Patent Publication Number: US-2004049010-A1

Title: Transmembrane proteins

Description:
TECHNICAL FIELD  
       [0001] This invention relates to nucleic acid and amino acid sequences of transmembrane proteins and to the use of these sequences in the diagnosis, treatment, and prevention of reproductive, developmental, cardiovascular, neurological, gastrointestinal, lipid metabolism, cell proliferative, and autoimmune/inflammatory disorders, and in the assessment of the effects of exogenous compounds on the expression of nucleic acid and amino acid sequences of transmembrane proteins.  
       BACKGROUND OF THE INVENTION  
       [0002] Eukaryotic organisms are distinct from prokaryotes in possessing many intracellular membrane-bound compartments such as organelles and vesicles. Many of the metabolic reactions which distinguish eukaryotic biochemistry from prokaryotic biochemistry take place within these compartments. In particular, many cellular functions require very stringent reaction conditions, and the organelles and vesicles enable compartmentalization and isolation of reactions which might otherwise disrupt cytosolic metabolic processes. The organelles include mitochondria, smooth and rough endoplasmic reticula, sarcoplasmic reticulum, and the Golgi body. The vesicles include phagosomes, lysosomes, endosomes, peroxisomes, and secretory vesicles. Organelles and vesicles are bounded by single or double membranes.  
       [0003] Biological membranes surround organelles, vesicles, and the cell itself. Membranes are highly selective permeability barriers made up of lipid bilayer sheets composed of phosphoglycerides, fatty acids, cholesterol, phospholipids, glycolipids, proteoglycans, and proteins. Membranes contain ion pumps, ion channels, and specific receptors for external stimuli which transmit biochemical signals across the membranes. These membranes also contain second messenger proteins which interact with these pumps, channels, and receptors to amplify and regulate transmission of these signals.  
       Plasma Membrane Proteins  
       [0004] Transmembrane proteins (TMP) are characterized by extracellular, transmembrane, and intracellular domains. TMP domains are typically comprised of 15 to 25 hydrophobic amino acids which are predicted to adopt an α-helical conformation. TNT are classified as bitopic (Types I and II) proteins, which span the membrane once, and polytopic (Types III and IV) (Singer, S. J. (1990) Annu. Rev. Cell Biol. 6:247-96) proteins, which contain multiple membrane-spanning segments. TMP that act as cell-surface receptor proteins involved in signal transduction include growth and differentiation factor receptors, and receptor-interacting proteins such as Drosophila pecanex and frizzled proteins, LIV-1 protein, NF2 protein, and GNS1/SUR4 eukaryotic integral membrane proteins. TMP also act as transporters of ions or metabolites, such as gap junction channels (connexins) and ion channels, and as cell anchoring proteins, such as lectins, integrins, and fibronectins. TMP function as vesicle and organelle-forming molecules, such as caveolins; or cell recognition molecules, such as cluster of differentiation (CD) antigens, glycoproteins, and mucins.  
       [0005] The transport of hydrophilic molecules across membranes is facilitated by the presence of channel proteins which form aqueous pores which can perforate a lipid bilayer. Many channels consist of protein complexes formed by the assembly of multiple subunits, at least one of which is an integral membrane protein that contributes to formation of the pore. In some cases, the pore is constructed to allow selective passage of only one or a few molecular species. Distinct types of membrane channels that differ greatly in their distribution and selectivity include: (1) aquaporins, which transport water; (2) protein-conducting channels, which transport proteins across the endoplasmic reticulum membrane; (3) gap junctions, which facilitate diffusion of ions and small organic molecules between neighboring cells; and (4) ion channels, which regulate ion flux through various membranes.  
       [0006] Gap junctions (also called connexons) are specialized regions of the plasma membrane comprising transmembrane channels that function chemically and electrically to couple the cytoplasms of neighboring cells in many tissues. Gap junctions function as electrical synapses for intercellular propagation of action potentials in excitable tissues. In nonexcitable tissues, gap junctions have roles in tissue homeostasis, coordinated physiological response, metabolic cooperation, growth control, and the regulation of development and differentiation.  
       [0007] Each connexon, which spans the lipid bilayer of the plasma membrane, is composed of six identical subunits called connexins. At least fourteen distinct connexin proteins exist, with each having similar structures but differing tissue distributions. Structurally, the connexins consist of a short cytoplasmic N-terminal domain connected to four transmembrane spanning regions (M1, M2, M3 and M4) which separate two extracellular and one cytoplasmic loop followed by a C-terminal, cytoplasmic domain of variable length (20 resides in Cx26 to 260 residues in Cx56). The M2-M3 loop and the N- and C-termini are oriented towards the cell cytoplasm. Conserved regions include the membrane spanning regions and the two extracellular loops. Within the extracellular loops are three conserved cysteines which are involved in disulfide bond formation. Signature patterns for these two loops are either: C-[DN]-T-x-Q-P-G-C-x-(2)-V-C-Y-D or C-x(3,4)-P-C-x(3)-[LIVM]-[DEN]-C-[FY]-[LIVM]-[SA]-[KR]-P (PDOC00341, Profilescan and S. Rabman and W. H. Evans, (1991) J. Cell Sci. 100:567-578). The variable regions, which include the cytoplasmic loop and the C-terminal region, may be responsible for the regulation of different connexins. (See Hennemann, H. et al. (1992) J. Biol. Chem. 267:17225-17233; PRINTS PR00206 connexin signature; Yeager, M. et al., (1998) Curr. O. Structr. Biol. 8:517-524.)  
       [0008] Gap junctions help to synchronize heart and smooth muscle contraction, speed neural transmission, and propagate extracellular signals. Gap junctions can open and close in response to particular stimuli (e.g., pH, Ca +2 , and cAMP). The effective pore size of a gap junction is approximately 1.5 nm, which enables small molecules (e.g., those under 1000 daltons) to diffuse freely through the pore. Transported molecules include ions, small metabolites, and second messengers (e.g., Ca +2  and cAMP).  
       [0009] Connexins have many disease associations. Female mice lacking connexin 37 (Cx37) are infertile due to the absence of the oocyte-granulosa cell signaling pathway. Mice lacking Cx43 die shortly after birth and show cardiac defects reminiscent of some forms of stenosis of the pulmonary artery in humans. Mutations in Cx32 are associated with the X-linked form of Charcot-Marie-Tooth disease, a motor and sensory neuropathy of the peripheral nervous system Cx26 is expressed in the placenta, and Cx26-deficient mice show decreased transplacental transport of a glucose analog from the maternal to the fetal circulation. In humans, Cx26 has been identified as the first susceptibility gene for non-syndromnic sensorineural autosomal deafness. Mutations in in Cx31 have been linked with an autosomal-dominant hearing impairment (a nonsense or missense mutation in the second extracellular loop) and in a dominantly transmitted skin disorder, erythrokeratodermia variabilis (missense mutations in either the N-terminal domain or the M2 domain.) (See A. M. Simon, (1999) Trends Cell Biol. 9:169-170). Cx46 is expressed in lens fiber cells, and Cx46-deficient mice develop early-onset cataracts that resemble human nuclear cataracts. (See Nicholson, S. M. and R. Bruzzone (1997) Curr. Biol. 7:R340-R344.)  
       [0010] Plasma membrane proteins (MPs) are divided into two groups based upon methods of protein extraction from the membrane. Extrinsic or peripheral membrane proteins can be released using extremes of ionic strength or pH, urea, or other disruptors of protein interactions. Intrinsic or integral membrane proteins are released only when the lipid bilayer of the membrane is dissolved by detergent.  
       [0011] Many membrane proteins (MPs) contain amino acid sequence motifs that serve to localize proteins to specific subcellular sites. Examples of these motifs include PDZ domains, KDEL, RGD, NGR, and GSL sequence motifs, von Willebrand factor A (vWFA) domains, and EGF-like domains. RGD, NGR, and GSL motif-containing peptides have been used as drug delivery agents in targeted cancer treatment of tumor vasculature (Arap, W. et al. (1998) Science, 279:377-380). Membrane proteins may also contain amino acid sequence motifs that serve to interact with extracellular or intracellular molecules, such as carbohydrate recognition domains.  
       [0012] Chemical modification of amino acid residue side chains alters the manner in which MPs interact with other molecules, such as membrane phospholipids. Examples of such chemical modifications include the formation of covalent bonds with glycosaminoglycans, oligosaccharides, phospholipids, acetyl and palmitoyl moieties, ADP-ribose, phosphate, and sulphate groups.  
       [0013] RNA encoding membrane proteins may have alternative splice sites which give rise to proteins encoded by the same gene but with different messenger RNA and amino acid sequences. Splice variant membrane proteins may interact with other ligand and protein isoforms.  
       [0014] Transmembrane proteins of the plasma membrane also include cell surface receptors. These receptors recognize hormones such as catecholamines, e.g., epinephrine, norepinephrine, and histamine; peptide hormones, e.g., glucagon, insulin, gastrin, secretin, cholecystokinin, adrenocorticotropic hormone, follicle stimulating hormone, luteinizing hormone, thyroid stimulating hormone, parathyroid hormone, and vasopressin; growth and differentiation factors, e.g., epidermal growth factor, fibroblast growth factor, transforming growth factor, insulin-like growth factor, platelet-derived growth factor, nerve growth factor, colony-stimulating factors, and erythropoietin; cytokines, e.g., chemokines, interleukins, interferons, and tumor necrosis factor; small peptide factors such as bombesin, oxytocin, endothelin, angiotensin II, vasoactive intestinal peptide, and bradykinin; neurotransmitters such as neuropeptide Y, neurotensin, neuromedin N, melanocortins, opioids, e.g., enkephalins, endorphins and dynorphins; galanin, somatostatin, and tachykinins; and circulatory system-borne signaling molecules, e.g., angiotensin, complement, calcitonin, endothelins, and formyl-methionyl peptides. Cell surface receptors on immune system cells recognize antigens, antibodies, and major histocompatibility complex (MHC)-bound peptide. Other cell surface receptors bind ligands to be internalized by the cell. This receptor-mediated endocytosis functions in the uptake of low density lipoproteins (LDL), transferrin, glucose- or mannose-terminal glycoproteins, galactose-terminal glycoproteins, immunoglobulins, phosphovitellogenins, fibrin, proteinase-inhibitor complexes, plasminogen activators, and thrombospondin. (Lodish, H. et al. (1995)  Molecular Cell Biology , Scientific American Books, New York, N.Y., p. 723; and Mikhailenko, I. et al. (1997) J. Biol. Chem. 272:6784-6791.)  
       [0015] Many cell surface receptors have seven transmembrane regions, with an extracellular N-terminus that binds ligand and a cytoplasmic C-terminus that interacts with G proteins. (Strosberg, A. D. (1991) Eur. J. Biochem. 196:1-10.) Cysteine-rich domains are found in two families of cell surface receptors, the LDL receptor family and the tumor necrosis factor receptor/nerve growth factor (TNFR/NGFR) receptor family. Seven successive cysteine-rich repeats of about forty amino acids in the N-terminal extracellular region of the LDL receptor form the binding site for LDL and calcium; similar repeats have been found in vertebrate very low density lipoprotein receptor, vertebrate low-density lipoprotein receptor-related protein 1 (LRP1) (also known as α 2 -macroglobulin receptor), and vertebrate low-density lipoprotein receptor-related protein 2 (also known as gp330 or megalin) (WxPASy PROSITE d cument PDOC00929; and Bairoch, A et al. (1997) Nucl. Acids. Res. 25:217-221.) The structure f the repeat is a β-hairpin followed by a series of β-turns; there are six disulfide-bonded cysteines within each repeat.  
       [0016] The LDL receptor is an integral membrane protein which functions in lipid uptake by removing cholesterol from the blood. Most cells outside the liver and intestine take up cholesterol from the blood rather than synthesize it themselves. Cell surface LDL receptors bind LDL particles which are then internalized by endocytosis (Meyers, R. A (1995)  Molecular Biology and Biotechnology,  VCH Publishers, New York N.Y., pp. 494-501). Absence of the LDL receptor, the cause of the disease familial hypercholesterolemia, leads to increased plasma cholesterol levels and ultimately to atherosclerosis (Stryer, L. (1995)  Biochemistry, W. H. Freeman, New York N.Y., pp.  691-702).  
       G-Protein Coupled Receptors  
       [0017] G-protein coupled receptors (GPCR) comprise a superfamily of integral membrane proteins which transduce extracellular signals. GPCRs include receptors for biogenic amines, lipid mediators of inflammation, peptide hormones, and sensory signal mediators.  
       [0018] The structure of these highly-conserved receptors consists of seven hydrophobic transmembrane (serpentine) regions, cysteine disulfide bridges between the second and third extracellular loops, an extracellular N-terminus, and a cytoplasmic C-terminus. Three extracellular loops alternate with three intracellular loops to link the seven transmembrane regions. The most conserved parts of these proteins are the transmembrane regions and the first two cytoplasmic loops. Cysteine disulfide bridges connect the second and third extracellular loops. A conserved, acidic-Arg-aromatic residue triplet present in the second cytoplasmic loop may interact with G proteins. A GPCR consensus pattern is characteristic of most proteins belonging to this superfamily (ExPASy PROSITE document PS00237; and Watson, S. and S. Arkinstall (1994)  The G - protein Linked Receptor Facts Book,  Academic Press, San Diego, Calif., pp 2-6). Mutations and changes in transcriptional activation of GPCR-encoding genes have been associated with neurological disorders such as schizophrenia, Parkinson&#39;s disease, Alzheimer&#39;s disease, drug addiction, and feeding disorders. The juvenile development and fertility-2 (jdf-2) locus, also called runty-jerky-sterile (rjs), is associated with deletions and point mutations in HERC2, a gene encoding a guanine nucleotide exchange factor protein involved in vesicular trafficking (Walkowicz, M. et al. (1999) Mamm. Genome 10:870-878).  
       [0019] A GPCR known as FP is the receptor for prostaglandin F 2α  (PGF 2α ). The prostaglandins belong to a large family of naturally occurring paracrine/autocrine mediators of physiologic and inflammatory responses. PGF 2α  plays a role in responses of certain tissues such as reproductive tract, lung, bone, and heart, including the stimulation of myometrial contraction, corpus luteum breakdown, and bronchoconstriction. An FP-associated molecule (FPRP) is copurified with FP and is expressed only in those tissues where a physiological role for PGF 2α  has been described. FPRP is predicted to be a transmembrane protein with glycosolated extracellular immunoglobulin loops and a short, highly charged intracellular domain. FPRP appears to be a negative regulator of PGF 2α  binding to FP. As such, FPRP may be associated with PGF 2α  related diseases, which may include dysmenorrhea, infertility, asthma, or cardiomyophathy (Orlicky, D. J. et al. (1996) Hum. Genet. 97:655-658).  
       Scavenger Receptors  
       [0020] Macrophage scavenger receptors with broad ligand specificity may participate in the binding of low density lipoproteins (LDL) and foreign antigens. Scavenger receptors types I and II are trimeric membrane proteins with each subunit containing a small N-terminal intracellular domain, a transmembrane domain, a large extracellular domain, and a C-terminal cysteine-rich domain. The extracellular domain contains a short spacer domain, an α-helical coiled-coil domain, and a triple helical collagenous domain. These receptors have been shown to bind a spectrum of ligands, including chemically modified lipoproteins and albumin, polyribonucleotides, polysaccharides, phospholipids, and asbestos (Matsumoto, A. et al. (1990) Proc. Natl. Acad. Sci. 87:9133-9137; and Elomaa, O. et al. (1995) Cell 80:603-609). The scavenger receptors are thought to play a key role in atherogenesis by mediating uptake of modified LDL in arterial walls, and in host defense by binding bacterial endotoxins, bacteria, and protozoa.  
       Tetraspan Family Proteins  
       [0021] The transmembrane 4 superfamily (TM4SF), or tetraspan family, is a multigene family encoding type III integral membrane proteins (Wright, M. D. and Tomlinson, M. G. (1994) Immunol. Today 15:588-594). TM4SF is comprised of membrane proteins which traverse the cell membrane four times. Members of the TM4SF include platelet and endothelial cell membrane proteins, melanoma-associated antigens, leukocyte surface glycoproteins, colonal carcinoma antigens, tumor-associated antigens, and surface proteins of the schistosome parasites (Jankowski, S. A. (1994) Oncogene 9:1205-1211). Members of the TM4SP share about 25-30% amino acid sequence identity with one another.  
       [0022] A number of TM4SF members have been implicated in signal transduction, control of cell adhesion, regulation of cell growth and proliferation, including development and oncogenesis, and cell motility, including tumor cell metastasis. Expression of TM4SF proteins is associated with a variety of tumors, and the level of expression may be altered when cells are growing or activated.  
       Tumor Antigens  
       [0023] Tumor antigens are surface molecules that are differentially expressed in tumor cells relative to normal cells. Tumor antigens distinguish tumor cells immunologically from normal cells and provide diagnostic and therapeutic targets for human cancers (Takagi, S. et al. (1995) Int. J. Cancer 61: 706-715; Liu, E. et al. (1992) Oncogene 7: 1027-1032).  
       Ion Channels  
       [0024] Ion channels are found in the plasma membranes of virtually every cell in the body. For example, chloride channels mediate a variety of cellular functions including regulation of membrane potential and absorption and secretion of ions across epithelial membranes. When present in intracellular membranes of the Golgi apparatus and endocytic vesicles, chloride channels also regulate organelle pH (see, e.g., Greger, R. (1988) Annu. Rev. Physiol. 50:111-122). Electrophysiological and pharmacological properties of chloride channels, including ion conductance, current-voltage relationships, and sensitivity to modulators, suggest that different chloride channels exist in muscles, neurons, fibroblasts, epithelial cells, and lymphocytes.  
       [0025] Many channels have sites for phosphorylation by one or more protein kinases including protein kinase A, protein kinase C, casein kinase II, and tyrosine kinases, all of which regulate ion channel activity in cells. Inappropriate phosphorylation of membrane proteins has been correlated with pathological changes in cell cycle progression and cell differentiation. Changes in the cell cycle have been linked to induction of apoptosis or cancer. Changes in cell differentiation have been linked to diseases and disorders of the reproductive system, immune system, and skeletal muscle.  
       [0026] Cerebellar granule neurons possess a non-inactivating potassium current which modulates firing frequency upon receptor stimulation by neurotransmitters and controls the resting membrane potential. Potassium channels that exhibit non-inactivating currents include the ether a go-go (EAG) channel. A membrane protein designated KCR1 specifically binds to rat EAG by means of its C-terminal region and regulates the cerebellar non-inactivating potassium current. KCR1 is predicted to contain 12 transmembrane domains, with intracellular amino and carboxyl termini. Structural characteristics of these transmembrane regions appear to be similar to those of the transporter superfamily, but no homology between KCR1 and known transporters was found, suggesting that KCR1 belongs to a novel class of transporters. KCR1 appears to be the regulatory component of non-inactivating potassium channels (Hoshi, N. et al. (1998) J. Biol. Chem. 273:23080-23085).  
       Proton Pumps  
       [0027] Proton ATPases are a large class of membrane proteins that use the energy of ATP hydrolysis to generate an electrochemical proton gradient across a membrane. The resultant gradient may be used to transport other ions across the membrane (Na + , K + , or Cl − ) or to maintain organelle pH. Proton ATPases are further subdivided into the mitochondrial F-ATPases, the plasma membrane ATPases, and the vacuolar ATPases. The vacuolar ATPases establish and maintain an acidic pH within various vesicles involved in the processes of endocytosis and exocytosis (Mellman, I. et al. (1986) Ann. Rev. Biochem. 55:663-700).  
       [0028] Proton-coupled, 12 membrane-spanning domain transporters such as PEPT 1 and PEPT 2 are responsible for gastrointestinal absorption and for renal reabsorption of peptides using an electrochemical H +  gradient as the driving force. Another type of peptide transporter, the TAP transporter, is a heterodimer consisting of TAP 1 and TAP 2 and is associated with antigen processing. Peptide antigens are transported across the membrane of the endoplasmic reticulum by TAP so they can be expressed on the cell surface in association with MHC molecules. Each TAP protein consists of multiple hydrophobic membrane spanning segments and a highly conserved ATP-binding cassette (Boll, M. et al. (1996) Proc. Natl. Acad. Sci. 93:284-289). Pathogenic microorganisms, such as herpes simplex virus, may encode inhibitors of TAP-mediated peptide transport in order to evade immune surveillance (Marusina, K. and Manaco, J. J. (1996) Curr. Opin. Hematol. 3:19-26).  
       ABC Transporters  
       [0029] The ATP-binding cassette (ABC) transporters, also called the “traffic ATPases,” comprise a superfamily of membrane proteins that mediate transport and channel functions in prokaryotes and eukaryotes (Higgins, C. F. (1992) Annu. Rev. Cell Biol. 8:67-113). ABC proteins share a similar overall structure and significant sequence homology. All ABC proteins contain a conserved domain of approximately two hundred amino acid residues which includes one or more nucleotide binding domains. Mutations in ABC transporter genes are associated with various disorders, such as hyperbilirubinemia II/Dubin-Johnson syndrome, recessive Stargardt&#39;s disease, X-linked adrenoluekodystrophy, multidrug resistance, celiac disease, and cystic fibrosis.  
       Membrane Proteins Associated with Intercellular Communication  
       [0030] Intercellular communication is essential for the development and survival of multicellular organisms. Cells communicate with one another through the secretion and uptake of protein signaling molecules. The uptake of proteins into the cell is achieved by endocytosis, in which the interaction of signaling molecules with the plasma membrane surface, often via binding to specific receptors, results in the formation of plasma membrane-derived vesicles that enclose and transport the molecules into the cytosol. The secretion of proteins from the cell is achieved by exocytosis, in which molecules inside of the cell are packaged into membrane-bound transport vesicles derived from the trans Golgi network. These vesicles fuse with the plasma membrane and release their contents into the surrounding extracellular space. Endocytosis and exocytosis result in the removal and addition of plasma membrane components, and the recycling of these components is essential to maintain the integrity, identity, and functionality of both the plasma membrane and internal membrane-bound compartments.  
       [0031] Synaptobrevins are synaptic vesicle-associated membrane proteins (VAMPs) which were first discovered in rat brain. These proteins were initially thought to be limited to neuronal cells and to function in the movement of vesicles from the plasmalemma of one cell, across the synapse, to the plasmalemma of another cell. Synaptobrevins are now known to occur and function in constitutive vesicle trafficking pathways involving receptor-mediated endocytotic and exocytotic pathways of many non-neuronal cell types. This regulated vesicle trafficking pathway may be blocked by the highly specific action of clostridial neurotoxins which cleave the synaptobrevin molecule.  
       [0032] In vitro studies of various cellular membranes (Galli et al. (1994) J. Cell. Biol. 125:1015-24; Link et al. (1993) J. Biol. Chem. 268:18423-6) have shown that VAMPS are widely distributed. These important membrane trafficking proteins appear to participate in axon extension via exocytosis during development, in the release of neurotransmitters and modulatory peptides, and in endocytosis. Endocytotic vesicular transport includes such intracellular events as the fusions and fissions of the nuclear membrane, endoplasmic reticulum, Golgi apparatus, and various inclusion bodies such as peroxisomes or lysosomes. Endocytotic processes appear to be universal in eukaryotic cells as diverse as yeast,  Caenorhabditis elegans,  Drosophila, and mammals.  
       [0033] VAMP-1B is involved in subcellular targeting and is an isoform of VAMP-1A (Isenmann, S. et al. (1998) Mol. Biol. Cell 9:1649-1660). Four additional splice variants (VAMP-1C to F) have recently been identified. Each variant has variable sequences only at the extreme C-terminus, suggesting that the C-terminus is important in vesicle targeting (Berglund, L. et al. (1999) Biochem. Biophys. Res. Commun. 264:777-780).  
       [0034] Lysosomes are the site of degradation of intracellular material during autophagy, and of extracellular molecules following endocytosis. Lysosomal enzymes are packaged into vesicles which bud from the trans-Golgi network. These vesicles fuse with endosomes to form the mature lysosome in which hydrolytic digestion of endocytosed material occurs. Lysosomes can fuse with autophagosomes to form a unique compartment in which the degradation of organelles and other intracellular components occurs.  
       [0035] Protein sorting by transport vesicles, such as the endosome, has important consequences for a variety of physiological processes including cell surface growth, the biogenesis of distinct intracellular organelles, endocytosis, and the controlled secretion of hormones and neurotransmitters (Rothman, J. E. and Wieland, F. T. (1996) Science 272:227-234). In particular, neurodegenerative disorders and other neuronal pathologies are associated with biochemical flaws during endosomal protein sorting or endosomal biogenesis (Mayer R. J. et al. (1996) Adv. Exp. Med. Biol. 389:261-269).  
       [0036] Peroxisomes are organelles independent from the secretory pathway. They are the site of many peroxide-generating oxidative reactions in the cell. Peroxisomes are unique among eukaryotic organelles in that their size, number, and enzyme content vary depending upon organism, cell type, and metabolic needs (Waterham, H. R. and Cregg, J. M. (1997) BioEssays 19:57-66). Genetic defects in peroxisome proteins which result in peroxisomal deficiencies have been linked to a number of human pathologies, including Zellweger syndrome, rhizomelic chondrodysplasia punctata, X-linked adrenoleukodystrophy, acyl-CoA oxidase deficiency, bifunctional enzyme deficiency, classical Refsum&#39;s disease, DHAP alkyl transferase deficiency, and acatalasemia (Moser, H. W. and Moser, A. B. (1996) Ann. NY Acad. Sci. 804:427-441). In addition, Gartner, J. et al. (1991; Pediatr. Res. 29:141-146) found a 22 kDa integral membrane protein associated with lower density peroxisome-like subcellular fractions in patients with Zellweger syndrome.  
       [0037] Normal embryonic development and control of germ cell maturation is modulated by a number of secretory proteins which interact with their respective membrane-bound receptors. Cell fate during embryonic development is determined by members of the activin/TGF-β superfamily, cadherins, IGF-2, and other morphogens. In addition, proliferation, maturation, and redifferentiation of germ cell and reproductive tissues are regulated, for example, by IGF-2, inhibins, activins, and follistatins (Petraglia, F. (1997) Placenta 18:3-8; Mather, J. P. et al. (1997) Proc. Soc. Exp. Biol. Med. 215:209-222).  
       Endoplasmic Reticulum Membrane Proteins  
       [0038] The normal functioning of the eukaryotic cell requires that all newly synthesized proteins be correctly folded, modified, and delivered to specific intra- and extracellular sites. Newly synthesized membrane and secretory proteins enter a cellular sorting and distribution network during or immediately after synthesis and are routed to specific locations inside and outside of the cell. The initial compartment in this process is the endoplasmic reticulum (ER) where proteins undergo modifications such as glycosylation, disulfide bond formation, and oligomerization. The modified proteins are then transported through a series of membrane-bound compartments which include the various cisternae of the Golgi complex, where further carbohydrate modifications occur. Transport between compartments occurs by means of vesicle budding and fusion. Once within the secretory pathway, proteins do not have to cross a membrane to reach the cell surface.  
       [0039] Although the majority of proteins processed through the ER are transported out of the organelle, some are retained. The signal for retention in the ER in mammalian cells consists of the tetrapeptide sequence, KDEL, located at the carboxyl terminus of resident ER membrane proteins (Munro, S. (1986) Cell 46:291-300). Proteins containing this sequence leave the ER but are quickly retrieved from the early Golgi cisternae and returned to the ER, while proteins lacking this signal continue through the secretory pathway.  
       [0040] Disruptions in the cellular secretory pathway have been implicated in several human diseases. In familial hypercholesterolemia the low density lipoprotein receptors remain in the ER, rather than moving to the cell surface (Pathak, R. K. (1988) J. Cell Biol. 106:1831-1841). Altered transport and processing of the β-amyloid precursor protein (βAPP) involves the putative vesicle transport protein presenilin and may play a role in early-onset Alzheimer&#39;s disease (Levy-Lahad, E. et al. (1995) Science 269:973-977). Changes in ER-derived calcium homeostasis have been associated with diseases such as cardiomyopathy, cardiac hypertrophy, myotonic dystrophy, Brody disease, Smith-McCort dysplasia, and diabetes mellitus.  
       Mit Chondrial Membrane Proteins  
       [0041] The mitochondrial electron transport (or respiratory) chain is a series of three enzyme complexes in the mitochondrial membrane that is responsible for the transport of electrons from NADH to oxygen and the coupling of this oxidation to the synthesis of ATP (oxidative phosphorylation). ATP then provides the primary source of energy for driving the many energy-requiring reactions of a cell.  
       [0042] Most of the protein components of the mitochondrial respiratory chain are the products of nuclear encoded genes that are imported into the mitochondria, and the remainder are products of mitochondrial genes. Defects and altered expression of enzymes in the respiratory chain are associated with a variety of disease conditions in man, including, for example, neurodegenerative diseases, myopathies, and cancer.  
       Lymphocyte and Leukocyte Membrane Proteins  
       [0043] The B-cell response to antigens is an essential component of the normal immune system. Mature B cells recognize foreign antigens through B cell receptors (BCR) which are membrane-bound, specific antibodies that bind foreign antigens. The antigen/receptor complex is internalized, and the antigen is proteolytically processed. To generate an efficient response to complex antigens, the BCR, BCR-associated proteins, and T cell response are all required. Proteolytic fragments of the antigen are complexed with major histocompatability complex-II (MHCII) molecules on the surface of the B cells where the complex can be recognized by T cells. In contrast, macrophages and other lymphoid cells present antigens in association with MHCI molecules to T cells. T cells recognize and are activated by the MHCI-antigen complex through interactions with the T cell receptor/CD3 complex, a T cell-surface multimeric protein located in the plasma membrane. T cells activated by antigen presentation secrete a variety of lymphokines that induce B cell maturation and T cell proliferation, and activate macrophages, which kill target cells.  
       [0044] Leukocytes have a fundamental role in the inflammatory and immune response, and include monocytes/macrophages, mast cells, polymorphonucleoleukocytes, natural killer cells, neutrophils, eosinophils, basophils, and myeloid precursors. Leukocyte membrane proteins include members of the CD antigens, N-CAM, I-CAM, human leukocyte antigen (HLA) class I and HLA class II gene products, immunoglobulins, immunoglobulin receptors, complement, complement receptors, interferons, interferon receptors, interleukin receptors, and chemokine receptors.  
       [0045] Abnormal lymphocyte and leukocyte activity has been associated with acute disorders such as AIDS, immune hypersensitivity, leukemias, leukopenia, systemic lupus, granulomatous disease, and eosinophilia.  
       Apoptosis-Associated Membrane Proteins  
       [0046] A variety of ligands, receptors, enzymes, tumor suppressors, viral gene products, pharmacological agents, and inorganic ions have important positive or negative roles in regulating and implementing the apoptotic destruction of a cell. Although some specific components of the apoptotic pathway have been identified and characterized, many interactions between the proteins involved are undefined, leaving major aspects of the pathway unknown.  
       [0047] A requirement for calcium in apoptosis was previously suggested by studies showing the involvement of calcium levels in DNA cleavage and Fas-mediated cell death (Hewish, D. R. and L. A. Burgoyne (1973) Biochem. Biophys. Res. Comm. 52:504-510; Vignaux, F. et al. (1995) J. Exp. Med. 181:781-786; Oshimi, Y. and S. Miyazaki (1995) J. Immunol. 154:599-609). Other studies show that intracellular calcium concentrations increase when apoptosis is triggered in thymocytes by either T cell receptor cross-linking or by glucocorticoids, and cell death can be prevented by blocking this increase (McConkey, D. J. et al. (1989) J. Immunol. 143:1801-1806; McConkey, D. J. et al. (1989) Arch. Biochem. Biophys. 269:365-370). Therefore, membrane proteins such as calcium channels and the Fas receptor are important for the apoptotic response.  
       [0048] The discovery of new transmembrane proteins, and the polynucleotides encoding them, satisfies a need in the art by providing new compositions which are useful in the diagnosis, prevention, and treatment of reproductive, developmental, cardiovascular, neurological, gastrointestinal, lipid metabolism, cell proliferative, and autoimmune/inflammatory disorders, and in the assessment of the effects of exogenous compounds on the expression of nucleic acid and amino acid sequences of transmembrane proteins.  
       SUMMARY OF THE INVENTION  
       [0049] The invention features purified polypeptides, transmembrane proteins, referred to collectively as “TNT” and individually as “TMP-1,” “TMP-2,” “TMP-3,” “TMP-4,” “TMP-5,” “TMP-6,” “TMP-7,” “TMP-8,” “TMP-9,” “TMP-10,” “TMP-11,” “TMP-12,” “TMP-13,” “TMP-14,” “TMP-15,” “TMP-16,” and “TMP-17.” In one aspect, the invention provides an isolated polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-17. In one alternative, the invention provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO:1-17.  
       [0050] The invention further provides an isolated polynucleotide encoding a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-17. In one alternative, the polynucleotide encodes a polypeptide selected from the group consisting of SEQ ID NO:1-17. In another alternative, the polynucleotide is selected from the group consisting of SEQ ID NO:18-34.  
       [0051] Additionally, the invention provides a recombinant polynucleotide comprising a promoter sequence operably linked to a polynucleotide encoding a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-17. In one alternative, the invention provides a cell transformed with the recombinant polynucleotide. In another alternative, the invention provides a transgenic organism comprising the recombinant polynucleotide.  
       [0052] The invention also provides a method for producing a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-17. The method comprises a) culturing a cell under conditions suitable for expression of the polypeptide, wherein said cell is transformed with a recombinant polynucleotide comprising a promoter sequence operably linked to a polynucleotide encoding the polypeptide, and b) recovering the polypeptide so expressed.  
       [0053] Additionally, the invention provides an isolated antibody which specifically binds to a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-17.  
       [0054] The invention further provides an isolated polynucleotide selected from the group consisting of a) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:18-34, b) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:18-34,c) a polynucleotide complementary to the polynucleotide of a), d) a polynucleotide complementary to the polynucleotide of b), and e) an RNA equivalent of a)-d). In one alternative, the polynucleotide comprises at least 60 contiguous nucleotides.  
       [0055] Additionally, the invention provides a method for detecting a target polynucleotide in a sample, said target polynucleotide having a sequence of a polynucleotide selected from the group consisting of a) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:18-34, b) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:18-34, c) a polynucleotide complementary to the polynucleotide of a), d) a polynucleotide complementary to the polynucleotide of b), and e) an RNA equivalent of a)-d). The method comprises a) hybridizing the sample with a probe comprising at least 20 contiguous nucleotides comprising a sequence complementary to said target polynucleotide in the sample, and which probe specifically hybridizes to said target polynucleotide, under conditions whereby a hybridization complex is formed between said probe and said target polynucleotide or fragments thereof, and b) detecting the presence or absence of said hybridization complex, and optionally, if present, the amount thereof. In one alternative, the probe comprises at least 60 contiguous nucleotides.  
       [0056] The invention further provides a method for detecting a target polynucleotide in a sample, said target polynucleotide having a sequence of a polynucleotide selected from the group consisting of a) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:18-34, b) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:18-34, c) a polynucleotide complementary to the polynucleotide of a), d) a polynucleotide complementary to the polynucleotide of b), and e) an RNA equivalent of a)-d). The method comprises a) amplifying said target polynucleotide or fragment thereof using polymerase chain reaction amplification, and b) detecting the presence or absence of said amplified target polynucleotide or fragment thereof, and, optionally, if present, the amount thereof.  
       [0057] The invention further provides a composition comprising an effective amount of a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, and a pharmaceutically acceptable excipient. In one embodiment, the composition comprises an amino acid sequence selected from the group consisting of SEQ ID NO:1-17. The invention additionally provides a method of treating a disease or condition associated with decreased expression of functional TMP, comprising administering to a patient in need of such treatment the composition.  
       [0058] The invention also provides a method for screening a compound for effectiveness as an agonist of a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-17. The method comprises a) exposing a sample comprising the polypeptide to a compound, and b) detecting agonist activity in the sample. In one alternative, the invention provides a composition comprising an agonist compound identified by the method and a pharmaceutically acceptable excipient. In another alternative, the invention provides a method of treating a disease or condition associated with decreased expression of functional TMP, comprising administering to a patient in need of such treatment the composition.  
       [0059] Additionally, the invention provides a method for screening a compound for effectiveness as an antagonist of a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-17. The method comprises a) exposing a sample comprising the polypeptide to a compound, and b) detecting antagonist activity in the sample. In one alternative, the invention provides a composition comprising an antagonist compound identified by the method and a pharmaceutically acceptable excipient. In another alternative, the invention provides a method of treating a disease or condition associated with overexpression of functional TMP, comprising administering to a patient in need of such treatment the composition.  
       [0060] The invention further provides a method of screening for a compound that specifically binds to a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-17. The method comprises a) combining the polypeptide with at least one test compound under suitable conditions, and b) detecting binding of the polypeptide to the test compound, thereby identifying a compound that specifically binds to the polypeptide.  
       [0061] The invention further provides a method of screening for a compound that modulates the activity of a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-17, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 1-17, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-17. The method comprises a) combining the polypeptide with at least one test compound under conditions permissive for the activity of the polypeptide, b) assessing the activity of the polypeptide in the presence of the test compound, and c) comparing the activity of the polypeptide in the presence of the test compound with the activity of the polypeptide in the absence of the test compound, wherein a change in the activity of the polypeptide in the presence of the test compound is indicative of a compound that modulates the activity of the polypeptide.  
       [0062] The invention further provides a method for screening a compound for effectiveness in altering expression of a target polynucleotide, wherein said target polynucleotide comprises a polynucleotide sequence selected from the group consisting of SEQ ID NO:18-34, the method comprising a) exposing a sample comprising the target polynucleotide to a compound, and b) detecting altered expression of the target polynucleotide.  
       [0063] The invention further provides a method for assessing toxicity of a test compound, said method comprising a) treating a biological sample containing nucleic acids with the test compound; b) hybridizing the nucleic acids of the treated biological sample with a probe comprising at least 20 contiguous nucleotides of a polynucleotide selected from the group consisting of i) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:18-34, ii) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:18-34, iii) a polynucleotide having a sequence complementary to i), iv) a polynucleotide complementary to the polynucleotide of ii), and v) an RNA equivalent of i)-iv). Hybridization occurs under conditions whereby a specific hybridization complex is formed between said probe and a target polynucleotide in the biological sample, said target polynucleotide selected from the group consisting of i) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:18-34, ii) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:18-34, iii) a polynucleotide complementary to the polynucleotide of i), iv) a polynucleotide complementary to the polynucleotide of ii), and v) an RNA equivalent of i)-iv). Alternatively, the target polynucleotide comprises a fragment of a polynucleotide sequence selected from the group consisting of i)-v) above; c) quantifying the amount of hybridization complex; and d) comparing the amount of hybridization complex in the treated biological sample with the amount of hybridization complex in an untreated biological sample, wherein a difference in the amount of hybridization complex in the treated biological sample is indicative of toxicity of the test compound.  
       BRIEF DESCRIPTION OF THE TABLES  
       [0064] Table 1 summaries the nomenclature for the full length polynucleotide and polypeptide sequences of the present invention.  
       [0065] Table 2 shows the GenBank identification number and annotation of the nearest GenBank homolog for polypeptides of the invention. The probability scores for the matches between each polypeptide and its homolog(s) are also shown. Table 3 shows structural features of polypeptide sequences of the invention, including predicted motifs and domains, along with the methods, algorithms, and searchable databases used for analysis of the polypeptides.  
       [0066] Table 4 lists the cDNA and/or genomic DNA fragments which were used to assemble polynucleotide sequences of the invention, along with selected fragments of the polynucleotide sequences.  
       [0067] Table 5 shows the representative cDNA library for polynucleotides of the invention.  
       [0068] Table 6 provides an appendix which describes the tissues and vectors used for construction of the cDNA libraries shown in Table 5.  
       [0069] Table 7 shows the tools, programs, and algorithms used to analyze the polynucleotides and polypeptides of the invention, along with applicable descriptions, references, and threshold parameters.  
       DESCRIPTION OF THE INVENTION  
       [0070] Before the present proteins, nucleotide sequences, and methods are described, it is understood that this invention is not limited to the particular machines, materials and methods described, as these may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention which will be limited only by the appended claims.  
       [0071] It must be noted that as used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural reference unless the context clearly dictates otherwise. Thus, for example, a reference to “a host cell” includes a plurality of such host cells, and a reference to “an antibody” is a reference to one or more antibodies and equivalents thereof known to those skilled in the art, and so forth.  
       [0072] Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any machines, materials, and methods similar or equivalent to those described herein can be used to practice or test the present invention, the preferred machines, materials and methods are now described. All publications mentioned herein are cited for the purpose of describing and disclosing the cell lines, protocols, reagents and vectors which are reported in the publications and which might be used in connection with the invention. Nothing herein is to be construed as an admission that the invention is not entitled to antedate such disclosure by virtue of prior invention.  
       DEFINITIONS  
       [0073] “TMP” refers to the amino acid sequences of substantially purified TMP obtained from any species, particularly a mammalian species, including bovine, ovine, porcine, murine, equine, and human, and from any source, whether natural, synthetic, semi-synthetic, or recombinant.  
       [0074] The term “agonist” refers to a molecule which intensifies or mimics the biological activity of TMP. Agonists may include proteins, nucleic acids, carbohydrates, small molecules, or any other compound or composition which modulates the activity of TMP either by directly interacting with TMP or by acting on components of the biological pathway in which TMP participates.  
       [0075] An “allelic variant” is an alternative form of the gene encoding TMP. Allelic variants may result from at least one mutation in the nucleic acid sequence and may result in altered mRNAs or in polypeptides whose structure or function may or may not be altered. A gene may have none, one, or many allelic variants of its naturally occurring form. Common mutational changes which give rise to allelic variants are generally ascribed to natural deletions, additions, or substitutions of nucleotides. Each of these types of changes may occur alone, or in combination with the others, one or more times in a given sequence.  
       [0076] “Altered” nucleic acid sequences encoding TMP include those sequences with deletions, insertions, or substitutions of different nucleotides, resulting in a polypeptide the same as TMP or a polypeptide with at least one functional characteristic of TMP. Included within this definition are polymorphisms which may or may not be readily detectable using a particular oligonucleotide probe of the polynucleotide encoding TMP, and improper or unexpected hybridization to allelic variants, with a locus other than the normal chromosomal locus for the polynucleotide sequence encoding TMP. The encoded protein may also be “altered,” and may contain deletions, insertions, or substitutions of amino acid residues which produce a silent change and result in a functionally equivalent TMP. Deliberate amino acid substitutions may be made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity, and/or the amphipathic nature of the residues, as long as the biological or immunological activity of TMP is retained. For example, negatively charged amino acids may include aspartic acid and glutamic acid, and positively charged amino acids may include lysine and arginine. Amino acids with uncharged polar side chains having similar hydrophilicity values may include: asparagine and glutamine; and serine and threonine. Amino acids with uncharged side chains having similar hydrophilicity values may include: leucine, isoleucine, and valine; glycine and alanine; and phenylalanine and tyrosine.  
       [0077] The terms “amino acid” and “amino acid sequence” refer to an oligopeptide, peptide, polypeptide, or protein sequence, or a fragment of any of these, and to naturally occurring or synthetic molecules. Where “amino acid sequence” is recited to refer to a sequence of a naturally occurring protein molecule, “amino acid sequence” and like terms are not meant to limit the amino acid sequence to the complete native amino acid sequence associated with the recited protein molecule.  
       [0078] “Amplification” relates to the production of additional copies of a nucleic acid sequence. Amplification is generally carried out using polymerase chain reaction (PCR) technologies well known in the art.  
       [0079] The term “antagonist” refers to a molecule which inhibits or attenuates the biological activity of TMP. Antagonists may include proteins such as antibodies, nucleic acids, carbohydrates, small molecules, or any other compound or composition which modulates the activity of TMP either by directly interacting with TMP or by acting on components of the biological pathway in which TMP participates.  
       [0080] The term “antibody” refers to intact immunoglobulin molecules as well as to fragments thereof, such as Fab, F(ab′) 2 , and Fv fragments, which are capable of binding an epitopic determinant. Antibodies that bind TMP polypeptides can be prepared using intact polypeptides or using fragments containing small peptides of interest as the immunizing antigen. The polypeptide or oligopeptide used to immunize an animal (e.g., a mouse, a rat, or a rabbit) can be derived from the translation of RNA, or synthesized chemically, and can be conjugated to a carrier protein if desired. Commonly used carriers that are chemically coupled to peptides include bovine serum albumin, thyroglobulin, and keyhole limpet hemocyanin (KLH). The coupled peptide is then used to immunize the animal.  
       [0081] The term “antigenic determinant” refers to that region of a molecule (i.e., an epitope) that makes contact with a particular antibody. When a protein or a fragment of a protein is used to immunize a host animal, numerous regions of the protein may induce the production of antibodies which bind specifically to antigenic determinants (particular regions or three-dimensional structures on the protein). An antigenic determinant may compete with the intact antigen (i.e., the immunogen used to elicit the immune response) for binding to an antibody.  
       [0082] The term “aptamer” refers to a nucleic acid or oligonucleotide molecule that binds to a specific molecular target. Aptamers are derived from an in vitro evolutionary process (e.g., SELEX (Systematic Evolution of Ligands by Exponential Enrichment), described in U.S. Pat. No. 5,270,163), which selects for target-specific aptamer sequences from large combinatorial libraries. Aptamer compositions may be double-stranded or single-stranded, and may include deoxyribonucleotides, ribonucleotides, nucleotide derivatives, or other nucleotide-like molecules. The nucleotide components of an aptamer may have modified sugar groups (e.g., the 2′-OH group of a ribonucleotide may be replaced by 2′-F or 2′-NH 2 ), which may improve a desired property, e.g., resistance to nucleases or longer lifetime in blood. Aptamers may be conjugated to other molecules, e.g., a high molecular weight carrier to slow clearance of the aptamer from the circulatory system. Aptamers may be specifically cross-linked to their cognate ligands, e.g., by photo-activation of a cross-linker. (See, e.g., Brody, E. N. and L. Gold (2000) J. Biotechnol. 74:5-13.)  
       [0083] The term “intramer” refers to an aptamer which is expressed in vivo. For example, a vaccinia virus-based RNA expression system has been used to express specific RNA aptamers at high levels in the cytoplasm of leukocytes (Blind, M. et al. (1999) Proc. Natl. Acad. Sci. USA 96:3606-3610).  
       [0084] The term “spiegelmer” refers to an aptamer which includes L-DNA, L-RNA, or other left-handed nucleotide derivatives or nucleotide-like molecules. Aptamers containing left-handed nucleotides are resistant to degradation by naturally occurring enzymes, which normally act on substrates containing right-handed nucleotides.  
       [0085] The term “antisense” refers to any composition capable of base-pairing with the “sense” (coding) strand of a specific nucleic acid sequence. Antisense compositions may include DNA; RNA; peptide nucleic acid (PNA); oligonucleotides having modified backbone linkages such as phosphorothioates, methylphosphonates, or benzylphosphonates; oligonucleotides having modified sugar groups such as 2′-methoxyethyl sugars or 2′-methoxyethoxy sugars; or oligonucleotides having modified bases such as 5-methyl cytosine, 2′-deoxyuracil, or 7-deaza-2′-deoxyguanosine. Antisense molecules may be produced by any method including chemical synthesis or transcription. Once introduced into a cell, the complementary antisense molecule base-pairs with a naturally occurring nucleic acid sequence produced by the cell to form duplexes which block either transcription or translation. The designation “negative” or “minus” can refer to the antisense strand, and the designation “positive” or “plus” can refer to the sense strand of a reference DNA molecule.  
       [0086] The term “biologically active” refers to a protein having structural, regulatory, or biochemical functions of a naturally occurring molecule. Likewise, “immunologically active” or “immunogenic” refers to the capability of the natural, recombinant, or synthetic TMP, or of any oligopeptide thereof, to induce a specific immune response in appropriate animals or cells and to bind with specific antibodies.  
       [0087] “Complementary” describes the relationship between two single-stranded nucleic acid sequences that anneal by base-pairing. For example, 5′-AGT-3′ pairs with its complement, 3′-TCA-5′.  
       [0088] A “composition comprising a given polynucleotide sequence” and a “composition comprising a given amino acid sequence” refer broadly to any composition containing the given polynucleotide or amino acid sequence. The composition may comprise a dry formulation or an aqueous solution. Compositions comprising polynucleotide sequences encoding TMP or fragments of TMP may be employed as hybridization probes. The probes may be stored in freeze-dried form and may be associated with a stabilizing agent such as a carbohydrate. In hybridizations, the probe may be deployed in an aqueous solution containing salts (e.g., NaCl), detergents (e.g., sodium dodecyl sulfate; SDS), and other components (e.g., Denhardt&#39;s solution, dry milk, salmon sperm DNA, etc.).  
       [0089] “Consensus sequence” refers to a nucleic acid sequence which has been subjected to repeated DNA sequence analysis to resolve uncalled bases, extended using the XL-PCR kit (Applied Biosystems, Foster City Calif.) in the 5′ and/or the 3′ direction, and resequenced, or which has been assembled from one or more overlapping cDNA, EST, or genomic DNA fragments using a computer program for fragment assembly, such as the GELVIEW fragment assembly system (GCG, Madison Wis.) or Phrap (University of Washington, Seattle Wash.). Some sequences have been both extended and assembled to produce the consensus sequence.  
       [0090] “Conservative amino acid substitutions” are those substitutions that are predicted to least interfere with the properties of the original protein, i.e., the structure and especially the function of the protein is conserved and not significantly changed by such substitutions. The table below shows amino acids which may be substituted for an original amino acid in a protein and which are regarded as conservative amino acid substitutions.  
                                   Original Residue   Conservative Substitution                  Ala   Gly, Ser       Arg   His, Lys       Asn   Asp, Gln, His       Asp   Asn, Glu       Cys   Ala, Ser       Gln   Asn, Glu, His       Glu   Asp, Gln, His       Gly   Ala       His   Asn, Arg, Gln, Glu       Ile   Leu, Val       Leu   Ile, Val       Lys   Arg, Gln, Glu       Met   Leu, Ile       Phe   His, Met, Leu, Trp, Tyr       Ser   Cys, Thr       Thr   Ser, Val       Trp   Phe, Tyr       Tyr   His, Phe, Trp       Val   Ile, Leu, Thr                  
 
