Patent Publication Number: US-2004053394-A1

Title: Human kinases

Description:
TECHNICAL FIELD  
       [0001] This invention relates to nucleic acid and amino acid sequences of human kinases and to the use of these sequences in the diagnosis, treatment, and prevention of cancer, immune disorders, disorders affecting growth and development, cardiovascular diseases, and lipid disorders, and in the assessment of the effects of exogenous compounds on the expression of nucleic acid and amino acid sequences of human kinases.  
       BACKGROUND OF THE INVENTION  
       [0002] Kinases comprise the largest known enzyme superfamily and vary widely in their target molecules. Kinases catalyze the transfer of high energy phosphate groups from a phosphate donor to a phosphate acceptor. Nucleotides usually serve as the phosphate donor in these reactions, with most kinases utilizing adenosine triphosphate (ATP). The phosphate acceptor can be any of a variety of molecules, including nucleosides, nucleotides, lipids, carbohydrates, and proteins. Proteins are phosphorylated on hydroxyamino acids. Addition of a phosphate group alters the local charge on the acceptor molecule, causing internal conformational changes and potentially influencing intermolecular contacts. Reversible protein phosphorylation is the primary method for regulating protein activity in eukaryotic cells. In general, proteins are activated by phosphorylation in response to extracellular signals such as hormones, neurotransmitters, and growth and differentiation factors. The activated proteins initiate the cell&#39;s intracellular response by way of intracellular signaling pathways and second messenger molecules such as cyclic nucleotides, calcium-calmodulin, inositol, and various mitogens, that regulate protein phosphorylation.  
       [0003] Kinases are involved in all aspects of a cell&#39;s function, from basic metabolic processes, such as glycolysis, to cell-cycle regulation, differentiation, and communication with the extracellular environment through signal transduction cascades. Inappropriate phosphorylation of proteins in cells has been linked to 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.  
       [0004] There are two classes of protein kinases. One class, protein tyrosine kinases (PTMKs), phosphorylates tyrosine residues, and the other class, protein serine/threonine kinases (STKs), phosphorylates serine and threonine residues. Some PTKs and STKs possess structural characteristics of both families and hav dual specificity for both tyrosine and s rine/threonine residues. Almost all kinases contain a conserved 250-300 amino acid catalytic domain containing specific residues and sequence motifs characteristic of the kinase family. The protein kinase catalytic domain can be further divided into 11 subdomains. N-terminal subdomains I-IV fold into a tw -lobed structure which binds and orients the ATP donor molecule, and subdomain V spans the two lobes. C-terminal subdomains VI-XI bind the protein substrate and transfer the gamma phosphate from ATP t the hydroxyl group of a tyrosine, serine, or threonine residue. Each of the 11 subdomains contains specific catalytic residues or amino acid motifs characteristic of that subdomain. For example, subdomain I contains an 8-amino acid glycine-rich ATP binding consensus motif, subdomain II contains a critical lysine residue required for maximal catalytic activity, and subdomains VI through IX comprise the highly conserved catalytic core. PTKs and STKs also contain distinct sequence motifs in subdomains VI and VIII which may confer hydroxyamino acid specificity.  
       [0005] In addition, kinases may also be classified by additional amino acid sequences, generally between 5 and 100 residues, which either flank or occur within the kinase domain. These additional amino acid sequences regulate kinase activity and determine substrate specificity. (Reviewed in Hardie, G. and Hanks, S. (1995) The Protein Kinase Facts Book. Vol I p.p. 17-20 Academic Press, San Diego, Calif.). In particular, two protein linase signature sequences have been identified in the kinase domain, the first containing an active site lysine residue involved in ATP binding, and the second containing an aspartate residue important for catalytic activity. If a protein analyzed includes the two protein kinase signatures, the probability of that protein being a protein kinase is close to 100% (PROSITE: PDOC00100, November 1995).  
       [0006] Protein Tyrosine Kinases  
       [0007] Protein tyrosine kinases (PTKs) may be classified as either transmembrane, receptor PTKs or nontransmembrane, nonreceptor PTK proteins. Transmembrane tyrosine kinases function as receptors for most growth factors. Growth factors bind to the receptor tyrosine kinase (RTK), which causes the receptor to phosphorylate itself (autophosphorylation) and specific intracellular second messenger proteins. Growth factors (GF) that associate with receptor PTKs include epidermal GF, platelet-derived GF, fibroblast GF, hepatocyte GF, insulin and insulin-like GFs, nerve GF, vascular endothelial GF, and macrophage colony stimulating factor.  
       [0008] Nontransmembrane, nonreceptor PTKs lack transmembrane regions and, instead, form signaling complexes with the cytosolic domains of plasma membrane receptors. Receptors that function through non-receptor PTKs include those for cytokines and hormones (growth hormone and prolactin), and antigen-specific receptors on T and B lymphocytes.  
       [0009] Many PTKs were first identified as ncogene products in cancer cells in which PTK activation was no longer subject to normal cellular controls. In fact, ab ut one third of the known oncogenes encode PTKs. Furthermore, cellular transformation (oncogenesis) is ften accompanied by increased tyrosine phosphorylation activity (Charbonneau, H L and Tonks, N. K. (1992) Annu. Rev. Cell Biol. 8:463-93). Regulation of PTK activity may therefore be an important strategy in controlling some types of cancer.  
       [0010] Protein Serine/Threonine Kinases  
       [0011] Protein serine/threonine kinases (STKs) are nontransmembrane proteins. A subclass of STKs are known as ERKs (extracellular signal regulated kinases) or MAPs (mitogen-activated protein kinases) and are activated after cell stimulation by a variety of hormones and growth factors. Cell stimulation induces a signaling cascade leading to phosphorylation of MEK (MAP/ERK kinase) which, in turn, activates ERK via serine and threonine phosphorylation. A varied number of proteins represent the downstream effectors for the active ERK and implicate it in the control of cell proliferation and differentiation, as well as regulation of the cytoskeleton. Activation of ERK is normally transient, and cells possess dual specificity phosphatases that are responsible for its down-regulation. Also, numerous studies have shown that elevated ERK activity is associated with some cancers. Other STKs include the second messenger dependent protein kinases such as the cyclic-AMP dependent protein kinases (PKA), calcium-calmodulin (CaM) dependent protein kinases, and the mitogen-activated protein kinases (MAP); the cyclin-dependent protein kinases; checkpoint and cell cycle kinases; proliferation-related kinases; 5′-AMP-activated protein kinases; and kinases involved in apoptosis.  
       [0012] The second messenger dependent protein kinases primarily mediate the effects of second messengers such as cyclic AMP (cAMP), cyclic GMP, inositol triphosphate, phosphatidylinositol, 3,4,5-triphosphate, cyclic ADPribose, arachidonic acid, diacylglycerol and calcium calmodulin. The PKAs are involved in mediating hormone-induced cellular responses and are activated by cAMP produced within the cell in response to hormone stimulation. cAMP is an intracellular mediator of hormone action in all animal cells that have been studied. Hormone-induced cellular responses include thyroid hormone secretion, cortisol secretion, progesterone secretion, glycogen breakdown, bone resorption, and regulation of heart rate and force of heart muscle contraction. PKA is found in all animal cells and is thought to account for the effects of cAMP in most of these cells. Altered PKA expression is implicated in a variety of disorders and diseases including cancer, thyroid disorders, diabetes, atherosclerosis, and cardiovascular disease (Isselbacher, K. J. et al. (1994)  Harrison&#39;s Principles of Internal Medicine , McGraw-Hill, New Y rk, N.Y., pp. 416-431, 1887).  
       [0013] The casein kinase I (CKI) gene family is another subfamily f serine/threonine protein kinases. This continuously expanding group of kinases have been implicated in the regulation of numerous cyt plasmic and nuclear processes, including cell metabolism, and DNA replication and repair. CKI enzymes are present in the membranes, nucleus, cytoplasm and cytoskeleton of eukaryotic cells, and on the mitotic spindles of mammalian cells (Fish, K. J. et al., (1995) J. Biol. Chem. 270:14875-14883.  
       [0014] The CKI family members all have a short amino-terminal domain of 9-76 amino acids, a highly conserved kinase domain of 284 amino acids, and a variable carboxyl-terminal domain that ranges from 24 to over 200 amino acids in length (Cegielska, A. et al., (1998) J. Biol. Chem. 273:1357-1364.) The CKI family is comprised of highly related proteins, as seen by the identification of isoforms of casein kinase I from a variety of sources. There are at least five mammalian isoforms, α, β, γ, δ, and ε. Fish et al., identified CKI-epsilon from a human placenta cDNA library. It is a basic protein of 416 amino acids and is closest to CKI-delta. Through recombinant expression, it was determined to phosphorylate known CKI substrates and was inhibited by the CKI-specific inhibitor CKI-7. The human gene for CKI-epsilon was able to rescue yeast with a slow-growth phenotype caused by deletion of the yeast CKI locus, HRR250 (Fish et al, supra.)  
       [0015] The mammalian circadian mutation tau was found to be a semidominant autosomal allele of CKI-epsilon that markedly shortens period length of circadian rhythms in Syrian hamsters. The tau locus is encoded by casein kinase I-epsilon, which is also a homolog of the  Drosophila circadian  gene double-time. Studies of both the wildtype and tau mutant CKI-epsilon enzyme indicated that the mutant enzyme has a noticeable reduction in the maximum velocity and autophosphorylation state. Further, in vitro, CKI-epsilon is able to interact with mammalian PERIOD proteins, while the mutant enzyme is deficient in its ability to phosphorylate PERIOD. Lowrey et al., have proposed that CKI-epsilon plays a major role in delaying the negative feedback signal within the transcription-translation-based autoregulatory loop that composes the core of the circadian mechanism. Therefore the CKI-epsilon enzyme is an ideal target for pharmaceutical compounds influencing circadian rhythms, jet-lag and sleep, in addition to other physiologic and metabolic processes under circadian regulation (Lowrey, P. L. et al., (2000) Science 288:483-491.)  
       [0016] Calcium-Calmodulin Dependent Protein Kinases  
       [0017] Calcium-calmodulin dependent (CaM) kinases are involved in regulation of smooth muscle contraction, glycogen breakdown (phosphorylase kinase), and neurotransmission (CaM kinase I and CaM kinase II). CaM dependent protein kinases are activated by calmodulin, an intracellular calcium receptor, in response to the concentration of free calcium in the cell. Many CaM kinases are also activated by phosphorylation. Some CaM kinases are also activated by autophosphorylation or by other regulatory kinases. CaM kinase I phosphorylates a variety of substrates including the neurotransmitter-related proteins synapsin I and II, the gene transcription regulator, CREB, and the cystic fibrosis conductance regulator protein, CFTR (Hanbabu, B. et al. (1995) EMBO J urnal 14:3679-3686). CaM kinase II also phosphorylates synapsin at different sites and controls the synthesis of catecholamines in the brain through phosphorylation and activation of tyrosine hydroxylase. CaM kinase II controls the synthesis of catecholamines and seratonin, through phosphorylation/activation of tyrosine hydroxylase and tryptophan hydroxylase, respectively (Fujisawa, H. (1990) BioEssays 12:27-29). The mRNA encoding a calmodulin-binding protein kinase-like protein was found to be enriched in mammalian forebrain. This protein is associated with vesicles in both axons and dendrites and accumulates largely postnatally. The amino acid sequence of this protein is similar to CaM-dependent STKs, and the protein binds calmodulin in the presence of calcium (Godbout, M. et al. (1994) J. Neurosci. 14:1-13).  
       [0018] Mitogen-Activated Protein Kinases  
       [0019] The mitogen-activated protein kinases (MAP) which mediate signal transduction from the cell surface to the nucleus via phosphorylation cascades are another STK family that regulates intracellular signaling pathways. Several subgroups have been identified, and each manifests different substrate specificities and responds to distinct extracellular stimuli (Egan, S. E. and Weinberg, R. A. (1993) Nature 365:781-783). MAP kinase signaling pathways are present in mammalian cells as well as in yeast The extracellular stimuli which activate MAP kinase pathways include epidermal growth factor (EGF), ultraviolet light, hyperosmolar medium, heat shock, endotoxic lipopolysaccharide (LPS), and pro-inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-1 (IL-1). Altered MAP kinase expression is implicated in a variety of disease conditions including cancer, inflammation, immune disorders, and disorders affecting growth and development  
       [0020] Cyclin-Dependent Protein Kinases  
       [0021] The cyclin-dependent protein kinases (CDKs) are STKs that control the progression of cells through the cell cycle. The entry and exit of a cell from mitosis are regulated by the synthesis and destruction of a family of activating proteins called cyclins. Cyclins are small regulatory proteins that bind to and activate CDKs, which then phosphorylate and activate selected proteins involved in the mitotic process. CDKs are unique in that they require multiple inputs to become activated. In addition to cyclin binding, CDK activation requires the phosphorylation of a specific threonine residue and the dephosphorylation of a specific tyrosine residue on the CDK.  
       [0022] Another family of STKs associated with the cell cycle are the NIMA (never in mitosis)-related kinases (Neks). Both CDKs and Neks are involved in duplication, maturation, and separation of the microtubule organizing center, the centrosome, in animal cells (Fry, A. M., et al. (1998) EMBO J. 17:470-481). The NIM-related kinases also include NIK1 histidine kinases, which function in signal transmission (Yamada-Okabe, T. et al. (1999) J. Bacteriol. 181:7243-7247).  
       [0023] Checkpoint and Cell Cycle Kinases  
       [0024] In the process of cell division, the order and timing of cell cycle transitions are under control of cell cycle checkpoints, which ensure that critical events such as DNA replication and chromosome segregation are carried out with precision. If DNA is damaged, e.g. by radiation, a checkpoint pathway is activated that arrests the cell cycle to provide time for repair. If the damage is extensive, apoptosis is induced. In the absence of such checkpoints, the damaged DNA is inherited by aberrant cells which may cause proliferative disorders such as cancer. Protein kinases play an important role in this process. For example, a specific kinase, checkpoint kinase 1 (Chk1), has been identified in yeast and mammals, and is activated by DNA damage in yeast. Activation of Chk1 leads to the arrest of the cell at the G2/M transition. (Sanchez, Y. et al. (1997) Science 277:1497-1501.) Specifically, Chk1 phosphorylates the cell division cycle phosphatase CDC25, inhibiting its normal function which is to dephosphorylate and activate the cyclin-dependent kinase Cdc2. Cdc2 activation controls the entry of cells into mitosis. (Peng, C -Y et al. (1997) Science 277:1501-1505.) Thus, activation of Chk1 prevents the damaged cell from entering mitosis. A similar deficiency in a checkpoint kinase, such as Chk1, may also contribute to cancer by failure to arrest cells with damaged DNA at other checkpoints such as G2/M.  
       [0025] Proliferation-Related Kinases  
       [0026] Proliferation-related kinase is a serum/cytokine inducible STK that is involved in regulation of the cell cycle and cell proliferation in human megakarocytic cells (Li, B. et al. (1996) J. Biol. Chem. 271:19402-8). Proliferation-related kinase is related to the polo (derived from Drosophila polo gene) family of STKs implicated in cell division. Proliferation-related kinase is downregulated in lung tumor tissue and may be a proto-oncogene whose deregulated expression in normal tissue leads to oncogenic transformation.  
       [0027] The RET (rearranged during transfection) proto-oncogene encodes a tyrosine kinase receptor involved in both multiple endocrine neoplasia type 2, an inherited cancer syndrome, and Hirschsprung disease, a developmental defect of enteric neurons. RET and its functional ligand, glial cell line-derived neurotrophic factor, play key roles in the development of the human enteric nervous system (Pachnis, V. et al (1998) Am. J. Physiol. 275:G183-G186).  
       [0028] 5′-AMP-Activated Protein Kinase  
       [0029] A ligand-activated STK protein kinase is 5′-AMP-activated protein kinase (AMPK) (Gao, G. et al. (1996) J. Biol Chem. 271:8675-8681). Mammalian AMPK is a regulator of fatty acid and sterol synthesis through phosphorylation f the enzymes acetyl-CoA carboxylase and hydroxymethylglutaryl-CoA reductase and mediates responses of these pathways to cellular stresses such as heat shock and depletion of glucose and ATP. AMPK is a heterotrimeric complex comprised of a catalytic alpha subunit and two non-catalytic beta and gamma subunits that are believed to regulate the activity of the alpha subunit. Subunits of AMPK have a much wider distribution in non-lipogenic tissues such as brain, heart, spleen, and lung than expected. This distribution suggests that its role may extend beyond regulation of lipid metabolism alone.  
       [0030] Kinases in Apoptosis  
       [0031] Apoptosis is a highly regulated signaling pathway leading to cell death that plays a crucial role in tissue development and homeostasis. Deregulation of this process is associated with the pathogenesis of a number of diseases including autoimmune disease, neurodegenerative disorders, and cancer. Various STKs play key roles in this process. ZIP kinase is an STK containing a C-terminal leucine zipper domain in addition to its N-terminal protein kinase domain. This C-terminal domain appears to mediate homodimerization and activation of the kinase as well as interactions with transcription factors such as activating transcription factor, ATF4, a member of the cyclic-AMP responsive element binding protein (ATF/CREB) family of transcriptional factors (Sanjo, H. et al. (1998) J. Biol. Chem, 273:29066-29071). DRAK1 and DRAK2 are STKs that share homology with the death-associated protein kinases (DAP kinases), known to function in interferon-γ induced apoptosis (Sanjo et al. supra). Like ZIP kinase, DAP kinases contain a C-terminal protein-protein interaction domain, in the form of ankyrin repeats, in addition to the N-terminal kinase domain. ZIP, DAP, and DRAK kinases induce morphological changes associated with apoptosis when transfected into NIH3T3 cells (Sanjo et al. supra). However, deletion of either the N-terminal kinase catalytic domain or the C-terminal domain of these proteins abolishes apoptosis activity, indicating that in addition to the kinase activity, activity in the C-terminal domain is also necessary for apoptosis, possibly as an interacting domain with a regulator or a specific substrate.  
       [0032] RICK is another STK recently identified as mediating a specific apoptotic pathway involving the death receptor, CD95 (Inohara, N. et al. (1998) J. Biol. Chem. 273:12296-12300). CD95 is a member of the tumor necrosis factor receptor superfamily and plays a critical role in the regulation and homeostasis of the immune system (Nagata, S. (1997) Cell 88:355-365). The CD95 receptor signaling pathway involves recruitment of various intracellular molecules to a receptor complex following ligand binding. This process includes recruitment of the cysteine protease caspase-8 which, in turn, activates a caspase cascade leading to cell death. RICK is composed of an N-terminal kinase catalytic domain and a C-terminal “caspase-recruitment” domain that interacts with caspase-like domains, indicating that RICK plays a role in the recruitment f caspase-8. This interpretation is supported by the fact that the expressi n of RICK in human 293T cells promotes activati n f caspase-8 and potentiates the induction of apoptosis by various proteins involved in the CD95 apoptosis pathway (Inohara et al. supra).  
       [0033] Mitochondrial Protein Kinases  
       [0034] A novel class of eukaryotic kinases, related by sequence to prokaryotic histidine protein kinases, are the mitochondrial protein kinases (MPKs) which seem to have no sequence similarity with other eukaryotic protein kinases. These protein kinases are located exclusively in the mitochondrial matrix space and may have evolved from genes originally present in respiration-dependent bacteria which were endocytosed by primitive eukaryotic cells. MPKs are responsible for phosphorylation and inactivation of the branched-chain alpha-ketoacid dehydrogenase and pyruvate dehydrogenase complexes (Harris, R. A. et al. (1995) Adv. Enzyme Regul. 34:147-162). Five MPKs have been identified. Four members correspond to pyruvate dehydrogenase kinase isozymes, regulating the activity of the pyruvate dehydrogenase complex, which is an important regulatory enzyme at the interface between glycolysis and the citric acid cycle. The fifth member corresponds to a branched-chain alpha-ketoacid dehydrogenase kinase, important in the regulation of the pathway for the disposal of branched-chain amino acids. (Harris, R. A. et al. (1997) Adv. Enzyme Regul. 37:271-293). Both starvation and the diabetic state are known to result in a great increase in the activity of the pyruvate dehydrogenase kinase in the liver, heart and muscle of the rat This increase contributes in both disease states to the phosphorylation and inactivation of the pyruvate dehydrogenase complex and conservation of pyruvate and lactate for gluconeogenesis (Harris (1995) supra).  
       [0035] Kinases with Non-Protein Substrates  
       [0036] Lipid and Inositol Kinases  
       [0037] Lipid kinases phosphorylate hydroxyl residues on lipid head groups. A family of kinases involved in phosphorylation of phosphatidylinositol (PI) has been described, each member phosphorylating a specific carbon on the inositol ring (Leevers, S. J. et al. (1999) Curr. Opin. Cell. Biol. 11:219-225). The phosphorylation of phosphatidylinositol is involved in activation of the protein kinase C signaling pathway. The inositol phospholipids (phosphoinositides) intracellular signaling pathway begins with binding of a signaling molecule to a G-protein linked receptor in the plasma membrane. This leads to the phosphorylation of phosphatidylinositol (PI) residues on the inner side of the plasma membrane by inosit 1kinases, thus c nverting PI residues to the biphosphate state (PIP 2 ). PIP 2  is then cleaved into inositol triphosphate (IP 3 ) and diacylglycerol. These two products act as mediators f r separate signaling pathways. Cellular responses that are mediated by these pathways are glycogen breakdown in the liver in response to vasopressin, smooth muscle contraction in response to acetylcholine, and thrombin-induced platelet aggregation.  
       [0038] PI 3-kinase (PI3K), which phosphorylates the D3 position of PI and its derivatives, has a central role in growth factor signal cascades involved in cell growth, differentiation, and metabolism. PI3K is a heterodimer consisting of an adapter subunit and a catalytic subunit. The adapter subunit acts as a scaffolding protein, interacting with specific tyrosine-phosphorylated proteins, lipid moieties, and other cytosolic factors. When the adapter subunit binds tyrosine phosphorylated targets, such as the insulin responsive substrate (IRS)-1, the catalytic subunit is activated and converts PI (4,5) bisphosphate (PIP 2 ) to PI (3,4,5) P 3  (PIP 3 ). PIP 3  then activates a number of other proteins, including PKA, protein kinase B (PKB), protein kinase C (PKC), glycogen synthase kinase (GSK)-3, and p70 ribosomal s6 kinase. PI3K also interacts directly with the cytoskeletal organizing proteins, Rac, rho, and cdc42 (Shepherd, P. R., et al. (1998) Biochem. J. 333:471-490). Animal models for diabetes, such as obese and fat mice, have altered PI3K adapter subunit levels. Specific mutations in the adapter subunit have also been found in an insulin-resistant Danish population, suggesting a role for PI3K in type-2 diabetes (Shepard, supra).  
       [0039] PKC is also activated by diacylglycerol (DAG). Phorbol esters (PE) are analogs of DAG and tumor promoters that cause a variety of physiological changes when administered to cells and tissues. PE and DAG bind to the N-terminal region of PKC. This region contains one or more copies of a cysteine-rich domain about 50 amino-acid residues long and essential for DAG/PE-binding. Diacylglycerol kinase (DGK), the enzyme that converts DAG into phosphatidate, contains two copies of the DAG/PE-binding domain in its N-terminal section (Azzi, A. et al. (1992) Eur. J. Biochem. 208:547-557).  
       [0040] An example of lipid kinase phosphorylation activity is the phosphorylation of D-erythro-sphingosine to the sphingolipid metabolite, sphingosine-1-phosphate (SPP). SPP has emerged as a novel lipid second-messenger with both extracellular and intracellular actions (Kohama, T. et al. (1998) J. Biol. Chem. 273:23722-23728). Extracellularly, SPP is a ligand for the G-protein coupled receptor EDG-1 (endothelial-derived, G-protein coupled receptor). Intracellularly, SPP regulates cell growth, survival, motility, and cytoskeletal changes. SPP levels are regulated by sphingosine kinases that specifically phosphorylate D-erythro-sphingosine to SPP. The importance of sphingosine kinase in cell signaling is indicated by the fact that various stimuli, including platelet-derived growth factor (PDGF), nerve gr wth factor, and activation of protein kinase C, increase cellular levels of SPP by activation of sphingosine kinas , and the fact that competitive inhibitors of the enzyme selectively inhibit cell proliferation induced by PDGF (Kohama et al. supra).  
       [0041] Purine Nucleotide Kinases  
       [0042] The purine nucleotide kinases, adenylate kinase (ATP:AMP phosphotransferase, or AdK) and guanylate kinase (ATP:GMP phosphotransferase, or GuK) play a key role in nucleotide metabolism and are crucial to the synthesis and regulation of cellular levels of ATP and GTP, respectively. These two molecules are precursors in DNA and RNA synthesis in growing cells and provide the primary source of biochemical energy in cells (ATP), and signal transduction pathways (GTP). Inhibition of various steps in the synthesis of these two molecules has been the basis of many antiproliferative drugs for cancer and antiviral therapy (Pillwein, K. et al. (1990) Cancer Res. 50:1576-1579).  
       [0043] AdK is found in almost all cell types and is especially abundant in cells having high rates of ATP synthesis and utilization such as skeletal muscle. In these cells AdK is physically associated with mitochondria and myofibrils, the subcellular structures that are involved in energy production and utilization, respectively. Recent studies have demonstrated a major function for AdK in transferring high energy phosphoryls from metabolic processes generating ATP to cellular components consuming ATP (Zeleznikar, R. J. et al. (1995) J. Biol. Chem. 270:7311-7319). Thus AdK may have a pivotal role in maintaining energy production in cells, particularly those having a high rate of growth or metabolism such as cancer cells, and may provide a target for suppression of its activity to treat certain cancers. Alternatively, reduced AdK activity may be a source of various metabolic, muscle-energy disorders that can result in cardiac or respiratory failure and may be treatable by increasing AdK activity.  
       [0044] GuK, in addition to providing a key step in the synthesis of GTP for RNA and DNA synthesis, also fulfills an essential function in signal transduction pathways of cells through the regulation of GDP and GTP. Specifically, GTP binding to membrane associated G proteins mediates the activation of cell receptors, subsequent intracellular activation of adenyl cyclase, and production of the second messenger, cyclic AMP. GDP binding to G proteins inhibits these processes. GDP and GTP levels also control the activity of certain oncogenic proteins such as p21 ras  known to be involved in control of cell proliferation and oncogenesis (Bos, J. L. (1989) Cancer Res. 49:4682-4689). High ratios of GTP:GDP caused by suppression of GuK cause activation of p21 ras  and promote oncogenesis. Increasing GuK activity to increase levels of GDP and reduce the GTP:GDP ratio may provide a therapeutic strategy to reverse oncogenesis.  
       [0045] GuK is an important enzyme in the phosphorylation and activation f certain antiviral drugs useful in the treatment of herpes virus infections. These drugs include the guanine homologs acyclovir nd buciclovir (Miller, W. H. and Miller R. L. (1980) J. Biol. Chem. 255:7204-7207; Stenberg, K. et al. 1986) J. Biol. Chem. 261:2134-2139). Increasing GuK activity in infected cells may provide a therapeutic strategy for augmenting the effectiveness of these drugs and possibly for reducing the necessary dosages of the drugs.  
       [0046] Pyrmidine Kinases  
       [0047] The pyrimidine kinases are deoxycytidine kinase and thymidine kinase 1 and 2. Deoxycytidine kinase is located in the nucleus, and thymidine kinase 1 and 2 are found in the cytosol (Johansson, M. et al. (1997) Proc. Natl. Acad. Sci. U.S.A. 94:11941-11945). Phosphorylation of deoxyribonucleosides by pyrimidine kinases provides an alternative pathway for de novo synthesis of DNA precursors. The role of pyrimidine kinases, like purine kinases, in phosphorylation is critical to the activation of several chemotherapeutically important nucleoside analogues (Arner E. S. and Eriksson, S. (1995) Pharmacol. Ther. 67:155-186).  
       [0048] The discovery of new human kinases, 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 cancer, immune disorders, disorders affecting growth and development, cardiovascular diseases, and lipid disorders, and in the assessment of the effects of exogenous compounds on the expression of nucleic acid and amino acid sequences of human kinases.  
       SUMMARY OF THE INVENTION  
       [0049] The invention features purified polypeptides, human kinases, referred to collectively. as “PKIN” and individually as “PKIN-1,” “PKIN-2,”“PKIN-3,” “PKIN4,” “PKIN-5,” “PKIN-6,” “PKIN-7,” “PKIN-8,” “PKIN-9,” “PKIN-10,” “PKIN-11,” “KIN-12,” “PKIN-13, ” “PKIM-14,” “PKIN-15,” “PKIN-16,” “PKIN-17,” “PKIN-18,” “PKIN-19,” “PKIN-20,” “PKIN-21,” and “PKIN22.” 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:1-22, 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:1-22, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-22, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 1-22. In one alternative, the invention provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 1-22.  
       [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:1-22, b) a polypeptide comprising a naturally ccurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-22, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-22, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-22. In one alternative, the polynucleotide encodes a polypeptide selected from the group consisting of SEQ ID NO:1-22. In another alternative, the polynucleotide is selected from the group consisting of SEQ ID NO:23-44.  
       [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:1-22, 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:1-22, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group. consisting of SEQ ID NO:1-22, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-22. 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:1-22, 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:1-22, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-22, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-22. 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:1-22, 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:1-22, c) a biologically active fragment of a polypeptide having an amin acid sequence selected from the group consisting of SEQ ID NO:1-22, and d) an immunog nic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-22.  
       [0054] The invention further provides an isolated polynucleotide selected from the group consisting f a) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:23-44, 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:23-44, 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:23-44, 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:23-44, 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:23-44, 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:23-44, 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 fr m the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-22, 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:1-22, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-22, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-22, and a pharmaceutically acceptable excipient. In one embodiment, the composition comprises an amino acid sequence selected from the group consisting of SEQ ID NO:1-22. The invention additionally provides a method of treating a disease or condition associated with decreased expression of functional PKIN, 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:1-22, 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:1-22, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-22, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 1-22. 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 PKIN, 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:1-22, 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:1-22, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-22, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-22. 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 PKIN, 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:1-22, 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:1-22, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-22, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-22. 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:1-22, 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: 1-22, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-22, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-22. 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:23-44, 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:23-44, 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:23-44, iii) a polynucleotide having a sequence complementary to i), iv) a polynucleotide complementary to the polynucleotide f 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:23-44, 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:23-44, 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 summarizes 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 score for the match between each polypeptide and its GenBank homolog is also shown.  
       [0066] 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.  
       [0067] 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 polynucleotid sequences.  
       [0068] Table 5 shows the representative cDNA library for polynucleotides of the invention.  
       [0069] Table 6 provides an appendix which describes the tissues and vectors used for construction f the cDNA libraries shown in Table 5.  
       [0070] 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  
       [0071] 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.  
       [0072] 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.  
       [0073] 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.  
       [0074] Definitions  
       [0075] “PKIN” refers to the amino acid sequences of substantially purified PKIN 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.  
       [0076] The term “agonist” refers to a molecule which intensifies or mimics the biological activity of PKIN. Agonists may include proteins, nucleic acids, carbohydrates, small molecules, or any other compound or composition which modulates the activity of PKEN either by directly interacting with PKIN or by acting on components of the biological pathway in which PKIN participates.  
       [0077] An “allelic variant” is an alternative form of th gene encoding PKIN. 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.  
       [0078] “Altered” nucleic acid sequences encoding PKIN include those sequences with deletions, insertions, or substitutions of different nucleotides, resulting in a polypeptide the same as PKIN or a polypeptide with at least one functional characteristic of PKIN. Included within this definition are polymorphisms which may or may not be readily detectable using a particular oligonucleotide probe of the polynucleotide encoding PKIN, and improper or unexpected hybridization to allelic variants, with a locus other than the normal chromosomal locus for the polynucleotide sequence encoding PKIN. 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 PKIN. 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 PKIN 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.  
       [0079] 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.  
       [0080] “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.  
       [0081] The term “antagonist” refers to a molecule which inhibits or attenuates the biological activity of PKIN. Antagonists may include proteins such as antibodies, nucleic acids, carbohydrates, small molecules, r any other compound or composition which modulates the activity of PKIN either by directly interacting with PKIN r by acting n components of the bi logical pathway in which PKIN participates.  
       [0082] 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 PKIN 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 (KUI). The coupled peptide is then used to immunize the animal.  
       [0083] 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.  
       [0084] 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.)  
       [0085] 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).  
       [0086] The term “spiegelmer” refers to an aptamer which includes L-DNA, L-RNA, or other left-handed nucleotide derivatives or nucleotid -like molecules. Aptamers containing left-handed nucleotides are resistant to degradation by naturally occurring enzymes, which normally act on substrates containing right-handed nucleotides.  
       [0087] 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.  
       [0088] 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 PKIN, or of any oligopeptide thereof, to induce a specific immune response in appropriate animals or cells and to bind with specific antibodies.  
       [0089] “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′.  
       [0090] 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 PKIN or fragments of PKIN 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.).  
       [0091] “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 r 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.  
       [0092] “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                      
 
