  145 150 155 160

  Glu Lys Asn Glu Lys Leu Glu Gly Asp Ala Ala Leu Asn Arg Leu Phe

  165 170 175

  Gln Gln Ile Tyr Ser Asp Gly Ser Asp Glu Val Lys Arg Ala Met Asn

  180 185 190

  Lys Ser Phe Met Glu Ser Gly Gly Thr Val Leu Ser Thr Asn Trp Ser

  195 200 205

  Asp Val Gly Lys Arg Lys Val Glu Ile Asn Pro Pro Asp Asp Met Glu

  210 215 220

  Trp Lys Lys Tyr

  225

  <210> SEQ ID NO 402

  <211> LENGTH: 29

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 402

  Thr Cys Lys Asn Leu Ser Leu Ser Thr Tyr Gln Asn Gln Ser Ala Ser

  1 5 10 15

  Gln Trp Thr His Gln Ser Lys Ile Lys Tyr Asp Trp Tyr

  20 25

  <210> SEQ ID NO 403

  <211> LENGTH: 24

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 403

  Glu Lys Glu Leu Ser Ala Leu Val Lys Leu Pro Ser Gly Glu Asp Tyr

  1 5 10 15

  Asn Leu Lys Leu Glu Leu Leu His

  20

  <210> SEQ ID NO 404

  <211> LENGTH: 29

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 404

  Leu His Pro Ile Ile Pro Glu Gln Ser Thr Phe Lys Val Leu Ser Thr

  1 5 10 15

  Lys Ile Glu Ile Lys Leu Lys Lys Pro Glu Ala Val Arg

  20 25

  <210> SEQ ID NO 405

  <211> LENGTH: 24

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 405

  Lys Gln Phe Val Ala Asp Val Lys Asn Leu Tyr Pro Ser Ser Ser Pro

  1 5 10 15

  Tyr Thr Arg Asn Trp Asp Lys Leu

  20

  <210> SEQ ID NO 406

  <211> LENGTH: 17

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 406

  Gly Ser Lys Gly Gln Glu Arg Lys Trp Arg Val Arg Met Gly Tyr Leu

  1 5 10 15

  Asn

  <210> SEQ ID NO 407

  <211> LENGTH: 55

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 407

  Gln Arg Tyr Arg Leu Leu Pro Leu Phe Cys Tyr Val Cys Ser Arg Lys

  1 5 10 15

  Ile Lys Leu Asn Glu Asn Leu Phe Val Phe Ser Ala Tyr Ser Leu Ala

  20 25 30

  Thr Leu Pro His Thr Tyr Leu Phe Ser Ile Val Glu Cys Ser Ser Phe

  35 40 45

  Cys Leu Ser Gly Thr Arg Asn

  50 55

  <210> SEQ ID NO 408

  <211> LENGTH: 27

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 408

  Phe Ser Ala Tyr Ser Leu Ala Thr Leu Pro His Thr Tyr Leu Phe Ser

  1 5 10 15

  Ile Val Glu Cys Ser Ser Phe Cys Leu Ser Gly

  20 25

  <210> SEQ ID NO 409

  <211> LENGTH: 35

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 409

  Ala Ser Phe Gly Ser Cys Ser Leu Ser Leu Pro Cys Ser Ala Arg Glu

  1 5 10 15

  Arg Thr Pro Glu Gly Gly Gly Trp Pro Gly Gly Arg Leu Ser Glu Pro

  20 25 30

  Leu Pro Ala

  35

  <210> SEQ ID NO 410

  <211> LENGTH: 7

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 410

  Ala Pro Asn Val Val Leu Val

  1 5

  <210> SEQ ID NO 411

  <211> LENGTH: 6

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 411

  Asp Gly Arg Leu Thr Phe

  1 5

  <210> SEQ ID NO 412

  <211> LENGTH: 14

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 412

  Pro Gly Ser Gln Val Val Lys Leu Pro Phe Ile Asn Phe Met

  1 5 10

  <210> SEQ ID NO 413

  <211> LENGTH: 9

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 413

  Phe Leu Asn Ala Tyr Thr Asn Ser Pro

  1 5

  <210> SEQ ID NO 414

  <211> LENGTH: 36

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 414

  Ile Cys Cys Pro Ser Arg Ala Ala Met Trp Ser Gly Leu Phe Thr His

  1 5 10 15

  Leu Thr Glu Ser Trp Asn Asn Phe Lys Gly Leu Asp Pro Asn Tyr Thr

  20 25 30

  Thr Trp Met Asp

  35

  <210> SEQ ID NO 415

  <211> LENGTH: 6

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 415

  Thr Gln Lys Phe Gly Lys

  1 5

  <210> SEQ ID NO 416

  <211> LENGTH: 9

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 416

  Asp Tyr Thr Ser Gly His His Ser Ile

  1 5

  <210> SEQ ID NO 417

  <211> LENGTH: 21

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 417

  Ser Asn Arg Val Glu Ala Trp Thr Arg Asp Val Ala Phe Leu Leu Arg

  1 5 10 15

  Gln Glu Gly Arg Pro

  20

  <210> SEQ ID NO 418

  <211> LENGTH: 8

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 418

  Asp Trp Gln Asn Thr Asp Lys Ala

  1 5

  <210> SEQ ID NO 419

  <211> LENGTH: 34

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 419

  Tyr Leu Gly Leu Asn Leu Pro His Pro Tyr Pro Ser Pro Ser Ser Gly

  1 5 10 15

  Glu Asn Phe Gly Ser Ser Thr Phe His Thr Ser Leu Tyr Trp Leu Glu

  20 25 30

  Lys Val

  <210> SEQ ID NO 420

  <211> LENGTH: 8

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 420

  Asp Ala Ile Lys Ile Pro Lys Trp

  1 5

  <210> SEQ ID NO 421

  <211> LENGTH: 7

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 421

  Tyr Thr Lys Asn Cys Thr Gly

  1 5

  <210> SEQ ID NO 422

  <211> LENGTH: 25

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 422

  Asn Ile Arg Ala Phe Tyr Tyr Ala Met Cys Ala Glu Thr Asp Ala Met

  1 5 10 15

  Leu Gly Glu Ile Ile Leu Ala Leu His

  20 25

  <210> SEQ ID NO 423

  <211> LENGTH: 11

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 423

  Leu Asp Leu Leu Gln Lys Thr Ile Val Ile Tyr

  1 5 10

  <210> SEQ ID NO 424

  <211> LENGTH: 15

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 424

  Met Glu His Arg Gln Phe Tyr Lys Met Ser Met Tyr Glu Ala Ser

  1 5 10 15

  <210> SEQ ID NO 425

  <211> LENGTH: 13

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 425

  His Val Pro Leu Leu Met Met Gly Pro Gly Ile Lys Ala

  1 5 10

  <210> SEQ ID NO 426

  <211> LENGTH: 17

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 426

  Val Val Ser Leu Val Asp Ile Tyr Pro Thr Met Leu Asp Ile Ala Gly

  1 5 10 15

  Ile

  <210> SEQ ID NO 427

  <211> LENGTH: 7

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 427

  Asp Pro Asp Glu Leu Thr Asn

  1 5

  <210> SEQ ID NO 428

  <211> LENGTH: 6

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 428

  Trp Lys Tyr Ile Ala Tyr

  1 5

  <210> SEQ ID NO 429

  <211> LENGTH: 82

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 429

  Asn Phe Pro Glu Ile Thr Tyr Ser Leu Asp Gln Lys Leu His Ser Ile

  1 5 10 15

  Ile Asn Tyr Pro Lys Val Ser Ala Ser Val His Gln Tyr Asn Lys Glu

  20 25 30

  Gln Phe Ile Lys Trp Lys Gln Ser Ile Gly Gln Asn Tyr Ser Asn Val

  35 40 45

  Ile Ala Asn Phe Arg Trp His Gln Asp Trp Gln Lys Glu Pro Arg Lys

  50 55 60

  Tyr Glu Asn Ala Ile Asp Gln Trp Leu Lys Thr His Met Asn Pro Arg

  65 70 75 80

  Ala Val

  <210> SEQ ID NO 430

  <211> LENGTH: 12

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 430

  Phe Pro Glu Ile Thr Tyr Ser Leu Asp Gln Lys Leu

  1 5 10

  <210> SEQ ID NO 431

  <211> LENGTH: 18

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 431

  Asn Tyr Pro Lys Val Ser Ala Ser Val His Gln Tyr Asn Lys Glu Gln

  1 5 10 15

  Phe Ile

  <210> SEQ ID NO 432

  <211> LENGTH: 9

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 432

  Gly Gln Asn Tyr Ser Asn Val Ile Ala

  1 5

  <210> SEQ ID NO 433

  <211> LENGTH: 7

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 433

  Arg Trp His Gln Asp Trp Gln

  1 5

  <210> SEQ ID NO 434

  <211> LENGTH: 8

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 434

  Pro Arg Lys Tyr Glu Asn Ala Ile

  1 5

  <210> SEQ ID NO 435

  <211> LENGTH: 35

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 435

  Arg Asn Ser Leu His Cys Tyr Asn Glu Gln Pro Pro Asn Ala Ser Gly

  1 5 10 15

  Leu Ile Gln Trp Ser Ser Asp Leu Ile Pro Ile Ser Leu Gln Cys Gly

  20 25 30

  Cys Ser Trp

  35

  <210> SEQ ID NO 436

  <211> LENGTH: 162

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (1)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (33)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (48)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 436

  Xaa Leu Trp Asp Pro Gly Leu Pro Gly Val Cys Arg Cys Gly Ser Ile

  1 5 10 15

  Val Leu Lys Ser Ala Phe Ser Val Gly Ile Thr Thr Ser Tyr Pro Glu

  20 25 30

  Xaa Arg Leu Pro Ile Ile Phe Asn Lys Val Leu Leu Pro Arg Gly Xaa

  35 40 45

  Ala Leu Gln Pro Cys His Arg Gly Ser Ser Ser Val Leu Ser Gln Gly

  50 55 60

  Ile Tyr Tyr Phe Ser Tyr Asp Ile Thr Leu Ala Asn Lys His Leu Ala

  65 70 75 80

  Ile Gly Leu Val His Asn Gly Gln Tyr Arg Ile Lys Thr Phe Asp Ala

  85 90 95

  Asn Thr Gly Asn His Asp Val Ala Ser Gly Ser Thr Val Ile Tyr Leu

  100 105 110

  Gln Pro Glu Asp Glu Val Trp Leu Glu Ile Phe Phe Thr Asp Gln Asn

  115 120 125

  Gly Leu Phe Ser Asp Pro Gly Trp Ala Asp Ser Leu Phe Ser Gly Phe

  130 135 140

  Leu Leu Tyr Val Asp Thr Asp Tyr Leu Asp Ser Ile Ser Glu Asp Asp

  145 150 155 160

  Glu Leu

  <210> SEQ ID NO 437

  <211> LENGTH: 15

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 437

  Gly Ser Ile Val Leu Lys Ser Ala Phe Ser Val Gly Ile Thr Thr

  1 5 10 15

  <210> SEQ ID NO 438

  <211> LENGTH: 14

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 438

  Gly Ile Tyr Tyr Phe Ser Tyr Asp Ile Thr Leu Ala Asn Lys

  1 5 10

  <210> SEQ ID NO 439

  <211> LENGTH: 13

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 439

  Asp Ser Leu Phe Ser Gly Phe Leu Leu Tyr Val Asp Thr

  1 5 10

  <210> SEQ ID NO 440

  <211> LENGTH: 13

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 440

  Asn His Asp Val Ala Ser Gly Ser Thr Val Ile Tyr Leu

  1 5 10

  <210> SEQ ID NO 441

  <211> LENGTH: 14

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 441

  Ser Asn Ser His Thr His Thr His Val Lys Ser Phe Leu Arg

  1 5 10

  <210> SEQ ID NO 442

  <211> LENGTH: 10

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 442

  Ile Thr Pro Leu Gly Leu Gly Ala Ala Asp

  1 5 10

  <210> SEQ ID NO 443

  <211> LENGTH: 149

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 443

  Thr Leu Arg Val Leu Gly Lys Val Pro Ala Val Cys Pro Trp Cys Ala

  1 5 10 15

  Leu Trp Arg Lys Ala Gly Met Asp Met Thr Tyr Ser Trp Leu Ser Arg

  20 25 30

  Gly Asp Ser Thr Tyr Thr Phe His Glu Gly Pro Val Leu Ser Thr Ser

  35 40 45

  Trp Arg Pro Gly Asp Ser Ala Leu Ser Tyr Thr Cys Arg Ala Asn Asn

  50 55 60

  Pro Ile Ser Asn Val Ser Ser Cys Pro Ile Pro Asp Gly Pro Phe Tyr

  65 70 75 80

  Ala Asp Pro Asn Tyr Ala Ser Glu Lys Pro Ser Thr Ala Phe Cys Leu

  85 90 95

  Leu Ala Lys Gly Leu Leu Ile Phe Leu Leu Leu Val Ile Leu Ala Met

  100 105 110

  Gly Leu Trp Val Ile Arg Val Gln Lys Arg His Lys Met Pro Arg Met

  115 120 125

  Lys Lys Leu Met Arg Asn Arg Met Lys Leu Arg Lys Glu Ala Lys Pro

  130 135 140

  Gly Ser Ser Pro Ala

  145

  <210> SEQ ID NO 444

  <211> LENGTH: 21

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 444

  Ala Val Cys Pro Trp Cys Ala Leu Trp Arg Lys Ala Gly Met Asp Met

  1 5 10 15

  Thr Tyr Ser Trp Leu

  20

  <210> SEQ ID NO 445

  <211> LENGTH: 24

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 445

  Pro Gly Asp Ser Ala Leu Ser Tyr Thr Cys Arg Ala Asn Asn Pro Ile

  1 5 10 15

  Ser Asn Val Ser Ser Cys Pro Ile

  20

  <210> SEQ ID NO 446

  <211> LENGTH: 24

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 446

  Tyr Ala Ser Glu Lys Pro Ser Thr Ala Phe Cys Leu Leu Ala Lys Gly

  1 5 10 15

  Leu Leu Ile Phe Leu Leu Leu Val

  20

  <210> SEQ ID NO 447

  <211> LENGTH: 26

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 447

  Gln Lys Arg His Lys Met Pro Arg Met Lys Lys Leu Met Arg Asn Arg

  1 5 10 15

  Met Lys Leu Arg Lys Glu Ala Lys Pro Gly

  20 25

  <210> SEQ ID NO 448

  <211> LENGTH: 23

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 448

  Ile Ala Trp Ser Gly Asn Ile Pro Ser Leu Leu Cys Leu Phe Glu His

  1 5 10 15

  Asp Met Ser Phe Gln Asp Glu

  20

  <210> SEQ ID NO 449

  <211> LENGTH: 89

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (60)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (75)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 449