       [0091] Conservative amino acid substitutions generally maintain (a) the structure of the polypeptide backbone in the area of the substitution, for example, as a beta sheet or alpha helical conformation, (b) the charge or hydrophobicity of the molecule at the site of the substitution, and/or (c) the bulk of the side chain.  
       [0092] A “deletion” refers to a change in the amino acid or nucleotide sequence that results in the absence of one or more amino acid residues or nucleotides:  
       [0093] The term “derivative” refers to a chemically modified polynucleotide or polypeptide. Chemical modifications of a polynucleotide can include, for example, replacement of hydrogen by an alkyl, acyl, hydroxyl, or amino group. A derivative polynucleotide encodes a polypeptide which retains at least one biological or immunological function of the natural molecule. A derivative polypeptide is one modified by glycosylation, pegylation, or any similar process that retains at least one biological or immunological function of the polypeptide from which it was derived.  
       [0094] A “detectable label” refers to a reporter molecule or enzyme that is capable of generating a measurable signal and is covalently or noncovalently joined to a polynucleotide or polypeptide.  
       [0095] “Differential expression” refers to increased or upregulated; or decreased, downregulated, or absent gene or protein expression, determined by comparing at least two different samples. Such comparisons may be carried out between, for example, a treated and an untreated sample, or a diseased and a normal sample.  
       [0096] “Exon shuffling” refers to the recombination of different coding regions (exons). Since an exon may represent a structural or functional domain of the encoded protein, new proteins may be assembled through the novel reassortment of stable substructures, thus allowing acceleration of the evolution of new protein functions.  
       [0097] A “fragment” is a unique portion of TMP or the polynucleotide encoding TMP which is identical in sequence to but shorter in length than the parent sequence. A fragment may comprise up to the entire length of the defined sequence, minus one nucleotide/amino acid residue. For example, a fragment may comprise from 5 to 1000 contiguous nucleotides or amino acid residues. A fragment used as a probe, primer, antigen, therapeutic molecule, or for other purposes, may be at least 5, 10, 15, 16, 20, 25, 30, 40, 50, 60, 75, 100, 150, 250 or at least 500 contiguous nucleotides or amino acid residues in length. Fragments may be preferentially selected from certain regions of a molecule. For example, a polypeptide fragment may comprise a certain length of contiguous amino acids selected from the first 250 or 500 amino acids (or first 25% or 50%) of a polypeptide as shown in a certain defined sequence. Clearly these lengths are exemplary, and any length that is supported by the specification, including the Sequence Listing, tables, and figures, may be encompassed by the present embodiments.  
       [0098] A fragment of SEQ ID NO:18-34 comprises a region of unique polynucleotide sequence that specifically identifies SEQ ID NO:18-34, for example, as distinct from any other sequence in the genome from which the fragment was obtained. A fragment of SEQ ID NO:18-34is useful, for example, in hybridization and amplification technologies and in analogous methods that distinguish SEQ ID NO:18-34 from related polynucleotide sequences. The precise length of a fragment of SEQ ID NO:18-34 and the region of SEQ ID NO:18-34 to which the fragment corresponds are routinely determinable by one of ordinary skill in the art based on the intended purpose for the fragment.  
       [0099] A fragment of SEQ ID NO:1-17 is encoded by a fragment of SEQ ID NO:18-34. A fragment of SEQ ID NO:1-17 comprises a region of unique amino acid sequence that specifically identifies SEQ ID NO:1-17. For example, a fragment of SEQ ID NO:1-17 is useful as an immunogenic peptide for the development of antibodies that specifically recognize SEQ ID NO:1-17. The precise length of a fragment of SEQ ID NO:1-17 and the region of SEQ ID NO:1-17 to which the fragment corresponds are routinely determinable by one of ordinary skill in the art based on the intended purpose for the fragment.  
       [0100] A “full length” polynucleotide sequence is one containing at least a translation initiation codon (e.g., methionine) followed by an open reading frame and a translation termination codon. A “full length” polynucleotide sequence encodes a “full length” polypeptide sequence.  
       [0101] “Homology” refers to sequence similarity or, interchangeably, sequence identity, between two or more polynucleotide sequences or two or more polypeptide sequences.  
       [0102] The terms “percent identity” and “% identity,” as applied to polynucleotide sequences, refer to the percentage of residue matches between at least two polynucleotide sequences aligned using a standardized algorithm Such an algorithm may insert, in a standardized and reproducible way, gaps in the sequences being compared in order to optimize alignment between two sequences, and therefore achieve a more meaningful comparison of the two sequences.  
       [0103] Percent identity between polynucleotide sequences may be determined using the default parameters of the CLUSTAL V algorithm as incorporated into the MEGALIGN version 3.12e sequence alignment program. This program is part of the LASERGENE software package, a suite of molecular biological analysis programs (DNASTAR, Madison Wis.). CLUSTAL V is described in Higgins, D. G. and P. M. Sharp (1989) CABIOS 5:151-153 and in Higgins, D. G. et al. (1992) CABIOS 8:189-191. For pairwise alignments of polynucleotide sequences, the default parameters are set as follows: Ktuple=2, gap penalty=5, window=4, and “diagonals saved”=4. The “weighted” residue weight table is selected as the default. Percent identity is reported by CLUSTAL V as the “percent similarity” between aligned polynucleotide sequences.  
       [0104] Alternatively, a suite of commonly used and freely available sequence comparison algorithms is provided by the National Center for Biotechnology Information (NCBI) Basic Local Alignment Search Tool (BLAST) (Altschul, S. F. et al. (1990) J. Mol. Biol. 215:403-410), which is available from several sources, including the NCBI, Bethesda, Md., and on the Internet at http://www.ncbi.nlm.nih.gov/BLAST/. The BLAST software suite includes various sequence analysis programs including “blastn,” that is used to align a known polynucleotide sequence with other polynucleotide sequences from a variety of databases. Also available is a tool called “BLAST 2 Sequences” that is used for direct pairwise comparison of two nucleotide sequences. “BLAST 2 Sequences” can be accessed and used interactively at http://www.ncbi.nlm.nih.gov/gorf/b12.html. The “BLAST 2 Sequences” tool can be used for both blastn and blastp (discussed below). BLAST programs are commonly used with gap and other parameters set to default settings. For example, to compare two nucleotide sequences, one may use blastn with the “BLAST 2 Sequences” tool Version 2.0.12 (Apr. 21, 2000) set at default parameters. Such default parameters may be, for example:  
       [0105] Matrix: BLOSUM62  
       [0106] Reward for match: 1  
       [0107] Penalty for mismatch: −2  
       [0108] Open Gap: 5 and Extension Gap: 2 penalties  
       [0109] Gap×drop-off. 50  
       [0110] Expect: 10  
       [0111] Word Size: 11  
       [0112] Filter: on  
       [0113] Percent identity may be measured over the length of an entire defined sequence, for example, as defined by a particular SEQ ID number, or may be measured over a shorter length, for example, over the length of a fragment taken from a larger, defined sequence, for instance, a fragment of at least 20, at least 30, at least 40, at least 50, at least 70, at least 100, or at least 200 contiguous nucleotides. Such lengths are exemplary only, and it is understood that any fragment length supported by the sequences shown herein, in the tables, figures, or Sequence Listing, may be used to describe a length over which percentage identity may be measured.  
       [0114] Nucleic acid sequences that do not show a high degree of identity may nevertheless encode similar amino acid sequences due to the degeneracy of the genetic code. It is understood that changes in a nucleic acid sequence can be made using this degeneracy to produce multiple nucleic acid sequences that all encode substantially the same protein.  
       [0115] The phrases “percent identity” and “% identity,” as applied to polypeptide sequences, refer to the percentage of residue matches between at least two polypeptide sequences aligned using a standardized algorithm. Methods of polypeptide sequence alignment are well-known. Some alignment methods take into account conservative amino acid substitutions. Such conservative substitutions, explained in more detail above, generally preserve the charge and hydrophobicity at the site of substitution, thus preserving the structure (and therefore function) of the polypeptide.  
       [0116] Percent identity between polypeptide sequences may be determined using the default parameters of the CLUSTAL V algorithm as incorporated into the MEGALIGN version 3.12e sequence alignment program (described and referenced above). For pairwise alignments of polypeptide sequences using CLUSTAL V, the default parameters are set as follows: Ktuple=1, gap penalty=3, window=5, and “diagonals saved”=5. The PAM250 matrix is selected as the default residue weight table. As with polynucleotide alignments, the percent identity is reported by CLUSTAL V as the “percent similarity” between aligned polypeptide sequence pairs.  
       [0117] Alternatively the NCBI BLAST software suite may be used. For example, for a pairwise comparison of two polypeptide sequences, one may use the “BLAST 2 Sequences” tool Version 2.0.12 (Apr. 21, 2000) with blastp set at default parameters. Such default parameters may be, for example:  
       [0118] Matrix: BLOSUM62  
       [0119] Open Gap: 11 and Extension Gap: 1 penalties  
       [0120] Gap×drop-off: 50  
       [0121] Expect: 10  
       [0122] Word Size: 3  
       [0123] Filter: on  
       [0124] Percent identity may be measured over the length of an entire defined polypeptide sequence, for example, as defined by a particular SEQ ID number, or may be measured over a shorter length, for example, over the length of a fragment taken from a larger, defined polypeptide sequence, for instance, a fragment of at least 15, at least 20, at least 30, at least 40, at least 50, at least 70 or at least 150 contiguous residues. Such lengths are exemplary only, and it is understood that any fragment length supported by the sequences shown herein, in the tables, figures or Sequence Listing, may be used to describe a length over which percentage identity may be measured.  
       [0125] “Human artificial chromosomes” (HACs) are linear microchromosomes which may contain DNA sequences of about 6 kb to 10 Mb in size and which contain all of the elements required for chromosome replication, segregation and maintenance.  
       [0126] The term “humanized antibody” refers to an antibody molecule in which the amino acid sequence in the non-antigen binding regions has been altered so that the antibody more closely resembles a human antibody, and still retains its original binding ability.  
       [0127] “Hybridization” refers to the process by which a polynucleotide strand anneals with a complementary strand through base pairing under defined hybridization conditions. Specific hybridization is an indication that two nucleic acid sequences share a high degree of complementarity. Specific hybridization complexes form under permissive annealing conditions and remain hybridized after the “washing” step(s). The washing step(s) is particularly important in determining the stringency of the hybridization process, with more stringent conditions allowing less non-specific binding, i.e., binding between pairs of nucleic acid strands that are not perfectly matched. Permissive conditions for annealing of nucleic acid sequences are routinely determinable by one of ordinary skill in the art and may be consistent among hybridization experiments, whereas wash conditions may be varied among experiments to achieve the desired stringency, and therefore hybridization specificity. Permissive annealing conditions occur, for example, at 68° C. in the presence of about 6×SSC, about 1% (w/v) SDS, and about 100 μg/ml sheared, denatured salmon sperm DNA.  
       [0128] Generally, stringency of hybridization is expressed, in part, with reference to the temperature under which the wash step is carried out. Such wash temperatures are typically selected to be about 5° C. to 20° C. lower than the thermal melting point (T m ) for the specific sequence at a defined ionic strength and pH. The T m  is the temperature (under defined ionic strength and pH) at which 50% of the target sequence hybridizes to a perfectly matched probe. An equation for calculating T m  and conditions for nucleic acid hybridization are well known and can be found in Sambrook, J. et al. (1989)  Molecular Cloning: A Laboratory Manual,  2 nd  ed., vol. 1-3, Cold Spring Harbor Press, Plainview N.Y.; specifically see volume 2, chapter 9.  
       [0129] High stringency conditions for hybridization between polynucleotides of the present invention include wash conditions of 68° C. in the presence of about 0.2×SSC and about 0.1% SDS, for 1 hour. Alternatively, temperatures of about 65° C., 60° C., 55° C., or 42° C. may be used. SSC concentration may be varied from about 0.1 to 2×SSC, with SDS being present at about 0.1%. Typically, blocking reagents are used to block non-specific hybridization. Such blocking reagents include, for instance, sheared and denatured salmon sperm DNA at about 100-200 μg/ml. Organic solvent, such as formamide at a concentration of about 35-50% v/v, may also be used under particular circumstances, such as for RNA:DNA hybridizations. Useful variations on these wash conditions will be readily apparent to those of ordinary skill in the art. Hybridization, particularly under high stringency conditions, may be suggestive of evolutionary similarity between the nucleotides. Such similarity is strongly indicative of a similar role for the nucleotides and their encoded polypeptides.  
       [0130] The term “hybridization complex” refers to a complex formed between two nucleic acid sequences by virtue of the formation of hydrogen bonds between complementary bases. A hybridization complex may be formed in solution (e.g., C 0 t or R 0 t analysis) or formed between one nucleic acid sequence present in solution and another nucleic acid sequence immobilized on a solid support (e.g., paper, membranes, filters, chips, pins or glass slides, or any other appropriate substrate to which cells or their nucleic acids have been fixed).  
       [0131] The words “insertion” and “addition” refer to changes in an amino acid or nucleotide sequence resulting in the addition of one or more amino acid residues or nucleotides, respectively.  
       [0132] “Immune response” can refer to c nditions associated with inflammation, trauma, immune disorders, or infectious or genetic disease, etc. These conditions can be characterized by expression of various factors, e.g., cytokines, chemokines, and other signaling molecules, which may affect cellular and systemic defense systems.  
       [0133] An “immunogenic fragment” is a polypeptide or oligopeptide fragment of TMP which is capable of eliciting an immune response when introduced into a living organism, for example, a mammal. The term “immunogenic fragment” also includes any polypeptide or oligopeptide fragment of TMP which is useful in any of the antibody production methods disclosed herein or known in the art.  
       [0134] The term “microarray” refers to an arrangement of a plurality of polynucleotides, polypeptides, or other chemical compounds on a substrate.  
       [0135] The terms “element” and “array element” refer to a polynucleotide, polypeptide, or other chemical compound having a unique and defined position on a microarray.  
       [0136] The term “modulate” refers to a change in the activity of TMP. For example, modulation may cause an increase or a decrease in protein activity, binding characteristics, or any other biological, functional, or immunological properties of TMP.  
       [0137] The phrases “nucleic acid” and “nucleic acid sequence” refer to a nucleotide, oligonucleotide, polynucleotide, or any fragment thereof. These phrases also refer to DNA or RNA of genomic or synthetic origin which may be single-stranded or double-stranded and may represent the sense or the antisense strand, to peptide nucleic acid (PNA), or to any DNA-like or RNA-like material.  
       [0138] “Operably linked” refers to the situation in which a first nucleic acid sequence is placed in a functional relationship with a second nucleic acid sequence. For instance, a promoter is operably linked to a coding sequence if the promoter affects the transcription or expression of the coding sequence. Operably linked DNA sequences may be in close proximity or contiguous and, where necessary to join two protein coding regions, in the same reading frame.  
       [0139] “Peptide nucleic acid” (PNA) refers to an antisense molecule or anti-gene agent which comprises an oligonucleotide of at least about 5 nucleotides in length linked to a peptide backbone of amino acid residues ending in lysine. The terminal lysine confers solubility to the composition. PNAs preferentially bind complementary single stranded DNA or RNA and stop transcript elongation, and may be pegylated to extend their lifespan in the cell.  
       [0140] “Post-translational modification” of an TMP may involve lipidation, glycosylation, phosphorylation, acetylation, racemization, proteolytic cleavage, and other modifications known in the art. These processes may occur synthetically or biochemically. Biochemical modifications will vary by cell type depending on the enzymatic milieu of TMP.  
       [0141] “Probe” refers to nucleic acid sequences encoding TMP, their complements, or fragments thereof, which are used to detect identical, allelic or related nucleic acid sequences. Probes are isolated oligonucleotides or polynucleotides attached to a detectable label or reporter molecule. Typical labels include radioactive isotopes, ligands, chemiluminescent agents, and enzymes. “Primers” are short nucleic acids, usually DNA oligonucleotides, which may be annealed to a target polynucleotide by complementary base-pairing. The primer may then be extended along the target DNA strand by a DNA polymerase enzyme. Primer pairs can be used for amplification (and identification) of a nucleic acid sequence, e.g., by the polymerase chain reaction (PCR).  
       [0142] Probes and primers as used in the present invention typically comprise at least 15 contiguous nucleotides of a known sequence. In order to enhance specificity, longer probes and primers may also be employed, such as probes and primers that comprise at least 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, or at least 150 consecutive nucleotides of the disclosed nucleic acid sequences. Probes and primers may be considerably longer than these examples, and it is understood that any length supported by the specification, including the tables, figures, and Sequence Listing, may be used.  
       [0143] Methods for preparing and using probes and primers are described in the references, for example Sambrook, J. et al. (1989)  Molecular Cloning: A Laboratory Manual,  2 nd  ed., vol. 1-3, Cold Spring Harbor Press, Plainview N.Y.; Ausubel, F. M. et al. (1987)  Current Protocols in Molecular Biology,  Greene Publ. Assoc. &amp; Wiley-lntersciences, New York N.Y.; Innis, M. et al. (1990)  PCR Protocols, A Guide to Methods and Applications,  Academic Press, San Diego Calif. PCR primer pairs can be derived from a known sequence, for example, by using computer programs intended for that purpose such as Primer (Version 0.5, 1991, Whitehead Institute for Biomedical Research, Cambridge Mass.).  
       [0144] Oligonucleotides for use as primers are selected using software known in the art for such purpose. For example, OLIGO 4.06 software is useful for the selection of PCR primer pairs of up to 100 nucleotides each, and for the analysis of oligonucleotides and larger polynucleotides of up to 5,000 nucleotides from an input polynucleotide sequence of up to 32 kilobases. Similar primer selection programs have incorporated additional features for expanded capabilities. For example, the PrimOU primer selection program (available to the public from the Genome Center at University of Texas South West Medical Center, Dallas Tex.) is capable of choosing specific primers from megabase sequences and is thus useful for designing primers on a genome-wide scope. The Primer3 primer selection program (available to the public from the Whitehead Institute/MIT Center for Genome Research, Cambridge Mass.) allows the user to input a “mispriming library,” in which sequences to avoid as primer binding sites are user-specified. Primer3 is useful, in particular, for the selection of oligonucleotides for microarrays. (The source code for the latter two primer selection programs may also be obtained from their respective sources and modified to meet the user&#39;s specific needs.) The PrimeGen program. (available to the public from the UK Human Genome Mapping Project Resource Centre, Cambridge UK) designs primers based on multiple sequence alignments, thereby allowing selection of primers that hybridize to either the most conserved or least conserved regions of aligned nucleic acid sequences. Hence, this program is useful for identification of both unique and c nserved oligonucleotides and polynucleotide fragments. The oligonucleotides and polynucleotide fragments identified by any of the above selection methods are useful in hybridization technologies, for example, as PCR or sequencing primers, microarray elements, or specific probes to identify fully or partially complementary polynucleotides in a sample of nucleic acids. Methods of oligonucleotide selection are not limited to those described above.  
       [0145] A “recombinant nucleic acid” is a sequence that is not naturally occurring or has a sequence that is made by an artificial combination of two or more otherwise separated segments of sequence. This artificial combination is often accomplished by chemical synthesis or, more commonly, by the artificial manipulation of isolated segments of nucleic acids, e.g., by genetic engineering techniques such as those described in Sambrook, supra. The term recombinant includes nucleic acids that have been altered solely by addition, substitution, or deletion of a portion of the nucleic acid. Frequently, a recombinant nucleic acid may include a nucleic acid sequence operably linked to a promoter sequence. Such a recombinant nucleic acid may be part of a vector that is used, for example, to transform a cell.  
       [0146] Alternatively, such recombinant nucleic acids may be part of a viral vector, e.g., based on a vaccinia virus, that could be use to vaccinate a mammal wherein the recombinant nucleic acid is expressed, inducing a protective immunological response in the mammal.  
       [0147] A “regulatory element” refers to a nucleic acid sequence usually derived from untranslated regions of a gene and includes enhancers, promoters, introns, and 5′ and 3′ untranslated regions (UTRs). Regulatory elements interact with host or viral proteins which control transcription, translation, or RNA stability.  
       [0148] “Reporter molecules” are chemical or biochemical moieties used for labeling a nucleic acid, amino acid, or antibody. Reporter molecules include radionuclides; enzymes; fluorescent, chemiluminescent, or chromogenic agents; substrates; cofactors; inhibitors; magnetic particles; and other moieties known in the art.  
       [0149] An “RNA equivalent,” in reference to a DNA sequence, is composed of the same linear sequence of nucleotides as the reference DNA sequence with the exception that all occurrences of the nitrogenous base thymine are replaced with uracil, and the sugar backbone is composed of ribose instead of deoxyribose.  
       [0150] The term “sample” is used in its broadest sense. A sample suspected of containing TMP, nucleic acids encoding TMP, or fragments thereof may comprise a bodily fluid; an extract from a cell, chromosome, organelle, or membrane isolated from a cell; a cell; genomic DNA, RNA, or cDNA, in solution or bound to a substrate; a tissue; a tissue print; etc.  
       [0151] The terms “specific binding” and “specifically binding” refer to that interaction between a protein or peptide and an agonist, an antibody, an antagonist, a small molecule, or any natural or synthetic binding composition. The interaction is dependent upon the presence of a particular structure of the protein, e.g., the antigenic determinant or epitope, recognized by the binding molecule. For example, if an antibody is specific for epitope “A,” the presence of a polypeptide comprising the epitope A, or the presence of free unlabeled A, in a reaction containing free labeled A and the antibody will reduce the amount of labeled A that binds to the antibody.  
       [0152] The term “substantially purified” refers to nucleic acid or amino acid sequences that are removed from their natural environment and are isolated or separated, and are at least 60% free, preferably at least 75% free, and most preferably at least 90% free from other components with which they are naturally associated.  
       [0153] A “substitution” refers to the replacement of one or more amino acid residues or nucleotides by different amino acid residues or nucleotides, respectively.  
       [0154] “Substrate” refers to any suitable rigid or semi-rigid support including membranes, filters, chips, slides, wafers, fibers, magnetic or nonmagnetic beads, gels, tubing, plates, polymers, microparticles and capillaries. The substrate can have a variety of surface forms, such as wells, trenches, pins, channels and pores, to which polynucleotides or polypeptides are bound.  
       [0155] A “transcript image” or “expression profile” refers to the collective pattern of gene expression by a particular cell type or tissue under given conditions at a given time.  
       [0156] “Transformation” describes a process by which exogenous DNA is introduced into a recipient cell. Transformation may occur under natural or artificial conditions according to various methods well known in the art, and may rely on any known method for the insertion of foreign nucleic acid sequences into a prokaryotic or eukaryotic host cell. The method for transformation is selected based on the type of host cell being transformed and may include, but is not limited to, bacteriophage or viral infection, electroporation, heat shock, lipofection, and particle bombardment. The term “transformed cells” includes stably transformed cells in which the inserted DNA is capable of replication either as an autonomously replicating plasmid or as part of the host chromosome, as well as transiently transformed cells which express the inserted DNA or RNA for limited periods of time.  
       [0157] A “transgenic organism,” as used herein, is any organism, including but not limited to animals and plants, in which one or more of the cells of the organism contains heterologous nucleic acid introduced by way of human intervention, such as by transgenic techniques well known in the art. The nucleic acid is introduced into the cell, directly or indirectly by introduction into a precursor of the cell, by way of deliberate genetic manipulation, such as by microinjection or by infection with a recombinant virus. The term genetic manipulation does not include classical cross-breeding, or in vitro fertilization, but rather is directed to the introduction of a recombinant DNA molecule. The transgenic organisms contemplated in accordance with the present invention include bacteria, cyanobacteria, fungi, plants and animals. The isolated DNA of the present invention can be introduced into the host by methods known in the art, for example infection, transfection, transformation or transconjugation. Techniques for transferring the DNA of the present invention into such organisms are widely known and provided in references such as Sambrook et al. (1989), supra.  
       [0158] A “variant” of a particular nucleic acid sequence is defined as a nucleic acid sequence having at least 40% sequence identity to the particular nucleic acid sequence over a certain length of one of the nucleic acid sequences using blastn with the “BLAST 2 Sequences” tool Version 2.0.9 (May 7, 1999) set at default parameters. Such a pair of nucleic acids may show, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% or greater sequence identity over a certain defined length. A variant may be described as, for example, an “allelic” (as defined above), “splice,” “species,” or “polymorphic” variant. A splice variant may have significant identity to a reference molecule, but will generally have a greater or lesser number of polynucleotides due to alternate splicing of exons during mRNA processing. The corresponding polypeptide may possess additional functional domains or lack domains that are present in the reference molecule. Species variants are polynucleotide sequences that vary from one species to another. The resulting polypeptides will generally have significant amino acid identity relative to each other. A polymorphic variant is a variation in the polynucleotide sequence of a particular gene between individuals of a given species. Polymorphic variants also may encompass “single nucleotide polymorphisms” (SNPs) in which the polynucleotide sequence varies by one nucleotide base. The presence of SNPs may be indicative of, for example, a certain population, a disease state, or a propensity for a disease state.  
       [0159] A “variant” of a particular polypeptide sequence is defined as a polypeptide sequence having at least 40% sequence identity to the particular polypeptide sequence over a certain length of one of the polypeptide sequences using blastp with the “BLAST 2 Sequences” tool Version 2.0.9 (May 7, 1999) set at default parameters. Such a pair of polypeptides may show, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% or greater sequence identity over a certain defined length of one of the polypeptides.  
       THE INVENTION  
       [0160] The invention is based on the discovery of new human transmembrane proteins (TMP), the polynucleotides encoding TMP, and the use of these compositions for the diagnosis, treatment, or prevention of reproductive, developmental, cardiovascular, neurological, gastrointestinal, lipid metabolism, cell proliferative, and autoimmune/inflammatory disorders.  
       [0161] Table 1 summarizes the nomenclature for the full length polynucleotide and polypeptide sequences of the invention. Each polynucleotide and its corresponding polypeptide are correlated to a single Incyte project identification number (Incyte Project ID). Each polypeptide sequence is denoted by both a polypeptide sequence identification number (Polypeptide SEQ ID NO:) and an Incyte polypeptide sequence number (Incyte Polypeptide ID) as shown. Each polynucleotide sequence is denoted by both a polynucleotide sequence identification number (Polynucleotide SEQ ID NO:) and an Incyte polynucleotide consensus sequence number (Incyte Polynucleotide ID) as shown.  
       [0162] Table 2 shows sequences with homology to the polypeptides of the invention as identified by BLAST analysis against the GenBank protein (genpept) database. Columns 1 and 2 show the polypeptide sequence identification number (Polypeptide SEQ ID NO:) and the corresponding Incyte polypeptide sequence number (Incyte Polypeptide ID) for polypeptides of the invention. Column 3 shows the GenBank identification number (GenBank ID NO:) of the nearest GenBank homolog. Column 4 shows the probability scores for the matches between each polypeptide and its homolog(s). Column 5 shows the annotation of the GenBank homolog(s) along with relevant citations where applicable, all of which are expressly incorporated by reference herein.  
       [0163] Table 3 shows various structural features of the polypeptides of the invention. Columns 1 and 2 show the polypeptide sequence identification number (SEQ ID NO:) and the corresponding Incyte polypeptide sequence number (Incyte Polypeptide ID) for each polypeptide of the invention. Column 3 shows the number of amino acid residues in each polypeptide. Column 4 shows potential phosphorylation sites, and column 5 shows potential glycosylation sites, as determined by the MOTIFS program of the GCG sequence analysis software package (Genetics Computer Group, Madison Wis.). Column 6 shows amino acid residues comprising signature sequences, domains, and motifs. Column 7 shows analytical methods for protein structure/function analysis and in some cases, searchable databases to which the analytical methods were applied.  
       [0164] Together, Tables 2 and 3 summarize the properties of polypeptides of the invention, and these properties establish that the claimed polypeptides are transmembrane proteins. For example, SEQ ID NO:2 is 89% identical to rat prostaglandin F2a receptor regulatory protein (GenBank ID g1054884) as determined by the Basic Local Alignment Search Tool (BLAST). (See Table 2.) The BLAST probability score is 0.0, which indicates the probability of obtaining the observed polypeptide sequence alignment by chance. SEQ ID NO:2 also contains six immunoglobulin domains as determined by searching for statistically significant matches in the hidden Markov model (HMM)-based PFAM database of conserved protein family domains. (See Table 3.) In addition, SEQ ID NO:2 contains a signal peptide, a transmembrane domain, and an RGD motif, providing further corroborative evidence that SEQ ID NO:2 is a human transmembrane protein.  
       [0165] In the alternative, SEQ ID NO:4 is 56% identical to human connexin 31.1 (GenBank ID g4336903) as determined by the Basic Local Alignment Search Tool (BLAST). (See Table 2.) The BLAST probability score is 5.8e-68, which indicates the probability of obtaining the observed polypeptide sequence alignment by chance. SEQ ID NO:4 also contains a connexin domain as determined by searching for statistically significant matches in the hidden Markov model (HMM-based PFAM database of conserved protein family domains. (See Table 3.) Data from BLIMPS, MOTIFS, and PROFILESCAN analyses provide further corroborative evidence that SEQ ID NO:4 is a connexin. Note that six identical connexins compose a connexon (gap junction), a transmembrane channel in the plasma membrane which functions chemically and electrically to couple the cytoplasms of neighboring cells in many tissues. SEQ ID NO:5 is 1554 amino acids in length and is 99% identical over 1157 amino acids to human MEGF7 (GenBank ID g3449306) as determined by the Basic Local Alignment Search Tool (BLAST). (See Table 2.) The BLAST probability score is 0.0, which indicates the probability of obtaining the observed polypeptide sequence alignment by chance. SEQ ID NO:5 also contains low-density lipoprotein receptor repeats and low-density lipoprotein receptor domains as determined by searching for statistically significant matches in the hidden Markov model (HMM)-based PFAM database of conserved protein family domains. (See Table 3.) Data from BLIMPS analyses provide further corroborative evidence that SEQ ID NO:5 is a member of the LDL receptor family of proteins.  
       [0166] In another alternative, SEQ ID NO:6 is 36% identical to mouse low density lipoprotein receptor related protein LRP1B/LRP-DIT (GenBank ID g8926243) as determined by the Basic Local Alignment Search Tool (BLAST). (See Table 2.) The BLAST probability score is 1.5e-40, which indicates the probability of obtaining the observed polypeptide sequence alignment by chance. SEQ ID NO:6 also contains low-density lipoprotein receptor domains as determined by searching for statistically significant matches in the hidden Markov model (HMM)-based PFAM database of conserved protein family domains. (See Table 3.) Data from BLIMPS analyses provide further corroborative evidence that SEQ ID NO:6 is a low-density lipoprotein receptor-related molecule. Further, SEQ ID NO:14 is 59% identical to human TNF-inducible protein CG12-1 (GenBank ID g3978246) as determined by the Basic Local Alignment Search Tool (BLAST). (See Table 2.) The BLAST probability score is 1.2e-94, which indicates the probability of obtaining the observed polypeptide sequence alignment by chance. Data from HMMER analysis provides further corroborative evidence that SEQ ID NO:14 contains a transmembrane domain. SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:7-13, and SEQ ID NO:15-17 were analyzed and annotated in a similar manner. The algorithms and parameters for the analysis of SEQ ID NO:1-17 are described in Table 7.  
       [0167] As shown in Table 4, the full length polynucleotide sequences of the present invention were assembled using cDNA sequences or coding (exon) sequences derived from genomic DNA, or any combination of these two types of sequences. Columns 1 and 2 list the polynucleotide sequence identification number (Polynucleotide SEQ ID NO:) and the corresponding Incyte polynucleotide consensus sequence number (Incyte Polynucleotide ID) for each polynucleotide of the invention. Column 3 shows the length of each polynucleotide sequence in basepairs. Column 4 lists fragments of the polynucleotide sequences which are useful, for example, in hybridization or amplification technologies that identify SEQ ID NO:18-34 or that distinguish between SEQ ID NO:18-34 and related polynucleotide sequences. Column 5 shows identification numbers corresponding to cDNA sequences, coding sequences (exons) predicted from genomic DNA, and/or sequence assemblages comprised of both cDNA and genomic DNA. These sequences were used to assemble the full length polynucleotide sequences of the invention. Columns 6 and 7 of Table 4 show the nucleotide start (5′) and stop (3′) positions of the cDNA and/or genomic sequences in column 5 relative to their respective full length sequences.  
       [0168] The identification numbers in Column 5 of Table 4 may refer specifically, for example, to Incyte cDNAs along with their corresponding cDNA libraries. For example, 6798827J1 is the identification number of an Incyte cDNA sequence, and COLENOR03 is the cDNA library from which it is derived. Incyte cDNAs for which cDNA libraries are not indicated were derived from pooled cDNA libraries (e.g., 71760758V1). Alternatively, the identification numbers in column 5 may refer to GenBank cDNAs or ESTs (e.g., g1506355) which contributed to the assembly of the full length polynucleotide sequences. In addition, the identification numbers in column 5 may identify sequences derived from the ENSEMBL (The Sanger Centre, Cambridge, UK) database (i.e., those sequences including the designation “ENST”). Alternatively, the identification numbers in column 5 may be derived from the NCBI RefSeq Nucleotide Sequence Records Database (i.e., those sequences including the designation “NM” or “NT”) or the NCBI RefSeq Protein Sequence Records (i.e., those sequences including the designation “NP”). Alternatively, the identification numbers in column 5 may refer to assemblages of both cDNA and Genscan-predicted exons brought together by an “exon stitching” algorithm For example, FL_XXXXXX_N 1— N 2— YYYYY_N 3— N 4  represents a “stitched” sequence in which XXXXXX is the identification number of the cluster of sequences to which the algorithm was applied, and YYYYY is the number of the prediction generated by the algorithm, and N 1,2,3 . . .  , if present, represent specific exons that may have been manually edited during analysis (See Example V). Alternatively, the identification numbers in column 5 may refer to assemblages of exons brought together by an “exon-stretching” algorithm For example, FLXXXXXX_gAAAAA_gBBBBB — 1_N is the identification number of a “stretched” sequence, with XXXXXX being the Incyte project identification number, gAAAAA being the GenBank identification number of the human genomic sequence to which the “exon-stretching” algorithm was applied, gBBBBB being the GenBank identification number or NCBI RefSeq identification number of the nearest GenBank protein homolog, and N referring to specific exons (See Example V). In instances where a RefSeq sequence was used as a protein homolog for the “exon-stretching” algorithm, a RefSeq identifier (denoted by “NM,” “NP,” or “NT”) may be used in place of the GenBank identifier (i.e., gBBBBB).  
       [0169] Alternatively, a prefix identifies component sequences that were hand-edited, predicted from genomic DNA sequences, or derived from a combination of sequence analysis methods. The following Table lists examples of component sequence prefixes and corresponding sequence analysis methods associated with the prefixes (see Example IV and Example V).  
                                   Prefix   Type of analysis and/or examples of programs                  GNN, GFG,   Exon prediction from genomic sequences using, for       ENST   example, GENSCAN (Stanford University, CA, USA) or           FGENES (Computer Genomics Group, The Sanger Centre,           Cambridge, UK).       GBI   Hand-edited analysis of genomic sequences.       FL   Stitched or stretched genomic sequences (see Example V).       INCY   Full length transcript and exon prediction from mapping           of EST sequences to the genome. Genomic location and           EST composition data are combined to predict the exons           and resulting transcript.                  
 