       [0093] 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.  
       [0094] 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.  
       [0095] 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 encod s a polypeptide which retains at least one biological r 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.  
       [0096] 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.  
       [0097] “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.  
       [0098] “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.  
       [0099] A “fragment” is a unique portion of PKIN or the polynucleotide encoding PKIN 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.  
       [0100] A fragment of SEQ ID NO:23-44 comprises a region of unique polynucleotide sequence that specifically identifies SEQ ID NO:23-44, for example, as distinct from any other sequence in the genome from which the fragment was obtained. A fragment of SEQ ID NO:23-44 is useful, for example, in hybridization and amplification technologies and in analogous methods that distinguish SEQ ID NO:23-44 from related polynucleotide sequences. The precise length of a fragment of SEQ ID NO:23-44 and the region of SEQ ID NO:23-44 to which the fragment corresponds are routinely determinable by one of ordinary skill in the art based on the intended purpose for the fragment.  
       [0101] A fragment of SEQ ID NO:1-22 is encoded by a fragment of SEQ ID NO:23-44. A fragment of SEQ ID NO:1-22 comprises a region of unique amino acid sequence that specifically identifies SEQ ID NO:1-22. For example, a fragment of SEQ ID NO:1-22 is useful as an immunogenic peptide for the development f antibodies that specifically recognize SEQ ID NO:1-22. The precise length of a fragment of SEQ ID NO:1-22 and the region of SEQ ID NO:1-22 to which the fragment corresponds are routinely determinable by one of ordinary skill in the art based on the intended purpose for the fragment.  
       [0102] 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.  
       [0103] “Homology” refers to sequence similarity or, interchangeably, sequence identity, between two or more polynucleotide sequences or two or more polypeptide sequences.  
       [0104] 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.  
       [0105] 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.  
       [0106] 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.nhm.n.hgov/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.nlmnihgov/gorf/bl2.html. The “BLAST 2 Sequences” t ol 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 20.12 (Apr. 21, 2000) set at default parameters. Such default parameters may be, for example:  
       [0107] Matrix: BLOSUM62  
       [0108] Reward for match: 1  
       [0109] Penalty for mismatch: −2  
       [0110] Open Gap: 5 and Extension Gap: 2 penalties  
       [0111] Gap x drop-off: 50  
       [0112] Expect: 10  
       [0113] Word Size: 11  
       [0114] Filter: on  
       [0115] 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.  
       [0116] 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.  
       [0117] 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.  
       [0118] 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. Th 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.  
       [0119] 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:  
       [0120] Matrix: BLOSUM62  
       [0121] Open Gap: 11 and Extension Gap: 1 penalties  
       [0122] Gap x drop-off: 50  
       [0123] Expect: 10  
       [0124] Word Size: 3  
       [0125] Filter: on  
       [0126] 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.  
       [0127] “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.  
       [0128] 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.  
       [0129] “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 string nt 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 ne f 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.  
       [0130] 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 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.  
       [0131] 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.  
       [0132] 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).  
       [0133] 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.  
       [0134] “Immune response” can refer to conditions associated with inflammation, trauma, immune dis rders, 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.  
       [0135] An “immunogenic fragment” is a polypeptide or oligopeptide fragment of PKIN 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 PKIN which is useful in any of the antibody production methods disclosed herein or known in the art.  
       [0136] The term “microarray” refers to an arrangement of a plurality of polynucleotides, polypeptides, or other chemical compounds on a substrate.  
       [0137] The terms “element” and “array element” refer to a polynucleotide, polypeptide, or other chemical compound having a unique and defined position on a microarray.  
       [0138] The term “modulate” refers to a change in the activity of PKIN. For example, modulation may cause an increase or a decrease in protein activity, binding characteristics, or any other biological, functional, or immunological properties of PKIN.  
       [0139] 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.  
       [0140] “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.  
       [0141] “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 f 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.  
       [0142] “Post-translational modification” of an PKIN 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 f PKIN.  
       [0143] “Probe” refers to nucleic acid sequences encoding PKIN, their complements, or fragments thereof, which are used to detect identical, allelic or related nucleic acid sequences. Probes are isolated oligonucleotides or polynucle tides 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).  
       [0144] 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.  
       [0145] 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-Intersciences, 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.).  
       [0146] 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 ar 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 conserved oligonucleotides and polynucleotide fragments. The oligonucleotides and polynucleotide fragments identified by any of the above selection methods are useful in hybridization technologies, for example, as PCR or sequencing primers, microarray elements, or specific probes to identify fully or partially complementary polynucleotides in a sample of nucleic acids. Methods of oligonucleotide selection are not limited to those described above.  
       [0147] 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.  
       [0148] 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.  
       [0149] 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.  
       [0150] “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.  
       [0151] 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 thymin are replaced with uracil, and the sugar backbone is composed of ribose instead of deoxyribose.  
       [0152] The term “sample” is used in its broadest sense. A sample suspected of containing PKIN, nucleic acids encoding PKIN, 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.  
       [0153] 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.  
       [0154] 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.  
       [0155] A “substitution” refers to the replacement of one or more amino acid residues or nucleotides by different amino acid residues or nucleotides, respectively.  
       [0156] “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.  
       [0157] A “transcript image” refers to the collective pattern of gene expression by a particular cell type or tissue under given conditions at a given time.  
       [0158] “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.  
       [0159] 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.  
       [0160] 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 07, 1999) set at default parameters. Such a pair of nucleic acids may show, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 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 maybe 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.  
       [0161] 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 07, 1999) set at default parameters. Such a pair of polypeptides may show, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 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% r greater sequence identity over a certain defined length of one of the polypeptides.  
       [0162] The Invention  
       [0163] The invention is based on the discovery of new human human kinases (PKIN), the polynucleotides encoding PKIN, and the use of these compositions for the diagnosis, treatment, or prevention of cancer, immune disorders, disorders affecting growth and development, cardiovascular diseases, and lipid disorders.  
       [0164] 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.  
       [0165] 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 score for the match between each polypeptide and its GenBank homolog. Column 5 shows the annotation of the GenBank homolog along with relevant citations where applicable, all of which are expressly incorporated by reference herein.  
       [0166] 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 som cases, searchable databases to which the analytical methods were applied.  
       [0167] Together, Tables 2 and 3 summarize the properties of polypeptides f the invention, and these properties establish that the claimed polypeptides are human kinases.  
       [0168] For example, SEQ ID NO:1 is 91% identical to human casein kinase I-alpha (GenBank ID g852055) as determined by the Basic Local Alignment Search Tool (BLAST). (See Table 2.) The BLAST probability score is 2.9e-167, which indicates the probability of obtaining the observed polypeptide sequence alignment by chance. SEQ ID NO:1 also contains a eukaryotic protein kinase 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 PROFILSCAN analyses provide further corroborative evidence that SEQ ID NO:1 is a protein kinase.  
       [0169] For example, SEQ ID NO:10 is 91% identical to Mus musculus FYVE finger-containing phosphoinositide kinase (GenBank ID g4200446) 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:10 also contains a phosphatidyl inositol 4-phosphate 5-kinase 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 PRODOM analysis provides further corroborative evidence that SEQ ID NO:10 is a phosphoinositide kinase.  
       [0170] For example, SEQ ID NO:12 is 71% identical to human serine/threonine protein kinase (GenBank ID g7160989) as determined by the Basic Local Alignment Search Tool (BLAST). (See Table 2.) The BLAST probability score is 1.7e-148, which indicates the probability of obtaining the observed polypeptide sequence alignment by chance. SEQ ID NO:12 also contains a eukaryotic protein kinase 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 and MOTIFS analyses provide further corroborative evidence that SEQ ID NO:12 is protein kinase.  
       [0171] For example, SEQ ID NO:13 is 86% identical to murine pantothenate kinase 1 beta (GenBank ID g6690020) as determined by the Basic Local Alignment Search Tool (BLAST). (See Table 2.) The BLAST probability score is 1.6e-129, which indicates the probability of obtaining the observed polypeptide sequence alignment by chance. Pantothenate kinase (PanK) is proposed to be the master regulator of CoA biosynthesis in mammalian cells, by controlling flux through the CoA biosynthetic pathway. Changes in the level of tissue PanK activity is reflected by the concurrent changes in the levels of CoA as seen in various metabolic states. Alterations in CoA levels and PanK activity are seen during starvation/feeding, pathological states such as diabetes and by treatment with hypolipidemic drugs (Rock, C. O. et al., (2000) J. Biol. Chem. 275:1377-1383.)  
       [0172] For example, SEQ ID NO:16 is 68% identical to  Mus musculus  Nck-interacting kinas -like embryo specific kinase (GenBank ID g6472874) 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:16 also contains a eukaryotic protein kinase 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:16 is a protein kinase.  
       [0173] For example, SEQ ID NO:19 is 99% identical to human RET tyrosine kinase receptor (GenBank ID g5419753) 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:19 also contains a eukaryotic protein kinase 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:19 is a tyrosine kinase.  
       [0174] For example, SEQ ID NO:22 is 33% identical to Gallus gallus smooth muscle myosin light chain kinase precursor (GenBank ID g212661) as determined by the Basic Local Alignment Search Tool (BLAST). (See Table 2.) The BLAST probability score is 1.2 e-60, which indicates the probability of obtaining the observed polypeptide sequence alignment by chance. SEQ ID NO:22 also contains two eukaryotic protein kinase 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, MOTIFS, and PROFILESCAN analyses provide further corroborative evidence that SEQ ID NO:22 is a protein kinase.  
       [0175] SEQ ID NO:2-9, SEQ ID NO:11, SEQ ID NO:14-15, SEQ ID NO:17-18, and SEQ ID NO:20-21 were analyzed and annotated in a similar manner. The algorithm and parameters for the analysis of SEQ ID NO:1-22 are described in Table 7.  
       [0176] 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 P lynucleotide 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:23-44 or that distinguish between SEQ ID NO:23-44 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.  
       [0177] 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, 183812R7 is the identification number of an Incyte cDNA sequence, and CARDNOT01 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., 71583296V1). Alternatively, the identification numbers in column 5 may refer to GenBank cDNAs or ESTs 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 S 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”) ay be used in place of the GenBank identifier (i.e., GBBBBB).  
       [0178] 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,   Exon prediction from genomic sequences using, for example,       GFG,   GENSCAN (Stanford University, CA, USA) or FGENES       ENST   (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.                  
 
       [0179] 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.  
       [0180] 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.  
       [0181] The invention also encompasses PKIN variants. A preferred PKIN 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 PKIN amino acid sequence, and which contains at least one functional or structural characteristic of PKIN.  
       [0182] The invention also encompasses polynucleotides which encode PKIN. In a particular embodiment, the invention encompasses a polynucleotide sequence comprising a sequence selected from the group consisting of SEQ ID NO:23-44, which encodes PKIN. The polynucleotide sequences of SEQ ID NO:23-44, 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 deoxyrib se.  
       [0183] The invention also enc mpasses a variant f a polynucleotide sequence encoding PKIN. 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 PKIN. 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:23-44 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:23-44. Any one of the polynucleotide variants described above can encode an amino acid sequence which contains at least one functional or structural characteristic of PKIN.  
       [0184] 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 PKIN, 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 PKIN, and all such variations are to be considered as being specifically disclosed.  
       [0185] Although nucleotide sequences which encode PKIN and its variants are generally capable of hybridizing to the nucleotide sequence of the naturally occurring PKIN under appropriately selected conditions of stringency, it may be advantageous to produce nucleotide sequences encoding PKIN 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 PKIN 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.  
       [0186] The invention also encompasses production of DNA sequences which encode PKIN and PKIN 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 PKIN or any fragment thereof.  
       [0187] 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:23-44 and fragments thereof under various conditions of stringency. (See, e.g., Wahl, G. M. and S. L. Berger (1987) Methods Enzymol. 152:399407; Kimmel, A. R. (1987) Methods Enzymol. 152:507-511.) Hybridization conditions, including annealing and wash conditions, are described in “Definitions.” 
       [0188] 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 17 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 (M J 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.)  
       [0189] The nucleic acid sequences encoding PKIN 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 maybe 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 b fore 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, ne 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.  
       [0190] 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.  
       [0191] 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.  
       [0192] In another embodiment of the invention, polynucleotide sequences or fragments thereof which encode PKIN may be cloned in recombinant DNA molecules that direct expression of PKIN, 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 PKIN.  
       [0193] The nucleotide sequences of the present invention can be engineered using methods generally known in the art in order to alter PKIN-encoding sequences for a variety of purposes including, but not limited to, modification of the cloning, processing, and/or expression of the gene product. DNA shuffling by random fragmentation and PCR reassembly of gene fragments and synthetic oligonucleotides may be used to engineer the nucleotide sequences. For example, oligonucleotide-mediated site-directed mutagenesis may be used to introduce mutations that create new restriction sites, alter glycosylation patterns, change codon preference, produce splice variants, and so forth.  
       [0194] The nucleotides of the present invention may be subjected to DNA shuffling techniques such as MOLECULARBREEDING (Maxygen Inc., 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 PKIN, 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 optimiz. 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.  
       [0195] In another embodiment, sequences encoding PKIN 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, PKIN itself or a fragment thereof may be synthesized using chemical methods. For example, peptide synthesis can be performed using various solution-phase or solid-phase techniques. (See, e.g., Creighton, T. (1984) Proteins. Structures and Molecular Properties, WH Freeman, New York N.Y., pp. 55-60; and Roberge, J. Y. et al. (1995) Science 269:202-204.) Automated synthesis maybe achieved using the ABI 431A peptide synthesizer (Applied Biosystems). Additionally, the amino acid sequence of PKIN, 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.  
       [0196] 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.)  
       [0197] In order to express a biologically active PKIN, the nucleotide sequences encoding PKIN 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 s quences, such as enhancers, constitutive and inducible promoters, and 5′ and 3′ untranslated regions in the vect r and in polynucleotide sequences encoding PKIN. Such elements may vary in their strength and specificity. Specific initiation signals may also be used to achieve more efficient translation of sequences encoding PKIN. Such signals include the ATG initiation codon and adjacent sequences, e.g. the Kozak sequence. In cases where sequences encoding PKIN 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.)  
       [0198] Methods which are well known to those skilled in the art may be used to construct expression vectors containing sequences encoding PKIN 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.)  
       [0199] A variety of expression vector/host systems may be utilized to contain and express sequences encoding PKIN. 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 deliv ry of nucleotide sequences to the targeted organ, tissue, or cell population. (See, e.g., Di Nicola, M. et al. (1998) Cancer Gen. Ther. 5(6):350-356; Yu, M. et al. (1993) Proc. Natl. Acad. Sci. USA 90(13):6340-6344; Buller, R. M. et al. (1985) Nature 317(6040):813-815; McGregor, D. P. et al. (1994) Mol. Immunol. 31(3):219-226; and Verma, I. M. and N. Somia (1997) Nature 389:239-242.) The invention is not limited by the host cell employed.  
       [0200] In bacterial systems, a number of cloning and expression vectors may be selected depending upon the use intended for polynucleotide sequences encoding PKIN. For example, routine cloning, subcloning, and propagation of polynucleotide sequences encoding PKIN 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 PKIN 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 PKIN are needed, e.g. for the production of antibodies, vectors which direct high level expression of PKIN may be used. For example, vectors containing the strong, inducible SP6 or T7 bacteriophage promoter may be used.  
       [0201] Yeast expression systems may be used for production of PKIN. 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.)  
       [0202] Plant systems may also be used for expression of PKIN. Transcription of sequences encoding PKIN 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 may be 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.)  
       [0203] 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 PKIN may be ligated into an adenovirus transcription/translation complex consisting of the late promoter and tripartite leader sequence. Insertion in a non-essential E1 r E3 region f the viral genome may be used to btain infective virus which expresses PKIN 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.  
       [0204] 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.)  
       [0205] For long term production of recombinant proteins in mammalian systems, stable expression of PKIN in cell lines is preferred. For example, sequences encoding PKIN 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.  
       [0206] Any number of selection systems may be used to recover transformed cell lines. These include, but are not limited to, the herpes simplex virus thymidine kinase and adenine phosphoribosyltransferase genes, for use in tk −  and apr −  cells, respectively. (See, e.g., Wigler, M. et al. (1977) Cell 11:223-232; Lowy, I. et al. (1980) Cell 22:817-823.) Also, antimetabolite, antibiotic, or herbicide resistance can be used as the basis for selection. For example, dhfr confers resistance to methotrexate; neo confers resistance to the aminoglycosides neomycin and G418, and als and pat confer resistance to chlorsulfuron and phosplinotricin acetyltransferase, respectively. (See, e.g., Wigler, M. et al. (1980) Proc. Natl. Acad. Sci. USA 77:3567-3570; Colbere-Garapin, F. et al. (1981) J. Mol. Biol. 150:1-14.) Additional selectable genes have been described, e.g., trpB and hisD, which alter cellular requirements for metabolites. (See, e.g., Hartman, S. C. and R. C. Mulligan (1988) Proc. Natl. Acad. Sci. USA 85:8047-8051.) Visible markers, e.g., anthocyanins, green fluorescent proteins (GFP; Clontech), β glucuronidase and its substrate β-glucuronide, or luciferase and its substrate luciferin may be used. These mark rs can be used not only to identify transformants, but also to quantify the amount of transient or stable protein expression attributable to a specific vector system. (See, e.g., Rhodes, C. A. (1995) Methods Mol. Biol. 55:121-131.) Although the presence/absence of marker gene expression suggests that the gene of interest is also present, the presence and expression of the gene may need to be confirmed. For example, if the sequence encoding PKIN is inserted within a marker gene sequence, transformed cells containing sequences encoding PKIN can be identified by the absence of marker gene function. Alternatively, a marker gene can be placed in tandem with a sequence encoding PKIN 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.  
       [0207] In general, host cells that contain the nucleic acid sequence encoding PKIN and that express PKIN 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.  
       [0208] Immunological methods for detecting and measuring the expression of PKIN 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 PKIN 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)  Serolopical 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.).  
       [0209] 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 PKIN include oligolabeling, nick translation, end-labeling, or PCR amplification using a labeled nucleotide. Alternatively, the sequences encoding PKIN, 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.  
       [0210] Host cells transformed with nucleotide sequences encoding PKIN 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 PKIN may be designed to contain signal sequences which direct secretion of PKIN through a prokaryotic or eukaryotic cell membrane.  
       [0211] 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.  
       [0212] In another embodiment of the invention, natural, modified, or recombinant nucleic acid sequences encoding PKIN 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 PKIN protein containing a heterologous moiety that can be recognized by a commercially available antibody may facilitate the screening of peptide libraries for inhibitors of PKIN 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 thes epitope tags. A fusion protein may also be engineered to contain a proteolytic cleavage site located between the PKIN encoding sequence and the heterologous protein sequence, so that PKIN may be cleaved away from the heterol gous moiety following purification. Methods for fusi n protein expression and purification are discussed in Ausubel (1995, supra, ch. 10). A variety f commercially available kits may also be used to facilitate expression and purification of fusion proteins.  
       [0213] In a further embodiment of the invention, synthesis of radiolabeled PKIN 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.  
       [0214] PKIN of the present invention or fragments thereof may be used to screen for compounds that specifically bind to PKIN. At least one and up to a plurality of test compounds may be screened for specific binding to PKIN. Examples of test compounds include antibodies, oligonucleotides, proteins (e.g., receptors), or small molecules.  
       [0215] In one embodiment, the compound thus identified is closely related to the natural ligand of PKIN, 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 PKIN 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 PKIN, either as a secreted protein or on the cell membrane. Preferred cells include cells from mammals, yeast, Drosoyhila, or  E. coli.  Cells expressing PKIN or cell membrane fractions which contain PKIN are then contacted with a test compound and binding, stimulation, or inhibition of activity of either PKIN or the compound is analyzed.  
       [0216] 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, th assay may comprise the steps of combining at least one test compound with PKIN, either in solution or affixed to a solid support, and detecting the binding of PIKN 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) maybe flee in solution or affixed to a solid support.  
       [0217] PKIN of the present invention or fragments thereof may be used to screen for compounds that modulate the activity f PKIN. Such compounds may include agonists, antagonists, or partial or inverse agonists. In one embodim nt, an assay is performed under conditions permissive for PKIN activity, wherein PKIN is combined with at least one test compound, and the activity of PKIN in the presence of a test compound is compared with the activity of PKIN in the absence of the test compound. A change in the activity of PKIN in the presence of the test compound is indicative of a compound that modulates the activity of PKIN. Alternatively, a test compound is combined with an in vitro or cell-free system comprising PKIN under conditions suitable for PKIN activity, and the assay is performed. In either of these assays, a test compound which modulates the activity of PKIN 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.  
       [0218] In another embodiment, polynucleotides encoding PKIN 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 chumeric progeny are genotyped and bred to produce heterozygous or homozygous strains. Transgenic animals thus generated may be tested with potential therapeutic or toxic agents.  
       [0219] Polynucleotides encoding PKIN 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).  
       [0220] Polynucleotides encoding PKIN 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 PKIN is injected into animal ES cells, and the injected sequence integrates into the animal cell genom . Transformed cells are injected into blastulae, and the blastulae are implanted as described above. Transgenic progeny or inbred lines are studied and treated with potential pharmaceutical agents to obtain information on treatment of a human disease. Alternatively, a mammal inbred to verexpress PKIN, e.g., by secreting PKIN in its milk, may also serve as a convenient source of that protein (Janne, J. et al. (1998) Biotechnol. Annu. Rev. 4:55-74).  
       [0221] Therapeutics  
       [0222] Chemical and structural similarity, e.g., in the context of sequences and motifs, exists between regions of PKIN and human kinases. In addition, the expression of PKIN is closely associated with brain, breast tumor, cardiovascular, digestive, fallopian tube tumor, fetal stomach, nervous, ovarian tumor, pancreatic tumor, peritoneal tumor, pituitary gland, placental, prostate tumor, neural, spinal cord, and testicular tissues, and with umbilical cord blood dendritic cells. Therefore, PKIN appears to play a role in cancer, immune disorders, disorders affecting growth and development, cardiovascular diseases, and lipid disorders. In the treatment of disorders associated with increased PKIN expression or activity, it is desirable to decrease the expression or activity of PKIN. In the treatment of disorders associated with decreased PKIN expression or activity, it is desirable to increase the expression or activity of PKIN.  
       [0223] Therefore, in one embodiment, PKIN 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 PKIN. Examples of such disorders include, but are not limited to, a cancer, such as 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, leukemias such as multiple myeloma and lymphomas such as Hodgkin&#39;s disease; an immune disorder, such as acquired immunodeficiency syndrome (AIDS), Addison&#39;s disease, adult respiratory distress syndrome, allergies, ankylosing spondylitis, amyloidosis, anemia, asthma, atherosclerosis, autoimmune hemolytic anemia, autoimmune thyroiditis, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), bronchitis, cholecystitis, contact dermatitis, Crohn&#39;s disease, atopic dermatitis, dermatomyositis, diabetes melitus, 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, Sjbgren&#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; a growth and developmental disord r, such as actinic keratosis, arteriosclerosis, atherosclerosis, bursitis, cirrhosis, hepatitis, mixed c nnective 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, 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 disease, 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, ballo n angioplasty, vascular replacement, and 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, and complications of cardiac transplantation, congenital lung anomalies, atelectasis, pulmonary congestion and edema, pulmonary embolism, pulmonary hemorrhag , 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 collag n-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; and a lipid 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, metaciromatic leukodystrophy, adrenoleukodystrophy, GM 2  gangliosidosis, and ceroid lipofuscinosis, abetalipoproteinemia, Tangier disease, hyperlipoproteinemnia, 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, hypocholesteroleria, Tay-Sachs disease, Sandhoff&#39;s disease, hyperlipidemia, hyperlipemia, lipid myopathies, and obesity.  
       [0224] In another embodiment, a vector capable of expressing PKIN 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 PKIN including, but not limited to, those described above.  
       [0225] In a further embodiment, a composition comprising a substantially purified PKIN 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 PKIN including, but not limited to, those provided above.  
       [0226] In still another embodiment, an agonist which modulates the activity of PKIN may be administered to a subject to treat or prevent a disorder associated with decreased expression or activity of PKIN including, but not limited to, those listed above.  
       [0227] In a further embodiment, an antagonist of PKIN may be administered to a subject to treat or prevent a disorder associated with increased expression or activity of PKIN. Examples of such disorders include, but are not limited to, those cancer, immune disorders, disorders affecting growth and development, cardiovascular diseases, and lipid disorders described above. In one aspect, an antibody which specifically binds PKIN 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 PKIN.  
       [0228] In an additional embodiment, a vector expressing the complement of the polynucleotide encoding PKIN may be administered to a subject to treat or prevent a disorder associated with increased expression or activity of PKIN including, but not limited to, those described above.  
       [0229] In other mbodiments, any of the proteins, antagonists, antibodies, agonists, complementary sequences, or vectors of the invention may be administered in combination with other appropriate therapeutic agents. Selection of the appropriate agents for use in combination therapy may be made by one of rdinary 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.  
       [0230] An antagonist of PKIN may be produced using methods which are generally known in the art. In particular, purified PKIN may be used to produce antibodies or to screen libraries of pharmaceutical agents to identify those which specifically bind PKIN. Antibodies to PKIN 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.  
       [0231] For the production of antibodies, various hosts including goats, rabbits, rats, mice, humans, and others may be immunized by injection with PKIN 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 Calmette-Guerin) and  Corynebacterium parvum  are especially preferable.  
       [0232] It is preferred that the oligopeptides, peptides, or fragments used to induce antibodies to PKIN 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 PKIN amino acids may be fused with those of another protein, such as KLH, and antibodies to the chimeric molecule may be produced.  
       [0233] Monoclonal antibodies to PKIN 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.).  
       [0234] In addition, techniques developed for the production of “chimeric antibodies,” such as the splicing of mouse antibody genes to human antibody genes t obtain a molecule with appropriate antigen specificity and biological activity, can be used. (See, e.g., M rrison, 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 PKIN-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.).  
       [0235] 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. Nad. Acad. Sci. USA 86:3833-3837; Winter, G. et al. (1991) Nature 349:293-299.).  
       [0236] Antibody fragments which contain specific binding sites for PKIN may also be generated. For example, such fragments include, but are not limited to, F(ab′) 2  fragments produced by pepsin is 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.).  
       [0237] 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 PKIN and its specific antibody. A two-site, monoclonal-based immunoassay utilizing monoclonal antibodies reactive to two non-interfering PKIN epitopes is generally used, but a competitive binding assay may also be employed (Pound, supra).  
       [0238] Various methods such as Scatchard analysis in conjunction with radioimmunoassay techniques may be used to assess the affinity of antibodies for PKIN. Affinity is expressed as an association constant, K a , which is defined as the molar concentration of PKIN-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 PKIN epitopes, represents the average affinity, or avidity, of the antibodies for PKIN. The K a  determined for a preparation of monoclonal antibodies, which are monospecific for a particular PKIN 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 PKIN-antibody complex must withstand rigorous manipulations. Low-affinity antibody preparations with K a  ranging from ab ut 10 6  to 10 7  L/mole are preferred for use in immun purification and similar procedures which ultimately require dissociation of PKIN, 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.).  
       [0239] 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 PKIN-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.).  
       [0240] In another embodiment of the invention, the polynucleotides encoding PKIN, 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 PKIN. 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 PKIN. (See, e.g., Agrawal, S., ed. (1996)  Antisense Therapeutics , Humana Press Inc., Totawa N.J.).  
       [0241] 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, sunra; 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(14):2730-2736.)  
       [0242] In another embodiment of the invention, polynucleotides encoding PKIN 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 270:475480; 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 270:404410; Verma, I. M. and N. Somia (1997) Nature 389:239-242)), (ii) express a conditionally lethal gene product (e.g., in the case of cancers which result from unregulated cell proliferation), or (iii) express a protein which affords protection against intracellular parasites (e.g., against human retroviruses, such as human immunodeficiency virus (HIV) (Baltimore, D. (1988) Nature 335:395-396; Poeschla, E. et al. (1996) Proc. Natl. Acad. Sci. USA. 93:11395-11399), hepatitis B or C virus (HBV, HCV); fungal parasites, such as  Candida albicans  and  Paracoccidioides brasiliensis ; and protozoan parasites such as  Plasmodium falciparum  and  Trypanosoma cruzi ). In the case where a genetic deficiency in PKIN expression or regulation causes disease, the expression of PKIN from an appropriate population of transduced cells may alleviate the clinical manifestations caused by the genetic deficiency.  
       [0243] In a further embodiment of the invention, diseases or disorders caused by deficiencies in PKIN are treated by constructing mammalian expression vectors encoding PKIN and introducing these vectors by mechanical means into PIN-deficient cells. Mechanical transfer technologies for use with cells in vivo or ex vitro include (i) direct DNA microinjection into individual cells, (ii) ballistic gold particle delivery, (iii) liposome-mediated transfection, (iv) receptor-mediated gene transfer, and (v) the use of DNA transposons (Morgan, R. A. and W. F. Anderson (1993) Annu. Rev. Biochem. 62:191-217; Ivics, Z. (1997) Cell 91:501-510; Boulay, J -L. and H. Récipon (1998) Curr. Opin. Biotechnol. 9:445450).  
       [0244] Expression vectors that may be effective for the expression of PKIN 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, PTME2-LUC, PTK-HYG (Clontech, Palo Alto Calif.). PKIN may be expressed using (i) a constitutively active promoter, ( .g., from cytomegalovirus (CMV), Rous sarcoma virus (RSV), SV40 virus, thymidine kinase (TK), or β-actin g nes), (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 Blau, H. M. supra)), or (iii) a tissue-specific promoter or the native promoter of the endogenous gene encoding PKIN from a normal individual.  
       [0245] 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.  
       [0246] In another embodiment of the invention, diseases or disorders caused by genetic defects with respect to PKIN expression are treated by constructing a retrovirus vector consisting of (i) the polynucleotide encoding PKIN 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; Bau r, 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).  
       [0247] In the alternative, an adenovirus-based gene therapy delivery system is used t deliver polynucleotides encoding PKIN to cells which have one or more genetic abnormalities with respect to the expression of PKIN. 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.  
       [0248] In another alternative, a herpes-based, gene therapy delivery system is used to deliver polynucleotides encoding PKIN to target cells which have one or more genetic abnormalities with respect to the expression of PKIN. The use of herpes simplex virus (HSV)-based vectors may be especially valuable for introducing PKIN 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.  
       [0249] In another alternative, an alphavirus (positive, single-stranded RNA virus) vector is used to deliver polynucleotides encoding PKIN 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 PKIN into the alphavirus genome in place of the capsid-coding region results in the production of a large number of PKIN-coding RNAs and the synthesis of high levels of PKIN 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 PKIN 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.  
       [0250] Oligonucleotides derived from the transcription initiation site, e.g., between about positions −10 and +10 from the start site, may also be employed to inhibit gene expression. Similarly, inhibition can be achieved using triple helix base-pairing methodology. Triple helix pairing is useful because it causes inhibition of the ability of the double helix to open sufficiently for the binding of polymerases, transcription factors, or regulatory molecules. Recent therapeutic advances using triplex DNA have been described in the literature. (See, e.g., Gee, J. E. et al. (1994) in Huber, B. E. and B. I. Carr,  Molecular and 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.  
       [0251] 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 nbozyme molecules may specifically and efficiently catalyze endonucleolytic cleavage of sequences encoding PKIN.  
       [0252] 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 c mplementary oligonucleotides using ribonuclease protection assays.  
       [0253] 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 PKIN. Such DNA sequences may be incorporated into a wide variety of vectors with suitable RNA polymerase promoters such as 17 or SP6. Alternatively, these cDNA constructs that synthesize complementary RNA, constitutively or inducibly, can be introduced into cell lines, cells, or tissues.  
       [0254] 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.  
       [0255] An additional embodiment of the invention encompasses a method for screening for a compound which is effective in altering expression of a polynucleotide encoding PKIN. 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 PKIN expression or activity, a compound which specifically inhibits expression of the polynucleotide encoding PKIN may be therapeutically useful, and in the treatment of disorders associated with decreased PKIN expression or activity, a compound which specifically promotes expression of the polynucleotide encoding PKIN may be therapeutically useful.  
       [0256] 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 r proprietary library of naturally-occurring or non-natural chemical compounds; rational design f a compound based on chemical and/or structural properties f the target polynucleotide; and selection from a library of chemical compounds created combinatorially or randomly. A sample comprising a polynucleotide encoding PKIN 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 PKIN 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 PKIN. The amount of hybridization maybe 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).  
       [0257] 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.).  
       [0258] 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.  
       [0259] 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 editi n of Remington&#39;s  Pharmaceutical Sciences  (Maack Publishing, Easton Pa.). Such compositions may c nsist of PKIN, antibodies to PKIN, and mimetics, agonists, antagonists, or inhibitors of PKIN.  
       [0260] 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.  
       [0261] 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.  
       [0262] 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.  
       [0263] Specialized forms of compositions may be prepared for direct intracellular delivery of macromolecules comprising PKIN or fragments thereof. For example, liposome preparations containing a cell-impermeable macromolecule may promote cell fusion and intracellular delivery of the macromolecule. Alternatively, PKIN 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).  
       [0264] 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.  
       [0265] A therapeutically effective dose refers to that amount of active ingredient, for example PKIN or fragments thereof, antibodies of PKIN, and agonists, antagonists or inhibitors of PKIN, 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) r LD 50  (the dose lethal to 50% of the population) statistics. The dos rati 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.  
       [0266] 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.  
       [0267] 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.  
       [0268] Diagnostics  
       [0269] In another embodiment, antibodies which specifically bind PKIN may be used for the diagnosis of disorders characterized by expression of PKIN, or in assays to monitor patients being treated with PKIN or agonists, antagonists, or inhibitors of PKIN. Antibodies useful for diagnostic purposes may be prepared in the same manner as described above for therapeutics. Diagnostic assays for PKIN include methods which utilize the antibody and a label to detect PKIN 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.  
       [0270] A variety of protocols for measuring PKIN, including ELISAs, RIAs, and FACS, are known in the art and provide a basis for diagnosing altered or abnormal levels of PKIN xpression. Normal or standard values for PKIN expression are established by combining body fluids or cell extracts taken from normal mammalian subjects, for example, human subjects, with antib dies to PKIN under conditions suitable for complex formation. The amount of standard complex formation may be quantitated by various methods, such as photometric means. Quantities of PKIN 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.  
       [0271] In another embodiment of the invention, the polynucleotides encoding PKIN may be used for diagnostic purposes. The polynucleotides which maybe 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 PKIN may be correlated with disease. The diagnostic assay may be used to determine absence, presence, and excess expression of PKIN, and to monitor regulation of PKIN levels during therapeutic intervention.  
       [0272] In one aspect, hybridization with PCR probes which are capable of detecting polynucleotide sequences, including genomic sequences, encoding PKIN or closely related molecules may be used to identify nucleic acid sequences which encode PKIN. 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 PKIN, allelic variants, or related sequences.  
       [0273] Probes may also be used for the detection of related sequences, and may have at least 50% sequence identity to any of the PKIN 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:23-44 or from genomic sequences including promoters, enhancers, and introns of the PKIN gene.  
       [0274] Means for producing specific hybridization probes for DNAs encoding PKIN include the cloning of polynucleotide sequences encoding PKIN or PKIN 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 avidinibiotin coupling systems, and the like.  
       [0275] Polynucleotide sequences encoding PKIN may be used for the diagnosis of disorders associated with expression of PKIN. Examples of such disorders include, but are not limited to, a cancer, such as 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, vary, pancreas, parathyroid, penis, prostate, salivary glands, skin, spleen, testis, thymus, thyroid, and uterus, leukemias such as multiple myeloma and lymphomas such as Hodgkin&#39;s disease; an immune disorder, such as acquired immunodeficiency syndrome (AIDS), Addison&#39;s disease, adult respiratory distress syndrome, allergies, ankylosing spondylitis, amyloidosis, anemia, asthma, atherosclerosis, autoimmune hemolytic anemia, autoimmune thyroiditis, autoimmune polyendocrinopathy-candidiasis-todermal 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, Sjogren&#39;s syndrome, systemic anaphylaxis, systemic lupus erythematosus, systemic sclerosis, tbrombocytopenic purpura, ulcerative colitis, uveitis, Werner syndrome, complications of cancer, hemodialysis, and extracorporeal circulation, viral, bacterial fungal, parasitic, protozoal, and helminthic infections, and trauma; a growth and developmental 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, 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 disease, 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, and coronary artery bypass graft surgery, congestive heart failure, ischemic heart disease, angina pectoris, myocardial infarction, hypertensive heart disease, d generative 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, and 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-organizig 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; and a lipid 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 lipofiscinosis, 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, hyperlipernia, lipid myopathies, and obesity. The polynucleotide sequences encoding PKIN 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 PKIN expression. Such qualitative or quantitative methods are well known in the art.  
       [0276] In a particular aspect, the nucleotide sequences encoding PKIN may be useful in assays that detect the presence of associated disorders, particularly those mentioned above. The nucleotide sequences encoding PKIN may be labeled by standard methods and added to a fluid or tissue sample from a patient under conditions suitable for the formati n of hybridizati n complexes. After a suitable incubation period, the sample is washed and the signal is quantified and c mpared 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 PKIN 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.  
       [0277] In order to provide a basis for the diagnosis of a disorder associated with expression of PKIN, 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 PKIN, under conditions suitable for hybridization or amplification. Standard hybridization may be quantified by comparing the values obtained from normal subjects with values from an experiment in which a known amount of a substantially purified polynucleotide is used. Standard values obtained in this manner may be compared with values obtained from samples from patients who are symptomatic for a disorder. Deviation from standard values is used to establish the presence of a disorder.  
       [0278] 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.  
       [0279] 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 or further progression of the cancer.  
       [0280] Additional diagnostic uses for oligonucleotides designed from the sequences encoding PKIN 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 PKIN, or a fragment of a polynucleotide complementary to the polynucleotide encoding PKIN, and will be employed under optimized conditions for identification of a specific gene or condition. Oligomers may also be employed under less stringent c nditions for detection r quantification of closely related DNA or RNA sequences.  
       [0281] In a particular aspect, oligonucleotide primers derived from the polynucleotide sequences encoding PKIN 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 PKIN 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, Inc., San Diego Calif.).  
       [0282] Methods which may also be used to quantify the expression of PKIN 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 maybe 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 gives rapid quantitation.  
       [0283] 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 b used to determine g ne function, to understand the genetic basis of a disorder, to diagnose a disorder, to monitor progression/regression f disease as a function of g ne 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 pharmacogenonic profile of a patient in rder 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.  
       [0284] In another embodiment, PKIN, fragments of PKIN, or antibodies specific for PKIN 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.  
       [0285] 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 maybe 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.  
       [0286] 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.  
       [0287] 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 c ntain expression information from a large number of genes and gene families. Ideally, a genome-wide measurement f 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 f these genes are used t n rmalize 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/newshtoxchip.htm.) Therefore, it is important and desirable in toxicological screening using toxicant signatures to include all expressed gene sequences.  
       [0288] 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.  
       [0289] 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 f 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.  
       [0290] A proteomic profile may also be generated using antibodies specific for PKIN to quantify the levels of PKIN 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 maybe 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.  
       [0291] Toxicant signatures at the proteome level are also useful for toxicological screening, and should be analyzed in parallel with toxicant signatures at the taanscript 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.  
       [0292] In another embodiment, the toxicity of a test compound is assessed by treating a biological sample containing proteins with the test compound. Proteins that are expressed in the treated biological sample are separated so that the amount of each protein can be quantified. The amount of each protein is compared to the amount of the corresponding protein in an untreated biological sample. A difference in the amount of protein between the two samples is indicative of a toxic response to the test compound in the treated sample. Individual proteins are identified by sequencing the amino acid residues of the individual proteins and comparing these partial sequences to the polypeptides of the present invention.  
       [0293] 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 f protein in the treated biological sampl 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.  
       [0294] 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. N .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.  
       [0295] In another embodiment of the invention, nucleic acid sequences encoding PKIN 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.).  
       [0296] 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 PKIN 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.  
       [0297] 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.  
       [0298] In another embodiment of the invention, PKIN, its catalytic or immunogenic fragments, or oligopeptides thereof can be used for screening libraries of compounds in any of a variety of drug screening techniques. The fragment employed in such screening may be free in solution, affixed to a solid support, borne on a cell surface, or located intracellularly. The formation of binding complexes between PKIN and the agent being tested may be measured.  
       [0299] Another technique for drug screening provides for high throughput screening of compounds having suitable binding affinity to the protein of interest. (See, e.g., Geysen, et al. (1984) PCT application WO84/03564.) In this method, large numbers of different small test compounds are synthesized on a solid substrate. The test compounds are reacted with PKIN, or fragments thereof, and washed. Bound PKIN is then detected by methods well known in the art. Purified PKIN 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.  
       [0300] In another embodiment, one may use competitive drug screening assays in which neutralizing antibodies capable of binding PKIN specifically compete with a test compound for binding PKIN. In this manner, antibodies can be used to detect the presence of any peptide which shares one or more antigenic determinants with PKIN.  
       [0301] In additional embodiments, the nucleotide sequences which encode PKIN 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.  
       [0302] 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.  
       [0303] Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. The following preferred specific embodiments are, therefore, to be construed as merely illustrative, and not limitative f the remainder f the disclosure in any way whatsoever.  
       [0304] The disclosures of all patents, applications, and publications mentioned above and below, in particular U.S. Ser. No. 60/242,410, U.S. Ser. No. 60/244,068, U.S. Ser. No. 60/245,708, U.S. Ser. No. 60/247,672, U.S. Ser. No. 60/249,565, U.S. Ser. No. 60/252,730, and U.S. Ser. No. 60/250,807, are hereby expressly incorporated by reference. 
     