  Glu Asn Phe Leu Leu Arg Tyr Lys Gly Pro Ser Asp His Trp Ile Gly

  1 5 10 15

  Leu Ser Arg Glu Gln Gly Gln Pro Trp Lys Trp Ile Asn Gly Thr Glu

  20 25 30

  Trp Thr Arg Gln Leu Val Met Lys Glu Asp Gly Ala Asn Leu Tyr Val

  35 40 45

  Ala Lys Val Ser Gln Val Pro Arg Met Asn Pro Xaa Leu Ser Trp Val

  50 55 60

  Leu Leu Cys Tyr Pro Gly Trp Ser Ala Val Xaa Thr Ile Val Ala His

  65 70 75 80

  Cys Ser Leu Asp Phe Pro Gly Ser Lys

  85

  <210> SEQ ID NO 450

  <211> LENGTH: 63

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 450

  Glu Leu Thr Ala Ile Lys Ser His Gln Tyr Val Leu Gln Ala Ala Cys

  1 5 10 15

  Pro Glu Ser Trp Ile Gly Phe Gln Arg Lys Cys Phe Tyr Phe Ser Asp

  20 25 30

  Asp Thr Lys Asn Trp Thr Ser Ser Gln Arg Phe Cys Asp Ser Gln Asp

  35 40 45

  Ala Asp Leu Ala Gln Val Glu Ser Phe Gln Glu Leu Val Arg Lys

  50 55 60

  <210> SEQ ID NO 451

  <211> LENGTH: 17

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 451

  Trp Ile Gly Leu Ser Arg Glu Gln Gly Gln Pro Trp Lys Trp Ile Asn

  1 5 10 15

  Gly

  <210> SEQ ID NO 452

  <211> LENGTH: 12

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 452

  Cys Pro Glu Ser Trp Ile Gly Phe Gln Arg Lys Cys

  1 5 10

  <210> SEQ ID NO 453

  <211> LENGTH: 16

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 453

  Asn Phe Leu Leu Arg Tyr Lys Gly Pro Ser Asp His Trp Ile Gly Leu

  1 5 10 15

  <210> SEQ ID NO 454

  <211> LENGTH: 50

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 454

  Ala Ser His Leu Arg Leu Leu Ser Ser Trp Asp Tyr Arg Phe Pro Ile

  1 5 10 15

  Leu Gly Ala Gly Glu Cys Ala Tyr Leu Asn Asp Lys Gly Ala Ser Ser

  20 25 30

  Ala Arg His Tyr Thr Glu Arg Lys Trp Ile Cys Ser Lys Ser Asp Ile

  35 40 45

  His Val

  50

  <210> SEQ ID NO 455

  <211> LENGTH: 89

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (60)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (75)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 455

  Glu Asn Phe Leu Leu Arg Tyr Lys Gly Pro Ser Asp His Trp Ile Gly

  1 5 10 15

  Leu Ser Arg Glu Gln Gly Gln Pro Trp Lys Trp Ile Asn Gly Thr Glu

  20 25 30

  Trp Thr Arg Gln Leu Val Met Lys Glu Asp Gly Ala Asn Leu Tyr Val

  35 40 45

  Ala Lys Val Ser Gln Val Pro Arg Met Asn Pro Xaa Leu Ser Trp Val

  50 55 60

  Leu Leu Cys Tyr Pro Gly Trp Ser Ala Val Xaa Thr Ile Val Ala His

  65 70 75 80

  Cys Ser Leu Asp Phe Pro Gly Ser Lys

  85

  <210> SEQ ID NO 456

  <211> LENGTH: 76

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (9)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (22)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (29)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 456

  Ser Trp Thr Ser Ser Leu Leu Asn Xaa Cys Leu His Ser Lys Glu His

  1 5 10 15

  Ser Ile Lys Ala Thr Xaa Ile Trp Arg Leu Phe Phe Xaa Ile Leu Thr

  20 25 30

  Ile Ile Leu Cys Gly Met Val Ala Ala Leu Ser Ala Ile Arg Ala Asn

  35 40 45

  Cys His Gln Glu Pro Ser Val Cys Ser Ser Ser Cys Met Pro Arg Lys

  50 55 60

  Leu Asp Trp Phe Ser Lys Lys Val Phe Leu Phe Phe

  65 70 75

  <210> SEQ ID NO 457

  <211> LENGTH: 39

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 457

  Glu Gln Leu Glu Glu Leu Glu Leu Lys Lys Lys Asp Phe Ile Lys Ile

  1 5 10 15

  Leu Glu Ser Val Gln Gly Asn Trp Arg Gln Asn Glu Asp Ser Gly Lys

  20 25 30

  Gly Pro Gln Arg Ser Cys Leu

  35

  <210> SEQ ID NO 458

  <211> LENGTH: 19

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 458

  Phe Trp Pro Glu Ser Lys Ile Gln Pro Tyr Lys Asp Met Phe Ser Cys

  1 5 10 15

  Glu Ile Ile

  <210> SEQ ID NO 459

  <211> LENGTH: 58

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 459

  Glu Gln Leu Glu Glu Leu Glu Leu Lys Lys Lys Asp Phe Ile Lys Ile

  1 5 10 15

  Leu Glu Ser Val Gln Gly Asn Trp Arg Gln Asn Glu Asp Ser Gly Lys

  20 25 30

  Gly Pro Gln Arg Ser Cys Leu His Ser Lys Glu His Ser Ile Lys Ala

  35 40 45

  Thr Leu Ile Trp Arg Leu Phe Phe Leu Ile

  50 55

  <210> SEQ ID NO 460

  <211> LENGTH: 36

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (18)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (19)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 460

  Glu Asn Phe Leu Leu Arg Tyr Lys Gly Pro Ser Asp His Trp Ile Gly

  1 5 10 15

  Leu Xaa Xaa Glu Gln Gly Gln Pro Trp Lys Trp Ile Asn Gly Thr Glu

  20 25 30

  Trp Thr Arg Gln

  35

  <210> SEQ ID NO 461

  <211> LENGTH: 7

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 461

  Arg His Glu Pro Asp Pro Met

  1 5

  <210> SEQ ID NO 462

  <211> LENGTH: 109

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (24)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (25)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (31)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 462

  Leu Lys Gly Arg Glu Ala Gly Ala Gly Pro Gly Thr Ala Gly Ala Pro

  1 5 10 15

  Gly Arg Glu Asp Ala Asn Gly Xaa Xaa Arg Gly Arg Gly Gly Xaa His

  20 25 30

  Gln Leu Tyr Leu Trp Val Asp Asn Ile Pro Leu Ser Arg Pro Lys Arg

  35 40 45

  Asn Leu Ser Arg Asp Phe Ser Asp Gly Val Leu Val Ala Glu Val Ile

  50 55 60

  Lys Phe Tyr Phe Pro Lys Met Val Glu Met His Asn Tyr Val Gly Thr

  65 70 75 80

  Ser Ser Leu Gln Gln Lys Leu Ser Asn Trp Gly His Leu Asn Arg Lys

  85 90 95

  Val Leu Lys Arg Leu Asn Phe Ser Val Pro Asp Asp Val

  100 105

  <210> SEQ ID NO 463

  <211> LENGTH: 25

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 463

  Trp Val Asp Asn Ile Pro Leu Ser Arg Pro Lys Arg Asn Leu Ser Arg

  1 5 10 15

  Asp Phe Ser Asp Gly Val Leu Val Ala

  20 25

  <210> SEQ ID NO 464

  <211> LENGTH: 25

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 464

  Tyr Val Gly Thr Ser Ser Leu Gln Gln Lys Leu Ser Asn Trp Gly His

  1 5 10 15

  Leu Asn Arg Lys Val Leu Lys Arg Leu

  20 25

  <210> SEQ ID NO 465

  <211> LENGTH: 97

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 465

  Gly Ser Ala Trp Arg Arg Gly Arg Gly Ala Gly Ser Arg Ala Pro Ala

  1 5 10 15

  Pro Tyr Arg Ser Trp Leu Pro Arg Met Ala Val Ala Thr Trp Met Trp

  20 25 30

  Val Tyr Pro Arg Arg Pro Glu Val Lys Val Ser Arg Thr Pro Arg Glu

  35 40 45

  Gly Val Ser Ser Ala Gly Thr Gly Arg Arg Arg Leu Gly Leu Gln Arg

  50 55 60

  Ile Thr Gly Arg Cys Arg Ala Thr Pro Ala Ser Ser Ser Arg Ser Leu

  65 70 75 80

  Lys Arg Ser Arg Ser Cys Trp Pro Leu Lys Arg Pro Cys Arg Ser Cys

  85 90 95

  Arg

  <210> SEQ ID NO 466

  <211> LENGTH: 21

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 466

  Trp Leu Pro Arg Met Ala Val Ala Thr Trp Met Trp Val Tyr Pro Arg

  1 5 10 15

  Arg Pro Glu Val Lys

  20

  <210> SEQ ID NO 467

  <211> LENGTH: 23

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 467

  Cys Arg Ala Thr Pro Ala Ser Ser Ser Arg Ser Leu Lys Arg Ser Arg

  1 5 10 15

  Ser Cys Trp Pro Leu Lys Arg

  20

  <210> SEQ ID NO 468

  <211> LENGTH: 347

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (241)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <221> NAME/KEY: SITE