       [0170] In some cases, Incyte cDNA coverage redundant with the sequence coverage shown in column 5 was obtained to confirm the final consensus polynucleotide sequence, but the relevant Incyte cDNA identification numbers are not shown.  
       [0171] Table 5 shows the representative cDNA libraries for those full length polynucleotide sequences which were assembled using Incyte cDNA sequences. The representative cDNA library is the Incyte cDNA library which is most frequently represented by the Incyte cDNA sequences which were used to assemble and confirm the above polynucleotide sequences. The tissues and vectors which were used to construct the cDNA libraries shown in Table 5 are described in Table 6.  
       [0172] The invention also encompasses TMP variants. A preferred TMP variant is one which has at least about 80%, or alternatively at least about 90%, or even at least about 95% amino acid sequence identity to the TMP amino acid sequence, and which contains at least one functional or structural characteristic of TMP.  
       [0173] The invention also encompasses polynucleotides which encode TMP. In a particular embodiment, the invention encompasses a polynucleotide sequence comprising a sequence selected from the group consisting of SEQ ID NO:18-34, which encodes TMP. The polynucleotide sequences of SEQ ID NO:18-34, as presented in the Sequence Listing, embrace the equivalent RNA sequences, wherein occurrences of the nitrogenous base thymine are replaced with uracil, and the sugar backbone is composed of ribose instead of deoxyribose.  
       [0174] The invention also encompasses a variant of a polynucleotide sequence encoding TMP. In particular, such a variant polynucleotide sequence will have at least about 70%, or alternatively at least about 85%, or even at least about 95% polynucleotide sequence identity to the polynucleotide sequence encoding TMP. A particular aspect of the invention encompasses a variant of a polynucleotide sequence comprising a sequence selected from the group consisting of SEQ ID NO:18-34 which has at least about 70%, or alternatively at least about 85%, or even at least about 95% polynucleotide sequence identity to a nucleic acid sequence selected from the group consisting of SEQ ID NO:18-34. Any one of the polynucleotide variants described above can encode an amino acid sequence which contains at least one functional or structural characteristic of TMP.  
       [0175] In addition, or in the alternative, a polynucleotide variant of the invention is a splice variant of a polynucleotide sequence encoding TMP. A splice variant may have portions which have significant sequence identity to the polynucleotide sequence encoding TMP, but will generally have a greater or lesser number of polynucleotides due to additions or deletions of blocks of sequence arising from alternate splicing of exons during mRNA processing. A splice variant may have less than about 70%, or alternatively less than about 60%, or alternatively less than about 50% polynucleotide sequence identity to the polynucleotide sequence encoding TMP over its entire length; however, portions of the splice variant will have at least about 70%, or alternatively at least about 85%, or alternatively at least about 95%, or alternatively 100% polynucleotide sequence identity to portions of the polynucleotide sequence encoding TMP. Any one of the splice variants described above can encode an amino acid sequence which contains at least one functional or structural characteristic of TMP.  
       [0176] It will be appreciated by those skilled in the art that as a result of the degeneracy of the genetic code, a multitude of polynucleotide sequences encoding TMP, some bearing minimal similarity to the polynucleotide sequences of any known and naturally occurring gene, may be produced. Thus, the invention contemplates each and every possible variation of polynucleotide sequence that could be made by selecting combinations based on possible codon choices. These combinations are made in accordance with the standard triplet genetic code as applied to the polynucleotide sequence of naturally occurring TMP, and all such variations are to be considered as being specifically disclosed.  
       [0177] Although nucleotide sequences which encode TMP and its variants are generally capable of hybridizing to the nucleotide sequence of the naturally occurring TMP under appropriately selected conditions of stringency, it may be advantageous to produce nucleotide sequences encoding TMP or its derivatives possessing a substantially different codon usage, e.g., inclusion of non-naturally occurring codons. Codons may be selected to increase the rate at which expression of the peptide occurs in a particular prokaryotic or eukaryotic host in accordance with the frequency with which particular codons are utilized by the host. Other reasons for substantially altering the nucleotide sequence encoding TMP and its derivatives without altering the encoded amino acid sequences include the production of RNA transcripts having more desirable properties, such as a greater half-life, than transcripts produced from the naturally occurring sequence.  
       [0178] The invention also encompasses production of DNA sequences which encode TMP and TMP derivatives, or fragments thereof, entirely by synthetic chemistry. After production, the synthetic sequence may be inserted into any of the many available expression vectors and cell systems using reagents well known in the art. Moreover, synthetic chemistry may be used to introduce mutations into a sequence encoding TMP or any fragment thereof.  
       [0179] Also encompassed by the invention are polynucleotide sequences that are capable of hybridizing to the claimed polynucleotide sequences, and, in particular, to those shown in SEQ ID NO:18-34 and fragments thereof under various conditions of stringency. (See e.g., Wahl, G. M. and S. L. Berger (1987) Methods Enzymol. 152:399-407; Kimmel, A. R. (1987) Methods Enzymol. 152:507-511.) Hybridization conditions, including annealing and wash conditions, are described in “Definitions.” 
       [0180] Methods for DNA sequencing are well known in the art and may be used to practice any of the embodiments of the invention. The methods may employ such enzymes as the Klenow fragment of DNA polymerase I, SEQUENASE (US Biochemical, Cleveland Ohio), Taq polymerase (Applied Biosystems), thermostable T7 polymerase (Amersham Pharmacia Biotech, Piscataway N.J.), or combinations of polymerases and proofreading exonucleases such as those found in the ELONGASE amplification system (Life Technologies, Gaithersburg Md.). Preferably, sequence preparation is automated with machines such as the MICROLAB 2200 liquid transfer system (Hamilton, Reno Nev.), PTC200 thermal cycler (MJ Research, Watertown Mass.) and ABI CATALYST 800 thermal cycler (Applied Biosystems). Sequencing is then carried out using either the ABI 373 or 377 DNA sequencing system (Applied Biosystems), the MEGABACE 1000 DNA sequencing system (Molecular Dynamics, Sunnyvale Calif.), or other systems known in the art. The resulting sequences are analyzed using a variety of algorithms which are well known in the art. (See, e.g., Ausubel, F. M. (1997)  Short Protocols in Molecular Biology,  John Wiley &amp; Sons, New York N.Y., unit 7.7; Meyers, R. A. (1995)  Molecular Biology and Biotechnology,  Wiley VCH, New York, N.Y., pp. 856-853.)  
       [0181] The nucleic acid sequences encoding TMP may be extended utilizing a partial nucleotide sequence and employing various PCR-based methods known in the art to detect upstream sequences, such as promoters and regulatory elements. For example, one method which may be employed, restriction-site PCR, uses universal and nested primers to amplify unknown sequence from genomic DNA within a cloning vector. (See, e.g., Sarkar, G. (1993) PCR Methods Applic. 2:318-322.) Another method, inverse PCR, uses primers that extend in divergent directions to amplify unknown sequence from a circularized template. The template is derived from restriction fragments comprising a known genomic locus and surrounding sequences. (See, e.g., Triglia, T. et al. (1988) Nucleic Acids Res. 16:8186.) A third method, capture PCR, involves PCR amplification of DNA fragments adjacent to known sequences in human and yeast artificial chromosome DNA. (See, e.g., Lagerstrom, M. et al. (1991) PCR Methods Applic. 1:111-119.) In this method, multiple restriction enzyme digestions and ligations may be used to insert an engineered double-stranded sequence into a region of unknown sequence before performing PCR. Other methods which may be used to retrieve unknown sequences are known in the art. (See, e.g., Parker, J. D. et al. (1991) Nucleic Acids Res. 19:3055-3060). Additionally, one may use PCR, nested primers, and PROMOTERFINDER libraries (Clontech, Palo Alto Calif.) to walk genomic DNA. This procedure avoids the need to screen libraries and is useful in finding intron/exon junctions. For all PCR-based methods, primers may be designed using commercially available software, such as OLIGO 4.06 primer analysis software (National Biosciences, Plymouth Minn.) or another appropriate program, to be about 22 to 30 nucleotides in length, to have a GC content of about 50% or more, and to anneal to the template at temperatures of about 68° C. to 72° C.  
       [0182] When screening for full length cDNAs, it is preferable to use libraries that have been size-selected to include larger cDNAs. In addition, random-primed libraries, which often include sequences containing the 5′ regions of genes, are preferable for situations in which an oligo d(T) library does not yield a full-length cDNA. Genomic libraries may be useful for extension of sequence into 5′ non-transcribed regulatory regions.  
       [0183] Capillary electrophoresis systems which are commercially available may be used to analyze the size or confirm the nucleotide sequence of sequencing or PCR products. In particular, capillary sequencing may employ flowable polymers for electrophoretic separation, four different nucleotide-specific, laser-stimulated fluorescent dyes, and a charge coupled device camera for detection of the emitted wavelengths. Output/light intensity may be converted to electrical signal using appropriate software (e.g., GENOTYPER and SEQUENCE NAVIGATOR, Applied Biosystems), and the entire process from loading of samples to computer analysis and electronic data display may be computer controlled. Capillary electrophoresis is especially preferable for sequencing small DNA fragments which may be present in limited amounts in a particular sample.  
       [0184] In another embodiment of the invention, polynucleotide sequences or fragments thereof which encode TMP may be cloned in recombinant DNA molecules that direct expression of TMP, or fragments or functional equivalents thereof, in appropriate host cells. Due to the inherent degeneracy of the genetic code, other DNA sequences which encode substantially the same or a functionally equivalent amino acid sequence may be produced and used to express TMP.  
       [0185] The nucleotide sequences of the present invention can be engineered using methods generally known in the art in order to alter TMP-encoding sequences for a variety of purposes including, but not limited to, modification of the cl ning, processing, and/or expression of the gene product. DNA shuffling by random fragmentation and PCR reassembly of gene fragments and synthetic oligonucleotides may be used to engineer the nucleotide sequences. For example, oligonucleotide-mediated site-directed mutagenesis may be used to introduce mutations that create new restriction sites, alter glycosylation patterns, change codon preference, product splice variants, and so forth.  
       [0186] The nucleotides of the present invention may be subjected to DNA shuffling techniques such as MOLECULARBREEDING (Maxygen, Santa Clara Calif.; described in U.S. Pat. No. 5,837,458; Chang, C.-C. et al. (1999) Nat. Biotechnol: 17:793-797; Christians, F. C. et al. (1999) Nat. Biotechnol. 17:259-264; and Crameri, A. et al. (1996) Nat. Biotechnol. 14:315-319) to alter or improve the biological properties of TMP, such as its biological or enzymatic activity or its ability to bind to other molecules or compounds. DNA shuffling is a process by which a library of gene variants is produced using PCR-mediated recombination of gene fragments. The library is then subjected to selection or screening procedures that identify those gene variants with the desired properties. These preferred variants may then be pooled and further subjected to recursive rounds of DNA shuffling and selection/screening. Thus, genetic diversity is created through “artificial” breeding and rapid molecular evolution. For example, fragments of a single gene containing random point mutations may be recombined, screened, and then reshuffled until the desired properties are optimized. Alternatively, fragments of a given gene may be recombined with fragments of homologous genes in the same gene family, either from the same or different species, thereby maximizing the genetic diversity of multiple naturally occurring genes in a directed and controllable manner.  
       [0187] In another embodiment, sequences encoding TMP may be synthesized, in whole or in part, using chemical methods well known in the art. (See, e.g., Caruthers, M. H. et al. (1980) Nucleic Acids Symp. Ser. 7:215-223; and Horn, T. et al. (1980) Nucleic Acids Symp. Ser. 7:225-232.) Alternatively, TMP itself or a fragment thereof may be synthesized using chemical methods. For example, peptide synthesis can be performed using various solution-phase or solid-phase techniques. (See, e.g., Creighton, T. (1984)  Proteins, Structures and Molecular Properties,  W H Freeman, New York N.Y., pp. 55-60; and Roberge, J. Y. et al. (1995) Science 269:202-204.) Automated synthesis may be achieved using the ABI 431A peptide synthesizer (Applied Biosystems). Additionally, the amino acid sequence of TMP, or any part thereof, may be altered during direct synthesis and/or combined with sequences from other proteins, or any part thereof, to produce a variant polypeptide or a polypeptide having a sequence of a naturally occurring polypeptide.  
       [0188] The peptide may be substantially purified by preparative high performance liquid chromatography. (See, e.g., Chiez, R. M. and F. Z. Regnier (1990) Methods Enzymol. 182:392-421.) The composition of the synthetic peptides may be confirmed by amino acid analysis or by sequencing. (See, e.g., Creighton, supra, pp. 28-53.)  
       [0189] In order to express a biologically active TMP, the nucleotide sequences encoding TMP or derivatives thereof may be inserted into an appropriate expression vector, i.e., a vector which contains the necessary elements for transcriptional and translational control of the inserted coding sequence in a suitable host. These elements include regulatory sequences, such as enhancers, constitutive and inducible promoters, and 5′ and 3′ untranslated regions in the vector and in polynucleotide sequences encoding TMP. Such elements may vary in their strength and specificity. Specific initiation signals may also be used to achieve more efficient translation of sequences encoding TMP. Such signals include the ATG initiation codon and adjacent sequences, e.g. the Kozak sequence. In cases where sequences encoding TMP and its initiation codon and upstream regulatory sequences are inserted into the appropriate expression vector, no additional transcriptional or translational control signals may be needed. However, in cases where only coding sequence, or a fragment thereof, is inserted, exogenous translational control signals including an in-frame ATG initiation codon should be provided by the vector. Exogenous translational elements and initiation codons may be of various origins, both natural and synthetic. The efficiency of expression may be enhanced by the inclusion of enhancers appropriate for the particular host cell system used. (See, e.g., Scharf, D. et al. (1994) Results Probl. Cell Differ. 20:125-162.)  
       [0190] Methods which are well known to those skilled in the art may be used to construct expression vectors containing sequences encoding TMP and appropriate transcriptional and translational control elements. These methods include in vitro recombinant DNA techniques, synthetic techniques, and in vivo genetic recombination. (See, e.g., Sambrook, J. et al. (1989)  Molecular Cloning, A Laboratory Manual,  Cold Spring Harbor Press, Plainview N.Y., ch. 4, 8, and 16-17; Ausubel, F. M. et al. (1995)  Current Protocols in Molecular Biology,  John Wiley &amp; Sons, New York N.Y., ch. 9, 13, and 16.)  
       [0191] A variety of expression vector/host systems may be utilized to contain and express sequences encoding TMP. These include, but are not limited to, microorganisms such as bacteria transformed with recombinant bacteriophage, plasmid, or cosmid DNA expression vectors; yeast transformed with yeast expression vectors; insect cell systems infected with viral expression vectors (e.g., baculovirus); plant cell systems transformed with viral expression vectors (e.g., cauliflower mosaic virus, CaMV, or tobacco mosaic virus, TMV) or with bacterial expression vectors (e.g., Ti or pBR322 plasmids); or animal cell systems. (See, e.g., Sambrook, supra; Ausubel, supra; Van Heeke, G. and S. M. Schuster (1989) J. Biol. Chem. 264:5503-5509; Engelhard, E. K. et al. (1994) Proc. Natl. Acad. Sci. USA 91:3224-3227; Sandig, V. et al. (1996) Hum. Gene Ther. 7:1937-1945; Takamatsu, N. (1987) EMBO J. 6:307-311;  The McGraw Hill Yearbook of Science and Technology  (1992) McGraw Hill, New York N.Y., pp. 191-196; Logan, J. and T. Shenk (1984) Proc. Natl. Acad. Sci. USA 81:3655-3659; and Harrington, J. J. et al. (1997) Nat. Genet. 15:345-355.) Expression vectors derived from retroviruses, adenoviruses, or herpes or vaccinia viruses, or from various bacterial plasmids, may be used for delivery of nucleotide sequences to the targeted organ, tissue, or cell population. (See, e.g., Di Nicola, M. et al. (1998) Cancer Gen. Ther. 5(6):350-356; Yu, M. et al. (1993) Pr c. Natl. Acad. Sci. USA 90(13):6340-6344; Buller, R. M. et al. (1985) Nature 317(6040):813-815; McGregor, D. P. et al. (1994) Mol. Immunol. 31(3):219-226; and Verma, I. M. and N. Somia (1997) Nature 389:239-242.) The invention is not limited by the host cell employed.  
       [0192] In bacterial systems, a number of cloning and expression vectors may be selected depending upon the use intended for polynucleotide sequences encoding TMP. For example, routine cloning, subcloning, and propagation of polynucleotide sequences encoding TMP can be achieved using a multifunctional  E. coli  vector such as PBLUESCRIPT (Stratagene, La Jolla Calif.) or PSPORT1 plasmid (Life Technologies). Ligation of sequences encoding TMP into the vector&#39;s multiple cloning site disrupts the lacZ gene, allowing a colorimetric screening procedure for identification of transformed bacteria containing recombinant molecules. In addition, these vectors may be useful for in vitro transcription, dideoxy sequencing, single strand rescue with helper phage, and creation of nested deletions in the cloned sequence. (See, e.g., Van Heeke, G. and S. M. Schuster (1989) J. Biol. Chem 264:5503-5509.) When large quantities of TMP are needed, e.g. for the production of antibodies, vectors which direct high level expression of TMP may be used. For example, vectors containing the strong, inducible SP6 or T7 bacteriophage promoter may be used.  
       [0193] Yeast expression systems may be used for production of TMP. A number of vectors containing constitutive or inducible promoters, such as alpha factor, alcohol oxidase, and PGH promoters, may be used in the yeast  Saccharomyces cerevisiae  or  Pichia pastoris.  In addition, such vectors direct either the secretion or intracellular retention of expressed proteins and enable integration of foreign sequences into the host genome for stable propagation (See, e.g., Ausubel, 1995, supra; Bitter, G. A. et al. (1987) Methods Enzymol. 153:516-544; and Scorer, C. A. et al. (1994) Bio/Technology 12:181-184.)  
       [0194] Plant systems may also be used for expression of TMP. Transcription of sequences encoding TMP may be driven by viral promoters, e.g., the 35S and 19S promoters of CaMV used alone or in combination with the omega leader sequence from TMV (Takamatsu, N. (1987) EMBO J. 6:307-311). Alternatively, plant promoters such as the small subunit of RUBISCO or heat shock promoters maybe used. (See, e.g., Coruzzi, G. et al. (1984) EMBO J. 3:1671-1680; Broglie, R. et al. (1984) Science 224:838-843; and Winter, J. et al. (1991) Results Probl. Cell Differ. 17:85-105.) These constructs can be introduced into plant cells by direct DNA transformation or pathogen-mediated transfection. (See, e.g.,  The McGraw Hill Yearbook of Science and Technology  (1992) McGraw Hill, New York N.Y., pp. 191-196.)  
       [0195] In mammalian cells, a number of viral-based expression systems may be utilized. In cases where an adenovirus is used as an expression vector, sequences encoding TMP may be ligated into an adenovirus transcription/translation complex consisting of the late promoter and tripartite leader sequence. Insertion in a non-essential E1 or E3 region of the viral genome may be used to btain infective virus which expresses TMP in host cells. (See, e.g., Logan, J. and T. Shenk (1984) Proc. Natl. Acad. Sci. USA 81:3655-3659.) In addition, transcription enhancers, such as the Rous sarcoma virus (RSV) enhancer, may be used to increase expression in mammalian host cells. SV40 or EBV-based vectors may also be used for high-level protein expression.  
       [0196] Human artificial chromosomes (HACs) may also be employed to deliver larger fragments of DNA than can be contained in and expressed from a plasmid. HACs of about 6 kb to 10 Mb are constructed and delivered via conventional delivery methods (liposomes, polycationic amino polymers, or vesicles) for therapeutic purposes. (See, e.g., Harrington, J. J. et al. (1997) Nat. Genet. 15:345-355.)  
       [0197] For long term production of recombinant proteins in mammalian systems, stable expression of TMP in cell lines is preferred. For example, sequences encoding TMP can be transformed into cell lines using expression vectors which may contain viral origins of replication and/or endogenous expression elements and a selectable marker gene on the same or on a separate vector. Following the introduction of the vector, cells may be allowed to grow for about 1 to 2 days in enriched media before being switched to selective media. The purpose of the selectable marker is to confer resistance to a selective agent, and its presence allows growth and recovery of cells which successfully express the introduced sequences. Resistant clones of stably transformed cells may be propagated using tissue culture techniques appropriate to the cell type.  
       [0198] Any number of selection systems may be used to recover transformed cell lines. These include but are not limited to, the herpes simplex virus thymidine kinase and adenine phosphoribosyltransferase genes, for use in tk -  and apr -  cells, respectively. (See, e.g., Wigler, M. et al. (1977) Cell 11:223-232; Lowry, I. et al. (1980) Cell 22:817-823.) Also, antimetabolite, antibiotic, or herbicide resistance can be used as the basis for selection. For example, dhfr confers resistance to methotrexate; neo confers resistance to the aminoglycosides neomycin and G-418; and als and pat confer resistance to chlorosulfuron and phosphinotricin acetyltransferase, respectively. (See, e.g., Wigler, M. et al. (1980) Proc. Natl. Acad. Sci. USA 7:3567-3570; Colbere-Garapin, F. et al. (1981) J. Mol. Biol. 150:1-14.) Additional selectable genes have been described, e.g., trpB and hisD, which alter cellular requirements for metabolites. (See, e.g., Hartman, S. C. and R. C. Mulligan (1988) Proc. Natl. Acad. Sci. USA 85:8047-8051.) Visible markers, e.g., anthocyanins, green fluorescent proteins (GFP; Clontech), β glucuronidase and its substrate β-glucuronide, or luciferase and its substrate luciferin may be used. These markers can be used not only to identify transformants, but also to quantify the amount of transient or stable protein expression attributable to a specific vector system. (See, e.g., Rhodes, C. A. (1995) Methods Mol. Biol. 5:121-131.)  
       [0199] Although the presence/absence of marker gene expression suggests that the gene of interest is also present, the presence and expression of the gene may need to be confirmed. For example, if the sequence encoding TMP is inserted within a marker gene sequence, transformed cells containing sequences encoding TMP can be identified by the absence of marker gene function. Alternatively, a marker gene can be placed in tandem with a sequence encoding TMP under the control of a single promoter. Expression of the marker gene in response to induction or selection usually indicates expression of the tandem gene as well.  
       [0200] In general, host cells that contain the nucleic acid sequence encoding TMP and that express TMP may be identified by a variety of procedures known to those of skill in the art. These procedures include, but are not limited to, DNA-DNA or DNA-RNA hybridizations, PCR amplification, and protein bioassay or immunoassay techniques which include membrane, solution, or chip based technologies for the detection and/or quantification of nucleic acid or protein sequences.  
       [0201] Immunological methods for detecting and measuring the expression of TMP using either specific polyclonal or monoclonal antibodies are known in the art. Examples of such techniques include enzyme-linked immunosorbent assays (ELISAs), radioimmunoassays (RIAs), and fluorescence activated cell sorting (FACS). A two-site, monoclonal-based immunoassay utilizing monoclonal antibodies reactive to two non-interfering epitopes on TMP is preferred, but a competitive binding assay may be employed. These and other assays are well known in the art. (See, e.g., Hampton, R. et al. (1990)  Serological Methods, a Laboratory Manual,  APS Press, St. Paul Minn., Sect. IV; Coligan, J. E. et al. (1997)  Current Protocols in Immunology,  Greene Pub. Associates and Wiley-Interscience, New York N.Y.; and Pound, J. D. (1998)  Immunochemical Protocols,  Humana Press, Totowa N.J.).  
       [0202] A wide variety of labels and conjugation techniques are known by those skilled in the art and may be used in various nucleic acid and amino acid assays. Means for producing labeled hybridization or PCR probes for detecting sequences related to polynucleotides encoding TMP include oligolabeling, nick translation, end-labeling, or PCR amplification using a labeled nucleotide. Alternatively, the sequences encoding TMP, or any fragments thereof, may be cloned into a vector for the production of an mRNA probe. Such vectors are known in the art, are commercially available, and may be used to synthesize RNA probes in vitro by addition of an appropriate RNA polymerase such as T7, T3, or SP6 and labeled nucleotides. These procedures may be conducted using a variety of commercially available kits, such as those provided by Amersham Pharmacia Biotech, Promega (Madison Wis.), and US Biochemical. Suitable reporter molecules or labels which may be used for ease of detection include radionuclides, enzymes, fluorescent, chemiluminescent, or chromogenic agents, as well as substrates, cofactors, inhibitors, magnetic particles, and the like.  
       [0203] Host cells transformed with nucleotide sequences encoding TMP may be cultured under conditions suitable for the expression and recovery of the protein from cell culture. The protein produced by a transformed cell may be secreted or retained intracellularly depending on the sequence and/or the vector used. As will be understood by those of skill in the art, expression vectors containing polynucleotides which encode TMP may be designed to contain signal sequences which direct secretion of TMP through a prokaryotic or eukaryotic cell membrane.  
       [0204] In addition, a host cell strain may be chosen for its ability to modulate expression of the inserted sequences or to process the expressed protein in the desired fashion. Such modifications of the polypeptide include, but are not limited to, acetylation, carboxylation, glycosylation, phosphorylation, lipidation, and acylation. Post-translational processing which cleaves a “prepro” or “pro” form of the protein may also be used to specify protein targeting, folding, and/or activity. Different host cells which have specific cellular machinery and characteristic mechanisms for post-translational activities (e.g., CHO, HeLa, MDCK, HEK293, and WI38) are available from the American Type Culture Collection (ATCC, Manassas Va.) and may be chosen to ensure the correct modification and processing of the foreign protein.  
       [0205] In another embodiment of the invention, natural, modified, or recombinant nucleic acid sequences encoding TMP may be ligated to a heterologous sequence resulting in translation of a fusion protein in any of the aforementioned host systems. For example, a chimeric TMP protein containing a heterologous moiety that can be recognized by a commercially available antibody may facilitate the screening of peptide libraries for inhibitors of TMP activity. Heterologous protein and peptide moieties may also facilitate purification of fusion proteins using commercially available affinity matrices. Such moieties include, but are not limited to, glutathione S-transferase (GST), maltose binding protein (MBP), thioredoxin (Trx), calmodulin binding peptide (CBP), 6-His, FLAG, c-myc, and hemagglutinin (HA). GST, MBP, Trx, CBP, and 6-His enable purification of their cognate fusion proteins on immobilized glutathione, maltose, phenylarsine oxide, calmodulin, and metal-chelate resins, respectively. FLAG, c-myc, and hemagglutinin (HA) enable immunoaffinity purification of fusion proteins using commercially available monoclonal and polyclonal antibodies that specifically recognize these epitope tags. A fusion protein may also be engineered to contain a proteolytic cleavage site located between the TMP encoding sequence and the heterologous protein sequence, so that TMP may be cleaved away from the heterologous moiety following purification. Methods for fusion protein expression and purification are discussed in Ausubel (1995, supra, ch. 10). A variety of commercially available kits may also be used to facilitate expression and purification of fusion proteins.  
       [0206] In a further embodiment of the invention, synthesis of radiolabeled TMP may be achieved in vitro using the TNT rabbit reticulocyte lysate or wheat germ extract system (Promega). These systems couple transcription and translation of protein-coding sequences operably associated with the T7, T3, or SP6 promoters. Translation takes place in the presence of a radiolabeled amino acid precursor, for example,  35 S-methionine.  
       [0207] TMP of the present invention or fragments thereof may be used to screen for compounds that specifically bind to TMP. At least one and up to a plurality of test compounds may be screened for specific binding to TMP. Examples of test compounds include antibodies, ligonucleotides, proteins (e.g., receptors), or small molecules.  
       [0208] In one embodiment, the compound thus identified is closely related to the natural ligand of TMP, e.g., a ligand or fragment thereof, a natural substrate, a structural or functional mimetic, or a natural binding partner. (See, e.g., Coligan, J. E. et al. (1991)  Current Protocols in Immunology  1(2): Chapter 5.) Similarly, the compound can be closely related to the natural receptor to which TMP binds, or to at least a fragment of the receptor, e.g., the ligand binding site. In either case, the compound can be rationally designed using known techniques. In one embodiment, screening for these compounds involves producing appropriate cells which express TMP, either as a secreted protein or on the cell membrane. Preferred cells include cells from mammals, yeast, Drosophila, or  E. coli.  Cells expressing TMP or cell membranes fractions which contain TMP are then contacted with a test compound and binding, stimulation, or inhibition of activity of either TMP or the compound is analyzed.  
       [0209] An assay may simply test binding of a test compound to the polypeptide, wherein binding is detected by a fluorophore, radioisotope, enzyme conjugate, or other detectable label. For example, the assay may comprise the steps of combining at least one test compound with TMP, either in solution or affixed to a solid support, and detecting the binding of TMP to the compound. Alternatively, the assay may detect or measure binding of a test compound in the presence of a labeled competitor. Additionally, the assay may be carried out using cell-free preparations, chemical libraries, or natural product mixtures, and the test compound(s) may be free in solution or affixed to a solid support.  
       [0210] TMP of the present invention or fragments thereof may be used to screen for compounds that modulate the activity of TMP. Such compounds may include agonists, antagonists, or partial or inverse agonists. In one embodiment, an assay is performed under conditions permissive for TMP activity, wherein TMP is combined with at least one test compound, and the activity of TMP in the presence of a test compound is compared with the activity of TMP in the absence of the test compound. A change in the activity of TMP in the presence of the test compound is indicative of a compound that modulates the activity of TMP. Alternatively, a test compound is combined with an in vitro or cell-free system comprising TMP under conditions suitable for TMP activity, and the assay is performed. In either of these assays, a test compound which modulates the activity of TMP may do so indirectly and need not come in direct contact with the test compound. At least one and up to a plurality of test compounds may be screened.  
       [0211] In another embodiment, polynucleotides encoding TMP or their mammalian homologs may be “knocked out” in an animal model system using homologous recombination in embryonic stem (ES) cells. Such techniques are well known in the art and are useful for the generation of animal models of human disease. (See, e.g., U.S. Pat. No. 5,175,383 and U.S. Pat. No. 5,767,337.) For example, mouse ES cells, such as the mouse 129/SvJ cell line, are derived from the early mouse embryo and grown in culture. The ES cells are transformed with a vector containing the gene of interest disrupted by a marker gene, e.g., the neomycin phosphotransferase gene (neo; Capecchi, M. R. (1989) Science 244:1288-1292). The vector integrates into the corresponding region of the host genome by homologous recombination. Alternatively, homologous recombination takes place using the Cre-loxP system to knockout a gene of interest in a tissue- or developmental stage-specific manner (Marth, J. D. (1996) Clin. Invest. 97:1999-2002; Wagner, K. U. et al. (1997) Nucleic Acids Res. 25:4323-4330). Transformed ES cells are identified and microinjected into mouse cell blastocysts such as those from the C57BL/6 mouse strain. The blastocysts are surgically transferred to pseudopregnant dams, and the resulting chimeric progeny are genotyped and bred to produce heterozygous or homozygous strains. Transgenic animals thus generated may be tested with potential therapeutic or toxic agents.  
       [0212] Polynucleotides encoding TMP may also be manipulated in vitro in ES cells derived from human blastocysts. Human ES cells have the potential to differentiate into at least eight separate cell lineages including endoderm, mesoderm, and ectodermal cell types. These cell lineages differentiate into, for example, neural cells, hematopoietic lineages, and cardiomyocytes (Thomson, J. A. et al. (1998) Science 282:1145-1147).  
       [0213] Polynucleotides encoding TMP can also be used to create “knockin” humanized animals (pigs) or transgenic animals (mice or rats) to model human disease. With knockin technology, a region of a polynucleotide encoding TMP is injected into animal ES cells, and the injected sequence integrates into the animal cell genome. Transformed cells are injected into blastulae, and the blastulae are implanted as described above. Transgenic progeny or inbred lines are studies and treated with potential pharmaceutical agent to obtain information on treatment of a human disease. Alternatively, a mammal inbred to overexpress TMP, e.g., by secreting TMP in its milk, may also serve as a convenient source of that protein (Janne, J. et al. (1998) Biotechnol. Annu. Rev. 4:55-74).  
       THERAPEUTICS  
       [0214] Chemical and structural similarity, e.g., in the context of sequences and motifs, exists between regions of TMP and transmembrane proteins. In addition, the expression of TMP is closely associated with brain, prostate, smooth muscle, cardiovascular, pituitary, gastrointestinal, lung, pancreatic, and small intestine tissues. Therefore, TMP appears to play a role in reproductive, developmental, cardiovascular, neurological, gastrointestinal, lipid metabolism, cell proliferative, and autoimmune/inflammatory disorders. In the treatment of disorders associated with increased TMP expression or activity, it is desirable to decrease the expression or activity of TMP. In the treatment of disorders associated with decreased TMP expression or activity, it is desirable to increase the expression or activity of TMP.  
       [0215] Therefore, in one emb diment, TMP or a fragment or derivative thereof may be administered to a subject to treat or prevent a disorder associated with decreased expression or activity of TMP. Examples of such disorders include, but are not limited to, a reproductive disorder such as a disorder of prolactin production, infertility, including tubal disease, ovulatory defects, endometriosis, a disruption of the estrous cycle, a disruption of the menstrual cycle, polycystic ovary syndrome, ovarian hyperstimulation syndrome, an endometrial or ovarian tumor, a uterine fibroid, autoimmune disorders, ectopic pregnancy, teratogenesis, cancer of the breast, fibrocystic breast disease, galacatorrhea, a disruption of spermatogenesis, abnormal sperm physiology, cancer of the testis, cancer of the prostate, benign prostatic hyperplasia, prostatitis, Peyronie&#39;s disease, impotence, carcinoma of the male breast, gynecomastia, hypergonadotropic and hypogonadotropic hypogonadism, pseudohermaphroditism, azoospermia, premature ovarian failure, acrosin deficiency, delayed puberty, retrograde ejaculation and anejaculation, haemangioblastomas, cystsphaeochromocytomas, paraganglioma, cystadenomas of the epididymis, and endolymphatic sac tumours; a developmental disorder such as renal tubular acidosis, anemia, Cushing&#39;s syndrome, achondroplastic dwarfism, Duchenne and Becker muscular dystrophy, epilepsy, gonadal dysgenesis, WAGR syndrome (Wilms&#39; tumor, aniridia, genitourinary abnormalities, and mental retardation), Smith-Magenis syndrome, myelodysplastic syndrome, hereditary mucoepithelial dysplasia, hereditary keratodermas, hereditary neuropathies such as Charcot-Marie-Tooth disease and neurofibromatosis, hypothyroidism, hydrocephalus, seizure disorders such as Syndenham&#39;s chorea and cerebral palsy, spina bifida, anencephaly, craniorachischisis, congenital glaucoma, cataract, and sensorineural hearing loss; a cardiovascular disorder such as arteriovenous fistula, atherosclerosis, hypertension, vasculitis, Raynaud&#39;s disease, aneurysms, arterial dissections, varicose veins, thrombophlebitis and phlebothrombosis, vascular tumors, and complications of thrombolysis, balloon angioplasty, vascular replacement, coronary artery bypass graft surgery, congestive heart failure, ischemic heart disease, angina pectoris, myocardial infarction, hypertensive heart disease, degenerative valvular heart disease, calcific aortic valve stenosis, congenitally bicuspid aortic valve, mitral annular calcification, mitral valve prolapse, rheumatic fever and rheumatic heart disease, infective endocarditis, nonbacterial thrombotic endocarditis, endocarditis of systemic lupus erythematosus, carcinoid heart disease, cardiomyopathy, myocarditis, pericarditis, neoplastic heart disease, congenital heart disease, complications of cardiac transplantation, congenital lung anomalies, atelectasis, pulmonary congestion and edema, pulmonary embolism, pulmonary hemorrhage, pulmonary infarction, pulmonary hypertension, vascular sclerosis, obstructive pulmonary disease, restrictive pulmonary disease, chronic obstructive pulmonary disease, emphysema, chronic bronchitis, bronchial asthma, bronchiectasis, bacterial pneumonia, viral and mycoplasmal pneumonia, lung abscess, pulmonary tuberculosis, diffuse interstitial diseases, pneumoconioses, sarcoidosis, idiopathic pulmonary fibrosis, desquamative interstitial pneumonitis, hypersensitivity pneumonitis, pulmonary eosinophilia bronchiolitis obliterans-organizing pneumonia, diffuse pulmonary hemorrhage syndromes, Goodpasture&#39;s syndromes, idiopathic pulmonary hemosiderosis, pulmonary involvement in collagen-vascular disorders, pulmonary alveolar proteinosis, lung tumors, inflammatory and noninflammatory pleural effusions, pneumothorax, pleural tumors, drug-induced lung disease, radiation-induced lung disease, and complications of lung transplantation; a neurological disorders such as epilepsy, ischemic cerebrovascular disease, stroke, cerebral neoplasms, Alzheimer&#39;s disease, Pick&#39;s disease, Huntington&#39;s disease, dementia, Parkinson&#39;s disease and other extrapyramidal disorders, amyotrophic lateral sclerosis and other motor neuron disorders, progressive neural muscular atrophy, retinitis pigmentosa, hereditary ataxias, multiple sclerosis and other demyelinating diseases, bacterial and viral meningitis, brain abscess, subdural empyema, epidural abscess, suppurative intracranial thrombophlebitis, myelitis and radiculitis, viral central nervous system disease, prion diseases including kuru, Creutzfeldt-Jakob disease, and Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, nutritional and metabolic diseases of the nervous system, neurofibromatosis, tuberous sclerosis, cerebelloretinal hemangioblastomatosis, encephalotrigeminal syndrome, mental retardation and other developmental disorders of the central nervous system including Down syndrome, cerebral palsy, neuroskeletal disorders, autonomic nervous system disorders, cranial nerve disorders, spinal cord diseases, muscular dystrophy and other neuromuscular disorders, peripheral nervous system disorders, dermatomyositis and polymyositis, inherited, metabolic, endocrine, and toxic myopathies, myasthenia gravis, periodic paralysis, mental disorders including mood, anxiety, and schizophrenic disorders, seasonal affective disorder (SAD), akathesia, amnesia, catatonia, diabetic neuropathy, tardive dyskinesia, dystonias, paranoid psychoses, postherpetic neuralgia, Tourette&#39;s disorder, progressive supranuclear palsy, corticobasal degeneration, and familial frontotemporal dementia; a gastrointestinal disorder such as dysphagia, peptic esophagitis, esophageal spasm, esophageal stricture, esophageal carcinoma, dyspepsia, indigestion, gastritis, gastric carcinoma, anorexia, nausea, emesis, gastroparesis, antral or pyloric edema, abdominal angina, pyrosis, gastroenteritis, intestinal obstruction, infections of the intestinal tract, peptic ulcer, cholelithiasis, cholecystitis, cholestasis, pancreatitis, pancreatic carcinoma, biliary tract disease, hepatitis, hyperbilirubinemia, cirrhosis, passive congestion of the liver, hepatoma, infectious colitis, ulcerative colitis, ulcerative proctitis, Crohn&#39;s disease, Whipple&#39;s disease, Mallory-Weiss syndrome, colonic carcinoma, colonic obstruction, irritable bowel syndrome, short bowel syndrome, diarrhea, constipation, gastrointestinal hemorrhage, acquired immunodeficiency syndrome (AIDS) enteropathy, jaundice, hepatic encephalopathy, hepatorenal syndrome, hepatic steatosis, hemochromatosis, Wilson&#39;s disease, alpha 1 -antitrypsin deficiency, Reye&#39;s syndrome, primary sclerosing cholangitis, liver infarction, portal vein obstruction and thrombosis, centrilobular necrosis, peliosis hepatis, hepatic vein thrombosis, veno-occlusive disease, preeclampsia, eclampsia, acute fatty liver of pregnancy, intrahepatic cholestasis of pregnancy, and hepatic tumors including nodular hyperplasias, adenomas, and carcinomas; a lipid metabolism disorder such as fatty liver, cholestasis, primary biliary cirrhosis, carnitine deficiency, carnitine palmitoyltransferase deficiency, myoadenylate deaminase deficiency, hypertriglyceridemia, lipid storage disorders such Fabry&#39;s disease, Gaucher&#39;s disease, Niemann-Pick&#39;s disease, metachromatic leukodystrophy, adrenoleukodystrophy, GM 2  gangliosidosis, and ceroid lipofuscinosis, abetalipoproteinemia, Tangier disease, hyperlipoproteinemia, diabetes mellitus, lipodystrophy, lipomatoses, acute panniculitis, disseminated fat necrosis, adiposis dolorosa, lipoid adrenal hyperplasia, minimal change disease, lipomas, atherosclerosis, hypercholesterolemia, hypercholesterolemia with hypertriglyceridemia, primary hypoalphalipoproteinemia, hypothyroidism, renal disease, liver disease, lecithin:cholesterol acyltransferase deficiency, cerebrotendinous xanthomatosis, sitosterolemia, hypocholesterolemia, Tay-Sachs disease, Sandhoff&#39;s disease, hyperlipidemia, hyperlipemia, lipid myopathies, and obesity; a cell proliferative disorder such as actinic keratosis, arteriosclerosis, atherosclerosis, bursitis, cirrhosis, hepatitis, mixed connective tissue disease (MCTD), myelofibrosis, paroxysmal nocturnal hemoglobinuria, polycythemia vera, psoriasis, primary thrombocythemia, and cancers including adenocarcinoma, leukemia, lymphoma, melanoma, myeloma, sarcoma, teratocarcinoma, and, in particular, cancer of the adrenal gland, bladder, bone, bone marrow, brain, breast, cervix, gall bladder, ganglia, gastrointestinal tract, heart, kidney, liver, lung, muscle, ovary, pancreas, parathyroid, penis, prostate, salivary glands, skin, spleen, testis, thymus, thyroid, and uterus; and an autoimmune/inflammatory disorder such as acquired immunodeficiency syndrome (AIDS), Addison&#39;s disease, adult respiratory distress syndrome, ankylosing spondylitis, amyloidosis, anemia, asthma, atherosclerosis, autoimmune hemolytic anemia, autoimmune thyroiditis, autoimmune polyenodocrinopathy-candidiasis-ectodermal dystrophy (APECED), bronchitis, cholecystitis, contact dermatitis, Crohn&#39;s disease, atopic dermatitis, dermatomyositis, diabetes mellitus, emphysema, episodic lymphopenia with lymphocytotoxins, erythroblastosis fetalis, erythema nodosum, atrophic gastritis, glomerulonephritis, Goodpasture&#39;s syndrome, gout, Graves&#39; disease, Hashimoto&#39;s thyroiditis, hypereosinophilia, irritable bowel syndrome, multiple sclerosis, myasthenia gravis, myocardial or pericardial inflammation, osteoarthritis, osteoporosis, pancreatitis, polymyositis, psoriasis, Reiter&#39;s syndrome, rheumatoid arthritis, scleroderma, Sjögren&#39;s syndrome, systemic anaphylaxis, systemic lupus erythematosus, systemic sclerosis, thrombocytopenic purpura, ulcerative colitis, uveitis, Werner syndrome, complications of cancer, hemodialysis, and extracorporeal circulation, viral, bacterial, fungal, parasitic, protozoal, and helminthic infections, and trauma.  
       [0216] In another embodiment, a vector capable of expressing TMP or a fragment or derivative thereof may be administered to a subject to treat or prevent a disorder associated with decreased expression or activity of TMP including, but not limited to, those described above.  
       [0217] In a further embodiment, a composition comprising a substantially purified TMP in conjunction with a suitable pharmaceutical carrier may be administered to a subject to treat or prevent a disorder associated with decreased expression or activity of TMP including, but not limited to, those provided above.  
       [0218] In still another embodiment, an agonist which modulates the activity of TMP may be administered to a subject to treat or prevent a disorder associated with decreased expression or activity of TMP including, but not limited to, those listed above.  
       [0219] In a further embodiment, an antagonist of TMP may be administered to a subject to treat or prevent a disorder associated with increased expression or activity of TMP. Examples of such disorders include, but are not limited to, those reproductive, developmental, cardiovascular, neurological, gastrointestinal, lipid metabolism, cell proliferative, and autoimmune/inflammatory disorders described above. In one aspect, an antibody which specifically binds TMP may be used directly as an antagonist or indirectly as a targeting or delivery mechanism for bringing a pharmaceutical agent to cells or tissues which express TMP.  
       [0220] In an additional embodiment, a vector expressing the complement of the polynucleotide encoding the TMP may be administered to a subject to treat or prevent a disorder associated with increased expression or activity of TMP including, but not limited to, those described above.  
       [0221] In other embodiments, any of the proteins, antagonists, antibodies, agonists, complementary sequences, or vectors of the invention may be administered in combination with other appropriate therapeutic agents. Selection of the appropriate agents for use in combination therapy may be made by one or ordinary skill in the art, according to conventional pharmaceutical principles. The combination of therapeutic agents may act synergistically to effect the treatment or prevention of the various disorders described above. Using this approach, one may be able to achieve therapeutic efficacy with lower dosages of each agent, thus reducing the potential for adverse side effects.  
       [0222] An antagonist of TMP may be produced using methods which are generally known in the art. In particular, purified TMP may be used to produce antibodies or to screen libraries of pharmaceutical agents to identify those which specifically bind TMP. Antibodies to TMP may also be generated using methods that are well known in the art. Such antibodies may include, but are not limited to, polyclonal, monoclonal, chimeric, and single chain antibodies, Fab fragments, and fragments produced by a Fab expression library. Neutralizing antibodies (i.e., those which inhibit dimer formation) are generally preferred for therapeutic use.  
       [0223] For the production of antibodies, various hosts including goats, rabbits, rats, mice, humans, and others may be immunized by injection with TMP or with any fragment or oligopeptide thereof which has immunogenic properties. Depending on the host species, various adjuvants may be used to increase immunological response. Such adjuvants include, but are not limited to, Freund&#39;s, mineral gels such as aluminum hydroxide, and surface active substances such as lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, KLH, and dinitrophenol. Among adjuvants used in humans, BCG (bacilli Clamette-Guerin) and  Corynebacterium parvum  are especially preferable.  
       [0224] It is preferred that the oligopeptides, peptides, or fragments used to induce antibodies to TMP have an amino acid sequence consisting of at least about 5 amino acids, and generally will consist of at least about 10 amino acids. It is also preferable that these oligopeptides, peptides, or fragments are identical to a portion of the amino acid sequence of the natural protein. Short stretches of TMP amino acids may be fused with those of another protein, such as KLH, and antibodies to the chimeric molecule may be produced.  
       [0225] Monoclonal antibodies to TMP may be prepared using any technique which provides for the production of antibody molecules by continuous cell lines in culture. These include, but are not limited to, the hybridoma technique, the human B-cell hybridoma technique, and the EBV-hybridoma technique. (See, e.g., Kohler, G. et al. (1975) Nature 256:495-497; Kozbor, D. et al. (1985) J. Immunol. Methods 81:31-42; Cote, R. J. et al. (1983) Proc. Natl. Acad. Sci. USA 80:2026-2030; and Cole, S. P. et al. (1984) Mol. Cell Biol. 62:109-120.)  
       [0226] In addition, techniques developed for the production of “chimeric antibodies,” such as the splicing of mouse antibody genes to human antibody genes to obtain a molecule with appropriate antigen specificity and biological activity, can be used. (See, e.g., Morrison, S. L. et al. (1984) Proc. Natl. Acad. Sci. USA 81:6851-6855; Neuberger, M. S. et al. (1984) Nature 312:604-608; and Takeda, S. et al. (1985) Nature 314:452-454.) Alternatively, techniques described for the production of single chain antibodies may be adapted, using methods known in the art, to produce TMP-specific single chain antibodies. Antibodies with related specificity, but of distinct idiotypic composition, may be generated by chain shuffling from random combinatorial immunoglobulin libraries. (See, e.g., Burton, D. R. (1991) Proc. Natl. Acad. Sci. USA 88:10134-10137.)  
       [0227] Antibodies may also be produced by inducing in vivo production in the lymphocyte population or by screening immunoglobulin libraries or panels of highly specific binding reagents as disclosed in the literature. (See, e.g., Orlandi, R. et al. (1989) Proc. Natl. Acad. Sci. USA 86:3833-3837; Winter, G. et al. (1991) Nature 349:293-299.)  
       [0228] Antibody fragments which contain specific binding sites for TMP may also be generated. For example, such fragments include, but are not limited to, F(ab′) 2  fragments produced by pepsin digestion of the antibody molecule and Fab fragments generated by reducing the disulfide bridges of the F(ab′)2 fragments. Alternatively, Fab expression libraries may be constructed to allow rapid and easy identification of monoclonal Fab fragments with the desired specificity. (See, e.g., Huse, W. D. et al. (1989) Science 246:1275-1281.)  
       [0229] Various immunoassays may be used for screening to identify antibodies having the desired specificity. Numerous protocols for competitive binding or immunoradiometric assays using either polyclonal or monoclonal antibodies with established specificities are well known in the art. Such immunoassays typically involve the measurement of complex formation between TMP and its specific antibody. A two-site, monoclonal-based immunoassay utilizing monoclonal antibodies reactive to two non-interfering TMP epitopes is generally used, but a competitive binding assay may also be employed (Pound, supra).  
       [0230] Various methods such as Scatchard analysis in conjunction with radioimmunoassay techniques ,ay be used to assess the affinity of antibodies for TMP. Affinity is expressed as an association constant, K a , which is defined as the molar concentration of TMP-antibody complex divided by the molar concentrations of free antigen and free antibody under equilibrium conditions. The K a  determined for a preparation of polyclonal antibodies, which are heterogeneous in their affinities for multiple TMP epitopes, represents the average affinity, or avidity, of the antibodies for TMP. The K a  determined for a preparation of monoclonal antibodies, which are monospecific for a particular TMP epitope, represents a true measure of affinity. High-affinity antibody preparations with K a  ranging from about 10 9  to 10 12  L/mole are preferred for use in immunoassays in which the TMP-antibody complex must withstand rigorous manipulations. Low-affinity antibody preparations with K a  ranging from about 10 6  to 10 7  L/mole are preferred for use in immunopurification and similar procedures which ultimately require dissociation of TMP, preferably in active form, from the antibody (Catty, D. (1988)  Antibodies, Volume I: A Practical Approach,  IRL Press, Washington, D.C.; Liddell, J. E. and A. Cryer (1991)  A Practical Guide to Monoclonal Antibodies,  John Wiley &amp; Sons, New York N.Y.).  
       [0231] The titer and avidity of polyclonal antibody preparations may be further evaluated to determine the quality and suitability of such preparations for certain downstream applications. For example, a polyclonal antibody preparation containing at least 1-2 mg specific antibody/ml, preferably 5-10 mg specific antibody/ml, is generally employed in procedures requiring precipitation of TMP-antibody complexes. Procedures for evaluating antibody specificity, titer, and avidity, and guidelines for antibody quality and usage in various applications, are generally available. (See, e.g., Catty, supra, and Coligan et al. supra.)  
       [0232] In another embodiment of the invention, the polynucleotides encoding TMP, or any fragment or complement thereof, may be used for therapeutic purposes. In one aspect, modifications of gene expression can be achieved by designing complementary sequences or antisense molecules (DNA, RNA, PNA, or modified oligonucleotides) to the coding or regulatory regions of the gene encoding TMP. Such technology is well known in the art, and antisense oligonucleotides or larger fragments can be designed from various locations along the coding or control regions of sequences encoding TMP. (See, e.g., Agrawal, S., ed. (1996)  Antisense Therapeutics,  Humana Press, Totawa N.J.)  
       [0233] In therapeutic use, any gene delivery system suitable for introduction of the antisense sequences into appropriate target cells can be used. Antisense sequences can be delivered intracellularly in the form of an expression plasmid which, upon transcription, produces a sequence complementary to at least a portion of the cellular sequence encoding the target protein. (See, e.g., Slater, J. E. et al. (1998) J. Allergy Clin. Immunol. 102(3):469-475; and Scanlon, K. J. et al. (1995) 9(13):1288-1296.) Antisense sequences can also be introduced intracellularly through the use of viral vectors, such as retrovirus and adeno-associated virus vectors. (See, e.g., Miller, A. D. (1990) Blood 76:271; Ausubel, supra; Uckert, W. and W. Walther (1994) Pharmacol. Ther. 63(3):323-347.) Other gene delivery mechanisms include liposome-derived systems, artificial viral envelopes, and other systems known in the art. (See, e.g., Rossi, J. J. (1995) Br. Med. Bull. 51(1):217-225; Boado, R. J. et al. (1998) J. Pharm. Sci. 87(11):1308-1315; and Morris, M. C. et al. (1997) Nucleic Acids Res. 25(4):2730-2736.)  
       [0234] In another embodiment of the invention, polynucleotides encoding TMP may be used for somatic or germline gene therapy. Gene therapy may be performed to (i) correct a genetic deficiency (e.g., in the cases of severe combined immunodeficiency (SCID)-X1 disease characterized by X-linked inheritance (Cavazzana-Calvo, M. et al. (2000) Science 288:669-672), severe combined immunodeficiency syndrome associated with an inherited adenosine deaminase (ADA) deficiency (Blaese, R. M. et al. (1995) Science 270:475-480; Bordignon, C. et al. (1995) Science 270:470-475), cystic fibrosis (Zabner, J. et al. (1993) Cell 75:207-216; Crystal, R. G. et al. (1995) Hum. Gene Therapy 6:643-666; Crystal, R. G. et al. (1995) Hum. Gene Therapy 6:667-703), thalassamias, familial hypercholesterolemia, and hemophilia resulting from Factor VIII or Factor IX deficiencies (Crystal, R. G. (1995) Science 270:404-410; Verma, I. M. and N. Somia (1997) Nature 389:239-242)), (ii) express a conditionally lethal gene produce (e.g., in the case of cancers which result from unregulated cell proliferation), or (iii) express a protein which affords protection against intracellular parasites (e.g., against human retroviruses, such as human immunodeficiency virus (HIV) (Baltimore, D. (1988) Nature 335:395-396; Poeschla, E. et al. (1996) Proc. Natl. Acad. Sci. USA 93:11395-11399), hepatitis B or C virus (HBV, HCV); fungal parasites, such as  Candida albicans  and  Paracoccidioides brasiliensis ; and protozoan parasites such as  Plasmodium falciparum  and  Trypanosoma cruzi ). In the case where a genetic deficiency in TMP expression or regulation causes disease, the expression of TMP from an appropriate population of transduced cells may alleviate the clinical manifestations caused by the genetic deficiency.  
       [0235] In a further embodiment of the invention, diseases or disorders caused by deficiencies in TMP are treated by constructing mammalian expression vectors encoding TMP and introducing these vectors by mechanical means into TMP-deficient cells. Mechanical transfer technologies for use with cells in vivo or ex vitro include (i) direct DNA microinjection into individual cells, (ii) ballistic gold particle delivery, (iii) liposome-mediated transfection, (iv) receptor-mediated gene transfer, and (v) the use DNA transposons (Morgan, R. A. and W. F. Anderson (1993) Annu. Rev. Biochem. 62:191-217; Ivics, Z. (1997) Cell 91:501-510; Boulay, J-L. and H. Récipon (1998) Curr. Opin. Biotechnol. 9:445-450).  
       [0236] Expression vectors that may be effective for the expression of TMP include, but are not limited to, the PCDNA 3.1, EPITAG, PRCCMV2, PREP, PVAX, PCR2-TOPOTA vectors (Invitrogen, Carlsbad Calif), PCMV-SCRIPT, PCMV-TAG, PEGSH/PERV (Stratagene, La Jolla Calif.), and PTET-OFF, PTET-ON, PTRE2, PTRE2-LUC, PTK-HYG (Clontech, Palo Alto Calif.). TMP may be expressed using (i) a constitutively active promoter, (e.g., from cytomegalovirus (CMV), Rous sarcoma virus (RSV), SV40 virus, thymidine kinase (TK), or β-actin genes), (ii) an inducible promoter (e.g., the tetracycline-regulated promoter (Gossen, M. and H. Bujard (1992) Proc. Natl. Acad. Sci. USA 89:5547-5551; Gossen, M. et al. (1995) Science 268:1766-1769; Rossi, F. M. V. and H. M. Blau (1998) Curr. Opin. Biotechnol. 9:451-456), commercially available in the T-REX plasmid (Invitrogen)); the ecdysone-inducible promoter (available in the plasmids PVGRXR and PIND; Invitrogen); the FK506/rapamycin inducible promoter; or the RU486/mifepristone inducible promoter (Rossi, F. M. V. and H. M. Blau, supra)), or (iii) a tissue-specific promoter or the native promoter of the endogenous gene encoding TMP from a normal individual.  
       [0237] Commercially available liposome transformation kits (e.g., the PERFECT LIPID TRANSFECTION KIT, available from Invitrogen) allow one with ordinary skill in the art to deliver polynucleotides to target cells in culture and require minimal effort to optimize experimental parameters. In the alternative, transformation is performed using the calcium phosphate method (Graham, F. L. and A. J. Eb (1973) Virology 52:456-467), or by electroporation (Neumann, E. et al. (1982) EMBO J. 1:841-845). The introduction of DNA to primary cells requires modification of these standardized mammalian transfection protocols.  
       [0238] In another embodiment of the invention, diseases or disorders caused by genetic defects with respect to TMP expression are treated by constructing a retrovirus vector consisting of (i) the polynucleotide encoding TMP under the control of an independent promoter or the retrovirus long terminal repeat (LTR) promoter, (ii) appropriate RNA packaging signals, and (iii) a Rev-responsive element (RRE) along with additional retrovirus cis-acting RNA sequences and coding sequences required for efficient vector propagation. Retrovirus vectors (e.g., PFB and PFBNEO) are commercially available (Stratagene) and are based on published data (Riviere, I. et al. (1995) Proc. Natl. Acad. Sci. USA 92:6733-6737), incorporated by reference herein. The vector is propagated in an appropriate vector producing cell line (VPCL) that expresses an envelope gene with a tropism for receptors on the target cells or a promiscuous envelope protein such as VSVg (Armentano, D. et al. (1987) J. Virol. 61:1647-1650; Bender, M. A. et al. (1987) J. Virol. 61:1639-1646; Adam, M. A. and A. D. Miller (1988) J. Virol. 62:3802-3806; Dull, T. et al. (1998) J. Virol. 72:8463-8471; Zufferey, R. et al. (1998) J. Virol. 72:9873-9880). U.S. Pat. No. 5,910,434 to Rigg (“Method for obtaining retrovirus packaging cell lines producing high transducing efficiency retroviral supernatant”) discloses a method for obtaining retrovirus packaging cell lines and is hereby incorporated by reference. Propagation of retrovirus vectors, transduction of a population of cells (e.g., CD4 +  T-cells), and the return of transduced cells to a patient are procedures well known to persons skilled in the art of gene therapy and have been well documented (Ranga, U. et al. (1997) J. Virol. 71:7020-7029; Bauer, G. et al. (1997) Blood 89:2259-2267; Bonyhadi, M. L. (1997) J. Virol. 71:4707-4716; Ranga, U. et al. (1998) Proc. Natl. Acad. Sci. USA 95:1201-1206; Su, L. (1997) Blood 89:2283-2290).  
       [0239] In the alternative, an adenovirus-based gene therapy delivery system is used to deliver polynucleotides encoding TMP to cells which have one or more genetic abnormalities with respect to the expression of TMP. The construction and packaging of adenovirus-based vectors are well known to those with ordinary skill in the art. Replication defective adenovirus vectors have proven to be versatile for importing genes encoding immunoregulatory proteins into intact islets in the pancreas (Csete, M. E. et al. (1995) Transplantation 27:263-268). Potentially useful adenoviral vectors are described in U.S. Pat. No. 5,707,618 to Armentano (“Adenovirus vectors for gene therapy”), hereby incorporated by reference. For adenoviral vectors, see also Antinozzi, P. A. et al. (1999) Annu. Rev. Nutr. 19:511-544 and Verma, I. M. and N. Somia (1997) Nature 18:389:239-242, both incorporated by reference herein.  
       [0240] In another alternative, a herpes-based, gene therapy delivery system is used to deliver polynucleotides encoding TMP to target cells which have one or more genetic abnormalities with respect to the expression of TMP. The use of herpes simplex virus (HSV)-based vectors may be especially valuable for introducing TMP to cells of the central nervous system, for which HSV has a tropism. The construction and packaging of herpes-based vectors are well known to those with ordinary skill in the art. A replication-competent herpes simplex virus (HSV) type 1-based vector has been used to deliver a reporter gene to the eyes of primates (Liu, X. et al. (1999) Exp. Eye Res. 169:385-395). The construction of a HSV-1 virus vector has also been disclosed in detail in U.S. Pat. No. 5,804,413 to DeLuca (“Herpes simplex virus strains for gene transfer”), which is hereby incorporated by reference. U.S. Pat. No. 5,804,413 teaches the use of recombinant HSV d92 which consists of a genome containing at least one exogenous gene to be transferred to a cell under the control of the appropriate promoter for purposes including human gene therapy. Also taught by this patent are the construction and use of recombinant HSV strains deleted for ICP4, ICP27 and ICP22. For HSV vectors, see also Goins, W. F. et al. (1999) J. Virol. 73:519-532 and Xu, H. et al. (1994) Dev. Biol. 163:152-161, hereby incorporated by reference. The manipulation of cloned herpesvirus sequences, the generation of recombinant virus following the transfection of multiple plasmids containing different segments of the large herpesvirus genomes, the growth and propagation of herpesvirus, and the infection of cells with herpesvirus are techniques well known to those of ordinary skill in the art.  
       [0241] In another alternative, an alphavirus (positive, single-stranded RNA virus) vector is used to deliver polynucleotides encoding TMP to target cells. The biology of the prototypic alphavirus, Semliki Forest Virus (SFV), has been studied extensively and gene transfer vectors have been based on the SFV genome (Garoff, H. and K.-J. Li (1998) Curr. Opin. Biotechnol. 9:464-469). During alphavirus RNA replication, a subgenomic RNA is generated that normally encodes the viral capsid proteins. This subgenomic RNA replicates to higher levels than the full length genomic RNA, resulting in the overproduction of capsid proteins relative to the viral proteins with enzymatic activity (e.g., protease and polymerase). Similarly, inserting the coding sequence for TMP into the alphavirus genome in place of the capsid-coding region results in the production of a large number of TMP-coding RNAs and the synthesis of high levels of TMP in vector transduced cells. While alphavirus infection is typically associated with cell lysis within a few days, the ability to establish a persistent infection in hamster normal kidney cells (BHK-21) with a variant of Sindbis virus (SIN) indicates that the lytic replication of alphaviruses can be altered to suit the needs of the gene therapy application (Dryga, S. A. et al. (1997) Virology 228:74-83). The wide host range of alphaviruses will allow the introduction of TMP into a variety of cell types. The specific transduction of a subset of cells in a population may require the sorting of cells prior to transduction. The methods of manipulating infectious cDNA clones of alphaviruses, performing alphavirus cDNA and RNA transfections, and performing alphavirus infections, are well known to those with ordinary skill in the art.  
       [0242] Oligonucleotides derived from the transcription initiation site, e.g., between about position −10 and +10 from the start site, may also be employed to inhibit gene expression. Similarly, inhibition can be achieved using triple helix base-pairing methodology. Triple helix pairing is useful because it causes inhibition of the ability of the double helix to open sufficiently for the binding of polymerases, transcription factors, or regulatory molecules. Recent therapeutic advances using triplex DNA have been described in the literature. (See, e.g., Gee, J. E. et al. (1994) in Huber, B. E. and B. I. Carr,  Molecular and Immunologic Approaches,  Futura Publishing, Mt. Kisco N.Y., pp. 163-177.) A complementary sequence or antisense molecule may also be designed to block translation of mRNA by preventing the transcript from binding to ribosomes.  
       [0243] Ribozymes, enzymatic RNA molecules, may also be used to catalyze the specific cleavage of RNA. The mechanism of ribozyme action involves sequence-specific hybridization of the ribozyme molecule to complementary target RNA, followed by endonucleolytic cleavage. For example, engineered hammerhead motif ribozyme molecules may specifically and efficiently catalyze endonucleolytic cleavage of sequences encoding TMP.  
       [0244] Specific ribozyme cleavage sites within any potential RNA target are initially identified by scanning the target molecule for ribozyme cleavage sites, including the following sequences: GUA, GUU, and GUC. Once identified, short RNA sequences of between 15 and 20 ribonucleotides, corresponding to the region of the target gene containing the cleavage site, may be evaluated for secondary structural features which may render the oligonucleotide inoperable. The suitability of candidate targets may also be evaluated by testing accessibility to hybridization with complementary oligonucleotides using ribonuclease protection assays.  
       [0245] Complementary ribonucleic acid molecules and ribozymes of the invention may be prepared by any method known in the art for the synthesis of nucleic acid molecules. These include techniques for chemically synthesizing oligonucleotides such as solid phase phosphoramidite chemical synthesis. Alternatively, RNA molecules may be generated by in vitro and in vivo transcription of DNA sequences encoding TMP. Such DNA sequences may be incorporated into a wide variety of vectors with suitable RNA polymerase promoters such as T7 or SP6. Alternatively, these cDNA constructs that synthesize complementary RNA, constitutively or inducibly, can be introduced into cell lines, cells, or tissues.  
       [0246] RNA molecules may be modified to increase intracellular stability and half-life. Possible modifications include, but are not limited to, the addition of flanking sequences at the 5′ and/or 3′ ends of the molecule, or the use of phosphorothioate or 2′O-methyl rather than phosphodiesterase linkages within the backbone of the molecule. This concept is inherent in the production of PNAs and can be extended in all of these molecules by the inclusion of nontraditional bases such as inosine, queosine, and wybutosine, as well as acetyl-, methyl-, thio-, and similarly modified forms of adenine, cytidine, guanine, thymine, and uridine which are not as easily recognized by endogenous endonucleases.  
       [0247] An additional embodiment of the invention encompasses a method for screening for a compound which is effective in altering expression of a polynucleotide encoding TMP. Compounds which may be effective in altering expression of a specific polynucleotide may include, but are not limited to, oligonucleotides, antisense oligonucleotides, triple helix-forming oligonucleotides, transcription factors and other polypeptide transcriptional regulators, and non-macromolecular chemical entities which are capable of interacting with specific polynucleotide sequences. Effective compounds may alter polynucleotide expression by acting as either inhibitors or promoters of polynucleotide expression. Thus, in the treatment of disorders associated with increased TMP expression or activity, a compound which specifically inhibits expression of the polynucleotide encoding TMP may be therapeutically useful, and in the treatment of disorders associated with decreased TMP expression or activity, a compound which specifically promotes expression of the polynucleotide encoding TMP may be therapeutically useful.  
       [0248] At least one, and up to a plurality, of test compounds may be screened for effectiveness in altering expression of a specific polynucleotide. A test compound may be obtained by any method commonly known in the art, including chemical modification of a compound known to be effective in altering polynucleotide expression; selection from an existing, commercially-available or proprietary library of naturally-occurring or non-natural chemical compounds; rational design of a compound based on chemical and/or structural properties of the target polynucleotide; and selection from a library of chemical compounds created combinatorially or randomly. A sample comprising a polynucleotide encoding TMP is exposed to at least one test compound thus obtained. The sample may comprise, for example, an intact or permeabilized cell, or an in vitro cell-free or reconstituted biochemical system. Alterations in the expression of a polynucleotide encoding TMP are assayed by any method commonly known in the art. Typically, the expression of a specific nucleotide is detected by hybridization with a probe having a nucleotide sequence complementary to the sequence of the polynucleotide encoding TMP. The amount of hybridization may be quantified, thus forming the basis for a comparison of the expression of the polynucleotide both with and without exposure to one or more test compounds. Detection of a change in the expression of a polynucleotide exposed to a test compound indicates that the test compound is effective in altering the expression of the polynucleotide. A screen for a compound effective in altering expression of a specific polynucleotide can be carried out, for example, using a  Schizosaccharomyces pombe  gene expression system (Atkins, D. et al. (1999) U.S. Pat. No. 5,932,435; Arndt, G. M. et al. (2000) Nucleic Acids Res. 28:E15) or a human cell line such as HeLa cell (Clarke, M. L. et al. (2000) Biochem. Biophys. Res. Commun. 268:8-13). A particular embodiment of the present invention involves screening a combinatorial library of oligonucleotides (such as deoxyribonucleotides, ribonucleotides, peptide nucleic acids, and modified oligonucleotides) for antisense activity against a specific polynucleotide sequence (Bruice, T. W. et al. (1997) U.S. Pat. No. 5,686,242; Bruice, T. W. et al. (2000) U.S. Pat. No. 6,022,691).  
       [0249] Many methods for introducing vectors into cells or tissues are available and equally suitable for use in vivo, in vitro, and ex vivo. For ex vivo therapy, vectors may be introduced into stem cells taken from the patient and clonally propagated for autologous transplant back into that same patient. Delivery by transfection, by liposome injections, or by polycationic amino polymers may be achieved using methods which are well known in the art. (See, e.g., Goldman, C. K. et al. (1997) Nat. Biotechnol. 15:462-466.)  
       [0250] Any of the therapeutic methods described above may be applied to any subject in need of such therapy, including, for example, mammals such as humans, dogs, cats, cows, horses, rabbits, and monkeys.  
       [0251] An additional embodiment of the invention relates to the administration of a composition which generally comprises an active ingredient formulated with a pharmaceutically acceptable excipient. Excipients may include, for example, sugars, starches, celluloses, gums, and proteins. Various formulations are commonly known and are thoroughly discussed in the latest edition of  Remington&#39;s Pharmaceutical Sciences  (Maack Publishing, Easton Pa.). Such compositions may consist of TMP, antibodies to TMP, and mimetics, agonists, antagonists, or inhibitors of TMP.  
       [0252] The compositions utilized in this invention may be administered by any number of routes including, but not limited to, oral, intravenous, intramuscular, intra-arterial, intramedullary, intrathecal, intraventricular, pulmonary, transdermal, subcutaneous, intraperitoneal, intranasal, enteral, topical sublingual, or rectal means.  
       [0253] Compositions for pulmonary administration may be prepared in liquid or dry powder form. These compositions are generally aerosolized immediately prior to inhalation by the patient. In the case of small molecules (e.g. traditional low molecular weight organic drugs), aerosol delivery of fast-acting formulations is well-known in the art. In the case of macromolecules (e.g. larger peptides and proteins), recent developments in the field of pulmonary delivery via the alveolar region of the lung have enabled the practical delivery of drugs such as insulin to blood circulation (see, e.g., Patton, J. S. et al., U.S. Pat. No. 5,997,848). Pulmonary delivery has the advantage of administration without needle injection, and obviates the need for potentially toxic penetration enhancers.  
       [0254] Compositions suitable for use in the invention include compositions wherein the active ingredients are contained in an effective amount to achieve the intended purpose. The determination of an effective dose is well within the capability of those skilled in the art.  
       [0255] Specialized forms of compositions may be prepared for direct intracellular delivery of macromolecules comprising TMP or fragments thereof. For example, liposome preparations containing a cell-impermeable macromolecule may promote cell fusion and intracellular delivery of the macromolecule. Alternatively, TMP or a fragment thereof may be joined to a short cationic N-terminal portion from the HIV Tat-1 protein. Fusion proteins thus generated have been found to transduce into the cells of all tissues, including the brain, in a mouse model system (Schwarze, S. R. et al. (1999) Science 285:1569-1572).  
       [0256] For any compound, the therapeutically effective dose can be estimated initially either in cell culture assays, e.g., of neoplastic cells, or in animal models such as mice, rats, rabbits, dogs, monkeys, or pigs. An animal model may also be used to determine the appropriate concentration range and route of administration. Such information can then be used to determine useful doses and routes for administration in humans.  
       [0257] A therapeutically effective dose refers to that amount of active ingredient, for example TMP for fragments thereof, antibodies of TMP, and agonists, antagonists or inhibitors of TMP, which ameliorates the symptoms or condition. Therapeutic efficacy and toxicity may be determined by standard pharmaceutical procedures in cell cultures or with experimental animals, such as by calculating the ED 50  (the dose therapeutically effective in 50% of the population) or LD 50  (the dose lethal to 50% of the population) statistics. The dose ratio of toxic to therapeutic effects is the therapeutic index, which can be expressed as the LD 50 /ED 50  ratio. Compositions which exhibit large therapeutic indices are preferred. The data obtained from cell culture assays and animal studies are used to formulate a range of dosage for human use. The dosage contained in such compositions is preferably within a range of circulating concentrations that includes the ED 50  with little or no toxicity. The dosage varies within this range depending upon the dosage form employed, the sensitivity of the patient, and the route of administration.  
       [0258] The exact dosage will be determined by the practitioner, in light of factors related to the subject requiring treatment. Dosage and administration are adjusted to provide sufficient levels of the active moiety or to maintain the desired effect. Factors which may be taken into account include the severity of the disease state, the general health of the subject, the age, weight, and gender of the subject, time and frequency of administration, drug combination(s), reaction sensitivities, and response to therapy. Long-acting compositions may be administered every 3 to 4 days, every week, or biweekly depending on the half-life and clearance rate of the particular formulation.  
       [0259] Normal dosage amounts may vary from about 0.1 μg to 100,000 μg, up to a total dose of about 1 gram, depending upon the route of administration. Guidance as to particular dosages and methods of delivery is provided in the literature and generally available to practitioners in the art. Those skilled in the art will employ different formulations for nucleotides than for proteins or their inhibitors. Similarly, delivery of polynucleotides or polypeptides will be specific to particular cells, conditions, locations, etc.  
       DIAGNOSTICS  
       [0260] In another embodiment, antibodies which specifically bind TMP may be used for the diagnosis of disorders characterized by expression of TMP, or in assays to monitor patients being treated with TMP or agonists, antagonists, or inhibitors of TMP. Antibodies useful for diagnostic purposes may be prepared in the same manner as described above for therapeutics. Diagnostic assays for TMP include methods which utilize the antibody and a label to detect TMP in human body fluids or in extracts of cells or tissues. The antibodies may be used with or without modification, and may be labeled by covalent or non-covalent attachment of a reporter molecule. A wide variety of reporter molecules, several of which are described above, are known in the art and may be used.  
       [0261] A variety of protocols for measuring TMP, including ELISAs, RIAs, and FACS, are known in the art and provide a basis for diagnosing altered or abnormal levels of TMP expression. Normal or standard values for TMP expression are established by combining body fluids or cell extracts taken from normal mammalian subjects, for example, human subjects, with antibodies to TMP under conditions suitable for complex formation. The amount of standard complex formation may be quantitated by various methods, such as photometric means. Quantities of TMP expressed in subject, control, and disease samples from biopsied tissues are compared with the standard values. Deviation between standard and subject values establishes the parameters for diagnosing disease.  
       [0262] In another embodiment of the invention, the polynucleotides encoding TMP may be used for diagnostic purposes. The polynucleotides which may be used include oligonucleotide sequences, complementary RNA and DNA molecules, and PNAs. The polynucleotides may be used to detect and quantify gene expression in biopsied tissues in which expression of TMP may be correlated with disease. The diagnostic assay may be used to determine absence, presence, and excess expression of TMP, and to monitor regulation of TMP levels during therapeutic intervention.  
       [0263] In one aspect, hybridization with PCR probes which are capable of detecting polynucleotide sequences, including genomic sequences, encoding TMP or closely related molecules may be used to identify nucleic acid sequences which encode TMP. The specificity of the probe, whether it is made from a highly specific region, e.g., the 5′ regulatory region, or from a less specific region, e.g., a conserved motif, and the stringency of the hybridization or amplification will determine whether the probe identifies only naturally occurring sequences encoding TMP, allelic variants, or related sequences.  
       [0264] Probes may also be used for the detection of related sequences, and may have at least 50% sequence identity to any of the TMP encoding sequences. The hybridization probes of the subject invention may be DNA or RNA and may be derived from the sequence of SEQ ID NO:18-34 or from genomic sequences including promoters, enhancers, and introns of the TMP gene.  
       [0265] Means for producing specific hybridization probes for DNAs encoding TMP include the cloning of polynucleotide sequences encoding TMP or TMP derivatives into vectors for the production of mRNA probes. Such vectors are known in the art, are commercially available, and may be used to synthesize RNA probes in vitro by means of the addition of the appropriate RNA polymerases and the appropriate labeled nucleotides. Hybridization probes may be labeled by a variety of reporter groups, for example, by radionuclides such as  32 P or  35 S, or by enzymatic labels, such as alkaline phosphatase coupled to the probe via avidin/biotin coupling systems, and the like.  
       [0266] Polynucleotide sequences encoding TMP may be used for the diagnosis of disorders associated with expression of TMP. Examples of such disorders include, but are not limited to, a reproductive disorder such as a disorder of prolactin production, infertility, including tubal disease, ovulatory defects, endometriosis, a disruption of the estrous cycle, a disruption of the menstrual cycle, polycystic ovary syndrome, ovarian hyperstimulation syndrome, an endometrial or ovarian tumor, a uterine fibroid, autoimmune disorders, ectopic pregnancy, teratogenesis, cancer of the breast, fibrocystic breast disease, galactorrhea, a disruption of spermatogenesis, abnormal sperm physiology, cancer of the testis, cancer of the prostate, benign prostatic hyperplasia, prostatitis, Peyronie&#39;s disease, impotence, carcinoma of the male breast, gynecomastia, hypergonadotropic and hypogonadotropic hypogonadism, pseudohermaphroditism, azoospermia, premature ovarian failure, acrosin deficiency, delayed puberty, retrograde ejaculation and anejaculation, haemangioblastomas, cystsphaeochromocytomas, paraganglioma, cystadenomas of the epididymis, and endolymphatic sac tumours; a developmental disorder such as renal tubular acidosis, anemia, Cushing&#39;s syndrome, achondroplastic dwarfism, Duchenne and Becker muscular dystrophy, epilepsy, gonadal dysgenesis, WAGR syndrome (Wilms&#39; tumor, aniridia, genitourinary abnormalities, and mental retardation), Smith-Magenis syndrome, myelodysplastic syndrome, hereditary mucoepithelial dysplasia, hereditary keratodermas, hereditary neuropathies such as Charcot-Marie-Tooth disease and neurofibromatosis, hypothyroidism, hydrocephalus, seizure disorders such as Syndenham&#39;s chorea and cerebral palsy, spina bifida, anencephaly, craniorachischisis, congenital glaucoma, cataract, and sensorineural hearing loss; a cardiovascular disorder such as arteriovenous fistula, atherosclerosis, hypertension, vasculitis, Raynaud&#39;s disease, aneurysms, arterial dissections, varicose veins, thrombophlebitis and phlebothrombosis, vascular tumors, and complications of thrombolysis, balloon angioplasty, vascular replacement, coronary artery bypass graft surgery, congestive heart failure, ischemic heart disease, angina pectoris, myocardial infarction, hypertensive heart disease, degenerative valvular heart disease, calcific aortic valve stenosis, congenitally biscuspid aortic valve, mitral annular calcification, mitral valve prolapse, rheumatic fever and rheumatic heart disease, infective endocarditis, nonbacterial thrombotic endocarditis, endocarditis of systemic lupus erythematosus, carcinoid heart disease, cardiomyopathy, myocarditis, pericarditis, neoplastic heart disease, congenital heart disease, complications of cardiac transplantation, congenital lung anomalies, atelectasis, pulmonary congestion and edema, pulmonary embolism, pulmonary hemorrhage, pulmonary infarction, pulmonary hypertension, vascular sclerosis, obstructive pulmonary disease, restrictive pulmonary disease, chronic obstructive pulmonary disease, emphysema, chronic bronchitis, bronchial asthma, bronchiectasis, bacterial pneumonia, viral and mycoplasmal pneumonia, lung abscess, pulmonary tuberculosis, diffuse interstitial diseases, pneumoconioses, sarcoidosis, idiopathic pulmonary fibrosis, desquamative interstitial pneumonitis, hypersensitivity pneumonitis, pulmonary eosinophilia bronchiolitis obliternas-organizing pneumonia, diffuse pulmonary hemorrhage syndromes, Goodpasture&#39;s syndromes, idiopathic pulmonary hemosiderosis, pulmonary involvement in collagen-vascular disorders, pulmonary alveolar proteinosis, lung tumors, inflammatory and noninflammatory pleural effusions, pneumothorax, pleural tumors, drug-induced lung disease, radiation-induced lung disease, and complications of lung transplantation; a neurological disorder such as epilepsy, ischemic cerebrovascular disease, stroke, cerebral neoplasms, Alzheimer&#39;s disease, Pick&#39;s disease, Huntington&#39;s disease, dementia, Parkinson&#39;s disease and other extrapyramidal disorders, amyotrophic lateral sclerosis and other motor neuron disorders, progressive neural muscular atrophy, retinitis pigmentosa, hereditary ataxias, multiple sclerosis and other demyelinating diseases, bacterial and viral meningitis, brain abscess, subdural empyema, epidural abscess, suppurative intracranial thrombophlebitis, myelitis and radiculitis, viral central nervous system disease, prion diseases including kuru, Creutzfeldt-Jakob disease, and Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, nutritional and metabolic diseases of the nervous system, neurofibromatosis, tuberous sclerosis, cerebelloretinal hemangioblastomatosis, encephalotrigeminal syndrome, mental retardation and other developmental disorders of the central nervous system including Down syndrome, cerebral palsy, neuroskeletal disorders, autonomic nervous system disorders, cranial nerve disorders, spinal cord diseases, muscular dystrophy and other neuromuscular disorders, peripheral ner us system disorders, dermatomyositis and polymyositis, inherited, metabolic, endocrine, and toxic myopathies, myasthenia gravis, periodic paralysis, mental disorders including mood, anxiety, and schizophrenic disorders, seasonal affective disorder (SAD), akathesia, amnesia, catatonia, diabetic neuropathy, tardive dyskinesia, dystonias, paranoid psychoses, postherpetic neuralgia, Tourette&#39;s disorder, progressive supranuclear palsy, corticobasal degeneration, and familial frontotemporal dementia; a gastrointestinal disorder such as dysphagia, peptic esophagitis, esophageal spasm, esophageal stricture, esophageal carcinoma, dyspepsia, indigestion, gastritis, gastric carcinoma, anorexia, nausea, emesis, gastroparesis, antral or pyloric edema, abdominal angina, pyrosis, gastroenteritis, intestinal obstruction, infections of the intestinal tract, peptic ulcer, cholelithiasis, cholecystitis, cholestasis, pancreatitis, pancreatic carcinoma, biliary tract disease, hepatitis, hyperbilirubinemia, cirrhosis, passive congestion of the liver, hepatoma, infectious colitis, ulcerative colitis, ulcerative proctitis, Crohn&#39;s disease, Whipple&#39;s disease, Mallory-Weiss syndrome, colonic carcinoma, colonic obstruction, irritable bowel syndrome, short bowel syndrome, diarrhea, constipation, gastrointestinal hemorrhage, acquired immunodeficiency syndrome (AIDS) enteropathy, jaundice, hepatic encephalopathy, hepatorenal syndrome, hepatic steatosis, hemochromatosis, Wilson&#39;s disease, alpha 1 -antitrypsin deficiency, Reye&#39;s syndrome, primary sclerosing cholangitis, liver infarction, portal vein obstruction and thrombosis, centrilobular necrosis, peliosis hepatis, hepatic vein thrombosis, vena-occlusive disease, preeclampsia, eclampsia, acute fatty liver of pregnancy, intrahepatic cholestasis of pregnancy, and hepatic tumors including nodular hyperplasias, adenomas, and carcinomas; a lipid metabolism disorder such as fatty liver, cholestasis, primary biliary cirrhosis, carnitine deficiency, carnitine palmitoyltransferase deficiency, myoadenylate deaminase deficiency, hypertriglyceridemia, lipid storage disorders such Fabry&#39;s disease, Gaucher&#39;s disease, Niemann-Pick&#39;s disease, metachromatic leukodystrophy, adrenoleukodystrophy, GM 2  gangliosidosis, and ceroid lipofuscinosis, abetalipoproteinemia, Tangier disease, hyperlipoproteinemia, diabetes mellitus, lipodystrophy, lipomatoses, acute panniculitis, disseminated fat necrosis, adiposis dolorosa, lipoid adrenal hyperplasia, minimal change disease, lipomas, atherosclerosis, hypercholesterolemia, hypercholesterolemia with hypertriglyceridemia, primary hypoalphalipoproteinemia, hypothyroidism, renal disease, liver disease, lecithin:cholesterol acyltransferase deficiency, cerebrotendinous xanthomatosis, sitosterolemia, hypocholesterolemia, Tay-Sachs disease, Sandhoff&#39;s disease, hyperlipidemia, hyperlipemia, lipid myopathies, and obesity; a cell proliferative disorder such as actinic keratosis, arteriosclerosis, atherosclerosis, bursitis, cirrhosis, hepatitis, mixed connective tissue disease (MCTD), myelofibrosis, paroxysmal nocturnal hemoglobinuria, polycythemia vera, psoriasis, primary thrombocythemia, and cancers including adenocarcinoma, leukemia, lymphoma, melanoma, myeloma, sarcoma, teratocarcinoma, and, in particular, cancers of the adrenal gland, bladder, bone, bone marrow, brain, breast, cervix, gall bladder, ganglia, gastrointestinal tract, heart, kidney, liver, lung, muscle, ovary, pancreas, parathyroid, penis, prostate, salivary glands, skin, spleen, testis, thymus, thyroid, and uterus; and an autoimmune/inflammatory disorder such as acquired immunodeficiency syndrome (AIDS), Addison&#39;s disease, adult respiratory distress syndrome, ankylosing spondylitis, amyloidosis, anemia, asthma, atherosclerosis, autoimmune hemolytic anemia, autoimmune thyroiditis, autoimmune polyenodocrinopathy-candidiasis-ectodermal dystrophy (APECED), bronchitis, cholecystitis, contact dermatitis, Crohn&#39;s disease, atopic dermatitis, dermatomyositis, diabetes mellitus, emphysema, episodic lymphopenia with lymphocytotoxins, erythroblastosis fetalis, erythema nodosum, atrophic gastritis, glomerulonephritis, Goodpasture&#39;s syndrome, gout, Grave&#39;s disease, Hashimoto&#39;s thyroiditis, hypereosinophilia, irritable bowel syndrome, multiple sclerosis, myasthenia gravis, myocardial or pericardial inflammation, osteoarthritis, osteoporosis, pancreatitis, polymyositis, psoriasis, Reiter&#39;s syndrome, rheumatoid arthritis, scleroderma, Sjögren&#39;s syndrome, systemic anaphylaxis, systemic lupus erythematosus, systemic sclerosis, thrombocytopenic purpura, ulcerative colitis, uveitis, Werner syndrome, complications of cancer, hemodialysis, and extracorporeal circulation, viral, bacterial, fungal, parasitic, protozoal, and helminthic infections, and trauma. The polynucleotide sequences encoding TMP may be used in Southern or northern analysis, dot blot, or other membrane-based technologies; in PCR technologies, in dipstick, pin, and multiformat ELISA-like assays; and in microarrays utilizing fluids or tissues from patients to detect altered TMP expression. Such qualitative or quantitative methods are well known in the art.  
       [0267] In a particular aspect, the nucleotide sequences encoding TMP may be useful in assays that detect the presence of associated disorders, particularly those mentioned above. The nucleotide sequences encoding TMP may be labeled by standard methods and added to a fluid or tissue sample from a patient under conditions suitable for the formation of hybridization complexes. After a suitable incubation period, the sample is washed and the signal is quantified and compared with a standard value. If the amount of signal in the patient sample is significantly altered in comparison to a control sample then the presence of altered levels of nucleotide sequences encoding TMP in the sample indicates the presence of the associated disorder. Such assays may also be used to evaluate the efficacy of a particular therapeutic treatment regimen in animal studies, in clinical trials, or to monitor the treatment of an individual patient.  
       [0268] In order to provide a basis for the diagnosis of a disorder associated with expression of TMP, a normal or standard profile for expression is established. This may be accomplished by combining body fluids or cell extracts taken from normal subjects, either animal or human, with a sequence, or a fragment thereof, encoding TMP, under conditions suitable for hybridization or amplification. Standard hybridization may be quantified by comparing the values obtained from normal subjects with values from an experiment in which a known amount of a substantially purified polynucleotide is used. Standard values obtained in this manner may be compared with values obtained from samples from patients who are symptomatic for a disorder.  
       [0269] Once the presence of a disorder is established and a treatment protocol is initiated, hybridization assays may be repeated on a regular basis to determine if the level of expression in the patient begins to approximate that which is observed in the normal subject. The results obtained from successive assays may be used to show the efficacy of treatment over a period ranging from several days to months.  
       [0270] With respect to cancer, the presence of an abnormal amount of transcript (either under- or overexpressed) in biopsied tissue from an individual may indicate a predisposition for the development of the disease, or may provide a means for detecting the disease prior to the appearance of actual clinical symptoms. A more definitive diagnosis of this type may allow health professionals to employ preventative measures or aggressive treatment earlier thereby preventing the development of further progression of the cancer.  
       [0271] Additional diagnostic uses for oligonucleotides designed from the sequences encoding TMP may involve the use of PCR. These oligomers may be chemically synthesized, generated enzymatically, or produced in vitro. Oligomers will preferably contain a fragment of a polynucleotide encoding TMP, or a fragment of a polynucleotide complementary to the polynucleotide encoding TMP, and will be employed under optimized conditions for identification of a specific gene or condition. Oligomers may also be employed under less stringent conditions for detection or quantification of closely related DNA or RNA sequences.  
       [0272] In a particular aspect, oligonucleotide primers derived from the polynucleotide sequences encoding TMP may be used to detect single nucleotide polymorphisms (SNPs). SNPs are substitutions, insertions and deletions that are a frequent cause of inherited or acquired genetic disease in humans. Methods of SNP detection include, but are not limited to, single-stranded conformation polymorphism (SSCP) and fluorescent SSCP (fSSCP) methods. In SSCP, oligonucleotide primers derived from the polynucleotide sequences encoding TMP are used to amplify DNA using the polymerase chain reaction (PCR). The DNA may be derived, for example, from diseased or normal tissue, biopsy samples, bodily fluids, and the like. SNPs in the DNA cause differences in the secondary and tertiary structures of PCR products in single-stranded form, and these differences are detectable using gel electrophoresis in non-denaturing gels. In fSCCP, the oligonucleotide primers are fluorescently labeled, which allows detection of the amplimers in high-throughput equipment such as DNA sequencing machines. Additionally, sequence database analysis methods, termed in silico SNP (isSNP), are capable of identifying polymorphisms by comparing the sequence of individual overlapping DNA fragments which assemble into a common consensus sequence. These computer-based methods filter out sequence variations due to laboratory preparation of DNA and sequencing errors using statistical models and automated analyses of DNA sequence chromatograms. In the alternative, SNPs may be detected and characterized by mass spectrometry using, for example, the high throughput MASSARRAY system (Sequenom, San Diego Calif.).  
       [0273] Methods which may also be used to quantify the expression of TMP include radiolabeling or biotinylating nucleotides, coamplification of a control nucleic acid, and interpolating results from standard curves. (See, e.g., Melby, P. C. et al. (1993) J. Immunol. Methods 159:235-244; Duplaa, C. et al. (1993) Anal. Biochem. 212:229-236.) The speed of quantitation of multiple samples may be accelerated by running the assay in a high-throughput format where the oligomer or polynucleotide of interest is presented in various dilutions and a spectrophotometric or colorimetric response give rapid quantitation.  
       [0274] In further embodiments, oligonucleotides or longer fragments derived from any of the polynucleotide sequences described herein may be used as elements on a microarray. The microarray can be used in transcript imaging techniques which monitor the relative expression levels of large numbers of genes simultaneously as described below. The microarray may also be used to identify genetic variants, mutations, and polymorphisms. This information may be used to determine gene function, to understand the genetic basis of a disorder, to diagnose a disorder, a monitor progression/regression of disease as a function of gene expression , and to develop and monitor the activities of therapeutic agents in the treatment of disease. In particular, this information may be used to develop a pharmacogenomic profile of a patient in order to select the most appropriate and effective treatment regimen for that patient. For example, therapeutic agents which are highly effective and display the fewest side effects may be selected for a patient based on his/her pharmacogenomic profile.  
       [0275] In another embodiment, TMP, fragments of TMP, or antibodies specific for TMP may be used as elements on a microarray. The microarray may be used to monitor or measure protein-protein interactions, drug-target interactions, and gene expression profiles, as described above.  
       [0276] A particular embodiment relates to the use of the polynucleotides of the present invention to generate a transcript image of a tissue or cell type. A transcript image represents the global pattern of gene expression by a particular tissue or cell type. Global gene expression patterns are analyzed by quantifying the number of expressed genes and their relative abundance under given conditions and at a given time. (See Seilhamer et al., “Comparative Gene Transcript Analysis,” U.S. Pat. No. 5,840,484, expressly incorporated by reference herein.) Thus a transcript image may be generated by hybridizing the polynucleotides of the present invention or their complements to the totality of transcripts or reverse transcripts of a particular tissue or cell type. In one embodiment, the hybridization takes place in high-throughput format, wherein the polynucleotides of the present invention or their complements comprise a subset of a plurality of elements on a microarray. The resultant transcript image would provide a profile of gene activity.  
       [0277] Transcript images may be generated using transcripts isolated from tissues, cell lines, biopsies, or other biological samples. The transcript image may thus reflect gene expression in vivo, as in the case of a tissue or biopsy sample, or in vitro, as in the case of a cell line.  
       [0278] Transcript images which profile the expression of the polynucleotides of the present invention may also be used in conjunction with in vitro model systems and preclinical evaluation of pharmaceuticals, as well as toxicological testing of industrial and naturally-occurring environmental compounds. All compounds induce characteristic gene expression patterns, frequently termed molecular fingerprints or toxicant signatures, which are indicative of mechanisms of action and toxicity (Nuwaysir, E. F. et al. (1999) Mol. Carcinog. 24:153-159; Steiner, S. and N. L. Anderson (2000) Toxicol. Lett. 112-113:467-471, expressly incorporated by reference herein). If a test compound has a signature similar to that of a compound with known toxicity, it is likely to share those toxic properties. These fingerprints or signatures are most useful and refined when they contain expression information from a large number of genes and gene families. Ideally, a genome-wide measurement of expression provides the highest quality signature. Even genes whose expression is not altered by any tested compounds are important as well, as the levels of expression of these genes are used to normalize the rest of the expression data. The normalization procedure is useful for comparison of expression data after treatment with different compounds. While the assignment of gene function to elements of a toxicant signature aids in interpretation of toxicity mechanisms, knowledge of gene function is not necessary for the statistical matching of signatures which leads to prediction of toxicity. (See, for example, Press Release 00-02 from the National Institute of Environmental Health Sciences, released Feb. 29, 2000, available at http://www.niehs.nih.gov/oc/news/toxchip.htm.) Therefore, it is important and desirable in toxicological screening using toxicant signatures to include all expressed gene sequences.  
       [0279] In one embodiment, the toxicity of a test compound is assessed by treating a biological sample containing nucleic acids with the test compound. Nucleic acids that are expressed in the treated biological sample are hybridized with one or more probes specific to the polynucleotides of the present invention, so that transcript levels corresponding to the polynucleotides of the present invention may be quantified. The transcript levels in the treated biological sample are compared with levels in an untreated biological sample. Differences in the transcript levels between the two samples are indicative of a toxic response caused by the test compound in the treated sample.  
       [0280] Another particular embodiment relates to the use of the polypeptide sequences of the present invention to analyze the proteome of a tissue or cell type. The term proteome refers to the global pattern of protein expression in a particular tissue or cell type. Each protein component of a proteome can be subjected individually to further analysis. Proteome expression patterns, or profiles, are analyzed by quantifying the number of expressed proteins and their relative abundance under given conditions and at a given time. A profile of a cell&#39;s proteome may thus be generated by separating and analyzing the polypeptides of a particular tissue or cell type. In one embodiment, the separation is achieved using two-dimensional gel electrophoresis, in which proteins from a sample are separated by isoelectric focusing in the first dimension, and then according to molecular weight by sodium dodecyl sulfate slab gel electrophoresis in the second dimension (Steiner and Anderson, supra). The proteins are visualized in the gel as discrete and uniquely positioned spots, typically by staining the gel with an agent such as Coomassie Blue or silver or fluorescent stains. The optical density of each protein spot is generally proportional to the level of the protein in the sample. The optical densities of equivalently positioned protein spots from different samples, for example, from biological samples either treated or untreated with a test compound or therapeutic agent, are compared to identify any changes in protein spot density related to the treatment. The proteins in the spots are partially sequenced using, for example, standard methods employing chemical or enzymatic cleavage followed by mass spectrometry. The identity of the protein in a spot may be determined by comparing its partial sequence, preferably of at least 5 contiguous amino acid residues, to the polypeptide sequences of the present invention. In some cases, further sequence data may be obtained for definitive protein identification.  
       [0281] A proteomic profile may also be generated using antibodies specific for TMP to quantify the levels of TMP expression. In one embodiment, the antibodies are used as elements on a microarray, and protein expression levels are quantified by exposing the microarray to the sample and detecting the levels of protein bound to each array element (Lueking, A. et al. (1999) Anal. Biochem. 270:103-111; Mendoze, L. G. et al. (1999) Biotechniques 27:778-788). Detection may be performed by a variety of methods known in the art, for example, by reacting the proteins in the sample with a thiol- or amino-reactive fluorescent compound and detecting the amount of fluorescence bound at each array element.  
       [0282] Toxicant signatures at the proteome level are also useful for toxicological screening, and should be analyzed in parallel with toxicant signatures at the transcript level. There is a poor correlation between transcript and protein abundances for some proteins in some tissues (Anderson, N. L. and J. Seilhamer (1997) Electrophoresis 18:533-537), so proteome toxicant signatures may be useful in the analysis of compounds which do not significantly affect the transcript image, but which alter the proteomic profile. In addition, the analysis of transcripts in body fluids is difficult, due to rapid degradation of mRNA, so proteomic profiling may be more reliable and informative in such cases.  
       [0283] In another embodiment, the toxicity of a test compound is assessed by treating a biological sample are separated so that the amount of each protein can be quantified. The amount of each protein is compared to the amount of the c rresponding protein in an untreated biological sample. A difference in the amount of protein between the two samples is indicative of a toxic response to the test c mpound in the treated sample. Individual proteins are identified by sequencing the amino acid residues of the individual proteins and comparing these partial sequences to the polypeptides of the present invention.  
       [0284] In another embodiment, the toxicity of a test compound is assessed by treating a biological sample containing proteins with the test compound. Proteins from the biological sample are incubated with antibodies specific to the polypeptides of the present invention. The amount of protein recognized by the antibodies is quantified. The amount of protein in the treated biological sample is compared with the amount in an untreated biological sample. A difference in the amount of protein between the two samples is indicative of a toxic response to the test compound in the treated sample.  
       [0285] Microarrays may be prepared, used, and analyzed using methods known in the art. (See, e.g., Brennan, T. M. et al. (1995) U.S. Pat. No. 5,474,796; Schena, M. et al. (1996) Proc. Natl. Acad. Sci. USA 93:10614-10619; Baldeschweiler et al. (1995) PCT application WO95/251116; Shalon, D. et al. (1995) PCT application WO95/35505; Heller, R. A. et al. (1997) Proc. Natl. Acad. Sci. USA 94:2150-2155; and Heller, M. J. et al. (1997) U.S. Pat. No. 5,605,662.) Various types of microarrays are well known and thoroughly described in  DNA Microarrays: A Practical Approach,  M. Schena, ed. (1999) Oxford University Press, London, hereby expressly incorporated by reference.  
       [0286] In another embodiment of the invention, nucleic acid sequences encoding TMP may be used to generate hybridization probes useful in mapping the naturally occurring genomic sequence. Either coding or noncoding sequences may be used, and in some instances, noncoding sequences may be preferable over coding sequences. For example, conservation of a coding sequence among members of a multi-gene family may potentially cause undesired cross hybridization during chromosomal mapping. The sequences may be mapped to a particular chromosome, to a specific region of a chromosome, or to artificial chromosome constructions, e.g., human artificial chromosomes (HACs), yeast artificial chromosomes (YACs), bacterial artificial chromosomes (BACs), bacterial P1 constructions, or single chromosome cDNA libraries. (See, e.g., Harrington, J. J. et al. (1997) Nat. Genet. 15:345-355; Price, C. M. (1993) Blood Rev. 7:127-134; and Trask, B. J. (1991) Trends Genet. 7:149-154.) Once mapped, the nucleic acid sequences of the invention may be used to develop genetic linkage maps, for example, which correlate the inheritance of a disease state with the inheritance of a particular chromosome region or restriction fragment length polymorphism (RFLP). (See, for example, Lander, E. S. and D. Botstein (1986) Proc. Natl. Acad. Sci. USA 83:7353-7357.)  
       [0287] Fluorescent in situ hybridization (FISH) may be correlated with other physical and genetic map data. (See, e.g., Heinz-Ulrich, et al. (1995) in Meyers, supra, pp. 965-968.) Examples of genetic map data can be found in various scientific journals or at the Online Mendelian Inheritance in Man (OMIM) World Wide Web site. Correlation between the location of the gene encoding TMP on a physical map and a specific disorder, or a predisposition to a specific disorder, may help define the region of DNA associated with that disorder and thus may further positional cloning efforts.  
       [0288] In situ hybridization of chromosomal preparations and physical mapping techniques, such as linkage analysis using established chromosomal markers, may be used for extending genetic maps. Often the placement of a gene on the chromosome of another mammalian species, such as mouse, may reveal associated markers even if the exact chromosomal locus is not known. This information is valuable to investigators searching for disease genes using positional cloning or other gene discovery techniques. Once the gene or genes responsible for a disease or syndrome have been crudely localized by genetic linkage to a particular genomic region, e.g., ataxia-telangiectasia to 11q22-23, any sequences mapping to that area may represent associated or regulatory genes for further investigation. (See, e.g., Gatti, R. A. et al. (1988) Nature 336:577-580.) The nucleotide sequence of the instant invention may also be used to detect differences in the chromosomal location due to translocation, inversion, etc., among normal, carrier, or affected individuals.  
       [0289] In another embodiment of the invention, TMP, is catalytic or immunogenic fragments, or oligopeptides thereof can be used for screening libraries of compounds in any of a variety of drug screening techniques. The fragment employed in such screening may be free in solution, affixed to a solid support, borne on a cell surface, or located intracellularly. The formation of binding complexes between TMP and the agent being tested may be measured.  
       [0290] Another technique for drug screening provides for throughput screening of compounds having suitable binding affinity to the protein of interest. (See, e.g., Geysen, et al. (1984) PCT application WO84/03564.) In this method, large numbers of different small test compounds are synthesized on a solid substrate. The test compounds are reacted with TMP, or fragments thereof, and washed. Bound TMP is then detected by methods well known in the art. Purified TMP can also be coated directly onto plates for use in the aforementioned drug screening techniques. Alternatively, non-neutralizing antibodies can be used to capture the peptide and immobilize it on a solid support.  
       [0291] In another embodiment, one may use competitive drug screening assays in which neutralizing antibodies capable of binding TMP specifically compete with a test compound for binding TMP. In this manner, antibodies can be used to detect the presence of any peptide which shares one or more antigenic determinants with TMP.  
       [0292] In additional embodiments, the nucleotide sequences which encode TMP may be used in any molecular biology techniques that have yet to be developed, provided the new techniques rely on properties of nucleotide sequences that are currently known, including, but not limited to, such properties as the triplet genetic code and specific base pair interactions.  
       [0293] Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. The following embodiments are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.  
       [0294] The disclosure of all patents, applications, and publications mentioned above and below, including U.S. Ser. No. 60/244,017, U.S. Ser. No. 60/252,855, U.S. Ser. NO. 60/251,825, and U.S. Ser. No. 60/255,085, are hereby expressly incorporated by reference. 
     