    
    
     EXAMPLES  
     [0305] I. Construction of cDNA Libraries  
     [0306] 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 others 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.  
     [0307] 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.).  
     [0308] 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 SUPERSCRIRT 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 restricti n nzyme 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 SOIR from Stratagene or DH5α, DH10B, or ElectroMAX DH10B from Life Technologies.  
     [0309] II. Isolation of cDNA Clones  
     [0310] 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, QIAWEL 8 Plus Plasmid, QIAWEL 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.  
     [0311] Alternatively, plasmid DNA was amplified from host cell lysates using direct link PCR in a high-throughput format (Rao, V. B. (1994) Anal. Biochem. 216:1-14). Host cell lysis and thermal cycling steps were carried out in a single reaction mixture. Samples were processed and stored in 384-well plates, and the concentration of amplified plasmid DNA was quantified fluorometrically using PICOGREEN dye (Molecular Probes, Eugene Oreg.) and a FLUOROSKAN II fluorescence scanner (Labsystems Oy, Helsinki, Finland).  
     [0312] III. Sequencing and Analysis  
     [0313] Incyte cDNA recovered in plasmids as described in Example B 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.  
     [0314] 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, 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, 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 algorithm as incorporated into the MEGALIGN multisequence alignment program (DNASTAR), which also calculates the percent identity between aligned sequences.  
     [0315] Table 7 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 valu , the greater the identity between two sequences).  
     [0316] The programs described above for the assembly and analysis f full length polynucleotide and polypeptide sequences were also used to identify polynucleotide sequence fragments from SEQ ID NO:23-44. Fragments from about 20 to about 4000 nucleotides which are useful in hybridization and amplification technologies are described in Table 4, column 4.  
     [0317] IV. Identification and Editing of Coding Sequences from Genomic DNA  
     [0318] Putative human kinases 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 human kinases, the encoded polypeptides were analyzed by querying against PFAM models for human kinases. Potential human kinases were also identified by homology to Incyte cDNA sequences that had been annotated as human kinases. 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.  
     [0319] V. Assembly of Genomic Sequence Data with cDNA Sequence Data  
     [0320] “Stitched” Sequences  
     [0321] 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.  
     [0322] “Stretched” Sequences  
     [0323] 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 public 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.  
     [0324] VI. Chromosomal Mapping of PKIN Encoding Polynucleotides  
     [0325] The sequences which were used to assemble SEQ ID NO:23-44 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:23-44 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 Genethon 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.  
     [0326] 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.  
     [0327] In this manner, SEQ ID NO:29 was mapped to chromosome 1 within the interval from 199.20 to 203.00 centiMorgans, to chromosome 13 within the interval from 105.20 centiMorgans to the q terminus, and to chromosome 6 within the interval from 59.60 to 72.20 centiMorgans. More than one map location is reported for SEQ ID NO:29, indicating that sequences having different map locations were assembled into a single cluster. This situation occurs, for example, when sequences having strong similarity, but not complete identity, are assembled into a single cluster.  
     [0328] VII. Analysis of Polynucleotide Expression  
     [0329] 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.).  
     [0330] 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     )         }                     
 
     [0331] The product score takes into account both the degree of similarity between two sequences and the length of the sequence match. The product score is a normalized value between 0 and 100, and is calculated as follows: the BLAST score is multiplied by the percent nucleotide identity and the product is divided by (5 times the length of the shorter of the two sequences). The BLAST score is calculated by assigning a score of +5 for every base that matches in a high-scoring segment pair (HSP), and −4 for every mismatch. Two sequences may share more than one HSP (separated by gaps). If there is more than one HSP, then the pair with the highest BLAST score is used to calculate the product score. The product score represents a balance between fractional overlap and quality in a BLAST alignment For example, a product score of 100 is produced only for 100% identity over the entire length of the shorter of the two sequences being compared. A product score of 70 is produced either by 100% identity and 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.  
     [0332] Alternatively, polynucleotide sequences encoding PKIN 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 PKIN. cDNA sequences and cDNA library/tissue information are found in the LIFESEQ GOLD database (Incyte Genomics, Palo Alto Calif.).  
     [0333] VIII. Extension of PKIN Encoding Polynucleotides  
     [0334] 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′ extensi n of the known fragment, and the other primer was synthesized to initiate 3′ extension of th 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.  
     [0335] 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.  
     [0336] High fidelity amplification was obtained by PCR using methods well known in the art. PCR was performed in 96-well plates using the PTC-200 thermal cycler (MJ Research, Inc.). The reaction mix contained DNA template, 200 nmol of each primer, reaction buffer containing 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.  
     [0337] 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.  
     [0338] 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 w re selected n antiboti-containing media, and individual colonies were picked and cultured overnight at 37° C. in 384-well plates in LB/2×carb liquid media.  
     [0339] 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).  
     [0340] 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.  
     [0341] IX. Labeling and Use of Individual Hybridization Probes  
     [0342] Hybridization probes derived from SEQ ID NO:23-44 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).  
     [0343] 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.  
     [0344] X. Microarrays  
     [0345] 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), supra). 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.).  
     [0346] Full length cDNAs, Expressed Sequence Tags (ESTs), or fragments or oligomers thereof may comprise the elements of the microarray. Fragments or oligomers suitable for hybridization can be selected using software well known in the art such as LASERGENE software (DNASTAR). The array elements are hybridized with polynucleotides in a biological sample. The polynucleotides in the biological sample are conjugated to a fluorescent label or other molecular tag for ease of detection. After hybridization, nonhybridized nucleotides from the biological sample are removed, and a fluorescence scanner is used to detect hybridization at each array element Alternatively, laser desorbtion and mass spectrometry may be used for detection of hybridization. The degree of complementarity and the relative abundance of each polynucleotide which hybridizes to an element on the microarray may be assessed. In one embodiment, microarray preparation and usage is described in detail below.  
     [0347] Tissue or Cell Sample Preparation  
     [0348] 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 (21mer), 1× first strand buffer, 0.03 units/μl RNase inhibitor, 500 μM DATP, 500 μM dGTP, 500 μM dTIP, 40 μM dCIP, 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, Inc. (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 Inc., Holbrook N.Y.) and resuspended in 14 μl 5×SSC/0.2% SDS.  
     [0349] Microarray Preparation  
     [0350] 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 μg. Amplified array elements are then purified using SEPHACRYL-400 (Amersham Pharmacia Biotech).  
     [0351] 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.  
     [0352] 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.  
     [0353] Microarrays are UV-crosslinked using a STRATALINKER UV-crosslinker (Stratagene). Microarrays are washed at room temperature once in 0.2% SDS and three times in distilled water. Non-specific binding sites are blocked by incubation of microarrays in 0.2% casein in phosphate buffered saline (PBS) (Tropix, Inc., Bedford Mass.) for 30 minutes at 60° C. followed by washes in 0.2% SDS and distilled water as before.  
     [0354] Hybridization  
     [0355] 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 larg r 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 ab ut 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.  
     [0356] Detection  
     [0357] Reporter-labeled hybridization complexes are detected with a microscope equipped with an Innova 70 mixed gas 10 W laser (Coherent, Inc., 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, Inc., 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.  
     [0358] 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.  
     [0359] 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.  
     [0360] The output of the photomultiplier tube is digitized using a 12-bit RTI-835H analog-to-digital (A/D) conversion board (Analog Devices, Inc., Norwood 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 tw 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.  
     [0361] A grid is superimposed ver 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).  
     [0362] XI. Complementary Polynucleotides  
     [0363] Sequences complementary to the PKIN-encoding sequences, or any parts thereof, are used to detect, decrease, or inhibit expression of naturally occurring PKIN. 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 PKIN. 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 PKIN-encoding transcript.  
     [0364] XII. Expression of PKIN  
     [0365] Expression and purification of PKIN is achieved using bacterial or virus-based expression systems. For expression of PKIN 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 PKIN upon induction with isopropyl beta-D-thiogalactopyranoside (IPTG). Expression of PKIN 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 PKIN 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 frugiverda  (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.)  
     [0366] In most expression systems, PKIN 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 purificati n 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 PKIN 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 PKIN obtained by these methods can be used directly in the assays shown in Examples XVI, XVII, and XVIII, where applicable.  
     [0367] XIII. Functional Assays  
     [0368] PKIN function is assessed by expressing the sequences encoding PKIN 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 (nitrogen, 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.  
     [0369] The influence of PKIN on gene expression can be assessed using highly purified populations of cells transfected with sequences encoding PKIN and either CD64 or CD64-GFP. CD64 and CD64-GFP are expressed on the surface of transfected cells and bind to conserved regions of human immunoglobulin G (IgG). Transfected cells are efficiently separated from nontransfected cells using magnetic beads coated with either human IgG or antibody against CD64 (DYNAL, Lake Success N.Y.). mRNA can be purified from the cells using methods well known by those of skill in the art Expression of mRNA encoding PKIN and other genes of interest can be analyzed by northern analysis or microarray techniques.  
     [0370] XIV. Production of PKIN Specific Antibodies  
     [0371] PKIN 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.  
     [0372] Alternatively, the PKIN 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.) 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-PKIN activity by, for example, binding the peptide or PKIN to a substrate, blocking with 1% BSA, reacting with rabbit antisera, washing, and reacting with radio-iodinated goat anti-rabbit IgG.  
     [0373] XV. Purification of Naturally Occurring PKIN Using Specific Antibodies  
     [0374] Naturally occurring or recombinant PKIN is substantially purified by immunoaffinity chromatography using antibodies specific for PKIN. An immunoaffinity column is constructed by covalently coupling anti-PKIN 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.  
     [0375] Media containing PKIN are passed over the immunoaffinity column, and the column is washed under conditions that allow the preferential absorbance of PKIN (e.g., high ionic strength buffers in the presence of detergent). The column is eluted under conditions that disrupt antibody/PKIN binding (e.g., a buffer of pH 2 to pH 3, or a high concentration f a chaotrope, such as urea or thiocyanate ion), and PKIN is collected.  
     [0376] XVI. Identification of Molecules which Interact with PKIN  
     [0377] PKIN, 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 PKIN, washed, and any wells with labeled PKIN complex are assayed. Data obtained using different concentrations of PKIN are used to calculate values for the number, affinity, and association of PKIN with the candidate molecules.  
     [0378] Alternatively, molecules interacting with PKIN 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).  
     [0379] PKIN 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).  
     [0380] XVII. Demonstration of PKIN Activity  
     [0381] Generally, protein kinase activity is measured by quantifying the phosphorylation of a protein substrate by PKIN in the presence of gamma-labeled  32 P-ATP. PKIN is incubated with the protein substrate,  32 P-ATP, and an appropriate kinase buffer. The  32 P incorporated into the substrate is separated from free  32 P-ATP by electrophoresis and the incorporated  32 P is counted using a radioisotope counter. The amount of incorporated  32 P is proportional to the activity of PKIN. A determination of the specific amino acid residue phosphorylated is made by phosphoamino acid analysis of the hydrolyzed protein.  
     [0382] In one alternative, protein kinase activity is measured by quantifying the transfer of gamma phosphate from adenosine triphosphate (ATP) to a serine, threonine or tyrosine residue in a protein substrate. The reaction occurs between a protein kinase sample with a biotinylated peptide substrate and gamma  32 P-ATP. Following the reaction, free avidin in solution is added for binding to the biotinylated  32 P-peptide product. The binding sample then undergoes a centrifugal ultrafiltration process with a membrane which will retain the product-avidin complex and allow passage of free gamma  32 P-ATP. The reservoir of the centrifuged unit containing the  32 P-peptide product as retentate is then counted in a scintillation counter. This procedure allows assay of any type of protein kinase sample, depending on the peptide substrate and kinase reaction buffer selected. This assay is provided in kit form (ASUA, Affinity Ultrafiltration Separation Assay, Transbio Corporation, Baltimore Md., U.S. Pat. No. 5,869,275). Suggested substrates and their respective enzymes are as follows: Histone H1 (Sigma) and p34 cdc2 kinase, Annexin I, Angiotensin (Sigma) and EGF receptor kinase, Annexin II and src kinase, ERK1 &amp; ERK2 substrates and MEK, and myelin basic protein and ERK (Pearson, J. D. et al. (1991) Methods in Enzymology 200:62-81).  
     [0383] In another alternative, protein kinase activity of PKIN is demonstrated in vitro in an assay containing PKIN, 50 μl of kinase buffer, 1 μg substrate, such as myelin basic protein (MBP) or synthetic peptide substrates, 1 mM DTT, 10 μg ATP, and 0.5 μCi [γ 33 P]ATP. The reaction is incubated at 30° C. for 30 minutes and stopped by pipetting onto P81 paper. The unincorporated [γ- 33 P]ATP is removed by washing and the incorporated radioactivity is measured using a radioactivity scintillation counter. Alternatively, the reaction is stopped by heating to 100° C. in the presence of SDS loading buffer and visualized on a 12% SDS polyacrylamide gel by autoradiography. Incorporated radioactivity is corrected for reactions carried out in the absence of PKIN or in the presence of the inactive kinase, K38A.  
     [0384] In yet another alternative, adenylate kinase or guanylate kinase activity may be measured by the incorporation of  32 P from gamma-labeled  32 P-ATP into ADP or GDP using a gamma radioisotope counter. The enzyme, in a kinase buffer, is incubated together with the appropriate nucleotide mono-phosphate substrate (AMP or GMP) and  32 P-labeled ATP as the phosphate donor. The reaction is incubated at 37° C. and terminated by addition of trichloroacetic acid. The acid extract is neutraliz and subjected to gel electrophoresis to separate the mono-, di-, and triphosphonucleotide fractions. The diphosphonucleotide fraction is cut out and counted. The radioactivity recovered is proportional to the enzyme activity.  
     [0385] In yet another alternative, other assays for PKIN include scintillation proximity assays (SPA), scintillation plate technology and filter binding assays. Useful substrates include recombinant proteins tagged with glutathione transferase, or synthetic peptide substrates tagged with biotin. Inhibitors of PKIN activity, such as small organic molecules, proteins or peptides, may be identified by such assays.  
     [0386] Kinase activity of PKIN may be determined by its ability to convert polyphosphate substrate (PolyP) to ATP in the presence of ADP. PKIN and Poly P are incubated at 37° C. for 40 minutes and then at 90° C. for 2 minutes in a buffer containing 50 mM Tris-HCl, pH 7.4, 40 mM ammonium sulfate, 4 mM MgCl 2 , and 5 μM ADP. The reaction mixture is diluted 1:100 in 100 mM Tris-HCl (pH 8.0), 4 mM EDTA, which is then diluted 1:1 in luciferase reaction mixture (ATP Bioluminescence Assay Kit CLS II; Boehringer Mannheim). The ATP generated is then quantitated using a luminometer (Kornberg, A. et al. (1999) Annu. Rev. Biochem. 68:89-125; Ault-Riché, D. et al. (1998) J. Bacteriol. 180:1841-1847).  
     [0387] Kinase activity of PKIN, as measured by phosphorylation of substrate, may be determined using an immune complex kinase assay well known in the art. COS7 cells are transfected with an expression plasmid constructed from a FLAG tag expression vector (pME18S-FLAG) containing PKIN DNA. A control transfection using vector alone without the PKIN DNA insert is done in parallel. After 48 hours, the cells are lysed in buffer A (20 mM HEPES-NaOH, pH 7.5, 3 mM MgCl 2 , 100 mM NaCl 2 , 1 mM dithiothreitol, 1 mM phenylmethanesulfonyl fluoride, 1 μg/ml leupeptin, 1 mM EGTA, 1 mM Na 3 Vo 4 , 10 mM NaF, 20 mM β-glycerophosphate, and 0.5% Triton X-100) and centrifuged at 14,000 rpm. Supernatants are incubated with anti-FLAG antibody (M2 monoclonal antibody; Eastman Kodak Co.) in a 50% slurry of protein A-Sepharose (Amersham Pharmacia Biotech) for 1.5 hours at 4° C. Immune complexes are precipitated and washed twice in buffer A and twice in buffer B (20 mM HEPES-NaOH, pH 7.5, 1 mM dithiothreitol, 10 μM Na 3 Vo 4 , 2 mM β-glycerophosphate, 0.1 mM phenylmethanesulfonyl fluoride, 0.1 μg/ml leupeptin, 0.1 mM EGTA.) Precipitates are incubated in buffer B containing 0.17 mg/ml myelin basic protein (MBP) (Sigma), 20 μM ATP, and 5 μCi of [γ- 32 P]ATP (NEN Life Science Products) at 30° C. for 20 minutes. The reaction is stopped by the addition of 4× Laemmli sample buffer (50 mM Tris-HCl, pH 6.8, 2% SDS, 30 mM dithiothreitol, and 10% glycerol) and heated at 95° C. for 5 minutes. Proteins are separated by SDS-polyacrylamide gel electrophoresis and radioactivity incorporated into MBP is detected by autoradiography (Nakano, K. et al. (2000) J. Biol. Chem. 275:20533-20539.)  
     [0388] In yet another alternative, an assay for PanK activity of PKIN includes the enzyme preparation method as described in Vallari, D. S. et al., (1987) J. Biol. Chem. 262:2468-247. Pantothenate kinase-specific activities in cell lysates are calculated as a function of protein concentration with the assay being linear with respect to both time and protein input. Protein concentrations are measured using the Bradford assay using bovine γ-globulin as a standard. Standard assays contain D-[1- 14 C]pantothenate (45.5 μM; specific activity 55 mCi/mmol), ATP (2.5 mM, pH 7.0), MgCl 2  (2.5 mM), Tris-HCl (0.1 M, pH 7.5), and 15 μg of protein from a soluble cell extract in a total volume of 40 μl. The mixture is incubated for 10 min. at 37° C., and the reaction is stopped by depositing a 30-μl aliquot onto a Whatman DE81 ion-exchange filter disc which is then washed in three changes of 1% acetic acid in 95% ethanol (25 ml/disc) to remove unreacted pantothenate. 4′-Phosphopantothenate is quantitated by counting the dried disc in 3 ml of scintillation solution (Rock, supra).  
     [0389] XVIII. Enhancement/Inhibition f Protein Kinase Activity  
     [0390] Agonists or antagonists of PKIN activation or inhibition may be tested using assays described in section XVII. Agonists cause an increase in PKIN activity and antagonists cause a decrease in PKIN activity.  
     [0391] 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                           Poly-                       peptide       Incyte   SEQ   Incyte   Polynucleotide   Incyte       Project ID   ID NO:   Polypeptide ID   SEQ ID NO:   Polynucleotide ID                                                    7482896   1   7482896CD1   23   7482896CB1       7483046   2   7483046CD1   24   7483046CB1       71636374   3   71636374CD1   25   71636374CB1       7480597   4   7480597CD1   26   7480597CB1       3227248   5   3227248CD1   27   3227248CB1       4207273   6   4207273CD1   28   4207273CB1       7483334   7   7483334CD1   29   7483334CB1       7483337   8   7483337CD1   30   7483337CB1       6035509   9   6035509CD1   31   6035509CB1       7373485   10   7373485CD1   32   7373485CB1       5734965   11   5734965CD1   33   5734965CB1       7473788   12   7473788CD1   34   7473788CB1       3107989   13   3107989CD1   35   3107989CB1       7482887   14   7482887CD1   36   7482887CB1       2963414   15   2963414CD1   37   2963414CB1       7477139   16   7477139CD1   38   7477139CB1       55009053   17   55009053CD1   39   55009053CB1       7474648   18   7474648CD1   40   7474648CB1       7483053   19   7483053CD1   41   7483053CB1       7483117   20   7483117CD1   42   7483117CB1       7484498   21   7484498CD1   43   7484498CB1       7638121   22   7638121CD1   44   7638121CB1                  
 