  <222> LOCATION: (243)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 468

  Glu His Asn Thr Asp Phe Asn Gly Ala Ala Leu Ser Arg Asn Leu Gln

  1 5 10 15

  Thr Phe Arg Leu Ser Thr Pro Cys Ala Arg Arg Glu Gly Arg Leu Leu

  20 25 30

  Arg Ala His Arg Arg Cys Pro Pro Tyr Ser Trp Arg Ser His Ala Ser

  35 40 45

  Pro Leu Pro Leu Gln Leu Leu Arg Ser Pro Ser Pro Arg Trp Val Pro

  50 55 60

  Gly Lys Leu Pro Gly Gly Ala Gly Glu Pro Leu Ser Gly Pro Gly Gln

  65 70 75 80

  Ile Pro Pro Trp Leu Arg Ala Trp Gly Thr Ser Leu Asp Gly Asp Ala

  85 90 95

  Ala Val Leu Gly Ala Gly Arg Gly Pro Asp Ser Gly Gly Val Asp Arg

  100 105 110

  Ala Lys Gly Pro Pro Pro Lys Ala Gln Arg Arg Glu Met Gln Gly Arg

  115 120 125

  Ala Gln Gly Val Gly His Cys Phe Gly Gly Gln Ala Arg Ser Leu His

  130 135 140

  Val Ala Ser Gly Leu Trp Lys Ala Val His Ser Pro Asp Pro Asp Leu

  145 150 155 160

  Arg Ser Gly Arg Arg Arg Leu Ser Pro Gly Pro Ala Leu Leu Glu Phe

  165 170 175

  Leu Ser His Leu Leu His Ala His Pro Ser Gln Gly Arg Arg Ala Leu

  180 185 190

  Gly Pro Gln Gln Ala Arg Glu Ser Ser Gly Leu Arg Pro Pro Asn Gly

  195 200 205

  Leu Ser Ile Gly Gly Trp Val Arg Arg Gly Val Gly Ala Leu Ala Gly

  210 215 220

  Thr Arg Ala Ser Pro Arg Gly Pro Gly Arg Arg Ser Pro Leu Leu Thr

  225 230 235 240

  Xaa Arg Xaa Leu Glu Pro Pro Gly Glu Val Phe Asp Pro His Ile Leu

  245 250 255

  Glu Leu Glu Gln Val Leu Gln Ala Pro Tyr Leu His Leu Gln Asp Leu

  260 265 270

  His Gly Leu Leu Arg Gly Gln Gln Leu Leu Leu Leu Phe Ser Asp Leu

  275 280 285

  Glu Asp Glu Ala Gly Val Ala Leu Gln Arg Pro Val Ile Arg Trp Arg

  290 295 300

  Pro Arg Arg Arg Arg Pro Val Pro Ala Glu Leu Thr Pro Ser Leu Gly

  305 310 315 320

  Val Arg Asp Thr Phe Thr Ser Gly Leu Leu Gly Tyr Thr His Ile His

  325 330 335

  Val Ala Thr Ala Ile Leu Gly Ser Gln Leu Leu

  340 345

  <210> SEQ ID NO 469

  <211> LENGTH: 26

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 469

  Thr Asp Phe Asn Gly Ala Ala Leu Ser Arg Asn Leu Gln Thr Phe Arg

  1 5 10 15

  Leu Ser Thr Pro Cys Ala Arg Arg Glu Gly

  20 25

  <210> SEQ ID NO 470

  <211> LENGTH: 25

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 470

  Arg Cys Pro Pro Tyr Ser Trp Arg Ser His Ala Ser Pro Leu Pro Leu

  1 5 10 15

  Gln Leu Leu Arg Ser Pro Ser Pro Arg

  20 25

  <210> SEQ ID NO 471

  <211> LENGTH: 24

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 471

  Gly Ala Gly Glu Pro Leu Ser Gly Pro Gly Gln Ile Pro Pro Trp Leu

  1 5 10 15

  Arg Ala Trp Gly Thr Ser Leu Asp

  20

  <210> SEQ ID NO 472

  <211> LENGTH: 30

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 472

  Leu Gly Ala Gly Arg Gly Pro Asp Ser Gly Gly Val Asp Arg Ala Lys

  1 5 10 15

  Gly Pro Pro Pro Lys Ala Gln Arg Arg Glu Met Gln Gly Arg

  20 25 30

  <210> SEQ ID NO 473

  <211> LENGTH: 23

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 473

  Gln Ala Arg Ser Leu His Val Ala Ser Gly Leu Trp Lys Ala Val His

  1 5 10 15

  Ser Pro Asp Pro Asp Leu Arg

  20

  <210> SEQ ID NO 474

  <211> LENGTH: 20

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 474

  His Pro Ser Gln Gly Arg Arg Ala Leu Gly Pro Gln Gln Ala Arg Glu

  1 5 10 15

  Ser Ser Gly Leu

  20

  <210> SEQ ID NO 475

  <211> LENGTH: 27

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 475

  Ile Gly Gly Trp Val Arg Arg Gly Val Gly Ala Leu Ala Gly Thr Arg

  1 5 10 15

  Ala Ser Pro Arg Gly Pro Gly Arg Arg Ser Pro

  20 25

  <210> SEQ ID NO 476

  <211> LENGTH: 25

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 476

  Glu Pro Pro Gly Glu Val Phe Asp Pro His Ile Leu Glu Leu Glu Gln

  1 5 10 15

  Val Leu Gln Ala Pro Tyr Leu His Leu

  20 25

  <210> SEQ ID NO 477

  <211> LENGTH: 28

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 477

  Val Pro Ala Glu Leu Thr Pro Ser Leu Gly Val Arg Asp Thr Phe Thr

  1 5 10 15

  Ser Gly Leu Leu Gly Tyr Thr His Ile His Val Ala

  20 25

  <210> SEQ ID NO 478

  <211> LENGTH: 187

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 478

  Ala Lys Asn Ser Gln Lys Glu Glu Asn Pro Glu His Val Glu Ile Gln

  1 5 10 15

  Lys Met Met Asp Ser Leu Phe Leu Lys Leu Asp Ala Leu Ser Asn Phe

  20 25 30

  His Phe Ile Pro Lys Pro Pro Val Pro Glu Ile Lys Val Val Ser Asn

  35 40 45

  Leu Pro Ala Ile Thr Met Glu Glu Val Ala Pro Val Ser Val Ser Asp

  50 55 60

  Ala Ala Leu Leu Ala Pro Glu Glu Ile Lys Glu Lys Asn Lys Ala Gly

  65 70 75 80

  Asp Ile Lys Thr Ala Ala Glu Lys Thr Ala Thr Asp Lys Lys Arg Glu

  85 90 95

  Arg Arg Lys Lys Lys Tyr Gln Lys Arg Met Lys Ile Lys Glu Lys Glu

  100 105 110

  Lys Arg Arg Lys Leu Leu Glu Lys Ser Ser Val Asp Gln Ala Gly Lys

  115 120 125

  Tyr Ser Lys Thr Val Ala Ser Glu Lys Leu Lys Gln Leu Thr Lys Thr

  130 135 140

  Gly Lys Ala Ser Phe Ile Lys Val Arg Thr Arg Glu Arg Lys Leu Leu

  145 150 155 160

  Lys Gly Thr Phe Val Gly Glu Val Asp Ser Lys Cys Trp Val Thr Gly

  165 170 175

  Met Ser Glu Pro Ala Asp Ser Pro Pro Val Gly

  180 185

  <210> SEQ ID NO 479

  <211> LENGTH: 51

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 479

  Leu Gln Asp Glu Gly Lys Asp Lys Ala Leu Lys Ser Ser Gln Ala Phe

  1 5 10 15

  Phe Ser Lys Leu Gln Asp Gln Val Lys Met Gln Ile Asn Asp Ala Lys

  20 25 30

  Lys Thr Glu Lys Lys Lys Lys Lys Arg Gln Asp Ile Ser Val His Lys

  35 40 45

  Leu Lys Leu

  50

  <210> SEQ ID NO 480

  <211> LENGTH: 29

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 480

  Asp Glu Gly Lys Asp Lys Ala Leu Lys Ser Ser Gln Ala Phe Phe Ser

  1 5 10 15

  Lys Leu Gln Asp Gln Val Lys Met Gln Ile Asn Asp Ala

  20 25

  <210> SEQ ID NO 481

  <211> LENGTH: 28

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 481

  Glu Glu Asn Pro Glu His Val Glu Ile Gln Lys Met Met Asp Ser Leu

  1 5 10 15

  Phe Leu Lys Leu Asp Ala Leu Ser Asn Phe His Phe

  20 25

  <210> SEQ ID NO 482

  <211> LENGTH: 13

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 482

  Ser Asn Leu Pro Ala Ile Thr Met Glu Glu Val Ala Pro

  1 5 10

  <210> SEQ ID NO 483

  <211> LENGTH: 31

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 483

  Ser Ser Val Asp Gln Ala Gly Lys Tyr Ser Lys Thr Val Ala Ser Glu

  1 5 10 15

  Lys Leu Lys Gln Leu Thr Lys Thr Gly Lys Ala Ser Phe Ile Lys

  20 25 30

  <210> SEQ ID NO 484

  <211> LENGTH: 23

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 484

  Val Ser Val Ser Asp Ala Ala Leu Leu Ala Pro Glu Glu Ile Lys Glu

  1 5 10 15

  Lys Asn Lys Ala Gly Asp Ile

  20

  <210> SEQ ID NO 485

  <211> LENGTH: 11

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 485

  Val Leu Glu Val Met Val Thr Val Ala Pro Lys

  1 5 10

  <210> SEQ ID NO 486

  <211> LENGTH: 35

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 486

  Leu Gln Asp Glu Gly Lys Asp Lys Ala Leu Lys Ser Ser Gln Ala Phe

  1 5 10 15

  Phe Ser Lys Leu Gln Asp Gln Val Lys Met Gln Ile Asn Asp Ala Lys

  20 25 30

  Lys Thr Glu

  35

  <210> SEQ ID NO 487

  <211> LENGTH: 34

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 487

  His Glu Ala Ala Gln Gly Ala Val Cys Arg Gly Gln Gly Ala Pro Ala

  1 5 10 15

  Thr Asn Pro Gln Ala Pro Val Ala Ala Ala Ala Arg Val Ala Arg Arg

  20 25 30

  Val Asn

  <210> SEQ ID NO 488

  <211> LENGTH: 255

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 488

  Lys Ile Pro Ser Ala Asn Arg Arg Ala Thr Arg Cys Leu Gly Cys Asp

  1 5 10 15

  His Gln Asn Phe Val Lys Val Arg Asn Lys His Lys Gly Lys Pro Thr

  20 25 30

  Phe Met Glu Glu Val Leu Glu His Leu Pro Gly Lys Thr Gln Asp Glu

  35 40 45

  Val Gln Gln His Glu Lys Trp Tyr Gln Lys Phe Leu Ala Leu Glu Glu

  50 55 60

  Arg Lys Lys Glu Ser Ile Gln Ile Trp Lys Thr Lys Lys Gln Gln Lys

  65 70 75 80

  Arg Glu Glu Ile Phe Lys Leu Lys Glu Lys Ala Asp Asn Thr Pro Val

  85 90 95

  Leu Phe His Asn Lys Gln Glu Asp Asn Gln Lys Gln Lys Glu Glu Gln

  100 105 110

  Arg Lys Lys Gln Lys Leu Ala Val Glu Ala Trp Lys Lys Gln Lys Ser

  115 120 125

  Ile Glu Met Ser Met Lys Cys Ala Ser Gln Leu Lys Lys Lys Lys Lys

  130 135 140

  Lys Lys Lys Lys Asn Gln Lys Glu Arg Gln Arg Gln Phe Lys Leu Lys

  145 150 155 160

  Leu Leu Leu Glu Ser Tyr Thr Gln Gln Lys Lys Glu Gln Glu Glu Phe

  165 170 175

  Leu Arg Leu Glu Lys Glu Ile Arg Glu Lys Ala Glu Lys Ala Glu Lys

  180 185 190

  Arg Lys Asn Ala Ala Asp Glu Ile Ser Arg Phe Gln Glu Arg Asp Leu

  195 200 205

  His Lys Leu Glu Leu Lys Ile Leu Asp Arg Gln Ala Lys Glu Asp Glu

  210 215 220

  Lys Ser Gln Lys Gln Arg Arg Leu Ala Lys Leu Lys Glu Lys Val Glu

  225 230 235 240

  Asn Asn Val Ser Arg Asp Pro Ser Arg Leu Tyr Lys Pro Thr Lys

  245 250 255

  <210> SEQ ID NO 489

  <211> LENGTH: 24

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 489

  Val Lys Val Arg Asn Lys His Lys Gly Lys Pro Thr Phe Met Glu Glu

  1 5 10 15

  Val Leu Glu His Leu Pro Gly Lys

  20

  <210> SEQ ID NO 490

  <211> LENGTH: 23

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 490

  Gln His Glu Lys Trp Tyr Gln Lys Phe Leu Ala Leu Glu Glu Arg Lys

  1 5 10 15

  Lys Glu Ser Ile Gln Ile Trp

  20

  <210> SEQ ID NO 491

  <211> LENGTH: 31

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 491

  Phe Lys Leu Lys Glu Lys Ala Asp Asn Thr Pro Val Leu Phe His Asn

  1 5 10 15

  Lys Gln Glu Asp Asn Gln Lys Gln Lys Glu Glu Gln Arg Lys Lys

  20 25 30

  <210> SEQ ID NO 492

  <211> LENGTH: 36

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 492

  Phe Leu Arg Leu Glu Lys Glu Ile Arg Glu Lys Ala Glu Lys Ala Glu

  1 5 10 15

  Lys Arg Lys Asn Ala Ala Asp Glu Ile Ser Arg Phe Gln Glu Arg Asp

  20 25 30

  Leu His Lys Leu

  35

  <210> SEQ ID NO 493

  <211> LENGTH: 24

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 493

  Lys Gln Arg Arg Leu Ala Lys Leu Lys Glu Lys Val Glu Asn Asn Val

  1 5 10 15

  Ser Arg Asp Pro Ser Arg Leu Tyr

  20

  <210> SEQ ID NO 494

  <211> LENGTH: 18

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 494

  Val Lys Pro Pro Asp Gln Ser Cys Asn His Trp Arg Asp Glu Gln Cys

  1 5 10 15

  Leu Val

  <210> SEQ ID NO 495

  <211> LENGTH: 20

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 495

  Met Ala Ile Pro Ala Phe Ser Ser Cys Gln Gln Ile Ser Ser Ala Ala

  1 5 10 15

  Ala Leu Gln Ile

  20

  <210> SEQ ID NO 496

  <211> LENGTH: 14

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 496

  Cys Asn Gly Pro Phe Lys His Phe Ser Phe Thr Val Ser Thr

  1 5 10

  <210> SEQ ID NO 497

  <211> LENGTH: 18

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 497

  Ile Arg His Glu Arg Leu Trp Ala Glu Leu Ala Leu Leu Thr Gly Arg

  1 5 10 15

  Asn Glu

  <210> SEQ ID NO 498

  <211> LENGTH: 59

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 498

  Gly Thr Glu Ser Pro Met Val Met Cys Cys Arg Glu Val Ser Gln Ser

  1 5 10 15

  Glu Asn Cys Leu Phe Leu Asp Thr Thr Phe Arg Phe Ile Phe Gly Lys

  20 25 30

  Thr Phe Thr Asn His Asp Tyr Ile Ser Ile His Phe Tyr Phe Leu Lys

  35 40 45

  Ala Phe Leu Phe Ser Phe Phe Tyr Ser Asn Val

  50 55

  <210> SEQ ID NO 499

  <211> LENGTH: 15

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 499

  Ile Arg His Glu Glu Lys Gly Gly Lys Ala Gln Arg Trp Ala Glu

  1 5 10 15

  <210> SEQ ID NO 500

  <211> LENGTH: 11

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 500

  Cys Arg Trp Arg Pro Glu Ser Ala Ala Pro Cys

  1 5 10

  <210> SEQ ID NO 501

  <211> LENGTH: 12

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 501

  Thr Arg Pro Gly Arg Gly Ala Gln Ala Pro Val Lys

  1 5 10

  <210> SEQ ID NO 502

  <211> LENGTH: 21

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 502

  Met Val Ser Trp Met Ile Ser Arg Ala Val Val Leu Val Phe Gly Met

  1 5 10 15

  Leu Tyr Pro Ala Tyr

  20

  <210> SEQ ID NO 503

  <211> LENGTH: 17

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 503

  Gly Met Leu Tyr Pro Ala Tyr Tyr Ser Tyr Lys Ala Val Lys Thr Lys

  1 5 10 15

  Asn

  <210> SEQ ID NO 504

  <211> LENGTH: 17

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 504

  Glu Tyr Val Arg Trp Met Met Tyr Trp Ile Val Phe Ala Leu Tyr Thr

  1 5 10 15

  Val

  <210> SEQ ID NO 505

  <211> LENGTH: 17

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 505

  Tyr Pro Ala Tyr Tyr Ser Tyr Lys Ala Val Lys Thr Lys Asn Val Lys

  1 5 10 15

  Glu

  <210> SEQ ID NO 506

  <211> LENGTH: 13

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 506

  Val Ala Trp Phe Pro Leu Tyr Tyr Glu Leu Lys Ile Ala

  1 5 10

  <210> SEQ ID NO 507

  <211> LENGTH: 186

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (181)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 507