    
    
     EXAMPLES  
     [0295] I. Construction of cDNA Libraries  
     [0296] Incyte cDNAs were derived from cDNA libraries described in the LIFESEQ GOLD database (Incyte Genomics, Palo Alto Calif.) and shown in Table 4, column 5. Some tissues were homogenized and lysed in guanidinium isothiocyanate, while other were homogenized and lysed in phenol or in a suitable mixture of denaturants, such as TRIZOL (Life Technologies), a monophasic solution of phenol and guanidine isothiocyanate. The resulting lysates were centrifuged over CsCl cushions or extracted with chloroform. RNA was precipitated from the lysates with either isopropanol or sodium acetate and ethanol, or by other routine methods.  
     [0297] Phenol extraction and precipitation of RNA were repeated as necessary to increase RNA purity. In some cases, RNA was treated with DNase. For most libraries, poly(A)+ RNA was isolated using oligo d(T)-coupled paramagnetic particles (Promega), OLIGOTEX latex particles (QIAGEN, Chatsworth Calif.), or an OLIGOTEX mRNA purification kit (QIAGEN). Alternatively, RNA was isolated directly from tissue lysates using other RNA isolation kits, e.g., the POLY(A)PURE mRNA purification kit (Ambion, Austin Tex.).  
     [0298] In some cases, Stratagene was provided with RNA and constructed the corresponding cDNA libraries. Otherwise, cDNA was synthesized and cDNA libraries were constructed with the UNIZAP vector system (Stratagene) or SUPERSCRIPT plasmid system (Life Technologies), using the recommended procedures or similar methods known in the art. (See, e.g., Ausubel, 1997, supra, units 5.1-6.6.) Reverse transcription was initiated using oligo d(T) or random primers. Synthetic oligonucleotide adapters were ligated to double stranded cDNA, and the cDNA was digested with the appropriate restriction enzyme or enzymes. For most libraries, the cDNA was size-selected (300-1000 bp) using SEPHACRYL S1000, SEPHAROSE CL2B, or SEPHAROSE CL4B column chromatography (Amersham Pharmacia Biotech) or preparative agarose gel electrophoresis. cDNAs were ligated into compatible restriction enzyme sites of the polylinker of a suitable plasmid, e.g., PBLUESCRIPT plasmid (Stratagene), PSPORT1 plasmid (Life Technologies), PCDNA2.1 plasmid (Invitrogen, Carlsbad Calif.), PBK-CMV plasmid (Stratagene), PCR2-TOPOTA plasmid (Invitrogen), PCMV-ICIS plasmid (Stratagene), pIGEN (Incyte Genomics, Palo Alto Calif.), or pINCY (Incyte Genomics), or derivatives thereof. Recombinant plasmids were transformed into competent  E. coli  cells including XL1-Blue, XL1-BlueMRF, or SOLR from Stratagene or DH5α, DH10B, or ElectroMAX DH10B from Life Technologies.  
     [0299] II. Isolation of cDNA Clones  
     [0300] Plasmids obtained as described in Example I were recovered from host cells by in vivo excision using the UNIZAP vector system (Stratagene) or by cell lysis. Plasmids were purified using at least one of the following: a Magic or WIZARD Minipreps DNA purification system (Promega); an AGTC Miniprep purification kit (Edge Biosystems, Gaithersburg Md.); and QIAWELL 8 Plasmid, QIAWELL 8 Plus Plasmid, QIAWELL 8 Ultra Plasmid purification systems or the R.E.A.L. PREP 96 plasmid purification kit from QIAGEN. Following precipitation, plasmids were resuspended in 0.1 ml of distilled water and stored, with or without lyophilization, at 4° C.  
     [0301] Alternatively, plasmid DNA were amplified from host cell lysates using direct link PCR in a high-throughput format (Rao, V. B. (1994) Anal. Biochem. 216:1-14). Host cell lysis and thermal cycling steps were carried out in a single reaction mixture. Samples were processed and stored in 384-well plates, and the concentration of amplified plasmid DNA were quantified fluorometrically using PICOGREEN dye (Molecular Probes, Eugene Oreg.) and a FLUOROSKAN II fluorescence scanner (Labsystems Oy, Helsinki, Finland).  
     [0302] III Sequencing and Analysis  
     [0303] Incyte cDNA recovered in plasmids as described in Example II were sequenced as follows. Sequencing reactions were processed using standard methods or high-throughput instrumentation such as the ABI CATALYST 800 (Applied Biosystems) thermal cycler or the PTC-200 thermal cycler (MJ Research) in conjunction with the HYDRA microdispenser (Robbins Scientific) or the MICROLAB 2200 (Hamilton) liquid transfer system. cDNA sequencing reactions were prepared using reagents provided by Amersham Pharmacia Biotech or supplied in ABI sequencing kits such as the ABI PRISM BIGDYE Terminator cycle sequencing ready reaction kit (Applied Biosystems). Electrophoretic separation of cDNA sequencing reactions and detection of labeled polynucleotides were carried out using the MEGABACE 1000 DNA sequencing system (Molecular Dynamics); the ABI PRISM 373 or 377 sequencing system (Applied Biosystems) in conjunction with standard ABI protocols and base calling software; or other sequence analysis systems known in the art. Reading frames within the cDNA sequences were identified using standard methods (reviewed in Ausubel, 1997, supra, unit 7.7). Some of the cDNA sequences were selected for extension using the techniques disclosed in Example VIII.  
     [0304] The polynucleotide sequences derived from Incyte cDNAs were validated by removing vector, linker, and poly(A) sequences and by masking ambiguous bases, using algorithms and programs based on BLAST, dynamic programming, and dinucleotide nearest neighbor analysis. The Incyte cDNA sequences or translations thereof were then queried against a selection of public databases such as the GenBank primate, rodent, mammalian, vertebrate, and eukaryote databases, and BLOCKS, PRINTS, DOMO, PRODOM; PROTEOME databases with sequences from  Homo sapiens, Rattus norvegicus, Mus musculus, Caenorhabditis elegans, Saccharomyces cerevisiae, Schizosaccharomyces pombe,  and  Candida albicans  (Incyte Genomics, Palo Alto Calif.); and hidden Markov model (HMM)-based protein family databases such as PFAM. (HMM is a probabilistic approach which analyzes consensus primary structures of gene families. See, for example, Eddy, S. R. (1996) Curr. Opin. Struct. Biol. 6:361-365). The queries were performed using programs based on BLAST, FASTA, BLIMPS, and HMMER. The Incyte cDNA sequences were assembled to produce full length polynucleotide sequences. Alternatively, GenBank cDNAs, GenBank ESTs, stitched sequences, stretched sequences, or Genscan-predicted coding sequences (see Examples IV and V) were used to extend Incyte cDNA assemblages to full length. Assembly was performed using programs based on Phred, Phrap, and Consed, and cDNA assemblages were screened for open reading frames using programs based on GeneMark, BLAST, and FASTA. The full length polynucleotide sequences were translated to derive the corresponding full length polypeptide sequences. Alternatively, a polypeptide of the invention may begin at any of the methionine residues of the full length translated polypeptide. Full length polypeptide sequences were subsequently analyzed by querying against databases such as the GenBank protein databases (genpept), SwissProt, the PROTEOME databases, BLOCKS, PRINTS, DOMO, PRODOM, Prosite, and hidden Markov model (HMM)-based protein family databases such as PFAM. Full length polynucleotide sequences are also analyzed using MACDNASIS PRO software (Hitachi Software Engineering, South San Francisco Calif.) and LASERGENE software (DNASTAR). Polynucleotide and polypeptide sequence alignments are generated using default parameters specified by the CLUSTAL algorithms as incorporated into the MEGALIGN multisequence alignment program (DNASTAR), which also calculates the percent identity between aligned sequences.  
     [0305] Table7 summarizes the tools, programs, and algorithms used for the analysis and assembly of Incyte cDNA and full length sequences and provides applicable descriptions, references, and threshold parameters. The first column of Table 7 shows the tools, programs, and algorithms used, the second column provides brief descriptions thereof, the third column presents appropriate references, all of which are incorporated by reference herein in their entirety, and the fourth column presents, where applicable, the scores, probability values, and other parameters used to evaluate the strength of a match between two sequences (the higher the score or the lower the probability value, the greater the identity between two sequences).  
     [0306] The programs described above for the assembly and analysis of full length polynucleotide and polypeptide sequences were also used to identify polynucleotide sequence fragments from SEQ ID NO:18-34. Fragments from about 20 to about 4000 nucleotides which are useful in hybridization and amplification technologies are described in Table 4, column 4.  
     [0307] IV. Identification and Editing of Coding Sequences from Genomic DNA  
     [0308] Putative transmembrane proteins were initially identified by running the Genscan gene identification program against public genomic sequence databases (e.g., gbpri and gbhtg). Genscan is a general-purpose gene identification program which analyzes genomic DNA sequences from a variety of organisms (See Burge, C. and S. Karlin (1997) J. Mol. Biol. 268:78-94, and Burge, C. and S. Karlin (1998) Curr. Opin. Struct. Biol. 8:346-354). The program concatenates predicted exons to form an assembled cDNA sequence extending from a methionine to a stop codon. The output of Genscan is a FASTA database of polynucleotide and polypeptide sequences. The maximum range of sequence for Genscan to analyze at once was set to 30 kb. To determine which of these Genscan predicted cDNA sequences encode transmembrane proteins, the encoded polypeptides were analyzed by querying against PFAM models for transmembrane proteins. Potential transmembrane proteins were also identified by homology to Incyte cDNA sequences that had been annotated as transmembrane proteins. These selected Genscan-predicted sequences were then compared by BLAST analysis to the genpept and gbpri public databases. Where necessary, the Genscan predicted sequences were then edited by comparison, to the top BLAST hit from genpept to correct errors in the sequence predicted by Genscan, such as extra or omitted exons. BLAST analysis was also used to find any Incyte cDNA or public cDNA coverage of the Genscan-predicted sequences, thus providing evidence for transcription. When Incyte cDNA coverage was available, this information was used to correct or confirm the Genscan predicted sequence. Full length polynucleotide sequences were obtained by assembling Genscan-predicted coding sequences with Incyte cDNA sequences and/or public cDNA sequences using the assembly process described in Example III. Alternatively, full length polynucleotide sequences were derived entirely from edited or unedited Genscan-predicted coding sequences.  
     [0309] V. Assembly of Genomic Sequence Data with cDNA Sequence Data  
     [0310] “Stitched” Sequences  
     [0311] Partial cDNA sequences were extended with exons predicted by the Genscan gene identification program described in Example IV. Partial cDNAs assembled as described in Example III were mapped to genomic DNA and parsed into clusters containing related cDNAs and Genscan exon predictions from one or more genomic sequences. Each cluster was analyzed using an algorithm based on graph theory and dynamic programming to integrate cDNA and genomic information, generating possible splice variants that were subsequently confirmed, edited, or extended to create a full length sequence. Sequence intervals in which the entire length of the interval was present on more than one sequence in the cluster were identified, and intervals thus identified were considered to be equivalent by transitivity. For example, if an interval was present on a cDNA and two genomic sequences, then all three intervals were considered to be equivalent. This process allows unrelated but consecutive genomic sequences to be brought together, bridged by cDNA sequence. Intervals thus identified were then “stitched” together by the stitching algorithm in the order that they appear along their parent sequences to generate the longest possible sequence, as well as sequence variants. Linkages between intervals which proceed along one type of parent sequence (cDNA to cDNA or genomic sequence to genomic sequence) were given preference over linkages which change parent type (cDNA to genomic sequence). The resultant stitched sequences were translated and compared by BLAST analysis to the genpept and gbpri public databases. Incorrect exons predicted by Genscan were corrected by comparison to the top BLAST hit from genpept. Sequences were further extended with additional cDNA sequences, or by inspection of genomic DNA, when necessary.  
     [0312] “Stretched” Sequences  
     [0313] Partial DNA sequences were extended to full length with an algorithm based on BLAST analysis. First, partial cDNAs assembled as described in Example III were queried against pubic databases such as the GenBank primate, rodent, mammalian, vertebrate, and eukaryote databases using the BLAST program. The nearest GenBank protein homolog was then compared by BLAST analysis to either Incyte cDNA sequences or GenScan exon predicted sequences described in Example IV. A chimeric protein was generated by using the resultant high-scoring segment pairs (HSPs) to map the translated sequences onto the GenBank protein homolog. Insertions or deletions may occur in the chimeric protein with respect to the original GenBank protein homolog. The GenBank protein homolog, the chimeric protein, or both were used as probes to search for homologous genomic sequences from the public human genome databases. Partial DNA sequences were therefore “stretched” or extended by the addition of homologous genomic sequences. The resultant stretched sequences were examined to determine whether it contained a complete gene.  
     [0314] Chromosomal Mapping of TMP Encoding Polynucleotides  
     [0315] The sequences which were used to assemble SEQ ID NO:18-34 were compared with sequences from the Incyte LIFESEQ database and public domain databases using BLAST and other implementations of the Smith-Waterman algorithm. Sequences from these databases that matched SEQ ID NO:18-34 were assembled into clusters of contiguous and overlapping sequences using assembly algorithms such as Phrap (Table 7). Radiation hybrid and genetic mapping data available from public resources such as the Stanford Human Genome Center (SHGC), Whitehead Institute for Genome Research (WIGR), and Généthon were used to determine if any of the clustered sequences had been previously mapped. Inclusion of a mapped sequence in a cluster resulted in the assignment of all sequences of that cluster, including its particular SEQ ID NO:, to that map location.  
     [0316] Map locations are represented by ranges, or intervals, of human chromosomes. The map position of an interval, in centiMorgans, is measured relative to the terminus of the chromosome&#39;s p-arm. (The centiMorgan (cM) is a unit of measurement based on recombination frequencies between chromosomal markers. On average, 1 cM is roughly equivalent to 1 megabase (Mb) of DNA in humans, although this can vary widely due to hot and cold spots of recombination.) The cM distances are based on genetic markers mapped by Généthon which provide boundaries for radiation hybrid markers whose sequences were included in each of the clusters. Human genome maps and other resources available to the public, such as the NCBI “GeneMap &#39;99” World Wide Web site (http://www.ncbi.nlm.nih.gov/genemap/), can be employed to determine if previously identified disease genes map within or in proximity to the intervals indicated above.  
     [0317] In this manner, SEQ ID NO:22 was mapped to chromosome 11 within the interval from 59.50 to 62.50 centiMorgans and SEQ ID NO:26 was mapped to chromosome 1 within the interval from 179.2 to 186.4 centiMorgans.  
     [0318] VII. Analysis of Polynucleotide Expression  
     [0319] Northern analysis is a laboratory technique used to detect the presence of a transcript of a gene and involves the hybridization of a labeled nucleotide sequence to a membrane on which RNAs from a particular cell type or tissue have been bound. (See, e.g., Sambrook, supra, ch. 7; Ausubel (1995) supra, ch. 4 and 16.)  
     [0320] Analogous computer techniques applying BLAST were used to search for identical or related molecules in cDNA databases such as GenBank or LIFESEQ (Incyte Genomics). This analysis is much faster than multiple membrane-based hybridizations. In addition, the sensitivity of the computer search can be modified to determine whether any particular match is categorized as exact or similar. The basis of the search is the product score, which is defined as:  
         BLAST                 Score   ×   Percent                 Identity       5   ×   minimum                   {       length                   (     Seq   .              1     )       ,     length                   (     Seq   .              2     )         }                     
 
     [0321] The product score takes into account both the degree of similarity between two sequences and the length of the sequence match. The product score is a normalized value between 0 and 100, and is calculated as follows: the BLAST score is multiplied by the percent nucleotide identity and the product is divided by (5 times the length of the shorter of the two sequences). The BLAST score is calculated by assigning a score of +5 for every base that matches in a high-scoring segment pair (HSP), and −4 for every mismatch. Two sequence may share more than one HSP (separated by gaps). If there is more than one HSP, then the pair with the highest BLAST score is used to calculate the product score. The product score represents a balance between fractional overlap and quality in a BLAST alignment. For example, a product score of 100 is produced only for 100% identity over the entire length of the shorter of the two sequences being compared. A product score of 70 is produced either by 100% identity and 70% overlap at one end, or by 88% identity and 100% overlap at the other. A product score of 50 is produced either by 100% identity and 50% overlap at one end, or 79% identity and 100% overlap.  
     [0322] Alternatively, polynucleotide sequences encoding TMP are analyzed with respect to the tissue sources from which they were derived. For example, some full length sequences are assembled, at least in part, with overlapping Incyte cDNA sequences (see Example III). Each cDNA sequence is derived from a cDNA library constructed from a human tissue. Each human tissue is classified into one of the following organ/tissue categories: cardiovascular system; connective tissue; digestive system; embryonic structures; endocrine system; exocrine glands; genitalia, female; genitalia, male; germ cells; hemic and immune system; liver; musculoskeletal system; nervous system; pancreas; respiratory system; sense organs; skin; stomatognathic system; unclassified/mixed; or urinary tract. The number of libraries in each category is counted and divided by the total number of libraries across all categories. Similarly, each human tissue is classified into one of the following disease/condition categories: cancer, cell line, developmental, inflammation, neurological, trauma, cardiovascular, pooled, and other, and the number of libraries in each category is counted and divided by the total number of libraries across all categories. The resulting percentages reflect the tissue- and disease-specific expression of cDNA encoding TMP. cDNA sequences and cDNA library/tissue information are found in the LIFESEQ GOLD database (Incyte Genomics, Palo Alto Calif.). VIII. Extension of TMP Encoding Polynucleotides Full length polynucleotide sequences were also produced by extension of an appropriate fragment of the full length molecule using oligonucleotide primers designed from this fragment. One primer was synthesized to initiate 5′ extension of the known fragment, and the other primer was synthesized to initiate 3′ extension of the known fragment. The initial primers were designed using OLIGO 4.06 software (National Biosciences), or another appropriate program, to be about 22 to 30 nucleotides in length, to have a GC content of about 50% or more, and to anneal to the target sequence at temperatures of about 68° C. to about 72° C. Any stretch of nucleotides which would result in hairpin structures and primer-primer dimerizations was avoided.  
     [0323] Selected human cDNA libraries were used to extend the sequence. If more than one extension was necessary or desired, additional or nested sets of primers were designed.  
     [0324] High fidelity amplification was obtained by PCR using methods well known in the art. PCR was performed in 96-well plates using the PTC-200 thermal cycler (MJ Research). The reaction mix contained DNA template, 200 nmol of each primer, reaction buffer containing Mg 2+ , (NH 4 ) 2 SO 4 , and 2-mercaptoethanol, Taq DNA polymerase (Amersham Pharmacia Biotech), ELONGASE enzyme (Life Technologies), and Pfu DNA polymerase (Stratagene), with the following parameters for primer pair PCI A and PCI B: Step 1: 94° C, 3 min; Step 2: 94° C, 15 sec; Step 3: 60° C, 1 min; Step 4: 68° C, 2 min; Step 5: Steps 2, 3, and 4 repeated 20 times; Step 6: 68° C, 5 min; Step 7: storage at 4° C. In the alternative, the parameters for primer pair T7 and SK+ were as follows: Step 1: 94° C, 3 min; Step 2: 94° C, 15 sec; Step 3: 57° C, 1 min; Step 4: 68° C, 2 min; Step 5: Steps 2, 3, and 4 repeated 20 times; Step 6: 68° C., 5 min; Step 7: storage at 4° C.  
     [0325] The concentration of DNA in each well was determined by dispensing 100 μl PICOGREEN quantitation reagent (0.25% (v/v) PICOGREEN; Molecular Probes, Eugene Oreg.) dissolved in 1× TE and 0.5 μl of undiluted PCR product into each well of an opaque fluorimeter plate (Corning Costar, Acton Mass.), allowing the DNA to bind to the reagent. The plate was scanned in a Fluoroskan II (Labsystems Oy, Helsinki, Finland) to measure the fluorescence of the sample and to quantify the concentration of DNA. A 5 μl to 10 μl aliquot of the reaction mixture was analyzed by electrophoresis on a 1% agarose gel to determine which reactions were successful in extending the sequence.  
     [0326] The extended nucleotides were desalted and concentrated, transferred to 384-well plates, digested with CviJI cholera virus endonuclease (Molecular Biology Research, Madison Wis.), and sonicated or sheared prior to religation into pUC 18 vector (Amersham Pharmacia Biotech). For shotgun sequencing, the digested nucleotides were separated on low concentration (0.6 to 0.8%) agarose gels, fragments were excised, and agar digested with Agar ACE (Promega). Extended clones were religated using T4 ligase (New England Biolabs, Beverly Mass.) into pUC 18 vector (Amersham Pharmacia Biotech), treated with Pfu DNA polymerase (Stratagene) to fill-in restriction site overhangs, and transfected into competent  E. coli  cells. Transformed cells were selected on antibiotic-containing media, and individual colonies were picked and cultured overnight at 37° C. in 384-well plates in LB/2× carb liquid media.  
     [0327] The cells were lysed, and DNA was amplified by PCR using Taq DNA polymerase (Amersham Pharmacia Biotech) and Pfu DNA polymerase (Stratagene) with the following parameters: Step 1: 94° C., 3 min; Step 2: 94° C., 15 sec; Step 3: 60° C., 1 min; Step 4: 72° C., 2 min; Step 5: steps 2, 3, and 4 repeated 29 times; Step 6: 72° C., 5 min; Step 7: storage at 4° C. DNA was quantified by PICOGREEN reagent (Molecular Probes) as described above. Samples with low DNA recoveries were reamplified using the same conditions as described above. Samples were diluted with 20% dimethysulfoxide (1:2, v/v), and sequenced using DYENAMIC energy transfer sequencing primers and the DYENAMIC DIRECT kit (Amersham Pharmacia Biotech) or the ABI PRISM BIGDYE Terminator cycle sequencing ready reaction kit (Applied Biosystems).  
     [0328] In like manner, full length polynucleotide sequences are verified using the above procedure or are used to obtain 5′ regulatory sequences using the above procedure along with oligonucleotides designed for such extension, and an appropriate genomic library.  
     [0329] IX. Labeling and Use of Individual Hybridization Probes  
     [0330] Hybridization probes derived from SEQ ID NO:18-34 are employed to screen cDNAs, genomic DNAs, or mRNAs. Although the labeling of oligonucleotides, consisting of about 20 base pairs, is specifically described, essentially the same procedure is used with larger nucleotide fragments. Oligonucleotides are designed using state-of-the-art software such as OLIGO 4.06 software (National Biosciences) and labeled by combining 50 pmol of each oligomer, 250 μCi of [γ- 32 P] adenosine triphosphate (Amersham Pharmacia Biotech), and T4 polynucleotide kinase (DuPont NEN, Boston Mass.). The labeled oligonucleotides are substantially purified using a SEPHADEX G-25 superfine size exclusion dextran bead column (Amersham Pharmacia Biotech). An aliquot containing 10 7  counts per minute of the labeled probe is used in a typical membrane-based hybridization analysis of human genomic DNA digested with one of the following endonucleases: Ase I, Bgl II, Eco RI, Pst I, Xba I, or Pvu II (DuPont NEN).  
     [0331] The DNA from each digest is fractionated on a 0.7% agarose gel and transferred to nylon membranes Nytran Plus, Schleicher &amp; Schuell, Durham N.H.). Hybridization is carried out for 16 hours at 40° C. To remove nonspecific signals, blots are sequentially washed at room temperature under conditions of up to, for example, 0.1× saline sodium citrate and 0.5% sodium dodecyl sulfate. Hybridization patterns are visualized using autoradiography or an alternative imaging means and compared.  
     [0332] X. Microarrays  
     [0333] The linkage or synthesis of array elements upon a microarray can be achieved utilizing photolithography, piezoelectric printing (ink-jet printing, See, e.g., Baldeschweiler, supra.), mechanical microspotting technologies, and derivatives thereof. The substrate in each of the aforementioned technologies should be uniform and solid with a non-porous surface (Schena (1999), sung). Suggested substrates include silicon, silica, glass slides, glass chips, and silicon wafers. Alternatively, a procedure analogous to a dot or slot blot may also be used to arrange and link elements to the surface of a substrate using thermal, UV, chemical, or mechanical bonding procedures. A typical array may be produced using available methods and machines well known to those of ordinary skill in the art and may contain any appropriate number of elements. (See, e.g., Schena, M. et al. (1995) Science 270:467-470; Shalon, D. et al. (1996) Genome Res. 6:639-645; Marshall, A and J. Hodgson (1998) Nat. Biotechnol. 16:27-31.)  
     [0334] Pull length cDNAs, Expressed Sequence Tags (ESTs), or fragments or oligomers thereof may comprise the elements of the microarray. Fragments or oligomers suitable for hybridization can be selected using software well known in the art such as LASERGENE software (DNASTAR). The array elements are hybridized with polynucleotides in a biological sample. The polynucleotides in the biological sample are conjugated to a fluorescent label or other molecular tag for ease of detection. After hybridization, nonhybridized nucleotides from the biological sample are removed, and a fluorescence scanner is used to detect hybridization at each array element. Alternatively, laser desorbtion and mass spectrometry may be used for detection of hybridization. The degree of complementarity and the relative abundance of each polynucleotide which hybridizes to an element on the microarray may be assessed. In one embodiment, microarray preparation and usage is described in detail below.  
     [0335] Tissue or Cell Sample Preparation  
     [0336] Total RNA is isolated from tissue samples using the guanidinium thiocyanate method and poly(A) +  RNA is purified using the oligo-(dT) cellulose method. Each poly(A) +  RNA sample is reverse transcribed using MMLV reverse-transcriptase, 0.05 pg/μl oligo-(dT) primer (21 mer), 1× first strand buffer, 0.03 units/μl RNase inhibitor, 500 μM dATP, 500 μM dGTP, 500 μM dTTP, 40 μM dCTP, 40 μM dCTP-Cy3 (BDS) or dCTP-Cy5 (Amersham Pharmacia Biotech). The reverse transcription reaction is performed in a 25 ml volume containing 200 ng poly(A) +  RNA with GEMBRIGHT kits (Incyte). Specific control poly(A) +  RNAs are synthesized by in vitro transcription from non-coding yeast genomic DNA. After incubation at 37° C. for 2 hr, each reaction sample (one with Cy3 and another with Cy5 labeling) is treated with 2.5 ml of 0.5M sodium hydroxide and incubated for 20 minutes at 85° C. to the stop the reaction and degrade the RNA. Samples are purified using two successive CHROMA SPIN 30 gel filtration spin columns (CLONTECH Laboratories (CLONTECH), Palo Alto Calif.) and after combining, both reaction samples are ethanol precipitated using 1 ml of glycogen (1 mg/ml), 60 ml sodium acetate, and 300 ml of 100% ethanol. The sample is then dried to completion using a SpeedVAC (Savant Instruments, Holbrook N.Y.) and resuspended in 14 μl 5× SSC/0.2% SDS.  
     [0337] Microarray Preparation  
     [0338] Sequences of the present invention are used to generate array elements. Each array element is amplified from bacterial cells containing vectors with cloned cDNA inserts. PCR amplification uses primers complementary to the vector sequences flanking the cDNA insert. Array elements are amplified in thirty cycles of PCR from an initial quantity of 1-2 ng to a final quantity greater than 5 jig. Amplified array elements are then purified using SEPHACRYL-400 (Amersham Pharmacia Biotech).  
     [0339] Purified array elements are immobilized on polymer-coated glass slides. Glass microscope slides (Corning) are cleaned by ultrasound in 0.1% SDS and acetone, with extensive distilled water washes between and after treatments. Glass slides are etched in 4% hydrofluoric acid (VWR Scientific Products Corporation (VWR), West Chester Pa.), washed extensively in distilled water, and coated with 0.05% aminopropyl silane (Sigma) in 95% ethanol. Coated slides are cured in a 110° C. oven.  
     [0340] Array elements are applied to the coated glass substrate using a procedure described in U.S. Pat. No. 5,807,522, incorporated herein by reference. 1 μl of the array element DNA, at an average concentration of 100 ng/μl, is loaded into the open capillary printing element by a high-speed robotic apparatus. The apparatus then deposits about 5 nl of array element sample per slide.  
     [0341] Microarrays are UV-crosslinked using a STRATALINKER UV-crosslinker (Stratagene). Microarrays are washed at room temperature once in 0.2% SDS and three times in distilled water. Non-specific binding sites are blocked by incubation of microarrays in 0.2% casein in phosphate buffered saline (PBS) (Tropix, Bedford Mass.) for 30 minutes at 60° C. followed by washes in 0.2% SDS and distilled water as before.  
     [0342] Hybridization  
     [0343] Hybridization reactions contain 9 μl of sample mixture consisting of 0.2 μg each of Cy3 and Cy5 labeled cDNA synthesis products in 5× SSC, 0.2% SDS hybridization buffer. The sample mixture is heated to 65° C. for 5 minutes and is aliquoted onto the microarray surface and covered with an 1.8 cm 2  coverslip. The arrays are transferred to a waterproof chamber having a cavity just slightly larger than a microscope slide. The chamber is kept at 100% humidity internally by the addition of 140 μl of 5× SSC in a corner of the chamber. The chamber containing the arrays is incubated for about 6.5 hours at 60° C. The arrays are washed for 10 min at 45° C. in a first wash buffer (1× SSC, 0.1% SDS), three times for 10 minutes each at 45° C. in a second wash buffer (0.1× SSC), and dried.  
     [0344] Detection  
     [0345] Reporter-labeled hybridization complexes are detected with a microscope equipped with an Innova 70 mixed gas 10 W laser (Coherent, Santa Clara Calif.) capable of generating spectral lines at 488 nm for excitation of Cy3 and at 632 nm for excitation of Cy5. The excitation laser light is focused on the array using a 20× microscope objective (Nikon, Melville N.Y.). The slide containing the array is placed on a computer-controlled X-Y stage on the microscope and raster-scanned past the objective. The 1.8 cm×1.8 cm array used in the present example is scanned with a resolution of 20 micrometers.  
     [0346] In two separate scans, a mixed gas multiline laser excites the two fluorophores sequentially. Emitted light is split, based on wavelength, into two photomultiplier tube detectors (PMT R1477, Hamamatsu Photonics Systems, Bridgewater N.J.) corresponding to the two fluorophores. Appropriate filters positioned between the array and the photomultiplier tubes are used to filter the signals. The emission maxima of the fluorophores used are 565 nm for Cy3 and 650 nm for Cy5. Each array is typically scanned twice, one scan per fluorophore using the appropriate filters at the laser source, although the apparatus is capable of recording the spectra from both fluorophores simultaneously.  
     [0347] The sensitivity of the scans is typically calibrated using the signal intensity generated by a cDNA control species added to the sample mixture at a known concentration. A specific location on the array contains a complementary DNA sequence, allowing the intensity of the signal at that location to be correlated with a weight ratio of hybridizing species of 1:100,000. When two samples from different sources (e.g., representing test and control cells), each labeled with a different fluorophore, are hybridized to a single array for the purpose of identifying genes that are differentially expressed, the calibration is done by labeling samples of the calibrating cDNA with the two fluorophores and adding identical amounts of each to the hybridization mixture.  
     [0348] The output of the photomultiplier tube is digitized using a 12-bit RTI-835H analog-to-digital (A/D) conversion board (Analog Devices, Norwood Mass.) installed in an IBM-compatible PC computer. The digitized data are displayed as an image where the signal intensity is mapped using a linear 20-color transformation to a pseudocolor scale ranging from blue (low signal) to red (high signal). The data is also analyzed quantitatively. Where two different fluorophores are excited and measured simultaneously, the data are first corrected for optical crosstalk (due to overlapping emission spectra) between the fluorophores using each fluorophore&#39;s emission spectrum.  
     [0349] A grid is superimposed over the fluorescence signal image such that the signal from each spot is centered in each element of the grid. The fluorescence signal within each element is then integrated to obtain a numerical value corresponding to the average intensity of the signal. The software used for signal analysis is the GEMTOOLS gene expression analysis program (Incyte).  
     [0350] XI. Complementary Polynucleotides  
     [0351] Sequences complementary to the TMP-encoding sequences, or any parts thereof, are used to detect, decrease, or inhibit expression of naturally occurring TMP. Although use of oligonucleotides comprising from about 15 to 30 base pairs is described, essentially the same procedure is used with smaller or with larger sequence fragments. Appropriate oligonucleotides are designed using OLIGO 4.06 software (National Biosciences) and the coding sequence of TMP. To inhibit transcription, a complementary oligonucleotide is designed from the most unique 5′ sequence and used to prevent promoter binding to the coding sequence. To inhibit translation, a complementary oligonucleotide is designed to prevent ribosomal binding to the TMP-encoding transcript.  
     [0352] XII. Expression of TMP  
     [0353] Expression and purification of TMP is achieved using bacterial or virus-based expression systems. For expression of TMP in bacteria, cDNA is subcloned into an appropriate vector containing an antibiotic resistance gene and an inducible promoter that directs high levels of cDNA transcription. Examples of such promoters include, but are not limited to, the trp-lac (tac) hybrid promoter and the T5 or T7 bacteriophage promoter in conjunction with the lac operator regulatory element. Recombinant vectors are transformed into suitable bacterial hosts, e.g., BL21(DE3). Antibiotic resistant bacteria express TMP upon induction with isopropyl beta-D-thiogalactopyranoside (IPTG). Expression of TMP in eukaryotic cells is achieved by infecting insect or mammalian cell lines with recombinant  Autographica californica  nuclear polyhedrosis virus (AcMNPV), commonly known as baculovirus. The nonessential polyhedrin gene of baculovirus is replaced with cDNA encoding TMP by either homologous recombination or bacterial-mediated transposition involving transfer plasmid intermediates. Viral infectivity is maintained and the strong polyhedrin promoter drives high levels of cDNA transcription. Recombinant baculovirus is used to infect  Spodoptera frugiperda  (Sf9) insect cells in most cases, or human hepatocytes, in some cases. Infection of the latter requires additional genetic modifications to baculovirus. (See Engelhard, E. K. et al. (1994) Proc. Natl. Acad. Sci. USA 91:3224-3227; Sandig, V. et al. (1996) Hum. Gene Ther. 7:1937-1945.)  
     [0354] In most expression systems, TMP is synthesized as a fusion protein with, e.g., glutathione S-transferase (GST) or a peptide epitope tag, such as FLAG or 6-His, permitting rapid, single-step, affinity-based purification of recombinant fusion protein from crude cell lysates. GST, a 26-kilodalton enzyme from  Schistosoma japonicum,  enables the purification of fusion proteins on immobilized glutathione under conditions that maintain protein activity and antigenicity (Amersham Pharmacia Biotech). Following purification, the GST moiety can be proteolytically cleaved from TMP at specifically engineered sites. FLAG, an 8-amino acid peptide, enables immunoaffinity purification using commercially available monoclonal and polyclonal anti-FLAG antibodies (Eastman Kodak). 6-His, a stretch of six consecutive histidine residues, enables purification on metal-chelate resins (QIAGEN). Methods for protein expression and purification are discussed in Ausubel (1995, supra, ch. 10 and 16). Purified TMP obtained by these methods can be used directly in the assays shown in Examples XVI and XVII where applicable.  
     [0355] XIII. Functional Assays  
     [0356] TMP function is assessed by expressing the sequences encoding TMP at physiologically elevated levels in mammalian cell culture systems. cDNA is subcloned into a mammalian expression vector containing a strong promoter that drives high levels of cDNA expression. Vectors of choice include PCMV SPORT (Life Technologies) and PCR3.1 (Invitrogen, Carlsbad Calif.), both of which contain the cytomegalovirus promoter. 5-10 μg of recombinant vector are transiently transfected into a human cell line, for example, an endothelial or hematopoietic cell line, using either liposome formulations or electroporation. 1-2 μg of an additional plasmid containing sequences encoding a marker protein are co-transfected. Expression of a marker protein provides a means to distinguish transfected cells from nontransfected cells and is a reliable predictor of cDNA expression from the recombinant vector. Marker proteins of choice include, e.g., Green Fluorescent Protein (GFP; Clontech), CD64, or a CD64-GFP fusion protein. Flow cytometry (FCM), an automated, laser optics-based technique, is used to identify transfected cells expressing GFP or CD64-GFP and to evaluate the apoptotic state of the cells and other cellular properties. FCM detects and quantifies the uptake of fluorescent molecules that diagnose events preceding or coincident with cell death. These events include changes in nuclear DNA content as measured by staining of DNA with propidium iodide; changes in cell size and granularity as measured by forward light scatter and 90 degree side light scatter; down-regulation of DNA synthesis as measured by decrease in bromodeoxyuridine uptake; alterations in expression of cell surface and intracellular proteins as measured by reactivity with specific antibodies; and alterations in plasma membrane composition as measured by the binding of fluorescein-conjugated Annexin V protein to the cell surface. Methods in flow cytometry are discussed in Ormerod, M. G. (1994) Flow Cytometry, Oxford, New York N.Y.  
     [0357] The influence of TMP on gene expression can be assessed using highly purified populations of cells transfected with sequences encoding TMP and either CD64 or CD64GFP. CD64 and CD64GFP are expressed on the surface of transfected cells and bind to conserved regions of human immunoglobulin G (IgG). Transfected cells are efficiently separated from nontransfected cells using magnetic beads coated with either human IgG or antibody against CD64 (DYNAL, Lake Success N.Y.). mRNA can be purified from the cells using methods well known by those of skill in the art. Expression of mRNA encoding TMP and other genes of interest can be analyzed by northern analysis or microarray techniques.  
     [0358] XIV. Production of TMP Specific Antibodies  
     [0359] TMP substantially purified using polyacrylamide gel electrophoresis (PAGE; see, e.g., Harrington, M. G. (1990) Methods Enzymol. 182:488-495), or other purification techniques, is used to immunize rabbits and to produce antibodies using standard protocols.  
     [0360] Alternatively, the TMP amino acid sequence is analyzed using LASERGENE software (DNASTAR) to determine regions of high immunogenicity, and a corresponding oligopeptide is synthesized and used to raise antibodies by means known to those of skill in the art. Methods for selection of appropriate epitopes, such as those near the C-terminus or in hydrophilic regions are well described in the art. (See, e.g., Ausubel, 1995, supra, ch. 11.)  
     [0361] Typically, oligopeptides of about 15 residues in length are synthesized using an ABI 431A peptide synthesizer (Applied Biosystems) using FMOC chemistry and coupled to KLH (Sigma-Aldrich, St. Louis Mo.) by reaction with N-maleimidobenzoyl-N-hydroxysuccinimide ester (MBS) to increase immunogenicity. (See, e.g., Ausubel, 1995, supra.) Rabbits are immunized with the oligopeptide-KLH complex in complete Freund&#39;s adjuvant. Resulting antisera are tested for antipeptide and anti-TMP activity by, for example, binding the peptide or TMP to a substrate, blocking with 1% BSA, reacting with rabbit antisera, washing, and reacting with radio-iodinated goat anti-rabbit IgG.  
     [0362] XV. Purification of Naturally Occurring TMP Using Specific Antibodies  
     [0363] Naturally occurring or recombinant TMP is substantially purified by immunoaffinity chromatography using antibodies specific for TMP. An immunoaffinity column is constructed by covalently coupling anti-TMP antibody to an activated chromatographic resin, such as CNBr-activated SEPHAROSE (Amersham Pharmacia Biotech). After the coupling, the resin is blocked and washed according to the manufacturer&#39;s instructions.  
     [0364] Media containing TMP are passed over the immunoaffinity column, and the column is washed under conditions that allow the preferential absorbance of TMP (e.g., high ionic strength buffers in the presence of detergent). The column is eluted under conditions that disrupt antibody/TMP binding (e.g., a buffer of pH 2 to pH 3, or a high concentration of a chaotrope, such as urea or thiocyanate ion), and TMP is collected.  
     [0365] XVI. Identification of Molecules Which Interact with TMP  
     [0366] TMP, or biologically active fragments thereof, are labeled with  125 I Bolton-Hunter reagent (See, e.g., Bolton, A. E. and W. M. Hunter (1973) Biochem. J. 133:529-539.) Candidate molecules previously arrayed in the wells of a multi-well plate are incubated with the labeled TMP, washed, and any wells with labeled TMP complex are assayed. Data obtained using different concentrations of TMP are used to calculate values for the number, affinity, and association of TMP with the candidate molecules.  
     [0367] Alternatively, molecules interacting with TMP are analyzed using the yeast two-hybrid system as described in Fields, S. and O. Song (1989) Nature 340:245-246, or using commercially available kits based on the two-hybrid system, such as the MATCHMAKER system (Clontech).  
     [0368] TMP may also be used in the PATHCALLING process (CuraGen Corp., New Haven Conn.) which employs the yeast two-hybrid system in a high-throughput manner to determine all interactions between the proteins encoded by two large libraries of genes Nandabalan, K. et al. (2000) U.S. Pat. No. 6,057,101).  
     [0369] XVII. Demonstration of TMP Activity  
     [0370] Gap Junction Activity of TMP  
     [0371] Gap junction activity of TMP is demonstrated as the ability to induce the formation of intercellular channels between paired  Xenopus laevis  oocytes injected with TMP cRNA (Hennemann, supra. One week prior to the experimental injection with TMP cRNA, oocytes are injected with antisense oligonucleotide to TMP to reduce background. TMP cRNA-injected oocytes are incubated overnight, stripped of vitelline membranes, and paired for recording of junctional currents by dual cell voltage clamp. The measured conductances are proportional to gap junction activity of TMP.  
     [0372] Alternatively, an assay for TMP activity measures the ion channel activity of TMP using an electrophysiological assay for ion conductance. TMP can be expressed by transforming a mammalian cell line such as COS7, HeLa or CHO with a eukaryotic expression vector encoding TMP. Eukaryotic expression vectors are commercially available, and the techniques to introduce them into cells are well known to those skilled in the art. A second plasmid which expresses any one of a number of marker genes, such as β-galactosidase, is co-transformed into the cells to allow rapid identification of those cells which have taken up and expressed the foreign DNA. The cells are incubated for 48-72 hours after transformation under conditions appropriate for the cell line to allow expression and accumulation of TMP and β-galactosidase.  
     [0373] Transformed cells expressing β-galactosidase are stained blue when a suitable colorimetric substrate is added to the culture media under c nditions that are well known in the art. Stained cells are tested for differences in membrane conductance by electrophysiological techniques that are well known in the art. Untransformed cells, and/or cells transformed with either vector sequences alone or β-galactosidase sequences alone, are used as controls and tested in parallel. Cells expressing TMP will have higher anion or cation conductance relative to control cells. The contribution of TMP to conductance can be confirmed by incubating the cells using antibodies specific for TMP. The antibodies will bind to the extracellular side of TMP, thereby blocking the pore in the ion channel, and the associated conductance.  
     [0374] Transmembrane Protein Activity of TMP  
     [0375] An assay for TMP activity measures the expression of TMP on the cell surface. cDNA encoding TMP is transfected into an appropriate mammalian cell line. Cell surface proteins are labeled with biotin as described (de la Fuente, M. A. et al. (1997) Blood 90:2398-2405). Immunoprecipitations are performed using TMP-specific antibodies, and immunoprecipitated samples are analyzed using SDS-PAGE and immunoblotting techniques. The ratio of labeled immunoprecipitant to unlabeled immunoprecipitant is proportional to the amount of TMP expressed on the cell surface.  
     [0376] An alternative assay for TMP activity is based on a prototypical assay for ligand/receptor-mediated modulation of cell proliferation. This assay measures the amount of newly synthesized DNA in Swiss mouse 3T3 cells expressing TMP. An appropriate mammalian expression vector containing cDNA encoding TMP is added to quiescent 3T3 cultured cells using transfection methods well known in the art. The transfected cells are incubated in the presence of [ 3 H]thymidine and varying amounts of TMP ligand. Incorporation of [ 3 H]thymidine into acid-precipitable DNA is measured over an appropriate time interval using a tritium radioisotope counter, and the amount incorporated is directly proportional to the amount of newly synthesized DNA. A linear dose-response curve over at least a hundred-fold TMP ligand concentration range is indicative of receptor activity. One unit of activity per milliliter is defined as the concentration of TMP producing a 50% response level, where 100% represents maximal incorporation of [ 3 H]thymidine into acid-precipitable DNA (McKay, I. and Leigh, I., eds. (1993)  Growth Factors: A Practical Approach,  Oxford University Press, New York, N.Y., p. 73).  
     [0377] Various modifications and variations of the described methods and systems of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with certain embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention which are obvious to those skilled in molecular biology or related fields are intended to be within the scope of the following claims.  
                               TABLE 1                       Incyte       Incyte   Poly-   Incyte       Project   Polypeptide   Polypeptide   nucleotide   Polynucleotide       ID   SEQ ID NO:   ID   SEQ ID NO:   ID                                                    6431478   1   6431478CD1   18   6431478CB1       3584654   2   3584654CD1   19   3584654CB1       3737084   3   3737084CD1   20   3737084CB1       71426238   4   71426238CD1   21   71426238CB1       7475123   5   7475123CD1   22   7475123CB1       7481952   6   7481952CD1   23   7481952CB1       382654   7   382654CD1   24   382654CB1       1867351   8   1867351CD1   25   1867351CB1       3323104   9   3323104CD1   26   3323104CB1       4769306   10   4769306CD1   27   4769306CB1       2720058   11   2720058CD1   28   2720058CB1       7481255   12   7481255CD1   29   7481255CB1       1510242   13   1510242CD1   30   1510242CB1       162131   14   162131CD1   31   162131CB1       1837725   15   1837725CD1   32   1837725CB1       3643847   16   3643847CD1   33   3643847CB1       6889872   17   6889872CD1   34   6889872CB1                  
 