     [0392]                               TABLE 2                       Polypeptide   Incyte Polypeptide   GenBank ID   Probability           SEQ ID NO:   ID   NO:   Score   GenBank Homolog                                                    1   7482896CD1   g852055   2.90E−167   [ Homo sapiens ] casein kinase I-alpha                       Fish, K. J. et al., (1995) J. Biol. Chem. 270: 14875-14883       2   7483046CD1   g2736151   4.20E−167   [ Rattus norvegicus ] mytonic dystrophy kinase-related                       Leung, T. et al., (1998) Mol. Cell. Biol. 18: 130-140       3   71636374CD1   g7549223   0   [ Mus musculus ] PALS1                       (proteins associated with Lin-7, a membrane-associated guanylate kinase)                       Kamberov, E. et al., (2000) J. Biol. Chem. 275: 11425-11431       4   7480597CD1   g2224679   1.40E−97   [ Homo sapiens ] KIAA0369 doublecortin-like kinase                       Nagase, T. et al., (1997) DNA Res. 4: 141-150                       Burgess, H. A. et al. (1999) J. Neurosci. Res. 58: 567-575       5   3227248CD1   g6690020   4.90E−199   [ Mus musculus ] pantothenate kinase 1 beta                       Rock, C. O. et al. (2000) J. Biol. Chem. 275: 1377-1383       6   4207273CD1   g4028547   4.70E−68   [ Dictyostelium discoideum ] MEK kinase alpha                       Chung, C. Y. et al. (1998) Genes Dev. 12: 3564-3578       7   7483334CD1   g479173   1.70E−251   [ Homo sapiens ] protein kinase                       Schultz, S. J. et al. (1994) Cell Growth Differ. 5: 625-635       8   7483337CD1   g9280288   3.10E−27   [ Arabidopsis thaliana ] receptor protein kinase                       Kaneko, T. et al. (2000) DNA Res. 7: 217-221       9   6035509CD1   g6110362   3.60E−76   [ Homo sapiens ] Traf2 and NCK interacting kinase, splice variant 7                       Fu, C. A. et al. (1999) J. Biol. Chem. 274: 30729-30737       10   7373485CD1   g4200446   0   [ Mus musculus ] FYVE finger-containing phosphoinositide kinase                       Shisheva, A. et al. (1999) Mol. Cell. Biol. 19: 623-634       11   5734965CD1   g2905643   4.60E−109   [ Klebsiella pneumoniae ] ribitol kinase                       Heuel H, et al. (1998) Microbiology 144(Pt 6): 1631-9       12   7473788CD1   g7160989   1.70E−148   [ Homo sapiens ] serine/threonine protein kinase                       Ruiz-Perez VL, et al. (2000) Nat. Genet. 24(3): 283-6       13   3107989CD1   g6690020   1.60E−129   [ Mus musculus ] pantothenate kinase 1 beta                       Rock, C. O. et al. (2000) J. Biol. Chem. 275: 1377-1383       14   7482887CD1   g205662   3.90E−48   [ Rattus norvegicus ] nucleoside diphosphate kinase                       Kimura, N. et al. J. Biol. Chem. (1990) 265: 15744-15749       15   2963414CD1   g6524024   8.90E−106   [ Mus musculus ] mammalian inositol hexakisphosphate kinase 1                       Saiardi, A. et al. Curr. Biol. (1999) 9: 1323-1326       16   7477139CD1   g6472874   0   [ Mus musculus ] Nck-interacting kinase-like embryo specific kinase                       Nakano, K. et al. J. Biol. Chem. (2000) 275: 20533-20539       17   55009053CD1   g15131540   0   [f1][ Homo sapiens ] (AJ316534) serine/threonine protein kinase       18   7474648CD1   g14346040   0   [f1][ Homo sapiens ] serine/threonine kinase PSKH2       19   7483053CD1   g5419753   0   [ Homo sapiens ] RET tyrosine kinase receptor                       Bordeaux, M. C. et al. (2000) EMBO J. 19: 4056-4063       20   7483117CD1   g644770   2.70E−136   [ Xenopus laevis ] Wee1A kinase                       Mueller, P. R. et al. (1995) Mol. Biol. Cell 6: 119-134       21   7484498CD1   g3599509   0   [ Mus musculus ] rho/rac-interacting citron kinase                       Di Cunto, F. et al. (1998) J. Biol. Chem. 273: 29706-29711       22   7638121CD1   g212661   1.20E−60   [ Gallus gallus ] smooth muscle myosin light chain kinase precursor                       Olson, N. J. et al. (1990) Proc. Natl. Acad. Sci. U.S.A. 87: 2284-2288                    
     [0393]                                       TABLE 3                                               Analytical       SEQ       Amino               Methods       ID   Incyte   Acid   Potential Phosphorylation   Potential       and       NO:   Polypeptide ID   Residues   Sites   Glycosylation Sites   Signature Sequences, Domains and Motifs   Databases                                                            1   7482896CD1   337   S105 S122 S199 S237   N167 N215 N3   Eukaryotic protein kinase domain: Y17-F211   HMMER-                   S242 S27 S49 S7 S96           PFAM                   T109 T146 T184 T228       Protein kinases signatures and profile: T112-R168   PROFILE-                   T243 T323 T327 T38           SCAN                   Y209 Y274       PROTEIN KINASE DOMAIN DM00004   BLAST-                           P35506|19-273: L19-Y274   DOMO                           P54367|22-276: L19-Y274                           P48730|11-265: L19-Y274                           B56406|19-273: L19-Y274                           CASEIN KINASE I TRANSFERASE   BLAST-                           SERINE/THREONINE PROTEIN ATP-BINDING   PRODOM                           ISOFORM ALPHA CKI ALPHA MULTIGENE                           PD006522: R282-G324                           Tyrosine kinase catalytic domain PR00109: Y126-   BLIMPS-                           M144   PRINTS                           Kinase Protein Domain PD00584: V20-G29   BLIMPS-                               PRODOM                           Protein kinases ATP-binding region signature: I23-   MOTIFS                           K46                           Serine/Threonine protein kinases active-site signature:   MOTIFS                           F132-M144                           signal_cleavage: M1-G40   SPSCAN       2   7483046CD1   475   S161 S280 S307 S363       Eukaryotic portein kinase domain: F71-F337   HMMER-                   S407 S430 T455           PFAM                           PROTEIN KINASE DOMAIN DM00004|   BLAST-                           Q09013|83-336: I73-R325   DOMO                           S42867|75-498: I73-H252                           I38133|90-369: E72-L220                           P53894|353-658: L74-G215                           KINASE PHORBOLESTER BINDING   BLAST-                           DYSTROPHY KINASE RELATED CDC42   PRODOM                           BINDING SIMILAR SERINE/THREONINE                           PROTEIN GENGHIS KHAN PD012280: L25-D70                           Tyrosine kinase catalytic domain PR00109: M148-   BLIMPS-                           S161, S185-L203, C257-E279   PRINTS                           Protein kinase C terminal domain: P351-D366   HMMER-                               PFAM                           Protein kinases ATP-binding region signature: I77-   MOTIFS                           K100                           Serine/Threonine protein kinases active-site signature:   MOTIFS                           Y191-L203                           signal_cleavage: M1-S37   SPSCAN       3   71636374CD1   675   S130 S14 S143 S25 S383   N82   Guanylate kinase: T515-I624   HMMER-                   S432 S517 S562 S569           PFAM                   S576 S581 S646 S84       GUANYLATE KINASE DM00755   BLAST-                   T137 T253 T270 T422       A57653|370-570: P475-P670   DOMO                   T465 T514 T558 T584       P54936|769-955: R478-P670                   T97 Y593       I38757|709-898: Q474-P670                           P31016|529-718: R480-P670                           PROTEIN DOMAIN SH3 KINASE GUANYLATE   BLAST-                           TRANSFERASE ATPBINDING REPEAT GMP   PRODOM                           MEMBRANE PD001338: T514-E620                           SIMILAR TO GUANYLATE KINASE PD065809:   BLAST                           G41-Q337   PRODOM                           Guanylate kinase protein BL00856: V511-V531,   BLIMPS-                           D539-R586   BLOCKS                           SH3 domain signature PR00452: D386-E395, I348-   BLIMPS-                           P358, L369-Q384   PRINTS                           PDZ domain (Also known as DHR or GLGF). PDZ:   HMMER-                           I256-S335,   PFAM                           SH3 domain SH3: I348-Q415   HMMER-                               PFAM                           ATP/GTP-binding site motif A (P-loop): A404-S411   MOTIFS                           Guanylate_Kinase signature and profile: T514-V531   MOTIFS       4   7480597CD1   835   S11 S153 S174 S223   N768   Eukaryotic protein kinase domain pkinase: Y543-I800   HMMER-                   S249 S271 S292 S349           PFAM                   S369 S380 S389 S393       Protein kinases signatures and profile: D640-I697   PROFILE-                   S405 S525 S54 S59 S633           SCAN                   S713 T129 T194 T246       PROTEIN KINASE DOMAIN DM00004   BLAST-                   T278 T300 T319 T33       S57347|21-266: V548-T790   DOMO                   T451 T477 T499 T514       P08414|44-285: I549-T790                   T545 T610 T63 T681       A44412|16-262: I549-A791                   T790 T808       JU0270|16-262: I549-A791                           KINASE PROTEIN TRANSFERASE ATP-   BLAST-                           BINDING SERINE/THREONINE PROTEIN   PRODOM                           PHOSPHORYLATION RECEPTOR TYROSINE                           PROTEIN PRECURSOR TRANSMEMBRANE                           PD000001: E609-V693                           Octicosapeptide repeat p PF00564: Y543-S597, H605-   BLIMPS-                           M655, K473-G526   PFAM                           Tyrosine kinase catalytic domain PR00109: L618-   BLIMPS-                           I631, H654-V672   PRINTS                           Protein kinases ATP-binding region signature: I549-   MOTIFS                           K572                           Serine/Threonine protein kinases active-site signature:   MOTIFS                           I660-V672       5   3227248CD1   373   S100 S283 S285 S330   N103 N72                   S47 T10 T167 T209                   T226 T230 T244 T34       6   4207273CD1   735   S100 S111 S113 S124   N289 N312 N341   PROTEIN KINASE DOMAIN   BLAST-                   S152   N392    DM00004|A48084|98-348:   DOMO                   S170 S179 S185   N400 N61   K470-A722 DM00004|Q01389|1176-1430: K470-                   S186 S20 S202 S215   N624 N647   A722 DM00004|P41892|11-249: G471-R719                   S221 S225 S240 S267       DM00004|Q10407|826-1084: K470-A722                   S271 S302 S459 S503       KINASE PROTEIN TRANSFERASE ATP-   BLAST-                   S729 S9 T10 T105 T13       BINDING SERINE/THREONINE PROTEIN   PRODOM                   T30 T402 T417 T425       PHOSPHORYLATION RECEPTOR TYROSINE                   T469 T626 T663 T669       PROTEIN PRECURSOR TRANSMEMBRANE                   T84 Y512       PD000001: L631-P673, E472-C537, Y533-S633,                           S701-S734                           Tyrosine kinase catalytic domain signature   BLIMPS-                           PR00109: M547-N560, Y583-L601, G636-I646, S655-   PRINTS                           M677                           Eukaryotic protein kinase domain pkinase: W468-   HMMER-                           L731   PFAM                           Protein_Kinase_Atp L474-K496   MOTIFS                           Protein_Kinase_St V589-L601   MOTIFS                           Protein kinases signatures and profile   PROFILE-                           protein_kinase_tyr.prf: V569-A619   SCAN       7   7483334CD1   506   S148 S206 S243 S319   N181 N345 N377   PROTEIN KINASE DOMAIN DM00004   BLAST-                   S325 S354 S47 T197   N401   P51954|6-248: L7-S247   DOMO                   T288 T293 T308 T321       P51957|8-251: L7-S247                   T373 T386 T402 T403       P51955|10-261: V6-S247                   T479       Q08942|22-269: M9-S247                           Tyrosine kinase catalytic domain signature   BLIMPS-                           PR00109: M79-K92, H117-L135, S183-N205, Y226-   PRINTS                           A248                           Eukaryotic protein kinase domain pkinase:   HMMER-                           Y4-V257   PFAM                           Protein_Kinase_Atp I10-K33   MOTIFS                           Protein_Kinase_St V123-L135   MOTIFS                           Protein kinases signatures and profile   PROFILE-                           protein_kinase_tyr.prf: M103-M156   SCAN       8   7483337CD1   2014   S1076 S1151 S1177   N1024 N1119   PROTEIN KINASE DOMAIN DM00004   BLAST-                   S1217 S1274 S1279   N1338 N1599   I38044|100-349: I1295-P1549   DOMO                   S1454 S15 S1515 S1679   N1674 N307 N371   I49663|194-437: E1341-P1549                   S1700 S1811 S1833   N409   A53800|119-368: R1343-P1549                   S1887 S1890 S1999       S29851|157-404: E1341-P1549                   S203 S25 S321 S337       Tyrosine kinase catalytic domain signature PR00109:   BLIMPS-                   S401 S531 S56 S565       Y1414-V1432, V1483-H1505, Q1529-A1551   PRINTS                   S599 S81 S843 S863       transmembrane domain transmem_domain: P1367-   HMMER                   S887 S900 T1091 T1099       N1387                   T1113 T1187 T1189       Eukaryotic protein kinase domain pkinase: E1280-   HMMER-                   T1234 T1401 T1543       P1549   PFAM                   T1605 T1634 T1660       Protein kinases signatures and profile   PROFILE-                   T1872 T1895 T2010       protein_kinase_tyr.prf: L1400-E1457   SCAN                   T280 T494 T517 T524                   T533 T537 T680 T687       Atp_Gtp_A G672-S679   MOTIFS                   T699 T702 T703 T753                   T795 T811 T835 T909                   Y1225 Y1997 Y907       9   6035509CD1   348   S101 S171 S199 S271   N177   PROTEIN KINASE DOMAIN DM00004   BLAST-                   S50 S7 T178 T213 T311       P10676|18-272: I17-P270   DOMO                   T318 T33       A53714|17-262: I17-S271                           P38692|24-266: E19-S271                           P08458|20-262: I21-S271                           Tyrosine kinase catalytic domain signature   BLIMPS-                           PR00109: H134-L152, G181-I191, W250-V272   PRINTS                           Eukaryotic protein kinase domain pkinase: W15-I281   HMMER-                               PFAM                           Protein_Kinase_Atp I21-K44   MOTIFS                           Protein_Kinase_St I140-L152   MOTIFS                           Protein kinases signatures and profile   PROFILE-                           protein_kinase_tyr.prf: M120-T172   SCAN       10   7373485CD1   2042   S1020 S105 S1079   N1061 N1274   Probable phosphatidyl inositol 4-phosphate 5-kinase   BLAST-                   S1125 S1130 S1148 S13   N1647 N1671   FAB1 EC 2.7.1.68 1-phosphatidyl inositol 4-   PRODOM                   S1377 S1419 S1429   N1870 N303 N310   phosphate 5-kinase diphosphoinositide transferase                   S1440 S1466 S1483   N333   PD136025: H461-F821, W1147-K1437, L1375-                   S1488 S1544 S1545       S1702, K638-K767, P1663-V1780, D1372-Q1458,                   S1620 S1639 S1648       F959-I1069, R960-D1053, F200-R262, D1895-                   S168 S1685 S1703       S1950; PD041996: L1974-W2035                   S1784 S1785 S1830       5-KINASE PHOSPHATIDYL INOSITOL 4-   BLAST-                   S1899 S228 S244 S257       PHOSPHATE KINASE TYPE TRANSFERASE   PRODOM                   S261 S286 S291 S367       DIPHOSPHOINOSITIDE 1-PHOSPHATIDYL                   S423 S475 S502 S576       INOSITOL 4-PHOSPHATE II ALPHA                   S789 S810 S835 S85       PHOSPHATIDYL INOSITOL PD002308: P1751-                   S872 S896 S977 T1005       G1966, L1974-F2028, I493-H533                   T1013 T109 T1149       FYVE zinc finger FYV: Q153-C213   MOTIFS                   T1295 T1386 T1524       Phosphatidylinositol-4-phosphate 5-Kinase   MOTIFS                   T1567 T1670 T1674       PIP5: R1791-F2028                   T1681 T1708 T1722                   T173 T1743 T1813                   T1852 T1872 T1909                   T1970 T341 T342 T591                   T666 T731 T782 T976                   T984 Y1290                   Y1716 Y1933 Y659       11   5734965CD1   551   S107 S176 S2 S21 S257   N127 N219   FGGY family of carbohydrate kinases: L423-A490   HMMER-                   S368 S502 S54 T183           PFAM                   T286 T334 T356 T403       FGGY FAMILY OF CARBOHYDRATE KINASES   BLAST-                   T66 Y526 Y531       DM01757|P21939|1-480: V13-A184   DOMO                           XYLULOKINASE DM02388|P18157|1-492: T383-   BLAST-                           E539   DOMO                           FGGY FAMILY OF CARBOHYDRATE KINASES   BLAST-                           DM01757|P37677|1-479: R10-D260   DOMO                           FGGY FAMILY OF CARBOHYDRATE KINASES   BLAST-                           DM01757|P46834|1-488: Y11-V268   DOMO                           MPA43 PROTEIN PD130314: V13-I210   BLAST-                               PRODOM                           FGGY family of carbohydrate kinases proteins   BLIMPS-                           BL00933: Y11-L34, R109-A119, V137-N156, G456-   BLOCKS                           I471       12   7473788CD1   485   S10 S159 S3 S343 S362   N405   Eukaryotic protein kinase domain: F93-Q345   HMMER-                   S415 S417 T115 T192           PFAM                   T466 T469 T76 Y119       PROTEIN KINASE DOMAIN   BLAST-                           DM00004|P54644|122-362: I95-S342   DOMO                           PROTEIN KINASE DOMAIN   BLAST-                           DM00004|P28178|155-393: I95-L341   DOMO                           PROTEIN KINASE DOMAIN DM08046   BLAST-                           P05986|1-397: K65-P372   DOMO                           P06244|1-396: F93-P372                           Tyrosine kinase catalytic domain signature   BLIMPS-                           PR00109: V170-Q183, Y206-L224   PRINTS                           Protein kinases ATP-binding region signature I99-   MOTIFS                           K122                           Serine/Threonine protein kinases active-site signature   MOTIFS                           I212-L224                           signal_cleavage: M1-A24   SPSCAN       13   3107989CD1   282   S148 S152 S192 S194   N12   signal_cleavage: M1-A27   SPSCAN                   S239 S78 T118 T138                   T139 T153 T36       14   7482887CD1   151   S42 S97 T35 Y141       NUCLEOSIDE DIPHOSPHATE KINASES   BLAST-                           DM00773|P48817|3-152: I7-Y150   DOMO                           DM00773|I39074|19-168: I7-Y150                           DM00773|Q07661|1-148: I7-Y150                           DM00773|P50590|1-150: I7-Y150                           KINASE DIPHOSPHATE NUCLEOSIDE   BLAST-                           TRANSFERASE NDK NDP ATP-BINDING   PRODOM                           PROTEIN I PRECURSOR PD001018: I7-Y150                           Nucleoside diphosphate kinases proteins   BLIMPS-                           BL00469: E77-L131   BLOCKS                           Nucleoside diphosphate kinases NDK: I7-A151   HMMER-                               PFAM                           Nucleoside diphosphate kinases active site   PROFILE-                           ndp_kinases: G96-R142   SCAN       15   2963414CD1   410   S134 S156 S276 S318   N117 N290   PROTEIN ARGININE METABOLISM   BLAST-                   T259 T361 T374 T383       REGULATION III TRANSCRIPTION   PRODOM                   T62       SIMILARITY SACCHAROMYCES CEREVISIAE                           PUTATIVE                           PD011544: S188-Q333, S355-L403                           PUTATIVE BZIP TRANSCRIPTION FACTOR   BLAST-                           CHROMOSOME IV READING FRAME ORF   PRODOM                           YDR017C PD024140: G15-R197                           Aldo/keto reductase family putative active site   MOTIFS                           signature I312-L327       16   7477139CD1   1581   S101 S1107 S1112   N1137 N1201 N146   PROTEIN KINASE DOMAIN   BLAST-                               DOMO                   S1139 S1178 S1233   N654 N668 N990   DM00004|P10676|18-272: Y83-P302                   S1291 S1346 S136       DM00004|A53714|17-262: L43-S304                   S1400 S1426 S1435       DM00004|P38692|24-266: S84-C293, K29-N57                   S148 S1537 S1577 S211       DM00004|P50527|388-627: K77-S304, I31-E65                   S283 S376 S498 S580                   S671 S676 S700 S709                   S718 S749 S807 S84                   S890 S891 S892 S910                   T1071 T1123 T1194                   T1367 T1508 T1546                   T1556 T246 T276 T294                   T357 T573 T664 T690                   T899 T981 T992       17   55009053CD1   1084   S1024 S1031 S1038   N953   Serine/Threonine protein kinases active-site signature   MOTIFS                   S1042 S1058 S157 S172       I139-I151                   S231 S25 S422 S452       Protein kinases signatures and profile   PROFILE-                   S478 S52 S521 S552       protein_kinase_tyr.prf: L118-F173   SCAN                   S569 S604 S623 S709       Eukaryotic protein kinase domain pkinase: L15-F273   HMMER-                   S80 S862 S882 S895           PFAM                   S914 S962 S968 S969       Tyrosine kinase catalytic domain PR00109: T95-   BLIMPS-                   S981 S988 T102 T1037       R108, H133-I151, V197-C219, K242-I264   PRINTS                   T167 T230 T256 T263       PROTEIN KINASE DOMAIN DM00004 S49611|   BLAST-                   T37 T420 T48 T543       39-259: I21-K242 Q05609|553-797: E20-C253   DOMO                   T593 T631 T8 Y1005       P51957|8-251: I21-R261 P41892|11-249: I21-R261       18   7474648CD1   600   S206 S331 S369 S425   N18 N495   Protein kinases ATP-binding region signature I284-   MOTIFS                   S456 S543 S55 S571       K307                   S577 S585 T117 T14       Eukaryotic protein kinase domain pkinase: Y278-   HMMER-                   T25 T299 T300 T356       V535   PFAM                   T371 T395 T433 T58       Tyrosine kinase catalytic PR00109: M352-I365,   BLIMPS-                           Y388-Y406, V458-E480   PRINTS                           PROTEIN KINASE DOMAIN DM00004 S57347|   BLAST-                           21-266: D279-L516 P08414|44-285: I280-S525   DOMO                           JN0323|25-268: I284-R523 S46284|28-274:                            I284-A526       19   7483053CD1   1114   S1034 S104 S110 S131   N1092 N151 N199   signal peptide: M1-G28   HMMER                   S159 S173 S224 S363   N336 N343 N361   Signal_cleavage: M1-A26   SPSCAN                   S413 S457 S522 S561   N367 N377 N394   Transmembrane domain: L13-F31   HMMER                   S65 S670 S691 S696   N448 N468 N554   Protein kinases ATP-binding region signature L730-   MOTIFS                   S765 S811 S819 S836   N834 N975 N98   K758                   S922 T1022 T1055       Tyrosine protein kinases specific active-site signature   MOTIFS                   T1078 T261 T295 T315       L870-V882                   T328 T350 T456 T492       Protein kinases signatures and profile   PROFILE-                   T538 T564 T675 T729       protein_kinase_tyr.prf: D850-D903   SCAN                   T75 T847 T930 Y1096       Receptor tyrosine kinase class II signature   PROFILE-                   Y483 Y905       receptor_tyr_kin_ii.prf: R878-D925   SCAN                           Cadherin domain cadherin: P172-T261   HMMER-                               PFAM                           Eukaryotic protein kinase domain pkinase: L724-   HMMER-                           L1005   PFAM                           Receptor tyrosine kinase BL00239: D903-Y952,   BLIMPS-                           P957-I1001, E775-V822, L851-R873, A876-E901   BLOCKS                           BL00240: K716-A764, A764-E818, D850-K887,                           E902-G949, G949-I1001 BL00790: G748-L801,                           A855-A876, A877-D903, Q910-W942, H968-L1016                           Tyrosine kinase catalyti PR00109: V804-R817, Y864-   BLIMPS-                           V882, I913-L923, S932-G954, C976-F998   PRINTS                           RECEPTOR KINASE PRECURSOR SIGNAL RET   BLAST-                           TYROSINE PROTOONCOGENE TYROSINE   PRODOM                           CRET TRANSFERASE PD014372: P273-K666,                           D300-V725; PD014143: Y30-C197; PD007958:                           V1010-G1063, PD010335: M1064-S1114                           PROTEIN-TYROSINE KINASE RET DM05080   BLAST-                           P07949|302-723: D302-L724 I48735|303-724: D302-   DOMO                           L724 PROTEIN KINASE DOMAIN DM00004                           JN0290|88-360: V725-F998 P07949|725-997: V725-                           F998       20   7483117CD1   567   S162 S17 S206 S243   N15 N332   Protein kinases ATP-binding region signature I218-   MOTIFS                   S278 S543 S552 S70       K241                   T112 T125 T22 T246       Serine/Threonine protein kinases active-site signature   MOTIFS                   T544 T559 T68 Y238       M335-I347                           Eukaryotic protein kinase domain pkinase: F212-L480   HMMER                               PFAM                           Tyrosine kinase catalytic site PR00109: N289-S302,   BLIMPS-                           Y329-I347, A415-G437, L455-A477   PRINTS                           WEEI HOMOLOG WEEILIKE PROTEIN KINASE   BLAST-                           MITOSIS TRANSFERASE TYROSINEPROTEIN   PRODOM                           ATPBINDING PHOSPHORYLATION PD028078:                           N483-G561                           PROTEIN KINASE DOMAIN DM00004   BLAST-                           P47817|211-470: L213-A477 P30291|300-559: E214-   DOMO                           A477 P54350|241-507: E214-A477 A57247|104-343:                           K217-I347, A366-R474       21   7484498CD1   2054   S81 S93 S140 S248 S308   N835 N1622 N1745   CNH (NIK-1 like kinase) domain: L1619-Y1916   HMMER-                   S361 S381 S386 S410   N1768       PFAM                   S436 S445 S480 S487       Phorbol esters/diacylglycerol binding: H1390-C1438   HMMER-                   S501 S516 S529 S546           PFAM                   S577 S582 S699 S883       PH (pleckstrin homology) domain: L1471-A1590   HMMER-                   S888 S924 S1031 S1049           PFAM                   S1097 S1158 S1160       Eukaryotic protein kinase domain: F97-F360   HMMER-                   S1234 S1315 S1364           PFAM                   S1365 S1370 S1371       Phorbol esters/diacylglycerol binding domain   PROFILE-                   S1377 S1574 S1845       dag_pe_binding_domain.prf: C1403-E1466   SCAN                   S1915 S1933 S2014       Tyrosine kinase catalytic domain signature PR00109:   BLIMPS-                   S2028 T83 T378 T498       S211-V229, C284-G306, M174-N187   PRINTS                   T604 T840 T951 T956       Domain found in NIK1-like kinase, mouse citron and   BLIMPS-                   T989 T1041 T1062       yeast ROM1, ROM2 PF00780: K534-I542, N891-   PFAM                   T1112 T1186 T1231       T933, I964-Q975, Q1015-Q1067, Q1217-E1255,                   T1309 T1326 T1336       I1388-L1434, E1759-A1802, N1819-F1831, K1851-                   T1372 T1543 T1583       Q1880                   T1775 T1787 T1943       CITRON PROTEIN COILED COIL   BLAST-                   T1955 T1961 T2015       RHO/RACINTERACTING KINASE   PRODOM                   Y763       PD155701: F859-L1071                           PD143273: G1439-V1631                           PD082663: L1201-P1389                           PD143272: A1881-V2054                           PROTEIN KINASE DOMAIN DM00004   BLAST-                           Q09013|83-336: V99-L349   DOMO                           S42867|75-498: S101-G241, I258-S445                           S42864|41-325: E98-G241, N249-L349                           P53894|353-658: L102-G241 I258-L349                           Protein kinases ATP-binding region signature V103-   MOTIFS                           K126                           Serine/Threonine protein kinases active-site signature:   MOTIFS                           Y217-V229                           Leucine zipper pattern: L854-L875, L991-L1012,   MOTIFS                           L1057-L1078, L1159-L1180                           Carbamoyl-phosphate synthase subdomain signature   MOTIFS                           2: M1172-S1179                           Phorbol esters/diacylglycerol binding domain:   MOTIFS                           H1390-C1438       22   7638121CD1   1665   S97 S152 S156 S163   N1005   Immunoglobulin domain: G68-A128, G1174-V1235   HMMER-                   S242 S364 S450 S459           PFAM                   S491 S493 S528 S536       Eukaryotic protein kinase domain: Y165-F418, F1369-   HMMER-                   S588 S762 S827 S875       L1621   PFAM                   S915 S917 S929 S947       Protein kinases signatures and profile   PROFILE-                   S961 S997 S1087 S1147       protein_kinase_tyr.prf: E260-A314   SCAN                   S1203 S1336 S1351       Tyrosine kinase catalytic domain signature PR00109:   BLIMPS-                   S1365 S1391 S1434       S341-E363, L387-A409, L238-Y251, Y274-M292   PRINTS                   S1446 S1459 S1461       KINASE PROTEIN TRANSFERASE ATPBINDING   BLAST-                   S1521 T59 T230 T257       SERINE/THREONINEPROTEIN   PRODOM                   T312 T668 T870 T966       PHOSPHORYLATION RECEPTOR                   T1211 T1310 T1320       TYROSINEPROTEIN PRECURSOR                   T1638       TRANSMEMBRANE PD000001: V256-V327, S323-                           D365, S380-P423                           PROTEIN KINASE DOMAIN DM00004   BLAST-                           JN0583|727-969: V167-R401, Q1372-P1563   DOMO                           P07313|298-541: K168-A409, Q1378-P1563                           P53355|15-257: E169-R406, Q1374-P1563                           S07571|5152-5396: E166-R406, Q1374-P1606                           Protein kinases ATP-binding region signature I171-   MOTIFS                           K194                           Tyrosine protein kinases specific active-site signature   MOTIFS                           I1484-I1496                           Protein kinase St V280-M192   MOTIFS                    
     [0394]                                       TABLE 4                       Polynucleotide       Sequence   Selected                   SEQ ID NO:   Incyte ID   Length   Fragments   Sequence Fragments   5′ Position   3′ Position                                                            23   7482896CB1   1014    982-1014   GNN.g7899226_000043_002.   1   1014                       edit       24   7483046CB1   1530    719-770,   71583296V1   889   1476                     1-61,   71581650V1   778   1455                   1036-1104,   71601507V1   1124   1530                   1271-1461,   55143579J1   1   272                    313-464   71579961V1   266   884                       55140831J1   118   522       25   71636374CB1   3150   1294-1806,   183812R7 (CARDNOT01)   2581   3148                     1-115,   7676860H1 (NOSETUE01)   250   864                   2593-2616   8252304H1 (BRAHDIT10)   25   804                       5223511F9 (OVARDIT07)   1225   1397                       GBI.g7452884_edit   1125   2085                       GBI.g8919852_edit   1099   1898                       7214961H1 (LUNGFEC01)   1   250                       7710619J1 (TESTTUE02)   1611   2273                       7391509H1 (LIVRFEE02)   751   1302                       5958404H1 (BRATNOT05)   2796   3150                       5971916H1 (BRAZNOT01)   2211   2832       26   7480597CB1   2901   1907-1981,   55150024J1   1377   2056                     1-156,   55073631J1   630   1518                    748-1606,   55150108J1   1711   2070                    255-313   2841337T6 (DRGLNOT01)   2251   2901                       55144761T1   2132   2833                       5543295F7 (TESTNOC01)   137   574                       GNN.g7658410_000016_002   1   2013                       56001404J1   1790   2434       27   3227248CB1   1671     1-85,   70944845V1   997   1646                   1593-1671,   7207691H1 (FIBPFEA01)   451   1050                   1327-1360   8283762T1 (LIVRNON08)   180   562                       GBI.g9796547_edit   1   1539                       71281138V1   1089   1671                       5260904F6 (CONDTUT01)   569   1065       28   4207273CB1   2577     1-1641,   5543515F6 (TESTNOC01)   907   1376                   1845-1889   5357164H1 (TESTNOC01)   238   440                       55144823H1   2112   2577                       GNN.g9230839_000001_002   1   1293                       55073166J1   1115   1773                       4919885T6 (TESTNOT11)   1445   2141       29   7483334CB1   2110     1-640,   71341632V1   1559   2110                   1255-1314,   71341335V1   1145   1708                    948-1005   940589R6 (ADRENOT03)   1916   2110                       6512850H1 (THYMDIT01)   1007   1688                       6102073H1 (UTRENOT09)   797   1087                       4970029F7 (KIDEUNC10)   1   677                       7659406H1 (OVARNOE02)   509   1081       30   7483337CB1   7093     1-3002,   7383958R8 (FTUBTUE01)   1   694                   4789-5840,   3245584H1 (BRAINOT19)   2681   2928                   7069-7093,   72334852V1   5219   5761                   3561-3671   7383958F8 (FTUBTUE01)   537   1196                       58002303T1   6221   7093                       70771904V1   5851   6475                       GNN.g6693375_000016_002.   986   3303                       edit                       55046508H1   2906   3666                       55144427J1   5514   6397                       5208289H1 (BRAFNOT02)   4900   5138                       7036825F6 (UTRSTMR02)   3953   4647                       55046508J1   3448   4132                       70772942V1   5079   5680                       6436908H1 (LUNGNON07)   908   1407                       GNN.g6721428_000012_004.   3780   6267                       edit       31   6035509CB1   1800    152-333,   71927475V1   1340   1800                     1-25,   6035509F8 (PITUNOT06)   848   1614                   1463-1800,   55071284J1   818   1098                    770-862   72420180D1   1   729                       55071288J1   480   1096       32   7373485CB1   6347   4445-5413,   72375809V1   2075   2717                    728-786,   8116978H1 (TONSDIC01)   1   659                   6321-6347,   GNN.g6114949_010.edit5p   1497   3728                   1497-3441,   6919538R8 (PLACFER06)   1156   1644                   4019-4079,   GNN.g6850654_000027_002   998   1496                    877-1082                       7368965H1 (ADREFEC01)   5742   6347                       6460173H2 (OSTEUNC01)   5357   5883                       6801172F6 (COLENOR03)   4290   4817                       7212618T8 (LUNGFEC01)   3001   3712                       6919538F8 (PLACFER06)   390   1143                       55073317H1   2592   3387                       58003367H1   4871   5725                       7271932R8 (OVARDIJ01)   3542   4220                       5623962R8 (THYMNOR02)   4544   5050                       72373545V1   1602   2203                       5623962F8 (THYMNOR02)   3970   4319       33   5734965CB1   1876     1-902   3254961T6 (OVARTUN01)   1276   1876                       5897065H1 (BRAYDIN03)   1   291                       70810516V1   181   806                       70162895V1   1002   1658                       70809778V1   915   1490                       70807962V1   302   989       34   7473788CB1   1487     1-121,   70995937V1   1024   1487                   1450-1487   7177378H1 (BRAXDIC01)   29   554                       GNN: g3983531_000002_002.   1   260                       edit.1                       70996158V1   594   1243                       7177563H2 (BRAXDIC01)   489   1180       35   3107989CB1   1884     1-306,   70942785V1   1153   1507                   1253-1884   3107989F6 (BRSTTUT15)   232   609                       7363877H1 (OVARDIC01)   1358   1884                       GNN.g9368012.edit1   375   1465                       2243506F6 (PANCTUT02)   1   385       36   7482887CB1   1070     1-660,   56009164H1   1   725                    891-948   GBI.g5815507.edit   612   997                       GBI.g9716284_order_0.edit2   988   1070       37   2963414CB1   2890     1-270,   71883559V1   470   1087                   1973-2064,   6741017F6 (BRAFDIT02)   1687   2299                   2658-2890,   72524920V1   984   1725                    726-1584   7090654H1 (BRAUTDR03)   2284   2876                       7595015H1 (LIVRNOC07)   1   450                       71882107V1   424   985                       70523289V1   1123   1749                       7236935H1 (BRAINOY02)   1904   2302                       2601508H1 (UTRSNOT10)   2660   2890       38   7477139CB1   5198   2528-2698,   GNN.g1149521_002   948   3957                   1296-2145,   71143326V1   4891   5198                   2792-4455,   55117016H1   1   919                    528-724,   2879284F6 (UTRSTUT05)   4388   4874                    177-214   3900926H1 (LUNGNON03)   3689   3971                       GNN.g2780172_002.edit   3433   4943                       72615067V1   701   1315                       6775332H1 (OVARDIR01)   4605   5193                       7369832H1 (ADREFEC01)   4063   4606       39   55009053CB1   3969   1393-2860,   8036923H1 (SMCRUNE01)   1289   2065                     1-649                       72480126D1   3325   3969                       7263320F6 (PROSTMC02)   1510   2343                       55009061H1   570   1318                       72476437D1   3306   3968                       6583144F8 (BRAVTXC01)   1   452                       72508467V1   2287   3200                       72509180V1   2494   3329                       55009045J1   288   982       40   7474648CB1   1803    198-1803   FL7474648_g7596812_0000   823   1497                       12_g7981277_1_1                       GNN.g7596812_2   1   1803       41   7483053CB1   3472     1-305,   GBI.g6981824_000001.edit   1   337                   3134-3472   2493520F6 (ADRETUT05)   2055   2525                       72498890V1   1524   2231                       GNN.g6981824_000001_042.   74   3187                       edit                       55081239H1   847   1704                       6872245H1 (BRAGNON02)   2354   3059                       7995993H1 (ADRETUC01)   2942   3472                       7742567H1 (ADRETUE04)   647   1183       42   7483117CB1   1704     1-342,   GBI.g4153871_000001.edit   1536   1704                    509-539,   7369322F8 (ADREFEC01)   343   501                    582-758   GNN.g4153871_006.edit   1   1678       43   7484498CB1   6298   4050-4677,   55058386H1   601   1357                     1-195,   7073440H1 (BRAUTDR04)   5165   5621                    623-1785,                   2406-2578,   7032228R8 (BRAXTDR12)   4000   4590                   3211-3637,   55053104J1   1618   2321                   2139-2261   7014254F6 (KIDNNOC01)   4579   5133                       7066070H1 (BRATNOR01)   2926   3470                       55053152H1   848   1564                       55058386J1   1   701                       7073642H1 (BRAUTDR04)   5045   5617                       6892089F6 (BRAITDR03)   2294   2708                       8267244H1 (MIXDUNF04)   4401   5097                       7076436H1 (BRAUTDR04)   3497   4047                       7068147R8 (BRATNOR01)   5186   5924                       GNN.g4508157_002.edit   1166   1941                       7741468H1 (THYMNOE01)   3001   3627                       6850478H1 (BRAIFEN08)   5720   6298                       7068147F8 (BRATNOR01)   4092   4592       44   7638121CB1   5454   1718-3145,   6756753J1 (SINTFER02)   3907   4637                     1-989,   7361161H1 (BRAIFEE05)   1   637                   3982-4016   55057003J1   252   937                       56000546J1   1303   2019                       7354408H1 (HEARNON03)   5008   5454                       5863411F6 (MUSLTDT01)   3355   4178                       71873215V1   4520   5227                       71875134V1   3114   3669                       6496171T6 (COLNNOT41)   4710   5416                       55141853J2   810   1390                       7647137H1 (UTRSTUE01)   1920   2257                       7600017R6 (ESOGTME01)   1475   2041                       6200811F6 (PITUNON01)   3037   3632                       55052669H1   2245   3081                    
     [0395]                               TABLE 5                                   Polynucleotide   Incyte Project               SEQ ID NO:   ID:   Representative Library                                                        24   7483046CB1   COLCTUT03           25   71636374CB1   CARDNOT01           26   7480597CB1   DRGLNOT01           27   3227248CB1   COTRNOT01           28   4207273CB1   TESTNOC01           29   7483334CB1   ADRENOT03           30   7483337CB1   UTRSTMR02           31   6035509CB1   PITUNOT06           32   7373485CB1   MCLDTXT02           33   5734965CB1   PROSTUS23           34   7473788CB1   BRAINOT19           35   3107989CB1   STOMFET02           37   2963414CB1   SCORNOT04           38   7477139CB1   PLACFER06           39   55009053CB1   SINITME01           41   7483053CB1   BRAYDIN03           42   7483117CB1   ADREFEC01           43   7484498CB1   BRAITDR03           44   7638121CB1   MUSLTDR02                        
     [0396]                       TABLE 6                       Library   Vector   Library Description                  ADREFEC01   pINCY   This large size-fractionated library was constructed               using RNA isolated from adrenal tissue removed from a Caucasian               female fetus who died from anencephalus after 16-weeks&#39; gestation.               Serology was negative. Family history included taking               daily prenatal vitamins and mitral valve prolapse in the mother.       ADRENOT03   PSPORT1   Library was constructed using RNA isolated from               the adrenal tissue of a 17-year-old Caucasian male, who died from               cerebral anoxia.       BRAINOT19   pINCY   Library was constructed using RNA isolated from diseased               brain tissue removed from the left frontal lobe of a 27-year-old               Caucasian male during a brain lobectomy. Pathology               indicated a focal deep white matter lesion, characterized by marked               gliosis, calcifications, and hemosiderin-laden macrophages,               consistent with a remote perinatal injury. This tissue also               showed mild to moderate generalized gliosis, predominantly               subpial and subcortical, consistent with chronic seizure               disorder. The left temporal lobe, including the mesial               temporal structures, showed focal, marked pyramidal cell loss and               gliosis in hippocampal sector CA1, consistent with mesial               temporal sclerosis. GFAP was positive for astrocytes. The               patient presented with intractable epilepsy, focal epilepsy,               hemiplegia, and an unspecified brain injury. Patient history               included cerebral palsy, abnormality of gait, and               depressive disorder. Family history included brain cancer.       BRAITDR03   PCDNA2.1   This random primed library was constructed using RNA               isolated from allocortex, cingulate posterior 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.       BRAYDIN03   pINCY   This normalized library was constructed from 6.7 million               independent clones from a brain tissue library. Starting RNA was               made from RNA isolated from diseased hypothalamus tissue               removed from a 57-year-old Caucasian male who died from a               cerebrovascular accident. Patient history included               Huntington&#39;s disease and emphysema. The library was normalized in 2               rounds using conditions adapted from Soares et al.,               PNAS (1994) 91:9228 and Bonaldo et al., Genome Research (1996)               6:791, except that a significantly longer (48-hours/round)               reannealing hybridization was used. The library was linearized               and recircularized to select for insert containing clones.       CARDNOT01   PBLUESCRIPT   Library was constructed using RNA isolated from               the cardiac muscle of a 65-year-old Caucasian male, who died from a               gunshot wound.       COLCTUT03   pINCY   Library was constructed using RNA isolated from cecal               tumor tissue removed from a 70-year-old Caucasian female during               right hemicolectomy, open liver biopsy, flexible               sigmoidoscopy, colonoscopy, and permanent colostomy. Pathology               indicated invasive grade 2 adenocarcinoma forming an               ulcerated mass 2 cm distal to the ileocecal valve and invading the               muscularis propria. One regional lymph node (of 16) was               positive for metastatic adenocarcinoma. Patient history included               a deficiency anemia, malignant breast neoplasm, type II               diabetes, hyperlipidemia, viral hepatitis, an unspecified thyroid               disorder, osteoarthritis, a malignant skin neoplasm, and               normal delivery. Family history included cardiovascular and               cerebrovascular disease, hyperlipidemia, and breast and ovarian cancer.       COTRNOT01   pINCY   Library was constructed using RNA isolated from diseased               transverse colon tissue obtained from a 26-year-old Caucasian               male during a total abdominal colectomy and colostomy.               Pathology indicated minimally active pancolitis with areas of               focal severe colitis with perforation, consistent with Crohn&#39;s disease.       DRGLNOT01   pINCY   Library was constructed using RNA isolated from dorsal               root ganglion tissue removed from the cervical spine of a 32-year-               old Caucasian male who died from acute pulmonary edema and               bronchopneumonia, bilateral pleural and pericardial               effusions, and malignant lymphoma (natural killer cell type).               Patient history included probable cytomegalovirus, infection,               hepatic congestion and steatosis, splenomegaly, hemorrhagic               cystitis, thyroid hemorrhage, and Bell&#39;s palsy. Surgeries               included colonoscopy, large intestine biopsy, adenotonsillectomy,               and nasopharyngeal endoscopy and biopsy; treatment               included radiation therapy.       MCLDTXT02   pINCY   Library was constructed using RNA isolated from treated               umbilical cord blood dendritic cells removed from a male. The               cells were treated with granulocyte/macrophage colony stimulating               factor (GM-CSF), tumor necrosis factor alpha (TNF               alpha), stem cell factor (SCF), phorbol myristate acetate (PMA),               and ionomycin. The GM-CSF was added at time 0 at 100 ng/ml,               the TNF alpha was added at time 0 at 2.5 ng/ml, the SCF was               added at time 0 at 25 ng/ml. The PMA and ionomycin               were added at 13 days for five hours. Incubation time was 13 days.       MUSLTDR02   PCDNA2.1   This random primed library was constructed using RNA               isolated from right lower thigh muscle tissue removed from a 58-               year-old Caucasian male during a wide resection of the right               posterior thigh. Pathology indicated no residual tumor was               identified in the right posterior thigh soft tissue. Changes               were consistent with a previous biopsy site. On section through               the soft tissue and muscle there was a smooth cystic cavity               with hemorrhage around the margin on one side. The wall of the               cyst was smooth and pale-tan. Pathology for the matched tumor               tissue indicated a grade II liposarcoma. Patient history               included liposarcoma (right thigh), and hypercholesterolemia.               Previous surgeries included resection of right thigh mass.               Family history included myocardial infarction and an               unspecified rare blood disease.       PITUNOT06   pINCY   Library was constructed using RNA isolated from               pituitary gland tissue removed from a 55-year-old male who died from               chronic obstructive pulmonary disease. Neuropathology               indicated there were no gross abnormalities, other than mild               ventricular enlargement. There was no apparent microscopic               abnormality in any of the neocortical areas examined, except               for a number of silver positive neurons with apical dendrite               staining, particularly in the frontal lobe. The significance of this               was undetermined. The only other microscopic abnormality               was that there was prominent silver staining with some swollen               axons in the CA3 region of the anterior and posterior               hippocampus. Microscopic sections of the cerebellum revealed mild               Bergmann&#39;s gliosis in the Purkinje cell layer. Patient               history included schizophrenia.       PLACFER06   pINCY   This random primed library was constructed using RNA               isolated from placental tissue removed from a Caucasian fetus who               died after 16 weeks&#39; gestation from fetal demise and               hydrocephalus. Patient history included umbilical cord wrapped               around the head (3 times) and the shoulders (1 time).               Serology was positive for anti-CMV. Family history included               multiple pregnancies and live births, and an abortion.       PROSTUS23   pINCY   This subtracted prostate tumor library was constructed               using 10 million clones from a pooled prostate tumor library that               was subjected to 2 rounds of subtractive hybridization               with 10 million clones from a pooled prostate tissue library. The               starting library for subtraction was constructed               by pooling equal numbers of clones from 4 prostate tumor libraries using               mRNA isolated from prostate tumor removed from               Caucasian males at ages 58 (A), 61 (B), 66 (C), and 68 (D) during               prostatectomy with lymph node excision. Pathology indicated               adenocarcinoma in all donors. History included elevated               PSA, induration and tobacco abuse in donor A; elevated PSA, induration,               prostate hyperplasia, renal failure, osteoarthritis,               renal artery stenosis, benign HTN, thrombocytopenia, hyperlipidemia,               tobacco/alcohol abuse and hepatitis C (carrier) in               donor B; elevated PSA, induration, and tobacco abuse in donor C; and elevated PSA,               induration, hypercholesterolemia, and               kidney calculus in donor D. The hybridization probe for subtraction was               constructed by pooling equal numbers of cDNA               clones from 3 prostate tissue libraries derived from prostate tissue,               prostate epithelial cells, and fibroblasts from prostate str       SCORNOT04   pINCY   Library was constructed using RNA isolated from cervical spinal               cord tissue removed from a 32-year-old Caucasian male               who died from acute pulmonary edema and bronchopneumonia, bilateral               pleural and pericardial effusions, and malignant               lymphoma (natural killer cell type). Patient history included probable               cytomegalovirus, infection, hepatic congestion and               steatosis, splenomegaly, hemorrhagic cystitis, thyroid hemorrhage,               and Bell&#39;s palsy. Surgeries included colonoscopy, large               intestine biopsy, adenotonsillectomy, and nasopharyngeal               endoscopy and biopsy; treatment included radiation therapy.       SINITME01   pINCY   This 5′ biased random primed library was constructed using RNA isolated               from ileum tissue removed from a 70-year-old Caucasian female during right hemicolectomy,               open liver biopsy, flexible sigmoidoscopy, colonoscopy, and permanent               colostomy. Pathology for the matched tumor tissue indicated invasive               grade 2 adenocarcinoma forming an ulcerated mass,               situated 2 cm distal to the ileocecal valve. Patient               history included a malignant breast neoplasm, type II diabetes,               hyperlipidemia, viral hepatitis, an unspecified thyroid               disorder, osteoarthritis, a malignant skin neoplasm, deficiency               anemia, and normal delivery. Family history included breast               cancer, atherosclerotic coronary artery disease, benign               hypertension, cerebrovascular disease, ovarian cancer, and hyperlipidemia.       STOMFET02   pINCY   Library was constructed using RNA isolated from stomach tissue removed from a Hispanic               male fetus, who died at 18 weeks&#39; gestation.       TESTNOC01   PBLUESCRIPT   This large size fractionated library was constructed using RNA isolated from               testicular tissue removed from a pool of               eleven, 10 to 61-year-old Caucasian males.       UTRSTMR02   PCDNA2.1   This random primed library was constructed using pooled cDNA from two different               donors. cDNA was generated using               mRNA isolated from endometrial tissue removed from a 32-year-old               female (donor A) and using mRNA isolated from               myometrium removed from a 45-year-old female (donor B)               during vaginal hysterectomy and bilateral salpingo-               oophorectomy. In donor A, pathology indicated the endometrium was secretory phase.               The cervix showed severe dysplasia               (CIN III) focally involving the squamocolumnar junction at the 1, 6 and 7 o&#39;clock               positions. Mild koilocytotic dysplasia               was also identified within the cervix. In donor B,               pathology for the matched tumor tissue indicated multiple (23)               subserosal, intramural, and submucosal leiomyomata. Patient history included               stress incontinence, extrinsic asthma without               status asthmaticus and normal delivery in donor B.               Family history included cerebrovascular disease, depression, and               atherosclerotic coronary artery disease in donor B.                    
     [0397]                           TABLE 7                       Program   Description   Reference   Parameter Threshold                  ABI   A program that removes vector sequences   Applied Biosystems, Foster City,           FACTURA   and masks ambiguous bases in nucleic acid   CA.           sequences.       ABI/PARACEL   A Fast Data Finder useful in comparing and   Applied Biosystems, Foster City,   Mismatch &lt; 50%       FDF   annotating amino acid or nucleic acid   CA; Paracel Inc., Pasadena, CA.           sequences.       ABI Auto   A program that assembles nucleic acid   Applied Biosystems, Foster City,       Assembler   sequences.   CA.       BLAST   A Basic Local Alignment Search Tool useful   Altschul, S. F. et al. (1990) J. Mol.   ESTs: Probability value = 1.0E−8           in sequence similarity search for amino acid   Biol. 215: 403-410; Altschul, S. F. et   or less; Full Length           and nucleic acid sequences. BLAST includes   al. (1997) Nucleic Acids Res.   sequences: Probability value = 1.0E−10           five functions: blastp, blastn, blastx, tblastn,   25: 3389-3402.   or less           and tblastx.       FASTA   A Pearson and Lipman algorithm that searches   Pearson, W. R. and D. J. Lipman   ESTs: fasta E value = 1.06E−6;           for similarity between a query sequence and a   (1988) Proc. Natl. Acad Sci. USA   Assembled ESTs: fasta           group of sequences of the same type. FASTA   85: 2444-2448; Pearson, W. R.   Identity = 95% or greater and           comprises as least five functions: fasta, tfasta,   (1990) Methods Enzymol. 183: 63-98;   Match length = 200 bases or           fastx, tfastx, and ssearch.   and Smith, T. F. and M. S. Waterman   greater; fastx E value = 1.0E−8               (1981) Adv. Appl. Math.   or less; Full Length sequences:               2: 482-489.   fastx score = 100 or greater       BLIMPS   A BLocks IMProved Searcher that matches a   Henikoff, S. and J. G. Henikoff   Probability value = 1.0E−3 or           sequence against those in BLOCKS, PRINTS,   (1991) Nucleic Acids Res. 19: 6565-6572;   less           DOMO, PRODOM, and PFAM databases to   Henikoff, J. G. and S.           search for gene families, sequence homology,   Henikoff (1996) Methods Enzymol.           and structural fingerprint regions.   266: 88-105; and Attwood, T. K. et               al. (1997) J. Chem. Inf. Comput.               Sci. 37: 417-424.       HMMER   An algorithm for searching a query sequence   Krogh, A. et al. (1994) J. Mol. Biol.   PFAM hits: Probability value = 1.0E−3           against hidden Markov model (HMM)-based   235: 1501-1531; Sonnhammer, E. L. L.   or less; Signal peptide           databases of protein family consensus   et al. (1988) Nucleic Acids   hits: Score = 0 or greater           sequences, such as PFAM.   Res. 26: 320-322; Durbin, R. et al.               (1998) Our World View, in a               Nutshell, Cambridge Univ. Press,               pp. 1-350.       ProfileScan   An algorithm that searches for structural and   Gribskov, M. et al. (1988) CABIOS   Normalized quality           sequence motifs in protein sequences that   4: 61-66; Gribskov, M. et al. (1989)   score ≧ GCG-specified “HIGH”           match sequence patterns defined in Prosite.   Methods Enzymol. 183: 146-159;   value for that particular               Bairoch, A. et al. (1997) Nucleic   Prosite motif. Generally,               Acids Res. 25: 217-221.   score = 1.4-2.1.       Phred   A base-calling algorithm that examines   Ewing, B. et al. (1998) Genome           automated sequencer traces with high   Res. 8: 175-185; Ewing, B. and P.           sensitivity and probability.   Green (1998) Genome Res. 8: 186-194.       Phrap   A Phils Revised Assembly Program including   Smith, T. F. and M. S. Waterman   Score = 120 or greater; Match           SWAT and CrossMatch, programs based on   (1981) Adv. Appl. Math. 2: 482-489;   length = 56 or greater           efficient implementation of the Smith-   Smith, T. F. and M. S. Waterman           Waterman algorithm, useful in searching   (1981) J. Mol. Biol.           sequence homology and assembling DNA   147: 195-197; and Green, P.,           sequences.   University of Washington, Seattle,               WA.       Consed   A graphical tool for viewing and editing Phrap   Gordon, D. et al. (1998) Genome           assemblies.   Res. 8: 195-202.       SPScan   A weight matrix analysis program that scans   Nielson, H. et al. (1997) Protein   Score = 3.5 or greater           protein sequences for the presence of   Engineering 10: 1-6; Claverie, J. M.           secretory signal peptides.   and S. Audic (1997) CABIOS               12: 431-439.       TMAP   A program that uses weight matrices to   Persson, B. and P. Argos (1994) J.           delineate transmembrane segments on protein   Mol. Biol. 237: 182-192; Persson, B.           sequences and determine orientation.   and P. Argos (1996) Protein Sci.               5: 363-371.       TMHMMER   A program that uses a hidden Markov model   Sonnhammer, E. L. et al. (1998)           (HMM) to delineate transmembrane segments   Proc. Sixth Intl. Conf. On           on protein sequences and determine   Intelligent Systems for Mol. Biol.,           orientation.   Glasgow et al., eds., The Am.               Assoc. for Artificial Intelligence               (AAAI) Press, Menlo Park, CA, and               MIT Press, Cambridge, MA, pp.               175-182.       Motifs   A program that searches amino acid sequences   Bairoch, A. et al. (1997) Nucleic           for patterns that matched those defined in   Acids Res. 25: 217-221; Wisconsin           Prosite.   Package Program Manual, version               9, page M51-59, Genetics Computer               Group, Madison, WI.                    
     [0398] 
    