  Met Val Ser Trp Met Ile Ser Arg Ala Val Val Leu Val Phe Gly Met

  1 5 10 15

  Leu Tyr Pro Ala Tyr Tyr Ser Tyr Lys Ala Val Lys Thr Lys Asn Val

  20 25 30

  Lys Glu Tyr Val Arg Trp Met Met Tyr Trp Ile Val Phe Ala Leu Tyr

  35 40 45

  Thr Val Ile Glu Thr Val Ala Asp Gln Thr Val Ala Trp Phe Pro Leu

  50 55 60

  Tyr Tyr Glu Leu Lys Ile Ala Phe Val Ile Trp Leu Leu Ser Pro Tyr

  65 70 75 80

  Thr Lys Gly Ala Ser Leu Ile Tyr Arg Lys Phe Leu His Pro Leu Leu

  85 90 95

  Ser Ser Lys Glu Arg Glu Ile Asp Asp Tyr Ile Val Gln Ala Lys Glu

  100 105 110

  Arg Gly Tyr Glu Thr Met Val Asn Phe Gly Arg Gln Gly Leu Asn Leu

  115 120 125

  Ala Ala Thr Ala Ala Val Thr Ala Ala Val Lys Ser Gln Gly Ala Ile

  130 135 140

  Thr Glu Arg Leu Arg Ser Phe Ser Met His Asp Leu Thr Thr Ile Gln

  145 150 155 160

  Gly Asp Glu Pro Val Gly Gln Arg Pro Tyr Gln Pro Leu Pro Glu Ala

  165 170 175

  Lys Lys Lys Ser Xaa Gln Pro Pro Val Asn

  180 185

  <210> SEQ ID NO 508

  <211> LENGTH: 15

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 508

  Gln Pro Tyr Gln Val Leu Pro Ser Arg Gln Val Phe Ala Leu Ile

  1 5 10 15

  <210> SEQ ID NO 509

  <211> LENGTH: 24

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 509

  Val Phe Ser Cys Ile Tyr Gly Glu Gly Tyr Ser Asn Ala His Glu Ser

  1 5 10 15

  Lys Gln Met Tyr Cys Val Phe Asn

  20

  <210> SEQ ID NO 510

  <211> LENGTH: 18

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 510

  Arg Asn Glu Asp Ala Cys Arg Tyr Gly Ser Ala Ile Gly Val Leu Ala

  1 5 10 15

  Phe Leu

  <210> SEQ ID NO 511

  <211> LENGTH: 17

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 511

  Leu Val Val Asp Ala Tyr Phe Pro Gln Ile Ser Asn Ala Thr Asp Arg

  1 5 10 15

  Lys

  <210> SEQ ID NO 512

  <211> LENGTH: 25

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 512

  Ser Ala Leu Trp Thr Phe Leu Trp Phe Val Gly Phe Cys Phe Leu Thr

  1 5 10 15

  Asn Gln Trp Ala Val Thr Asn Pro Lys

  20 25

  <210> SEQ ID NO 513

  <211> LENGTH: 82

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 513

  Leu Asn Ile Asp Ser Phe Asp Tyr Gly Lys Phe Glu Ser Leu Leu Ala

  1 5 10 15

  Lys Gln His Tyr Lys Phe Ser Phe Leu Leu Pro Leu Ala Ala Gly Thr

  20 25 30

  Glu Arg Cys Lys Trp Trp Leu Lys Ile Glu Glu Ala Ser Ser Asp Gln

  35 40 45

  Cys Gly Cys Trp Phe Leu Val Lys Cys Val Pro Lys Pro Pro Ser Pro

  50 55 60

  Cys Arg Gln Pro Pro Thr Gln Val Ser Lys Ile Gly His Ala Pro Phe

  65 70 75 80

  Phe Leu

  <210> SEQ ID NO 514

  <211> LENGTH: 13

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 514

  Ser Leu Gln Tyr Arg Ile Arg Ile Pro Gly Arg Pro Thr

  1 5 10

  <210> SEQ ID NO 515

  <211> LENGTH: 22

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 515

  Asp Leu Val Thr Tyr Thr Ser Ser Leu Gln Tyr Arg Ile Arg Ile Pro

  1 5 10 15

  Gly Arg Pro Thr Arg Pro

  20

  <210> SEQ ID NO 516

  <211> LENGTH: 36

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 516

  Leu Gly Asn Lys Lys Tyr Ile Asn Ile Arg Cys Leu Glu Met Gln Val

  1 5 10 15

  Thr Leu Lys Ile Leu Cys Glu Ile Glu Lys Lys Glu Arg Arg Gly Thr

  20 25 30

  His Cys Leu Val

  35

  <210> SEQ ID NO 517

  <211> LENGTH: 22

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 517

  Val Lys Thr Ala Glu Cys Tyr Ser Ile Pro Leu Gly Ser Cys Pro Val

  1 5 10 15

  Asn Ile Gln Arg Val Arg

  20

  <210> SEQ ID NO 518

  <211> LENGTH: 60

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 518

  Leu Phe Tyr Leu Leu Thr Cys Ser Cys Ala Pro Gly His Leu Ala Phe

  1 5 10 15

  Val Cys Ser Gln Cys Leu Pro Phe Asp Met Gly Lys Glu Leu Trp Pro

  20 25 30

  Lys Ser Pro Ser Ser Cys Thr Ser Thr Ser Val Ala Gln Gly Trp Gly

  35 40 45

  Gly Arg Gly Arg Pro Ser Pro Tyr Ile Cys Val Val

  50 55 60

  <210> SEQ ID NO 519

  <211> LENGTH: 61

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 519

  Ile Gln Gly Ser Arg Leu Pro Pro Leu Pro Ala Pro Leu His Pro Leu

  1 5 10 15

  Pro Leu Ile Tyr Leu Leu Leu Gly Ser Pro Ala Gln Ser Trp Leu Leu

  20 25 30

  Val Pro Ser Trp Gly His Pro Ser Thr Leu Thr Leu Thr Met Ala Ala

  35 40 45

  Glu His Gln Ala Trp Pro Ser Gly Phe His Gly Asp His

  50 55 60

  <210> SEQ ID NO 520

  <211> LENGTH: 23

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 520

  Val Asp Pro Pro Gly Cys Arg Asn Ser Ala Arg Gly Cys Thr Arg Leu

  1 5 10 15

  Leu Arg Gly Ser Ser Lys Ile

  20

  <210> SEQ ID NO 521

  <211> LENGTH: 12

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 521

  Ile Thr Leu Cys Leu Val Cys Ile Val Ala Asn Ala

  1 5 10

  <210> SEQ ID NO 522

  <211> LENGTH: 24

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 522

  Val Thr Ala Tyr Gln Asn Gln Gln Ile Thr Arg Leu Lys Ile Asp Arg

  1 5 10 15

  Asn Pro Phe Ala Lys Gly Phe Arg

  20

  <210> SEQ ID NO 523

  <211> LENGTH: 16

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 523

  Gly Thr Ala Thr Val Thr Ala Tyr Gln Asn Gln Gln Ile Thr Arg Leu

  1 5 10 15

  <210> SEQ ID NO 524

  <211> LENGTH: 24

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 524

  Lys Ile Asp Arg Asn Pro Phe Ala Lys Gly Phe Arg Asp Ser Gly Arg

  1 5 10 15

  Asn Arg Met Gly Leu Glu Ala Leu

  20

  <210> SEQ ID NO 525

  <211> LENGTH: 21

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 525

  Ser Thr Leu Leu Gln Val Leu Gly Met Ala Phe Leu Pro Leu Thr Leu

  1 5 10 15

  Thr Phe Cys Leu Ala

  20

  <210> SEQ ID NO 526

  <211> LENGTH: 30

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 526

  Val Glu Ser Tyr Ala Phe Trp Arg Pro Ser Leu Arg Thr Leu Thr Phe

  1 5 10 15

  Glu Asp Ile Pro Gly Ile Pro Lys Gln Gly Asn Ala Ser Ser

  20 25 30

  <210> SEQ ID NO 527

  <211> LENGTH: 14

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 527

  Gln Ala Gln Ser Asp Cys Ser Cys Ser Thr Val Ser Pro Gly

  1 5 10

  <210> SEQ ID NO 528

  <211> LENGTH: 24

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 528

  Val Leu Ala Gly Ile Val Met Gly Asp Leu Val Leu Thr Val Leu Ile

  1 5 10 15

  Ala Leu Ala Val Tyr Phe Leu Gly

  20

  <210> SEQ ID NO 529

  <211> LENGTH: 37

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 529

  Val Pro Arg Gly Arg Gly Ala Ala Glu Ala Thr Arg Lys Gln Arg Ile

  1 5 10 15

  Thr Glu Thr Glu Ser Pro Tyr Gln Glu Leu Gln Gly Gln Arg Ser Asp

  20 25 30

  Val Tyr Ser Asp Leu

  35

  <210> SEQ ID NO 530

  <211> LENGTH: 22

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 530

  Glu Thr Glu Ser Pro Tyr Gln Glu Leu Gln Gly Gln Arg Ser Asp Val

  1 5 10 15

  Tyr Ser Asp Leu Asn Thr

  20

  <210> SEQ ID NO 531

  <211> LENGTH: 28

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 531

  Phe Leu Cys Ala Leu Ser Pro Leu Gly Gln Leu Leu Gln Asp Arg Tyr

  1 5 10 15

  Gly Trp Arg Gly Gly Phe Leu Ile Leu Gly Gly Leu

  20 25

  <210> SEQ ID NO 532

  <211> LENGTH: 27

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (22)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 532

  Leu Leu Asn Cys Cys Val Cys Ala Ala Leu Met Arg Pro Leu Val Val

  1 5 10 15

  Thr Ala Gln Pro Gly Xaa Gly Pro Pro Arg Pro

  20 25

  <210> SEQ ID NO 533

  <211> LENGTH: 25

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (5)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 533

  Ser Arg Arg Leu Xaa Asp Leu Ser Val Phe Arg Asp Arg Gly Phe Val

  1 5 10 15

  Leu Tyr Ala Val Ala Ala Ser Val Met

  20 25

  <210> SEQ ID NO 534

  <211> LENGTH: 57

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 534

  Met Met Ala Thr Pro Ser Thr Arg Pro Pro Pro Pro Ala Ala Ser Thr

  1 5 10 15

  Thr Ser Ala Thr Ala Pro Ala Leu Pro Pro Arg Pro Pro Trp Pro Trp

  20 25 30

  Pro Pro Ser Ser Trp Pro Pro Ser Gly Val Ser Ser Lys Ala Pro Glu

  35 40 45

  Ala Asp Pro Leu Lys Asn Lys Ala Leu

  50 55

  <210> SEQ ID NO 535

  <211> LENGTH: 76

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 535

  Leu Leu Leu Thr Ser Pro Leu Pro Arg Cys Pro Pro Ala Cys Ser His

  1 5 10 15

  Asp Ala Pro Ala His Pro Asp Pro Gly Gly Pro His Gly Leu Thr Ser

  20 25 30

  Gly Pro Gly Leu Gly Leu Pro Arg Val Cys Leu Gln Arg Arg Gln Leu

  35 40 45

  Leu Gln Pro His Ala Leu Pro Gly Tyr Gly Cys Leu Leu His Asp His

  50 55 60

  Ala His Leu Leu His Pro His Gln Asp Glu Gly Gln

  65 70 75

  <210> SEQ ID NO 536

  <211> LENGTH: 56

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 536

  Trp Leu Leu Gln Ala Arg Val His His Leu Leu Leu Pro Val Arg Pro

  1 5 10 15

  Leu Gln Arg His Arg Pro Cys His Pro Gly His Pro Gly Pro Gly Pro

  20 25 30

  His Pro Pro Gly His Pro Leu Gly Ser Pro Leu Lys Pro Pro Arg Gln

  35 40 45

  Thr His Ser Arg Thr Lys Leu Ser

  50 55

  <210> SEQ ID NO 537

  <211> LENGTH: 52

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 537

  Gln Glu Phe Gln Thr Gly Leu Gly Asn Met Val Lys Pro Cys Leu Tyr

  1 5 10 15

  Glu Lys Tyr Arg Asn Ile Ser Trp Leu Trp Trp His Thr Pro Val Val

  20 25 30

  Pro Ala Thr Trp Glu Ala Glu Val Gly Gly Ser Leu Glu Pro Gly Arg

  35 40 45

  Leu Arg Leu Gln

  50

  <210> SEQ ID NO 538

  <211> LENGTH: 65

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 538

  Ile Leu Gly Gly Glu Ser Ile Leu Ile Leu Ser Trp Val Phe Ser Tyr

  1 5 10 15

  Ile Phe Phe Arg Ile Ala Leu Glu Ile Thr Ile Tyr Ile Leu Asn Val

  20 25 30

  Ser Pro Phe Cys Leu Gly Arg Trp Leu Met Pro Val Ile Pro Ala Leu

  35 40 45

  Trp Glu Ala Glu Val Gly Gly Leu Pro Glu Leu Arg Ser Ser Arg Pro

  50 55 60

  Ala

  65

  <210> SEQ ID NO 539

  <211> LENGTH: 15

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 539

  Met Pro Lys Gln Leu Ala Gln Leu Leu Tyr Arg Leu Pro Arg Gly

  1 5 10 15

  <210> SEQ ID NO 540

  <211> LENGTH: 46

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 540

  Leu Phe Gln Ala Ile Ser Val Ser Gly Ser His Arg Gln Gly Ser Arg

  1 5 10 15

  Thr Trp Asn Thr Leu Thr Glu Gly Asn Ala Glu Ala Ala Cys Thr Val

  20 25 30

  Ala Leu Gln Thr Ser Lys Arg Leu Ile Leu Ala Ser Arg Trp

  35 40 45

  <210> SEQ ID NO 541

  <211> LENGTH: 50

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 541

  Thr Leu Ser Phe Met Asn Ser His Cys Val Pro Ile Lys Ala Leu Phe

  1 5 10 15

  Phe Leu Ser Val Val Ser Tyr Ile Phe Ile Met Pro His His Ile Phe

  20 25 30

  Phe Thr Val Lys Ile Leu Lys Ser Cys Phe Gln Val Gly Gln Leu Met

  35 40 45

  Lys Leu

  50

  <210> SEQ ID NO 542

  <211> LENGTH: 109

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 542

  Arg Pro Thr Arg Pro Ile Thr Phe Ser Ser Asn Ile Ser Glu Trp Val

  1 5 10 15

  Pro Ser Thr Gly Phe Gln Asp Leu Glu His Phe Asn Arg Arg Lys Cys

  20 25 30

  Arg Ser Ser Leu His Ser Cys Phe Thr Asp Phe Gln Glu Ala Asp Ser

  35 40 45

  Gly Phe Lys Met Glu Pro Trp Ser Trp Phe Phe Phe Phe Phe Phe Phe

  50 55 60

  Phe Pro Gln Arg Thr Cys Gly Cys Ala Leu Cys Val Leu Phe Leu Phe

  65 70 75 80

  Ser Ile Trp Gly Pro His Gly Lys Glu Leu Leu Asn Ser Phe Leu Tyr

  85 90 95

  Glu Leu Pro Leu Cys Ser Tyr Lys Gly Pro Phe Leu Ser

  100 105

  <210> SEQ ID NO 543

  <211> LENGTH: 62

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 543

  Val Asp Pro Arg Val Arg Leu Pro Leu Phe Trp Trp Gln Pro Ser Cys

  1 5 10 15

  Ala Val Tyr Leu Phe Pro Arg Val Tyr Asn Asn Met Cys Thr Arg Val

  20 25 30

  Leu Gly Thr Leu Pro His Cys Trp Asp Leu Ala Thr Leu Leu Gln Pro

  35 40 45

  Ser Ser Arg Ile Trp Gly Asn Val Ser Glu Ala Pro Gly Met

  50 55 60

  <210> SEQ ID NO 544

  <211> LENGTH: 87

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 544

  Val Pro Tyr His Ile Ala Gly Thr Leu Pro His Cys Cys Ser Leu Pro

  1 5 10 15

  Val Gly Tyr Gly Gly Met Ser Val Arg Leu Gln Gly Cys Arg Tyr Val

  20 25 30

  Gly Asn Val Gly Pro Gln Gly Asn Met Gln Ser Gly Arg Ser Trp Ala

  35 40 45

  Leu Lys Met Val Leu Leu Cys Asn Ser Cys Leu Gly Leu Gly Val Gly

  50 55 60

  Ser Val Gly Pro Ser Met Ser Ser Leu Phe Gly Ala Val Leu Ser Glu

  65 70 75 80

  Thr Pro Gly Ser Ser Val Tyr

  85

  <210> SEQ ID NO 545

  <211> LENGTH: 29

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 545

  Met Leu Asp Pro Arg Ala Thr Cys Asn Leu Val Gly Val Gly Leu Ser

  1 5 10 15

  Lys Trp Cys Cys Cys Val Thr Ala Ala Trp Val Leu Gly

  20 25

  <210> SEQ ID NO 546

  <211> LENGTH: 65

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (48)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 546

  His Gly Asp Trp Ile Tyr Val His Ile Val Glu Gln Leu Asn Gln Ala

  1 5 10 15

  Asn Asn Lys Ser Val Thr Ser His Thr Tyr Phe Val Val Lys Thr Cys

  20 25 30

  Lys Ile His Ser Leu Ser Asn Phe Gln Ala Ser Asn Thr Leu Leu Xaa

  35 40 45

  Thr Val Val Thr Met Leu Tyr Asn Arg Ser Leu Glu Leu Ile Leu Pro

  50 55 60

  Val

  65

  <210> SEQ ID NO 547

  <211> LENGTH: 68

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (26)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 547