     [0378]                               TABLE 2                       Polypeptide   Incyte   GenBank   Probability           SEQ ID NO:   Polypeptide ID   ID NO:   score   GenBank Homolog                                                    1   6431478CD1   g310100   4.0E−216   [Rattus norvegicus] developmentally                       regulated protein       2   3584654CD1   g1054884   0.0   [Rattus norvegicus] prostaglandin                       F2a receptor regulatory protein                       Orlicky, D. J. (1996) Negative                       regulatory activity of a                       prostaglandin F2a receptor                       associated protein (FPRP).                       Prostaglandins Leukot. Essent. Fatty                       Acids 54, 247-259       3   3737084CD1   g3513451   1.7E−233   [Rattus norvegicus] potassium                       channel regulator 1                       Hoshi, N., et al (1998) KCR1, a                       membrane protein that facilitates                       functional expression of non-                       inactivating K+ currents associates                       with rat EAG voltage-dependent K+                       channels. J. Biol. Chem. 273, 23080-                       23085       4   71426238CD1   g15990851   1.0E−130   [f1] [Homo sapiens] (AJ414563)                       connexin25       5   7475123CD1   g3449306   0.0   [Homo sapiens] MEGF7 (multiple                       EGF-like 7 protein)                       Nakayama, M. et al., (1998)                       Genomics 51:27-34       6   7481952CD1   g8926243   1.5E−40   [Mus musculus] low density                       lipoprotein receptor related protein                       LRP1B/LRP-DIT       9   3323104CD1   g11414879   0.0   [f1] [Homo sapiens]                       mannosyltransferase                       Maeda, Y. et al. (2001) PIG-M                       transfers the first mannose to                       glycosylphosphatidylinositol on the                       lumenal side of the ER. EMBO J.                       20:250-261       11   2720058CD1   g6013381   1.5E−12   TM6P1 (integral membrane protein)                       [Rattus norvegicus] (Zhang, J. et                       al. (2000) Biochim. Biophys. Acta                       1492:280-284)       12   7481255CD1   g4150939   4.2E−27   [Mus musculus] GSG1       13   1510242CD1   g4263743   5.3E−163   similar to UNC-93; similar to U89424                       (PID:g3642687)       14   162131CD1   g13374351   0.0   [f1] [Homo sapiens] apolipoprotein L4       15   1837725CD1   g6850311   6.0E−52   Contains similarity to a vacuolar                       sorting receptor homolog from                       [Arabidopsis thaliana] gb | U79959       16   3643847CD1   g9944332   2.8E−95   [Mus musculus] Ttyh1                       Campbell, H. D. et al. (2000)                       Genomics 68:89-92       17   6889872CD1   g3191975   1.3E−95   dJ63G5.3 (putative Leucine rich                       protein) [Homo sapiens]                    
     [0379]                                       TABLE 3                               Amino                       SEQ   Incyte   Acid   Potential   Potential       Analytical       ID   Polypeptide   Resi-   Phosphorylation   Glycosylation   Signature Sequences,   Methods and       NO:   ID   dues   Sites   Sites   Domains and Motifs   Databases                                                            1    6431478CD1   461   S117 S190 S225   N113 N183   Transmembrane domains:   HMMER                   S280 S336 S34   N294   M38-T56, V94-I112, Y156-V174,                   T109 T221 T333       Y195-M216, I231-I248, Y388-M406,                   T386       PROTEIN PLACENTAL DIFF33 DEVELOPMENTALLY   BLAST_PRODOM                           REGULATED R11H6.2 PD011773: I76-P283,                           K192-S460                           PROTEIN PLACENTAL DIFF33 R11H6.2   BLAST_PRODOM                           DEVELOPMENTALLY REGULATED PD018175: M1-                           E70       2    3584654CD1   879   S150 S158 S244   N286 N300   Signal cleavage: M1-G21   SPSCAN                   S288 S349 S46   N383 N413   Signal peptide: M1-R25   HMMER                   S574 S580 S598   N44 N525   Transmembrane domain: L833-G851   HMMER                   S623 S66 S72   N600 N618   Immunoglobulin domains:   HMMER_PFAM                   S747 S758 S772   N691   G36-T121, G162-V249, G292-V375,                   T303 T402 T472       D422-V517, G564-V657, G704-V795                   T505 T506 T570       PROTEIN PROSTAGLANDIN F2ALPHA RECEPTOR   BLAST_PRODOM                   T757 T820 T866       REGULATORY PRECURSOR ASSOCIATED SIGNAL                   T97 Y640       IMMUNOGLOBULIN FOLD                           PD025644: L9-S814                           PROSTAGLANDIN F2ALPHA RECEPTOR   BLAST_PRODOM                           REGULATORY PROTEIN PRECURSOR                           ASSOCIATED SIGNAL                           IMMUNOGLOBULIN FOLD TRANSMEMBRANE                           GLYCOPROTEIN PD185779: K815-D879                           IMMUNOGLOBULIN   BLAST_DOMO                           DM00001|I39207|25-139: V26-Y132                           DM00001|I39207|141-259: V140-E255                           RGD motif: R703-D705   MOTIFS       3    3737084CD1   473   S243 S280 S383   N246 N457   Transmembrane domains:   HMMER                   S387 S56 T368       M95-Y112, P141-M166, Y257-G277,                   T434 Y417 Y444       N396-I419                           PROTEIN CHANNEL DIE2 POTASSIUM REGULATOR   BLAST_PRODOM                           IONIC C56F8.06C CHROMOSOME I PRECURSOR                           PD025171:                           E33-S387, W395-N428, S435-W473                           POTASSIUM CHANNEL REGULATOR 1   BLAST_PRODOM                           IONIC CHANNEL PD184319: M1-R32       4   71426238CD1   223   T132 T174       Connexin: M1-L201   HMMER_PFAM                           CONNEXINS DM00590   BLAST_DOMO                           |Q02739|1-268: M1-P218                           |P28231|1-269: M1-K208                           |Q02738|1-262: M1-L206                           |P08034|1-276: M1-K204                           GAP JUNCTION CONNEXIN PROTEIN   BLAST_PRODOM                           TRANSMEMBRANE ALPHA1 CX43 ALPHA8 ALPHA5                           BETA1 PD001135: W3-K108, M16-L201                           GAP JUNCTION PROTEIN CONNEXIN   BLAST_PRODOM                           TRANSMEMBRANE BETA2 CX26 BETA4 CX31.1                           DISEASE PD001118: G119-L201                           Connexins proteins. BL00407: S2-V38,   BLIMPS_BLOCKS                           A39-F69, P70-Y97, G118-D147, C157-L201                           CONNEXIN SIGNATURE PR00206: I20-W44, F51-   BLIMPS_PRINTS                           Q73, L76-A96, L120-Y146, C157-T177, I178-                           L201                           transmembrane domain: I23-A39, L120-Y143,   HMMER                           T177-F200                           Connexins signature 2: C157-P173   MOTIFS                           Connexins signatures connexins_1: L33-T86   PROFILESCAN                           Connexins signatures connexins_2: I136-L193   PROFILESCAN       5    7475123CD1   1553   S1007 S1011   N1063 N1115   signal_cleavage: M1-A20   SPSCAN                   S1016 S1065   N1409 N1449   LDL RECEPTOR LIGAND-BINDING REPEAT   BLAST_DOMO                   S1103 S1108   N549 N725   DM00045 |P01130|37-111: C44-D113,                   S1117 S1152       G81-S149, G120-P183                   S1234 S1313       LDL RECEPTOR LIGAND-BINDING REPEAT   BLAST_DOMO                   S1337 S1346       DM00045|P98160|295-336: G81-C122                   S1416 S1420       LDL RECEPTOR LIGAND-BINDING REPEAT   BLAST_DOMO                   S1465 S1479       DM00045|I48623|82-120: C83-C122                   S149 S1504       GLYCOPROTEIN PROTEIN RECEPTOR EGF-LIKE   BLAST_PRODOM                   S1535 S1548       DOMAIN LIPOPROTEIN PRECURSOR SIGNAL                   S177 S21 S287       TRANSMEMBRANE RECEPTOR RELATED PD149641:                   S366 S390 S404       R431-D559, D1044-D1171, Q739-D867                   S430 S496 S529       LOW DENSITY LIPOPROTEIN RECEPTOR RELATED   BLAST_PRODOM                   S540 S562 S583       PROTEIN PRECURSOR LRP RECEPTOR                   S61 S72 S761       TRANSMEMBRANE REPEAT ENDOCYTOSIS                   S804 S816 S843       GLYCOPROTEIN SIGNAL CALCIUM BINDING EGF-                   S848       LIKE DOMAIN COATED PITS PD126644: V440-                   T1095 T1174       I707, I753-Y1040, I1057-C1287                   T1211 T1331       HYPOTHETICAL 294.4 KD PROTEIN HYPOTHETICAL   BLAST_PRODOM                   T1336 T1508       PROTEIN PD126659: C661-I1015                   T384 T389 T453       LDL-receptor class A (LDLRA) domain   BLIMPS_BLOCKS                   T461 T475 T485       proteins BL01209: C90-E102                   T623 T629 T727       LOW DENSITY LIPOPROTEIN PR00261: G81-E102,   BLIMPS_PRINTS                   T793 T880 T907       C42-E63, G158-E179, G201-E222                           signal peptide: M1-G18   HMMER                           transmembrane domain: I1372-A1390   HMMER                           Low-density lipoprotein receptor repeat:   HMMER_PFAM                           D433-V474 N476-M517 G519-G561 Q563-E604                           R605-R645 G741-I782 R784-E825 G827-A869                           S871-S911 Y912-A953 G1045-V1086 R1088-R1129                           G1131-D1173 R1175-T1220                           Low-density lipoprotein receptor domain:   HMMER_PFAM                           P23-L68, P69-P107, Q237-W275, P189-E227,                           R146-S184, R108-M145,       6    7481952CD1   1718   S1027 S1031   N1235 N126   Transmembrane domain: I1642-A1660   HMMER                   S1095 S1111   N1299 N1345   Low-density lipoprotein receptor domain:   HMMER_PFAM                   S1165 S1273   N1545 N1634   E383-P423, H610-M649, G1043-S1081,                   S1310 S1463   N1684 N183   S1463-L1502, P1507-N1545, K1546-E1586,                   S1482 S1510   N260 N375   R824-T864, E1244-H1283                   S1517 S1544   N496 N551   MAN domain:   HMMER_PFAM                   S1583 S1686   N611 N703   C38-I199, C216-L378, C427-L586,                   S200 S214 S240   N761 N910   C652-P818, C869-S1027, C1083-T1238,                   S274 S28 S366   N969 N976   C1291-T1454                   S553 S565 S580       LDL-receptor class A BL01209:   BLIMPS_BLOCKS                   S812 S866 S877       C1485-E1497                   S938 T1178       MAM domain proteins:   BLIMPS_BLOCKS                   T1238 T133       BL00740A: C434-W446,                   T1359 T1371       BL00740B: R1011-S1031                   T1391 T468 T504       Low density lipoprotein receptor PR00261:   BLIMPS_PRINTS                   T597 T613 T676       L1476-E1497, R397-E418, K836-E857                   T763 T827       MAM domain proteins:   BLAST_DOMO                           DM01344|P98072|352-509: E418-D578                           DM01344|P28824|595-796: E424-D577                           DM01344|A55620|961-1128: C421-I576                           Cell attachment sequences (RGD):   MOTIFS                           R1011-D1013, R1138-D1140       7    382654CD1   224   S139 S165 S48       Transmembrane domain: I51-W71   HMMER                   S74 T179 T202       8    1867351CD1   570   S317 S336 S356   N82   Signal peptide: M1-C63   SPScan                   S538 S94 T367       Transmembrane domains:   HMMER                           L38-I58, A302-N322, V338-C357,                           I414-M436, L438-I457, L542-R564                           Uncharacterized membrane protein family   HMMER_PFAM                           UPF0013:                           G43-L204, I264-A426                           Integral membrane protein PD004336:   BLAST_PRODOM                           V344-W462                           Integral membrane protein PD149928:   BLAST_PRODOM                           I55-P129                           Leucine zipper pattern: L537-L558   MOTIFS       9    3323104CD1   423   S141 S203 S3   N400   Transmembrane domains:   HMMER                   T263 T417 T48       L228-Y247, F386-I405                   T73 Y52       Leucine zipper pattern: L215-L236   MOTIFS                           Intergenic region transmembrane protein:   BLAST_PRODOM                           PD040574: W131-I408       10    4769306CD1   388   S141 S188 S232   N161 N195   Transmembrane domain: V200-I220   HMMER                   S279 S294 S303   N301 N336   CUB domain: C27-F139   HMMER_PFAM                   S357 S361 S377   N384   Low-density lipoprotein receptor domain:   HMMER_PFAM                   S4 S96 S97 T187       P145-E183                   T252 T385 T50       LDL-receptor class A BL01209: C166-E178   BLIMPS_BLOCKS       11   2720058CD1   231   S137 T177 T220   N54 N75   Signal peptide: M1-A14   SPScan                   T42 Y190       Transmembrane domains:   HMMER                           F6-S26, V95-H115, I196-D215       12    7481255CD1   293   S109 S148 S251   N243 N277   Signal peptide: M1-S28   HMMER                   S95 T236 T35   N59 N67   Signal peptide: M1-S22   SPScan                           Transmembrane domains:   HMMER                           I126-G144, W156-I184                           PMP-22/EMP/MP20 family BL01221:   BLIMPS_BLOCKS                           F88-N101, Y203-T229       13    1510242CD1   526   S279 S479 T22   N180 N201   Transmembrane domains:   HMMER                   Y125   N378   L146-L172, V217-L235, P333-W351       14    162131CD1   348   S45 S187 S344       transmembrane domain: I149-L175   HMMER                   T33 T54 T207       APOLIPOPROTEIN L PRECURSOR APOL PLASMA   BLAST_PRODOM                   T246 T271 Y39       LIPID TRANSPORT GLYCOPROTEIN SIGNAL                   Y77       DJ6802.1 PD042084: T9-A347       15    1837725CD1   520   S8 S54 S141 T37   N35 N58   signal_cleavage: M1-A25   SPSCAN                   T151 T157 T202   N66 N74   signal_peptide: M1-A28   HMMER                   T331 T505   N116 N126   transmembrane domain: M172-G191, F218-L237,   HMMER                       N149 N155   W243-Y261, V287-F306, L346-E371       16    3643847CD1   534   S35 S40 S124   N31 N129   signal_cleavage: M1-G57   SPSCAN                   S133 S338 S512   N283 N352   transmembrane domain: L46-F62, L214-G233,   HMMER                   S519 T143 T170       L390-C408                   T339 T418 Y207       TWEETY F42E11.2 PROTEIN PD043235: V20-D429   BLAST_PRODOM                           Cell attachment sequence R164-D166   MOTIFS       17    6889872CD1   820   S92 S160 S164   N54 N80 N85   signal_cleavage: M1-A22   SPSCAN                   S217 S289 S363   N117 N205   signal_peptide: M1-A22   HMMER                   S367 S530 S568   N247 N329   transmembrane domain: T394-Y416   HMMER                   S636 S639 S672   N371   Leucine Rich Repeat: T56-G79, N80-S103,   HMMER_PFAM                   S725 S737 S741       S104-S127, R128-P151, S152-A175                   S747 S757 T56                   T87 T338 T378                   T437 T483 T493                   T625 T766 Y443                   Y743 Y785                    
     [0380]                                       TABLE 4                       Polynucleotide   Incyte   Sequence   Selected           3′       SEQ ID NO:   Polynucleotide ID   Length   Fragment(s)   Sequence Fragments   5′ Position   Position                                                            18    6431478CB1   2653   1-606, 2109-2306   6798827J1 (COLENOR03)   2076   2653                       6882379J1 (BRAHTDR03)   1679   2342                       7162277F8 (PLACNOR01)   1427   2173                       7757207J1 (SPLNTUE01)   418   1133                       6109577F6 (MCLDTXT03)   870   1464                       7196064F8 (LUNGFER04)   1   735       19    3584654CB1   3531   1-1782   71760758V1   2094   2675                       71760788V1   2684   3350                       71761160V1   2577   3331                       7658349J1 (UTREDME06)   1341   1989                       70815172V1   1481   2064                       71764416V1   2978   3531                       71754337V1   1965   2648                       7183593H1 (BONRFEC01)   1   603                       7709623J1 (PANCNOE02)   895   1480                       6807068F6 (SKIRNOR01)   293   1156       20    3737084CB1   2280   947-997, 1840-2280   70409519D1   1372   1947                       70408370D1   1720   2280                       70400676D1   859   1371                       2310625T6 (NGANNOT01)   1282   1832                       71685057V1   609   1268                       71683716V1   1   748       21   71426238CB1   1104   1-115, 550-624,   1947421R6 (PITUNOT01)   1   508                   198-513                       71433875V1   435   1104       22    7475123CB1   4966   1-957, 1328-3163   70879893V1   4038   4682                       8124425H1 (HEAONOC01)   4309   4966                       8253556H1 (BRAHDIT10)   3948   4663                       6891485J1 (BRAITDR03)   2762   3423                       6885135H1 (BRAHTDR03)   1   468                       593337R6 (BRAVUNT02)   3439   3968                       70673072V1   3303   3965                       GBI.g7705145_17_12_25 —     337   3773                       27.regenscan ()       23    7481952CB1   5401   4237-4630, 2834-3834,   55153856J1   1947   2415                   1-2283,                   4757-4851                       GNN.g10120165_000001 —     1   342                       006.edit                       6933885R6 (SINTTMR02)   2518   3182                       6933885H1 (SINTTMR02)   2339   3011                       72434542D1   4614   5401                       55153330J1   3010   3752                       899395H1 (BRSTTUT03)   1589   1891                       55153261H1   311   899                       71876387V1   4346   5105                       71932270V1   3716   4305                       55153293H1   364   1151                       55153285J1   886   1816                       72432008D1   4234   5099                       GNN.g9843576_000009_006   1678   2105       24    382654CB1   1949   1-247, 1882-1949   7629906H1 (BRAFTUE03)   1   517                       6618349J2 (BRAUTDR03)   1282   1949                       6884626H1 (BRAHTDR03)   541   1060                       6952509H1 (BRAITDR02)   1035   1600                       6891983H1 (BRAITDR03)   468   1056                       6891983J1 (BRAITDR03)   1121   1671       25    1867351CB1   2133   987-1049, 1927-2133,   70571014V1   1520   2133                   779-832                       70568556V1   1259   1924                       7261108H1 (UTRETMC01)   646   1135                       8004078H1 (MUSCTDC01)   1   704                       70570876V1   1151   1828                       55026730J1   692   1215                       (ADMEDNV22)       26    3323104CB1   2090   1-34, 415-1111   702759T6 (SYNORAT03)   1128   1767                       71220067V1   585   1119                       70833651V1   553   1114                       70769661V1   1061   1692                       8133288H1 (SCOMDIC01)   1   578                       70771538V1   1625   2090       27    4769306CB1   1618   1-208, 561-723   70954880V1   1126   1618                       3269667H1 (BRAINOT20)   1   244                       70955603V1   648   1272                       8103247H1 (MIXDDIE02)   229   797                       7076427H1 (BRAUTDR04)   49   677                       70953588V1   795   1368       28    2720058CB1   3269   2536-2564, 1-220,   2657501T6 (LUNGTUT09)   2502   3056                   2785-3269                       71520348V1   1839   2547                       71524606V1   1139   1824                       2657501F6 (LUNGTUT09)   594   1126                       7225843H1 (LUNGTMC01)   392   983                       71670642V1   1721   2424                       1305113F6 (PLACNOT02)   1   571                       1955363F6 (CONNNOT01)   2570   3058                       1375665F6 (LUNGNOT10)   2677   3269                       71521430V1   1054   1714       29    7481255CB1   1227   1-1227   3269676H1 (BRAINOT20)   5   96                       GBI.g7622436_000021_000024.   1   1227                       edit                       FL7481255_g8469082_000035 —     99   304                       g4150939_1_1                       4538535F6 (THYRTMT01)   654   1227       30    1510242CB1   2618   1-515, 2475-2618   6823120J1 (SINTNOR01)   1889   2437                       7036758F7 (UTRSTMR02)   1   705                       7355340H1 (HEARNON03)   2005   2618                       7930760H1 (COLNDIS02)   1224   1900                       6837255H1 (BRSTNON02)   673   1368                       70366002D1   1430   1904                       3413605H1 (PTHYNOT04)   2456   2618                       71808592V1   806   1433                       6823120H1 (SINTNOR01)   1820   2436       31    162131CB1   2188   1-25, 1173-1633   g1506355   1667   2188                       7243158H2 (PROSTMY01)   1351   1878                       1998635R6 (BRSTTUT03)   1632   2172                       70559145V1   454   1196                       70558921V1   1069   1787                       2818229F6 (BRSTNOT14)   1   540                       70558931V1   549   1305       32    1837725CB1   1969   1-400, 1927-1969   70377507D1   1400   1955                       g1378655   1517   1969                       70378490D1   639   1268                       6799889J1 (COLENOR03)   1   673                       8227475H1 (BRAUTDR02)   778   1463                       2352377H1 (COLSUCT01)   1763   1959       33    3643847CB1   3006   796-1137, 2849-3006   1478479H1 (CORPNOT02)   2745   3006                       6993355H1 (BRAQTDR02)   1129   1755                       5964485H1 (BRATNOT05)   1772   2489                       1419930H1 (KIDNNOT09)   2650   2892                       6789167H1 (BRACNOK01)   2091   2801                       6118619H1 (BRAHNON05)   1992   2546                       7436931H1 (ADRETUE02)   594   1202                       72018042V1   1   579                       72018222V1   413   1028                       1992275F6 (CORPNOT02)   1268   1809       34    6889872CB1   2884   1-319, 2090-2884,   8230901H1 (BRAUTDR02)   873   1610                   803-1585,                   379-418, 1991-2017                       8230892H1 (BRAUTDR02)   1   725                       8230892J1 (BRAUTDR02)   676   1356                       7634710H1 (SINTDIE01)   1577   2162                       GNN: g3191973_012   422   2884                    
     [0381]                       TABLE 5                       Polynucleotide   Incyte   Representative       SEQ ID NO:   Project ID   Library                  18   6431478CB1   BRAHTDR03       19   3584654CB1   PROSNOT11       20   3737084CB1   PROSNON01       21   71426238CB1   PITUNOT01       22   7475123CB1   CONUTUT01       23   7481952CB1   SINTTMR02       24   382654CB1   BRAHTDR03       25   1867351CB1   BRAITUT21       26   3323104CB1   LUNGNOT27       27   4769306CB1   BRAMNOT01       28   2720058CB1   LUNGTUT10       29   7481255CB1   THYRTMT01       30   1510242CB1   SINTFER02       31   162131CB1   PANCNOT15       32   1837725CB1   SINDNOT01       33   3643847CB1   CORPNOT02       34   6889872CB1   SINTDIE01                    
     [0382]                       TABLE 6                       Library   Vector   Library Description                  BRAHTDR03   PCDNA2.1   This random primed library was constructed using RNA isolated from archaecortex,               anterior hippocampus tissue removed from a 55-year-old Caucasian female who died from               cholangiocarcinoma. Pathology indicated mild meningeal fibrosis predominately over               the convexities, scattered axonal spheroids in the white matter of the cingulate               cortex and the thalamus, and a few scattered neurofibrillary tangles in the               entorhinal cortex and the periaqueductal gray region. Pathology for the associated               tumor tissue indicated well-differentiated cholangiocarcinoma of the liver with               residual or relapsed tumor. Patient history included cholangiocarcinoma, post-               operative Budd-Chiari syndrome, biliary ascites, hydrothorax, dehydration,               malnutrition, oliguria and acute renal failure. Previous surgeries included               cholecystectomy and resection of 85% of the liver.       BRAITUT21   pINCY   Library was constructed using RNA isolated from brain tumor tissue removed from the               midline frontal lobe of a 61-year-old Caucasian female during excision of a cerebral               meningeal lesion. Pathology indicated subfrontal meningothelial meningioma with no               atypia. One ethmoid and mucosal tissue sample indicated meningioma. Family history               included cerebrovascular disease, senile dementia, hyperlipidemia, benign               hypertension, atherosclerotic coronary artery disease, congestive heart failure, and               breast cancer.       BRAMNOT01   pINCY   Library was constructed using RNA isolated from medulla tissue removed from the brain               of a 35-year-old Caucasian male who died from cardiac failure. Pathology indicated               moderate leptomeningeal fibrosis and multiple microinfarctions of the cerebral               neocortex. Microscopically, the cerebral hemisphere revealed moderate fibrosis of the               leptomeninges with focal calcifications. There was evidence of shrunken and slightly               eosinophilic pyramidal neurons throughout the cerebral hemispheres. In addition,               scattered throughout the cerebral cortex, there were multiple small microscopic areas               of cavitation with surrounding gliosis. Patient history included dilated               cardiomyopathy, congestive heart failure, cardiomegaly and an enlarged spleen and               liver.       CONUTUT01   pINCY   Library was constructed using RNA isolated from sigmoid mesentery tumor tissue               obtained from a 61-year-old female during a total abdominal hysterectomy and               bilateral salpingo-oophorectomy with regional lymph node excision. Pathology               indicated a metastatic grade 4 malignant mixed mullerian tumor present in the sigmoid               mesentery at two sites.       CORPNOT02   pINCY   Library was constructed using RNA isolated from diseased corpus callosum tissue               removed from the brain of a 74-year-old Caucasian male who died from Alzheimer&#39;s               disease.       LUNGNOT27   pINCY   Library was constructed using RNA isolated from lung tissue removed from a 17-year-               old Hispanic female.       LUNGTUT10   pINCY   Library was constructed using RNA isolated from lung tumor tissue removed from the               left upper lobe of a 65-year-old Caucasian female during a segmental lung resection.               Pathology indicated a metastatic grade 2 myxoid liposarcoma and a metastatic grade 4               liposarcoma. Patient history included soft tissue cancer, breast cancer, and               secondary lung cancer.       PANCNOT15   pINCY   Library was constructed using RNA isolated from diseased pancreatic tissue removed               from a 15-year-old Caucasian male during a exploratory laparotomy with distal               pancreatectomy and total splenectomy. Pathology indicated islet cell hyperplasia               Family history included prostate cancer and cardiovacular disease.       PITUNOT01   PBLUESCRIPT   Library was constructed using RNA obtained from Clontech (CLON 6584-2, lot 35278).               The RNA was isolated from the pituitary glands removed from a pool of 18 male and               female Caucasian donors, 16 to 70 years old, who died from trauma.       PROSNON01   PSPORT1   This normalized prostate library was constructed from 4.4 M independent clones from a               prostate library. Starting RNA was made from prostate tissue removed from a 28-year-               old Caucasian male who died from a self-inflicted gunshot wound. The normalization               and hybridization conditions were adapted from Soares, M.B. et al. (1994) Proc. Natl.               Acad. Sci. U.S.A. 91: 9228-9232, using a longer (19 hour) reannealing hybridization               period.       PROSNOT11   pINCY   Library was constructed using RNA isolated from the prostate tissue of a 28-year-old               Caucasian male, who died from a self-inflicted gunshot wound.       SINDNOT01   pINCY   Library was constructed using RNA isolated from duodenum tissue removed from the               small intestine of a 16-year-old Caucasian male who died from head trauma. Patient               history included a kidney infection.       SINTDIE01   PCDNA2.1   This 5′ biased random primed library was constructed using RNA isolated from small               intestine tissue removed from a 49-year-old Caucasian female during               gastroenterostomy, exploratory laparotmy, and vagotomy. The patient presented with               acute stomach ulcer with obstruction, nausea and vomiting, and abnormal weight loss.               Patient history included backache, acute stomach ulcer with perforation, and normal               delivery. Previous surgeries included adenotonsillectomy and total abdominal               hysterectomy. Patient medications included Premarin. Family history included benign               hypertension, type II diabetes and congestive heart failure in the father.       SINTFER02   pINCY   This random primed library was constructed using RNA isolated from small intestine               tissue removed from a Caucasian male fetus who died from fetal demise.       SINTTMR02   PCDNA2.1   This random primed library was constructed using RNA isolated from small intestine               tissue removed from a 59-year-old male. Pathology for the matched tumor tissue               indicated multiple (9) carcinoid tumors, grade 1, in the small bowel. The largest               tumor was associated with a large mesenteric mass. Multiple convoluted segments of               bowel were adhered to the tumor. A single (1 of 13) regional lymph node was positive               for malignancy. The peritoneal biopsy indicated focal fat necrosis.       THYRTMT01   pINCY   Library was constructed using RNA isolated from left thyroid tissue removed from a               56-year-old Caucasian male during a unilateral thyroid lobectomy and fine needle               thyroid biopsy. Pathology for the associated tumor tissue indicated medullary               carcinoma invading the overlying skeletal muscle. Metastatic medullary carcinoma               involved one carotid sheath lymph node (of 9), one left neck lymph node with extra               nodular extension, and a central compartment node. A microscopic focus of grade 1               papillary carcinoma was identified within the right lobe of the thyroid lobe. The               left thyroid vein biopsy was negative for tumor. Patient history included               hyperlipidemia, headache, and atherosclerotic coronary artery disease. Family history               included cerebrovascular disease, cardiovasclar disease and bone cancer.                    
     [0383]                           TABLE 7                       Program   Description   Reference   Parameter Threshold                  ABI   A program that removes vector sequences and   Applied Biosystems, Foster City, CA.           FACTURA   masks ambiguous bases in nucleic acid sequences.       ABI/   A Fast Data Finder useful in comparing and   Applied Biosystems, Foster City, CA;   Mismatch &lt; 50%       PARACEL   annotating amino acid or nucleic acid sequences.   Paracel Inc., Pasadena, CA.       FDF       ABI Auto-   A program that assembles nucleic acid sequences.   Applied Biosystems, Foster City, CA.       Assembler       BLAST   A Basic Local Alignment Search Tool useful in   Altschul, S. F. et al. (1990) J. Mol. Biol.   ESTs: Probability value = 1.0E−8           sequence similarity search for amino acid and   215: 403-410; Altschul, S. F. et al. (1997)   or less           nucleic acid sequences. BLAST includes five   Nucleic Acids Res. 25: 3389-3402.   Full Length sequences: Probability           functions: blastp, blastn, blastx, tblastn, and tblastx.       value = 1.0E−10 or less       FASTA   A Pearson and Lipman algorithm that searches for   Pearson, W. R. and D. J. Lipman (1988) Proc.   ESTs: fasta E value = 1.06E−6           similarity between a query sequence and a group of   Natl. Acad Sci. USA 85: 2444-2448; Pearson,   Assembled ESTs: fasta Identity =           sequences of the same type. FASTA comprises as   W. R. (1990) Methods Enzymol. 183: 63-98;   95% or greater and           least five functions: fasta, tfasta, fastx, tfastx, and   and Smith, T. F. and M. S. Waterman (1981)   Match length = 200 bases or great-           ssearch.   Adv. Appl. Math. 2: 482-489.   er; fastx E value = 1.0E−8 or less                   Full Length sequences:                   fastx score = 100 or greater       BLIMPS   A BLocks IMProved Searcher that matches a   Henikoff, S. and J. G. Henikoff (1991) Nucleic   Probability value = 1.0E−3 or less           sequence against those in BLOCKS, PRINTS,   Acids Res. 19: 6565-6572; Henikoff, J. G. and           DOMO, PRODOM, and PFAM databases to search   S. Henikoff (1996) Methods Enzymol.           for gene families, sequence homology, and   266: 88-105; and Attwood, T. K. et al.           structural fingerprint regions.   (1997) J. Chem. Inf. Comput. Sci. 37:               417-424.       HMMER   An algorithm for searching a query sequence against   Krogh, A. et al. (1994) J. Mol. Biol.   PFAM hits: Probability value =           hidden Markov model (HMM)-based databases of   235: 1501-1531; Sonnhammer, E. L. L. et al.   1.0E−3 or less           protein family consensus sequences, such as PFAM.   (1988) Nucleic Acids Res. 26: 320-322;   Signal peptide hits: Score = 0 or               Durbin, R. et al. (1998) Our World View, in a   greater               Nutshell, Cambridge Univ. Press, pp. 1-350.       ProfileScan   An algorithm that searches for structural and   Gribskov, M. et al. (1988) CABIOS 4: 61-66;   Normalized quality score ≧ GCG-           sequence motifs in protein sequences that match   Gribskov, M. et al. (1989) Methods Enzymol.   specified “HIGH” value for that           defined in Prosite.   183: 146-159; Bairoch, A. et al. (1997)   particular Prosite motif.               Nucleic Acids Res. 25: 217-221.   Generally, score = 1.4-2.1.       Phred   A base-calling algorithm that examines automated   Ewing, B. et al. (1998) Genome Res.           sequencer traces with high sensitivity and   8: 175-185; Ewing, B. and P. Green           probability.   (1998) Genome Res. 8: 186-194.       Phrap   A Phils Revised Assembly Program including   Smith, T. F. and M. S. Waterman (1981) Adv.   Score = 120 or greater;           SWAT and CrossMatch, programs based on   Appl. Math. 2: 482-489; Smith, T. F. and   Match length = 56 or greater           efficient implementationof the Smith-Waterman   M. S. Waterman (1981) J. Mol. Biol. 147:           algorithm, useful in searching sequence homology   195-197; and Green, P., University of           and assembling DNA sequences.   Washington, Seattle, WA.       Consed   A graphical tool for viewing and editing Phrap   Gordon, D. et al. (1998) Genome Res.           assemblies.   8: 195-202.       SPScan   A weight matrix analysis program that scans protein   Nielson, H. et al. (1997) Protein Engineering   Score = 3.5 or greater           sequences for the presence of secretory   10: 1-6; Claverie, J. M. and S. Audic (1997)           signal peptides.   CABIOS 12: 431-439.       TMAP   A program that uses weight matrices to delineate   Persson, B. and P. Argos (1994) J. Mol. Biol.           transmembrane segments on protein sequences and   237: 182-192; Persson, B. and P. Argos (1996)           determine orientation.   Protein Sci. 5: 363-371.       TMHMMER   A program that uses a hidden Markov   Sonnhammer, E. L. et al. (1998) Proc. Sixth           model (HMM) to delineate transmembrane segments   Intl. Conf. on Intelligent Systems for Mol.           on protein sequences and determine orientation.   Biol., Glasgow et al., eds., The Am.               Assoc. for Artificial Intelligence Press,               Menlo Park, CA, pp. 175-182.       Motifs   A program that searches amino acid sequences for   Bairoch, A. et al. (1997) Nucleic Acids Res.           patterns that matched those defined in Prosite.   25: 217-221; Wisconsin Package Program               Manual, version 9, page M51-59, Genetics               Computer Group, Madison, WI.                    
     [0384] 
    
     
       
         1 
         
           
             34  
           
           
             1  
             461  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 6431478CD1  
             
           
            1 

Met Ser Ala Gln Cys Cys Ala Gly Gln Leu Ala Cys Cys Cys Gly 
  1               5                  10                  15 

Ser Ala Gly Cys Ser Leu Cys Cys Asp Cys Cys Pro Arg Ile Arg 
                 20                  25                  30 

Gln Ser Leu Ser Thr Arg Phe Met Tyr Ala Leu Tyr Phe Ile Leu 
                 35                  40                  45 

Val Val Val Leu Cys Cys Ile Met Met Ser Thr Thr Val Ala His 
                 50                  55                  60 

Lys Met Lys Glu His Ile Pro Phe Phe Glu Asp Met Cys Lys Gly 
                 65                  70                  75 

Ile Lys Ala Gly Asp Thr Cys Glu Lys Leu Val Gly Tyr Ser Ala 
                 80                  85                  90 

Val Tyr Arg Val Cys Phe Gly Met Ala Cys Phe Phe Phe Ile Phe 
                 95                 100                 105 

Cys Leu Leu Thr Leu Lys Ile Asn Asn Ser Lys Ser Cys Arg Ala 
                110                 115                 120 

His Ile His Asn Gly Phe Trp Phe Phe Lys Leu Leu Leu Leu Gly 
                125                 130                 135 

Ala Met Cys Ser Gly Ala Phe Phe Ile Pro Asp Gln Asp Thr Phe 
                140                 145                 150 

Leu Asn Ala Trp Arg Tyr Val Gly Ala Val Gly Gly Phe Leu Phe 
                155                 160                 165 

Ile Gly Ile Gln Leu Leu Leu Leu Val Glu Phe Ala His Lys Trp 
                170                 175                 180 

Asn Lys Asn Trp Thr Ala Gly Thr Ala Ser Asn Lys Leu Trp Tyr 
                185                 190                 195 

Ala Ser Leu Ala Leu Val Thr Leu Ile Met Tyr Ser Ile Ala Thr 
                200                 205                 210 

Gly Gly Leu Val Leu Met Ala Val Phe Tyr Thr Gln Lys Asp Ser 
                215                 220                 225 

Cys Met Glu Asn Lys Ile Leu Leu Gly Val Asn Gly Gly Leu Cys 
                230                 235                 240 

Leu Leu Ile Ser Leu Val Ala Ile Ser Pro Trp Val Gln Asn Arg 
                245                 250                 255 

Gln Pro His Ser Gly Leu Leu Gln Ser Gly Val Ile Ser Cys Tyr 
                260                 265                 270 

Val Thr Tyr Leu Thr Phe Ser Ala Leu Ser Ser Lys Pro Ala Glu 
                275                 280                 285 

Val Val Leu Asp Glu His Gly Lys Asn Val Thr Ile Cys Val Pro 
                290                 295                 300 

Asp Phe Gly Gln Asp Leu Tyr Arg Asp Glu Asn Leu Val Thr Ile 
                305                 310                 315 

Leu Gly Thr Ser Leu Leu Ile Gly Cys Ile Leu Tyr Ser Cys Leu 
                320                 325                 330 

Thr Ser Thr Thr Arg Ser Ser Ser Asp Ala Leu Gln Gly Arg Tyr 
                335                 340                 345 

Ala Ala Pro Glu Leu Glu Ile Ala Arg Cys Cys Phe Cys Phe Ser 
                350                 355                 360 

Pro Gly Gly Glu Asp Thr Glu Glu Gln Gln Pro Gly Lys Glu Gly 
                365                 370                 375 

Pro Arg Val Ile Tyr Asp Glu Lys Lys Gly Thr Val Tyr Ile Tyr 
                380                 385                 390 

Ser Tyr Phe His Phe Val Phe Phe Leu Ala Ser Leu Tyr Val Met 
                395                 400                 405 

Met Thr Val Thr Asn Trp Phe Asn Tyr Glu Ser Ala Asn Ile Glu 
                410                 415                 420 

Ser Phe Phe Ser Gly Ser Trp Ser Ile Phe Trp Val Lys Met Ala 
                425                 430                 435 

Ser Cys Trp Ile Cys Val Leu Leu Tyr Leu Cys Thr Leu Val Ala 
                440                 445                 450 

Pro Leu Cys Cys Pro Thr Arg Glu Phe Ser Val 
                455                 460 

 
           
             2  
             879  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 3584654CD1  
             
           
            2 

Met Gly Arg Leu Ala Ser Arg Pro Leu Leu Leu Ala Leu Leu Ser 
  1               5                  10                  15 

Leu Ala Leu Cys Arg Gly Arg Val Val Arg Val Pro Thr Ala Thr 
                 20                  25                  30 

Leu Val Arg Val Val Gly Thr Glu Leu Val Ile Pro Cys Asn Val 
                 35                  40                  45 

Ser Asp Tyr Asp Gly Pro Ser Glu Gln Asn Phe Asp Trp Ser Phe 
                 50                  55                  60 

Ser Ser Leu Gly Ser Ser Phe Val Glu Leu Ala Ser Thr Trp Glu 
                 65                  70                  75 

Val Gly Phe Pro Ala Gln Leu Tyr Gln Glu Arg Leu Gln Arg Gly 
                 80                  85                  90 

Glu Ile Leu Leu Arg Arg Thr Ala Asn Asp Ala Val Glu Leu His 
                 95                 100                 105 

Ile Lys Asn Val Gln Pro Ser Asp Gln Gly His Tyr Lys Cys Ser 
                110                 115                 120 

Thr Pro Ser Thr Asp Ala Thr Val Gln Gly Asn Tyr Glu Asp Thr 
                125                 130                 135 

Val Gln Val Lys Val Leu Ala Asp Ser Leu His Val Gly Pro Ser 
                140                 145                 150 

Ala Arg Pro Pro Pro Ser Leu Ser Leu Arg Glu Gly Glu Pro Phe 
                155                 160                 165 

Glu Leu Arg Cys Thr Ala Ala Ser Ala Ser Pro Leu His Thr His 
                170                 175                 180 

Leu Ala Leu Leu Trp Glu Val His Arg Gly Pro Ala Arg Arg Ser 
                185                 190                 195 

Val Leu Ala Leu Thr His Glu Gly Arg Phe His Pro Gly Leu Gly 
                200                 205                 210 

Tyr Glu Gln Arg Tyr His Ser Gly Asp Val Arg Leu Asp Thr Val 
                215                 220                 225 

Gly Ser Asp Ala Tyr Arg Leu Ser Val Ser Arg Ala Leu Ser Ala 
                230                 235                 240 

Asp Gln Gly Ser Tyr Arg Cys Ile Val Ser Glu Trp Ile Ala Glu 
                245                 250                 255 

Gln Gly Asn Trp Gln Glu Ile Gln Glu Lys Ala Val Glu Val Ala 
                260                 265                 270 

Thr Val Val Ile Gln Pro Thr Val Leu Arg Ala Ala Val Pro Lys 
                275                 280                 285 

Asn Val Ser Val Ala Glu Gly Lys Glu Leu Asp Leu Thr Cys Asn 
                290                 295                 300 

Ile Thr Thr Asp Arg Ala Asp Asp Val Arg Pro Glu Val Thr Trp 
                305                 310                 315 

Ser Phe Ser Arg Met Pro Asp Ser Thr Leu Pro Gly Ser Arg Val 
                320                 325                 330 

Leu Ala Arg Leu Asp Arg Asp Ser Leu Val His Ser Ser Pro His 
                335                 340                 345 

Val Ala Leu Ser His Val Asp Ala Arg Ser Tyr His Leu Leu Val 
                350                 355                 360 

Arg Asp Val Ser Lys Glu Asn Ser Gly Tyr Tyr Tyr Cys His Val 
                365                 370                 375 

Ser Leu Trp Ala Pro Gly His Asn Arg Ser Trp His Lys Val Ala 
                380                 385                 390 

Glu Ala Val Ser Ser Pro Ala Gly Val Gly Val Thr Trp Leu Glu 
                395                 400                 405 

Pro Asp Tyr Gln Val Tyr Leu Asn Ala Ser Lys Val Pro Gly Phe 
                410                 415                 420 

Ala Asp Asp Pro Thr Glu Leu Ala Cys Arg Val Val Asp Thr Lys 
                425                 430                 435 

Ser Gly Glu Ala Asn Val Arg Phe Thr Val Ser Trp Tyr Tyr Arg 
                440                 445                 450 

Met Asn Arg Arg Ser Asp Asn Val Val Thr Ser Glu Leu Leu Ala 
                455                 460                 465 

Val Met Asp Gly Asp Trp Thr Leu Lys Tyr Gly Glu Arg Ser Lys 
                470                 475                 480 

Gln Arg Ala Gln Asp Gly Asp Phe Ile Phe Ser Lys Glu His Thr 
                485                 490                 495 

Asp Thr Phe Asn Phe Arg Ile Gln Arg Thr Thr Glu Glu Asp Arg 
                500                 505                 510 

Gly Asn Tyr Tyr Cys Val Val Ser Ala Trp Thr Lys Gln Arg Asn 
                515                 520                 525 