     
       
         1 
         
           
             44  
           
           
             1  
             337  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7482896CD1  
             
           
            1 

Met Thr Asn Asn Ser Gly Ser Lys Ala Glu Leu Val Val Gly Gly 
1               5                   10                  15 

Lys Tyr Lys Leu Val Arg Lys Ile Gly Ser Gly Ser Phe Gly Asp 
                20                  25                  30 

Val Tyr Leu Gly Ile Thr Thr Thr Asn Gly Glu Asp Val Ala Val 
                35                  40                  45 

Lys Leu Glu Ser Gln Lys Val Lys His Pro Gln Leu Leu Tyr Glu 
                50                  55                  60 

Ser Lys Leu Tyr Thr Ile Leu Gln Gly Gly Val Gly Ile Pro His 
                65                  70                  75 

Met His Trp Tyr Gly Gln Glu Lys Asp Asn Asn Val Leu Val Met 
                80                  85                  90 

Asp Leu Leu Gly Pro Ser Leu Glu Asp Leu Phe Asn Phe Cys Ser 
                95                  100                 105 

Arg Arg Phe Thr Met Lys Thr Val Leu Met Leu Ala Asp Gln Met 
                110                 115                 120 

Ile Ser Arg Ile Glu Tyr Val His Thr Lys Asn Phe Leu His Arg 
                125                 130                 135 

Asp Ile Lys Pro Asp Asn Phe Leu Met Gly Thr Gly Arg His Cys 
                140                 145                 150 

Asn Lys Leu Phe Leu Ile Asp Phe Gly Leu Ala Lys Lys Tyr Arg 
                155                 160                 165 

Asp Asn Arg Thr Arg Gln His Ile Pro Tyr Arg Glu Asp Lys His 
                170                 175                 180 

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

Ile Glu Gln Ser Arg Arg Asp Asp Met Glu Ser Leu Gly Tyr Val 
                200                 205                 210 

Phe Met Tyr Phe Asn Arg Thr Ser Leu Pro Trp Gln Gly Leu Arg 
                215                 220                 225 

Ala Met Thr Lys Lys Gln Lys Tyr Glu Lys Ile Ser Glu Lys Lys 
                230                 235                 240 

Met Ser Thr Pro Val Glu Val Leu Cys Lys Gly Phe Pro Ala Glu 
                245                 250                 255 

Phe Ala Met Tyr Leu Asn Tyr Cys Arg Gly Leu Arg Phe Glu Glu 
                260                 265                 270 

Val Pro Asp Tyr Met Tyr Leu Arg Gln Leu Phe Arg Ile Leu Phe 
                275                 280                 285 

Arg Thr Leu Asn His Gln Tyr Asp Tyr Thr Phe Asp Trp Thr Met 
                290                 295                 300 

Leu Lys Gln Lys Ala Ala Gln Gln Ala Ala Ser Ser Ser Gly Gln 
                305                 310                 315 

Gly Gln Gln Ala Gln Thr Gln Thr Gly Lys Gln Thr Glu Lys Asn 
                320                 325                 330 

Lys Asn Asn Val Lys Asp Asn 
                335 

 
           
             2  
             475  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7483046CD1  
             
           
            2 

Met Glu Arg Arg Leu Arg Ala Leu Glu Gln Leu Ala Arg Gly Glu 
1               5                   10                  15 

Ala Gly Gly Cys Pro Gly Leu Asp Gly Leu Leu Asp Leu Leu Leu 
                20                  25                  30 

Ala Leu His His Glu Leu Ser Ser Gly Pro Leu Arg Arg Glu Arg 
                35                  40                  45 

Ser Val Ala Gln Phe Leu Ser Trp Ala Ser Pro Phe Val Ser Lys 
                50                  55                  60 

Val Lys Glu Leu Arg Leu Gln Arg Asp Asp Phe Glu Ile Leu Lys 
                65                  70                  75 

Val Ile Gly Arg Gly Ala Phe Gly Glu Val Thr Val Val Arg Gln 
                80                  85                  90 

Arg Asp Thr Gly Gln Ile Phe Ala Met Lys Met Leu His Lys Trp 
                95                  100                 105 

Glu Met Leu Lys Arg Ala Glu Thr Ala Cys Phe Arg Glu Glu Arg 
                110                 115                 120 

Asp Val Leu Val Lys Gly Asp Ser Arg Trp Val Thr Thr Leu His 
                125                 130                 135 

Tyr Ala Phe Gln Asp Glu Glu Tyr Leu Tyr Leu Val Met Asp Tyr 
                140                 145                 150 

Tyr Ala Gly Gly Asp Leu Leu Thr Leu Leu Ser Arg Phe Glu Asp 
                155                 160                 165 

Arg Leu Pro Pro Glu Leu Ala Gln Phe Tyr Leu Ala Glu Met Val 
                170                 175                 180 

Leu Ala Ile His Ser Leu His Gln Leu Gly Tyr Val His Arg Asp 
                185                 190                 195 

Val Lys Pro Asp Asn Val Leu Leu Asp Val Asn Gly His Ile Arg 
                200                 205                 210 

Leu Ala Asp Phe Gly Ser Cys Leu Arg Leu Asn Thr Asn Gly Met 
                215                 220                 225 

Val Asp Ser Ser Val Ala Val Gly Thr Pro Asp Tyr Ile Ser Pro 
                230                 235                 240 

Glu Ile Leu Gln Ala Met Glu Glu Gly Lys Gly His Tyr Gly Pro 
                245                 250                 255 

Gln Cys Asp Trp Trp Ser Leu Gly Val Cys Ala Tyr Glu Leu Leu 
                260                 265                 270 

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

Gly Lys Ile Met Asn His Glu Asp His Leu Gln Phe Pro Pro Asp 
                290                 295                 300 

Val Pro Asp Val Pro Ala Ser Ala Gln Asp Leu Ile Arg Gln Leu 
                305                 310                 315 

Leu Cys Arg Gln Glu Glu Arg Leu Gly Arg Gly Gly Leu Asp Asp 
                320                 325                 330 

Phe Arg Asn His Pro Phe Phe Glu Gly Val Asp Trp Glu Arg Leu 
                335                 340                 345 

Ala Ser Ser Thr Ala Pro Tyr Ile Pro Glu Leu Arg Gly Pro Met 
                350                 355                 360 

Asp Thr Ser Asn Phe Asp Val Asp Asp Asp Thr Leu Asn His Pro 
                365                 370                 375 

Gly Thr Leu Pro Pro Pro Ser His Gly Ala Phe Ser Gly His His 
                380                 385                 390 

Leu Pro Phe Val Gly Phe Thr Tyr Thr Ser Gly Ser His Ser Pro 
                395                 400                 405 

Glu Ser Ser Ser Glu Ala Trp Ala Ala Leu Glu Arg Lys Leu Gln 
                410                 415                 420 

Cys Leu Glu Gln Glu Lys Val Glu Leu Ser Arg Lys His Gln Glu 
                425                 430                 435 

Ala Leu His Ala Pro Thr Asp His Arg Glu Leu Glu Gln Leu Arg 
                440                 445                 450 

Lys Glu Val Gln Thr Leu Arg Asp Arg Leu Pro Gly Ile Pro Ser 
                455                 460                 465 

Ala His Pro His Pro Leu Leu Glu Phe Leu 
                470                 475 

 
           
             3  
             675  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 71636374CD1  
             
           
            3 

Met Thr Thr Ser His Met Asn Gly His Val Thr Glu Glu Ser Asp 
1               5                   10                  15 

Ser Glu Val Lys Asn Val Asp Leu Ala Ser Pro Glu Glu His Gln 
                20                  25                  30 

Lys His Arg Glu Met Ala Val Asp Cys Pro Gly Asp Leu Gly Thr 
                35                  40                  45 

Arg Met Met Pro Ile Arg Arg Ser Ala Gln Leu Glu Arg Ile Arg 
                50                  55                  60 

Gln Gln Gln Glu Asp Met Arg Arg Arg Arg Glu Glu Glu Gly Lys 
                65                  70                  75 

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

Ala Gln Ile Pro Pro Lys Thr Gly Ile Asp Asn Pro Met Phe Asp 
                95                  100                 105 

Thr Glu Glu Gly Ile Val Leu Glu Ser Pro His Tyr Ala Val Lys 
                110                 115                 120 

Ile Leu Glu Ile Glu Asp Leu Phe Ser Ser Leu Lys His Ile Gln 
                125                 130                 135 

His Thr Leu Val Asp Ser Gln Ser Gln Glu Asp Ile Ser Leu Leu 
                140                 145                 150 

Leu Gln Leu Val Gln Asn Lys Asp Phe Gln Asn Ala Phe Lys Ile 
                155                 160                 165 

His Asn Ala Ile Thr Val His Met Asn Lys Ala Ser Pro Pro Phe 
                170                 175                 180 

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

Val Leu Lys Pro Val His His Lys Glu Gly Gln Glu Leu Thr Ala 
                200                 205                 210 

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

Lys Val Ala Glu Gln Glu Met Gln Leu Glu Pro Ile Thr Asp Glu 
                230                 235                 240 

Arg Val Tyr Glu Ser Ile Gly Gln Tyr Gly Gly Glu Thr Val Lys 
                245                 250                 255 

Ile Val Arg Ile Glu Lys Ala Arg Asp Ile Pro Leu Gly Ala Thr 
                260                 265                 270 

Val Arg Asn Glu Met Asp Ser Val Ile Ile Ser Arg Ile Val Lys 
                275                 280                 285 

Gly Gly Ala Ala Glu Lys Ser Gly Leu Leu His Glu Gly Asp Glu 
                290                 295                 300 

Val Leu Glu Ile Asn Gly Ile Glu Ile Arg Gly Lys Asp Val Asn 
                305                 310                 315 

Glu Val Phe Asp Leu Leu Ser Asp Met His Gly Thr Leu Thr Phe 
                320                 325                 330 

Val Leu Ile Pro Ser Gln Gln Ile Lys Pro Pro Pro Ala Lys Glu 
                335                 340                 345 

Thr Val Ile His Val Lys Ala His Phe Asp Tyr Asp Pro Ser Asp 
                350                 355                 360 

Asp Pro Tyr Val Pro Cys Arg Glu Leu Gly Leu Ser Phe Gln Lys 
                365                 370                 375 

Gly Asp Ile Leu His Val Ile Ser Gln Glu Asp Pro Asn Trp Trp 
                380                 385                 390 

Gln Ala Tyr Arg Glu Gly Asp Glu Asp Asn Gln Pro Leu Ala Gly 
                395                 400                 405 

Leu Val Pro Gly Lys Ser Phe Gln Gln Gln Arg Glu Ala Met Lys 
                410                 415                 420 

Gln Thr Ile Glu Glu Asp Lys Glu Pro Glu Lys Ser Gly Lys Leu 
                425                 430                 435 

Trp Cys Ala Lys Lys Asn Lys Lys Lys Arg Lys Lys Val Leu Tyr 
                440                 445                 450 

Asn Ala Asn Lys Asn Asp Asp Tyr Asp Asn Glu Glu Ile Leu Thr 
                455                 460                 465 

Tyr Glu Glu Met Ser Leu Tyr His Gln Pro Ala Asn Arg Lys Arg 
                470                 475                 480 

Pro Ile Ile Leu Ile Gly Pro Gln Asn Cys Gly Gln Asn Glu Leu 
                485                 490                 495 

Arg Gln Arg Leu Met Asn Lys Glu Lys Asp Arg Phe Ala Ser Ala 
                500                 505                 510 

Val Pro His Thr Thr Arg Ser Arg Arg Asp Gln Glu Val Ala Gly 
                515                 520                 525 

Arg Asp Tyr His Phe Val Ser Arg Gln Ala Phe Glu Ala Asp Ile 
                530                 535                 540 

Ala Ala Gly Lys Phe Ile Glu His Gly Glu Phe Glu Lys Asn Leu 
                545                 550                 555 

Tyr Gly Thr Ser Ile Asp Ser Val Arg Gln Val Ile Asn Ser Gly 
                560                 565                 570 

Lys Ile Cys Leu Leu Ser Leu Arg Thr Gln Ser Leu Lys Thr Leu 
                575                 580                 585 

Arg Asn Ser Asp Leu Lys Pro Tyr Ile Ile Phe Ile Ala Pro Pro 
                590                 595                 600 

Ser Gln Glu Arg Leu Arg Ala Leu Leu Ala Lys Glu Gly Lys Asn 
                605                 610                 615 

Pro Lys Pro Glu Glu Leu Arg Glu Ile Ile Glu Lys Thr Arg Glu 
                620                 625                 630 

Met Glu Gln Asn Asn Gly His Tyr Phe Asp Thr Ala Ile Val Asn 
                635                 640                 645 

Ser Asp Leu Asp Lys Ala Tyr Gln Glu Leu Leu Arg Leu Ile Asn 
                650                 655                 660 

Lys Leu Asp Thr Glu Pro Gln Trp Val Pro Ser Thr Trp Leu Arg 
                665                 670                 675 

 
           
             4  
             835  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7480597CD1  
             
           
            4 

Met Ala Glu Gly Lys Glu Gly Gln Val Pro Ser Tyr Met Asp Gly 
1               5                   10                  15 

Ser Arg Gln Arg Glu Asn Glu Glu Asp Ala Lys Ala Glu Thr Pro 
                20                  25                  30 

Asp Val Thr Ile Arg Ser Tyr Glu Ile Tyr Ser Leu Pro Trp Asn 
                35                  40                  45 

Arg Gln Gln Gly Leu Cys Asp His Ser Leu Lys Tyr Leu Ser Ser 
                50                  55                  60 

Arg Ile Thr Glu Arg Lys Leu Gln Gly Ser Trp Leu Pro Ala Ser 
                65                  70                  75 

Arg Gly Asn Leu Glu Lys Pro Phe Leu Gly Pro Arg Gly Pro Val 
                80                  85                  90 

Val Pro Leu Phe Cys Pro Arg Asn Gly Leu His Ser Ala His Pro 
                95                  100                 105 

Glu Asn Ser Pro Leu Lys Pro Arg Val Val Thr Val Val Lys Leu 
                110                 115                 120 

Gly Gly Gln Arg Pro Arg Lys Ile Thr Leu Leu Leu Asn Arg Arg 
                125                 130                 135 

Ser Val Gln Thr Phe Glu Gln Leu Leu Ala Asp Ile Ser Glu Ala 
                140                 145                 150 

Leu Gly Ser Pro Arg Trp Lys Asn Asp Arg Val Arg Lys Leu Phe 
                155                 160                 165 

Asn Leu Lys Gly Arg Glu Ile Arg Ser Val Ser Asp Phe Phe Arg 
                170                 175                 180 

Glu Gly Asp Ala Phe Ile Ala Met Gly Lys Glu Pro Leu Thr Leu 
                185                 190                 195 

Lys Ser Ile Gln Val Ala Val Glu Glu Leu Tyr Pro Asn Lys Ala 
                200                 205                 210 

Arg Ala Leu Thr Leu Ala Gln His Ser Arg Ala Pro Ser Pro Arg 
                215                 220                 225 

Leu Arg Ser Arg Leu Phe Ser Lys Ala Leu Lys Gly Asp His Arg 
                230                 235                 240 

Cys Gly Glu Thr Glu Thr Pro Lys Ser Cys Ser Glu Val Ala Gly 
                245                 250                 255 

Cys Lys Ala Ala Met Arg His Gln Gly Lys Ile Pro Glu Glu Leu 
                260                 265                 270 

Ser Leu Asp Asp Arg Ala Arg Thr Gln Lys Lys Trp Gly Arg Gly 
                275                 280                 285 

Lys Trp Glu Pro Glu Pro Ser Ser Lys Pro Pro Arg Glu Ala Thr 
                290                 295                 300 

Leu Glu Glu Arg His Ala Arg Gly Glu Lys His Leu Gly Val Glu 
                305                 310                 315 

Ile Glu Lys Thr Ser Gly Glu Ile Ile Arg Cys Glu Lys Cys Lys 
                320                 325                 330 

Arg Glu Arg Glu Leu Gln Gln Ser Leu Glu Arg Glu Arg Leu Ser 
                335                 340                 345 

Leu Gly Thr Ser Glu Leu Asp Met Gly Lys Gly Pro Met Tyr Asp 
                350                 355                 360 

Val Glu Lys Leu Val Arg Thr Arg Ser Cys Arg Arg Ser Pro Glu 
                365                 370                 375 

Ala Asn Pro Ala Ser Gly Glu Glu Gly Trp Lys Gly Asp Ser His 
                380                 385                 390 

Arg Ser Ser Pro Arg Asn Pro Thr Gln Glu Leu Arg Arg Pro Ser 
                395                 400                 405 

Lys Ser Met Asp Lys Lys Glu Asp Arg Gly Pro Glu Asp Gln Glu 
                410                 415                 420 

Ser His Ala Gln Gly Ala Ala Lys Ala Lys Lys Asp Leu Val Glu 
                425                 430                 435 

Val Leu Pro Val Thr Glu Glu Gly Leu Arg Glu Val Lys Lys Asp 
                440                 445                 450 

Thr Arg Pro Met Ser Arg Ser Lys His Gly Gly Trp Leu Leu Arg 
                455                 460                 465 

Glu His Gln Ala Gly Phe Glu Lys Leu Arg Arg Thr Arg Gly Glu 
                470                 475                 480 

Glu Lys Glu Ala Glu Lys Glu Lys Lys Pro Cys Met Ser Gly Gly 
                485                 490                 495 

Arg Arg Met Thr Leu Arg Asp Asp Gln Pro Ala Lys Leu Glu Lys 
                500                 505                 510 

Glu Pro Lys Thr Arg Pro Glu Glu Asn Lys Pro Glu Arg Pro Ser 
                515                 520                 525 

Gly Arg Lys Pro Arg Pro Met Gly Ile Ile Ala Ala Asn Val Glu 
                530                 535                 540 

Lys His Tyr Glu Thr Gly Arg Val Ile Gly Asp Gly Asn Phe Ala 
                545                 550                 555 

Val Val Lys Glu Cys Arg His Arg Glu Thr Arg Gln Ala Tyr Ala 
                560                 565                 570 

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

Val Asp Ser Glu Ile Leu Ile Ile Gln Ser Leu Ser His Pro Asn 
                590                 595                 600 

Ile Val Lys Leu His Glu Val Tyr Glu Thr Asp Met Glu Ile Tyr 
                605                 610                 615 

Leu Ile Leu Glu Tyr Val Gln Gly Gly Asp Leu Phe Asp Ala Ile 
                620                 625                 630 

Ile Glu Ser Val Lys Phe Pro Glu Pro Asp Ala Ala Leu Met Ile 
                635                 640                 645 

Met Asp Leu Cys Lys Ala Leu Val His Met His Asp Lys Ser Ile 
                650                 655                 660 

Val His Arg Asp Leu Lys Pro Glu Asn Leu Leu Val Gln Arg Asn 
                665                 670                 675 

Glu Asp Lys Ser Thr Thr Leu Lys Leu Ala Asp Phe Gly Leu Ala 
                680                 685                 690 

Lys His Val Val Arg Pro Ile Phe Thr Val Cys Gly Thr Pro Thr 
                695                 700                 705 

Tyr Val Ala Pro Glu Ile Leu Ser Glu Lys Gly Tyr Gly Leu Glu 
                710                 715                 720 

Val Asp Met Trp Ala Ala Gly Val Ile Leu Tyr Ile Leu Leu Cys 
                725                 730                 735 

Gly Phe Pro Pro Phe Arg Ser Pro Glu Arg Asp Gln Asp Glu Leu 
                740                 745                 750 

Phe Asn Ile Ile Gln Leu Gly His Phe Glu Phe Leu Pro Pro Tyr 
                755                 760                 765 

Trp Asp Asn Ile Ser Asp Ala Ala Lys Asp Leu Val Ser Arg Leu 
                770                 775                 780 

Leu Val Val Asp Pro Lys Lys Arg Tyr Thr Ala His Gln Val Leu 
                785                 790                 795 

Gln His Pro Trp Ile Glu Thr Ala Gly Lys Thr Asn Thr Val Lys 
                800                 805                 810 

Arg Gln Lys Gln Val Ser Pro Ser Ser Glu Gly His Phe Arg Ser 
                815                 820                 825 

Gln His Lys Arg Val Val Glu Gln Val Ser 
                830                 835 

 
           
             5  
             373  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 3227248CD1  
             
           
            5 

Met Lys Leu Ile Asn Gly Lys Lys Gln Thr Phe Pro Trp Phe Gly 
1               5                   10                  15 

Met Asp Ile Gly Gly Thr Leu Val Lys Leu Val Tyr Phe Glu Pro 
                20                  25                  30 

Lys Asp Ile Thr Ala Glu Glu Glu Gln Glu Glu Val Glu Asn Leu 
                35                  40                  45 

Lys Ser Ile Arg Lys Tyr Leu Thr Ser Asn Thr Ala Tyr Gly Lys 
                50                  55                  60 

Thr Gly Ile Arg Asp Val His Leu Glu Leu Lys Asn Leu Thr Met 
                65                  70                  75 

Cys Gly Arg Lys Gly Asn Leu His Phe Ile Arg Phe Pro Ser Cys 
                80                  85                  90 

Ala Met His Arg Phe Ile Gln Met Gly Ser Glu Lys Asn Phe Ser 
                95                  100                 105 

Ser Leu His Thr Thr Leu Cys Ala Thr Gly Gly Gly Ala Phe Lys 
                110                 115                 120 

Phe Glu Glu Asp Phe Arg Met Ile Ala Asp Leu Gln Leu His Lys 
                125                 130                 135 

Leu Asp Glu Leu Asp Cys Leu Ile Gln Gly Leu Leu Tyr Val Asp 
                140                 145                 150 

Ser Val Gly Phe Asn Gly Lys Pro Glu Cys Tyr Tyr Phe Glu Asn 
                155                 160                 165 

Pro Thr Asn Pro Glu Leu Cys Gln Lys Lys Pro Tyr Cys Leu Asp 
                170                 175                 180 

Asn Pro Tyr Pro Met Leu Leu Val Asn Met Gly Ser Gly Val Ser 
                185                 190                 195 

Ile Leu Ala Val Tyr Ser Lys Asp Asn Tyr Lys Arg Val Thr Gly 
                200                 205                 210 

Thr Ser Leu Gly Gly Gly Thr Phe Leu Gly Leu Cys Cys Leu Leu 
                215                 220                 225 

Thr Gly Cys Glu Thr Phe Glu Glu Ala Leu Glu Met Ala Ala Lys 
                230                 235                 240 

Gly Asp Ser Thr Asn Val Asp Lys Leu Val Lys Asp Ile Tyr Gly 
                245                 250                 255 

Gly Asp Tyr Glu Arg Phe Gly Leu Gln Gly Ser Ala Val Ala Ser 
                260                 265                 270 

Ser Phe Gly Asn Met Met Ser Lys Glu Lys Arg Asp Ser Ile Ser 
                275                 280                 285 

Lys Glu Asp Leu Ala Arg Ala Thr Leu Val Thr Ile Thr Asn Asn 
                290                 295                 300 

Ile Gly Ser Ile Ala Arg Met Cys Ala Leu Asn Glu Asn Ile Asp 
                305                 310                 315 

Arg Val Val Phe Val Gly Asn Phe Leu Arg Ile Asn Met Val Ser 
                320                 325                 330 

Met Lys Leu Leu Ala Tyr Ala Met Asp Phe Trp Ser Lys Gly Gln 
                335                 340                 345 

Leu Lys Ala Leu Phe Leu Glu His Glu Gly Tyr Phe Gly Ala Val 
                350                 355                 360 

Gly Ala Leu Leu Glu Leu Phe Lys Met Thr Asp Asp Lys 
                365                 370 

 
           
             6  
             735  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 4207273CD1  
             
           
            6 

Met Pro Gln Ile Ala Lys Lys Gln Ser Thr His Arg Thr Gln Lys 
1               5                   10                  15 

Pro Lys Lys Gln Ser Phe Pro Cys Ile Cys Lys Asn Pro Gly Thr 
                20                  25                  30 

Gln Lys Ser Cys Val Pro Leu Ser Val Gln Pro Thr Glu Pro Arg 
                35                  40                  45 

Leu Asn Tyr Leu Asp Leu Lys Tyr Ser Asp Met Phe Lys Glu Ile 
                50                  55                  60 

Asn Ser Thr Ala Asn Gly Pro Gly Ile Tyr Glu Met Phe Gly Thr 
                65                  70                  75 

Pro Val Tyr Cys His Val Arg Glu Thr Glu Arg Asp Glu Asn Thr 
                80                  85                  90 