  Thr Tyr Ser Ser Cys Leu Thr Lys Ile Leu Tyr Ser Leu Ile Asn Ile

  1 5 10 15

  Tyr Pro Ile Pro His Cys Ser Pro Ala Xaa Ile Thr Thr Ile Leu Leu

  20 25 30

  Ser Ala Ser Met Asn Leu Thr Phe Phe Phe Phe Arg Phe His Ile Cys

  35 40 45

  Glu Ile Ala Gln Tyr Leu Ser Phe Cys Ala Trp Leu Ile Ser Leu Asn

  50 55 60

  Ile Lys Ser Leu

  65

  <210> SEQ ID NO 548

  <211> LENGTH: 33

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 548

  Met Asn Leu Thr Phe Phe Phe Phe Arg Phe His Ile Cys Glu Ile Ala

  1 5 10 15

  Gln Tyr Leu Ser Phe Cys Ala Trp Leu Ile Ser Leu Asn Ile Lys Ser

  20 25 30

  Leu

  <210> SEQ ID NO 549

  <211> LENGTH: 58

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 549

  Leu Val Cys Tyr Cys Ser Thr Lys Lys Glu Lys Lys Leu His Glu Ile

  1 5 10 15

  Ala Ile Gln Gln Gly Gln Asn Trp Arg Trp Leu Leu Phe Tyr Lys Glu

  20 25 30

  Ile Ser Val Pro Gly Phe Gln Ser Val Trp Cys Ser Tyr Lys Cys Leu

  35 40 45

  Cys Val Val Trp Lys Ala Gly Glu Gly Gly

  50 55

  <210> SEQ ID NO 550

  <211> LENGTH: 36

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 550

  Arg Arg Ser Cys Ser Gly Pro Pro Leu Val Asn Thr Ala Gly Lys Ile

  1 5 10 15

  Leu Ser Ser Ser Pro Ala Lys Leu Ala Cys Lys Arg Thr Asp Phe His

  20 25 30

  Ile Pro Ser Ile

  35

  <210> SEQ ID NO 551

  <211> LENGTH: 37

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 551

  Arg Ala Ser Ile Leu Gly Ile Asp Asn Glu Arg Gly Cys His Phe Arg

  1 5 10 15

  His Phe Asn Pro Leu Lys Glu Tyr Lys Arg Lys Lys Lys Glu Asn Lys

  20 25 30

  Ser Phe Arg Ile Val

  35

  <210> SEQ ID NO 552

  <211> LENGTH: 77

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 552

  Ser Lys Asn Lys Thr Arg Gly Gly Asp Trp Cys Val Thr Val Leu Arg

  1 5 10 15

  Lys Arg Arg Lys Ser Phe Met Lys Ser Pro Phe Ser Lys Asp Arg Thr

  20 25 30

  Gly Asp Gly Phe Ser Phe Thr Lys Lys Ser Leu Ser Gln Ala Phe Ser

  35 40 45

  Leu Phe Gly Val His Thr Ser Val Cys Val Leu Cys Gly Arg Arg Gly

  50 55 60

  Lys Ala Gly Glu Gly Gly Pro Val Gln Gly Pro Leu Trp

  65 70 75

  <210> SEQ ID NO 553

  <211> LENGTH: 55

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 553

  Met Lys Ser Pro Phe Ser Lys Asp Arg Thr Gly Asp Gly Phe Ser Phe

  1 5 10 15

  Thr Lys Lys Ser Leu Ser Gln Ala Phe Ser Leu Phe Gly Val His Thr

  20 25 30

  Ser Val Cys Val Leu Cys Gly Arg Arg Gly Lys Ala Gly Glu Gly Gly

  35 40 45

  Pro Val Gln Gly Pro Leu Trp

  50 55

  <210> SEQ ID NO 554

  <211> LENGTH: 24

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 554

  Met Gly Glu Ser Glu Cys Tyr Arg Arg Leu Ser Gly Ala Ser Cys Thr

  1 5 10 15

  Trp Thr Val His Val Asp Phe Ala

  20

  <210> SEQ ID NO 555

  <211> LENGTH: 33

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 555

  Met His Cys Gly Thr Arg Val Trp Lys Thr Met Lys His Asp Tyr Phe

  1 5 10 15

  Leu Leu Ala Cys Leu Ser Met Thr Ser Thr Gly Gly Ile Leu Cys Thr

  20 25 30

  Leu

  <210> SEQ ID NO 556

  <211> LENGTH: 67

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 556

  Ser Thr Leu Ser Leu Ile Pro Thr Ser Ser Ser Leu Ser Phe Trp Pro

  1 5 10 15

  Trp Cys Thr Ala Ile Ile Gly Ser Ile Phe Thr Tyr Cys Val Cys Val

  20 25 30

  Cys Val Cys Phe Val Val Met Asn Arg Thr Cys Tyr Leu Pro Asn Ser

  35 40 45

  Ile Ile Tyr His Asn Ser Lys Leu Ala Thr Ile Ile Asp Lys Ser Met

  50 55 60

  Thr Leu Ser

  65

  <210> SEQ ID NO 557

  <211> LENGTH: 20

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 557

  Met Trp Ile Leu Pro Lys Val Ser Leu Ile Cys Ile Val Glu Leu Gly

  1 5 10 15

  Tyr Gly Lys Pro

  20

  <210> SEQ ID NO 558

  <211> LENGTH: 62

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 558

  Met Ser Thr Gly Asp Gly Arg Asp Ala Glu Lys Gly Trp Pro Val Ser

  1 5 10 15

  Glu Glu Glu Asn Gln Arg Ser Val Tyr Pro Gly Tyr Pro Glu Cys Asp

  20 25 30

  Glu Arg Gln Ala Val Pro Gln His Cys Ala Ile Ala Ser Pro Ser Ser

  35 40 45

  Leu Gln Ser His His Pro Ala Ser Ala Cys Val Pro Arg Arg

  50 55 60

  <210> SEQ ID NO 559

  <211> LENGTH: 38

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 559

  Gln Gln Met Thr Leu Gly Thr Lys Ile Lys Trp Gly Gln Leu Gln Arg

  1 5 10 15

  Gly Gln Glu Ile Pro Thr Gly Asp Phe Thr Val Arg Asn Phe Met Arg

  20 25 30

  Phe Ser Ile Ile Tyr Cys

  35

  <210> SEQ ID NO 560

  <211> LENGTH: 31

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (11)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 560

  Pro Phe Leu Phe Cys Ala Ser Arg Ile Arg Xaa Gln Gly Ile Gly Ile

  1 5 10 15

  His Gly Gln Val Ala Cys Ser Ala Val Arg Met Tyr Asn Asn Arg

  20 25 30

  <210> SEQ ID NO 561

  <211> LENGTH: 45

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 561

  Val Leu Cys Glu Glu Ala Gly Gln Lys Val Pro Ser Thr Pro Ser Trp

  1 5 10 15

  Ser Ser Trp Thr Leu Gln Lys Arg Leu Arg Gly Ser Pro Ala Glu Ala

  20 25 30

  Asn Cys Ser Pro Ser Phe Pro Ala Pro Pro Gly Lys Glu

  35 40 45

  <210> SEQ ID NO 562

  <211> LENGTH: 103

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 562

  Met Ser Leu Ser Ala Leu Ala Cys Asp Phe Thr Pro Ile Gln Pro Trp

  1 5 10 15

  Glu Trp Glu Glu Tyr Glu Gln Ile Thr Leu Gly Leu Thr Ala Pro Ser

  20 25 30

  Asn Leu Leu Glu Ser Asn Tyr Leu Gly Gln Ala Ser Glu Cys Phe Val

  35 40 45

  Arg Lys Leu Val Arg Arg Phe Pro Gln Leu Leu Pro Gly Pro Pro Gly

  50 55 60

  His Cys Arg Lys Asp Leu Gly Asp Pro Gln Gln Arg Pro Ile Ala Leu

  65 70 75 80

  Leu Pro Ser Leu Pro His Gln Glu Arg Asn Asn Val His Arg Leu Glu

  85 90 95

  Ala Asp Ser Glu Val Asp Leu

  100

  <210> SEQ ID NO 563

  <211> LENGTH: 46

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 563

  Cys Val Asp Phe Asp Glu Tyr Phe Ser Ser Trp Glu Pro Leu Leu Lys

  1 5 10 15

  Met Met Phe Lys Gly Val Val Gly Gly Lys Met Lys Ala Trp Arg Arg

  20 25 30

  Lys Lys Arg Arg Lys Pro Leu Pro Tyr Lys Ile His Ala Asp

  35 40 45

  <210> SEQ ID NO 564

  <211> LENGTH: 30

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 564

  Met Met Phe Lys Gly Val Val Gly Gly Lys Met Lys Ala Trp Arg Arg

  1 5 10 15

  Lys Lys Arg Arg Lys Pro Leu Pro Tyr Lys Ile His Ala Asp

  20 25 30

  <210> SEQ ID NO 565

  <211> LENGTH: 37

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 565

  Leu Ile Ser Ser Val Asn Lys Thr Lys Gln Lys Arg Ser Asp Ala Thr

  1 5 10 15

  Leu Ser His Lys His Asp Arg Leu Leu Asn His Phe Val Phe Phe Gly

  20 25 30

  Asn Ser Tyr Asn Tyr

  35

  <210> SEQ ID NO 566

  <211> LENGTH: 127

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (95)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 566

  Ser Ser Lys Phe Pro Ser Asp Met Leu Leu Arg Ile Gln Gln Ile Ile

  1 5 10 15

  Tyr Cys His Lys Leu Thr Ile Ile Leu Thr Lys Trp Arg Asn Thr Ala

  20 25 30

  Arg His Lys Ser Lys Lys Lys Glu Asp Glu Leu Ile Leu Lys His Glu

  35 40 45

  Leu Gln Leu Lys Lys Trp Lys Asn Arg Leu Ile Leu Lys Arg Ala Ala

  50 55 60

  Ala Glu Glu Ser Asn Phe Pro Glu Arg Ser Ser Ser Glu Val Phe Leu

  65 70 75 80

  Val Asp Glu Thr Leu Lys Cys Asp Ile Ser Leu Leu Pro Glu Xaa Ala

  85 90 95

  Ile Leu Gln Val Cys Met Asn Ser Val Tyr Ile Ile Tyr Tyr Asn Leu

  100 105 110

  Pro Ser Val Val Val His Ala Cys Asn Pro Ser Cys Leu Gly Gly

  115 120 125

  <210> SEQ ID NO 567

  <211> LENGTH: 11

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 567

  Ser Leu Glu Ser Thr Asn Ala Ile Lys Ser Asn

  1 5 10

  <210> SEQ ID NO 568

  <211> LENGTH: 19

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 568

  Ile Arg Pro Asn Lys Asn Asp Gln Met Arg His Cys Leu Ile Asn Met

  1 5 10 15

  Ile Asp Tyr

  <210> SEQ ID NO 569

  <211> LENGTH: 37

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 569

  Ile Thr Leu Cys Phe Leu Glu Thr Ala Ile Thr Ile Asn Ile Tyr Ser

  1 5 10 15

  Asn Leu Val Asn Phe Leu Gln Ile Cys Tyr Cys Gly Tyr Asn Arg Ser

  20 25 30

  Ser Ile Val Thr Ser

  35

  <210> SEQ ID NO 570

  <211> LENGTH: 31

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 570

  Ile Ser Phe Arg Tyr Ala Ile Ala Asp Thr Thr Asp His Leu Leu Ser

  1 5 10 15

  Gln Ala Asn His Tyr Pro Asn Lys Met Ala Glu Tyr Ser Lys Thr

  20 25 30

  <210> SEQ ID NO 571

  <211> LENGTH: 86

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (18)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 571

  Pro Gln Ile Lys Leu Leu Asn Ser Asp Ala Leu Gly Met Arg Thr Thr

  1 5 10 15

  Ser Xaa Asp Leu Val Pro Cys Asn Gln Cys Phe Ile Pro Leu Pro Pro

  20 25 30

  Ser Cys Asn Arg Ile Ala Ser Arg Lys Ala Val Asn Trp Lys Gln Gln

  35 40 45

  Arg Leu Pro Ala Val Arg Gly Leu Leu Asn Asn Ala Pro His Arg Arg

  50 55 60

  Pro Pro Thr Pro Arg Thr Pro Cys Val Phe Pro Ser Glu Gly Pro Lys

  65 70 75 80

  Gly Tyr Gly Phe His Val

  85

  <210> SEQ ID NO 572

  <211> LENGTH: 39

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (5)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 572

  Glu Gln Leu Ala Xaa Ile Ser Cys Arg Val Ile Asn Val Ser Phe Arg

  1 5 10 15

  Cys Leu His His Val Ile Glu Ser Leu Pro Glu Arg Gln Leu Thr Gly

  20 25 30

  Ser Ser Arg Gly Ser Gln Pro

  35

  <210> SEQ ID NO 573

  <211> LENGTH: 73

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (45)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 573

  Glu Asp Cys Ser Thr Met Pro Pro Ile Ala Ala Pro Pro Pro Leu Ala

  1 5 10 15

  Pro Leu Val Phe Ser Pro Leu Arg Gly Pro Arg Val Met Ala Phe Met

  20 25 30

  Ser Arg Cys Gly Asp Arg Gly Gly Arg Gly Arg Ser Xaa Ala Gly Arg

  35 40 45

  Gly Trp Pro Trp Ser Glu Ser Gly Val Ile Asn Ala His Pro Lys Lys

  50 55 60

  Arg Pro Cys Pro Gly Pro Met Leu Ser

  65 70

  <210> SEQ ID NO 574

  <211> LENGTH: 48

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 574

  Glu Phe Gly Thr Arg Arg Gln Trp Gly Thr Arg Cys Phe Pro Pro Leu

  1 5 10 15

  Val Gly Arg Lys Gln Ser Ala Leu Arg Arg Arg Glu Gly Lys Ala Arg

  20 25 30

  Ala Gly Arg Cys Cys Gly Lys Arg Ser Val Lys Ala Gly Phe Asp Ala

  35 40 45

  <210> SEQ ID NO 575

  <211> LENGTH: 52

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 575

  Ala Phe Phe Leu Leu Gln Ala Leu Glu Ile Gln Ser Gln Leu Ala Thr

  1 5 10 15

  Pro Ala Ser Ser Thr Ala Arg Asn Pro Ala Pro Asp Leu His His Pro

  20 25 30

  His Gln Pro Thr Ile Glu Arg Phe Cys Arg His Ser Ser Ser Trp Glu

  35 40 45

  Arg Ile Glu Tyr

  50

  <210> SEQ ID NO 576

  <211> LENGTH: 42

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 576

  Ala Thr Val Pro Gly Ser Ile Tyr Asn Tyr Phe Tyr His Tyr Asn Ala

  1 5 10 15

  Gly Ala Leu Lys Pro Glu His Ala Ser Glu Ser Pro Arg Gly Leu Cys

  20 25 30

  Ala Gln Thr Ala Gly Pro Phe Pro Ser Phe

  35 40

  <210> SEQ ID NO 577

  <211> LENGTH: 56

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 577

  Ile Arg His Glu Pro Pro Pro Pro Arg Phe Lys Arg Phe Ser Cys Leu

  1 5 10 15

  Ser Leu Leu Ser Ser Trp Asp Tyr Arg Arg Ala Pro Pro His Val Ala

  20 25 30

  Ile Phe Cys Thr Leu Ser Arg Asp Gly Val Leu Pro His Trp Pro Gly

  35 40 45

  Trp Ser Gln Thr Pro Asp Leu Lys

  50 55

  <210> SEQ ID NO 578

  <211> LENGTH: 72

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 578

  Ser Thr His Leu Gly Leu Pro Arg Cys Trp Asp Tyr Arg His Glu Pro

  1 5 10 15

  Leu Cys Leu Ala Pro Phe Thr Thr Ile Ser Ile Ile Ile Met Gln Gly

  20 25 30

  Leu Ser Asn Leu Ser Met Pro Gln Asn Pro Pro Glu Gly Cys Ala His

  35 40 45

  Arg Leu Leu Asp Leu Ser Pro Ala Ser Asp Ser Val Pro Pro Glu Trp

  50 55 60

  Gly Ser Lys Ile Ala Phe Glu Val

  65 70

  <210> SEQ ID NO 579

  <211> LENGTH: 26

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 579

  Leu Arg Val Gly Gly Thr Ser Glu Asn Cys Cys Arg Gly Glu Cys Cys

  1 5 10 15

  Gly Ser Val Cys Ile Pro Pro Gly Arg Leu

  20 25

  <210> SEQ ID NO 580

  <211> LENGTH: 40

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 580

  Met Cys Val Thr Arg Met His Val Lys Cys Pro Pro Pro Ser Ala Ser

  1 5 10 15

  Val Thr Ala Val Lys Trp Pro Leu Ser Trp Ser Ser Ser Ser Phe Cys

  20 25 30

  Ile Ser Leu His Ala Gly Arg His

  35 40

  <210> SEQ ID NO 581

  <211> LENGTH: 36

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 581

  Glu Glu Arg Asn Lys Asn His Leu Ser Cys Gln Gly Leu Ser Thr Ile

  1 5 10 15

  Cys Cys Ser Tyr Leu Ser Ser Lys Gly Glu His Leu Arg Asn Leu Ser

  20 25 30

  Pro Tyr Ser Phe

  35

  <210> SEQ ID NO 582

  <211> LENGTH: 46

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 582

  Gly Leu Cys Met Val His Ser Leu Leu Thr Ser Ser Leu Gly Gly Arg

  1 5 10 15

  Cys Cys Asn Tyr Pro Tyr Ile Ala Asp Lys Asp Ile Glu Thr Glu Val

  20 25 30

  Lys Pro Pro Ser Gln Gly His Thr Trp His Leu His Cys Ser

  35 40 45

  <210> SEQ ID NO 583

  <211> LENGTH: 75

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 583

  Gln Leu Trp Cys Ile Thr Ala Leu Pro Ser Thr Arg His Cys Ser Lys

  1 5 10 15

  Gly Phe Ala Trp Phe Thr His Ser Leu Arg His Pro Ser Val Ala Gly

  20 25 30

  Ala Val Ile Ile Leu Ile Leu Gln Thr Arg Thr Leu Arg Gln Arg Ser

  35 40 45

  Ser His Leu Pro Lys Gly Thr His Gly Ile Cys Thr Ala Pro Asp Arg

  50 55 60

  Pro Thr Glu Arg Ala Ala Val Thr Ile Leu Lys

  65 70 75

  <210> SEQ ID NO 584

  <211> LENGTH: 39

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 584

  Ser Phe Asp Asn Asn Asn Ser Tyr Gly Val Ser Gln Leu Tyr Gln Val

  1 5 10 15

  Pro Asp Thr Val Leu Arg Ala Leu His Gly Ser Leu Thr Pro Tyr Val

  20 25 30

  Ile Pro Arg Trp Gln Val Leu

  35

  <210> SEQ ID NO 585

  <211> LENGTH: 38

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 585

  Asp Arg Gly Gln Ala Thr Phe Pro Arg Ala His Met Ala Ser Ala Leu

  1 5 10 15

  Leu Leu Thr Asp Arg Gln Arg Glu Leu Leu Ser Arg Ser Ser Asn Glu

  20 25 30

  Leu Cys Met Ser Lys Val

  35

  <210> SEQ ID NO 586

  <211> LENGTH: 73

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (66)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 586