Asn Ser Trp Val Lys Ser Lys Asp Val Phe Ser Lys Pro Val Asn 
                530                 535                 540 

Ile Phe Trp Ala Leu Glu Asp Ser Val Leu Val Val Lys Ala Arg 
                545                 550                 555 

Gln Pro Lys Pro Phe Phe Ala Ala Gly Asn Thr Phe Glu Met Thr 
                560                 565                 570 

Cys Lys Val Ser Ser Lys Asn Ile Lys Ser Pro Arg Tyr Ser Val 
                575                 580                 585 

Leu Ile Met Ala Glu Lys Pro Val Gly Asp Leu Ser Ser Pro Asn 
                590                 595                 600 

Glu Thr Lys Tyr Ile Ile Ser Leu Asp Gln Asp Ser Val Val Lys 
                605                 610                 615 

Leu Glu Asn Trp Thr Asp Ala Ser Arg Val Asp Gly Val Val Leu 
                620                 625                 630 

Glu Lys Val Gln Glu Asp Glu Phe Arg Tyr Arg Met Tyr Gln Thr 
                635                 640                 645 

Gln Val Ser Asp Ala Gly Leu Tyr Arg Cys Met Val Thr Ala Trp 
                650                 655                 660 

Ser Pro Val Arg Gly Ser Leu Trp Arg Glu Ala Ala Thr Ser Leu 
                665                 670                 675 

Ser Asn Pro Ile Glu Ile Asp Phe Gln Thr Ser Gly Pro Ile Phe 
                680                 685                 690 

Asn Ala Ser Val His Ser Asp Thr Pro Ser Val Ile Arg Gly Asp 
                695                 700                 705 

Leu Ile Lys Leu Phe Cys Ile Ile Thr Val Glu Gly Ala Ala Leu 
                710                 715                 720 

Asp Pro Asp Asp Met Ala Phe Asp Val Ser Trp Phe Ala Val His 
                725                 730                 735 

Ser Phe Gly Leu Asp Lys Ala Pro Val Leu Leu Ser Ser Leu Asp 
                740                 745                 750 

Arg Lys Gly Ile Val Thr Thr Ser Arg Arg Asp Trp Lys Ser Asp 
                755                 760                 765 

Leu Ser Leu Glu Arg Val Ser Val Leu Glu Phe Leu Leu Gln Val 
                770                 775                 780 

His Gly Ser Glu Asp Gln Asp Phe Gly Asn Tyr Tyr Cys Ser Val 
                785                 790                 795 

Thr Pro Trp Val Lys Ser Pro Thr Gly Ser Trp Gln Lys Glu Ala 
                800                 805                 810 

Glu Ile His Ser Lys Pro Val Phe Ile Thr Val Lys Met Asp Val 
                815                 820                 825 

Leu Asn Ala Phe Lys Tyr Pro Leu Leu Ile Gly Val Gly Leu Ser 
                830                 835                 840 

Thr Val Ile Gly Leu Leu Ser Cys Leu Ile Gly Tyr Cys Ser Ser 
                845                 850                 855 

His Trp Cys Cys Lys Lys Glu Val Gln Glu Thr Arg Arg Glu Arg 
                860                 865                 870 

Arg Arg Leu Met Ser Met Glu Met Asp 
                875 

 
           
             3  
             473  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 3737084CD1  
             
           
            3 

Met Ala Gln Leu Glu Gly Tyr Tyr Phe Ser Ala Ala Leu Ser Cys 
  1               5                  10                  15 

Thr Phe Leu Val Ser Cys Leu Leu Phe Ser Ala Phe Ser Arg Ala 
                 20                  25                  30 

Leu Arg Glu Pro Tyr Met Asp Glu Ile Phe His Leu Pro Gln Ala 
                 35                  40                  45 

Gln Arg Tyr Cys Glu Gly His Phe Ser Leu Ser Gln Trp Asp Pro 
                 50                  55                  60 

Met Ile Thr Thr Leu Pro Gly Leu Tyr Leu Val Ser Ile Gly Val 
                 65                  70                  75 

Ile Lys Pro Ala Ile Trp Ile Phe Gly Trp Ser Glu His Val Val 
                 80                  85                  90 

Cys Ser Ile Gly Met Leu Arg Phe Val Asn Leu Leu Phe Ser Val 
                 95                 100                 105 

Gly Asn Phe Tyr Leu Leu Tyr Leu Leu Phe Cys Lys Val Gln Pro 
                110                 115                 120 

Arg Asn Lys Ala Ala Ser Ser Ile Gln Arg Val Leu Ser Thr Leu 
                125                 130                 135 

Thr Leu Ala Val Phe Pro Thr Leu Tyr Phe Phe Asn Phe Leu Tyr 
                140                 145                 150 

Tyr Thr Glu Ala Gly Ser Met Phe Phe Thr Leu Phe Ala Tyr Leu 
                155                 160                 165 

Met Cys Leu Tyr Gly Asn His Lys Thr Ser Ala Phe Leu Gly Phe 
                170                 175                 180 

Cys Gly Phe Met Phe Arg Gln Thr Asn Ile Ile Trp Ala Val Phe 
                185                 190                 195 

Cys Ala Gly Asn Val Ile Ala Gln Lys Leu Thr Glu Ala Trp Lys 
                200                 205                 210 

Thr Glu Leu Gln Lys Lys Glu Asp Arg Leu Pro Pro Ile Lys Gly 
                215                 220                 225 

Pro Phe Ala Glu Phe Arg Lys Ile Leu Gln Phe Leu Leu Ala Tyr 
                230                 235                 240 

Ser Met Ser Phe Lys Asn Leu Ser Met Leu Leu Leu Leu Thr Trp 
                245                 250                 255 

Pro Tyr Ile Leu Leu Gly Phe Leu Phe Cys Ala Phe Val Val Val 
                260                 265                 270 

Asn Gly Gly Ile Val Ile Gly Asp Arg Ser Ser His Glu Ala Cys 
                275                 280                 285 

Leu His Phe Pro Gln Leu Phe Tyr Phe Phe Ser Phe Thr Leu Phe 
                290                 295                 300 

Phe Ser Phe Pro His Leu Leu Ser Pro Ser Lys Ile Lys Thr Phe 
                305                 310                 315 

Leu Ser Leu Val Trp Lys Arg Arg Ile Leu Phe Phe Val Val Thr 
                320                 325                 330 

Leu Val Ser Val Phe Leu Val Trp Lys Phe Thr Tyr Ala His Lys 
                335                 340                 345 

Tyr Leu Leu Ala Asp Asn Arg His Tyr Thr Phe Tyr Val Trp Lys 
                350                 355                 360 

Arg Val Phe Gln Arg Tyr Glu Thr Val Lys Tyr Leu Leu Val Pro 
                365                 370                 375 

Ala Tyr Ile Phe Ala Gly Trp Ser Ile Ala Asp Ser Leu Lys Ser 
                380                 385                 390 

Lys Ser Ile Phe Trp Asn Leu Met Phe Phe Ile Cys Leu Phe Thr 
                395                 400                 405 

Val Ile Val Pro Gln Lys Leu Leu Glu Phe Arg Tyr Phe Ile Leu 
                410                 415                 420 

Pro Tyr Val Ile Tyr Arg Leu Asn Ile Pro Leu Pro Pro Thr Ser 
                425                 430                 435 

Arg Leu Ile Cys Glu Leu Ser Cys Tyr Ala Val Val Asn Phe Ile 
                440                 445                 450 

Thr Phe Phe Ile Phe Leu Asn Lys Thr Phe Gln Trp Pro Asn Ser 
                455                 460                 465 

Gln Asp Ile Gln Arg Phe Met Trp 
                470 

 
           
             4  
             223  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 71426238CD1  
             
           
            4 

Met Ser Trp Met Phe Leu Arg Asp Leu Leu Ser Gly Val Asn Lys 
  1               5                  10                  15 

Tyr Ser Thr Gly Ile Gly Trp Ile Trp Leu Ala Val Val Phe Val 
                 20                  25                  30 

Phe Arg Leu Leu Val Tyr Met Val Ala Ala Glu His Val Trp Lys 
                 35                  40                  45 

Asp Glu Gln Lys Glu Phe Glu Cys Asn Ser Arg Gln Pro Gly Cys 
                 50                  55                  60 

Lys Asn Val Cys Phe Asp Asp Phe Phe Pro Ile Ser Gln Val Arg 
                 65                  70                  75 

Leu Trp Ala Leu Gln Leu Ile Met Val Ser Thr Pro Ser Leu Leu 
                 80                  85                  90 

Val Val Leu His Val Ala Tyr His Glu Gly Arg Glu Lys Arg His 
                 95                 100                 105 

Arg Lys Lys Leu Tyr Val Ser Pro Gly Thr Met Asp Gly Gly Leu 
                110                 115                 120 

Trp Tyr Ala Tyr Leu Ile Ser Leu Ile Val Lys Thr Gly Phe Glu 
                125                 130                 135 

Ile Gly Phe Leu Val Leu Phe Tyr Lys Leu Tyr Asp Gly Phe Ser 
                140                 145                 150 

Val Pro Tyr Leu Ile Lys Cys Asp Leu Lys Pro Cys Pro Asn Thr 
                155                 160                 165 

Val Asp Cys Phe Ile Ser Lys Pro Thr Glu Lys Thr Ile Phe Ile 
                170                 175                 180 

Leu Phe Leu Val Ile Thr Ser Cys Leu Cys Ile Val Leu Asn Phe 
                185                 190                 195 

Ile Glu Leu Ser Phe Leu Val Leu Lys Cys Leu Ile Lys Cys Cys 
                200                 205                 210 

Leu Gln Lys Tyr Leu Lys Lys Pro Gln Val Leu Ser Val 
                215                 220 

 
           
             5  
             1553  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7475123CD1  
             
           
            5 

Met Arg Arg Gln Trp Gly Ala Leu Leu Leu Gly Ala Leu Leu Cys 
  1               5                  10                  15 

Ala His Gly Leu Ala Ser Ser Pro Glu Cys Ala Cys Gly Arg Ser 
                 20                  25                  30 

His Phe Thr Cys Ala Val Ser Ala Leu Gly Glu Cys Thr Cys Ile 
                 35                  40                  45 

Pro Ala Gln Trp Gln Cys Asp Gly Asp Asn Asp Cys Gly Asp His 
                 50                  55                  60 

Ser Asp Glu Asp Gly Cys Ile Leu Pro Thr Cys Ser Pro Leu Asp 
                 65                  70                  75 

Phe His Cys Asp Asn Gly Lys Cys Ile Arg Arg Ser Trp Val Cys 
                 80                  85                  90 

Asp Gly Asp Asn Asp Cys Glu Asp Asp Ser Asp Glu Gln Asp Cys 
                 95                 100                 105 

Pro Pro Arg Glu Cys Glu Glu Asp Glu Phe Pro Cys Gln Asn Gly 
                110                 115                 120 

Tyr Cys Ile Arg Ser Leu Trp His Cys Asp Gly Asp Asn Asp Cys 
                125                 130                 135 

Gly Asp Asn Ser Asp Glu Gln Cys Asp Met Arg Lys Cys Ser Asp 
                140                 145                 150 

Lys Glu Phe Arg Cys Ser Asp Gly Ser Cys Ile Ala Glu His Trp 
                155                 160                 165 

Tyr Cys Asp Gly Asp Thr Asp Cys Lys Asp Gly Ser Asp Glu Glu 
                170                 175                 180 

Asn Cys Pro Ser Ala Val Pro Ala Pro Pro Cys Asn Leu Glu Glu 
                185                 190                 195 

Phe Gln Cys Ala Tyr Gly Arg Cys Ile Leu Asp Ile Tyr His Cys 
                200                 205                 210 

Asp Gly Asp Asp Asp Cys Gly Asp Trp Ser Asp Glu Ser Asp Cys 
                215                 220                 225 

Cys Glu Tyr Ser Gly Gln Leu Gly Ala Ser His Gln Pro Cys Arg 
                230                 235                 240 

Ser Gly Glu Phe Met Cys Asp Ser Gly Leu Cys Ile Asn Ala Gly 
                245                 250                 255 

Trp Arg Cys Asp Gly Asp Ala Asp Cys Asp Asp Gln Ser Asp Glu 
                260                 265                 270 

Arg Asn Cys Asn Trp Gln Thr Lys Ser Ile Gln Arg Val Asp Lys 
                275                 280                 285 

Tyr Ser Gly Arg Asn Lys Glu Thr Val Leu Ala Asn Val Glu Gly 
                290                 295                 300 

Leu Met Asp Ile Ile Val Val Ser Pro Gln Arg Gln Thr Gly Thr 
                305                 310                 315 

Asn Ala Cys Gly Val Asn Asn Gly Gly Cys Thr His Leu Cys Phe 
                320                 325                 330 

Ala Arg Ala Ser Asp Phe Val Cys Ala Cys Pro Asp Glu Pro Asp 
                335                 340                 345 

Ser Arg Pro Cys Ser Leu Val Pro Gly Leu Val Pro Pro Ala Pro 
                350                 355                 360 

Arg Ala Thr Gly Met Ser Glu Lys Ser Pro Val Leu Pro Asn Thr 
                365                 370                 375 

Pro Pro Thr Thr Leu Tyr Ser Ser Thr Thr Arg Thr Arg Thr Ser 
                380                 385                 390 

Leu Glu Glu Val Glu Gly Arg Met Asp Ile Arg Arg Ile Ser Phe 
                395                 400                 405 

Asp Thr Glu Asp Leu Ser Asp Asp Val Ile Pro Leu Ala Asp Val 
                410                 415                 420 

Arg Ser Ala Val Ala Leu Asp Trp Asp Ser Arg Asp Asp His Val 
                425                 430                 435 

Tyr Trp Thr Asp Val Ser Thr Asp Thr Ile Ser Arg Ala Lys Trp 
                440                 445                 450 

Asp Gly Thr Gly Gln Glu Val Val Val Asp Thr Ser Leu Glu Ser 
                455                 460                 465 

Pro Ala Gly Leu Ala Ile Asp Trp Val Thr Asn Lys Leu Tyr Trp 
                470                 475                 480 

Thr Asp Ala Gly Thr Asp Arg Ile Glu Val Ala Asn Thr Asp Gly 
                485                 490                 495 

Ser Met Arg Thr Val Leu Ile Trp Glu Asn Leu Asp Arg Pro Arg 
                500                 505                 510 

Asp Ile Val Val Glu Pro Met Gly Gly Tyr Met Tyr Trp Thr Asp 
                515                 520                 525 

Trp Gly Ala Ser Pro Lys Ile Glu Arg Ala Gly Met Asp Ala Ser 
                530                 535                 540 

Gly Arg Gln Val Ile Ile Ser Ser Asn Leu Thr Trp Pro Asn Gly 
                545                 550                 555 

Leu Ala Ile Asp Tyr Gly Ser Gln Arg Leu Tyr Trp Ala Asp Ala 
                560                 565                 570 

Gly Met Lys Thr Ile Glu Phe Ala Gly Leu Asp Gly Ser Lys Arg 
                575                 580                 585 

Lys Val Leu Ile Gly Ser Gln Leu Pro His Pro Phe Gly Leu Thr 
                590                 595                 600 

Leu Tyr Gly Glu Arg Ile Tyr Trp Thr Asp Trp Gln Thr Lys Ser 
                605                 610                 615 

Ile Gln Ser Ala Asp Arg Leu Thr Gly Leu Asp Arg Glu Thr Leu 
                620                 625                 630 

Gln Glu Asn Leu Glu Asn Leu Met Asp Ile His Val Phe His Arg 
                635                 640                 645 

Arg Arg Pro Pro Val Ser Thr Pro Cys Ala Met Glu Asn Gly Gly 
                650                 655                 660 

Cys Ser His Leu Cys Leu Arg Ser Pro Asn Pro Ser Gly Phe Ser 
                665                 670                 675 

Cys Thr Cys Pro Thr Gly Ile Asn Leu Leu Ser Asp Gly Lys Thr 
                680                 685                 690 

Cys Ser Pro Gly Met Asn Ser Phe Leu Ile Phe Ala Arg Arg Ile 
                695                 700                 705 

Asp Ile Arg Met Val Ser Leu Asp Ile Pro Tyr Phe Ala Asp Val 
                710                 715                 720 

Val Val Pro Ile Asn Ile Thr Met Lys Asn Thr Ile Ala Ile Gly 
                725                 730                 735 

Val Asp Pro Gln Glu Gly Lys Val Tyr Trp Ser Asp Ser Thr Leu 
                740                 745                 750 

His Arg Ile Ser Arg Ala Asn Leu Asp Gly Ser Gln His Glu Asp 
                755                 760                 765 

Ile Ile Thr Thr Gly Leu Gln Thr Thr Asp Gly Leu Ala Val Asp 
                770                 775                 780 

Ala Ile Gly Arg Lys Val Tyr Trp Thr Asp Thr Gly Thr Asn Arg 
                785                 790                 795 

Ile Glu Val Gly Asn Leu Asp Gly Ser Met Arg Lys Val Leu Val 
                800                 805                 810 

Trp Gln Asn Leu Asp Ser Pro Arg Ala Ile Val Leu Tyr His Glu 
                815                 820                 825 

Met Gly Phe Met Tyr Trp Thr Asp Trp Gly Glu Asn Ala Lys Leu 
                830                 835                 840 

Glu Arg Ser Gly Met Asp Gly Ser Asp Arg Ala Val Leu Ile Asn 
                845                 850                 855 

Asn Asn Leu Gly Trp Pro Asn Gly Leu Thr Val Asp Lys Ala Ser 
                860                 865                 870 

Ser Gln Leu Leu Trp Ala Asp Ala His Thr Glu Arg Ile Glu Ala 
                875                 880                 885 

Ala Asp Leu Asn Gly Ala Asn Arg His Thr Leu Val Ser Pro Val 
                890                 895                 900 

Gln His Pro Tyr Gly Leu Thr Leu Leu Asp Ser Tyr Ile Tyr Trp 
                905                 910                 915 

Thr Asp Trp Gln Thr Arg Ser Ile His Arg Ala Asp Lys Gly Thr 
                920                 925                 930 

Gly Ser Asn Val Ile Leu Val Arg Ser Asn Leu Pro Gly Leu Met 
                935                 940                 945 

Asp Met Gln Ala Val Asp Arg Ala Gln Pro Leu Gly Phe Asn Lys 
                950                 955                 960 

Cys Gly Ser Arg Asn Gly Gly Cys Ser His Leu Cys Leu Pro Arg 
                965                 970                 975 

Pro Ser Gly Phe Ser Cys Ala Cys Pro Thr Gly Ile Gln Leu Lys 
                980                 985                 990 

Gly Asp Gly Lys Thr Cys Asp Pro Ser Pro Glu Thr Tyr Leu Leu 
                995                1000                1005 

Phe Ser Ser Arg Gly Ser Ile Arg Arg Ile Ser Leu Asp Thr Ser 
               1010                1015                1020 

Asp His Thr Asp Val His Val Pro Val Pro Glu Leu Asn Asn Val 
               1025                1030                1035 

Ile Ser Leu Asp Tyr Asp Ser Val Asp Gly Lys Val Tyr Tyr Thr 
               1040                1045                1050 

Asp Val Phe Leu Asp Val Ile Arg Arg Ala Asp Leu Asn Gly Ser 
               1055                1060                1065 

Asn Met Glu Thr Val Ile Gly Arg Gly Leu Lys Thr Thr Asp Gly 
               1070                1075                1080 

Leu Ala Val Asp Trp Val Ala Arg Asn Leu Tyr Trp Thr Asp Thr 
               1085                1090                1095 

Gly Arg Asn Thr Ile Glu Ala Ser Arg Leu Asp Gly Ser Cys Arg 
               1100                1105                1110 

Lys Val Leu Ile Asn Asn Ser Leu Asp Glu Pro Arg Ala Ile Ala 
               1115                1120                1125 

Val Phe Pro Arg Lys Gly Tyr Leu Phe Trp Thr Asp Trp Gly His 
               1130                1135                1140 

Ile Ala Lys Ile Glu Arg Ala Asn Leu Asp Gly Ser Glu Arg Lys 
               1145                1150                1155 

Val Leu Ile Asn Thr Asp Leu Gly Trp Pro Asn Gly Leu Thr Leu 
               1160                1165                1170 

Asp Tyr Asp Thr Arg Arg Ile Tyr Trp Val Asp Ala His Leu Asp 
               1175                1180                1185 

Arg Ile Glu Ser Ala Asp Leu Asn Gly Lys Leu Arg Gln Val Leu 
               1190                1195                1200 

Val Ser His Val Ser His Pro Phe Ala Leu Thr Gln Gln Asp Arg 
               1205                1210                1215 

Trp Ile Tyr Trp Thr Asp Trp Gln Thr Lys Ser Ile Gln Arg Val 
               1220                1225                1230 

Asp Lys Tyr Ser Gly Arg Asn Lys Glu Thr Val Leu Ala Asn Val 
               1235                1240                1245 

Glu Gly Leu Met Asp Ile Ile Val Val Ser Pro Gln Arg Gln Thr 
               1250                1255                1260 

Gly Thr Asn Ala Cys Gly Val Asn Asn Gly Gly Cys Thr His Leu 
               1265                1270                1275 

Cys Phe Ala Arg Ala Ser Asp Phe Val Cys Ala Cys Pro Asp Glu 
               1280                1285                1290 

Pro Asp Ser Gln Pro Cys Ser Leu Val Pro Gly Leu Val Pro Pro 
               1295                1300                1305 

Ala Pro Arg Ala Thr Gly Met Ser Glu Lys Ser Pro Val Leu Pro 
               1310                1315                1320 

Asn Thr Pro Pro Thr Thr Leu Tyr Ser Ser Thr Thr Arg Thr Arg 
               1325                1330                1335 

Thr Ser Leu Glu Glu Val Glu Gly Arg Cys Ser Glu Arg Asp Ala 
               1340                1345                1350 

Arg Leu Gly Leu Cys Ala Arg Ser Asn Asp Ala Val Pro Ala Ala 
               1355                1360                1365 

Pro Gly Glu Gly Leu His Ile Ser Tyr Ala Ile Gly Gly Leu Leu 
               1370                1375                1380 

Ser Ile Leu Leu Ile Leu Val Val Ile Ala Ala Leu Met Leu Tyr 
               1385                1390                1395 

Arg His Lys Lys Ser Lys Phe Thr Asp Pro Gly Met Gly Asn Leu 
               1400                1405                1410 

Thr Tyr Ser Asn Pro Ser Tyr Arg Thr Ser Thr Gln Glu Val Lys 
               1415                1420                1425 

Ile Glu Ala Ile Pro Lys Pro Ala Met Tyr Asn Gln Leu Cys Tyr 
               1430                1435                1440 

Lys Lys Glu Gly Gly Pro Asp His Asn Tyr Thr Lys Glu Lys Ile 
               1445                1450                1455 

Lys Ile Val Glu Gly Ile Cys Leu Leu Ser Gly Asp Asp Ala Glu 
               1460                1465                1470 

Trp Asp Asp Leu Lys Gln Leu Arg Ser Ser Arg Gly Gly Leu Leu 
               1475                1480                1485 

Arg Asp His Val Cys Met Lys Thr Asp Thr Val Ser Ile Gln Ala 
               1490                1495                1500 

Ser Ser Gly Ser Leu Asp Asp Thr Glu Thr Glu Gln Leu Leu Gln 
               1505                1510                1515 

Glu Glu Gln Ser Glu Cys Ser Ser Val His Thr Ala Ala Thr Pro 
               1520                1525                1530 

Glu Arg Arg Gly Ser Leu Pro Asp Thr Gly Trp Lys His Glu Arg 
               1535                1540                1545 

Lys Leu Ser Ser Glu Ser Gln Val 
               1550 

 
           
             6  
             1718  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7481952CD1  
             
           
            6 

Met Asp Gln Ser Ile Ser Ile Thr Trp Glu Leu Ser Gly Asn Ala 
  1               5                  10                  15 

Glu Pro Gln Ala Leu Ala Gln Pro Tyr Arg Thr Lys Ser Tyr Met 
                 20                  25                  30 

Glu Gln Ala Lys His Leu Thr Cys Asp Phe Glu Ser Gly Phe Cys 
                 35                  40                  45 

Gly Trp Glu Pro Phe Leu Thr Glu Asp Ser His Trp Lys Leu Met 
                 50                  55                  60 

Lys Gly Leu Asn Asn Gly Glu His His Phe Pro Ala Ala Asp His 
                 65                  70                  75 

Thr Ala Asn Ile Asn His Gly Ser Phe Ile Tyr Leu Glu Ala Gln 
                 80                  85                  90 

Arg Ser Pro Gly Val Ala Lys Leu Gly Ser Pro Val Leu Thr Lys 
                 95                 100                 105 

Leu Leu Thr Ala Ser Thr Pro Cys Gln Val Gln Phe Trp Tyr His 
                110                 115                 120 

Leu Ser Gln His Ser Asn Leu Ser Val Phe Thr Arg Thr Ser Leu 
                125                 130                 135 

Asp Gly Asn Leu Gln Lys Gln Gly Lys Ile Ile Arg Phe Ser Glu 
                140                 145                 150 

Ser Gln Trp Ser His Ala Lys Ile Asp Leu Ile Ala Glu Ala Gly 
                155                 160                 165 

Glu Ser Thr Leu Pro Phe Gln Leu Ile Leu Glu Ala Thr Val Leu 
                170                 175                 180 

Ser Ser Asn Ala Thr Val Ala Leu Asp Asp Ile Ser Val Ser Gln 
                185                 190                 195 

Glu Cys Glu Ile Ser Tyr Lys Ser Leu Pro Arg Thr Ser Thr Gln 
                200                 205                 210 

Ser Lys Phe Ser Lys Cys Asp Phe Glu Ala Asn Ser Cys Asp Trp 
                215                 220                 225 

Phe Glu Val Ile Ser Gly Asp His Phe Asp Trp Ile Arg Ser Ser 
                230                 235                 240 

Gln Ser Glu Leu Ser Ala Asp Phe Glu His Gln Ala Pro Pro Arg 
                245                 250                 255 

Asp His Ser Leu Asn Ala Ser Gln Gly His Phe Met Phe Ile Leu 
                260                 265                 270 

Lys Lys Ser Ser Ser Leu Trp Gln Val Ala Lys Leu Gln Ser Pro 
                275                 280                 285 

Thr Phe Ser Gln Thr Gly Pro Gly Cys Ile Leu Ser Phe Trp Phe 
                290                 295                 300 

Tyr Asn Tyr Gly Leu Ser Val Gly Ala Ala Glu Leu Gln Leu His 
                305                 310                 315 

Met Glu Asn Ser His Asp Ser Thr Val Ile Trp Arg Val Leu Tyr 
                320                 325                 330 

Asn Gln Gly Lys Gln Trp Leu Glu Ala Thr Ile Gln Leu Gly Arg 
                335                 340                 345 

Leu Ser Gln Pro Phe His Leu Ser Leu Asp Lys Val Ser Leu Gly 
                350                 355                 360 

Ile Tyr Asp Gly Val Ser Ala Ile Asp Asp Ile Arg Phe Glu Asn 
                365                 370                 375 

Cys Thr Leu Pro Leu Pro Ala Glu Ser Cys Glu Gly Leu Asp His 
                380                 385                 390 

Phe Trp Cys Arg His Thr Arg Ala Cys Ile Glu Lys Leu Arg Leu 
                395                 400                 405 

Cys Asp Leu Val Asp Asp Cys Gly Asp Arg Thr Asp Glu Val Asn 
                410                 415                 420 

Cys Ala Pro Glu Leu Gln Cys Asn Phe Glu Thr Gly Ile Cys Asn 
                425                 430                 435 

Trp Glu Gln Asp Ala Lys Asp Asp Phe Asp Trp Thr Arg Asn Gln 
                440                 445                 450 

Gly Pro Thr Pro Thr Leu Asn Thr Gly Pro Met Lys Asp Asn Thr 
                455                 460                 465 

Leu Gly Thr Ala Lys Gly His Tyr Leu Tyr Ile Glu Ser Ser Glu 
                470                 475                 480 

Pro Gln Ala Phe Gln Asp Ser Ala Ala Leu Leu Ser Pro Ile Leu 
                485                 490                 495 

Asn Ala Thr Asp Thr Lys Gly Cys Thr Phe Arg Phe Tyr Tyr His 
                500                 505                 510 

Met Phe Gly Lys Arg Ile Tyr Arg Leu Ala Ile Tyr Gln Arg Ile 
                515                 520                 525 

Trp Ser Asp Ser Arg Gly Gln Leu Leu Trp Gln Ile Phe Gly Asn 
                530                 535                 540 

Gln Gly Asn Arg Trp Ile Arg Lys His Leu Asn Ile Ser Ser Arg 
                545                 550                 555 

Gln Pro Phe Gln Ile Leu Val Glu Ala Ser Val Gly Asp Gly Phe 
                560                 565                 570 

Thr Gly Asp Ile Ala Ile Asp Asp Leu Ser Phe Met Asp Cys Thr 
                575                 580                 585 

Leu Tyr Pro Gly Asn Leu Pro Ala Asp Leu Pro Thr Pro Pro Glu 
                590                 595                 600 

Thr Ser Val Pro Val Thr Leu Pro Pro His Asn Cys Thr Asp Ser 
                605                 610                 615 

Glu Phe Ile Cys Arg Ser Asp Gly His Cys Ile Glu Lys Met Gln 
                620                 625                 630 

Lys Cys Asp Phe Lys Tyr Asp Cys Pro Asp Lys Ser Asp Glu Ala 
                635                 640                 645 

Ser Cys Val Met Glu Val Cys Ser Phe Glu Lys Arg Ser Leu Cys 
                650                 655                 660 

Lys Trp Tyr Gln Pro Ile Pro Val His Leu Leu Gln Asp Ser Asn 
                665                 670                 675 

Thr Phe Arg Trp Gly Leu Gly Asn Gly Ile Ser Ile His His Gly 
                680                 685                 690 

Glu Glu Asn His Arg Pro Ser Val Asp His Thr Gln Asn Thr Thr 
                695                 700                 705 

Asp Gly Trp Tyr Leu Tyr Ala Asp Ser Ser Asn Gly Lys Phe Gly 
                710                 715                 720 

Asp Thr Ala Asp Ile Leu Thr Pro Ile Ile Ser Leu Thr Gly Pro 
                725                 730                 735 

Lys Cys Thr Leu Val Phe Trp Thr His Met Asn Gly Ala Thr Val 
                740                 745                 750 

Gly Ser Leu Gln Val Leu Ile Lys Lys Asp Asn Val Thr Ser Lys 
                755                 760                 765 

Leu Trp Ala Gln Thr Gly Gln Gln Gly Ala Gln Trp Lys Arg Ala 
                770                 775                 780 

Glu Val Phe Leu Gly Ile Arg Ser His Thr Gln Ile Val Phe Arg 
                785                 790                 795 

Ala Lys Arg Gly Ile Ser Tyr Ile Gly Asp Val Ala Val Asp Asp 
                800                 805                 810 

Ile Ser Phe Gln Asp Cys Ser Pro Leu Leu Ser Pro Glu Arg Lys 
                815                 820                 825 

Cys Thr Asp His Glu Phe Met Cys Ala Asn Lys His Cys Ile Ala 
                830                 835                 840 

Lys Asp Lys Leu Cys Asp Phe Val Asn Asp Cys Ala Asp Asn Ser 
                845                 850                 855 

Asp Glu Thr Thr Phe Ile Cys Arg Thr Ser Ser Gly Arg Cys Asp 
                860                 865                 870 

Phe Glu Phe Asp Leu Cys Ser Trp Lys Gln Glu Lys Asp Glu Asp 
                875                 880                 885 

Phe Asp Trp Asn Leu Lys Ala Ser Ser Ile Pro Ala Ala Gly Thr 
                890                 895                 900 

Glu Pro Ala Ala Asp His Thr Leu Gly Asn Ser Ser Gly His Tyr 
                905                 910                 915 

Ile Phe Ile Lys Ser Leu Phe Pro Gln Gln Pro Met Arg Ala Ala 
                920                 925                 930 

Arg Ile Ser Ser Pro Val Ile Ser Lys Arg Ser Lys Asn Cys Lys 
                935                 940                 945 

Ile Ile Phe His Tyr His Met Tyr Gly Asn Gly Ile Gly Ala Leu 
                950                 955                 960 

Thr Leu Met Gln Val Ser Val Thr Asn Gln Thr Lys Val Leu Leu 
                965                 970                 975 

Asn Leu Thr Val Glu Gln Gly Asn Phe Trp Arg Arg Glu Glu Leu 
                980                 985                 990 

Ser Leu Phe Gly Asp Glu Asp Phe Gln Leu Lys Phe Glu Gly Arg 
                995                1000                1005 

Val Gly Lys Gly Gln Arg Gly Asp Ile Ala Leu Asp Asp Ile Val 
               1010                1015                1020 

Leu Thr Glu Asn Cys Leu Ser Leu His Asp Ser Val Gln Glu Glu 
               1025                1030                1035 

Leu Ala Val Pro Leu Pro Thr Gly Phe Cys Pro Leu Gly Tyr Arg 
               1040                1045                1050 

Glu Cys His Asn Gly Lys Cys Tyr Arg Leu Glu Gln Ser Cys Asn 
               1055                1060                1065 

Phe Val Asp Asn Cys Gly Asp Asn Thr Asp Glu Asn Glu Cys Gly 
               1070                1075                1080 

Ser Ser Cys Thr Phe Glu Lys Gly Trp Cys Gly Trp Gln Asn Ser 
               1085                1090                1095 

Gln Ala Asp Asn Phe Asp Trp Val Leu Gly Val Gly Ser His Gln 
               1100                1105                1110 

Ser Leu Arg Pro Pro Lys Asp His Thr Leu Gly Asn Glu Asn Gly 
               1115                1120                1125 

His Phe Met Tyr Leu Glu Ala Thr Ala Val Gly Leu Arg Gly Asp 
               1130                1135                1140 

Lys Ala His Phe Arg Ser Thr Met Trp Arg Glu Ser Ser Ala Ala 
               1145                1150                1155 

Cys Thr Met Ser Phe Trp Tyr Phe Ile Ser Ala Lys Ala Thr Gly 
               1160                1165                1170 

Ser Ile Gln Ile Leu Ile Lys Thr Glu Lys Gly Leu Ser Lys Val 
               1175                1180                1185 

Trp Gln Glu Ser Lys Gln Asn Pro Gly Asn His Trp Gln Lys Ala 
               1190                1195                1200 

Asp Ile Leu Leu Gly Lys Leu Arg Asn Phe Glu Val Ile Phe Gln 
               1205                1210                1215 

Gly Ile Arg Thr Arg Asp Leu Gly Gly Gly Ala Ala Ile Asp Asp 
               1220                1225                1230 

Ile Glu Phe Lys Asn Cys Thr Thr Val Gly Glu Ile Ser Glu Leu 
               1235                1240                1245 

Cys Pro Glu Ile Thr Asp Phe Leu Cys Arg Asp Lys Lys Cys Ile 
               1250                1255                1260 

Ala Ser His Leu Leu Cys Asp Tyr Lys Pro Asp Cys Ser Asp Arg 
               1265                1270                1275 

Ser Asp Glu Ala His Cys Ala His Tyr Thr Ser Thr Thr Gly Ser 
               1280                1285                1290 

Cys Asn Phe Glu Thr Ser Ser Gly Asn Trp Thr Thr Ala Cys Ser 
               1295                1300                1305 

Leu Thr Gln Asp Ser Glu Asp Asp Leu Asp Trp Ala Ile Gly Ser 
               1310                1315                1320 

Arg Ile Pro Ala Lys Ala Leu Ile Pro Asp Ser Asp His Thr Pro 
               1325                1330                1335 

Gly Ser Gly Gln His Phe Leu Tyr Val Asn Ser Ser Gly Ser Lys 
               1340                1345                1350 

Glu Gly Ser Val Ala Arg Ile Thr Thr Ser Lys Ser Phe Pro Ala 
               1355                1360                1365 

Ser Leu Gly Met Cys Thr Val Arg Phe Trp Phe Tyr Met Ile Asp 
               1370                1375                1380 

Pro Arg Ser Met Gly Ile Leu Lys Val Tyr Thr Ile Glu Glu Ser 
               1385                1390                1395 

Gly Leu Asn Ile Leu Val Trp Ser Val Ile Gly Asn Lys Arg Thr 
               1400                1405                1410 

Gly Trp Thr Tyr Gly Ser Val Pro Leu Ser Ser Asn Ser Pro Phe 
               1415                1420                1425 

Lys Val Ala Phe Glu Ala Asp Leu Asp Gly Asn Glu Asp Ile Phe 
               1430                1435                1440 

Ile Ala Leu Asp Asp Ile Ser Phe Thr Pro Glu Cys Val Thr Gly 
               1445                1450                1455 

Gly Pro Val Pro Val Gln Pro Ser Pro Cys Glu Ala Asp Gln Phe 
               1460                1465                1470 

Ser Cys Ile Tyr Thr Leu Gln Cys Val Pro Leu Ser Gly Lys Cys 
               1475                1480                1485 

Asp Gly His Glu Asp Cys Ile Asp Gly Ser Asp Glu Met Asp Cys 
               1490                1495                1500 

Pro Leu Ser Pro Thr Pro Pro Leu Cys Ser Asn Met Glu Phe Pro 
               1505                1510                1515 

Cys Ser Thr Asp Glu Cys Ile Pro Ser Leu Leu Leu Cys Asp Gly 
               1520                1525                1530 

Val Pro Asp Cys His Phe Asn Glu Asp Glu Leu Ile Cys Ser Asn 
               1535                1540                1545 

Lys Ser Cys Ser Asn Gly Ala Leu Val Cys Ala Ser Ser Asn Ser 
               1550                1555                1560 

Cys Ile Pro Ala His Gln Arg Cys Asp Gly Phe Ala Asp Cys Met 
               1565                1570                1575 

Asp Phe Gln Leu Asp Glu Ser Ser Cys Ser Glu Cys Pro Leu Asn 
               1580                1585                1590 

Tyr Cys Arg Asn Gly Gly Thr Cys Val Val Glu Lys Asn Gly Pro 
               1595                1600                1605 

Met Cys Arg Cys Arg Gln Gly Trp Lys Gly Asn Arg Cys His Ile 
               1610                1615                1620 

Lys Phe Asn Pro Pro Ala Thr Asp Phe Thr Tyr Ala Gln Asn Asn 
               1625                1630                1635 

Thr Trp Thr Leu Leu Gly Ile Gly Leu Ala Phe Leu Met Thr His 
               1640                1645                1650 

Ile Thr Val Ala Val Leu Cys Phe Leu Ala Asn Arg Lys Val Pro 
               1655                1660                1665 

Ile Arg Lys Thr Glu Gly Ser Gly Asn Cys Ala Phe Val Asn Pro 
               1670                1675                1680 

Val Tyr Gly Asn Trp Ser Asn Pro Glu Lys Thr Glu Ser Ser Val 
               1685                1690                1695 

Tyr Ser Phe Ser Asn Pro Leu Tyr Gly Thr Thr Ser Gly Ser Leu 
               1700                1705                1710 

Glu Thr Leu Ser His His Leu Lys 
               1715 

 
           
             7  
             224  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 382654CD1  
             
           
            7 

Met Leu Leu Ser Pro Asp Gln Lys Val Leu Thr Ile Thr Arg Val 
  1               5                  10                  15 

Leu Met Glu Asp Asp Asp Leu Tyr Ser Cys Met Val Glu Asn Pro 
                 20                  25                  30 

Ile Ser Gln Gly Arg Ser Leu Pro Val Lys Ile Thr Val Tyr Arg 
                 35                  40                  45 

Arg Ser Ser Leu Tyr Ile Ile Leu Ser Thr Gly Gly Ile Phe Leu 
                 50                  55                  60 

Leu Val Thr Leu Val Thr Val Cys Ala Cys Trp Lys Pro Ser Lys 
                 65                  70                  75 

Arg Lys Gln Lys Lys Leu Glu Lys Gln Asn Ser Leu Glu Tyr Met 
                 80                  85                  90 

Asp Gln Asn Asp Asp Arg Leu Lys Pro Glu Ala Asp Thr Leu Pro 
                 95                 100                 105 

Arg Ser Gly Glu Gln Glu Arg Lys Asn Pro Met Ala Leu Tyr Ile 
                110                 115                 120 

Leu Lys Asp Lys Asp Ser Pro Glu Thr Glu Glu Asn Pro Ala Pro 
                125                 130                 135 

Glu Pro Arg Ser Ala Thr Glu Pro Gly Pro Pro Gly Tyr Ser Val 
                140                 145                 150 

Ser Pro Ala Val Pro Gly Arg Ser Pro Gly Leu Pro Ile Arg Ser 
                155                 160                 165 

Ala Arg Arg Tyr Pro Arg Ser Pro Ala Arg Ser Pro Ala Thr Gly 
                170                 175                 180 

Arg Thr His Ser Ser Pro Pro Arg Ala Pro Ser Ser Pro Gly Arg 
                185                 190                 195 

Ser Arg Ser Ala Ser Arg Thr Leu Arg Thr Ala Gly Val His Ile 
                200                 205                 210 

Ile Arg Glu Gln Asp Glu Ala Gly Pro Val Glu Ile Ser Ala 
                215                 220 

 
           
             8  
             570  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 1867351CD1  
             
           
            8 

Met Glu Ala Pro Glu Glu Pro Ala Pro Val Arg Gly Gly Pro Glu 
  1               5                  10                  15 

Ala Thr Leu Glu Val Arg Gly Ser Arg Cys Leu Arg Leu Ser Ala 
                 20                  25                  30 

Phe Arg Glu Glu Leu Arg Ala Leu Leu Val Leu Ala Gly Pro Ala 
                 35                  40                  45 

Phe Leu Val Gln Leu Met Val Phe Leu Ile Ser Phe Ile Ser Ser 
                 50                  55                  60 

Val Phe Cys Gly His Leu Gly Lys Leu Glu Leu Asp Ala Val Thr 
                 65                  70                  75 

Leu Ala Ile Ala Val Ile Asn Val Thr Gly Val Ser Val Gly Phe 
                 80                  85                  90 

Gly Leu Ser Ser Ala Cys Asp Thr Leu Ile Ser Gln Thr Tyr Gly 
                 95                 100                 105 

Ser Gln Asn Leu Lys His Val Gly Val Ile Leu Gln Arg Ser Ala 
                110                 115                 120 

Leu Val Leu Leu Leu Cys Cys Phe Pro Cys Trp Ala Leu Phe Leu 
                125                 130                 135 

Asn Thr Gln His Ile Leu Leu Leu Phe Arg Gln Asp Pro Asp Val 
                140                 145                 150 

Ser Arg Leu Thr Gln Thr Tyr Val Thr Ile Phe Ile Pro Ala Leu 
                155                 160                 165 

Pro Ala Thr Phe Leu Tyr Met Leu Gln Val Lys Tyr Leu Leu Asn 
                170                 175                 180 

Gln Gly Ile Val Leu Pro Gln Ile Val Thr Gly Val Ala Ala Asn 
                185                 190                 195 

Leu Val Asn Ala Leu Ala Asn Tyr Leu Phe Leu His Gln Leu His 
                200                 205                 210 

Leu Gly Val Ile Gly Ser Ala Leu Ala Asn Leu Ile Ser Gln Tyr 
                215                 220                 225 

Thr Leu Ala Leu Leu Leu Phe Leu Tyr Ile Leu Gly Lys Lys Leu 
                230                 235                 240 

His Gln Ala Thr Trp Gly Gly Trp Ser Leu Glu Cys Leu Gln Asp 
                245                 250                 255 

Trp Ala Ser Phe Leu Arg Leu Ala Ile Pro Ser Met Leu Met Leu 
                260                 265                 270 

Cys Met Glu Trp Trp Ala Tyr Glu Val Gly Ser Phe Pro Ser Gly 
                275                 280                 285 

Ile Leu Gly Met Val Glu Leu Gly Ala Gln Ser Ile Val Tyr Glu 
                290                 295                 300 

Leu Ala Ile Ile Val Tyr Met Val Pro Ala Asp Phe Ser Val Ala 
                305                 310                 315 

Ala Ser Val Arg Val Gly Asn Ala Leu Gly Ala Gly Asp Met Glu 
                320                 325                 330 

Gln Ala Arg Lys Ser Ser Thr Val Ser Leu Leu Ile Thr Val Leu 
                335                 340                 345 

Phe Ala Val Ala Phe Ser Val Leu Leu Leu Ser Cys Lys Asp His 
                350                 355                 360 

Val Gly Tyr Ile Phe Thr Thr Asp Arg Asp Ile Ile Asn Leu Val 
                365                 370                 375 

Ala Gln Val Val Pro Ile Tyr Ala Val Ser His Leu Phe Glu Ala 
                380                 385                 390 

Leu Ala Cys Thr Ser Gly Gly Val Leu Arg Gly Ser Gly Asn Gln 
                395                 400                 405 

Lys Val Gly Ala Ile Val Asn Thr Ile Gly Tyr Tyr Val Val Gly 
                410                 415                 420 

Leu Pro Ile Gly Ile Ala Leu Met Phe Ala Thr Thr Leu Gly Val 
                425                 430                 435 

Met Gly Leu Trp Ser Gly Ile Ile Ile Cys Thr Val Phe Gln Ala 
                440                 445                 450 

Val Cys Phe Leu Gly Phe Ile Ile Gln Leu Asn Trp Lys Lys Ala 
                455                 460                 465 

Cys Gln Gln Ala Gln Val His Ala Asn Leu Lys Val Asn Asn Val 
                470                 475                 480 

Pro Arg Ser Gly Asn Ser Ala Leu Pro Gln Asp Pro Leu His Pro 
                485                 490                 495 

Gly Cys Pro Glu Asn Leu Glu Gly Ile Leu Thr Asn Asp Val Gly 
                500                 505                 510 

Lys Thr Gly Glu Pro Gln Ser Asp Gln Gln Met Arg Gln Glu Glu 
                515                 520                 525 

Pro Leu Pro Glu His Pro Gln Asp Gly Ala Lys Leu Ser Arg Lys 
                530                 535                 540 

Gln Leu Val Leu Arg Arg Gly Leu Leu Leu Leu Gly Val Phe Leu 
                545                 550                 555 

Ile Leu Leu Val Gly Ile Leu Val Arg Phe Tyr Val Arg Ile Gln 
                560                 565                 570 

 
           
             9  
             423  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 3323104CD1  
             
           
            9 

Met Gly Ser Thr Lys His Trp Gly Glu Leu Leu Leu Asn Leu Lys 
  1               5                  10                  15 

Val Ala Pro Ala Gly Val Phe Gly Val Ala Phe Leu Ala Arg Val 
                 20                  25                  30 

Ala Leu Val Phe Tyr Gly Val Phe Gln Asp Arg Thr Leu His Val 
                 35                  40                  45 

Arg Tyr Thr Asp Ile Asp Tyr Gln Val Phe Thr Asp Ala Ala Arg 
                 50                  55                  60 

Phe Val Thr Glu Gly Arg Ser Pro Tyr Leu Arg Ala Thr Tyr Arg 
                 65                  70                  75 

Tyr Thr Pro Leu Leu Gly Trp Leu Leu Thr Pro Asn Ile Tyr Leu 
                 80                  85                  90 

Ser Glu Leu Phe Gly Lys Phe Leu Phe Ile Ser Cys Asp Leu Leu 
                 95                 100                 105 

Thr Ala Phe Leu Leu Tyr Arg Leu Leu Leu Leu Lys Gly Leu Gly 
                110                 115                 120 

Arg Arg Gln Ala Cys Gly Tyr Cys Val Phe Trp Leu Leu Asn Pro 
                125                 130                 135 

Leu Pro Met Ala Val Ser Ser Arg Gly Asn Ala Asp Ser Ile Val 
                140                 145                 150 

Ala Ser Leu Val Leu Met Val Leu Tyr Leu Ile Lys Lys Arg Leu 
                155                 160                 165 

Val Ala Cys Ala Ala Val Phe Tyr Gly Phe Ala Val His Met Lys 
                170                 175                 180 

Ile Tyr Pro Val Thr Tyr Ile Leu Pro Ile Thr Leu His Leu Leu 
                185                 190                 195 

Pro Asp Arg Asp Asn Asp Lys Ser Leu Arg Gln Phe Arg Tyr Thr 
                200                 205                 210 

Phe Gln Ala Cys Leu Tyr Glu Leu Leu Lys Arg Leu Cys Asn Arg 
                215                 220                 225 

Ala Val Leu Leu Phe Val Ala Val Ala Gly Leu Thr Phe Phe Ala 
                230                 235                 240 

Leu Ser Phe Gly Phe Tyr Tyr Glu Tyr Gly Trp Glu Phe Leu Glu 
                245                 250                 255 

His Thr Tyr Phe Tyr His Leu Thr Arg Arg Asp Ile Arg His Asn 
                260                 265                 270 

Phe Ser Pro Tyr Phe Tyr Met Leu Tyr Leu Thr Ala Glu Ser Lys 
                275                 280                 285 

Trp Ser Phe Ser Leu Gly Ile Ala Ala Phe Leu Pro Gln Leu Ile 
                290                 295                 300 

Leu Leu Ser Ala Val Ser Phe Ala Tyr Tyr Arg Asp Leu Val Phe 
                305                 310                 315 

Cys Cys Phe Leu His Thr Ser Ile Phe Val Thr Phe Asn Lys Val 
                320                 325                 330 

Cys Thr Ser Gln Tyr Phe Leu Trp Tyr Leu Cys Leu Leu Pro Leu 
                335                 340                 345 

Val Met Pro Leu Val Arg Met Pro Trp Lys Arg Ala Val Val Leu 
                350                 355                 360 

Leu Met Leu Trp Leu Ile Gly Gln Ala Met Trp Leu Ala Pro Ala 
                365                 370                 375 

Tyr Val Leu Glu Phe Gln Gly Lys Asn Thr Phe Leu Phe Ile Trp 
                380                 385                 390 

Leu Ala Gly Leu Phe Phe Leu Leu Ile Asn Cys Ser Ile Leu Ile 
                395                 400                 405 

Gln Ile Ile Ser His Tyr Lys Glu Glu Pro Leu Thr Glu Arg Ile 
                410                 415                 420 

Lys Tyr Asp 

 
           
             10  
             388  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 4769306CD1  
             
           
            10 

Met Gly Phe Ser Ala Arg Tyr Asn Phe Thr Pro Asp Pro Asp Phe 
  1               5                  10                  15 

Lys Asp Leu Gly Ala Leu Lys Pro Leu Pro Ala Cys Glu Phe Glu 
                 20                  25                  30 

Met Gly Gly Ser Glu Gly Ile Val Glu Ser Ile Gln Ile Met Lys 
                 35                  40                  45 

Glu Gly Lys Ala Thr Ala Ser Glu Ala Val Asp Cys Lys Trp Tyr 
                 50                  55                  60 

Ile Arg Ala Pro Pro Arg Ser Lys Ile Tyr Leu Arg Phe Leu Asp 
                 65                  70                  75 

Tyr Glu Met Gln Asn Ser Asn Glu Cys Lys Arg Asn Phe Val Ala 
                 80                  85                  90 

Val Tyr Asp Gly Ser Ser Ser Val Glu Asp Leu Lys Ala Lys Phe 
                 95                 100                 105 

Cys Ser Thr Val Ala Asn Asp Val Met Leu Arg Thr Gly Leu Gly 
                110                 115                 120 

Val Ile Arg Met Trp Ala Asp Glu Gly Ser Arg Asn Ser Arg Phe 
                125                 130                 135 

Gln Met Leu Phe Thr Ser Phe Gln Glu Pro Pro Cys Glu Gly Asn 
                140                 145                 150 

Thr Phe Phe Cys His Ser Asn Met Cys Ile Asn Asn Thr Leu Val 
                155                 160                 165 

Cys Asn Gly Leu Gln Asn Cys Val Tyr Pro Trp Asp Glu Asn His 
                170                 175                 180 

Cys Lys Glu Lys Arg Lys Thr Ser Leu Leu Asp Gln Leu Thr Asn 
                185                 190                 195 

Thr Ser Gly Thr Val Ile Gly Val Thr Ser Cys Ile Val Ile Ile 
                200                 205                 210 

Leu Ile Ile Ile Ser Val Ile Val Gln Ile Lys Gln Pro Arg Lys 
                215                 220                 225 

Lys Tyr Val Gln Arg Lys Ser Asp Phe Asp Gln Thr Val Phe Gln 
                230                 235                 240 

Glu Val Phe Glu Pro Pro His Tyr Glu Leu Cys Thr Leu Arg Gly 
                245                 250                 255 

Thr Gly Ala Thr Ala Asp Phe Ala Asp Val Ala Asp Asp Phe Glu 
                260                 265                 270 

Asn Tyr His Lys Leu Arg Arg Ser Ser Ser Lys Cys Ile His Asp 
                275                 280                 285 

His His Cys Gly Ser Gln Leu Ser Ser Thr Lys Gly Ser Arg Ser 
                290                 295                 300 

Asn Leu Ser Thr Arg Asp Ala Ser Ile Leu Thr Glu Met Pro Thr 
                305                 310                 315 

Gln Pro Gly Lys Pro Leu Ile Pro Pro Met Asn Arg Arg Asn Ile 
                320                 325                 330 

Leu Val Met Lys His Asn Tyr Ser Gln Asp Ala Ala Asp Ala Cys 
                335                 340                 345 

Asp Ile Asp Glu Ile Glu Glu Val Pro Thr Thr Ser His Arg Leu 
                350                 355                 360 

Ser Arg His Asp Lys Ala Val Gln Arg Phe Cys Leu Ile Gly Ser 
                365                 370                 375 

Leu Ser Lys His Glu Ser Glu Tyr Asn Thr Thr Arg Val 
                380                 385 

 
           
             11  
             231  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 2720058CD1  
             
           
            11 

Met Ala Phe Val Pro Phe Leu Leu Val Thr Trp Ser Ser Ala Ala 
  1               5                  10                  15 

Phe Ile Ile Ser Tyr Val Val Ala Val Leu Ser Gly His Val Asn 
                 20                  25                  30 

Pro Phe Leu Pro Tyr Ile Ser Asp Thr Gly Thr Thr Pro Pro Glu 
                 35                  40                  45 

Ser Gly Ile Phe Gly Phe Met Ile Asn Phe Ser Ala Phe Leu Gly 
                 50                  55                  60 

Ala Ala Thr Met Tyr Thr Arg Tyr Lys Ile Val Gln Lys Gln Asn 
                 65                  70                  75 

Gln Thr Cys Tyr Phe Ser Thr Pro Val Phe Asn Leu Val Ser Leu 
                 80                  85                  90 

Val Leu Gly Leu Val Gly Cys Phe Gly Met Gly Ile Val Ala Asn 
                 95                 100                 105 

Phe Gln Glu Leu Ala Val Pro Val Val His Asp Gly Gly Ala Leu 
                110                 115                 120 

Leu Ala Phe Val Cys Gly Val Val Tyr Thr Leu Leu Gln Ser Ile 
                125                 130                 135 

Ile Ser Tyr Lys Ser Cys Pro Gln Trp Asn Ser Leu Ser Thr Cys 
                140                 145                 150 

His Ile Arg Met Val Ile Ser Ala Val Ser Cys Ala Ala Val Ile 
                155                 160                 165 

Pro Met Ile Val Cys Ala Ser Leu Ile Ser Ile Thr Lys Leu Glu 
                170                 175                 180 

Trp Asn Pro Arg Glu Lys Asp Tyr Val Tyr His Val Val Ser Ala 
                185                 190                 195 