Tyr Tyr Arg Glu Ile Cys Ser Ala Pro Ser Gly Arg Arg Ile Thr 
                95                  100                 105 

Asn Lys Cys Arg Ser Ser His Ser Glu Arg Lys Ser Asn Ile Arg 
                110                 115                 120 

Thr Arg Leu Ser Gln Lys Lys Thr His Met Lys Cys Pro Lys Thr 
                125                 130                 135 

Ser Phe Gly Ile Lys Gln Glu His Lys Val Leu Ile Ser Lys Glu 
                140                 145                 150 

Lys Ser Ser Lys Ala Val His Ser Asn Leu His Asp Ile Glu Asn 
                155                 160                 165 

Gly Asp Gly Ile Ser Glu Pro Asp Trp Gln Ile Lys Ser Ser Gly 
                170                 175                 180 

Asn Glu Phe Leu Ser Ser Lys Asp Glu Ile His Pro Met Asn Leu 
                185                 190                 195 

Ala Gln Thr Pro Glu Gln Ser Met Lys Gln Asn Glu Phe Pro Pro 
                200                 205                 210 

Val Ser Asp Leu Ser Ile Val Glu Glu Val Ser Met Glu Glu Ser 
                215                 220                 225 

Thr Gly Asp Arg Asp Ile Ser Asn Asn Gln Ile Leu Thr Thr Ser 
                230                 235                 240 

Leu Arg Asp Leu Gln Glu Leu Glu Glu Leu His His Gln Ile Pro 
                245                 250                 255 

Phe Ile Pro Ser Glu Asp Ser Trp Ala Val Pro Ser Glu Lys Asn 
                260                 265                 270 

Ser Asn Lys Tyr Val Gln Gln Glu Lys Gln Asn Thr Ala Ser Leu 
                275                 280                 285 

Ser Lys Val Asn Ala Ser Arg Ile Leu Thr Asn Asp Leu Glu Phe 
                290                 295                 300 

Asp Ser Val Ser Asp His Ser Lys Thr Leu Thr Asn Phe Ser Phe 
                305                 310                 315 

Gln Ala Lys Gln Glu Ser Ala Ser Ser Gln Thr Tyr Gln Tyr Trp 
                320                 325                 330 

Val His Tyr Leu Asp His Asp Ser Leu Ala Asn Lys Ser Ile Thr 
                335                 340                 345 

Tyr Gln Met Phe Gly Lys Thr Leu Ser Gly Thr Asn Ser Ile Ser 
                350                 355                 360 

Gln Glu Ile Met Asp Ser Val Asn Asn Glu Glu Leu Thr Asp Glu 
                365                 370                 375 

Leu Leu Gly Cys Leu Ala Ala Glu Leu Leu Ala Leu Asp Glu Lys 
                380                 385                 390 

Asp Asn Asn Ser Cys Gln Lys Met Ala Asn Glu Thr Asp Pro Glu 
                395                 400                 405 

Asn Leu Asn Leu Val Leu Arg Trp Arg Gly Ser Thr Pro Lys Glu 
                410                 415                 420 

Met Gly Arg Glu Thr Thr Lys Val Lys Ile Gln Arg His Ser Ser 
                425                 430                 435 

Gly Leu Arg Ile Tyr Asp Arg Glu Glu Lys Phe Leu Ile Ser Asn 
                440                 445                 450 

Glu Lys Lys Ile Phe Ser Glu Asn Ser Leu Lys Ser Glu Glu Pro 
                455                 460                 465 

Ile Leu Trp Thr Lys Gly Glu Ile Leu Gly Lys Gly Ala Tyr Gly 
                470                 475                 480 

Thr Val Tyr Cys Gly Leu Thr Ser Gln Gly Gln Leu Ile Ala Val 
                485                 490                 495 

Lys Gln Val Ala Leu Asp Thr Ser Asn Lys Leu Ala Ala Glu Lys 
                500                 505                 510 

Glu Tyr Arg Lys Leu Gln Glu Glu Val Asp Leu Leu Lys Ala Leu 
                515                 520                 525 

Lys His Val Asn Ile Val Ala Tyr Leu Gly Thr Cys Leu Gln Glu 
                530                 535                 540 

Asn Thr Val Ser Ile Phe Met Glu Phe Val Pro Gly Gly Ser Ile 
                545                 550                 555 

Ser Ser Ile Ile Asn Arg Phe Gly Pro Leu Pro Glu Met Val Phe 
                560                 565                 570 

Cys Lys Tyr Thr Lys Gln Ile Leu Gln Gly Val Ala Tyr Leu His 
                575                 580                 585 

Glu Asn Cys Val Val His Arg Asp Ile Lys Gly Asn Asn Val Met 
                590                 595                 600 

Leu Met Pro Thr Gly Ile Ile Lys Leu Ile Asp Phe Gly Cys Ala 
                605                 610                 615 

Arg Arg Leu Ala Trp Ala Gly Leu Asn Gly Thr His Ser Asp Met 
                620                 625                 630 

Leu Lys Ser Met His Gly Thr Pro Tyr Trp Met Ala Pro Glu Val 
                635                 640                 645 

Ile Asn Glu Ser Gly Tyr Gly Arg Lys Ser Asp Ile Trp Ser Ile 
                650                 655                 660 

Gly Cys Thr Val Phe Glu Met Ala Thr Gly Lys Pro Pro Leu Ala 
                665                 670                 675 

Ser Met Asp Arg Met Ala Ala Met Phe Tyr Ile Gly Ala His Arg 
                680                 685                 690 

Gly Leu Met Pro Pro Leu Pro Asp His Phe Ser Glu Asn Ala Ala 
                695                 700                 705 

Asp Phe Val Arg Met Cys Leu Thr Arg Asp Gln His Glu Arg Pro 
                710                 715                 720 

Ser Ala Leu Gln Leu Leu Lys His Ser Phe Leu Glu Arg Ser His 
                725                 730                 735 

 
           
             7  
             506  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7483334CD1  
             
           
            7 

Met Asp Asp Tyr Met Val Leu Arg Met Ile Gly Glu Gly Ser Phe 
1               5                   10                  15 

Gly Arg Ala Leu Leu Val Gln Leu Glu Ser Ser Asn Gln Met Phe 
                20                  25                  30 

Ala Met Lys Glu Ile Arg Leu Pro Lys Ser Phe Ser Asn Thr Gln 
                35                  40                  45 

Asn Ser Arg Lys Glu Ala Val Leu Leu Ala Lys Met Lys His Pro 
                50                  55                  60 

Asn Ile Val Ala Phe Lys Glu Ser Phe Glu Ala Glu Gly His Leu 
                65                  70                  75 

Tyr Ile Val Met Glu Tyr Cys Asp Gly Gly Asp Leu Met Gln Lys 
                80                  85                  90 

Ile Lys Gln Gln Lys Gly Lys Leu Phe Pro Glu Asp Met Ile Leu 
                95                  100                 105 

Asn Trp Phe Thr Gln Met Cys Leu Gly Val Asn His Ile His Lys 
                110                 115                 120 

Lys Arg Val Leu His Arg Asp Ile Lys Ser Lys Asn Ile Phe Leu 
                125                 130                 135 

Thr Gln Asn Gly Lys Val Lys Leu Gly Asp Phe Gly Ser Ala Arg 
                140                 145                 150 

Leu Leu Ser Asn Pro Met Ala Phe Ala Cys Thr Tyr Val Gly Thr 
                155                 160                 165 

Pro Tyr Tyr Val Pro Pro Glu Ile Trp Glu Asn Leu Pro Tyr Asn 
                170                 175                 180 

Asn Lys Ser Asp Ile Trp Ser Leu Gly Cys Ile Leu Tyr Glu Leu 
                185                 190                 195 

Cys Thr Leu Lys His Pro Phe Gln Ala Asn Ser Trp Lys Asn Leu 
                200                 205                 210 

Ile Leu Lys Val Cys Gln Gly Cys Ile Ser Pro Leu Pro Ser His 
                215                 220                 225 

Tyr Ser Tyr Glu Leu Gln Phe Leu Val Lys Gln Met Phe Lys Arg 
                230                 235                 240 

Asn Pro Ser His Arg Pro Ser Ala Thr Thr Leu Leu Ser Arg Gly 
                245                 250                 255 

Ile Val Ala Arg Leu Val Gln Lys Cys Leu Pro Pro Glu Ile Ile 
                260                 265                 270 

Met Glu Tyr Gly Glu Glu Val Leu Glu Glu Ile Lys Asn Ser Lys 
                275                 280                 285 

His Asn Thr Pro Arg Lys Lys Thr Asn Pro Ser Arg Ile Arg Ile 
                290                 295                 300 

Ala Leu Gly Asn Glu Ala Ser Thr Val Gln Glu Glu Glu Gln Asp 
                305                 310                 315 

Arg Lys Gly Ser His Thr Asp Leu Glu Ser Ile Asn Glu Asn Leu 
                320                 325                 330 

Val Glu Ser Ala Leu Arg Arg Val Asn Arg Glu Glu Lys Gly Asn 
                335                 340                 345 

Lys Ser Val His Leu Arg Lys Ala Ser Ser Pro Asn Leu His Arg 
                350                 355                 360 

Arg Gln Trp Glu Lys Asn Val Pro Asn Thr Ala Leu Thr Ala Leu 
                365                 370                 375 

Glu Asn Ala Ser Ile Leu Thr Ser Ser Leu Thr Ala Glu Asp Asp 
                380                 385                 390 

Arg Gly Gly Ser Val Ile Lys Tyr Ser Lys Asn Thr Thr Arg Lys 
                395                 400                 405 

Gln Trp Leu Lys Glu Thr Pro Asp Thr Leu Leu Asn Ile Leu Lys 
                410                 415                 420 

Asn Ala Asp Leu Ser Leu Ala Phe Gln Thr Tyr Thr Ile Tyr Arg 
                425                 430                 435 

Pro Gly Ser Glu Gly Phe Leu Lys Gly Pro Leu Ser Glu Glu Thr 
                440                 445                 450 

Glu Ala Ser Asp Ser Val Asp Gly Gly His Asp Ser Val Ile Leu 
                455                 460                 465 

Asp Pro Glu Arg Leu Glu Pro Gly Leu Asp Glu Glu Asp Thr Asp 
                470                 475                 480 

Phe Glu Glu Glu Asp Asp Asn Pro Asp Trp Val Ser Glu Leu Lys 
                485                 490                 495 

Lys Arg Ala Gly Trp Gln Gly Leu Cys Asp Arg 
                500                 505 

 
           
             8  
             2014  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7483337CD1  
             
           
            8 

Met Glu Thr Leu Asn Gly Ala Gly Asp Thr Gly Gly Lys Pro Ser 
1               5                   10                  15 

Thr Arg Gly Gly Asp Pro Ala Ala Arg Ser Arg Arg Thr Glu Gly 
                20                  25                  30 

Ile Arg Ala Ala Tyr Arg Arg Gly Asp Arg Gly Gly Ala Arg Asp 
                35                  40                  45 

Leu Leu Glu Glu Ala Cys Asp Gln Cys Ala Ser Gln Leu Glu Lys 
                50                  55                  60 

Gly Gln Leu Leu Ser Ile Pro Ala Ala Tyr Gly Asp Leu Glu Met 
                65                  70                  75 

Val Arg Tyr Leu Leu Ser Lys Arg Leu Val Glu Leu Pro Thr Glu 
                80                  85                  90 

Pro Thr Asp Asp Asn Pro Ala Val Val Ala Ala Tyr Phe Gly His 
                95                  100                 105 

Thr Ala Val Val Gln Asn Thr Leu Pro Thr Glu Pro Thr Asp Asp 
                110                 115                 120 

Asn Pro Ala Val Val Ala Ala Tyr Phe Gly His Thr Ala Val Val 
                125                 130                 135 

Gln Glu Leu Leu Glu Ser Leu Pro Gly Pro Cys Ser Pro Gln Arg 
                140                 145                 150 

Leu Leu Asn Trp Met Leu Ala Leu Ala Cys Gln Arg Gly His Leu 
                155                 160                 165 

Gly Val Val Lys Leu Leu Val Leu Thr His Gly Ala Asp Pro Glu 
                170                 175                 180 

Ser Tyr Ala Val Arg Lys Asn Glu Phe Pro Val Ile Val Arg Leu 
                185                 190                 195 

Pro Leu Tyr Ala Ala Ile Lys Ser Gly Asn Glu Asp Ile Ala Ile 
                200                 205                 210 

Phe Leu Leu Arg His Gly Ala Tyr Phe Cys Ser Tyr Ile Leu Leu 
                215                 220                 225 

Asp Ser Pro Asp Pro Ser Lys His Leu Leu Arg Lys Tyr Phe Ile 
                230                 235                 240 

Glu Ala Ser Pro Leu Pro Ser Ser Tyr Pro Gly Lys Thr Ala Leu 
                245                 250                 255 

Arg Val Lys Trp Ser His Leu Arg Leu Pro Trp Val Asp Leu Asp 
                260                 265                 270 

Trp Leu Ile Asp Ile Ser Cys Gln Ile Thr Glu Leu Asp Leu Ser 
                275                 280                 285 

Ala Asn Cys Leu Ala Thr Leu Pro Ser Val Ile Pro Trp Gly Leu 
                290                 295                 300 

Ile Asn Leu Arg Lys Leu Asn Leu Ser Asp Asn His Leu Gly Glu 
                305                 310                 315 

Leu Pro Gly Val Gln Ser Ser Asp Glu Ile Ile Cys Ser Arg Leu 
                320                 325                 330 

Leu Glu Ile Asp Ile Ser Ser Asn Lys Leu Ser His Leu Pro Pro 
                335                 340                 345 

Gly Phe Leu His Leu Ser Lys Leu Gln Lys Leu Thr Ala Ser Lys 
                350                 355                 360 

Asn Cys Leu Glu Lys Leu Phe Glu Glu Glu Asn Ala Thr Asn Trp 
                365                 370                 375 

Ile Gly Leu Arg Lys Leu Gln Glu Leu Asp Ile Ser Asp Asn Lys 
                380                 385                 390 

Leu Thr Glu Leu Pro Ala Leu Phe Leu His Ser Phe Lys Ser Leu 
                395                 400                 405 

Asn Ser Leu Asn Val Ser Arg Asn Asn Leu Lys Val Phe Pro Asp 
                410                 415                 420 

Pro Trp Ala Cys Pro Leu Lys Cys Cys Lys Ala Ser Arg Asn Ala 
                425                 430                 435 

Leu Glu Cys Leu Pro Asp Lys Met Ala Val Phe Trp Lys Asn His 
                440                 445                 450 

Leu Lys Asp Val Asp Phe Ser Glu Asn Ala Leu Lys Glu Val Pro 
                455                 460                 465 

Leu Gly Leu Phe Gln Leu Asp Ala Leu Met Phe Leu Arg Leu Gln 
                470                 475                 480 

Gly Asn Gln Leu Ala Ala Leu Pro Pro Gln Glu Lys Trp Thr Cys 
                485                 490                 495 

Arg Gln Leu Lys Thr Leu Asp Leu Ser Arg Asn Gln Leu Gly Lys 
                500                 505                 510 

Asn Glu Asp Gly Leu Lys Thr Lys Arg Ile Ala Phe Phe Thr Thr 
                515                 520                 525 

Arg Gly Arg Gln Arg Ser Gly Thr Glu Ala Glu Thr Thr Met Glu 
                530                 535                 540 

Phe Ser Ala Ser Leu Val Thr Ile Val Phe Leu Ser Asn Asn Cys 
                545                 550                 555 

Asn Leu Cys Ala Tyr Thr Cys Ala Ala Ser Val Leu Glu Phe Pro 
                560                 565                 570 

Ala Phe Leu Ser Glu Ser Leu Glu Val Leu Cys Leu Asn Asp Asn 
                575                 580                 585 

His Leu Asp Thr Val Pro Pro Ser Val Cys Leu Leu Lys Ser Leu 
                590                 595                 600 

Ser Glu Leu Tyr Leu Gly Asn Asn Pro Gly Leu Arg Glu Leu Pro 
                605                 610                 615 

Pro Glu Leu Gly Gln Leu Gly Asn Leu Trp Gln Leu Asp Thr Glu 
                620                 625                 630 

Asp Leu Thr Ile Ser Asn Val Pro Ala Glu Ile Gln Lys Glu Gly 
                635                 640                 645 

Pro Lys Ala Met Leu Ser Tyr Leu Arg Ala Gln Leu Arg Lys Ala 
                650                 655                 660 

Glu Lys Cys Lys Leu Met Lys Met Ile Ile Val Gly Pro Pro Arg 
                665                 670                 675 

Gln Gly Lys Ser Thr Leu Leu Glu Ile Leu Gln Thr Gly Arg Ala 
                680                 685                 690 

Pro Gln Val Val His Gly Glu Ala Thr Ile Arg Thr Thr Lys Trp 
                695                 700                 705 

Glu Leu Gln Arg Pro Ala Gly Ser Arg Ala Lys Val Lys Asp Gly 
                710                 715                 720 

Leu Arg Ala Glu Ser Leu Trp Val Glu Ser Val Glu Phe Asn Val 
                725                 730                 735 

Trp Asp Ile Gly Gly Pro Ala Ser Met Ala Thr Val Asn Gln Cys 
                740                 745                 750 

Phe Phe Thr Asp Lys Ala Leu Tyr Val Val Val Trp Asn Leu Ala 
                755                 760                 765 

Leu Gly Glu Glu Ala Val Ala Asn Leu Gln Phe Trp Leu Leu Asn 
                770                 775                 780 

Ile Glu Ala Lys Ala Pro Asn Ala Val Val Leu Val Val Gly Thr 
                785                 790                 795 

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

Thr Leu Arg Ala Tyr Val Leu Ala Leu Cys Arg Ser Pro Ser Gly 
                815                 820                 825 

Ser Arg Ala Thr Gly Phe Pro Asp Ile Thr Phe Lys His Leu His 
                830                 835                 840 

Glu Ile Ser Cys Lys Ser Leu Glu Gly Gln Glu Gly Leu Arg Gln 
                845                 850                 855 

Leu Ile Phe His Val Thr Cys Ser Met Lys Asp Val Gly Ser Thr 
                860                 865                 870 

Ile Gly Cys Gln Arg Leu Ala Gly Arg Leu Ile Pro Arg Ser Tyr 
                875                 880                 885 

Leu Ser Leu Gln Glu Ala Val Leu Ala Glu Gln Gln Arg Arg Ser 
                890                 895                 900 

Arg Asp Asp Asp Val Gln Tyr Leu Thr Asp Arg Gln Leu Glu Gln 
                905                 910                 915 

Leu Val Glu Gln Thr Pro Asp Asn Asp Ile Lys Asp Tyr Glu Asp 
                920                 925                 930 

Leu Gln Ser Ala Ile Ser Phe Leu Ile Glu Thr Gly Thr Leu Leu 
                935                 940                 945 

His Phe Pro Asp Thr Ser His Gly Leu Arg Asn Leu Tyr Phe Leu 
                950                 955                 960 

Asp Pro Ile Trp Leu Ser Glu Cys Leu Gln Arg Ile Phe Asn Ile 
                965                 970                 975 

Lys Gly Ser Arg Ser Val Ala Lys Asn Gly Val Ile Arg Ala Glu 
                980                 985                 990 

Asp Leu Arg Met Leu Leu Val Gly Thr Gly Phe Thr Gln Gln Thr 
                995                 1000                1005 

Glu Glu Gln Tyr Phe Gln Phe Leu Ala Lys Phe Glu Ile Ala Leu 
                1010                1015                1020 

Pro Val Ala Asn Asp Ser Tyr Leu Leu Pro His Leu Leu Pro Ser 
                1025                1030                1035 

Lys Pro Gly Leu Asp Thr His Gly Met Arg His Pro Thr Ala Asn 
                1040                1045                1050 

Thr Ile Gln Arg Val Phe Lys Met Ser Phe Val Pro Val Gly Phe 
                1055                1060                1065 

Trp Gln Arg Phe Ile Ala Arg Met Leu Ile Ser Leu Ala Glu Met 
                1070                1075                1080 

Asp Leu Gln Leu Phe Glu Asn Lys Lys Asn Thr Lys Ser Arg Asn 
                1085                1090                1095 

Arg Lys Val Thr Ile Tyr Ser Phe Thr Gly Asn Gln Arg Asn Arg 
                1100                1105                1110 

Cys Ser Thr Phe Arg Val Lys Arg Asn Gln Thr Ile Tyr Trp Gln 
                1115                1120                1125 

Glu Gly Leu Leu Val Thr Phe Asp Gly Gly Tyr Leu Ser Val Glu 
                1130                1135                1140 

Ser Ser Asp Val Asn Trp Lys Lys Lys Lys Ser Gly Gly Met Lys 
                1145                1150                1155 

Ile Val Cys Gln Ser Glu Val Arg Asp Phe Ser Ala Met Ala Phe 
                1160                1165                1170 

Ile Thr Asp His Val Asn Ser Leu Ile Asp Gln Trp Phe Pro Ala 
                1175                1180                1185 

Leu Thr Ala Thr Glu Ser Asp Gly Thr Pro Leu Met Glu Gln Tyr 
                1190                1195                1200 

Val Pro Cys Pro Val Cys Glu Thr Ala Trp Ala Gln His Thr Asp 
                1205                1210                1215 

Pro Ser Glu Lys Ser Glu Asp Val Gln Tyr Phe Asp Met Glu Asp 
                1220                1225                1230 

Cys Val Leu Thr Ala Ile Glu Arg Asp Phe Ile Ser Cys Pro Arg 
                1235                1240                1245 

His Pro Asp Leu Pro Val Pro Leu Gln Glu Leu Val Pro Glu Leu 
                1250                1255                1260 

Phe Met Thr Asp Phe Pro Ala Arg Leu Phe Leu Glu Asn Ser Lys 
                1265                1270                1275 

Leu Glu His Ser Glu Asp Glu Gly Ser Val Leu Gly Gln Gly Gly 
                1280                1285                1290 

Ser Gly Thr Val Ile Tyr Arg Ala Arg Tyr Gln Gly Gln Pro Val 
                1295                1300                1305 

Ala Val Lys Arg Phe His Ile Lys Lys Phe Lys Asn Phe Ala Asn 
                1310                1315                1320 

Val Pro Ala Asp Thr Met Leu Arg His Leu Arg Ala Thr Asp Ala 
                1325                1330                1335 

Met Lys Asn Phe Ser Glu Phe Arg Gln Glu Ala Ser Met Leu His 
                1340                1345                1350 

Ala Leu Gln His Pro Cys Ile Val Ala Leu Ile Gly Ile Ser Ile 
                1355                1360                1365 

His Pro Leu Cys Phe Ala Leu Glu Leu Ala Pro Leu Ser Ser Leu 
                1370                1375                1380 

Asn Thr Val Leu Ser Glu Asn Ala Arg Asp Ser Ser Phe Ile Pro 
                1385                1390                1395 

Leu Gly His Met Leu Thr Gln Lys Ile Ala Tyr Gln Ile Ala Ser 
                1400                1405                1410 

Gly Leu Ala Tyr Leu His Lys Lys Asn Ile Ile Phe Cys Asp Leu 
                1415                1420                1425 

Lys Ser Asp Asn Ile Leu Val Trp Ser Leu Asp Val Lys Glu His 
                1430                1435                1440 

Ile Asn Ile Lys Leu Ser Asp Tyr Gly Ile Ser Arg Gln Ser Phe 
                1445                1450                1455 

His Glu Gly Ala Leu Gly Val Glu Gly Thr Pro Gly Tyr Gln Ala 
                1460                1465                1470 

Pro Glu Ile Arg Pro Arg Ile Val Tyr Asp Glu Lys Val Asp Met 
                1475                1480                1485 

Phe Ser Tyr Gly Met Val Leu Tyr Glu Leu Leu Ser Gly Gln Arg 
                1490                1495                1500 

Pro Ala Leu Gly His His Gln Leu Gln Ile Ala Lys Lys Leu Ser 
                1505                1510                1515 

Lys Gly Ile Arg Pro Val Leu Gly Gln Pro Glu Glu Val Gln Phe 
                1520                1525                1530 

Arg Arg Leu Gln Ala Leu Met Met Glu Cys Trp Asp Thr Lys Pro 
                1535                1540                1545 

Glu Lys Arg Pro Leu Ala Leu Ser Val Val Ser Gln Met Lys Asp 
                1550                1555                1560 

Pro Thr Phe Ala Thr Phe Met Tyr Glu Leu Cys Cys Gly Lys Gln 
                1565                1570                1575 

Thr Ala Phe Phe Ser Ser Gln Gly Gln Glu Tyr Thr Val Val Phe 
                1580                1585                1590 

Trp Asp Gly Lys Glu Glu Ser Arg Asn Tyr Thr Val Val Asn Thr 
                1595                1600                1605 

Glu Lys Gly Leu Met Glu Val Gln Arg Met Cys Cys Pro Gly Met 
                1610                1615                1620 

Lys Val Ser Cys Gln Leu Gln Val Gln Arg Ser Leu Trp Thr Ala 
                1625                1630                1635 

Thr Glu Asn Ser Tyr Leu Val Leu Ala Gly Leu Ala Asp Gly Leu 
                1640                1645                1650 

Val Ala Val Phe Pro Val Val Arg Gly Thr Pro Lys Asp Ser Cys 
                1655                1660                1665 

Ser Tyr Leu Cys Ser His Thr Ala Asn Arg Ser Lys Phe Ser Ile 
                1670                1675                1680 

Ala Asp Glu Asp Ala Arg Gln Asn Pro Tyr Pro Val Lys Ala Met 
                1685                1690                1695 

Glu Val Val Asn Ser Gly Ser Glu Val Trp Tyr Ser Asn Gly Pro 
                1700                1705                1710 

Gly Leu Leu Val Ile Asp Cys Ala Ser Leu Glu Ile Cys Arg Arg 
                1715                1720                1725 

Leu Glu Pro Tyr Met Ala Pro Ser Met Val Thr Ser Val Val Cys 
                1730                1735                1740 

Ser Ser Glu Gly Arg Gly Glu Glu Val Val Trp Cys Leu Asp Asp 
                1745                1750                1755 

Lys Ala Asn Ser Leu Val Met Tyr His Ser Thr Thr Tyr Gln Leu 
                1760                1765                1770 

Cys Ala Arg Tyr Phe Cys Gly Val Pro Ser Pro Leu Arg Asp Met 
                1775                1780                1785 

Phe Pro Val Arg Pro Leu Asp Thr Glu Pro Pro Ala Ala Ser His 
                1790                1795                1800 

Thr Ala Asn Pro Lys Val Pro Glu Gly Asp Ser Ile Ala Asp Val 
                1805                1810                1815 

Ser Ile Met Tyr Ser Glu Glu Leu Gly Thr Gln Ile Leu Ile His 
                1820                1825                1830 

Gln Glu Ser Leu Thr Asp Tyr Cys Ser Met Ser Ser Tyr Ser Ser 
                1835                1840                1845 

Ser Pro Pro Arg Gln Ala Ala Arg Ser Pro Ser Ser Leu Pro Ser 
                1850                1855                1860 

Ser Pro Ala Ser Ser Ser Ser Val Pro Phe Ser Thr Asp Cys Glu 
                1865                1870                1875 

Asp Ser Asp Met Leu His Thr Pro Gly Ala Ala Ser Asp Arg Ser 
                1880                1885                1890 

Glu His Asp Leu Thr Pro Met Asp Gly Glu Thr Phe Ser Gln His 
                1895                1900                1905 

Leu Gln Ala Val Lys Ile Leu Ala Val Arg Asp Leu Ile Trp Val 
                1910                1915                1920 

Pro Arg Arg Gly Gly Asp Val Ile Val Ile Gly Leu Glu Lys Asp 
                1925                1930                1935 

Ser Gly Ala Gln Arg Gly Arg Val Ile Ala Val Leu Lys Ala Arg 
                1940                1945                1950 

Glu Leu Thr Pro His Gly Val Leu Val Asp Ala Ala Val Val Ala 
                1955                1960                1965 

Lys Asp Thr Val Val Cys Thr Phe Glu Asn Glu Asn Thr Glu Trp 
                1970                1975                1980 

Cys Leu Ala Val Trp Arg Gly Trp Gly Ala Arg Glu Phe Asp Ile 
                1985                1990                1995 

Phe Tyr Gln Ser Tyr Glu Glu Leu Gly Arg Leu Glu Ala Cys Thr 
                2000                2005                2010 

Arg Lys Arg Arg 

 
           
             9  
             348  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 6035509CD1  
             
           
            9 

Met Met Leu Gly Leu Glu Ser Leu Pro Asp Pro Thr Asp Thr Trp 
1               5                   10                  15 

Glu Ile Ile Glu Thr Ile Gly Lys Gly Thr Tyr Gly Lys Val Tyr 
                20                  25                  30 

Lys Val Thr Asn Lys Arg Asp Gly Ser Leu Ala Ala Val Lys Ile 
                35                  40                  45 

Leu Asp Pro Val Ser Asp Met Asp Glu Glu Ile Glu Ala Glu Tyr 
                50                  55                  60 

Asn Ile Leu Gln Phe Leu Pro Asn His Pro Asn Val Val Lys Phe 
                65                  70                  75 

Tyr Gly Met Phe Tyr Lys Ala Asp His Cys Val Gly Gly Gln Leu 
                80                  85                  90 

Trp Leu Val Leu Glu Leu Cys Asn Gly Gly Ser Val Thr Glu Leu 
                95                  100                 105 

Val Lys Gly Leu Leu Arg Cys Gly Gln Arg Leu Asp Glu Ala Met 
                110                 115                 120 

Ile Ser Tyr Ile Leu Tyr Gly Ala Leu Leu Gly Leu Gln His Leu 
                125                 130                 135 

His Asn Asn Arg Ile Ile His Arg Asp Val Lys Gly Asn Asn Ile 
                140                 145                 150 

Leu Leu Thr Thr Glu Gly Gly Val Lys Leu Val Asp Phe Gly Val 
                155                 160                 165 

Ser Ala Gln Leu Thr Ser Thr Arg Leu Arg Arg Asn Thr Ser Val 
                170                 175                 180 

Gly Thr Pro Phe Trp Met Ala Pro Glu Val Ile Ala Cys Glu Gln 
                185                 190                 195 

Gln Tyr Asp Ser Ser Tyr Asp Ala Arg Cys Asp Val Trp Ser Leu 
                200                 205                 210 

Gly Ile Thr Ala Ile Glu Leu Gly Asp Gly Asp Pro Pro Leu Phe 
                215                 220                 225 

Asp Met His Pro Val Lys Thr Leu Phe Lys Ile Pro Arg Asn Pro 
                230                 235                 240 

Pro Pro Thr Leu Leu His Pro Glu Lys Trp Cys Glu Glu Phe Asn 
                245                 250                 255 

His Phe Ile Ser Gln Cys Leu Ile Lys Asp Phe Glu Arg Arg Pro 
                260                 265                 270 

Ser Val Thr His Leu Leu Asp His Pro Phe Ile Lys Gly Val His 
                275                 280                 285 

Gly Lys Val Leu Phe Leu Gln Lys Gln Leu Ala Lys Val Leu Gln 
                290                 295                 300 

Asp Gln Lys His Gln Asn Pro Val Ala Lys Thr Arg His Glu Arg 
                305                 310                 315 

Met His Thr Arg Arg Pro Tyr His Val Glu Asp Ala Glu Lys Tyr 
                320                 325                 330 

Cys Leu Glu Asp Asp Leu Val Asn Leu Glu Val Leu Asp Glu Val 
                335                 340                 345 

Leu Asn Ile 

 
           
             10  
             2042  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7373485CD1  
             
           
            10 

Met Ala Thr Asp Asp Lys Thr Ser Pro Thr Leu Asp Ser Ala Asn 
1               5                   10                  15 

Asp Leu Pro Arg Ser Pro Thr Ser Pro Ser His Leu Thr His Phe 
                20                  25                  30 

Lys Pro Leu Thr Pro Asp Gln Asp Glu Pro Pro Phe Lys Ser Ala 
                35                  40                  45 

Tyr Ser Ser Phe Val Asn Leu Phe Arg Phe Asn Lys Glu Arg Ala 
                50                  55                  60 

Glu Gly Gly Gln Gly Glu Gln Gln Pro Leu Ser Gly Ser Trp Thr 
                65                  70                  75 

Ser Pro Gln Leu Pro Ser Arg Thr Gln Ser Val Arg Ser Pro Thr 
                80                  85                  90 

Pro Tyr Lys Lys Gln Leu Asn Glu Glu Leu Gln Arg Arg Ser Ser 
                95                  100                 105 

Ala Leu Asp Thr Arg Arg Lys Ala Glu Pro Thr Phe Gly Gly His 
                110                 115                 120 

Asp Pro Arg Thr Ala Val Gln Leu Arg Ser Leu Ser Thr Val Leu 
                125                 130                 135 

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

Leu Lys Gln Tyr Trp Met Pro Asp Ser Gln Cys Lys Glu Cys Tyr 
                155                 160                 165 

Asp Cys Ser Glu Lys Phe Thr Thr Phe Arg Arg Arg His His Cys 
                170                 175                 180 

Arg Leu Cys Gly Gln Ile Phe Cys Ser Arg Cys Cys Asn Gln Glu 
                185                 190                 195 

Ile Pro Gly Lys Phe Met Gly Tyr Thr Gly Asp Leu Arg Ala Cys 
                200                 205                 210 

Thr Tyr Cys Arg Lys Ile Ala Leu Ser Tyr Ala His Ser Thr Asp 
                215                 220                 225 

Ser Asn Ser Ile Gly Glu Asp Leu Asn Ala Leu Ser Asp Ser Ala 
                230                 235                 240 

Cys Ser Val Ser Val Leu Asp Pro Ser Glu Pro Arg Thr Pro Val 
                245                 250                 255 

Gly Ser Arg Lys Ala Ser Arg Asn Ile Phe Leu Glu Asp Asp Leu 
                260                 265                 270 

Ala Trp Gln Ser Leu Ile His Pro Asp Ser Ser Asn Thr Pro Leu 
                275                 280                 285 

Ser Thr Arg Leu Val Ser Val Gln Glu Asp Ala Gly Lys Ser Pro 
                290                 295                 300 

Ala Arg Asn Arg Ser Ala Ser Ile Thr Asn Leu Ser Leu Asp Arg 
                305                 310                 315 

Ser Gly Ser Pro Met Val Pro Ser Tyr Glu Thr Ser Val Ser Pro 
                320                 325                 330 

Gln Ala Asn Arg Thr Tyr Val Arg Thr Glu Thr Thr Glu Asp Glu 
                335                 340                 345 

Arg Lys Ile Leu Leu Asp Ser Val Gln Leu Lys Asp Leu Trp Lys 
                350                 355                 360 

Lys Ile Cys His His Ser Ser Gly Met Glu Phe Gln Asp His Arg 
                365                 370                 375 

Tyr Trp Leu Arg Thr His Pro Asn Cys Ile Val Gly Lys Glu Leu 
                380                 385                 390 