  Leu Leu Leu Ile Leu Arg Pro Phe Leu Asn Ser Gln Phe Lys Leu Gln

  1 5 10 15

  Leu Pro Leu Val Leu Phe His Ser Ser Cys Thr Tyr Ile Cys Leu Leu

  20 25 30

  Tyr Asn Tyr Glu Leu Phe His Ile Val Ala Leu Thr Gly Lys Leu Met

  35 40 45

  Asn Leu Gly Leu His Leu Phe Ala His His Leu Ile Leu Ala Val Ala

  50 55 60

  His Xaa Gly Cys Ser Ile Pro Ile Tyr

  65 70

  <210> SEQ ID NO 587

  <211> LENGTH: 37

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 587

  Thr His Asn Ser Asn Tyr Ser Ser Leu Trp Phe Ser Ser Thr Ala Val

  1 5 10 15

  Val Leu Thr Tyr Val Tyr Tyr Ile Ile Met Asn Cys Phe Ile Leu Ser

  20 25 30

  Pro Leu Gln Val Asn

  35

  <210> SEQ ID NO 588

  <211> LENGTH: 53

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 588

  Thr Leu Val Ala Gly Ser Pro Cys Ser Leu Ser Arg Trp Ile Met Ala

  1 5 10 15

  Gly Phe Cys His Gly Glu Leu Val Gln Ser Asp Met Glu Ser Gln Glu

  20 25 30

  Trp Glu Arg Gly Gln Val Val Leu Ser His Thr Ser Leu Pro Trp Cys

  35 40 45

  Tyr Val Ser Pro Arg

  50

  <210> SEQ ID NO 589

  <211> LENGTH: 39

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 589

  Met Ala Gly Phe Cys His Gly Glu Leu Val Gln Ser Asp Met Glu Ser

  1 5 10 15

  Gln Glu Trp Glu Arg Gly Gln Val Val Leu Ser His Thr Ser Leu Pro

  20 25 30

  Trp Cys Tyr Val Ser Pro Arg

  35

  <210> SEQ ID NO 590

  <211> LENGTH: 94

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 590

  Met Ala Val Trp Ile Ser Gly Ser Tyr Ser Ser Phe Cys Ser Arg Ser

  1 5 10 15

  Asn Trp Asp Val Phe Ser Pro Asn Ile Val Leu Ala Ser Leu Pro Phe

  20 25 30

  Ser Phe Arg Ser Val Ser Lys Ala Ala Lys Pro Trp Trp Leu Ala Leu

  35 40 45

  Pro Ala Leu Phe Pro Asp Gly Leu Trp Leu Asp Ser Ala Met Gly Ser

  50 55 60

  Leu Tyr Ser Gln Thr Trp Lys Ala Arg Asn Gly Lys Glu Val Arg Trp

  65 70 75 80

  Phe Ser Pro Thr Pro His Cys Leu Gly Ala Met Ser His Leu

  85 90

  <210> SEQ ID NO 591

  <211> LENGTH: 19

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 591

  Gly Trp Leu Tyr Gly Ser Val Gly Leu Ile Pro His Ser Ala Ala Glu

  1 5 10 15

  Ala Thr Gly

  <210> SEQ ID NO 592

  <211> LENGTH: 82

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 592

  Arg Ser Lys Arg Gln Ser Gln Gly Ser Arg Cys Ser Val Pro Leu Leu

  1 5 10 15

  Ala Gln Gln Ser Arg Ser Pro Pro Val Pro Leu Gln Ala Gln Pro Ala

  20 25 30

  Trp Leu Leu Gly Ser Glu Thr Ile Ala Trp Ser Gly Gly Gly Ser Gly

  35 40 45

  Trp Glu Gly Pro Arg Asp Pro Gly Thr Ser Thr Ala Ala Gly Asn Ser

  50 55 60

  Gly Pro Gly Ile Gly Met Gly His Arg Thr Pro Pro Pro Ser His Thr

  65 70 75 80

  Gly Arg

  <210> SEQ ID NO 593

  <211> LENGTH: 30

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 593

  Arg Trp Asp Pro Ala Trp Gly Leu Asp Ile Pro Glu Ser Ser Cys Pro

  1 5 10 15

  Val Thr Met Gly Glu Leu Arg Ser Gly Asp Gly Ile Val Leu

  20 25 30

  <210> SEQ ID NO 594

  <211> LENGTH: 50

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 594

  Gly Ala Leu Leu Trp Asp Asn Ser Met Ile Ser Ala Pro Arg Gly Ser

  1 5 10 15

  His Arg Glu Ala Gly Ala Leu Phe Pro Ser Trp Leu Ser Asn Pro Ala

  20 25 30

  Val Leu Pro Ser Arg Ser Arg Pro Ser Gln Pro Gly Cys Leu Asp Pro

  35 40 45

  Arg Gln

  50

  <210> SEQ ID NO 595

  <211> LENGTH: 49

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 595

  Asn Ser Ala Arg Glu Pro Arg Arg Trp Ile Arg Pro Thr Arg Gly Ser

  1 5 10 15

  Gly Glu Thr Thr Ala Pro Cys Cys Phe Glu Pro Leu Asn Gly Gly Thr

  20 25 30

  Leu Val His Ala Ala Ala Met Ala Arg Ala Ser Glu Ala Ala Gly Thr

  35 40 45

  Gly

  <210> SEQ ID NO 596

  <211> LENGTH: 11

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 596

  Met Ala Arg Ala Ser Glu Ala Ala Gly Thr Gly

  1 5 10

  <210> SEQ ID NO 597

  <211> LENGTH: 84

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 597

  Cys Phe Thr Thr Ala Phe Gln Lys Ala Leu Arg Asp Pro Arg Pro Thr

  1 5 10 15

  Leu Pro Asp Thr His Gly Ser Leu Arg Asn Ala Pro Leu Lys Ser Leu

  20 25 30

  Thr Leu Pro Ala Ala Phe Val Val Ser Phe Phe Phe Leu Ser Leu Leu

  35 40 45

  Gln Asp Gly Ile Lys Glu Arg Ser Gln Thr Gln Asn Ala Thr Phe Phe

  50 55 60

  Phe His Asp Arg Ser Asp Ile Glu Gly Leu Ser Glu Glu Pro Cys Ser

  65 70 75 80

  Gly Thr Thr Pro

  <210> SEQ ID NO 598

  <211> LENGTH: 95

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 598

  Leu Ala Leu Gln Glu Ala Val Thr Gly Lys Gln Val Leu Cys Ser Pro

  1 5 10 15

  Pro Gly Ser Ala Ile Pro Gln Ser Ser Arg Pro Ala Pro Gly Pro Ala

  20 25 30

  Ser Leu Ala Ala Trp Ile Arg Asp Asn Ser Leu Val Trp Arg Arg Leu

  35 40 45

  Arg Val Gly Gly Thr Gln Gly Pro Gly His Gln Tyr Ser Ser Trp Glu

  50 55 60

  Phe Arg Pro Arg Asp Arg Asp Gly Ala Gln Asp Thr Thr Pro Ile Ser

  65 70 75 80

  His Arg Glu Met Lys Val Gly Ser Ser Met Gly Thr Gly His Pro

  85 90 95

  <210> SEQ ID NO 599

  <211> LENGTH: 47

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 599

  Met Ala Gly Arg Leu Phe Thr Leu Leu Leu Trp Gln Glu Leu Ala Arg

  1 5 10 15

  Arg Leu Val Pro Gly Asp Ala Ser Pro Arg Leu Ser Arg Lys Arg Ser

  20 25 30

  Val Thr Pro Gly Pro Pro Phe Pro Thr Leu Thr Val Pro Ser Glu

  35 40 45

  <210> SEQ ID NO 600

  <211> LENGTH: 42

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 600

  Met Phe Tyr Ser Lys Ile Phe Tyr Phe Leu Leu Leu Asn Ser Asp Thr

  1 5 10 15

  Ser Asn Asn Val Thr Ser Lys Thr Leu Val Ser Ser Ile Ser Ser Ser

  20 25 30

  Asn Asn Arg Leu Ala Val Ser Ile Val Phe

  35 40

  <210> SEQ ID NO 601

  <211> LENGTH: 47

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 601

  Ser Arg Gln Lys Asn Leu Leu Lys Leu His Ser Asn Pro Asn Cys Asp

  1 5 10 15

  Asn Phe Cys Phe Ile Phe Asn Tyr Lys Pro Lys Tyr Ile Cys Ile Phe

  20 25 30

  Lys Leu Ile Cys Leu Lys Ile Leu Leu Tyr Ile Phe Gly Ser Gly

  35 40 45

  <210> SEQ ID NO 602

  <211> LENGTH: 56

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <220> FEATURE:

  <221> NAME/KEY: SITE

  <222> LOCATION: (24)