Ile Cys Glu Trp Thr Val Ala Phe Gly Phe Ile Phe Tyr Phe Leu 
                200                 205                 210 

Thr Phe Ile Gln Asp Phe Gln Ser Val Thr Leu Arg Ile Ser Thr 
                215                 220                 225 

Glu Ile Asn Gly Asp Ile 
                230 

 
           
             12  
             293  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7481255CD1  
             
           
            12 

Met Asp Arg Ala Lys Gln Gln Gln Ala Leu Leu Leu Leu Pro Val 
  1               5                  10                  15 

Cys Leu Ala Leu Thr Phe Ser Leu Thr Ala Val Val Ser Ser His 
                 20                  25                  30 

Trp Cys Glu Gly Thr Arg Arg Val Val Lys Pro Leu Cys Gln Asp 
                 35                  40                  45 

Gln Pro Gly Gly Gln His Cys Ile His Phe Lys Arg Asp Asn Ser 
                 50                  55                  60 

Ser Asn Gly Arg Met Asp Asn Asn Ser Gln Ala Val Leu Tyr Ile 
                 65                  70                  75 

Trp Glu Leu Gly Asp Asp Lys Phe Ile Gln Arg Gly Phe His Val 
                 80                  85                  90 

Gly Leu Trp Gln Ser Cys Glu Glu Ser Leu Asn Gly Glu Asp Glu 
                 95                 100                 105 

Lys Cys Arg Ser Phe Arg Ser Val Val Pro Ala Glu Glu Gln Gly 
                110                 115                 120 

Val Leu Trp Leu Ser Ile Gly Gly Glu Val Leu Asp Ile Val Leu 
                125                 130                 135 

Ile Leu Thr Ser Ala Ile Leu Leu Gly Ser Arg Val Ser Cys Arg 
                140                 145                 150 

Ser Pro Gly Phe His Trp Leu Arg Val Asp Ala Leu Val Ala Ile 
                155                 160                 165 

Phe Met Val Leu Ala Gly Leu Leu Gly Met Val Ala His Met Met 
                170                 175                 180 

Tyr Thr Thr Ile Phe Gln Ile Thr Val Asn Leu Gly Pro Glu Asp 
                185                 190                 195 

Trp Lys Pro Gln Thr Trp Asp Tyr Gly Trp Ser Tyr Cys Leu Ala 
                200                 205                 210 

Trp Gly Ser Phe Ala Leu Cys Leu Ala Val Ser Val Ser Ala Met 
                215                 220                 225 

Ser Arg Phe Thr Ala Ala Arg Leu Glu Phe Thr Glu Lys Gln Gln 
                230                 235                 240 

Ala Gln Asn Gly Ser Arg His Ser Gln His Ser Phe Leu Glu Pro 
                245                 250                 255 

Glu Ala Ser Glu Ser Ile Trp Lys Thr Gly Ala Ala Pro Cys Pro 
                260                 265                 270 

Ala Glu Gln Ala Phe Arg Asn Val Ser Gly His Leu Pro Pro Gly 
                275                 280                 285 

Ala Pro Gly Lys Val Ser Ile Cys 
                290 

 
           
             13  
             526  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 1510242CD1  
             
           
            13 

Met Leu Thr Tyr Gly Val Tyr Leu Gly Leu Leu Gln Met Gln Leu 
  1               5                  10                  15 

Ile Leu His Tyr Asp Glu Thr Tyr Arg Glu Val Lys Tyr Gly Asn 
                 20                  25                  30 

Met Gly Leu Pro Asp Ile Asp Ser Lys Met Leu Met Gly Ile Asn 
                 35                  40                  45 

Val Thr Pro Ile Ala Ala Leu Leu Tyr Thr Pro Val Leu Ile Arg 
                 50                  55                  60 

Phe Phe Gly Thr Lys Trp Met Met Phe Leu Ala Val Gly Ile Tyr 
                 65                  70                  75 

Ala Leu Phe Val Ser Thr Asn Tyr Trp Glu Arg Tyr Tyr Thr Leu 
                 80                  85                  90 

Val Pro Ser Ala Val Ala Leu Gly Met Ala Ile Val Pro Leu Trp 
                 95                 100                 105 

Ala Ser Met Gly Asn Tyr Ile Thr Arg Met Ala Gln Lys Tyr His 
                110                 115                 120 

Glu Tyr Ser His Tyr Lys Glu Gln Asp Gly Gln Gly Met Lys Gln 
                125                 130                 135 

Arg Pro Pro Arg Gly Ser His Ala Pro Tyr Leu Leu Val Phe Gln 
                140                 145                 150 

Ala Ile Phe Tyr Ser Phe Phe His Leu Ser Phe Ala Cys Ala Gln 
                155                 160                 165 

Leu Pro Met Ile Tyr Phe Leu Asn His Tyr Leu Tyr Asp Leu Asn 
                170                 175                 180 

His Thr Leu Tyr Asn Val Gln Ser Cys Gly Thr Asn Ser His Gly 
                185                 190                 195 

Ile Leu Ser Gly Phe Asn Lys Thr Val Leu Arg Thr Leu Pro Arg 
                200                 205                 210 

Ser Gly Asn Leu Ile Val Val Glu Ser Val Leu Met Ala Val Ala 
                215                 220                 225 

Phe Leu Ala Met Leu Leu Val Leu Gly Leu Cys Gly Ala Ala Tyr 
                230                 235                 240 

Arg Pro Thr Glu Glu Ile Asp Leu Arg Ser Val Gly Trp Gly Asn 
                245                 250                 255 

Ile Phe Gln Leu Pro Phe Lys His Val Arg Asp Tyr Arg Leu Arg 
                260                 265                 270 

His Leu Val Pro Phe Phe Ile Tyr Ser Gly Phe Glu Val Leu Phe 
                275                 280                 285 

Ala Cys Thr Gly Ile Ala Leu Gly Tyr Gly Val Cys Ser Val Gly 
                290                 295                 300 

Leu Glu Arg Leu Ala Tyr Leu Leu Val Ala Tyr Ser Leu Gly Ala 
                305                 310                 315 

Ser Ala Ala Ser Leu Leu Gly Leu Leu Gly Leu Trp Leu Pro Arg 
                320                 325                 330 

Pro Val Pro Leu Val Ala Gly Ala Gly Val His Leu Leu Leu Thr 
                335                 340                 345 

Phe Ile Leu Phe Phe Trp Ala Pro Val Pro Arg Val Leu Gln His 
                350                 355                 360 

Ser Trp Ile Leu Tyr Val Ala Ala Ala Leu Trp Gly Val Gly Ser 
                365                 370                 375 

Ala Leu Asn Lys Thr Gly Leu Ser Thr Leu Leu Gly Ile Leu Tyr 
                380                 385                 390 

Glu Asp Lys Glu Arg Gln Asp Phe Ile Phe Thr Ile Tyr His Trp 
                395                 400                 405 

Trp Gln Ala Val Ala Ile Phe Thr Val Tyr Leu Gly Ser Ser Leu 
                410                 415                 420 

His Met Lys Ala Lys Leu Ala Val Leu Leu Val Thr Leu Val Ala 
                425                 430                 435 

Ala Ala Val Ser Tyr Leu Arg Met Glu Gln Lys Leu Arg Arg Gly 
                440                 445                 450 

Val Ala Pro Arg Gln Pro Arg Ile Pro Arg Pro Gln His Lys Val 
                455                 460                 465 

Arg Gly Tyr Arg Tyr Leu Glu Glu Asp Asn Ser Asp Glu Ser Asp 
                470                 475                 480 

Ala Glu Gly Glu His Gly Asp Gly Ala Glu Glu Glu Ala Pro Pro 
                485                 490                 495 

Ala Gly Pro Arg Pro Gly Pro Glu Pro Ala Gly Leu Gly Arg Arg 
                500                 505                 510 

Pro Cys Pro Tyr Glu Gln Ala Gln Gly Gly Asp Gly Pro Glu Glu 
                515                 520                 525 

Gln 

 
           
             14  
             348  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 162131CD1  
             
           
            14 

Met Gly Ser Trp Val Gln Leu Ile Thr Ser Val Gly Val Gln Gln 
  1               5                  10                  15 

Asn His Pro Gly Trp Thr Val Ala Gly Gln Phe Gln Glu Lys Lys 
                 20                  25                  30 

Arg Phe Thr Glu Glu Val Ile Glu Tyr Phe Gln Lys Lys Val Ser 
                 35                  40                  45 

Pro Val His Leu Lys Ile Leu Leu Thr Ser Asp Glu Ala Trp Lys 
                 50                  55                  60 

Arg Phe Val Arg Val Ala Glu Leu Pro Arg Glu Glu Ala Asp Ala 
                 65                  70                  75 

Leu Tyr Glu Ala Leu Lys Asn Leu Thr Pro Tyr Val Ala Ile Glu 
                 80                  85                  90 

Asp Lys Asp Met Gln Gln Lys Glu Gln Gln Phe Arg Glu Trp Phe 
                 95                 100                 105 

Leu Lys Glu Phe Pro Gln Ile Arg Trp Lys Ile Gln Glu Ser Ile 
                110                 115                 120 

Glu Arg Leu Arg Val Ile Ala Asn Glu Ile Glu Lys Val His Arg 
                125                 130                 135 

Gly Cys Val Ile Ala Asn Val Val Ser Gly Ser Thr Gly Ile Leu 
                140                 145                 150 

Ser Val Ile Gly Val Met Leu Ala Pro Phe Thr Ala Gly Leu Ser 
                155                 160                 165 

Leu Ser Ile Thr Ala Ala Gly Val Gly Leu Gly Ile Ala Ser Ala 
                170                 175                 180 

Thr Ala Gly Ile Ala Ser Ser Ile Val Glu Asn Thr Tyr Thr Arg 
                185                 190                 195 

Ser Ala Glu Leu Thr Ala Ser Arg Leu Thr Ala Thr Ser Thr Asp 
                200                 205                 210 

Gln Leu Glu Ala Leu Arg Asp Ile Leu His Asp Ile Thr Pro Asn 
                215                 220                 225 

Val Leu Ser Phe Ala Leu Asp Phe Asp Glu Ala Thr Lys Met Ile 
                230                 235                 240 

Ala Asn Asp Val His Thr Leu Arg Arg Ser Lys Ala Thr Val Gly 
                245                 250                 255 

Arg Pro Leu Ile Ala Trp Arg Tyr Val Pro Ile Asn Val Val Glu 
                260                 265                 270 

Thr Leu Arg Thr Arg Gly Ala Pro Thr Arg Ile Val Arg Lys Val 
                275                 280                 285 

Ala Arg Asn Leu Gly Lys Ala Thr Ser Gly Val Leu Val Val Leu 
                290                 295                 300 

Asp Val Val Asn Leu Val Gln Asp Ser Leu Asp Leu His Lys Gly 
                305                 310                 315 

Glu Lys Ser Glu Ser Ala Glu Leu Leu Arg Gln Trp Ala Gln Glu 
                320                 325                 330 

Leu Glu Glu Asn Leu Asn Glu Leu Thr His Ile His Gln Ser Leu 
                335                 340                 345 

Lys Ala Gly 

 
           
             15  
             520  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 1837725CD1  
             
           
            15 

Met Gly Pro Gln Arg Arg Leu Ser Pro Ala Gly Ala Ala Leu Leu 
  1               5                  10                  15 

Trp Gly Phe Leu Leu Gln Leu Thr Ala Ala Gln Glu Ala Ile Leu 
                 20                  25                  30 

His Ala Ser Gly Asn Gly Thr Thr Lys Asp Tyr Cys Met Leu Tyr 
                 35                  40                  45 

Asn Pro Tyr Trp Thr Ala Leu Pro Ser Thr Leu Glu Asn Ala Thr 
                 50                  55                  60 

Ser Ile Ser Leu Met Asn Leu Thr Ser Thr Pro Leu Cys Asn Leu 
                 65                  70                  75 

Ser Asp Ile Pro Pro Val Gly Ile Lys Ser Lys Ala Val Val Val 
                 80                  85                  90 

Pro Trp Gly Ser Cys His Phe Leu Glu Lys Ala Arg Ile Ala Gln 
                 95                 100                 105 

Lys Gly Gly Ala Glu Ala Met Leu Val Val Asn Asn Ser Val Leu 
                110                 115                 120 

Phe Pro Pro Ser Gly Asn Arg Ser Glu Phe Pro Asp Val Lys Ile 
                125                 130                 135 

Leu Ile Ala Phe Ile Ser Tyr Lys Asp Phe Arg Asp Met Asn Gln 
                140                 145                 150 

Thr Leu Gly Asp Asn Ile Thr Val Lys Met Tyr Ser Pro Ser Trp 
                155                 160                 165 

Pro Asn Phe Asp Tyr Thr Met Val Val Ile Phe Val Ile Ala Val 
                170                 175                 180 

Phe Thr Val Ala Leu Gly Gly Tyr Trp Ser Gly Leu Val Glu Leu 
                185                 190                 195 

Glu Asn Leu Lys Ala Val Thr Thr Glu Asp Arg Glu Met Arg Lys 
                200                 205                 210 

Lys Lys Glu Glu Tyr Leu Thr Phe Ser Pro Leu Thr Val Val Ile 
                215                 220                 225 

Phe Val Val Ile Cys Cys Val Met Met Val Leu Leu Tyr Phe Phe 
                230                 235                 240 

Tyr Lys Trp Leu Val Tyr Val Met Ile Ala Ile Phe Cys Ile Ala 
                245                 250                 255 

Ser Ala Met Ser Leu Tyr Asn Cys Leu Ala Ala Leu Ile His Lys 
                260                 265                 270 

Ile Pro Tyr Gly Gln Cys Thr Ile Ala Cys Arg Gly Lys Asn Met 
                275                 280                 285 

Glu Val Arg Leu Ile Phe Leu Ser Gly Leu Cys Ile Ala Val Ala 
                290                 295                 300 

Val Val Trp Ala Val Phe Arg Asn Glu Asp Arg Trp Ala Trp Ile 
                305                 310                 315 

Leu Gln Asp Ile Leu Gly Ile Ala Phe Cys Leu Asn Leu Ile Lys 
                320                 325                 330 

Thr Leu Lys Leu Pro Asn Phe Lys Ser Cys Val Ile Leu Leu Gly 
                335                 340                 345 

Leu Leu Leu Leu Tyr Asp Val Phe Phe Val Phe Ile Thr Pro Phe 
                350                 355                 360 

Ile Thr Lys Asn Gly Glu Ser Ile Met Val Glu Leu Ala Ala Gly 
                365                 370                 375 

Pro Phe Gly Asn Asn Glu Lys Leu Pro Val Val Ile Arg Val Pro 
                380                 385                 390 

Lys Leu Ile Tyr Phe Ser Val Met Ser Val Cys Leu Met Pro Val 
                395                 400                 405 

Ser Ile Leu Gly Phe Gly Asp Ile Ile Val Pro Gly Leu Leu Ile 
                410                 415                 420 

Ala Tyr Cys Arg Arg Phe Asp Val Gln Thr Gly Ser Ser Tyr Ile 
                425                 430                 435 

Tyr Tyr Val Ser Ser Thr Val Ala Tyr Ala Ile Gly Met Ile Leu 
                440                 445                 450 

Thr Phe Val Val Leu Val Leu Met Lys Lys Gly Gln Pro Ala Leu 
                455                 460                 465 

Leu Tyr Leu Val Pro Cys Thr Leu Ile Thr Ala Ser Val Val Ala 
                470                 475                 480 

Trp Arg Arg Lys Glu Met Lys Lys Phe Trp Lys Gly Asn Ser Tyr 
                485                 490                 495 

Gln Met Met Asp His Leu Asp Cys Ala Thr Asn Glu Glu Asn Pro 
                500                 505                 510 

Val Ile Ser Gly Glu Gln Ile Val Gln Gln 
                515                 520 

 
           
             16  
             534  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 3643847CD1  
             
           
            16 

Met Gln Ala Ala Arg Val Asp Tyr Ile Ala Pro Trp Trp Val Val 
  1               5                  10                  15 

Trp Leu His Ser Val Pro His Val Gly Leu Arg Leu Gln Pro Val 
                 20                  25                  30 

Asn Ser Thr Phe Ser Pro Gly Asp Glu Ser Tyr Gln Glu Ser Leu 
                 35                  40                  45 

Leu Phe Leu Gly Leu Val Ala Ala Val Cys Leu Gly Leu Asn Leu 
                 50                  55                  60 

Ile Phe Leu Val Ala Tyr Leu Val Cys Ala Cys His Cys Arg Arg 
                 65                  70                  75 

Asp Asp Ala Val Gln Thr Lys Gln His His Ser Cys Cys Ile Thr 
                 80                  85                  90 

Trp Thr Ala Val Val Ala Gly Leu Ile Cys Cys Ala Ala Val Gly 
                 95                 100                 105 

Val Gly Phe Tyr Gly Asn Ser Glu Thr Asn Asp Gly Ala Tyr Gln 
                110                 115                 120 

Leu Met Tyr Ser Leu Asp Asp Ala Asn His Thr Phe Ser Gly Ile 
                125                 130                 135 

Asp Ala Leu Val Ser Gly Thr Thr Gln Lys Met Lys Val Asp Leu 
                140                 145                 150 

Glu Gln His Leu Ala Arg Leu Ser Glu Ile Phe Ala Ala Arg Gly 
                155                 160                 165 

Asp Tyr Leu Gln Thr Leu Lys Phe Ile Gln Gln Met Ala Gly Ser 
                170                 175                 180 

Val Val Val Gln Leu Ser Gly Leu Pro Val Trp Arg Glu Val Thr 
                185                 190                 195 

Met Glu Leu Thr Lys Leu Ser Asp Gln Thr Gly Tyr Val Glu Tyr 
                200                 205                 210 

Tyr Arg Trp Leu Ser Tyr Leu Leu Leu Phe Ile Leu Asp Leu Val 
                215                 220                 225 

Ile Cys Leu Ile Ala Cys Leu Gly Leu Ala Lys Arg Ser Lys Cys 
                230                 235                 240 

Leu Leu Ala Ser Met Leu Cys Cys Gly Ala Leu Ser Leu Leu Leu 
                245                 250                 255 

Ser Trp Ala Ser Leu Ala Ala Asp Gly Ser Ala Ala Val Ala Thr 
                260                 265                 270 

Ser Asp Phe Cys Val Ala Pro Asp Thr Phe Ile Leu Asn Val Thr 
                275                 280                 285 

Glu Gly Gln Ile Ser Thr Glu Val Thr Arg Tyr Tyr Leu Tyr Cys 
                290                 295                 300 

Ser Gln Ser Gly Ser Ser Pro Phe Gln Gln Thr Leu Thr Thr Phe 
                305                 310                 315 

Gln Arg Ala Leu Thr Thr Met Gln Ile Gln Val Ala Gly Leu Leu 
                320                 325                 330 

Gln Phe Ala Val Pro Leu Phe Ser Thr Ala Glu Glu Asp Leu Leu 
                335                 340                 345 

Ala Ile Gln Leu Leu Leu Asn Ser Ser Glu Ser Ser Leu His Gln 
                350                 355                 360 

Leu Thr Ala Met Val Asp Cys Arg Gly Leu His Lys Asp Tyr Leu 
                365                 370                 375 

Asp Ala Leu Ala Gly Ile Cys Tyr Asp Gly Leu Gln Gly Leu Leu 
                380                 385                 390 

Tyr Leu Gly Leu Phe Ser Phe Leu Ala Ala Leu Ala Phe Ser Thr 
                395                 400                 405 

Met Ile Cys Ala Gly Pro Arg Ala Trp Lys His Phe Thr Thr Arg 
                410                 415                 420 

Asn Arg Glu Tyr Asp Asp Ile Asp Asp Asp Asp Pro Phe Asn Pro 
                425                 430                 435 

Gln Ala Trp Arg Met Ala Ala His Ser Pro Pro Arg Gly Gln Leu 
                440                 445                 450 

His Ser Phe Cys Ser Tyr Ser Ser Gly Leu Gly Ser Gln Thr Ser 
                455                 460                 465 

Leu Gln Pro Pro Ala Gln Thr Ile Ser Asn Ala Pro Val Ser Glu 
                470                 475                 480 

Tyr Met Asn Gln Ala Met Leu Phe Gly Arg Asn Pro Arg Tyr Glu 
                485                 490                 495 

Asn Val Pro Leu Ile Gly Arg Ala Ser Pro Pro Pro Thr Tyr Ser 
                500                 505                 510 

Pro Ser Met Arg Ala Thr Tyr Leu Ser Val Ala Asp Glu His Leu 
                515                 520                 525 

Arg His Tyr Gly Asn Gln Phe Pro Ala 
                530 

 
           
             17  
             820  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 6889872CD1  
             
           
            17 

Met Leu Arg Leu Gly Leu Cys Ala Ala Ala Leu Leu Cys Val Cys 
  1               5                  10                  15 

Arg Pro Gly Ala Val Arg Ala Asp Cys Trp Leu Ile Glu Gly Asp 
                 20                  25                  30 

Lys Gly Tyr Val Trp Leu Ala Ile Cys Ser Gln Asn Gln Pro Pro 
                 35                  40                  45 

Tyr Glu Thr Ile Pro Gln His Ile Asn Ser Thr Val His Asp Leu 
                 50                  55                  60 

Arg Leu Asn Glu Asn Lys Leu Lys Ala Val Leu Tyr Ser Ser Leu 
                 65                  70                  75 

Asn Arg Phe Gly Asn Leu Thr Asp Leu Asn Leu Thr Lys Asn Glu 
                 80                  85                  90 

Ile Ser Tyr Ile Glu Asp Gly Ala Phe Leu Gly Gln Ser Ser Leu 
                 95                 100                 105 

Gln Val Leu Gln Leu Gly Tyr Asn Lys Leu Ser Asn Leu Thr Glu 
                110                 115                 120 

Gly Met Leu Arg Gly Met Ser Arg Leu Gln Phe Leu Phe Val Gln 
                125                 130                 135 

His Asn Leu Ile Glu Val Val Thr Pro Thr Ala Phe Ser Glu Cys 
                140                 145                 150 

Pro Ser Leu Ile Ser Ile Asp Leu Ser Ser Asn Arg Leu Ser Arg 
                155                 160                 165 

Leu Asp Gly Ala Thr Phe Ala Ser Leu Ala Ser Leu Met Val Cys 
                170                 175                 180 

Glu Leu Ala Gly Asn Pro Phe Asn Cys Glu Cys Asp Leu Phe Gly 
                185                 190                 195 

Phe Leu Ala Trp Leu Val Val Phe Asn Asn Val Thr Lys Asn Tyr 
                200                 205                 210 

Asp Arg Leu Gln Cys Glu Ser Pro Arg Glu Phe Ala Gly Tyr Pro 
                215                 220                 225 

Leu Leu Val Pro Arg Pro Tyr His Ser Leu Asn Ala Ile Thr Val 
                230                 235                 240 

Leu Gln Ala Lys Cys Arg Asn Gly Ser Leu Pro Ala Arg Pro Val 
                245                 250                 255 

Ser His Pro Thr Pro Tyr Ser Thr Asp Ala Gln Arg Glu Pro Asp 
                260                 265                 270 

Glu Asn Ser Gly Phe Asn Pro Asp Glu Ile Leu Ser Val Glu Pro 
                275                 280                 285 

Pro Ala Ser Ser Thr Thr Asp Ala Ser Ala Gly Pro Ala Ile Lys 
                290                 295                 300 

Leu His His Val Thr Phe Thr Ser Ala Thr Leu Val Val Ile Ile 
                305                 310                 315 

Pro His Pro Tyr Ser Lys Met Tyr Ile Leu Val Gln Tyr Asn Asn 
                320                 325                 330 

Ser Tyr Phe Ser Asp Val Met Thr Leu Lys Asn Lys Lys Glu Ile 
                335                 340                 345 

Val Thr Leu Asp Lys Leu Arg Ala His Thr Glu Tyr Thr Phe Cys 
                350                 355                 360 

Val Thr Ser Leu Arg Asn Ser Arg Arg Phe Asn His Thr Cys Leu 
                365                 370                 375 

Thr Phe Thr Thr Arg Asp Pro Val Pro Gly Asp Leu Ala Pro Ser 
                380                 385                 390 

Thr Ser Thr Thr Thr His Tyr Ile Met Thr Ile Leu Gly Cys Leu 
                395                 400                 405 

Phe Gly Met Val Ile Val Leu Gly Ala Val Tyr Tyr Cys Leu Arg 
                410                 415                 420 

Lys Arg Arg Met Gln Glu Glu Lys Gln Lys Ser Val Asn Val Lys 
                425                 430                 435 

Lys Thr Ile Leu Glu Met Arg Tyr Gly Ala Asp Val Asp Ala Gly 
                440                 445                 450 

Ser Ile Val His Ala Ala Gln Lys Leu Gly Glu Pro Pro Val Leu 
                455                 460                 465 

Pro Val Ser Arg Met Ala Ser Ile Pro Ser Met Ile Gly Glu Lys 
                470                 475                 480 

Leu Pro Thr Ala Lys Gly Leu Glu Ala Gly Leu Asp Thr Pro Lys 
                485                 490                 495 

Val Ala Thr Lys Gly Asn Tyr Ile Glu Val Arg Thr Gly Ala Gly 
                500                 505                 510 

Gly Asp Gly Leu Ala Arg Pro Glu Asp Asp Leu Pro Asp Leu Glu 
                515                 520                 525 

Asn Gly Gln Gly Ser Ala Ala Glu Ile Ser Thr Ile Ala Lys Glu 
                530                 535                 540 

Val Asp Lys Val Asn Gln Ile Ile Asn Asn Cys Ile Asp Ala Leu 
                545                 550                 555 

Lys Leu Asp Ser Ala Ser Phe Leu Gly Gly Gly Ser Ser Ser Gly 
                560                 565                 570 

Asp Pro Glu Leu Ala Phe Glu Cys Gln Ser Leu Pro Ala Ala Ala 
                575                 580                 585 

Ala Ala Ser Ser Ala Thr Gly Pro Gly Ala Leu Glu Arg Pro Ser 
                590                 595                 600 

Phe Leu Ser Pro Pro Tyr Lys Glu Ser Ser His His Pro Leu Gln 
                605                 610                 615 

Arg Gln Leu Ser Ala Asp Ala Ala Val Thr Arg Lys Thr Cys Ser 
                620                 625                 630 

Val Ser Ser Ser Gly Ser Ile Lys Ser Ala Lys Val Phe Ser Leu 
                635                 640                 645 

Asp Val Pro Asp His Pro Ala Ala Thr Gly Leu Ala Lys Gly Asp 
                650                 655                 660 

Ser Lys Tyr Ile Glu Lys Gly Ser Pro Leu Asn Ser Pro Leu Asp 
                665                 670                 675 

Arg Leu Pro Leu Val Pro Ala Gly Ser Gly Gly Gly Ser Gly Gly 
                680                 685                 690 

Gly Gly Gly Ile His His Leu Glu Val Lys Pro Ala Tyr His Cys 
                695                 700                 705 

Ser Glu His Arg His Ser Phe Pro Ala Leu Tyr Tyr Glu Glu Gly 
                710                 715                 720 

Ala Asp Ser Leu Ser Gln Arg Val Ser Phe Leu Lys Pro Leu Thr 
                725                 730                 735 

Arg Ser Lys Arg Asp Ser Thr Tyr Ser Gln Leu Ser Pro Arg His 
                740                 745                 750 

Tyr Tyr Ser Gly Tyr Ser Ser Ser Pro Glu Tyr Ser Ser Glu Ser 
                755                 760                 765 

Thr His Lys Ile Trp Glu Arg Phe Arg Pro Tyr Lys Lys His His 
                770                 775                 780 

Arg Glu Glu Val Tyr Met Ala Ala Gly His Ala Leu Arg Lys Lys 
                785                 790                 795 

Val Gln Phe Ala Lys Asp Glu Asp Leu His Asp Ile Leu Asp Tyr 
                800                 805                 810 

Trp Lys Gly Val Ser Ala Gln Gln Lys Leu 
                815                 820 

 
           
             18  
             2653  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 6431478CB1  
             
           
            18 

gctgcggctg agcccagcgc tcgaggcgcg aggcagccag gagggcccgt gcggcgcggg     60 

gagccagcga gcgcgccttc ggcattggcc gccgcgatgt cagctcagtg ctgtgcgggc    120 

cagctggcct gctgctgtgg gtctgcaggc tgctctctct gctgtgattg ctgccccagg    180 

attcggcagt ccctcagcac ccgcttcatg tacgccctct acttcattct ggtcgtcgtc    240 

ctctgctgca tcatgatgtc aacaaccgtg gctcacaaga tgaaagagca cattcctttt    300 

tttgaagata tgtgtaaagg cattaaagct ggtgacacct gtgagaagct ggtgggatat    360 

tctgccgtgt atagagtctg ttttggaatg gcttgtttct tctttatctt ctgtctactg    420 

accttgaaaa tcaacaacag caaaagttgt agagctcata ttcacaatgg cttttggttc    480 

tttaaacttc tgctgttggg ggccatgtgc tcaggagctt tcttcattcc agatcaggac    540 

acctttctga acgcctggcg ctatgtggga gccgtcggag gcttcctctt cattggcatc    600 

cagctcctcc tgctcgtgga gtttgcacat aagtggaaca agaactggac agcaggcaca    660 

gccagtaaca agctgtggta cgcctccctg gccctggtga cgctcatcat gtattccatt    720 

gccactggag gcttggtttt gatggcagtg ttttatacac agaaagacag ctgcatggaa    780 

aacaaaattc tgctgggagt aaatggaggc ctgtgcctgc ttatatcatt ggtagccatc    840 

tcaccctggg tccaaaatcg acagccacac tcggggctct tacaatcagg ggtcataagc    900 

tgctatgtca cctacctcac cttctcagct ctgtccagca aacctgcaga agtagttcta    960 

gatgaacatg ggaaaaatgt tacaatctgt gtgcctgact ttggtcaaga cctgtacaga   1020 

gatgaaaact tggtgactat actggggacc agcctcttaa tcggatgtat cttgtattca   1080 

tgtttgacat caacaacaag atcgagttct gacgctctgc aggggcgata cgcagctcct   1140 

gaattggaga tagctcgctg ttgtttttgc ttcagtcctg gtggagagga cactgaagag   1200 

cagcagccgg ggaaggaggg accacgggtc atttatgacg agaagaaagg caccgtctac   1260 

atctactcct acttccactt cgtgttcttc ctagcttccc tgtatgtgat gatgaccgtc   1320 

accaactggt tcaactacga aagtgccaac atcgagagct tcttcagcgg gagctggtcc   1380 

atcttctggg tcaagatggc ctcctgctgg atatgcgtgc tgttgtacct gtgtacgctg   1440 

gtcgctcccc tctgctgccc cacccgggag ttctctgtgt gatgatatcg gcggtcccct   1500 

gggctttgtg ggcctacagc ctggaaagtg ccatcttttg aacagtgtcc ccggggcagg   1560 

gactggcgcc ctgtgcctga gtgggtctga aaaagctttg agagagaaaa aaaaaaatct   1620 

cctgattagc tttttacttt tgaaattcaa aaagaaacta ccagtttgtc ccaaaggaat   1680 

tgaaattttc aaccaaactg atcatggttg aaatatctta cccctaggaa ctggatacca   1740 

gttatgttga cttccttctg catgtttttg ccaaaacaga atttggggca cagcatcttt   1800 

tcacagggat aaaaatatct cgtggggcca gtcattctca tcctcggaat agaaaaacat   1860 

gccaaaatct tgagtcccca gcgcctaaca gaatccagac ccctctcact cacttccgcc   1920 

tcttagagcc ttgtccccag ggggctttga ggacaggact cagcctgcag ggcccctggt   1980 

atttataggg tccaagagga ggcacctgct tttcaactgc accctcagtg ctgcctcttc   2040 

acggccccta aacgtttccc tttgaggttg tgatgctggg aatcacagac ttcactctct   2100 

gcctgcaccc ttccccgagg tctcatcttt tctgggtccc acatctttgt aataatgtga   2160 

aaaagcacaa tttgtctgat caccccccag gtggttcccc accttattat cactacctga   2220 

tccgagttac tgcaataagt acggcgctta tttatggtgt tagtcacatg attatagaac   2280 

aagattcatg ttttctctgc ctaagcaatg gagggctatc attcttactt gtttgtgctg   2340 

ttgataatga taatactttt aggaccttaa ctgaaaagct gcttcgtgtt gaagcctgct   2400 

gcatgcactg ctctttcagt tgttgaggtc agcccctcag ttttttctcc accttgaggc   2460 

ctttgaaact gtaaaagcgg aagtcgtttt gtgttctgga tctgtaacgt gaccataccg   2520 

ttcaggttca tgctggcatc cttggagtag atttgctaat gtgagaattt ctgaggtgag   2580 

gatctcagac acactgacca gaagaagctt gttaggcaat gtgtggaagt ggccgaatat   2640 

acttaaaaag agg                                                      2653 

 
           
             19  
             3531  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 3584654CB1  
             
           
            19 

ggaagcggtc ggggctgcac actcggatcg gcggggccgg ctcccgggcc cggccggctg     60 

gaggagggag ggaaggaggc gggagggagc gagcggagcc atgggtgcgc acgtacgccc    120 

cagcgctggg atttatcggc tcgcgaggag agcggagcag gcgcgcggcc caggcggagg    180 

agcgccgact ctggagcagc cggagctgga agaggaggag gaggagaggc ggcggggaag    240 

gaggaggagg gggagagtcg ctcccgccgg gcgagcatgg ggcgcctggc ctcgaggccg    300 

ctgctgctgg cgctcctgtc gttggctctt tgccgagggc gtgtggtgag agtccccaca    360 

gcgaccctgg ttcgagtggt gggcactgag ctggtcatcc cctgcaacgt cagtgactat    420 

gatggcccca gcgagcaaaa ctttgactgg agcttctcat ctttggggag cagctttgtg    480 

gagcttgcaa gcacctggga ggtggggttc ccagcccagc tgtaccagga gcggctgcag    540 

aggggcgaga tcctgttaag gcggactgcc aacgacgccg tggagctcca cataaagaac    600 

gtccagcctt cagaccaagg ccactacaaa tgttcaaccc ccagcacaga tgccactgtc    660 

cagggaaact atgaggacac agtgcaggtt aaagtgctgg ccgactccct gcacgtgggc    720 

cccagcgcgc ggcccccgcc gagcctgagc ctgcgggagg gggagccctt cgagctgcgc    780 

tgcaccgccg cctccgcctc gccgctgcac acgcacctgg cgctgctgtg ggaggtgcac    840 

cgcggcccgg ccaggcggag cgtcctcgcc ctgacccacg agggcaggtt ccacccgggc    900 

ctggggtacg agcagcgcta ccacagtggg gacgtgcgcc tcgacaccgt gggcagcgac    960 

gcctaccgcc tctcagtgtc ccgggctctg tctgccgacc agggctccta caggtgtatc   1020 

gtcagcgagt ggatcgccga gcagggcaac tggcaggaaa tccaagaaaa ggccgtggaa   1080 

gttgccaccg tggtgatcca gccgacagtt ctgcgagcag ctgtgcccaa gaatgtgtct   1140 

gtggctgaag gaaaggaact ggacctgacc tgtaacatca caacagaccg agccgatgac   1200 

gtccggcccg aggtgacgtg gtccttcagc aggatgcctg acagcaccct acctggctcc   1260 

cgcgtgttgg cgcggcttga ccgtgattcc ctggtgcaca gctcgcctca tgttgctttg   1320 

agtcatgtgg atgcacgctc ctaccattta ctggttcggg atgttagcaa agaaaactct   1380 

ggctactatt actgccacgt gtccctgtgg gcacccggac acaacaggag ctggcacaaa   1440 

gtggcagagg ccgtgtcttc cccagctggt gtgggtgtga cctggctaga accagactac   1500 

caggtgtacc tgaatgcttc caaggtcccc gggtttgcgg atgaccccac agagctggca   1560 

tgccgggtgg tggacacgaa gagtggggag gcgaatgtcc gattcacggt ttcgtggtac   1620 

tacaggatga accggcgcag cgacaatgtg gtgaccagcg agctgcttgc agtcatggac   1680 

ggggactgga cgctaaaata tggagagagg agcaagcagc gggcccagga tggagacttt   1740 

attttttcta aggaacatac agacacgttc aatttccgga tccaaaggac tacagaggaa   1800 

gacagaggca attattactg tgttgtgtct gcctggacca aacagcggaa caacagctgg   1860 

gtgaaaagca aggatgtctt ctccaagcct gttaacatat tttgggcatt agaagattcc   1920 

gtgcttgtgg tgaaggcgag gcagccaaag cctttctttg ctgccggaaa tacatttgag   1980 

atgacttgca aagtatcttc caagaatatt aagtcgccac gctactctgt tctcatcatg   2040 

gctgagaagc ctgtcggcga cctctccagt cccaatgaaa cgaagtacat catctctctg   2100 

gaccaggatt ctgtggtgaa gctggagaat tggacagatg catcacgggt ggatggcgtt   2160 

gttttagaaa aagtgcagga ggatgagttc cgctatcgaa tgtaccagac tcaggtctca   2220 

gacgcagggc tgtaccgctg catggtgaca gcctggtctc ctgtcagggg cagcctttgg   2280 

cgagaagcag caaccagtct ctccaatcct attgagatag acttccaaac ctcaggtcct   2340 

atatttaatg cttctgtgca ttcagacaca ccatcagtaa ttcggggaga tctgatcaaa   2400 

ttgttctgta tcatcactgt cgagggagca gcactggatc cagatgacat ggcctttgat   2460 

gtgtcctggt ttgcggtgca ctcttttggc ctggacaagg ctcctgtgct cctgtcttcc   2520 

ctggatcgga agggcatcgt gaccacctcc cggagggact ggaagagcga cctcagcctg   2580 

gagcgcgtga gtgtgctgga attcttgctg caagtgcatg gctccgagga ccaggacttt   2640 

ggcaactact actgttccgt gactccatgg gtgaagtcac caacaggttc ctggcagaag   2700 

gaggcagaga tccactccaa gcccgttttt ataactgtga agatggatgt gctgaacgcc   2760 

ttcaagtatc ccttgctgat cggcgtcggt ctgtccacgg tcatcgggct cctgtcctgt   2820 

ctcatcgggt actgcagctc ccactggtgt tgtaagaagg aggttcagga gacacggcgc   2880 

gagcgccgca ggctcatgtc gatggagatg gactaggctg gcccgggagg ggagtgacag   2940 

agggacgttc taggagcaat tggggcaaga agaggacagt gatattttaa aacaaagtgt   3000 

gttacactaa aaaccagtcc tctctaatct caggtgggac ttggcgctct ctcttttctg   3060 

catgtcaagt tctgagcgcg gacatgttta ccagcacacg gctcttcttc ccacggcact   3120 

ttctgatgta acaatcgagt gtgtgttttc ccaactgcag ctttttaatg gttaaccttc   3180 

atctaatttt ttttctccca ctggtttata gatcctctga cttgtgtgtg tttatagctt   3240 

ttgtttcgcg gggttgtggt gaggaagggg tgatggcatg cggagttctt tgtcttcagt   3300 

gagaatgtgc ctgcccgcct gagagccagc ttccgcgttg gaggcacgtg ttcagagagc   3360 

tgctgagcgc caccctctac ccggctgaca gacaacacag acctgtgccg aaggctaatt   3420 

tgtggctttt acgaccctac cccaccccct gttttcaggg gtttagacta catttgaaat   3480 

ccaaacttgg agtatataac ttcttattga gcccaactgc tttttttttt t            3531 

 
           
             20  
             2280  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 3737084CB1  
             
           
            20 

gcgcgcccat ttcgagccca agtttccagc tcgggtttcc aggctcagaa ttttccagga     60 

gtaggttctt gggcagtggc tgtgggagct ggaatggcgc agctggaagg ttactatttc    120 

tcggccgcct tgagctgtac ctttttagta tcctgcctcc tcttctccgc cttcagccgg    180 

gcgttgcgag agccctacat ggacgagatc ttccacctgc ctcaggcgca gcgctactgt    240 

gagggccatt tctccctttc ccagtgggat cccatgatta ctacattacc tggcttgtac    300 

ctggtgtcaa ttggagtgat caaacctgcc atttggatct ttggatggtc tgaacatgtt    360 

gtctgctcca ttgggatgct cagatttgtt aatcttctct tcagtgttgg caacttctat    420 

ttactatatt tgcttttctg caaggtacaa cccagaaaca aggctgcctc aagtatccag    480 

agagtcttgt caacattaac actagcagta tttccaacac tttatttttt taacttcctt    540 

tattatacag aagcaggatc tatgtttttt actctttttg cgtatttgat gtgtctttat    600 

ggaaatcata aaacttcagc cttccttgga ttttgtggct tcatgtttcg gcaaacaaat    660 

atcatctggg ctgtcttctg tgcaggaaat gtcattgcac aaaagttaac ggaggcttgg    720 

aaaactgagc tacaaaagaa ggaagacaga cttccaccta ttaaaggacc atttgcagaa    780 

ttcagaaaaa ttcttcagtt tcttttggct tattccatgt cctttaaaaa cttgagtatg    840 

cttttgcttc tgacttggcc ctacatcctt ctgggatttc tgttttgtgc ttttgtagta    900 

gttaatggtg gaattgttat tggcgatcgg agtagtcatg aagcctgtct tcattttcct    960 

caactattct actttttttc atttactctc tttttttcct ttcctcatct cctgtctcct   1020 

agcaaaatta agacttttct ttccttagtt tggaaacgta gaattctgtt ttttgtggtt   1080 

accttagtct ctgtgttttt agtttggaaa ttcacttatg ctcataaata cttgctagca   1140 

gacaatagac attatacttt ctatgtgtgg aaaagagttt ttcaaagata tgaaactgta   1200 

aaatatttgt tagttccagc ctatatattt gctggttgga gtatagctga ctcattgaaa   1260 

tcaaagtcaa ttttttggaa tttaatgttt ttcatatgct tgttcactgt tatagttcct   1320 

cagaaactgc tggaatttcg ttacttcatt ttaccttatg tcatttatag gcttaacata   1380 

cctctgcctc ccacatccag actcatttgt gaactgagct gctatgcagt tgttaatttc   1440 

ataacttttt tcatctttct gaacaagact tttcagtggc caaatagtca ggacattcaa   1500 

aggtttatgt ggtaatatca gtgatatttc gaactgtgaa aatggactta ataattagac   1560 

catttctaca aagaacaact gaataggtgg aaaacatgga atttctttta ggtgcagtgg   1620 

tggtcttcaa attacattag ttttttttat atatatttta aacatatgta agaaattaag   1680 

tggcaaagaa ctgagaaagc ttaagacctg cttcaaaagc ctgaaaaatg gaaaaataaa   1740 

attgttttca gatatctcat atcactctca taatgttggc cccttaaaaa gcttgggaat   1800 

gttttgtatg tacaagttta ttaaaactgg gtatgcttca aaaaaaaaaa aaaagggggg   1860 

gggttcccac ccccaattcc gaaacctgga aaagcggttc cccggggaaa attttttacc   1920 

cccccaaatt cccccaaaaa ttggggcccg ggagcctaaa ggtactaccc cggggggccc   1980 

taaggggtgg gccccccccc attaattggg gtggccccaa tgccccgttt ccaattggga   2040 

aaccttttgg tcccacccct tttattaatt ggccaacccc cggggaaaag gggttttcct   2100 

tttgggggcc tttcccgttc cccggccaat aaaccggttc ccccgggttt tcgggttcgg   2160 

ggaagggttt ccagcccccc aaaggggggt aaacgggttt ccccaaaatt cggggggaaa   2220 

ccccggaaaa aacatttttg cccaaagggc ccccaaaagg ccaggcccct taaaaaggcc   2280 

 
           
             21  
             1104  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 71426238CB1  
             
           
            21 

taaagagagt tttgccttct tttgagccta agtcatgagt tggatgttcc tcagagatct     60 

cctgagtgga gtaaataaat actccactgg gattggatgg atttggctgg ctgtcgtgtt    120 

tgtcttccgt ttgctggtct acatggtggc agcagagcac gtgtggaaag atgagcagaa    180 

agagtttgag tgcaacagta gacagcccgg ttgcaaaaat gtgtgttttg atgacttctt    240 

ccccatttcc caagtcagac tttgggcctt acaactgata atggtctcca caccttcact    300 

tctggtggtt ttacatgtag cctatcatga gggtagagag aaaaggcaca gaaagaaact    360 

ctatgtcagc ccaggtacaa tggatggggg cctatggtac gcttatctta tcagcctcat    420 

tgttaaaact ggttttgaaa ttggcttcct tgttttattt tataagctat atgatggctt    480 

tagtgttccc taccttataa agtgtgattt gaagccttgt cccaacactg tggactgctt    540 

catctccaaa cccactgaga agacgatctt catcctcttc ttggtcatca cctcatgctt    600 

gtgtattgtg ttgaatttca ttgaactgag ttttttggtt ctcaagtgcc ttattaagtg    660 

ctgtctccaa aaatatttaa aaaaacctca agtcctcagt gtgtgagtgc cacagcctca    720 

gatatgttga atgtggtagg agagggaccc ctcccctact ccagaatctt cacacttggc    780 

cataaacaca ctccctctac ctgaagcaaa gctactctgt gacacacaag agggttaaac    840 

aaagaaaacc tgcatccctc ctcagcaagg cctaagctga gttggaagac aaagcacatc    900 

agctttagta tcatttggga ggaatttttt tacattgtca atatgctttc agttatgagc    960 

tctagacaga ggtctcattg ttttgttgta gggttctcca gtatgtggat aacattagtt   1020 

gttttagaat aggtaattgc aaattagtct gaagaaatct aacaggattc ttttaagagc   1080 

ttagattttt cagggaaaaa aaaa                                          1104 

 
           
             22  
             4966  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7475123CB1  
             
           
            22 

ggcggccgag ggcgattgcg gggcgcgcag gccgcgtgca cccgggacgc ttcccctcgg     60 

ggaccctccg cgggcttctc cgccgcgccg tccggcggga gccggcggga ccccgggcga    120 

gcggcgcggg cggcaccatg aggcggcagt ggggcgcgct gctgcttggc gccctgctct    180 

gcgcacacgg cctggccagc agccccgagt gtgcttgtgg tcggagccac ttcacatgtg    240 

cagtgagtgc tcttggagag tgtacctgca tccctgccca gtggcagtgt gatggagaca    300 

atgactgcgg ggaccacagc gatgaggatg gatgtatact acctacctgt tcccctcttg    360 

actttcactg tgacaatggc aagtgcatcc gccgctcctg ggtgtgtgac ggggacaacg    420 

actgtgagga tgactcggat gagcaggact gtcccccccg ggagtgtgag gaggacgagt    480 

ttccctgcca gaatggctac tgcatccgga gtctgtggca ctgcgatggt gacaatgact    540 

gtggcgacaa cagcgatgag cagtgtgaca tgcgcaagtg ctccgacaag gagttccgct    600 

gtagtgacgg aagctgcatt gctgagcatt ggtactgcga cggtgacacc gactgcaaag    660 

atggctccga tgaggagaac tgtccctcag cagtgccagc gcccccctgc aacctggagg    720 

agttccagtg tgcctatgga cgctgcatcc tcgacatcta ccactgcgat ggcgacgatg    780 

actgtggaga ctggtcagac gagtctgact gctgtgagta ctctggccag ctgggagcct    840 

cccaccagcc ctgccgctct ggggagttca tgtgtgacag tggcctgtgc atcaatgcag    900 

gctggcgctg cgatggtgac gcggactgtg atgaccagtc tgatgagcgc aactgcaact    960 

ggcagaccaa gtcaatccag cgtgttgaca aatactcagg ccggaacaag gagacagtgc   1020 

tggcaaatgt ggaaggactc atggatatca tcgtggtttc ccctcagcgg cagacaggga   1080 

ccaatgcctg tggtgtgaac aatggtggct gcacccacct ctgctttgcc agagcctcgg   1140 

acttcgtatg tgcctgtcct gacgaacctg atagccggcc ctgctccctt gtgcctggcc   1200 

tggtaccacc agctcctagg gctactggca tgagtgaaaa gagcccagtg ctacccaaca   1260 

caccacctac caccttgtat tcttcaacca cccggacccg cacgtctctg gaggaggtgg   1320 

aaggaaggat ggacatccgt cgaatcagct ttgacacaga ggacctgtct gatgatgtca   1380 

tcccactggc tgacgtgcgc agtgctgtgg cccttgactg ggactcccgg gatgaccacg   1440 

tgtactggac agatgtcagc actgatacca tcagcagggc caagtgggat ggaacaggac   1500 

aggaggtggt agtggatacc agtttggaga gcccagctgg cctggccatt gattgggtca   1560 

ccaacaaact gtactggaca gatgcaggta cagaccggat tgaagtagcc aacacagatg   1620 

gcagcatgag aacagtactc atctgggaga accttgatcg tcctcgggac atcgtggtgg   1680 

aacccatggg cgggtacatg tattggactg actggggtgc gagccccaag attgaacgag   1740 

ctggcatgga tgcctcaggc cgccaagtca ttatctcttc taatctgacc tggcctaatg   1800 

ggttagctat tgattatggg tcccagcgtc tatactgggc tgacgccggc atgaagacaa   1860 

ttgaatttgc tggactggat ggcagtaaga ggaaggtgct gattggaagc cagctccccc   1920 

acccatttgg gctgaccctc tatggagagc gcatctattg gactgactgg cagaccaaga   1980 

gcatacagag cgctgaccgg ctgacagggc tggaccggga gactctgcag gagaacctgg   2040 

aaaacctaat ggacatccat gtcttccacc gccgccggcc cccagtgtct acaccatgtg   2100 

ctatggagaa tggcggctgt agccacctgt gtcttaggtc cccaaatcca agcggattca   2160 

gctgtacctg ccccacaggc atcaacctgc tgtctgatgg caagacctgc tcaccaggca   2220 

tgaacagttt cctcatcttc gccaggagga tagacattcg catggtctcc ctggacatcc   2280 

cttattttgc tgatgtggtg gtaccaatca acattaccat gaagaacacc attgccattg   2340 

gagtagaccc ccaggaagga aaggtgtact ggtctgacag cacactgcac aggatcagtc   2400 

gtgccaatct ggatggctca cagcatgagg acatcatcac cacagggcta cagaccacag   2460 

atgggctcgc ggttgatgcc attggccgga aagtatactg gacagacacg ggaacaaacc   2520 

ggattgaagt gggcaacctg gacgggtcca tgcggaaagt gttggtgtgg cagaaccttg   2580 

acagtccccg ggccatcgta ctgtaccatg agatggggtt tatgtactgg acagactggg   2640 

gggagaatgc caagttagag cggtccggaa tggatggctc agaccgcgcg gtgctcatca   2700 

acaacaacct aggatggccc aatggactga ctgtggacaa ggccagctcc caactgctat   2760 

gggccgatgc ccacaccgag cgaattgagg ctgctgacct gaatggtgcc aatcggcata   2820 

cattggtgtc accggtgcag cacccatatg gcctcaccct gctcgactcc tatatctact   2880 

ggactgactg gcagactcgg agcatccacc gtgctgacaa gggtactggc agcaatgtca   2940 

tcctcgtgag gtccaacctg ccaggcctca tggacatgca ggctgtggac cgggcacagc   3000 

cactaggttt taacaagtgc ggctcgagaa atggcggctg ctcccacctc tgcttgcctc   3060 

ggccttctgg cttctcctgt gcctgcccca ctggcatcca gctgaaggga gatgggaaga   3120 

cctgtgatcc ctctcctgag acctacctgc tcttctccag ccgtggctcc atccggcgta   3180 

tctcactgga caccagtgac cacaccgatg tgcatgtccc tgttcctgag ctcaacaatg   3240 

tcatctccct ggactatgac agcgtggatg gaaaggtcta ttacacagat gtgttcctgg   3300 

atgttatcag gcgagcagac ctgaacggca gcaacatgga gacagtgatc gggcgagggc   3360 

tgaagaccac tgacgggctg gcagtggact gggtggccag gaacctgtac tggacagaca   3420 

caggtcgaaa taccattgag gcgtccaggc tggatggttc ctgccgcaaa gtactgatca   3480 

acaatagcct ggatgagccc cgggccattg ctgttttccc caggaagggg tacctcttct   3540 

ggacagactg gggccacatt gccaagatcg aacgggcaaa cttggatggt tctgagcgga   3600 

aggtcctcat caacacagac ctgggttggc ccaatggcct taccctggac tatgataccc   3660 

gcaggatcta ctgggtggat gcgcatctgg accggatcga gagtgctgac ctcaatggga   3720 

aactgcggca ggtcttggtc agccatgtgt cccacccctt tgccctcaca cagcaagaca   3780 

ggtggatcta ctggacagac tggcagacca agtcaatcca gcgtgttgac aaatactcag   3840 

gccggaacaa ggagacagtg ctggcaaatg tggaaggact catggatatc atcgtggttt   3900 

cccctcagcg gcagacaggg accaatgcct gtggtgtgaa caatggtggc tgcacccacc   3960 

tctgctttgc cagagcctcg gacttcgtat gtgcctgtcc tgacgaacct gatagccagc   4020 

cctgctccct tgtgcctggc ctggtaccac cagctcctag ggctactggc atgagtgaaa   4080 

agagcccagt gctacccaac acaccaccta ccaccttgta ttcttcaacc acccggaccc   4140 

gcacgtctct ggaggaggtg gaaggaagat gctctgaaag ggatgccagg ctgggcctct   4200 

gtgcacgttc caatgacgct gttcctgctg ctccagggga aggacttcat atcagctacg   4260 

ccattggtgg actcctcagt attctgctga ttttggtggt gattgcagct ttgatgctgt   4320 

acagacacaa aaaatccaag ttcactgatc ctggaatggg gaacctcacc tacagcaacc   4380 

cctcctaccg aacatccaca caggaagtga agattgaagc aatccccaaa ccagccatgt   4440 

acaaccagct gtgctataag aaagagggag ggcctgacca taactacacc aaggagaaga   4500 

tcaagatcgt agagggaatc tgcctcctgt ctggggatga tgctgagtgg gatgacctca   4560 

agcaactgcg aagctcacgg gggggcctcc tccgggatca tgtatgcatg aagacagaca   4620 

cggtgtccat ccaggccagc tctggctccc tggatgacac agagacggag cagctgttac   4680 

aggaagagca gtctgagtgt agcagcgtcc atactgcagc cactccagaa agacgaggct   4740 

ctctgccaga cacgggctgg aaacatgaac gcaagctctc ctcagagagc caggtctaaa   4800 

tgcccacatt ctcttccctg cctgcctgtt ccttctcctt tatggacgtc tagtccttgt   4860 

gctcgcttac accgcaggcc ccgcttctgt gtgcttgtcc tcctcctcct cccaccccat   4920 

aactgttcct aagccttcac cggagctgtt taccacgtga gtcata                  4966 

 
           
             23  
             5401  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7481952CB1  
             