Val Asn Trp Leu Ile Arg Asn Gly His Ile Ala Thr Arg Ala Gln 
                395                 400                 405 

Ala Ile Ala Ile Gly Gln Ala Met Val Asp Gly Arg Trp Leu Asp 
                410                 415                 420 

Cys Val Ser His His Asp Gln Leu Phe Arg Asp Glu Tyr Ala Leu 
                425                 430                 435 

Tyr Arg Pro Leu Gln Ser Thr Glu Phe Ser Glu Thr Pro Ser Pro 
                440                 445                 450 

Asp Ser Asp Ser Val Asn Ser Val Glu Gly His Ser Glu Pro Ser 
                455                 460                 465 

Trp Phe Lys Asp Ile Lys Phe Asp Asp Ser Asp Thr Glu Gln Ile 
                470                 475                 480 

Ala Glu Glu Gly Asp Asp Asn Leu Ala Lys Tyr Leu Ile Ser Asp 
                485                 490                 495 

Thr Gly Gly Gln Gln Leu Ser Ile Ser Asp Ala Phe Ile Lys Glu 
                500                 505                 510 

Ser Leu Phe Asn Arg Arg Val Glu Glu Lys Ser Lys Glu Leu Pro 
                515                 520                 525 

Phe Thr Pro Leu Gly Trp His His Asn Asn Leu Glu Leu Leu Arg 
                530                 535                 540 

Glu Glu Asn Gly Glu Lys Gln Ala Met Glu Arg Leu Leu Ser Ala 
                545                 550                 555 

Asn His Asn His Met Met Ala Leu Leu Gln Gln Leu Leu His Ser 
                560                 565                 570 

Asp Ser Leu Ser Ser Ser Trp Arg Asp Ile Ile Val Ser Leu Val 
                575                 580                 585 

Cys Gln Val Val Gln Thr Val Arg Pro Asp Val Lys Asn Gln Asp 
                590                 595                 600 

Asp Asp Met Asp Ile Arg Gln Phe Val His Ile Lys Lys Ile Pro 
                605                 610                 615 

Gly Gly Lys Lys Phe Asp Ser Val Val Val Asn Gly Phe Val Cys 
                620                 625                 630 

Thr Lys Asn Ile Ala His Lys Lys Met Asn Ser Cys Ile Lys Asn 
                635                 640                 645 

Pro Lys Ile Leu Leu Leu Lys Cys Ser Ile Glu Tyr Leu Tyr Arg 
                650                 655                 660 

Glu Glu Thr Lys Phe Thr Cys Ile Asp Pro Ile Val Leu Gln Glu 
                665                 670                 675 

Arg Glu Phe Leu Lys Asn Tyr Val Gln Arg Ile Val Asp Val Arg 
                680                 685                 690 

Pro Thr Leu Val Leu Val Glu Lys Thr Val Ser Arg Ile Ala Gln 
                695                 700                 705 

Asp Met Leu Leu Glu His Gly Ile Thr Leu Val Ile Asn Val Lys 
                710                 715                 720 

Ser Gln Val Leu Glu Arg Ile Ser Arg Met Thr Gln Gly Asp Leu 
                725                 730                 735 

Val Met Ser Met Asp Gln Leu Leu Thr Lys Pro Arg Leu Gly Thr 
                740                 745                 750 

Cys His Lys Phe Tyr Met Gln Ile Phe Gln Leu Pro Asn Glu Gln 
                755                 760                 765 

Thr Lys Thr Leu Met Phe Phe Glu Gly Cys Pro Gln His Leu Gly 
                770                 775                 780 

Cys Thr Ile Lys Leu Arg Gly Gly Ser Asp Tyr Glu Leu Ala Arg 
                785                 790                 795 

Val Lys Glu Ile Leu Ile Phe Met Ile Cys Val Ala Tyr His Ser 
                800                 805                 810 

Gln Leu Glu Ile Ser Phe Leu Met Asp Glu Phe Ala Met Pro Pro 
                815                 820                 825 

Thr Leu Met Gln Asn Pro Ser Phe His Ser Leu Ile Glu Gly Arg 
                830                 835                 840 

Gly His Glu Gly Ala Val Gln Glu Gln Tyr Gly Gly Gly Ser Ile 
                845                 850                 855 

Pro Trp Asp Pro Asp Ile Pro Pro Glu Ser Leu Pro Cys Asp Asp 
                860                 865                 870 

Ser Ser Leu Leu Glu Ser Arg Ile Val Phe Glu Lys Gly Glu Gln 
                875                 880                 885 

Glu Asn Lys Asn Leu Pro Gln Ala Val Ala Ser Val Lys His Gln 
                890                 895                 900 

Glu His Ser Thr Thr Ala Cys Pro Ala Gly Leu Pro Cys Ala Phe 
                905                 910                 915 

Phe Ala Pro Val Pro Glu Ser Leu Leu Pro Leu Pro Val Asp Asp 
                920                 925                 930 

Gln Gln Asp Ala Leu Gly Ser Glu Leu Pro Glu Ser Leu Gln Gln 
                935                 940                 945 

Thr Val Val Leu Gln Asp Pro Lys Ser Gln Ile Arg Ala Phe Arg 
                950                 955                 960 

Asp Pro Leu Gln Asp Asp Thr Gly Leu Tyr Val Thr Glu Glu Val 
                965                 970                 975 

Thr Ser Ser Glu Asp Lys Arg Lys Thr Tyr Ser Leu Ala Phe Lys 
                980                 985                 990 

Gln Glu Leu Lys Asp Val Ile Leu Cys Ile Ser Pro Val Ile Thr 
                995                 1000                1005 

Phe Arg Glu Pro Phe Leu Leu Thr Glu Lys Gly Met Arg Cys Ser 
                1010                1015                1020 

Thr Arg Asp Tyr Phe Ala Glu Gln Val Tyr Trp Ser Pro Leu Leu 
                1025                1030                1035 

Asn Lys Glu Phe Lys Glu Met Glu Asn Arg Arg Lys Lys Gln Leu 
                1040                1045                1050 

Leu Arg Asp Leu Ser Gly Leu Gln Gly Met Asn Gly Ser Ile Gln 
                1055                1060                1065 

Ala Lys Ser Ile Gln Val Leu Pro Ser His Glu Leu Val Ser Thr 
                1070                1075                1080 

Arg Ile Ala Glu His Leu Gly Asp Ser Gln Ser Leu Gly Arg Met 
                1085                1090                1095 

Leu Ala Asp Tyr Arg Ala Arg Gly Gly Arg Ile Gln Pro Lys Asn 
                1100                1105                1110 

Ser Asp Pro Phe Ala His Ser Lys Asp Ala Ser Ser Thr Ser Ser 
                1115                1120                1125 

Gly Lys Ser Gly Ser Lys Asn Glu Gly Asp Glu Glu Arg Gly Leu 
                1130                1135                1140 

Ile Leu Ser Asp Ala Val Trp Ser Thr Lys Val Asp Cys Leu Asn 
                1145                1150                1155 

Pro Ile Asn His Gln Arg Leu Cys Val Leu Phe Ser Ser Ser Ser 
                1160                1165                1170 

Ala Gln Ser Ser Asn Ala Pro Ser Ala Cys Val Ser Pro Trp Ile 
                1175                1180                1185 

Val Thr Met Glu Phe Tyr Gly Lys Asn Asp Leu Thr Leu Gly Ile 
                1190                1195                1200 

Phe Leu Glu Arg Tyr Cys Phe Arg Pro Ser Tyr Gln Cys Pro Ser 
                1205                1210                1215 

Met Phe Cys Asp Thr Pro Met Val His His Ile Arg Arg Phe Val 
                1220                1225                1230 

His Gly Gln Gly Cys Val Gln Ile Ile Leu Lys Glu Leu Asp Ser 
                1235                1240                1245 

Pro Val Pro Gly Tyr Gln His Thr Ile Leu Thr Tyr Ser Trp Cys 
                1250                1255                1260 

Arg Ile Cys Lys Gln Val Thr Pro Val Val Ala Leu Ser Asn Glu 
                1265                1270                1275 

Ser Trp Ser Met Ser Phe Ala Lys Tyr Leu Glu Leu Arg Phe Tyr 
                1280                1285                1290 

Gly His Gln Tyr Thr Arg Arg Ala Asn Ala Glu Pro Cys Gly His 
                1295                1300                1305 

Ser Ile His His Asp Tyr His Gln Tyr Phe Ser Tyr Asn Gln Met 
                1310                1315                1320 

Val Ala Ser Phe Ser Tyr Ser Pro Ile Arg Leu Leu Glu Val Cys 
                1325                1330                1335 

Val Pro Leu Pro Lys Ile Phe Ile Lys Arg Gln Ala Pro Leu Lys 
                1340                1345                1350 

Val Ser Leu Leu Gln Asp Leu Lys Asp Phe Phe Gln Lys Val Ser 
                1355                1360                1365 

Gln Val Tyr Val Ala Ile Asp Glu Arg Leu Ala Ser Leu Lys Thr 
                1370                1375                1380 

Asp Thr Phe Ser Lys Thr Arg Glu Glu Lys Met Glu Asp Ile Phe 
                1385                1390                1395 

Ala Gln Lys Glu Met Glu Glu Gly Glu Phe Lys Asn Trp Ile Glu 
                1400                1405                1410 

Lys Met Gln Ala Arg Leu Met Ser Ser Ser Val Asp Thr Pro Gln 
                1415                1420                1425 

Gln Leu Gln Ser Val Phe Glu Ser Leu Ile Ala Lys Lys Gln Ser 
                1430                1435                1440 

Leu Cys Glu Val Leu Gln Ala Trp Asn Asn Arg Leu Gln Asp Leu 
                1445                1450                1455 

Phe Gln Gln Glu Lys Gly Arg Lys Arg Pro Ser Val Pro Pro Ser 
                1460                1465                1470 

Pro Gly Arg Leu Arg Gln Gly Glu Glu Ser Lys Ile Ser Ala Met 
                1475                1480                1485 

Asp Ala Ser Pro Arg Asn Ile Ser Pro Gly Leu Gln Asn Gly Glu 
                1490                1495                1500 

Lys Glu Asp Arg Phe Leu Thr Thr Leu Ser Ser Gln Ser Ser Thr 
                1505                1510                1515 

Ser Ser Thr His Leu Gln Leu Pro Thr Pro Pro Glu Val Met Ser 
                1520                1525                1530 

Glu Gln Ser Val Gly Gly Pro Pro Glu Leu Asp Thr Ala Ser Ser 
                1535                1540                1545 

Ser Glu Asp Val Phe Asp Gly His Leu Leu Gly Ser Thr Asp Ser 
                1550                1555                1560 

Gln Val Lys Glu Lys Ser Thr Met Lys Ala Ile Phe Ala Asn Leu 
                1565                1570                1575 

Leu Pro Gly Asn Ser Tyr Asn Pro Ile Pro Phe Pro Phe Asp Pro 
                1580                1585                1590 

Asp Lys His Tyr Leu Met Tyr Glu His Glu Arg Val Pro Ile Ala 
                1595                1600                1605 

Val Cys Glu Lys Glu Pro Ser Ser Ile Ile Ala Phe Ala Leu Ser 
                1610                1615                1620 

Cys Lys Glu Tyr Arg Asn Ala Leu Glu Glu Leu Ser Lys Ala Thr 
                1625                1630                1635 

Gln Trp Asn Ser Ala Glu Glu Gly Leu Pro Thr Asn Ser Thr Ser 
                1640                1645                1650 

Asp Ser Arg Pro Lys Ser Ser Ser Pro Ile Arg Leu Pro Glu Met 
                1655                1660                1665 

Ser Gly Gly Gln Thr Asn Arg Thr Thr Glu Thr Glu Pro Gln Pro 
                1670                1675                1680 

Thr Lys Lys Ala Ser Gly Met Leu Ser Phe Phe Arg Gly Thr Ala 
                1685                1690                1695 

Gly Lys Ser Pro Asp Leu Ser Ser Gln Lys Arg Glu Thr Leu Arg 
                1700                1705                1710 

Gly Ala Asp Ser Ala Tyr Tyr Gln Val Gly Gln Thr Gly Lys Glu 
                1715                1720                1725 

Gly Thr Glu Asn Gln Gly Val Glu Pro Gln Asp Glu Val Asp Gly 
                1730                1735                1740 

Gly Asp Thr Gln Lys Lys Gln Leu Ile Asn Pro His Val Glu Leu 
                1745                1750                1755 

Gln Phe Ser Asp Ala Asn Ala Lys Phe Tyr Cys Arg Leu Tyr Tyr 
                1760                1765                1770 

Ala Gly Glu Phe His Lys Met Arg Glu Val Ile Leu Asp Ser Ser 
                1775                1780                1785 

Glu Glu Asp Phe Ile Arg Ser Leu Ser His Ser Ser Pro Trp Gln 
                1790                1795                1800 

Ala Arg Gly Gly Lys Ser Gly Ala Ala Phe Tyr Ala Thr Glu Asp 
                1805                1810                1815 

Asp Arg Phe Ile Leu Lys Gln Met Pro Arg Leu Glu Val Gln Ser 
                1820                1825                1830 

Phe Leu Asp Phe Ala Pro His Tyr Phe Asn Tyr Ile Thr Asn Ala 
                1835                1840                1845 

Val Gln Gln Lys Arg Pro Thr Ala Leu Ala Lys Ile Leu Gly Val 
                1850                1855                1860 

Tyr Arg Ile Gly Tyr Lys Asn Ser Gln Asn Asn Thr Glu Lys Lys 
                1865                1870                1875 

Leu Asp Leu Leu Val Met Glu Asn Leu Phe Tyr Gly Arg Lys Met 
                1880                1885                1890 

Ala Gln Val Phe Asp Leu Lys Gly Ser Leu Arg Asn Arg Asn Val 
                1895                1900                1905 

Lys Thr Asp Thr Gly Lys Glu Ser Cys Asp Val Val Leu Leu Asp 
                1910                1915                1920 

Glu Asn Leu Leu Lys Met Val Arg Asp Asn Pro Leu Tyr Ile Arg 
                1925                1930                1935 

Ser His Ser Lys Ala Val Leu Arg Thr Ser Ile His Ser Asp Ser 
                1940                1945                1950 

His Phe Leu Ser Ser His Leu Ile Ile Asp Tyr Ser Leu Leu Val 
                1955                1960                1965 

Gly Arg Asp Asp Thr Ser Asn Glu Leu Val Val Gly Ile Ile Asp 
                1970                1975                1980 

Tyr Ile Arg Thr Phe Thr Trp Asp Lys Lys Leu Glu Met Val Val 
                1985                1990                1995 

Lys Ser Thr Gly Ile Leu Gly Gly Gln Gly Lys Met Pro Thr Val 
                2000                2005                2010 

Val Ser Pro Glu Leu Tyr Arg Thr Arg Phe Cys Glu Ala Met Asp 
                2015                2020                2025 

Lys Tyr Phe Leu Met Val Pro Asp His Trp Thr Gly Leu Gly Leu 
                2030                2035                2040 

Asn Cys 

 
           
             11  
             551  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 5734965CD1  
             
           
            11 

Met Ser Gly Gly Glu Gln Lys Pro Glu Arg Tyr Tyr Val Gly Val 
1               5                   10                  15 

Asp Val Gly Thr Gly Ser Val Arg Ala Ala Leu Val Asp Gln Ser 
                20                  25                  30 

Gly Val Leu Leu Ala Phe Ala Asp Gln Pro Ile Lys Asn Trp Glu 
                35                  40                  45 

Pro Gln Phe Asn His His Glu Gln Ser Ser Glu Asp Ile Trp Ala 
                50                  55                  60 

Ala Cys Cys Val Val Thr Lys Lys Val Val Gln Gly Ile Asp Leu 
                65                  70                  75 

Asn Gln Ile Arg Gly Leu Gly Phe Asp Ala Thr Cys Ser Leu Val 
                80                  85                  90 

Val Leu Asp Lys Gln Phe His Pro Leu Pro Val Asn Gln Glu Gly 
                95                  100                 105 

Asp Ser His Arg Asn Val Ile Met Trp Leu Asp His Arg Ala Val 
                110                 115                 120 

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

Tyr Val Gly Gly Val Met Ser Val Glu Met Gln Ala Pro Lys Leu 
                140                 145                 150 

Leu Trp Leu Lys Glu Asn Leu Arg Glu Ile Cys Trp Asp Lys Ala 
                155                 160                 165 

Gly His Phe Phe Asp Leu Pro Asp Phe Leu Ser Trp Lys Ala Thr 
                170                 175                 180 

Gly Val Thr Ala Arg Ser Leu Cys Ser Leu Val Cys Lys Trp Thr 
                185                 190                 195 

Tyr Ser Ala Glu Lys Gly Trp Asp Asp Ser Phe Trp Lys Met Ile 
                200                 205                 210 

Gly Leu Glu Asp Phe Val Ala Asp Asn Tyr Ser Lys Ile Gly Asn 
                215                 220                 225 

Gln Val Leu Pro Pro Gly Ala Ser Leu Gly Asn Gly Leu Thr Pro 
                230                 235                 240 

Glu Ala Ala Arg Asp Leu Gly Leu Leu Pro Gly Ile Ala Val Ala 
                245                 250                 255 

Ala Ser Leu Ile Asp Ala His Ala Gly Gly Leu Gly Val Ile Gly 
                260                 265                 270 

Ala Asp Val Arg Gly His Gly Leu Ile Cys Glu Gly Gln Pro Val 
                275                 280                 285 

Thr Ser Arg Leu Ala Val Ile Cys Gly Thr Ser Ser Cys His Met 
                290                 295                 300 

Gly Ile Ser Lys Asp Pro Ile Phe Val Pro Gly Val Trp Gly Pro 
                305                 310                 315 

Tyr Phe Ser Ala Met Val Pro Gly Phe Trp Leu Asn Glu Gly Gly 
                320                 325                 330 

Gln Ser Val Thr Gly Lys Leu Ile Asp His Met Val Gln Gly His 
                335                 340                 345 

Ala Ala Phe Pro Glu Leu Gln Val Lys Ala Thr Ala Arg Cys Gln 
                350                 355                 360 

Ser Ile Tyr Ala Tyr Leu Asn Ser His Leu Asp Leu Ile Lys Lys 
                365                 370                 375 

Ala Gln Pro Val Gly Phe Leu Thr Val Asp Leu His Val Trp Pro 
                380                 385                 390 

Asp Phe His Gly Asn Arg Ser Pro Leu Ala Asp Leu Thr Leu Lys 
                395                 400                 405 

Gly Met Val Thr Gly Leu Lys Leu Ser Gln Asp Leu Asp Asp Leu 
                410                 415                 420 

Ala Ile Leu Tyr Leu Ala Thr Val Gln Ala Ile Ala Leu Gly Thr 
                425                 430                 435 

Arg Phe Ile Ile Glu Ala Met Glu Ala Ala Gly His Ser Ile Ser 
                440                 445                 450 

Thr Leu Phe Leu Cys Gly Gly Leu Ser Lys Asn Pro Leu Phe Val 
                455                 460                 465 

Gln Met His Ala Asp Ile Thr Gly Met Pro Val Val Leu Ser Gln 
                470                 475                 480 

Glu Val Glu Ser Val Leu Val Gly Ala Ala Val Leu Gly Ala Cys 
                485                 490                 495 

Ala Ser Gly Asp Phe Ala Ser Val Gln Glu Ala Met Ala Lys Met 
                500                 505                 510 

Ser Lys Val Gly Lys Val Val Phe Pro Arg Leu Gln Asp Lys Lys 
                515                 520                 525 

Tyr Tyr Asp Lys Lys Tyr Gln Val Phe Leu Lys Leu Val Glu His 
                530                 535                 540 

Gln Lys Glu Tyr Leu Ala Ile Met Asn Asp Asp 
                545                 550 

 
           
             12  
             485  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7473788CD1  
             
           
            12 

Met Arg Ser Gly Ala Glu Arg Arg Gly Ser Ser Ala Ala Ala Ser 
1               5                   10                  15 

Pro Gly Ser Pro Pro Pro Gly Arg Ala Arg Pro Ala Gly Ser Asp 
                20                  25                  30 

Ala Pro Ser Ala Leu Pro Pro Pro Ala Ala Gly Gln Pro Arg Ala 
                35                  40                  45 

Arg Asp Ser Gly Asp Val Arg Ser Gln Pro Arg Pro Leu Phe Gln 
                50                  55                  60 

Trp Ser Lys Trp Lys Lys Arg Met Gly Ser Ser Met Ser Ala Ala 
                65                  70                  75 

Thr Ala Arg Arg Pro Val Phe Asp Asp Lys Glu Asp Val Asn Phe 
                80                  85                  90 

Asp His Phe Gln Ile Leu Arg Ala Ile Gly Lys Gly Ser Phe Gly 
                95                  100                 105 

Lys Val Cys Ile Val Gln Lys Arg Asp Thr Glu Lys Met Tyr Ala 
                110                 115                 120 

Met Lys Tyr Met Asn Lys Gln Gln Cys Ile Glu Arg Asp Glu Val 
                125                 130                 135 

Arg Asn Val Phe Arg Glu Leu Glu Ile Leu Gln Glu Ile Glu His 
                140                 145                 150 

Val Phe Leu Val Asn Leu Trp Tyr Ser Phe Gln Asp Glu Glu Asp 
                155                 160                 165 

Met Phe Met Val Val Asp Leu Leu Leu Gly Gly Asp Leu Arg Tyr 
                170                 175                 180 

His Leu Gln Gln Asn Val Gln Phe Ser Glu Asp Thr Val Arg Leu 
                185                 190                 195 

Tyr Ile Cys Glu Met Ala Leu Ala Leu Asp Tyr Leu Arg Gly Gln 
                200                 205                 210 

His Ile Ile His Arg Asp Val Lys Pro Asp Asn Ile Leu Leu Asp 
                215                 220                 225 

Glu Arg Gly His Ala His Leu Thr Asp Phe Asn Ile Ala Thr Ile 
                230                 235                 240 

Ile Lys Asp Gly Glu Arg Ala Thr Ala Leu Ala Gly Thr Lys Pro 
                245                 250                 255 

Tyr Met Ala Pro Glu Ile Phe His Ser Phe Val Asn Gly Gly Thr 
                260                 265                 270 

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

Tyr Glu Leu Leu Arg Gly Trp Arg Pro Tyr Asp Ile His Ser Ser 
                290                 295                 300 

Asn Ala Val Glu Ser Leu Val Gln Leu Phe Ser Thr Val Ser Val 
                305                 310                 315 

Gln Tyr Val Pro Thr Trp Ser Lys Glu Met Val Ala Leu Leu Arg 
                320                 325                 330 

Lys Leu Leu Thr Val Asn Pro Glu His Arg Leu Ser Ser Leu Gln 
                335                 340                 345 

Asp Val Gln Ala Ala Pro Ala Leu Ala Gly Val Leu Trp Asp His 
                350                 355                 360 

Leu Ser Glu Lys Arg Val Glu Pro Gly Phe Val Pro Asn Lys Gly 
                365                 370                 375 

Arg Leu His Cys Asp Pro Thr Phe Glu Leu Glu Glu Met Ile Leu 
                380                 385                 390 

Glu Ser Arg Pro Leu His Lys Lys Lys Lys Arg Leu Ala Lys Asn 
                395                 400                 405 

Lys Ser Arg Asp Asn Ser Arg Asp Ser Ser Gln Ser Glu Asn Asp 
                410                 415                 420 

Tyr Leu Gln Asp Cys Leu Asp Ala Ile Gln Gln Asp Phe Val Ile 
                425                 430                 435 

Phe Asn Arg Glu Lys Leu Lys Arg Ser Gln Asp Leu Pro Arg Glu 
                440                 445                 450 

Pro Leu Pro Ala Leu Ser Pro Gly Met Leu Arg Ser Leu Trp Arg 
                455                 460                 465 

Thr Arg Arg Thr Leu Arg Leu Pro Met Cys Gly Pro Ile Cys Pro 
                470                 475                 480 

Ser Ala Gly Ser Gly 
                485 

 
           
             13  
             282  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 3107989CD1  
             
           
            13 

Met Pro Ala Phe Ile Gln Met Gly Arg Asp Lys Asn Phe Ser Ser 
1               5                   10                  15 

Leu His Thr Val Phe Cys Ala Thr Gly Gly Gly Ala Tyr Lys Phe 
                20                  25                  30 

Glu Gln Asp Phe Leu Thr Ile Gly Asp Leu Gln Leu Cys Lys Leu 
                35                  40                  45 

Asp Glu Leu Asp Cys Leu Ile Lys Gly Ile Leu Tyr Ile Asp Ser 
                50                  55                  60 

Val Gly Phe Asn Gly Arg Ser Gln Cys Tyr Tyr Phe Glu Asn Pro 
                65                  70                  75 

Ala Asp Ser Glu Lys Cys Gln Lys Leu Pro Phe Asp Leu Lys Asn 
                80                  85                  90 

Pro Tyr Pro Leu Leu Leu Val Asn Ile Gly Ser Gly Val Ser Ile 
                95                  100                 105 

Leu Ala Val Tyr Ser Lys Asp Asn Tyr Lys Arg Val Thr Gly Thr 
                110                 115                 120 

Ser Leu Gly Gly Gly Thr Phe Phe Gly Leu Cys Cys Leu Leu Thr 
                125                 130                 135 

Gly Cys Thr Thr Phe Glu Glu Ala Leu Glu Met Ala Ser Arg Gly 
                140                 145                 150 

Asp Ser Thr Lys Val Asp Lys Leu Val Arg Asp Ile Tyr Gly Gly 
                155                 160                 165 

Asp Tyr Glu Arg Phe Gly Leu Pro Gly Trp Ala Val Ala Ser Ser 
                170                 175                 180 

Phe Gly Asn Met Met Ser Lys Glu Lys Arg Asp Ser Ile Ser Lys 
                185                 190                 195 

Glu Asp Leu Ala Arg Ala Thr Leu Val Thr Ile Thr Asn Asn Ile 
                200                 205                 210 

Gly Ser Ile Ala Arg Met Cys Ala Leu Asn Glu Asn Ile Asp Arg 
                215                 220                 225 

Val Val Phe Val Gly Asn Phe Leu Arg Ile Asn Met Val Ser Met 
                230                 235                 240 

Lys Leu Leu Ala Tyr Ala Met Asp Phe Trp Ser Lys Gly Gln Leu 
                245                 250                 255 

Lys Ala Leu Phe Leu Glu His Glu Gly Tyr Phe Gly Ala Val Gly 
                260                 265                 270 

Ala Leu Leu Glu Leu Phe Lys Met Thr Asp Asp Lys 
                275                 280 

 
           
             14  
             151  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7482887CD1  
             
           
            14 

Met Ala Asn Thr Glu Ser Ile Ile Ile Asn Pro Ser Ala Val Gln 
1               5                   10                  15 

His Ser Leu Val Gly Glu Ile Ile Lys Tyr Ser Glu Gln Lys Gly 
                20                  25                  30 

Phe Tyr Leu Val Thr Met Lys Phe Leu Arg Ala Ser Glu Lys Pro 
                35                  40                  45 

Leu Lys Pro His Tyr Thr Asn Leu Lys Asp His Pro Phe Phe Pro 
                50                  55                  60 

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

Leu Glu Gly Leu Asn Val Ala Lys Thr Gly Leu Arg Met Leu Gly 
                80                  85                  90 

Glu Thr Asn Ser Leu Gly Ser Met Leu Glu Thr Ile Ile Arg Arg 
                95                  100                 105 

Asp Phe Cys Ala Lys Ile Gly Gly Asn Val Ile Gly Gly Ser Asp 
                110                 115                 120 

Ser Leu Gln Ser Ala Glu Lys Glu Ile Ser Leu Trp Phe Lys Pro 
                125                 130                 135 

Lys Glu Pro Val Asp Tyr Arg Ser Cys Ala Tyr Asp Trp Val Tyr 
                140                 145                 150 

Ala 

 
           
             15  
             410  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 2963414CD1  
             
           
            15 

Met Val Val Gln Asn Ser Ala Asp Ala Gly Asp Met Arg Ala Gly 
1               5                   10                  15 

Val Gln Leu Glu Pro Phe Leu His Gln Val Gly Gly His Met Ser 
                20                  25                  30 

Val Met Lys Tyr Asp Glu His Thr Val Cys Lys Pro Leu Val Ser 
                35                  40                  45 

Arg Glu Gln Arg Phe Tyr Glu Ser Leu Pro Leu Ala Met Lys Arg 
                50                  55                  60 

Phe Thr Pro Gln Tyr Lys Gly Thr Val Thr Val His Leu Trp Lys 
                65                  70                  75 

Asp Ser Thr Gly His Leu Ser Leu Val Ala Asn Pro Val Lys Glu 
                80                  85                  90 

Ser Gln Glu Pro Phe Lys Val Ser Thr Glu Ser Ala Ala Val Ala 
                95                  100                 105 

Ile Trp Gln Thr Leu Gln Gln Thr Thr Gly Ser Asn Gly Ser Asp 
                110                 115                 120 

Cys Thr Leu Ala Gln Trp Pro His Ala Gln Leu Ala Arg Ser Pro 
                125                 130                 135 

Lys Glu Ser Pro Ala Lys Ala Leu Leu Arg Ser Glu Pro His Leu 
                140                 145                 150 

Asn Thr Pro Ala Phe Ser Leu Val Glu Asp Thr Asn Gly Asn Gln 
                155                 160                 165 

Val Glu Arg Lys Ser Phe Asn Pro Trp Gly Leu Gln Cys His Gln 
                170                 175                 180 

Ala His Leu Thr Arg Leu Cys Ser Glu Tyr Pro Glu Asn Lys Arg 
                185                 190                 195 

His Arg Phe Leu Leu Leu Glu Asn Val Val Ser Gln Tyr Thr His 
                200                 205                 210 

Pro Cys Val Leu Asp Leu Lys Met Gly Thr Arg Gln His Gly Asp 
                215                 220                 225 

Asp Ala Ser Glu Glu Lys Lys Ala Arg His Met Arg Lys Cys Ala 
                230                 235                 240 

Gln Ser Thr Ser Ala Cys Leu Gly Val Arg Ile Cys Gly Met Gln 
                245                 250                 255 

Val Tyr Gln Thr Asp Lys Lys Tyr Phe Leu Cys Lys Asp Lys Tyr 
                260                 265                 270 

Tyr Gly Arg Lys Leu Ser Val Glu Gly Phe Arg Gln Ala Leu Tyr 
                275                 280                 285 

Gln Phe Leu His Asn Gly Ser His Leu Arg Arg Glu Leu Leu Glu 
                290                 295                 300 

Pro Ile Leu His Gln Leu Arg Ala Leu Leu Ser Ile Ile Arg Ser 
                305                 310                 315 

Gln Ser Ser Tyr Arg Phe Tyr Ser Ser Ser Leu Leu Val Ile Tyr 
                320                 325                 330 

Asp Gly Gln Glu Pro Pro Glu Arg Ala Pro Gly Ser Pro His Pro 
                335                 340                 345 

His Glu Ala Pro Gln Ala Ala His Gly Ser Ser Pro Gly Gly Leu 
                350                 355                 360 

Thr Lys Val Asp Ile Arg Met Ile Asp Phe Ala His Thr Thr Tyr 
                365                 370                 375 

Lys Gly Tyr Trp Asn Glu His Thr Thr Tyr Asp Gly Pro Asp Pro 
                380                 385                 390 

Gly Tyr Ile Phe Gly Leu Glu Asn Leu Ile Arg Ile Leu Gln Asp 
                395                 400                 405 

Ile Gln Glu Gly Glu 
                410 

 
           
             16  
             1581  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7477139CD1  
             
           
            16 

Met Ala Gly Pro Gly Gly Trp Arg Asp Arg Glu Val Thr Asp Leu 
1               5                   10                  15 

Gly His Leu Pro Asp Pro Thr Gly Ile Phe Ser Leu Asp Lys Thr 
                20                  25                  30 

Ile Gly Leu Gly Thr Tyr Gly Arg Ile Tyr Leu Gly Leu His Glu 
                35                  40                  45 

Lys Thr Gly Ala Phe Thr Ala Val Lys Val Met Asn Ala Arg Lys 
                50                  55                  60 

Thr Pro Leu Pro Glu Ile Gly Arg Arg Val Arg Val Asn Lys Tyr 
                65                  70                  75 

Gln Lys Ser Val Gly Trp Arg Tyr Ser Asp Glu Glu Glu Asp Leu 
                80                  85                  90 

Arg Thr Glu Leu Asn Leu Leu Arg Lys Tyr Ser Phe His Lys Asn 
                95                  100                 105 

Ile Val Ser Phe Tyr Gly Ala Phe Phe Lys Leu Ser Pro Pro Gly 
                110                 115                 120 

Gln Arg His Gln Leu Trp Met Val Met Glu Leu Cys Ala Ala Gly 
                125                 130                 135 

Ser Val Thr Asp Val Val Arg Met Thr Ser Asn Gln Ser Leu Lys 
                140                 145                 150 

Glu Asp Trp Ile Ala Tyr Ile Cys Arg Glu Ile Leu Gln Gly Leu 
                155                 160                 165 

Ala His Leu His Ala His Arg Val Ile His Arg Asp Ile Lys Gly 
                170                 175                 180 

Gln Asn Val Leu Leu Thr His Asn Ala Glu Val Lys Leu Val Asp 
                185                 190                 195 

Phe Gly Val Ser Ala Gln Val Ser Arg Thr Asn Gly Arg Arg Asn 
                200                 205                 210 

Ser Phe Ile Gly Thr Pro Tyr Trp Met Ala Pro Glu Val Ile Asp 
                215                 220                 225 

Cys Asp Glu Asp Pro Arg Arg Ser Tyr Asp Tyr Arg Ser Asp Val 
                230                 235                 240 

Trp Ser Val Gly Ile Thr Ala Ile Glu Met Ala Glu Gly Ala Pro 
                245                 250                 255 

Pro Leu Cys Asn Leu Gln Pro Leu Glu Ala Leu Phe Val Ile Leu 
                260                 265                 270 

Arg Glu Ser Ala Pro Thr Val Lys Ser Ser Gly Trp Ser Arg Lys 
                275                 280                 285 

Phe His Asn Phe Met Glu Lys Cys Thr Ile Lys Asn Phe Leu Phe 
                290                 295                 300 

Arg Pro Thr Ser Ala Asn Met Leu Gln His Pro Phe Val Arg Asp 
                305                 310                 315 

Ile Lys Asn Glu Arg His Val Val Glu Ser Leu Thr Arg His Leu 
                320                 325                 330 

Thr Gly Ile Ile Lys Lys Arg Gln Lys Lys Gly Ile Pro Leu Ile 
                335                 340                 345 

Phe Glu Arg Glu Glu Ala Ile Lys Glu Gln Tyr Thr Val Arg Arg 
                350                 355                 360 

Phe Arg Gly Pro Ser Cys Thr His Glu Leu Leu Arg Leu Pro Thr 
                365                 370                 375 