  <223> OTHER INFORMATION: Xaa equals any of the naturally occurring L-

  amino acids

  <400> SEQUENCE: 602

  Met Leu Leu Ser Leu Leu Met Val Phe Thr Ser Glu Leu Tyr Val Lys

  1 5 10 15

  Arg His Ile Ser Phe Lys Ser Xaa Asp Lys Pro His Cys His Lys Asn

  20 25 30

  Gln Asp Ile Asp Val Leu Phe Arg Lys Leu Leu Glu Lys His Phe Lys

  35 40 45

  Val Ile Asn Met Ile Cys Phe Pro

  50 55

  <210> SEQ ID NO 603

  <211> LENGTH: 12

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 603

  Phe Arg Glu Tyr Gly Phe Tyr Asn Leu His Phe Cys

  1 5 10

  <210> SEQ ID NO 604

  <211> LENGTH: 38

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 604

  Leu Val Thr Thr Asp Tyr Tyr Asp Gly Cys Asn Glu Asp Tyr Glu Tyr

  1 5 10 15

  Asn Trp Ser Tyr Met Phe Leu Asn Ser Glu Gln Leu Phe Ile Lys Phe

  20 25 30

  Tyr Pro Thr Phe Phe Cys

  35

  <210> SEQ ID NO 605

  <211> LENGTH: 52

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 605

  Asn Val Ile Ala Pro Gly Leu Glu Ser Ser Cys Ala Asn Ser Leu Phe

  1 5 10 15

  Leu Leu Phe Val Cys Leu Pro Val Ala His His Arg His Asn Phe Leu

  20 25 30

  Phe Ile Lys His Ser Leu Tyr Asn His Leu Arg Asp Tyr Glu Ser Asp

  35 40 45

  Phe Asp Lys Ile

  50

  <210> SEQ ID NO 606

  <211> LENGTH: 34

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 606

  Pro Lys Val Leu Ala Val Leu Lys Lys Lys Asn His Val Ala Leu Ser

  1 5 10 15

  Ile Phe Glu Leu Leu Ser Asn Asp Ile Cys Ser Phe Ile Ser Phe Phe

  20 25 30

  Met Ser

  <210> SEQ ID NO 607

  <211> LENGTH: 28

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 607

  Glu Gly Pro Asp Ile Asn Ser Asn Leu Lys Phe Leu Leu Cys Leu Lys

  1 5 10 15

  Lys Lys Ile Met Trp Pro Phe Gln Tyr Leu Asn Cys

  20 25

  <210> SEQ ID NO 608

  <211> LENGTH: 47

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 608

  Leu Leu Ser Leu Ile Leu Leu Arg Ile Trp Tyr Asp Phe Ser Lys Gln

  1 5 10 15

  Thr Val Phe Trp Phe Phe Leu Asn Val Phe Asn Phe Phe Ser Ser Cys

  20 25 30

  Asn Asn Asp Gly Ala Cys Ser Tyr Lys Tyr Arg Lys Val Gln Ile

  35 40 45

  <210> SEQ ID NO 609

  <211> LENGTH: 12

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 609

  His Thr Leu Phe Ile Ser Phe Leu Trp Ala Glu Gly

  1 5 10

  <210> SEQ ID NO 610

  <211> LENGTH: 28

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 610

  Met Leu Pro Val Phe Val Leu Phe Phe Cys Phe Thr Tyr Ser Ala Arg

  1 5 10 15

  Lys Gln Ser Val Phe Lys Lys Gly Asn Val Phe Glu

  20 25

  <210> SEQ ID NO 611

  <211> LENGTH: 63

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 611

  Ser Pro Cys Ser Ala Ala Glu Cys His Asn Leu Ser Leu Leu Ser Ser

  1 5 10 15

  Cys Ser Leu Val Ser Ser Asn Ile Leu Phe Ser Phe Pro Phe Phe Gly

  20 25 30

  Gln Lys Ala Arg Cys Cys Leu Phe Leu Phe Tyr Phe Ser Ala Ser His

  35 40 45

  Ile Ala His Glu Ser Arg Val Tyr Ser Lys Lys Glu Met Cys Leu

  50 55 60

  <210> SEQ ID NO 612

  <211> LENGTH: 65

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 612

  His Lys Cys Phe Gln Cys Phe Ile Leu Ala Asn Gly Phe Leu Lys Val

  1 5 10 15

  Ile Lys Pro Phe Gln Arg Asn Trp Ser Asp Lys Thr Phe Phe Leu Val

  20 25 30

  Cys Leu Asn Lys Ala Ile Ser Glu Ala Leu Leu Ser Lys Met Thr Phe

  35 40 45

  Leu Ser Phe Phe Lys Thr Asn Leu Leu Leu Leu Glu Thr Phe Cys Thr

  50 55 60

  Ile

  65

  <210> SEQ ID NO 613

  <211> LENGTH: 99

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 613

  Leu Leu Gly Val Leu Lys Pro Leu Tyr Phe Ser Val Glu Pro Val Leu

  1 5 10 15

  Gly Glu Arg Ser Val Ala Phe Glu Glu Val Arg Glu Lys Asn His Gly

  20 25 30

  Thr Ser Gly Phe Leu Ser Leu Tyr Ser Leu Ala Ala Ile Val Cys Gly

  35 40 45

  His Leu Met Phe Phe His Thr Leu Leu Gly Arg Gly Gly Asn Asp His

  50 55 60

  Pro Gly Gln Ser Pro Leu Pro Gly Met Arg Pro Leu Arg Gly Gly Leu

  65 70 75 80

  Ala Gly Gln Ala Pro Ser Gly His Pro Trp Met Gln Pro Leu Asp Thr

  85 90 95

  Cys Leu Leu

  <210> SEQ ID NO 614

  <211> LENGTH: 43

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 614

  Arg Pro Thr Arg Pro Pro Thr Arg Pro Asp Arg Pro Ser Leu Glu Leu

  1 5 10 15

  Ala Pro Gly Leu Cys Ala Asp Phe Leu Gly Ser Ser Asn His Cys Ile

  20 25 30

  Phe Leu Leu Ser Leu Tyr Leu Gly Arg Asp Gln

  35 40

  <210> SEQ ID NO 615

  <211> LENGTH: 49

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 615

  Glu Lys Arg Ile Met Val Pro Gln Gly Phe Phe Pro Phe Thr Arg Trp

  1 5 10 15

  Gln Pro Leu Ser Val Gly Thr Ser Cys Phe Ser Thr Leu Tyr Trp Ala

  20 25 30

  Val Glu Val Thr Ile Thr Gln Ala Ser Leu Leu Cys Leu Gly Cys Ala

  35 40 45

  Leu

  <210> SEQ ID NO 616

  <211> LENGTH: 123

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 616

  Met Thr Leu Asp Glu Trp Lys Asn Leu Gln Glu Gln Thr Arg Pro Lys

  1 5 10 15

  Pro Glu Phe Asn Ile Arg Lys Pro Glu Ser Thr Val Pro Ser Lys Ala

  20 25 30

  Val Val Ile Arg Glu Ser Lys Tyr Arg Asp Asp Met Val Lys Asp Asp

  35 40 45

  Tyr Glu Asp Asp Ser His Val Phe Arg Lys Pro Ala Asn Asp Ile Thr

  50 55 60

  Ser Gln Leu Glu Ile Asn Phe Gly Asn Leu Pro Arg Pro Gly Arg Gly

  65 70 75 80

  Ala Arg Gly Gly Thr Arg Gly Gly Arg Gly Arg Ile Arg Arg Ala Glu

  85 90 95

  Asn Tyr Gly Pro Arg Ala Glu Val Val Met Gln Asp Val Ala Pro Asn

  100 105 110

  Pro Asp Asp Pro Glu Asp Phe Pro Ala Leu Ser

  115 120

  <210> SEQ ID NO 617

  <211> LENGTH: 100

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 617

  Cys Lys Met Leu Pro Pro Thr Gln Met Thr Arg Lys Ile Ser Leu Arg

  1 5 10 15

  Cys Leu Glu Arg Ala Leu Phe Pro Ser Thr Ala Glu Leu His Cys Thr

  20 25 30

  Pro Val Gly Arg Leu Phe Gln Leu Gly Gln Gly Ser Gln Thr Leu Arg

  35 40 45

  Thr Ile Asp Val Ala Phe Pro Val Ser Cys Lys Phe Val Ala Leu Phe

  50 55 60

  Trp Ala Glu Leu Leu Glu Gly Leu Leu Gln Arg Leu Glu Ser Arg Pro

  65 70 75 80

  Phe Pro Lys Lys Met Lys Asn Gly Asp Cys Val Phe Ile Glu Gly Ile

  85 90 95

  Ser Asn Glu Glu

  100

  <210> SEQ ID NO 618

  <211> LENGTH: 41

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 618

  Pro Pro Ser Ser Trp Ala Trp Ser Gln Arg Arg His Pro Gly Arg Pro

  1 5 10 15

  Gly Lys Asp Gln Glu Gly Arg Glu Leu Trp Thr Gln Ser Arg Ser Gly

  20 25 30

  Asp Ala Arg Cys Cys Pro Gln Pro Arg

  35 40

  <210> SEQ ID NO 619

  <211> LENGTH: 22

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 619

  Cys Leu Lys Cys Val Tyr Arg Asp Ser Ile Asp Ser Ser Ala Glu Ala

  1 5 10 15

  Trp Arg Glu Arg Arg Leu

  20

  <210> SEQ ID NO 620

  <211> LENGTH: 29

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 620

  Leu Ser Tyr Ser Val Leu Leu Ile Leu Pro Leu Phe His Ser Leu Pro

  1 5 10 15

  Thr Leu Lys Asp Thr His Thr His Asn Lys Trp Val Glu

  20 25

  <210> SEQ ID NO 621

  <211> LENGTH: 61

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 621

  Glu Val Asn Gly Val Gly Tyr Lys His Ser Cys Phe Ser Asp Ile Ser

  1 5 10 15

  Ser Val Leu Glu Asn Lys Asp Ser Arg Met Arg Ala Pro His Tyr Ala

  20 25 30

  Ser Phe Gln His Phe Phe Ser Val Leu Leu Lys Leu Ser Pro Gln Ala

  35 40 45

  Cys Leu Thr Glu Ser Gln Cys Ile Pro Leu Thr Phe Tyr

  50 55 60

  <210> SEQ ID NO 622

  <211> LENGTH: 37

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 622

  Lys Thr His Thr His Thr Ile Ser Gly Trp Ser Lys Lys Ser Thr Glu

  1 5 10 15

  Leu Asp Ile Ser Ile Pro Ala Phe Leu Thr Ser Pro Val Ser Trp Arg

  20 25 30

  Thr Arg Ile Leu Glu

  35

  <210> SEQ ID NO 623

  <211> LENGTH: 29

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 623

  Ile Arg His Glu Leu Gly Ser Ser Asp Pro Pro Ala Glu Ala Ser Gln

  1 5 10 15

  Ile Ala Gly Thr Ala Ala Val Ser His His Ala Gln Pro

  20 25

  <210> SEQ ID NO 624

  <211> LENGTH: 25

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 624

  Met Leu Tyr Leu Ile Leu Ile Ser Leu Ser Ser Leu Ser Phe Ser Phe

  1 5 10 15

  Ser Leu Pro Pro Phe Ser Ile Ile Ile

  20 25

  <210> SEQ ID NO 625

  <211> LENGTH: 24

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 625

  Ser Ser Tyr Phe Leu Arg His Phe Arg Ile Tyr His Thr Cys Pro Lys

  1 5 10 15

  Tyr Phe Ser Met Asn Ile Ile Asn

  20

  <210> SEQ ID NO 626

  <211> LENGTH: 69

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 626

  Lys Leu Thr Leu Thr Lys Gly Asn Lys Ser Trp Ser Ser Thr Ala Val

  1 5 10 15

  Ala Ala Ala Leu Glu Leu Val Asp Pro Pro Gly Cys Arg Asn Ser Ala

  20 25 30

  Arg Asp Ser Leu Pro Asn Ser Thr Met Met Phe Tyr Tyr Ala Cys Phe

  35 40 45

  Ile Leu Tyr Ser Ser Leu Ser Pro Leu Ser Leu Ser Leu Ser Pro Ser

  50 55 60

  Leu Leu Ser Leu Leu

  65

  <210> SEQ ID NO 627

  <211> LENGTH: 14

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 627

  Gln Phe His Thr Gly Asn Ser Tyr Asp His Asp Tyr Ala Lys

  1 5 10

  <210> SEQ ID NO 628

  <211> LENGTH: 35

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 628

  Ala Val Cys Thr Gly Gly Tyr Cys Glu Ser Cys Arg Cys Glu His Cys

  1 5 10 15

  Val Cys Val Cys Val Asp Leu Cys Val Leu Phe Ser Gly Lys Glu Leu

  20 25 30

  Arg Val Arg

  35

  <210> SEQ ID NO 629

  <211> LENGTH: 72

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 629

  Val Ser Phe Phe Phe Val Phe Lys Trp Ser Phe Ala Glu Ile Lys Ser

  1 5 10 15

  Arg Glu Glu His Trp Ala Ser Leu Thr Pro Lys Pro Thr Leu Leu Ser

  20 25 30

  Ala Leu Leu Thr Cys Asp Val Leu Lys Ser Ser Ile Ile Phe Lys Cys

  35 40 45

  Cys Glu Ser Thr Glu Asp Lys Gly Phe Asp Ser Phe Phe Gln Ala Ser

  50 55 60

  Lys Asp Gly Ser Ser Ser Arg Ile

  65 70

  <210> SEQ ID NO 630

  <211> LENGTH: 99

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 630

  Arg Ser Trp Gly Ser Gln Arg Ser Leu Cys Leu Leu Phe Ile Pro Phe

  1 5 10 15

  Ala Ala Glu Ser Tyr Ser Val Val Trp Met Gly His Leu Phe Val Val

  20 25 30

  Cys Leu Leu Ser Ser Trp Trp Thr Phe Arg Pro Phe Ala Leu Ala Val

  35 40 45

  Thr Val Asn His Val Ala Val Asn Ile Val Cys Val Ser Ala Trp Thr

  50 55 60

  Cys Val Ser Cys Ser Leu Gly Arg Ser Cys Gly Leu Glu Gly Ser Phe

  65 70 75 80

  Leu Phe Pro Leu Glu Thr Leu Trp Phe Pro His Met Val Val Leu Cys

  85 90 95

  Leu Thr Phe

  <210> SEQ ID NO 631

  <211> LENGTH: 74

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 631

  Met Gly His Leu Phe Val Val Cys Leu Leu Ser Ser Trp Trp Thr Phe

  1 5 10 15

  Arg Pro Phe Ala Leu Ala Val Thr Val Asn His Val Ala Val Asn Ile

  20 25 30

  Val Cys Val Ser Ala Trp Thr Cys Val Ser Cys Ser Leu Gly Arg Ser

  35 40 45

  Cys Gly Leu Glu Gly Ser Phe Leu Phe Pro Leu Glu Thr Leu Trp Phe

  50 55 60

  Pro His Met Val Val Leu Cys Leu Thr Phe

  65 70

  <210> SEQ ID NO 632

  <211> LENGTH: 51

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 632

  His Asp Val Leu Gly Ala Arg Asn Ala Ala Cys Val Cys Cys Ser Phe

  1 5 10 15

  Leu Leu Gln Gln Asn Arg Ile Leu Leu Phe Gly Trp Ala Thr Cys Leu

  20 25 30

  Leu Ser Val Tyr Ser Pro Ala Gly Gly His Leu Gly Arg Leu His Trp

  35 40 45

  Arg Leu Leu

  50

  <210> SEQ ID NO 633

  <211> LENGTH: 130

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 633

  Met Leu Asp Phe Lys Thr Ser Gln Val Ser Lys Ala Leu Lys Arg Val

  1 5 10 15

  Gly Phe Gly Val Arg Leu Ala Gln Cys Ser Ser Leu Asp Leu Ile Ser

  20 25 30

  Ala Lys Leu His Leu Lys Thr Lys Lys Lys Glu Thr Tyr Ile Thr Ser

  35 40 45

  Thr Val Met Thr Ala Ala Ser Leu Phe Leu Ser Tyr Val Thr Ser Glu

  50 55 60

  Phe Thr Arg Ser Ile Met Ala Thr Phe Tyr Cys Phe Val Leu Lys Leu

  65 70 75 80

  His Ile Gly Glu Met Gly Thr Leu Gln Thr Ala Gly Gly Ser Lys Met

  85 90 95

  Thr Trp Pro Leu Gln Lys Ala Ile Trp Gln Phe Leu Lys Arg Leu Ser

  100 105 110

  Ile Lys Leu Pro Tyr Val Glu Thr Arg Glu Ser Pro Gly Glu Thr Lys

  115 120 125

  Asn Tyr

  130

  <210> SEQ ID NO 634

  <211> LENGTH: 28

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 634

  Leu Thr Arg Asn Ser Phe Pro Glu Asn Arg Thr His Lys Ser Thr Gln

  1 5 10 15

  Thr His Thr Gln Cys Ser Gln Arg His Asp Ser Gln

  20 25

  <210> SEQ ID NO 635

  <211> LENGTH: 90

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 635

  Ile Arg His Glu Gly Gln Ser Ser Ser Arg Gly Ser Ser His Cys Asp

  1 5 10 15

  Ser Pro Ser Pro Gln Glu Asp Gly Gln Ile Met Phe Asp Val Glu Met

  20 25 30

  His Thr Ser Arg Asp His Ser Ser Gln Ser Glu Glu Glu Val Val Glu

  35 40 45

  Gly Glu Lys Glu Val Glu Ala Leu Lys Lys Ser Ala Asp Trp Val Ser

  50 55 60

  Asp Trp Ser Ser Arg Pro Glu Asn Ile Pro Pro Lys Glu Phe His Phe

  65 70 75 80

  Arg His Pro Lys Arg Ser Val Ser Leu Ser

  85 90

  <210> SEQ ID NO 636

  <211> LENGTH: 40

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 636

  Gly Ile Leu Leu Thr Leu Tyr Pro Phe Trp Pro Glu Asp Ile Leu Glu

  1 5 10 15

  Phe Pro Asn Arg Val Tyr Cys Cys Leu Glu Ile Cys Lys Gly Phe Phe

  20 25 30

  Ser Ala Asn Ala Thr Ser Arg Leu

  35 40

  <210> SEQ ID NO 637

  <211> LENGTH: 47

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 637

  Glu Phe Gly Thr Arg Asp Arg Val Val Pro Glu Ala Val Leu Thr Val

  1 5 10 15

  Thr Ala Leu Arg His Lys Lys Met Gly Arg Ser Cys Leu Met Trp Lys

  20 25 30

  Cys Thr Pro Ala Gly Thr Ile Ala Leu Ser Gln Lys Lys Lys Leu

  35 40 45

  <210> SEQ ID NO 638

  <211> LENGTH: 52

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 638

  Ala His Pro Leu Pro Ala Pro Thr Glu Gly Lys Glu Lys Pro Leu Glu

  1 5 10 15

  Met Arg Val Thr Cys Glu Val Val Tyr Cys His Ser Ser Leu Phe Glu

  20 25 30

  Leu Glu Thr Ile Val Ser Met Thr Gln Pro Thr Thr Leu Phe Leu His

  35 40 45

  Ile Gln Phe Gln

  50

  <210> SEQ ID NO 639

  <211> LENGTH: 68

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 639

  Thr Phe Cys Val Phe Lys His Glu Glu Lys Trp Ser His Glu Glu Arg

  1 5 10 15

  Gly Tyr Phe Leu Arg Arg Ile Ser Glu Gly Val His Ser Ile Ser Leu

  20 25 30

  Pro Phe Ser Cys Phe Gly Phe Gly Ala Arg His Leu Tyr Trp Lys Ala

  35 40 45

  Thr Glu His Thr Leu Cys Gln His Leu Leu Arg Glu Arg Lys Ser Pro

  50 55 60

  Trp Lys Cys Val

  65

  <210> SEQ ID NO 640

  <211> LENGTH: 64

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 640

  Gln Ser Leu Leu Leu Phe Arg Asn Leu Gln Gly Leu Leu Phe Arg Lys

  1 5 10 15

  Cys His Gln Gln Ile Ile Ile Leu Ser Ala Met Leu Leu Ser Leu Ile

  20 25 30

  Ser Ala Thr Arg Leu Asp Leu Tyr His Ser Trp Tyr Lys Phe Tyr Ser

  35 40 45

  Cys Asn Ile Thr Thr Ile Ser Leu Leu Lys Arg Asp Gln Val Ser Lys

  50 55 60

  <210> SEQ ID NO 641

  <211> LENGTH: 22

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 641

  Ile Arg His Glu Glu Ser Phe Asn Pro Leu Thr Cys Gly Phe Ser Leu

  1 5 10 15

  Phe Phe Ser Leu Phe Ser

  20

  <210> SEQ ID NO 642

  <211> LENGTH: 27

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 642