           
            23 

atggaccaga gcatcagcat tacctgggaa cttagtggaa atgcagaacc tcaggccctg     60 

gcccagcctt acagaaccaa aagctacatg gaacaagcaa agcatctcac ctgtgacttt    120 

gagtcgggtt tctgcggttg ggagccattt ctcacagaag attcacactg gaagctgatg    180 

aaaggattga ataatggaga gcaccacttt cctgcagctg atcacacagc aaacataaat    240 

catggatcgt ttatttattt ggaggcacag cgctcccccg gggtggccaa gcttggaagt    300 

cctgttctta caaaattgct cactgcctct accccatgtc aggtgcagtt ttggtatcat    360 

ttgtctcaac attcaaatct ctcagttttt acaagaacgt ctctagatgg aaacttgcaa    420 

aagcagggca aaataatcag attctccgaa tctcagtgga gccacgcaaa aattgatctc    480 

attgcagaag cgggagaatc tactctacct tttcagttaa ttttggaagc tactgttttg    540 

tcgtcaaatg ctaccgttgc tctagatgac atcagtgtgt cccaggaatg tgaaatttcc    600 

tataaatcac taccaaggac cagtacacaa agcaagtttt ccaagtgtga ctttgaagca    660 

aacagctgtg attggtttga agtaattagt ggtgaccatt ttgactggat acggagctct    720 

cagagtgaac tttctgctga ttttgagcac caggctccac ctcgggatca tagtctcaac    780 

gcatctcaag ggcattttat gttcattctg aagaaaagca gcagcttgtg gcaagttgct    840 

aagcttcaga gcccaacttt cagccagaca ggacctggat gcatactttc cttctggttc    900 

tataactatg gcctgtcagt gggagcagct gagctgcagc tacatatgga aaattctcat    960 

gactcaacag tgatttggag agtattatac aatcagggca aacaatggtt ggaggcaacc   1020 

attcagctag ggcgcctttc gcagcccttc catttgtcac tagataaagt cagtctgggc   1080 

atttatgatg gggtctcagc tattgatgac atccgatttg aaaattgtac tctccctctt   1140 

cctgctgaga gctgtgaagg gctggatcat ttctggtgtc gccacaccag ggcttgcata   1200 

gaaaagcttc ggttatgtga tctggtggat gactgtggtg atcgtactga tgaagtcaac   1260 

tgtgcacctg agctgcagtg taactttgaa actggaatct gtaactggga acaagatgca   1320 

aaagatgact ttgattggac caggaaccag ggtccaactc caacacttaa cacagggcca   1380 

atgaaagata acactctggg cacagctaaa ggacactatc tctacataga atcttcagag   1440 

ccacaggctt ttcaagacag tgctgcctta ctcagcccaa tccttaatgc cactgataca   1500 

aaaggctgca ccttccgctt ctattaccac atgtttggaa agcgcattta taggttggca   1560 

atctaccaac gaatctggag tgactcaagg ggacagctgc tgtggcagat atttgggaat   1620 

caaggcaaca gatggattag gaaacacctc aacatttcca gcaggcagcc ctttcagata   1680 

ttggtggagg cttcagtggg agatggcttc actggagata ttgcgattga tgatctgtca   1740 

tttatggact gcaccctcta ccctggtaat ttgccagcag acctcccaac tccaccagaa   1800 

acgtcagttc ctgtaacatt acctccacac aactgcacag acagtgaatt tatctgcagg   1860 

tctgatggtc actgcattga aaaaatgcag aaatgtgatt ttaaatatga ctgccctgac   1920 

aaatcagatg aagcatcctg tgttatggaa gtttgcagct ttgagaaaag aagcctgtgt   1980 

aaatggtatc aaccaatccc agtacatttg cttcaagatt caaacacatt caggtggggg   2040 

cttgggaacg ggatcagcat tcatcatggg gaagaaaacc acaggccatc agtggatcat   2100 

acacaaaata ccactgatgg ctggtacctg tatgctgaca gttctaatgg gaaatttggt   2160 

gacacggctg acattctcac tcctatcatt tcactcacgg gaccaaaatg taccttggtg   2220 

ttctggacac atatgaatgg ggccaccgtt ggttctctcc aggtgctcat caagaaagat   2280 

aacgttactt ctaaattgtg ggctcaaact ggacagcaag gtgcacagtg gaagagagca   2340 

gaagtgtttt taggcattcg ttcacataca cagattgtct tcagagccaa acgtggtatc   2400 

agttacatag gagatgtagc agtggatgat atttccttcc aagattgctc ccctttgctt   2460 

agcccagaga gaaagtgtac tgatcatgaa ttcatgtgtg ctaataagca ctgcattgcc   2520 

aaagacaagc tgtgtgattt tgtgaatgat tgtgctgata attcagatga gactactttc   2580 

atttgccgta cctccagtgg gcgctgtgat ttcgaatttg atctttgttc ctggaagcag   2640 

gagaaagatg aggactttga ctggaacctg aaagctagca gcatccctgc agcaggcaca   2700 

gagccagcag cagatcacac tttgggaaat tcatctggtc attacatctt tataaagagt   2760 

ttgtttcctc agcagcccat gagagctgcc agaatttcaa gtccagttat aagtaagaga   2820 

agcaaaaact gcaagattat ttttcattat cacatgtatg gaaatggcat tggggcactc   2880 

accttaatgc aggtgtcagt cacaaaccaa acgaaggttc tacttaacct cactgtagaa   2940 

caaggcaatt tctggcggag agaagaactg tcactgtttg gtgatgaaga cttccaactc   3000 

aaatttgaag gtagagttgg gaaaggtcag cgtggagaca ttgcacttga tgacattgtg   3060 

cttacagaaa attgtctatc actccatgat tccgtgcaag aagaactggc agtgcctctt   3120 

ccaacaggtt tctgcccact tggctatagg gaatgtcata atggaaaatg ctataggctg   3180 

gaacaaagct gtaacttcgt agataactgt ggagataata ctgatgaaaa tgagtgtggt   3240 

agctcctgta cttttgaaaa aggctggtgt ggctggcaaa actcccaggc tgacaacttt   3300 

gattgggttt taggggttgg ctctcatcaa agcttaagac ctcccaaaga ccacacactt   3360 

ggaaatgaaa atgggcactt catgtatctg gaagctactg cagtgggcct tcggggtgac   3420 

aaagcacact tcaggagtac catgtggcga gaatccagtg cagcctgcac catgagcttc   3480 

tggtatttca tatctgcaaa ggccacagga tccattcaga ttctcatcaa gacagagaaa   3540 

ggactatcaa aagtatggca agaaagtaag cagaaccctg gtaatcattg gcaaaaggct   3600 

gacatcctgc taggaaagtt aaggaatttt gaagtcatat ttcaaggtat cagaacaagg   3660 

gacctgggag gaggagctgc aattgatgat attgaattta aaaactgcac aactgtggga   3720 

gagatctctg agctttgtcc ggaaatcact gattttttgt gccgggacaa gaagtgcatt   3780 

gcatcccacc ttctttgtga ctataagcca gactgctctg ataggtctga tgaagctcac   3840 

tgtgcacatt atacaagcac aacaggaagc tgcaattttg aaacaagttc aggaaactgg   3900 

accacagcct gcagtcttac tcaagactct gaggatgact tggactgggc cattggcagc   3960 

agaattcctg ccaaagcatt aattccagac tctgatcaca cgccaggtag tggtcagcac   4020 

ttcctgtacg tcaactcatc tggctccaag gaaggatccg ttgccagaat tactacttcc   4080 

aaatccttcc cagcaagcct tggaatgtgt actgttcggt tctggttcta catgattgat   4140 

cccaggagta tgggaatatt aaaggtgtat accattgaag aatcggggct aaacatcctg   4200 

gtgtggtcag tgattggaaa taaaagaacg ggatggacat atggctctgt gcctctctcc   4260 

agtaacagtc cgtttaaggt ggcatttgaa gctgatttgg atggaaatga ggacatcttt   4320 

attgctcttg atgacatctc ttttacccca gagtgtgtga ctggaggtcc tgtcccagtg   4380 

cagccatcac cctgtgaagc tgatcagttt tcttgtatct acacactcca atgtgtccct   4440 

ctctcaggga aatgtgatgg acatgaagac tgcatagatg gatctgatga aatggattgt   4500 

cctctcagcc ccacccctcc actctgtagt aacatggagt tcccgtgctc tacagacgag   4560 

tgtatacctt ccctcctgct atgcgatgga gtgcccgact gccactttaa tgaagatgag   4620 

ctcatctgct ccaacaaaag ctgttctaat ggagctctgg tgtgtgcctc ctccaacagc   4680 

tgtatcccag cccaccagcg ctgtgatggt tttgccgact gcatggattt ccagcttgat   4740 

gagtccagct gctcagaatg tccattaaat tactgcagaa atggtgggac ttgtgtagtg   4800 

gagaaaaatg gtcctatgtg tcgatgtaga caaggctgga aaggaaatcg atgccatatc   4860 

aagtttaatc ctcctgctac agacttcaca tacgctcaga ataatacatg gactctcctg   4920 

ggtattggat tagcattcct gatgactcac atcacagttg cagtcttgtg ttttcttgca   4980 

aacagaaagg taccaataag gaaaaccgag ggaagtggta actgtgcctt tgtcaatcca   5040 

gtttacggga actggagcaa cccagagaaa acagagagtt ctgtctattc cttctcaaac   5100 

ccattatatg gcacaacatc aggaagcctg gagaccctgt cacatcatct caaatagcag   5160 

catcgagacc aagtctgatc caacatgtgt agtttctaga aaattgaagt ctccacaatc   5220 

tgatagaaac tcatcttcta caatggtaaa aagagaaagg attgtaaatg ccagtgtaat   5280 

tataacattt atgaatgaat tttcttgcag aatatagaga atgtttatat ggaatcagaa   5340 

tcagtacctt atcttcactg aacatctgaa tattttaata aaatttctat ttaatcaaaa   5400 

a                                                                   5401 

 
           
             24  
             1949  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 382654CB1  
             
           
            24 

aggcagaggg ctaggtggaa aaagcattga aggccatgag atggctgtga gagagaacaa     60 

aggggcagaa gtgcacagag ctactgtggg ggaggagata gcacccaggc ttaagaagcc    120 

aggattggca gggagtgaag agccagagag gcgaagcttt gggagatcag agggcttaaa    180 

gttgggagtg ggctaaggag cccagggcct gatgcttccc tcttcctcat gggcctctgt    240 

tcacagaccc cctggagggg gtgaacatca ccagccccgt gcgcctgatc catggcaccg    300 

tggggaagtc ggctctgctt tctgtgcagt acagcagtac cagcagcgac aggcctgtag    360 

tgaagtggca gctgaagcgg gacaagccag tgaccgtggt gcagtccatt ggcacagagg    420 

tcatcggcac cctgcggcct gactatcgag accgtatccg actctttgaa aatggctccc    480 

tgcttctcag cgacctgcag ctggccgatg agggcaccta tgaggtcgag atctccatca    540 

ccgacgacac cttcactggg gagaagacca tcaaccttac tgtagatgtg cccatttcga    600 

ggccacaggt gttggtggct tcaaccactg tgctggagct cagcgaggcc ttcaccttga    660 

actgctcaca tgagaatggc accaagccca gctacacctg gctgaaggat ggcaagcccc    720 

tcctcaatga ctcgagaatg ctcctgtccc ccgaccaaaa ggtgctcacc atcacccgcg    780 

tgctcatgga ggatgacgac ctgtacagct gcatggtgga gaaccccatc agccagggcc    840 

gcagcctgcc tgtcaagatc accgtataca gaagaagctc cctttacatc atcttgtcta    900 

caggaggcat cttcctcctt gtgaccttgg tgacagtctg tgcctgctgg aaaccctcca    960 

aaaggaaaca gaagaagcta gaaaagcaaa actccctgga atacatggat cagaatgatg   1020 

accgcctgaa accagaagca gacaccctcc ctcgaagtgg tgagcaggaa cggaagaacc   1080 

ccatggcact ctatatcctg aaggacaagg actccccgga gaccgaggag aacccggccc   1140 

cggagcctcg aagcgcgacg gagcccggcc cgcccggcta ctccgtgtct cccgccgtgc   1200 

ccggccgctc gccggggctg cccatccgct ctgcccgccg ctacccgcgc tccccagcgc   1260 

gctccccagc caccggccgg acacactcgt cgccgcccag ggccccgagc tcgcccggcc   1320 

gctcgcgcag cgcctcgcgc acactgcgga ctgcgggcgt gcacataatc cgcgagcaag   1380 

acgaggccgg cccggtggag atcagcgcct gagccgcctc gggatcccct gagaggcgcc   1440 

cgcggtctgc ggccagtggc ccgggggaaa gctggggctg ggaagcccgg gcgcggcgcg   1500 

ctggggacga ggggaggtcc cgggggggcg ctggtgtctc gggtgtgaac gtgtatgagc   1560 

atgcgcagac ggaggcgggt gcgcggaggc ggcagtgttg atatggtgaa accgggtcgc   1620 

atttgcttcc ggtttactgg ctgtgtcctc acttggtata ggttgtgcca tggggttctt   1680 

ccgttcctgc tcaccacttc gagggagggt gtctgcttct ggtttcaggc ggtcatcatt   1740 

ctgatccatg tattccaggg agtttcgctt ttctagcttc ttctgtttcc ttttggaggg   1800 

tttccagcag gcacagactg tcaccaaggt cacaaggagg aagatgcctc ctgtagacaa   1860 

gatgatgtac agggagcttc tcctagggag agagagaagc gagagcagga gggcctcccg   1920 

gggccagatg tgtgaccact gccctacta                                     1949 

 
           
             25  
             2133  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 1867351CB1  
             
           
            25 

cactgccggc ctccgcggta cccactgccg gcctccgcgc tacccggccg cagcgcgcga     60 

gtcacatgga agctcctgag gagcccgcgc cagtgcgcgg aggcccggag gccacccttg    120 

aggtccgtgg gtcgcgctgc ttgcggctgt ccgccttccg agaagagctg cgggcgctct    180 

tggtcctggc tggccccgcg ttcttggttc agctgatggt gttcctgatc agcttcataa    240 

gctccgtgtt ctgtggccac ctgggcaagc tggagctgga tgcagtcacg ctggcaatcg    300 

cggttatcaa tgtcactggt gtctcagtgg gattcggctt atcttctgcc tgtgacaccc    360 

tcatctccca gacgtacggg agccagaacc tgaagcacgt gggcgtgatc ctgcagcgga    420 

gtgcgctcgt cctgctcctc tgctgcttcc cctgctgggc gctctttctc aacacccagc    480 

acatcctgct gctcttcagg caggacccag atgtgtccag gcttacccag acctatgtca    540 

cgatcttcat tccagctctt cctgcaacct ttctttatat gttacaagtt aaatatttgc    600 

tcaaccaggg aattgtactg ccccagatcg taactggagt tgcagccaac cttgtcaatg    660 

ccctcgccaa ctatctgttt ctccatcaac tgcatcttgg ggtgataggc tctgcactgg    720 

caaacttgat ttcccagtac accctggctc tactcctctt tctctacatc ctcgggaaaa    780 

aactgcatca agctacatgg ggaggctggt ccctcgagtg cctgcaggac tgggcctcct    840 

tcctccgcct ggccatcccc agcatgctca tgctgtgcat ggagtggtgg gcctatgagg    900 

tcgggagctt ccccagtggc atcctcggca tggtggagct gggcgctcag tccatcgtgt    960 

atgaactggc catcattgtg tacatggtcc ctgcagactt cagtgtggct gccagtgtcc   1020 

gggtaggaaa cgctctgggt gctggagaca tggagcaggc acggaagtcc tctaccgttt   1080 

ccctgctgat tacagtgctc tttgctgtag ccttcagtgt cctgctgtta agctgtaagg   1140 

atcacgtggg gtacattttt actaccgacc gagacatcat taatctggtg gctcaggtgg   1200 

ttccaattta tgctgtttcc cacctctttg aagctcttgc ttgcacgagt ggtggtgttc   1260 

tgagggggag tggaaatcag aaggttggag ccattgtgaa taccattggg tactatgtgg   1320 

ttggcctccc catcgggatc gcgctgatgt ttgcaaccac acttggagtg atgggtctgt   1380 

ggtcagggat catcatctgt acagtctttc aagctgtgtg ttttctaggc tttattattc   1440 

agctaaattg gaaaaaagcc tgtcagcagg ctcaggtaca cgccaatttg aaagtaaaca   1500 

acgtgcctcg gagtgggaat tctgctctcc ctcaggatcc gcttcaccca gggtgccctg   1560 

aaaaccttga aggaatttta acgaacgatg ttggaaagac aggcgagcct cagtcagatc   1620 

agcagatgcg ccaagaagaa cctttgccgg aacatccaca ggacggcgct aaattgtcca   1680 

ggaaacagct ggtgctgcgg cgagggcttc tgctcctggg ggtcttctta atcttgctgg   1740 

tggggatttt agtgagattc tatgtcagaa ttcagtgacg tggtaggaaa gaaagtcagg   1800 

tcaagtgatg cttttgagct tacacacaat tcacaggccc accagtgaca atttactgtg   1860 

agttaatgtc attcaggtgt gcccatggat tttgagggct ggaaatgcaa agacacattt   1920 

ttctataaaa agaaaaagca actaaggtta aaagctatat tgtggcccaa gacactgttt   1980 

gtgaaagatg ccatgattag taattcacca ctatcttgaa ccaagcacag gatcaatgtg   2040 

ctgactgcat cggccaatgg ctttgatact tctgctattt ttttagacac aacccataac   2100 

tacggggatn actagttcta agcgccggca ccg                                2133 

 
           
             26  
             2090  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 3323104CB1  
             
           
            26 

ggcggaagcg agaccgtcca tccagaggaa ggcaagtttt tggctcgggc ggctgagaag     60 

accgcgcggg gctggagaca ggtagcagta cgggggcggg gcttcatgcc ggatgtgata    120 

gtctgcagtc gtttcggttg gcagcctggc gggtgggaga tgcggcggcc acctgctgca    180 

aagaaccgaa gggaaggtta gaagtacgaa ggcagtttgg agctggggct aagcagctgt    240 

cgcacggtca gatcatgggc tccaccaagc actggggcga attgctcctg aacttgaagg    300 

tggctccagc cggcgtcttt ggtgtggcct ttctagccag agtcgccctg gttttctatg    360 

gcgtcttcca ggaccggacc ctgcacgtga ggtatacgga catcgactac caggtcttca    420 

ccgacgccgc gcgcttcgtc acggaggggc gctcgcctta cctgagagcc acgtaccgtt    480 

acaccccgct gctgggttgg ctcctcactc ccaacatcta cctcagcgag ctctttggaa    540 

agtttctctt catcagctgc gacctcctca ccgctttcct cttataccgc ctgctgctgc    600 

tgaaggggct ggggcgccgc caggcttgtg gctactgtgt cttttggctt cttaaccccc    660 

tgcctatggc agtatccagc cgcggtaatg cggactctat tgtcgcctcc ctggtcctga    720 

tggtcctcta cttgataaag aaaagactcg tcgcgtgtgc agctgtattc tatggtttcg    780 

cggtgcatat gaagatatat ccagtgactt acatccttcc cataaccctc cacctgcttc    840 

cagatcgcga caatgacaaa agcctccgtc aattccggta cactttccag gcttgtttgt    900 

acgagctcct gaaaaggctg tgtaatcggg ctgtgctgct gtttgtagca gttgctggac    960 

tcacgttttt tgccctgagc tttggttttt actatgagta cggctgggaa tttttggaac   1020 

acacctactt ttatcacctg actaggcggg atatccgtca caacttttct ccgtacttct   1080 

acatgctgta tttgactgca gagagcaagt ggagtttttc cctgggaatt gctgcattcc   1140 

tgccacagct catcttgctt tcagctgtgt ctttcgccta ttacagagac ctcgtttttt   1200 

gttgttttct tcatacgtcc atttttgtga cttttaacaa agtctgcacc tcccagtact   1260 

ttctttggta cctctgctta ctgcctcttg tgatgccact agtcagaatg ccttggaaaa   1320 

gagctgtagt tctcctaatg ttatggttaa tagggcaggc catgtggctg gctcctgcct   1380 

atgttctaga gtttcaagga aagaacacct ttctgtttat ttggttagct ggtttgttct   1440 

ttcttcttat caattgttcc atcctgattc aaattatttc ccattacaaa gaagaacccc   1500 

tgacagagag aatcaaatat gactagtgta tgttccacac cctctgctac tgtgttacat   1560 

tctgattgtc ttgtatggac cagaagagag ctttgggaca ttttttctga acattctaag   1620 

cattctagtg aaagttccca tgttccaaca gaacttaaaa gcaatgtttg ccttatatat   1680 

aaaagggaca caataattga ggtccacctt ctaggaaatc ctaggactcg tttatttggg   1740 

acatggtggg aataaaggtc acatattgga aaatggaaag gctgatgaaa ctatcagata   1800 

ctaaaacatt cttaaaatag aggaatatag ttagagacat caggtttaag ccagtatttg   1860 

ttcctgtttt acaatgcttc tgtcttaagc tgtgtcttaa cttttaacac ccatcttttc   1920 

tttctaaagc tttcctgaca gctgtgaaaa tccaaaaaat attcttaaac tgtgtatggt   1980 

ggcccttgcc tgtagtctca gcactttggg aggctgaggt gggagggtcg cttgagttca   2040 

ggagttctag acccacctgg ggcaagatgg tgagacctag tctcaaaaaa              2090 

 
           
             27  
             1618  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 4769306CB1  
             
           
            27 

agaatctatg ggattttcag ctcgatacaa tttcacacct gatcctgact ttaaggacct     60 

tggagctttg aaaccattac cagcgtgtga gtttgagatg ggcggttccg aaggaattgt    120 

ggagtctata caaattatga aggaaggcaa agctactgct agcgaggctg ttgattgcaa    180 

gtggtacatc cgagcacctc cacggtccaa gatttactta cgattcttgg actatgagat    240 

gcagaattca aatgagtgca agaggaattt tgtggctgtg tatgatggaa gcagttccgt    300 

ggaggatttg aaagctaagt tctgtagcac tgtggctaat gatgtcatgc tacgcacggg    360 

tcttggggtg atccgcatgt gggcagatga gggcagtcga aacagccgat ttcagatgct    420 

cttcacatcc tttcaagaac ctccttgtga aggcaacaca ttcttctgcc atagtaacat    480 

gtgtattaat aatactttgg tctgcaatgg actccagaac tgtgtgtatc cttgggatga    540 

aaatcactgt aaagagaaga ggaaaaccag cctgctggac cagctgacca acaccagtgg    600 

gactgtcatt ggcgtgactt cctgcatcgt gatcatcctc attatcatct ctgtcatcgt    660 

acagatcaaa cagcctcgta aaaagtatgt ccaaaggaaa tcagactttg accagacagt    720 

tttccaggag gtatttgaac ctcctcatta tgagttatgc actctcagag ggacaggagc    780 

tacagctgac tttgcagatg tggcagatga ctttgaaaat taccataaac tgcggaggtc    840 

atcttccaaa tgcattcatg accatcactg tggatcacag ctgtccagca ctaaaggcag    900 

ccgcagtaac ctcagcacaa gagatgcttc tatcttgaca gagatgccca cacagccagg    960 

aaaacccctc atcccaccca tgaacagaag aaatatcctt gtcatgaaac acaactactc   1020 

gcaagatgct gcagatgcct gtgacataga tgaaatcgaa gaggtgccga ccaccagtca   1080 

caggctgtcc agacacgata aagccgtcca gcggttctgc ctcattgggt ctctaagcaa   1140 

acatgaatct gaatacaaca caactagggt ctagaaagaa aattcaagac agcttgagaa   1200 

tagtgcgttc ctgaatgatt ttgaacatgc tacagtgaaa agtgacagtg tggaccatgg   1260 

aatcaccagc tagagatgag gaaactgaag agttttagta acttttttaa gattacacaa   1320 

taaacaatga tgaatcaagc tttgaagcca acctcaccaa ccacaagatc aaccaacact   1380 

cttcaccaat gtgtaatata accacgttaa tattcaacat agtacgtact gctgaaagaa   1440 

gttgatactt attcatatta accccgtagt tttgtgtttc ctcatctgta aaagtatgta   1500 

ttataacacc ttctctccac cttacagcgt gtgaggttca aatgaccatt cattggaaga   1560 

tattttttat atcctataat gcattataaa aataaatcat ttttcctaaa aaaaaaaa     1618 

 
           
             28  
             3269  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 2720058CB1  
             
           
            28 

cctgagggga atggctttcg tccccttcct cttggtgacc tggtcgtcag ccgccttcat     60 

tatctcctac gtggtcgccg tgctctccgg gcacgtcaac cccttcctcc cgtatatcag    120 

tgatacggga acaacacctc cagagagtgg tatttttgga tttatgataa acttctctgc    180 

atttcttggt gcagccacga tgtatacaag atacaaaata gtacagaagc aaaatcaaac    240 

ctgctatttc agcactcctg tttttaactt ggtgtcttta gtgcttggat tggtgggatg    300 

tttcggaatg ggcattgtcg ccaattttca ggagttagct gtgccagtgg ttcatgacgg    360 

gggcgctctt ttggcctttg tctgtggtgt cgtgtacacg ctcctacagt ccatcatctc    420 

ttacaaatca tgtccccagt ggaacagtct ctcgacatgc cacatacgga tggtcatctc    480 

tgccgtttct tgcgcagctg tcatccccat gattgtctgt gcttcactaa tttccataac    540 

caagctggag tggaatccaa gagaaaagga ttatgtatat cacgtagtga gtgcgatctg    600 

tgaatggaca gtggcctttg gttttatttt ctacttccta actttcatcc aagatttcca    660 

gagtgtcacc ctaaggatat ccacagaaat caatggtgat atttgaagaa agaagaattc    720 

agtctcactc agtgaatgtc gcaggccatt tctaaaagtg ctacagagga cagacagggt    780 

tttgaggcca ccctgattat tgggatgcat ctgcagcaca tccaggactt gaatttcatt    840 

acgagttcct aatagttgta tttctaaaga tgtgtttcct agagaatgta cagccttatg    900 

acactgtagt gatgttttta taattttcta agtagatttt tttatattaa caaattcata    960 

tacagaaaaa ataaggtgtt acaaaaaatg gagagctctt atttttgtac agattctgtc   1020 

gtttttgttt tatttgtgtg agatttatgg aaatacacta aatgagtaat tcaggttcag   1080 

tacatttatt acaaagtgaa atcaggggat attcatttgt aaattttatt cttagtgaat   1140 

gaactgtata atttttttta tcaggagagc acttataaaa ttcaatttat aaagatcata   1200 

tacccaaatc ataaagattt agttgataca ttaacactaa gatactctga tttttagccg   1260 

aactaaacaa agtgcttcta ctgagaggcc tttataccac catgtacagt aactctaagt   1320 

gaatacggaa gaccttggtt ttgaaattct gccaccttgt ttctccctgc tcatgaggtc   1380 

gcaccttttg ctcttgctgc taattgccca ttcgtagtgg gtgtaatgcc aggtggaatg   1440 

gtttcaacaa gtcaggtgaa aaccatcctt tattgttgct ggcacaactt gatatatagt   1500 

ctgactcaga actgaagctc acatctcaaa ttcatttcat gccagtaaat gtggcaaaga   1560 

gaagaaaggc ccaagagcga gacaagaaga atggagaagg gggcagccaa gaagaacttc   1620 

tgggttcagg gtactgttta tttgctcctt ctcttcatgc ctgtggctgg atgtcccaca   1680 

acactataag aaataagtca agccctttgt gttaagcaag aactacagac tccatctttt   1740 

cacccaaatc atgaatgacc aataaaaagc aagttattcc agaggaagaa gcagcccttg   1800 

aaatgttaag gcttaggctt gaaaggtgaa gagcaggaat tctctctttc aaatcctaga   1860 

gcataaaccc atgtgtggcc aagtgagatc agccctcaag ggcacatgcc aagggcagag   1920 

cagcccatgt agacagcttc ggagggcatg ggggtgtagg gagttcgggg tagctcctca   1980 

ttaactattt gttgggtgag taaaggggtg aggctcagtg gcaggtacct ctgcaatgac   2040 

aagctgcctc ccctctatgt gtttagcata tgttattaga acatgtccga cacccctacc   2100 

gctgccattt gggcccttta ataaagccaa gtagagaaat ctggcaataa aaggcaaatg   2160 

taagcatgct ttctttaaga cgcatcataa atggttttct ttaagtgaat ggaagagttt   2220 

gacagagata cacctttgta agaaaacatt aagaatgctg gctggctgtg gtggctcaca   2280 

cctgtattcc cagcactttg ggaggcctag gcaggaggat tgcttgagcc tgggacttcg   2340 

agaccagact gggaaacatg gcaaaatccc atctctacaa caaaaataca aaaattagcc   2400 

aagtgcggtg gtgtgcctgt agtcctagtt acttgggagg ctgaggtggg agaatcacct   2460 

gagcccagga ggtggaggct gcagtgagcc atgccaatgc actccagtct gggcaacaga   2520 

gtgagaccct gtctcaaaaa taaataaata aataaatgaa taaagagaat gctaatcatt   2580 

tctgggttca ctgcgactca ctgtagtgct ggggatcccc cttgtaacac tggaactgaa   2640 

agacagtgat gaaagctatg tcaagcattc attattctga agaggaggag aaatgccaca   2700 

tacctttccc atgggacctg tggtggaatg aatccatact tctgcctcac ttcgagcaga   2760 

cttttgttct cggcgctcct cacgatggag tttcatgctt cattttcaca tctctctgca   2820 

caattagatt gggagctcct tgagggcaga gtacgtgcct taatctttat ctttgtaatg   2880 

ccacaatgaa cagagtgcct cctggtacac tgtaggagct taagaaatac tcactgaatg   2940 

catgaatgaa tgaatgaaca aatgaaggaa tgactaagga tgtttgtagt gctataatat   3000 

agaatgggat ttactctgct ttaccagtta gtttcataat aaacaaatag tctgtaacag   3060 

aacattctgt acctgccata caggctcatg ttcatgccaa ttcttcctag agccaaataa   3120 

ataaagactt agggggggcc cccgaaaaaa gggccgccgc cccggggttt atctccggcc   3180 

cgggcctgaa gccgacaccg gttccccaag ggtacagctt tccccttggg ggactcaggg   3240 

gaacagggtt ccccggggca atttttacc                                     3269 

 
           
             29  
             1227  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7481255CB1  
             
           
            29 

atggacaggg ccaagcagca gcaggcgctg ctcctcctcc ctgtctgcct cgccctcacc     60 

ttctccctca ccgccgtggt cagcagccac tggtgtgagg ggacccgacg ggtggtgaag    120 

ccactgtgcc aggaccagcc gggagggcag cactgcattc acttcaaacg ggacaacagc    180 

agcaatggca ggatggacaa caatagccag gctgtcctgt acatttggga gctgggtgat    240 

gacaagttca ttcagcgggg gttccatgtg gggctctggc agtcctgcga ggagagcctc    300 

aacggtgaag atgaaaagtg taggagtttc cggagtgtag tgccagctga agaacaaggt    360 

gttttgtggc tgtccatcgg gggcgaggtc ctggatatcg ttctgatact gacaagcgcc    420 

atcctcctgg gctccagagt gagttgtcgc agccctgggt tccactggct cagggtggat    480 

gccttggtag ccatcttcat ggtgctggca gggcttctag gcatggtggc ccacatgatg    540 

tacacaacca tttttcaaat cactgtgaac cttggaccag aagattggaa gcctcagacc    600 

tgggactatg gctggtcata ttgccttgcc tggggttctt tcgccctctg cctggctgtg    660 

tcggtctcgg ccatgagcag gttcacggca gcccgcctgg aattcaccga gaagcagcag    720 

gcacagaacg gcagtcggca ctctcaacac agcttcctgg aacccgaggc ttcggagagc    780 

atttggaaaa caggagctgc tccttgccct gctgaacaag ccttcaggaa tgtttctgga    840 

cacctcccac caggcgcccc aggcaaggtg tccatatgct agccagtgtc catggctgcc    900 

acatccgcac aggcaaacaa gccaggcact gacactcaca atgtacaccc tgcctctggg    960 

ttggacttca ggagattgtt gtccagggaa agcttccatc cccacccctc cacatctcac   1020 

cttttactaa acacctttgg ctttagcctt tgattcctgt taaaatgcca gtaccttgaa   1080 

gtgagataat gcttactgaa gatatcaacc attgacactc tagtataaaa gagagcttct   1140 

taatgacagt gaatttgata aggataccaa agaaacaggg aggatgccag tactaaggga   1200 

agagaagttg aagaaagagg aaagcaa                                       1227 

 
           
             30  
             2618  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 1510242CB1  
             
           
            30 

agcctaatac cttctcaagt tgatctcccc ccaggcacag ccttgtccca gccggaagac     60 

tcaaatttta aaatttcgaa ttctgaatag tttattcatg tatataagtt actgacacag    120 

taagagggat ctttttttta tcttacaaga cctaaaaatt acttaatacc tttgaaataa    180 

aatgttttat ttctgccaaa tggcattatg aatataataa gacttaagag caccaaaagt    240 

tagttactac agcaagatac actagtatac gtatatctat ttatattaag aaactcaggg    300 

cacttgtcta taattcacaa gttaccaatc ttaaacattt aaggcgaccg ccgcgagtcc    360 

gcagtagttc gggccatgga ggcggagccg ccgctctacc cgatggcggg ggctgcgggg    420 

ccgcagggcg acgaggacct gctcggggtc ccggacgggc ccgaggcccc gctggacgag    480 

ctggtgggcg cgtaccccaa ctacaacgag gaggaggagg agcgccgcta ctaccgccgc    540 

aagcggcctg ggcgtgctca agaacgtgct ggctgccagc gccgggggca tgctcaccta    600 

cggcgtctac ctgggcctcc tgcagatgca gctgatcctg cactacgacg agacctaccg    660 

cgaggtgaag tatggcaaca tggggctgcc cgacatcgac agcaaaatgc tgatgggcat    720 

caacgtgact cccatcgccg ccctgctcta cacacctgtg ctcatcaggt tttttggaac    780 

gaagtggatg atgttcctcg ctgtgggcat ctacgccctc tttgtctcca ccaactactg    840 

ggagcgctac tacacgcttg tgccctcggc tgtggccctg ggcatggcca tcgtgcctct    900 

ttgggcttcc atgggcaact acatcaccag gatggcgcag aagtaccatg agtactccca    960 

ctacaaggag caggatgggc aggggatgaa gcagcggcct ccgcggggct cccacgcgcc   1020 

ctatctcctg gtcttccaag ccatcttcta cagcttcttc catctgagct tcgcctgcgc   1080 

ccagctgccc atgatttatt tcctgaacca ctacctgtat gacctgaacc acacgctgta   1140 

caatgtgcag agctgcggca ccaacagcca cgggatcctc agcggcttca acaagacggt   1200 

tctgcggacg ctcccgcgga gcggaaacct cattgtggtg gagagcgtgc tcatggcagt   1260 

ggccttcctg gccatgctgc tggtgctggg tttgtgcgga gccgcttacc ggcccacgga   1320 

ggagatcgat ctgcgcagcg tgggctgggg caacatcttc cagctgccct tcaagcacgt   1380 

gcgtgactac cgcctgcgcc acctcgtgcc tttctttatc tacagcggct tcgaggtgct   1440 

ctttgcctgc actggtatcg ccttgggcta tggcgtgtgc tcggtggggc tggagcggct   1500 

ggcttacctc ctcgtggctt acagcctggg cgcctcagcc gcctcactcc tgggcctgct   1560 

gggcctgtgg ctgccacgcc cggtgcccct ggtggccgga gcaggggtgc acctgctgct   1620 

caccttcatc ctctttttct gggcccctgt gcctcgggtc ctgcaacaca gctggatcct   1680 

ctatgtggca gctgcccttt ggggtgtggg cagtgccctg aacaagactg gactcagcac   1740 

actcctggga atcttgtacg aagacaagga gagacaggac ttcatcttca ccatctacca   1800 

ctggtggcag gctgtggcca tcttcaccgt gtacctgggc tcgagcctgc acatgaaggc   1860 

taagctggcg gtgctgctgg tgacgctggt ggcggccgcg gtctcctacc tgcggatgga   1920 

gcagaagctg cgccggggcg tggccccgcg ccagccccgc atcccgcggc cccagcacaa   1980 

ggtgcgcggt taccgctact tggaggagga caactcggac gagagcgacg cggagggcga   2040 

gcatggggac ggcgcggagg aggaggcgcc gcccgcaggg cccaggcctg gccccgagcc   2100 

cgctggactc ggccgccggc cctgcccgta cgaacaggcg caggggggag acgggccgga   2160 

ggagcagtga ggggccgcct ggtccccgga ctcagcctcc ctcctcgccg gcctcagttt   2220 

accacgtctg aggtcggggg gaccccctcc gagtcccgcg ctgtcttcaa aggcccctgt   2280 

ctcccctccc ccacgttggg gacgcccctc ccagagccca ggtcacctcc gggcttccgc   2340 

agccccctcc aaggcggagt ggagccttgg gaacccctcg gccaagcaca ggggttcgaa   2400 

aatacagctg aaaccccgcg ggcccttagc acgcgcccca gcgccggagc acggtcaggg   2460 

tcttcttgcg acccggcccg ctccagatcc ccacagctct cggccgcgga cccgggccgc   2520 

gtgtgagcgc actttgcacc tcctatcccc agggtccgcc gagagccacg attttttaca   2580 

gaaaatgagc aataaagaga ttttgtactg tcaaaaaa                           2618 

 
           
             31  
             2188  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 162131CB1  
             
           
            31 

ccggaattga ccaactggta gactcgccta gaggggacgc attgtgtcct agttgaggct     60 

aacagtcagt atccagcctc aacattcagc agaggcccca gatcagcgtc tgagccaggc    120 

caacaatgac caaggaggat gggatcctgg gtgcagctca tcacaagcgt cggggtgcag    180 

caaaaccatc caggctggac agtggctgga cagttccaag aaaagaaacg cttcactgaa    240 

gaagtcattg aatacttcca gaagaaagtt agcccagtgc atctgaaaat cctgctgact    300 

agcgatgaag cctggaagag attcgtgcgt gtggctgaat tgcccaggga agaagcagat    360 

gctctctatg aagctctgaa gaatcttaca ccatatgtgg ctattgagga caaagacatg    420 

cagcaaaaag aacagcagtt tagggagtgg tttttgaaag agtttcctca aatcagatgg    480 

aagattcagg agtccataga aaggcttcgt gtcattgcaa atgagattga aaaggtccac    540 

agaggctgcg tcatcgccaa tgtggtgtct ggctccactg gcatcctgtc tgtcattggc    600 

gttatgttgg caccatttac agcagggctg agcctgagca ttactgcagc tggggtaggg    660 

ctgggaatag catctgccac ggctgggatc gcctccagca tcgtggagaa cacatacaca    720 

aggtcagcag aactcacagc cagcaggctg actgcaacca gcactgacca attggaggca    780 

ttaagggaca ttctgcatga catcacaccc aatgtgcttt cctttgcact tgattttgac    840 

gaagccacaa aaatgattgc gaatgatgtc catacactca ggagatctaa agccactgtt    900 

ggacgccctt tgattgcttg gcgatatgta cctataaatg ttgttgagac actgagaaca    960 

cgtggggccc ccacccggat agtgagaaaa gtagcccgga acctgggcaa ggccacttca   1020 

ggtgtcctcg ttgtgctgga tgtagtcaac cttgtgcaag actcactgga cttgcacaag   1080 

ggggaaaaat ccgagtctgc tgagttgctg aggcagtggg ctcaggagct ggaggagaat   1140 

ctcaatgagc tcacccatat ccatcagagt ctaaaagcag gctaggccca attgttgcgg   1200 

gaagtcaggg accccaaacg gagggactgg ctgaagccat ggcagaagaa cgtggattgt   1260 

gaagatttca tggacattta ttagttcccc aaattaatac ttttataatt tcctatgcct   1320 

gtctttaccg caatctctaa acacaaattg tgaagatttc atggacactt atcacttccc   1380 

caatcaatac ccttgtgatt tcttatgcct gtctttactt taatctccta atcctgtcag   1440 

ctgaggagga tgtatgtcac ctcaggacca tgtgataatt gcgttaactg cacaaattgt   1500 

agagcatgtg tgtttgaaca atatgaaatc tgggcacctt gaaaaaagaa caggataaca   1560 

gcaattgttc agggaataag agagataacc ttaaactctg accaacagtg agcctggtgg   1620 

aacagagtca tatttctctt ctttcaaaag caaatgggag aaatatcgct gaattctttt   1680 

tctcagcaag gaacatccct gagaaagaga atgcacccct gagggtgggt ctataaatgg   1740 

cctccttggg tgtggccatc ttctatggtc gagactgtag ggatgaaata aaccccagtc   1800 

tcccatagtg ctcccaggct tattaggaag aggaaattcc cgcctaataa attttggtca   1860 

gaccggttgc tctcaaaacc ctgtctcctg ataagatgtt atcaatgaca atggtgcctg   1920 

aaacctcatt agcaatttta atttctcccc ggtcctgtgg tcctgtgatc tcaccctgcc   1980 

tccacttgcc ttgtgatatt ctattacctt gtgaagtagg tgatctttgt gacccacacc   2040 

cacaccctat tcatacactc cctccccttt tgaaagtccc taataaaaac ttgctggttt   2100 

tgcagcttgt gaggcatcac ggaacctacc gatgtgtgat gtctcccctg gacacctagc   2160 

tttaaaattt ctaaaaaaaa aaaaaaaa                                      2188 

 
           
             32  
             1969  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 1837725CB1  
             
           
            32 

gtagcagcgg cggtccagtc gtagcccggc cgcccgcgcc tgtccggtcc ggtccggcca     60 

cggaggcagc gcagcggcgg gactccgagc ctaccccgcc gagtgagctg cgccgcaccg    120 

tgccgtccca cccggcaccc accagtccga tggggccgca gcggcggctg tcccctgccg    180 

gggccgccct actctggggc ttcctgctcc agctgacagc cgctcaggaa gcaatcttgc    240 

atgcgtctgg aaatggcaca accaaggact actgcatgct ttataaccct tattggacag    300 

ctcttccaag taccctagaa aatgcaactt ccattagttt gatgaatctg acttccacac    360 

cactatgcaa cctttctgat attcctcctg ttggcataaa gagcaaagca gttgtggttc    420 

catggggaag ctgccatttt cttgaaaaag ccagaattgc acagaaagga ggtgctgaag    480 

caatgttagt tgtcaataac agtgtcctat ttcctccctc aggtaacaga tctgaatttc    540 

ctgatgtgaa aatactgatt gcatttataa gctacaaaga ctttagagat atgaaccaga    600 

ctctaggaga taacattact gtgaaaatgt attctccatc gtggcctaac tttgattata    660 

ctatggtggt tatttttgta attgcggtgt tcactgtggc attaggtgga tactggagtg    720 

gactagttga attggaaaac ttgaaagcag tgacaactga agatagagaa atgaggaaaa    780 

agaaggaaga atatttaact tttagtcctc ttacagttgt aatatttgtg gtcatctgct    840 

gtgttatgat ggtcttactt tatttcttct acaaatggtt ggtttatgtt atgatagcaa    900 

ttttctgcat agcatcagca atgagtctgt acaactgtct tgctgcacta attcataaga    960 

taccatatgg acaatgcacg attgcatgtc gtggcaaaaa catggaagtg agacttattt   1020 

ttctctctgg actgtgcata gcagtagctg ttgtttgggc tgtgtttcga aatgaagaca   1080 

ggtgggcttg gattttacag gatatcttgg ggattgcttt ctgtctgaat ttaattaaaa   1140 

cactgaagtt gcccaacttc aagtcatgtg tgatacttct aggccttctc ctcctctatg   1200 

atgtattttt tgttttcata acaccattca tcacaaagaa tggtgagagt atcatggttg   1260 

aactcgcagc tggacctttt ggaaataatg aaaagttgcc agtagtcatc agagtaccaa   1320 

aactgatcta tttctcagta atgagtgtgt gcctcatgcc tgtttcaata ttgggttttg   1380 

gagacattat tgtaccaggc ctgttgattg catactgtag aagatttgat gttcagactg   1440 

gttcttctta catatactat gtttcgtcta cagttgccta tgctattggc atgatactta   1500 

catttgttgt tctggtgctg atgaaaaagg ggcaacctgc tctcctctat ttagtacctt   1560 

gcacacttat tactgcctca gttgttgcct ggagacgtaa ggaaatgaaa aagttctgga   1620 

aaggtaacag ctatcagatg atggaccatt tggattgtgc aacaaatgaa gaaaaccctg   1680 

tgatatctgg tgaacagatt gtccagcaat aatattatgt ggaactgcta taatgtgtca   1740 

ttgattttct acaaatagac ttcgactttt taaattgact tttgaattga caatctgaaa   1800 

gagtcttcaa tgatatgctt gcaaaaatat atttttatga gctggtactg acagttacat   1860 

cataaataac taaaacgctt tgcttttaat gttaaagttg tgccttcaca ttaaataaaa   1920 

catatggtct gtgtagtttc cgaaaaaaaa aaaaaaaaaa aaaaaaaaa               1969 

 
           
             33  
             3006  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 3643847CB1  
             
           
            33 

gccatgcagg cggcgcgcgt ggactacatc gctccctggt gggtcgtgtg gctgcacagc     60 

gtcccgcacg tcggcctgcg cctgcagccc gtgaacagca ccttcagccc cggcgacgag    120 

agttaccagg agtcgctgct gttcctgggg ctggtggccg ccgtctgcct gggcctgaac    180 

ctcatcttcc ttgtggctta cctggtctgt gcatgccact gccggcggga cgatgcggtg    240 

cagaccaagc agcaccactc ctgctgcatc acctggacgg ccgtggtggc cgggctcatc    300 

tgctgtgctg cggtgggcgt tggtttctat ggaaacagcg agaccaacga tggggcgtac    360 

cagctgatgt actccttgga cgatgccaac cacaccttct ctgggatcga tgctctggtt    420 

tccggaacta cccagaagat gaaggtggac ctagagcagc acctggcccg gctcagtgag    480 

atctttgctg cccggggcga ttacctgcag accctgaagt tcatacagca gatggcgggc    540 

agcgttgttg ttcagctctc aggactgccc gtgtggaggg aggtcaccat ggagctgacc    600 

aagctatccg accagactgg ctacgtggag tactacaggt ggctctccta cctcctgctc    660 

tttatcctgg acctggtcat ctgcctcatt gcctgcctgg gactggccaa gcgctccaag    720 

tgtctcctgg cctcgatgct gtgctgtggg gcactgagcc tgctcctcag ttgggcatcc    780 

ctggccgctg atggctctgc ggcagtggcc accagtgact tctgtgtggc tcctgacacc    840 

ttcatcctga acgtcacgga gggccagatc agcacagagg tgactcgcta ctacctgtat    900 

tgcagccaga gtggaagcag ccccttccag cagaccctga ccaccttcca gcgcgcactc    960 

accaccatgc agatccaggt cgcggggctg ctgcagtttg ccgtgcccct cttctccact   1020 

gcagaggaag acctgcttgc aatccagctc ctgctgaact cctcagagtc cagccttcac   1080 

cagctgactg ccatggtgga ctgccgaggg ctgcacaagg attatctgga cgctcttgct   1140 

ggcatctgct acgacggcct ccagggcttg ctgtaccttg gcctcttctc cttcctggcc   1200 

gccctcgcct tctccaccat gatctgtgcg gggccaaggg cctggaagca cttcaccacc   1260 

agaaacagag aatacgatga cattgatgat gatgacccct ttaaccccca agcctggcgc   1320 

atggcggctc acagtccccc gaggggacag cttcacagct tctgcagcta cagcagtggc   1380 

ctgggaagtc agaccagcct gcagcccccg gcccagacca tctccaacgc ccctgtctcc   1440 

gagtacatga accaagccat gctctttggt aggaacccac gctacgagaa cgtgccacta   1500 

atcgggagag cctcccctcc gcctacgtac tctcccagca tgagagccac ctacctgtct   1560 

gtggcggatg agcacctgag gcactacggg aatcagtttc cagcctaaca gactttcggg   1620 

ggttcctgcc tcctttttcc gttctggttt ttaattagtg caaatacaag ctgcgtttct   1680 

ttaatagaaa ccaaaggcat ctggagcccg agaggcctcc tgctgtggca gaggagcagc   1740 

tgggattccc gaccaaagcc ccagggggtg cagaagactc accacgcggg ccagcctctc   1800 

tcttttgccc tgctctccac accagaaatg cccccaggtg cttggctgcc tcagaggtac   1860 

catccctgag ctggctgcct ggccctgctc acccctacgc ctcgcccttg ccaggagggg   1920 

agtggcagtg aggagggggc caggtcaggc accaccatca agagagctgt gtgttctctc   1980 

tggtcccaca acgatgactc tgcctcttgt cagcccagcc aagagcccag acgacccctc   2040 

tgtcctcgtt ccctgtcctc gttccctgca ggtaacatga gaagggctga tcaggagatg   2100 

ctctttaaga agttcgcacc cctgctgaca ccagaacagc ccaaatcaga gttcccaggg   2160 

ccagacaggc tcttcctggg ccacagaggg gaggcatcag gaaagctctg cagtgggggg   2220 

ctggtggctc cggggctggg ggatcacagg ctggtgaacc ccggtgggaa cagaggtgaa   2280 

agcctgccac attccgcctg tctccctaac cctccattgc ctcgcctcta ttccagaatc   2340 

aatgctgcag aatgtgttag ctgcagatag gcatggtctc aggtatgaac agacactttg   2400 

aaacgacttt aggtctttct tttctccagt gttttaaaca tgttgattat ccaaagaatt   2460 

gaaactccta gcacatccag tttttacaac agatttgcag ctcattcctt accctggtta   2520 

ggtcactact tttgcagatt ttgctggcac tgatctggag atctgcagat ctggaggaga   2580 

cgggaaggag tcgattctta aataaggatc agtgaggcat cctgtcccaa gctactgttt   2640 

ggtggggatc tgggttcatc tcacccacag agggaggatc tttaagagga gaaaaaagcc   2700 

aagagggaaa gccagagttc cctgttctag gggactagcc aaatgcctac atcagctgtc   2760 

ccctccctgt tgtctccaag taagtttgcc agaaaaggtt ttagcaaagt gctacaactg   2820 

tgtctttata ggaggatagg cctctgccct gccccacccc caccacctgt ccccacccag   2880 

tgtcccaggc cacaggagct tattggccag gagggaataa tgtcccccaa tactgcctgt   2940 

tgagggacca gagttggggt ctttggtgct tccaacctcc tgccaacctg gagttcacaa   3000 

caccag                                                              3006 

 
           
             34  
             2884  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 6889872CB1  
             
           
            34 

tcactcctgg ctcagtgcgg cactctccag cctcctgtgg gaatcatctg aagttctgag     60 

cccggaagcc aaggaggaag acgaggagga ggaggaggag gaggaggagg aggaggaggg    120 

agaggaagtc aagccctgag aacccttgca ccttcctagc aggagacaag gagcaacgct    180 

gcggtgggga gcaggctgtg gggcccccac ccccagccct agccaggcct agtgcctgct    240 

gtagcaccct agaagatccc cagcagttgg cactagctgt acccaccttg cctggggccc    300 

ccgtgctggg ggtcgccccc aagatggtgg cggccccagg gaggactgta ctgccagccc    360 

cagcctctgg ccgctaggca ccccctgcct tgccctggcc cctcactccg aggccagcgc    420 

catgctgcgc ctggggctgt gcgcggcggc gctgctgtgc gtgtgccggc cgggtgccgt    480 

gcgtgccgac tgctggctca ttgagggcga caagggctac gtgtggctgg ccatctgcag    540 

ccagaaccag ccgccctacg agaccatccc gcagcacatc aatagcaccg tgcacgacct    600 

gcggctcaac gagaacaagc tcaaagccgt gctctactcc tcgctcaacc gctttgggaa    660 

cctcaccgac ctcaacctca ccaagaacga gatctcctac atcgaggacg gtgccttcct    720 

gggccagtcg agcctgcagg tcctgcagct gggctacaac aagctcagca acctgacgga    780 

gggcatgctg cgaggcatga gccgcctgca gttcctcttt gtccagcaca acctcatcga    840 

ggtggtgacg cccaccgcct tctccgagtg cccgagcctc atcagcatcg acctgtcctc    900 

caaccgcctc agccgcctgg acggtgccac ctttgccagc ctcgccagcc tgatggtgtg    960 

tgagctggcc ggcaacccct tcaactgtga gtgcgacctc ttcggcttcc tggcctggct   1020 

ggtggtcttc aacaacgtca ccaagaacta cgaccgcctg cagtgtgagt cgccgcggga   1080 

gtttgccggc tacccgctgc tggtgccccg gccctaccac agcctcaacg ccatcaccgt   1140 

actccaggcc aagtgtcgga atggctcgct gcccgcccgg cccgtgagcc accccacgcc   1200 

ctactccacc gacgcccaga gggagccaga cgagaactcg ggcttcaacc ccgacgagat   1260 

cctttcggtg gagccgccgg cctcgtccac cacggatgcg tcggcagggc cagccatcaa   1320 

gctgcaccac gtcacgttca cctcggccac cctggtggtc atcattccac acccctacag   1380 

caagatgtac atcctcgtgc agtacaacaa cagctacttc tccgacgtca tgaccctcaa   1440 

gaacaagaag gagatcgtga cgctggacaa actgcgggcg cacactgagt acaccttctg   1500 

cgtgacctcg ctgcgcaaca gccgccgctt caaccacacc tgcctgacct tcaccacgcg   1560 

ggaccccgtc cccggagact tggcgcccag cacctccacc accacccact acatcatgac   1620 

catcctgggc tgcctcttcg gcatggttat cgtgctggga gccgtgtact actgcctgcg   1680 

caagcggcgc atgcaggagg agaagcagaa gtctgtcaac gtcaagaaga ccatcctgga   1740 

gatgcgctac ggggctgatg tggatgccgg ctccattgtg cacgccgccc agaagctggg   1800 

cgagcctccc gtgctgcccg tatctcgcat ggcctccatc ccctccatga tcggggagaa   1860 

gctgcccacc gccaaggggt tggaggccgg gctggacaca cccaaggtag ccaccaaagg   1920 

caactatata gaggtgcgca caggcgccgg cggggacggt ctggctcggc ccgaggatga   1980 

cctcccggac ctcgagaacg gccagggctc ggctgcagag atctccacca ttgccaagga   2040 

ggtggacaag gtcaaccaga tcattaacaa ctgcatcgat gctctcaagc tggactcggc   2100 

ctcttttctg ggaggcggca gcagcagtgg ggaccccgag ctggccttcg agtgccagtc   2160 

cctccctgca gctgctgccg cctcctcagc cactggcccc ggggccctgg agcggcccag   2220 

cttcctttcg cctccctaca aggagagctc ccaccaccca ctacagcgcc agctgagcgc   2280 

cgacgcggcc gtgacccgca agacctgcag cgtgtcgtcc agtggttcca tcaagagcgc   2340 

caaggtcttt agcctggacg tgcccgacca tccggccgcc acagggctgg ctaagggcga   2400 

ctccaagtac atcgagaagg gcagccccct caacagcccg ctggaccggc tcccgctggt   2460 

gccggcgggc agcggcgggg gcagcggcgg gggcgggggc atccaccacc tggaggtgaa   2520 

gccggcctac cactgcagcg agcaccggca cagctttccc gccctgtact acgaggaggg   2580 

tgccgacagc ctgagccagc gcgtgtcctt cctcaagccg ctgacccgct ccaagcgtga   2640 

ctccacctac tcgcagctct cccccagaca ctactactca gggtactcct ccagccccga   2700 

gtactcatcc gagagcacgc acaagatctg ggagcgcttc cggccctaca agaagcacca   2760 

ccgggaggag gtgtacatgg ccgccggtca cgccctgcgc aagaaggtcc agttcgccaa   2820 

ggacgaggat ctgcatgaca tccttgatta ctggaagggg gtctccgccc agcagaagct   2880 

gtga                                                                2884