  Met Glu Thr Leu Leu Leu Leu Leu Phe Phe Leu Ser Leu Leu Ile Phe

  1 5 10 15

  Arg Phe Arg Ile Leu Val Ser Gln Cys Ile Asn

  20 25

  <210> SEQ ID NO 643

  <211> LENGTH: 65

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 643

  Phe Leu Leu Thr Thr Val Leu Leu Phe Ser Ser Lys Val Arg Asp Pro

  1 5 10 15

  Arg Ala Asn Phe Asp Gln Ser Leu Arg Val Leu Lys His Ala Lys Lys

  20 25 30

  Val Gln Pro Asp Val Ile Ser Lys Thr Ser Ile Met Leu Gly Leu Gly

  35 40 45

  Glu Asn Asp Glu Gln Val Tyr Ala Thr Met Lys Gly Lys Glu Ile Glu

  50 55 60

  Lys

  65

  <210> SEQ ID NO 644

  <211> LENGTH: 23

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 644

  Gln Gln Ser Cys Cys Phe Pro Val Arg Phe Val Ile Leu Gly Pro Ile

  1 5 10 15

  Leu Ile Ser Pro Tyr Val Tyr

  20

  <210> SEQ ID NO 645

  <211> LENGTH: 59

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 645

  Val Trp Leu Leu Ser Ser Ile Leu Leu Arg Val Leu Trp Asn Arg Tyr

  1 5 10 15

  Thr Leu Gln Glu Leu Ser Phe Trp Leu Pro Trp Phe Ala Ser Arg Ala

  20 25 30

  Thr Ser Leu Val Leu Gln His Gly Asp Asn Tyr Leu Leu Phe Leu Phe

  35 40 45

  Cys Phe Val Cys Phe Val Leu Ala Met Pro Phe

  50 55

  <210> SEQ ID NO 646

  <211> LENGTH: 26

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 646

  Ile Arg His Glu Val Ser Met Ala Phe Val Phe His Leu Ala Gln Gly

  1 5 10 15

  Thr Leu Glu Pro Leu Tyr Ile Ala Gly Ala

  20 25

  <210> SEQ ID NO 647

  <211> LENGTH: 40

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 647

  Asn Ser Ala Arg Gly Glu Tyr Gly Phe Cys Leu Pro Ser Cys Ser Gly

  1 5 10 15

  Tyr Phe Gly Thr Ala Ile His Cys Arg Ser Leu Ala Ser Gly Tyr His

  20 25 30

  Gly Leu Leu Pro Glu Gln Gln Ala

  35 40

  <210> SEQ ID NO 648

  <211> LENGTH: 26

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 648

  His Glu Leu Thr Val Pro Ser Arg Met Gly Ser Lys Gly Lys Pro Tyr

  1 5 10 15

  Pro Cys Gly Phe Tyr Ser Ser Leu Ile Pro

  20 25

  <210> SEQ ID NO 649

  <211> LENGTH: 103

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 649

  Lys Cys Ile Tyr Pro Lys Pro Ala Arg Thr His His Cys Ser Ile Cys

  1 5 10 15

  Asn Arg Cys Val Leu Lys Met Asp His His Cys Pro Trp Leu Asn Asn

  20 25 30

  Cys Val Gly His Tyr Asn His Arg Tyr Phe Phe Ser Phe Cys Phe Phe

  35 40 45

  Met Thr Leu Gly Cys Val Tyr Cys Ser Tyr Gly Ser Trp Asp Leu Phe

  50 55 60

  Arg Glu Ala Tyr Ala Ala Ile Glu Lys Met Lys Gln Leu Asp Lys Asn

  65 70 75 80

  Lys Leu Gln Ala Val Ala Asn Gln Thr Tyr His Gln Thr Pro Pro Pro

  85 90 95

  Thr Phe Ser Phe Arg Glu Arg

  100

  <210> SEQ ID NO 650

  <211> LENGTH: 38

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 650

  Ala Arg Gly His Trp Asn Leu Ile Leu Ile Val Phe His Tyr Tyr Gln

  1 5 10 15

  Ala Ile Thr Thr Pro Pro Gly Tyr Pro Pro Gln Gly Arg Asn Asp Ile

  20 25 30

  Ala Thr Val Ser Ile Cys

  35

  <210> SEQ ID NO 651

  <211> LENGTH: 33

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 651

  Trp Gln Cys Glu Leu Asp Cys Val Ser His Asp Ser Ser Thr His Ser

  1 5 10 15

  Ala Pro Tyr Val Ile Ser Arg Ala Ser Lys Gly Ser Phe Ser Gln Asn

  20 25 30

  Pro

  <210> SEQ ID NO 652

  <211> LENGTH: 83

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 652

  Ser Lys Arg Ala Ser Gly Pro Ala Leu Gly Tyr His Ala Gly Gln Phe

  1 5 10 15

  Lys Asp Gln Pro Phe Tyr His Cys Arg Arg Lys Thr Gln Cys Gly Glu

  20 25 30

  Ile Leu Gly Leu Thr Ser Leu Tyr Ser Gly Lys Gln Lys Phe Gln Pro

  35 40 45

  Gln Thr Arg Gly Gln Ala Ala Ser Tyr Leu Pro Cys Pro Val Leu Thr

  50 55 60

  Arg Thr Ser Ser Arg Ile Gln His Trp Ser Trp Pro Pro Pro Leu Leu

  65 70 75 80

  Leu Ala Val

  <210> SEQ ID NO 653

  <211> LENGTH: 31

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 653

  Glu Ser Leu Gln Leu Arg Leu Leu Gly Gln Leu Glu Gly Ile Pro Gly

  1 5 10 15

  Cys Gly Tyr Arg Lys Ala Leu Ala Tyr Ser Gly Ala Leu Thr Phe

  20 25 30

  <210> SEQ ID NO 654

  <211> LENGTH: 66

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 654

  Ser Leu Ala Pro Trp Glu Trp Asn Glu Leu Gly Ala Pro Ser Leu Gly

  1 5 10 15

  Asp Cys Ser Leu Ser Leu Cys Asp Gly Ser Val Ser Trp Thr Val Ser

  20 25 30

  Ala Thr Thr Arg Ala Leu Ile Leu Leu Pro Met Leu Phe Gln Gly Pro

  35 40 45

  Pro Arg Ala Ala Phe Leu Arg Ile Leu Asp Gln Lys Glu Pro Val Gly

  50 55 60

  Leu Pro

  65

  <210> SEQ ID NO 655

  <211> LENGTH: 72

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 655

  Thr Ala Thr Leu Asn Ser Phe Phe Gly Gly Trp Gly Leu Ala Leu Leu

  1 5 10 15

  Leu Arg Leu Glu Cys Ser Asp Thr Ile Met Asp His Cys Ser Leu Asp

  20 25 30

  Leu Leu Gly Ser Ser Asn Pro Pro Ala Ser Ala Ser Gln Val Val Gly

  35 40 45

  Thr Thr Gly Ala Arg His His Ala Gln Leu Ile Phe Cys Phe Phe Val

  50 55 60

  Gln Thr Arg Ser His Ser Val Ala

  65 70

  <210> SEQ ID NO 656

  <211> LENGTH: 47

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 656

  Met Asp His Cys Ser Leu Asp Leu Leu Gly Ser Ser Asn Pro Pro Ala

  1 5 10 15

  Ser Ala Ser Gln Val Val Gly Thr Thr Gly Ala Arg His His Ala Gln

  20 25 30

  Leu Ile Phe Cys Phe Phe Val Gln Thr Arg Ser His Ser Val Ala

  35 40 45

  <210> SEQ ID NO 657

  <211> LENGTH: 14

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 657

  Gly Val Leu Lys Gln Ser Ser His Leu Val Leu Ser Lys Gly

  1 5 10

  <210> SEQ ID NO 658

  <211> LENGTH: 21

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 658

  Asp Tyr Ser Cys Glu Ser Leu Cys Pro Ala Leu Leu Ser Ile Ala Pro

  1 5 10 15

  Asp Ile Val Leu Asn

  20

  <210> SEQ ID NO 659

  <211> LENGTH: 27

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 659

  Thr Thr Ile His Lys Thr Gln Leu Gly Ser Tyr Lys Ile Leu Trp Glu

  1 5 10 15

  Pro Lys Glu Gly Tyr His Asn Ser Thr Trp Ile

  20 25

  <210> SEQ ID NO 660

  <211> LENGTH: 9

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 660

  Ile Arg Glu Ile Phe Leu Arg Arg Pro

  1 5

  <210> SEQ ID NO 661

  <211> LENGTH: 24

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 661

  Leu Lys Phe Gln Lys Pro Gly Lys Ile Gln Met Arg Gly Gly Gly Arg

  1 5 10 15

  Val Phe Trp Tyr Lys Asn Cys Lys

  20

  <210> SEQ ID NO 662

  <211> LENGTH: 30

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 662

  Asn Ser Ala Arg Val Thr Gln Lys Gly Glu Ser Val Gly Ser Val Gly

  1 5 10 15

  Cys Met Arg Ala Ile Ala Gly Phe Asp Asn Tyr Pro Leu Phe

  20 25 30

  <210> SEQ ID NO 663

  <211> LENGTH: 33

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 663

  Gly Thr Ile Gly Ile Phe Trp Pro Leu Pro Val Ala Ile Leu Ser Ser

  1 5 10 15

  Gly Asp Tyr Leu Gln Thr Gln Ile His Arg Pro Leu Leu His Arg Gly

  20 25 30

  Thr

  <210> SEQ ID NO 664

  <211> LENGTH: 20

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 664

  Leu Pro Leu Pro Leu Ser Ser Leu Leu His Ile Ala Thr Cys Asn Pro

  1 5 10 15

  Phe Pro Lys Thr

  20

  <210> SEQ ID NO 665

  <211> LENGTH: 46

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 665

  Ser Tyr Phe Phe Val Tyr Asn Leu Ile Leu Lys Ile Ile Gln Gly Asp

  1 5 10 15

  His Ala Ser Ile Ile Leu Leu Ala Thr Ile Pro Ile Phe Gly Asp Ile

  20 25 30

  Tyr Tyr Val Lys Gly Gln Leu Ala Ser Phe Gly Pro Tyr Leu

  35 40 45

  <210> SEQ ID NO 666

  <211> LENGTH: 21

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 666

  Leu Phe Tyr His Leu Glu Ile Ile Ser Arg His Lys Ser Ile Ala His

  1 5 10 15

  Cys Ser Ile Glu Ala

  20

  <210> SEQ ID NO 667

  <211> LENGTH: 12

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 667

  Cys Ser Cys His Cys Pro Ser Arg Ala Phe Ser Thr

  1 5 10

  <210> SEQ ID NO 668

  <211> LENGTH: 29

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 668

  Pro His Ala Ile His Ser Gln Lys Pro Ser Ser Ile Phe Leu Ile Thr

  1 5 10 15

  Asp Val Phe Pro Asp Pro Pro Val Gly Ile Tyr Leu Leu

  20 25

  <210> SEQ ID NO 669

  <211> LENGTH: 48

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 669

  Arg Lys Leu Phe His Lys Ile Asn Ser Lys Ser Phe His Leu Ser Gly

  1 5 10 15

  Met His Ile Leu Ile Ser Val Trp Ile Val Arg Ser Arg Ile Ile Lys

  20 25 30

  Val Lys Tyr Glu Leu Leu Leu Cys Phe Phe Asp Val Ile Phe Tyr Val

  35 40 45

  <210> SEQ ID NO 670

  <211> LENGTH: 41

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 670

  Asn Ser Ala Arg Asp Val Phe Phe Thr Gln Lys Ile Leu Tyr Ser Gln

  1 5 10 15

  Thr Cys Ile Phe Phe Pro Cys Leu Val Pro Phe Ser Phe Leu Phe Ser

  20 25 30

  Phe Phe Phe Phe Leu Ser Phe Val Gly

  35 40

  <210> SEQ ID NO 671

  <211> LENGTH: 56

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 671

  Met Phe Ser Ser Leu Lys Lys Phe Tyr Ile Leu Lys His Val Tyr Ser

  1 5 10 15

  Phe Pro Val Leu Phe His Phe Leu Phe Phe Phe Leu Phe Ser Phe Ser

  20 25 30

  Phe Leu Ser Trp Ala Glu Lys Gly Ala Gly Lys Met Lys Leu Ala Thr

  35 40 45

  Glu Asn Cys Lys Met Val Lys Ser

  50 55

  <210> SEQ ID NO 672

  <211> LENGTH: 39

  <212> TYPE: PRT

  <213> ORGANISM: Homo sapiens

  <400> SEQUENCE: 672

  Ile Gln Leu Leu Tyr Leu Lys Gly Ala Ala Met Lys Tyr Leu Ser Tyr

  1 5 10 15

  Val Ala Arg Leu Leu Phe Leu Lys Ala Leu Asp Leu Phe Ala Pro Lys

  20 25 30

  Met Val Gln Ile Asp Ser Phe

  35

Claims (70)

What is claimed is:

1. An isolated antibody or portion thereof that specifically binds to a protein whose sequence consists of amino acid residues 21 to 116 of SEQ ID NO:238.

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

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

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

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

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

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

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

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

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

(a) an enzyme label;

(b) a radioisotope; and

(c) a fluorescent label.

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

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

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

14. An isolated antibody produced by immunizing an animal with a protein whose sequence comprises of amino acid residues 21 to 116 of SEQ ID NO:238, wherein said antibody or portion thereof specifically binds to the protein of SEQ ID NO:238.

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

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

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

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

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

(a) an enzyme label;

(b) a radioisotope; and

(c) a fluorescent label.

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

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

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

23. An isolated antibody or portion thereof that specifically binds to a protein whose sequence consists of amino acid residues 1 to 116 of SEQ ID NO:238.

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

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

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

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

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

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

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

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

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

(a) an enzyme label;

(b) a radioisotope; and

(c) a fluorescent label.

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

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

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

36. An isolated antibody or portion thereof that specifically binds to a protein whose sequence consists of the amino acid sequence of the secreted polypeptide encoded by the HLHFPO3 cDNA contained in ATCC Deposit No. 209126.

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

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

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

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

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

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

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

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

45. The isolated antibody of claim 44, where in the label is selected from the group consisting of:

(a) an enzyme label;

(b) a radioisotope; and

(c) a fluorescent label.

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

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

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

49. An isolated antibody produced by immunizing an animal with a protein whose sequence comprises the amino acid sequence of the secreted polypeptide encoded by the HLIFP03 cDNA contained in ATCC Deposit No. 209126, wherein said antibody or portion thereof specifically binds to the polypeptide encoded by the HLHFP03 cDNA contained in ATCC Deposit No. 209126.

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

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

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

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

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

(a) an enzyme label;

(b) a radioisotope; and

(c) a fluorescent label.

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

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

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

58. An isolated antibody or portion thereof that specifically binds to a protein whose sequence consists of the amino acid sequence of the full-length polypeptide encoded by the HLHFP03 cDNA contained in ATCC Deposit No. 209126;

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

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

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

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

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

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

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

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

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

(a) an enzyme label;

(b) a radioisotope; and

(c) a fluorescent label.

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

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

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