Ser Ser Arg Cys Arg Pro Leu Arg Val Leu His Gly Glu Pro Ser 
                380                 385                 390 

Gln Pro Arg Trp Leu Pro Asp Arg Glu Glu Pro Gln Val Gln Ala 
                395                 400                 405 

Leu Gln Gln Leu Gln Gly Ala Ala Arg Val Phe Met Pro Leu Gln 
                410                 415                 420 

Ala Leu Asp Ser Ala Pro Lys Pro Leu Lys Gly Gln Ala Gln Ala 
                425                 430                 435 

Pro Gln Arg Leu Gln Gly Ala Ala Arg Val Phe Met Pro Leu Gln 
                440                 445                 450 

Ala Gln Val Lys Ala Lys Ala Ser Lys Pro Leu Gln Met Gln Ile 
                455                 460                 465 

Lys Ala Pro Pro Arg Leu Arg Arg Ala Ala Arg Val Leu Met Pro 
                470                 475                 480 

Leu Gln Ala Gln Val Arg Ala Pro Arg Leu Leu Gln Val Gln Ser 
                485                 490                 495 

Gln Val Ser Lys Lys Gln Gln Ala Gln Thr Gln Thr Ser Glu Pro 
                500                 505                 510 

Gln Asp Leu Asp Gln Val Pro Glu Glu Phe Gln Gly Gln Asp Gln 
                515                 520                 525 

Val Pro Glu Gln Gln Arg Gln Gly Gln Ala Pro Glu Gln Gln Gln 
                530                 535                 540 

Arg His Asn Gln Val Pro Glu Gln Glu Leu Glu Gln Asn Gln Ala 
                545                 550                 555 

Pro Glu Gln Pro Glu Val Gln Glu Gln Ala Ala Glu Pro Ala Gln 
                560                 565                 570 

Ala Glu Thr Glu Ala Glu Glu Pro Glu Ser Leu Arg Val Asn Ala 
                575                 580                 585 

Gln Val Phe Leu Pro Leu Leu Ser Gln Asp His His Val Leu Leu 
                590                 595                 600 

Pro Leu His Leu Asp Thr Gln Val Leu Ile Pro Val Glu Gly Gln 
                605                 610                 615 

Thr Glu Gly Ser Pro Gln Ala Gln Ala Trp Thr Leu Glu Pro Pro 
                620                 625                 630 

Gln Ala Ile Gly Ser Val Gln Ala Leu Ile Glu Gly Leu Ser Arg 
                635                 640                 645 

Asp Leu Leu Arg Ala Pro Asn Ser Asn Asn Ser Lys Pro Leu Gly 
                650                 655                 660 

Pro Leu Gln Thr Leu Met Glu Asn Leu Ser Ser Asn Arg Phe Tyr 
                665                 670                 675 

Ser Gln Pro Glu Gln Ala Arg Glu Lys Lys Ser Lys Val Ser Thr 
                680                 685                 690 

Leu Arg Gln Ala Leu Ala Lys Arg Leu Ser Pro Lys Arg Phe Arg 
                695                 700                 705 

Ala Lys Ser Ser Trp Arg Pro Glu Lys Leu Glu Leu Ser Asp Leu 
                710                 715                 720 

Glu Ala Arg Arg Gln Arg Arg Gln Arg Arg Trp Glu Asp Ile Phe 
                725                 730                 735 

Asn Gln His Glu Glu Glu Leu Arg Gln Val Asp Lys Thr Ser Trp 
                740                 745                 750 

Arg Gln Trp Gly Pro Ser Asp Gln Leu Ile Asp Asn Ser Phe Thr 
                755                 760                 765 

Gly Met Gln Asp Leu Lys Lys Tyr Leu Lys Gly Lys Thr Thr Phe 
                770                 775                 780 

His Asn Val Gln Val Val Ile Tyr Arg Ala Val Lys Gly Asn Asp 
                785                 790                 795 

Asp Val Ala Thr Arg Ser Thr Val Pro Gln Arg Ser Leu Leu Glu 
                800                 805                 810 

Gln Ala Gln Lys Pro Ile Asp Ile Arg Gln Arg Ser Ser Gln Asn 
                815                 820                 825 

Arg Gln Asn Trp Leu Ala Ala Ser Gly Asp Ser Lys His Lys Ile 
                830                 835                 840 

Leu Ala Gly Lys Thr Gln Ser Tyr Cys Leu Thr Ile Tyr Ile Ser 
                845                 850                 855 

Glu Val Lys Lys Glu Glu Phe Gln Glu Gly Met Asn Gln Lys Cys 
                860                 865                 870 

Gln Gly Ala Gln Val Gly Leu Gly Pro Glu Gly His Cys Ile Trp 
                875                 880                 885 

Gln Leu Gly Glu Ser Ser Ser Glu Glu Glu Ser Pro Val Thr Gly 
                890                 895                 900 

Arg Arg Ser Gln Ser Ser Pro Pro Tyr Ser Thr Ile Asp Gln Lys 
                905                 910                 915 

Leu Leu Val Asp Ile His Val Pro Asp Gly Phe Lys Val Gly Lys 
                920                 925                 930 

Ile Ser Pro Pro Val Tyr Leu Thr Asn Glu Trp Val Gly Tyr Asn 
                935                 940                 945 

Ala Leu Ser Glu Ile Phe Arg Asn Asp Trp Leu Thr Pro Ala Pro 
                950                 955                 960 

Val Ile Gln Pro Pro Glu Glu Asp Gly Asp Tyr Val Glu Leu Tyr 
                965                 970                 975 

Asp Ala Ser Ala Asp Thr Asp Gly Asp Asp Asp Asp Glu Ser Asn 
                980                 985                 990 

Asp Thr Phe Glu Asp Thr Tyr Asp His Ala Asn Gly Asn Asp Asp 
                995                 1000                1005 

Leu Asp Asn Gln Val Asp Gln Ala Asn Asp Val Cys Lys Asp His 
                1010                1015                1020 

Asp Asp Asp Asn Asn Lys Phe Val Asp Asp Val Asn Asn Asn Tyr 
                1025                1030                1035 

Tyr Glu Ala Pro Ser Cys Pro Ser Leu Leu Ser Gly Gln Ala Met 
                1040                1045                1050 

Ala Glu Met Glu Ala Ala Ser Lys Met Val Met Met Glu Val Val 
                1055                1060                1065 

Glu Lys Arg Lys Pro Thr Glu Ala Met Glu Ala Ile Gln Pro Ile 
                1070                1075                1080 

Glu Ala Met Glu Glu Val Gln Pro Val Arg Asp Asn Ala Ala Ile 
                1085                1090                1095 

Gly Asp Gln Glu Glu His Ala Ala Asn Ile Gly Ser Glu Arg Arg 
                1100                1105                1110 

Gly Ser Glu Gly Asp Gly Gly Lys Gly Val Val Arg Thr Ser Glu 
                1115                1120                1125 

Glu Ser Gly Ala Leu Gly Leu Asn Gly Glu Glu Asn Cys Ser Glu 
                1130                1135                1140 

Thr Asp Gly Pro Gly Leu Lys Arg Pro Ala Ser Gln Asp Phe Glu 
                1145                1150                1155 

Tyr Leu Gln Glu Glu Pro Gly Gly Gly Asn Glu Ala Ser Asn Ala 
                1160                1165                1170 

Ile Asp Ser Gly Ala Ala Pro Ser Ala Pro Asp His Glu Ser Asp 
                1175                1180                1185 

Asn Lys Asp Ile Ser Glu Ser Ser Thr Gln Ser Asp Phe Ser Ala 
                1190                1195                1200 

Asn His Ser Ser Pro Ser Lys Gly Ser Gly Met Ser Ala Asp Ala 
                1205                1210                1215 

Asn Phe Ala Ser Ala Ile Leu Tyr Ala Gly Phe Val Glu Val Pro 
                1220                1225                1230 

Glu Glu Ser Pro Lys Gln Pro Ser Glu Val Asn Val Asn Pro Leu 
                1235                1240                1245 

Tyr Val Ser Pro Ala Cys Lys Lys Pro Leu Ile His Met Tyr Glu 
                1250                1255                1260 

Lys Glu Phe Thr Ser Glu Ile Cys Cys Gly Ser Leu Trp Gly Val 
                1265                1270                1275 

Asn Leu Leu Leu Gly Thr Arg Ser Asn Leu Tyr Leu Met Asp Arg 
                1280                1285                1290 

Ser Gly Lys Ala Asp Ile Thr Lys Leu Ile Arg Arg Arg Pro Phe 
                1295                1300                1305 

Arg Gln Ile Gln Val Leu Glu Pro Leu Asn Leu Leu Ile Thr Ile 
                1310                1315                1320 

Ser Gly His Lys Asn Arg Leu Arg Val Tyr His Leu Thr Trp Leu 
                1325                1330                1335 

Arg Asn Lys Ile Leu Asn Asn Asp Pro Glu Ser Lys Arg Arg Gln 
                1340                1345                1350 

Glu Glu Met Leu Lys Thr Glu Glu Ala Cys Lys Ala Ile Asp Lys 
                1355                1360                1365 

Leu Thr Gly Cys Glu His Phe Ser Val Leu Gln His Glu Glu Thr 
                1370                1375                1380 

Thr Tyr Ile Ala Ile Ala Leu Lys Ser Ser Ile His Leu Tyr Ala 
                1385                1390                1395 

Trp Ala Pro Lys Ser Phe Asp Glu Ser Thr Ala Ile Lys Val Phe 
                1400                1405                1410 

Pro Thr Leu Asp His Lys Pro Val Thr Val Asp Leu Ala Ile Gly 
                1415                1420                1425 

Ser Glu Lys Arg Leu Lys Ile Phe Phe Ser Ser Ala Asp Gly Tyr 
                1430                1435                1440 

His Leu Ile Asp Ala Glu Ser Glu Val Met Ser Asp Val Thr Leu 
                1445                1450                1455 

Pro Lys Asn Asn Ile Ile Ile Leu Pro Asp Cys Leu Gly Ile Gly 
                1460                1465                1470 

Met Met Leu Thr Phe Asn Ala Glu Ala Leu Ser Val Glu Ala Asn 
                1475                1480                1485 

Glu Gln Leu Phe Lys Lys Ile Leu Glu Met Trp Lys Asp Ile Pro 
                1490                1495                1500 

Ser Ser Ile Ala Phe Glu Cys Thr Gln Arg Thr Thr Gly Trp Gly 
                1505                1510                1515 

Gln Lys Ala Ile Glu Val Arg Ser Leu Gln Ser Arg Val Leu Glu 
                1520                1525                1530 

Ser Glu Leu Lys Arg Arg Ser Ile Lys Lys Leu Arg Phe Leu Cys 
                1535                1540                1545 

Thr Arg Gly Asp Lys Leu Phe Phe Thr Ser Thr Leu Arg Asn His 
                1550                1555                1560 

His Ser Arg Val Tyr Phe Met Thr Leu Gly Lys Leu Glu Glu Leu 
                1565                1570                1575 

Gln Ser Asn Tyr Asp Val 
                1580 

 
           
             17  
             1084  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 55009053CD1  
             
           
            17 

Met Glu Thr Gln Ala Val Ala Thr Ser Pro Asp Gly Arg Tyr Leu 
1               5                   10                  15 

Lys Phe Asp Ile Glu Ile Gly Arg Gly Ser Phe Lys Thr Val Tyr 
                20                  25                  30 

Arg Gly Leu Asp Thr Asp Thr Thr Val Glu Val Ala Trp Cys Glu 
                35                  40                  45 

Leu Gln Thr Arg Lys Leu Ser Arg Ala Glu Arg Gln Arg Phe Ser 
                50                  55                  60 

Glu Glu Val Glu Met Leu Lys Gly Leu Gln His Pro Asn Ile Val 
                65                  70                  75 

Arg Phe Tyr Asp Ser Trp Lys Ser Val Leu Arg Gly Gln Val Cys 
                80                  85                  90 

Ile Val Leu Val Thr Glu Leu Met Thr Ser Gly Thr Leu Lys Thr 
                95                  100                 105 

Tyr Leu Arg Arg Phe Arg Glu Met Lys Pro Arg Val Leu Gln Arg 
                110                 115                 120 

Trp Ser Arg Gln Ile Leu Arg Gly Leu His Phe Leu His Ser Arg 
                125                 130                 135 

Val Pro Pro Ile Leu His Arg Asp Leu Lys Cys Asp Asn Val Phe 
                140                 145                 150 

Ile Thr Gly Pro Ser Gly Ser Val Lys Ile Gly Asp Leu Gly Leu 
                155                 160                 165 

Ala Thr Leu Lys Arg Ala Ser Phe Ala Lys Ser Val Ile Gly Thr 
                170                 175                 180 

Pro Glu Phe Met Ala Pro Glu Met Tyr Glu Glu Lys Tyr Asp Glu 
                185                 190                 195 

Ala Val Asp Val Tyr Ala Phe Gly Met Cys Met Leu Glu Met Ala 
                200                 205                 210 

Thr Ser Glu Tyr Pro Tyr Ser Glu Cys Gln Asn Ala Ala Gln Ile 
                215                 220                 225 

Tyr Arg Lys Val Thr Ser Gly Arg Lys Pro Asn Ser Phe His Lys 
                230                 235                 240 

Val Lys Ile Pro Glu Val Lys Glu Ile Ile Glu Gly Cys Ile Arg 
                245                 250                 255 

Thr Asp Lys Asn Glu Arg Phe Thr Ile Gln Asp Leu Leu Ala His 
                260                 265                 270 

Ala Phe Phe Arg Glu Glu Arg Gly Val His Val Glu Leu Ala Glu 
                275                 280                 285 

Glu Asp Asp Gly Glu Lys Pro Gly Leu Lys Leu Trp Leu Arg Met 
                290                 295                 300 

Glu Asp Ala Arg Arg Gly Gly Arg Pro Arg Asp Asn Gln Ala Ile 
                305                 310                 315 

Glu Phe Leu Phe Gln Leu Gly Arg Asp Ala Ala Glu Glu Val Ala 
                320                 325                 330 

Gln Glu Met Val Ala Leu Gly Leu Val Cys Glu Ala Asp Tyr Gln 
                335                 340                 345 

Pro Val Ala Arg Ala Val Arg Glu Arg Val Ala Ala Ile Gln Arg 
                350                 355                 360 

Lys Arg Glu Lys Leu Arg Lys Ala Arg Glu Leu Glu Ala Leu Pro 
                365                 370                 375 

Pro Glu Pro Gly Pro Pro Pro Ala Thr Val Pro Met Ala Pro Gly 
                380                 385                 390 

Pro Pro Ser Val Phe Pro Pro Glu Pro Glu Glu Pro Glu Ala Asp 
                395                 400                 405 

Gln His Gln Pro Phe Leu Phe Arg His Ala Ser Tyr Ser Ser Thr 
                410                 415                 420 

Thr Ser Asp Cys Glu Thr Asp Gly Tyr Leu Ser Ser Ser Gly Phe 
                425                 430                 435 

Leu Asp Ala Ser Asp Pro Ala Leu Gln Pro Pro Gly Gly Val Pro 
                440                 445                 450 

Ser Ser Leu Ala Glu Ser His Leu Cys Leu Pro Ser Ala Phe Ala 
                455                 460                 465 

Leu Ser Ile Pro Arg Ser Gly Pro Gly Ser Asp Phe Ser Pro Gly 
                470                 475                 480 

Asp Ser Tyr Ala Ser Asp Ala Ala Ser Gly Leu Ser Asp Val Gly 
                485                 490                 495 

Glu Gly Met Gly Gln Met Arg Arg Pro Pro Gly Arg Asn Leu Arg 
                500                 505                 510 

Arg Arg Pro Arg Ser Arg Leu Arg Val Thr Ser Val Ser Asp Gln 
                515                 520                 525 

Asn Asp Arg Val Val Glu Cys Gln Leu Gln Thr His Asn Ser Lys 
                530                 535                 540 

Met Val Thr Phe Arg Phe Asp Leu Asp Gly Asp Ser Pro Glu Glu 
                545                 550                 555 

Ile Ala Ala Ala Met Val Tyr Asn Glu Phe Ile Leu Pro Ser Glu 
                560                 565                 570 

Arg Asp Gly Phe Leu Arg Arg Ile Arg Glu Ile Ile Gln Arg Val 
                575                 580                 585 

Glu Thr Leu Leu Lys Arg Asp Thr Gly Pro Met Glu Ala Ala Glu 
                590                 595                 600 

Asp Thr Leu Ser Pro Gln Glu Glu Pro Ala Pro Leu Pro Ala Leu 
                605                 610                 615 

Pro Val Pro Leu Pro Asp Pro Ser Asn Glu Glu Leu Gln Ser Ser 
                620                 625                 630 

Thr Ser Leu Glu His Arg Ser Trp Thr Ala Phe Ser Thr Ser Ser 
                635                 640                 645 

Ser Ser Pro Gly Thr Pro Leu Ser Pro Gly Asn Pro Phe Ser Pro 
                650                 655                 660 

Gly Thr Pro Ile Ser Pro Gly Pro Ile Phe Pro Ile Thr Ser Pro 
                665                 670                 675 

Pro Cys His Pro Ser Pro Ser Pro Phe Ser Pro Ile Ser Ser Gln 
                680                 685                 690 

Val Ser Ser Asn Pro Ser Pro His Pro Thr Ser Ser Pro Leu Pro 
                695                 700                 705 

Phe Ser Ser Ser Thr Pro Glu Phe Pro Val Pro Leu Ser Gln Cys 
                710                 715                 720 

Pro Trp Ser Ser Leu Pro Thr Thr Ser Pro Pro Thr Phe Ser Pro 
                725                 730                 735 

Thr Cys Ser Gln Val Thr Leu Ser Ser Pro Phe Phe Pro Pro Cys 
                740                 745                 750 

Pro Ser Thr Ser Ser Phe Pro Ser Thr Thr Ala Ala Pro Leu Leu 
                755                 760                 765 

Ser Leu Ala Ser Ala Phe Ser Leu Ala Val Met Thr Val Ala Gln 
                770                 775                 780 

Ser Leu Leu Ser Pro Ser Pro Gly Leu Leu Ser Gln Ser Pro Pro 
                785                 790                 795 

Ala Pro Pro Ser Pro Leu Pro Ser Leu Pro Leu Pro Pro Pro Val 
                800                 805                 810 

Ala Pro Gly Gly Gln Glu Ser Pro Ser Pro His Thr Ala Glu Val 
                815                 820                 825 

Glu Ser Glu Ala Ser Pro Pro Pro Ala Arg Pro Leu Pro Gly Glu 
                830                 835                 840 

Ala Arg Leu Ala Pro Ile Ser Glu Glu Gly Lys Pro Gln Leu Val 
                845                 850                 855 

Gly Arg Phe Gln Val Thr Ser Ser Lys Glu Pro Ala Glu Pro Leu 
                860                 865                 870 

Pro Leu Gln Pro Thr Ser Pro Thr Leu Ser Gly Ser Pro Lys Pro 
                875                 880                 885 

Ser Thr Pro Gln Leu Thr Ser Glu Ser Ser Asp Thr Glu Asp Ser 
                890                 895                 900 

Ala Gly Gly Gly Pro Glu Thr Arg Glu Ala Leu Ala Glu Ser Asp 
                905                 910                 915 

Arg Ala Ala Glu Gly Leu Gly Ala Gly Val Glu Glu Glu Gly Asp 
                920                 925                 930 

Asp Gly Lys Glu Pro Gln Val Gly Gly Ser Pro Gln Pro Leu Ser 
                935                 940                 945 

His Pro Ser Pro Val Trp Met Asn Tyr Ser Tyr Ser Ser Leu Cys 
                950                 955                 960 

Leu Ser Ser Glu Glu Ser Glu Ser Ser Gly Glu Asp Glu Glu Phe 
                965                 970                 975 

Trp Ala Glu Leu Gln Ser Leu Arg Gln Lys His Leu Ser Glu Val 
                980                 985                 990 

Glu Thr Leu Gln Thr Leu Gln Lys Lys Glu Ile Glu Asp Leu Tyr 
                995                 1000                1005 

Ser Arg Leu Gly Lys Gln Pro Pro Pro Gly Ile Val Ala Pro Ala 
                1010                1015                1020 

Ala Met Leu Ser Ser Arg Gln Arg Arg Leu Ser Lys Gly Ser Phe 
                1025                1030                1035 

Pro Thr Ser Arg Arg Asn Ser Leu Gln Arg Ser Glu Pro Pro Gly 
                1040                1045                1050 

Pro Gly Ile Met Arg Arg Asn Ser Leu Ser Gly Ser Ser Thr Gly 
                1055                1060                1065 

Ser Gln Glu Gln Arg Ala Ser Lys Gly Val Thr Phe Ala Gly Asp 
                1070                1075                1080 

Val Gly Arg Met 

 
           
             18  
             600  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7474648CD1  
             
           
            18 

Met Gly Glu Ser Gly Asn His His Phe Gln Gln Thr Asn Thr Gly 
1               5                   10                  15 

Thr Glu Asn Gln Thr Ala His Val Leu Thr His Lys Trp Glu Leu 
                20                  25                  30 

Asp Asn Glu Asn Ile Trp Ala Gln Gly Gly Glu His His Lys Leu 
                35                  40                  45 

Gly Pro Val Met Gly Trp Lys Ala Arg Ser Gly Lys Thr Leu Gly 
                50                  55                  60 

Glu Ile Pro Asn Val Gly Thr Leu Thr Leu Leu Thr Gly Tyr Gly 
                65                  70                  75 

Gly Cys Gln Leu Pro Cys Cys Lys Asp Thr Gln Ala Ala Tyr Gly 
                80                  85                  90 

Glu Thr His Val Val Arg Ser Gly Gly Leu Leu Pro Thr Ala Ser 
                95                  100                 105 

Trp Glu Leu Arg Pro Ala Asp Ser His Thr Val Thr Ser Asp Asp 
               110                 115                 120 

Pro Gly Val Ser Val Val Ser Gly Tyr Pro Gly Gly Cys Leu Pro 
                125                 130                 135 

Asp His Asp Pro Pro Val Gly Phe Leu Ser Glu Gly Pro Ala Pro 
                140                 145                 150 

Arg Ser Cys Ser Leu Ile Lys Gly Gly Gly Thr Gly Leu Ala Ala 
                155                 160                 165 

Ser Arg Val Pro Arg Ser Arg Glu Arg Arg Ala Cys Cys Gly Tyr 
                170                 175                 180 

Gly Val Arg Arg Gln Gln Glu Gly Gly Pro Gly Ala Thr Ser Ala 
                185                 190                 195 

Gly Leu Gly Gln Ala Arg Arg Ser Lys Pro Ser Arg Arg Arg Arg 
                200                 205                 210 

Arg Gly Ala Trp Ala Arg Gly Gly Gly Pro Gly Gly Ala Glu Asp 
                215                 220                 225 

Thr Gly Gly Ser Leu Pro Ser Gln Val Arg Pro Pro Gly Pro Cys 
                230                 235                 240 

Gln Cys Pro Val Gln Phe Leu Phe Asp Ile Ser Glu Gln Gly Val 
                245                 250                 255 

Gln Arg Met Gly Lys Lys Arg Ala Gly Ala Ala Ala Asn Lys Gly 
                260                 265                 270 

Arg Asn Ser Tyr Leu Arg Arg Tyr Asp Ile Lys Ala Leu Ile Gly 
                275                 280                 285 

Thr Gly Ser Phe Ser Arg Val Val Arg Val Glu Gln Lys Thr Thr 
                290                 295                 300 

Lys Lys Pro Phe Ala Ile Lys Val Met Glu Thr Arg Glu Arg Glu 
                305                 310                 315 

Gly Arg Glu Ala Cys Val Ser Glu Leu Ser Val Leu Arg Arg Val 
                320                 325                 330 

Ser His Arg Tyr Ile Val Gln Leu Met Glu Ile Phe Glu Thr Glu 
                335                 340                 345 

Asp Gln Val Tyr Met Val Met Glu Leu Ala Thr Gly Gly Glu Leu 
                350                 355                 360 

Phe Asp Arg Leu Ile Ala Gln Gly Ser Phe Thr Glu Arg Asp Ala 
                365                 370                 375 

Val Arg Ile Leu Gln Met Val Ala Asp Gly Ile Arg Tyr Leu His 
                380                 385                 390 

Ala Leu Gln Ile Thr His Arg Asn Leu Lys Pro Glu Asn Leu Leu 
                395                 400                 405 

Tyr Tyr His Pro Gly Glu Glu Ser Lys Ile Leu Ile Thr Asp Phe 
                410                 415                 420 

Gly Leu Ala Tyr Ser Gly Lys Lys Ser Gly Asp Trp Thr Met Lys 
                425                 430                 435 

Thr Leu Cys Gly Thr Pro Glu Tyr Ile Ala Pro Glu Val Leu Leu 
                440                 445                 450 

Arg Lys Pro Tyr Thr Ser Ala Val Asp Met Trp Ala Leu Gly Val 
                455                 460                 465 

Ile Thr Tyr Ala Leu Leu Ser Gly Phe Leu Pro Phe Asp Asp Glu 
                470                 475                 480 

Ser Gln Thr Arg Leu Tyr Arg Lys Ile Leu Lys Gly Lys Tyr Asn 
                485                 490                 495 

Tyr Thr Gly Glu Pro Trp Pro Ser Ile Ser His Leu Ala Lys Asp 
                500                 505                 510 

Phe Ile Asp Lys Leu Leu Ile Leu Glu Ala Gly His Arg Met Ser 
                515                 520                 525 

Ala Gly Gln Ala Leu Asp His Pro Trp Val Ile Thr Met Ala Ala 
                530                 535                 540 

Gly Ser Ser Met Lys Asn Leu Gln Arg Ala Ile Ser Arg Asn Leu 
                545                 550                 555 

Met Gln Arg Ala Ser Pro His Ser Gln Ser Pro Gly Ser Ala Gln 
                560                 565                 570 

Ser Ser Lys Ser His Tyr Ser His Lys Ser Arg His Met Trp Ser 
                575                 580                 585 

Lys Arg Asn Leu Arg Ile Val Glu Ser Pro Leu Ser Ala Leu Leu 
                590                 595                 600 

 
           
             19  
             1114  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7483053CD1  
             
           
            19 

Met Ala Lys Ala Thr Ser Gly Ala Ala Gly Leu Arg Leu Leu Leu 
1               5                   10                  15 

Leu Leu Leu Leu Pro Leu Leu Gly Lys Val Ala Leu Gly Leu Tyr 
                20                  25                  30 

Phe Ser Arg Asp Ala Tyr Trp Glu Lys Leu Tyr Val Asp Gln Ala 
                35                  40                  45 

Ala Gly Thr Pro Leu Leu Tyr Val His Ala Leu Arg Asp Ala Pro 
                50                  55                  60 

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

Tyr Arg Thr Arg Leu His Glu Asn Asn Trp Ile Cys Ile Gln Glu 
                80                  85                  90 

Asp Thr Gly Leu Leu Tyr Leu Asn Arg Ser Leu Asp His Ser Ser 
                95                  100                 105 

Trp Glu Lys Leu Ser Val Arg Asn Arg Gly Phe Pro Leu Leu Thr 
                110                 115                 120 

Val Tyr Leu Lys Val Phe Leu Ser Pro Thr Ser Leu Arg Glu Gly 
                125                 130                 135 

Glu Cys Gln Trp Pro Gly Cys Ala Arg Val Tyr Phe Ser Phe Phe 
                140                 145                 150 

Asn Thr Ser Phe Pro Ala Cys Ser Ser Leu Lys Pro Arg Glu Leu 
                155                 160                 165 

Cys Phe Pro Glu Thr Arg Pro Ser Phe Arg Ile Arg Glu Asn Arg 
                170                 175                 180 

Pro Pro Gly Thr Phe His Gln Phe Arg Leu Leu Pro Val Gln Phe 
                185                 190                 195 

Leu Cys Pro Asn Ile Ser Val Ala Tyr Arg Leu Leu Glu Gly Glu 
                200                 205                 210 

Gly Leu Pro Phe Arg Cys Ala Pro Asp Ser Leu Glu Val Ser Thr 
                215                 220                 225 

Arg Trp Ala Leu Asp Arg Glu Gln Arg Glu Lys Tyr Glu Leu Val 
                230                 235                 240 

Ala Val Cys Thr Val His Ala Gly Ala Arg Glu Glu Val Val Met 
                245                 250                 255 

Val Pro Phe Pro Val Thr Val Tyr Asp Glu Asp Asp Ser Ala Pro 
                260                 265                 270 

Thr Phe Pro Ala Gly Val Asp Thr Ala Ser Ala Val Val Glu Phe 
                275                 280                 285 

Lys Arg Lys Glu Asp Thr Val Val Ala Thr Leu Arg Val Phe Asp 
                290                 295                 300 

Ala Asp Val Val Pro Ala Ser Gly Glu Leu Val Arg Arg Tyr Thr 
                305                 310                 315 

Ser Thr Leu Leu Pro Gly Asp Thr Trp Ala Gln Gln Thr Phe Arg 
                320                 325                 330 

Val Glu His Trp Pro Asn Glu Thr Ser Val Gln Ala Asn Gly Ser 
                335                 340                 345 

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

Asn Leu Ser Ile Ser Glu Asn Arg Thr Met Gln Leu Ala Val Leu 
                365                 370                 375 

Val Asn Asp Ser Asp Phe Gln Gly Pro Gly Ala Gly Val Leu Leu 
                380                 385                 390 

Leu His Phe Asn Val Ser Val Leu Pro Val Ser Leu His Leu Pro 
                395                 400                 405 

Ser Thr Tyr Ser Leu Ser Val Ser Arg Arg Ala Arg Arg Phe Ala 
                410                 415                 420 

Gln Ile Gly Lys Val Cys Val Glu Asn Cys Gln Ala Phe Ser Gly 
                425                 430                 435 

Ile Asn Val Gln Tyr Lys Leu His Ser Ser Gly Ala Asn Cys Ser 
                440                 445                 450 

Thr Leu Gly Val Val Thr Ser Ala Glu Asp Thr Ser Gly Ile Leu 
                455                 460                 465 

Phe Val Asn Asp Thr Lys Ala Leu Arg Arg Pro Lys Cys Ala Glu 
                470                 475                 480 

Leu His Tyr Met Val Val Ala Thr Asp Gln Gln Thr Ser Arg Gln 
                485                 490                 495 

Ala Gln Ala Gln Leu Leu Val Thr Val Glu Gly Ser Tyr Val Ala 
                500                 505                 510 

Glu Glu Ala Gly Cys Pro Leu Ser Cys Ala Val Ser Lys Arg Arg 
                515                 520                 525 

Leu Glu Cys Glu Glu Cys Gly Gly Leu Gly Ser Pro Thr Gly Arg 
                530                 535                 540 

Cys Glu Trp Arg Gln Gly Asp Gly Lys Gly Ile Thr Arg Asn Phe 
                545                 550                 555 

Ser Thr Cys Ser Pro Ser Thr Lys Thr Cys Pro Asp Gly His Cys 
                560                 565                 570 

Asp Val Val Glu Thr Gln Asp Ile Asn Ile Cys Pro Gln Asp Cys 
                575                 580                 585 

Leu Arg Gly Ser Ile Val Gly Gly His Glu Pro Gly Glu Pro Arg 
                590                 595                 600 

Gly Ile Lys Ala Gly Tyr Gly Thr Cys Asn Cys Phe Pro Glu Glu 
                605                 610                 615 

Glu Lys Cys Phe Cys Glu Pro Glu Asp Ile Gln Asp Pro Leu Cys 
                620                 625                 630 

Asp Glu Leu Cys Arg Thr Val Ile Ala Ala Ala Val Leu Phe Ser 
                635                 640                 645 

Phe Ile Val Ser Val Leu Leu Ser Ala Phe Cys Ile His Cys Tyr 
                650                 655                 660 

His Lys Phe Ala His Lys Pro Pro Ile Ser Ser Ala Glu Met Thr 
                665                 670                 675 

Phe Arg Arg Pro Ala Gln Ala Phe Pro Val Ser Tyr Ser Ser Ser 
                680                 685                 690 

Ser Ala Arg Arg Pro Ser Leu Asp Ser Met Glu Asn Gln Val Ser 
                695                 700                 705 

Val Asp Ala Phe Lys Ile Leu Glu Asp Pro Lys Trp Glu Phe Pro 
                710                 715                 720 

Arg Lys Asn Leu Val Leu Gly Lys Thr Leu Gly Glu Gly Glu Phe 
                725                 730                 735 

Gly Lys Val Val Lys Ala Thr Ala Phe His Leu Lys Gly Arg Ala 
                740                 745                 750 

Gly Tyr Thr Thr Val Ala Val Lys Met Leu Lys Glu Asn Ala Ser 
                755                 760                 765 

Pro Ser Glu Leu Arg Asp Leu Leu Ser Glu Phe Asn Val Leu Lys 
                770                 775                 780 

Gln Val Asn His Pro His Val Ile Lys Leu Tyr Gly Ala Cys Ser 
                785                 790                 795 

Gln Asp Gly Pro Leu Leu Leu Ile Val Glu Tyr Ala Lys Tyr Gly 
                800                 805                 810 

Ser Leu Arg Gly Phe Leu Arg Glu Ser Arg Lys Val Gly Pro Gly 
                815                 820                 825 

Tyr Leu Gly Ser Gly Gly Ser Arg Asn Ser Ser Ser Leu Asp His 
                830                 835                 840 

Pro Asp Glu Arg Ala Leu Thr Met Gly Asp Leu Ile Ser Phe Ala 
                845                 850                 855 

Trp Gln Ile Ser Gln Gly Met Gln Tyr Leu Ala Glu Met Lys Leu 
                860                 865                 870 

Val His Arg Asp Leu Ala Ala Arg Asn Ile Leu Val Ala Glu Gly 
                875                 880                 885 

Arg Lys Met Lys Ile Ser Asp Phe Gly Leu Ser Arg Asp Val Tyr 
                890                 895                 900 

Glu Glu Asp Ser Tyr Val Lys Arg Ser Gln Gly Arg Ile Pro Val 
                905                 910                 915 

Lys Trp Met Ala Ile Glu Ser Leu Phe Asp His Ile Tyr Thr Thr 
                920                 925                 930 

Gln Ser Asp Val Trp Ser Phe Gly Val Leu Leu Trp Glu Ile Val 
                935                 940                 945 

Thr Leu Gly Gly Asn Pro Tyr Pro Gly Ile Pro Pro Glu Arg Leu 
                950                 955                 960 

Phe Asn Leu Leu Lys Thr Gly His Arg Met Glu Arg Pro Asp Asn 
                965                 970                 975 

Cys Ser Glu Glu Met Tyr Arg Leu Met Leu Gln Cys Trp Lys Gln 
                980                 985                 990 

Glu Pro Asp Lys Arg Pro Val Phe Ala Asp Ile Ser Lys Asp Leu 
                995                 1000                1005 

Glu Lys Met Met Val Lys Arg Arg Asp Tyr Leu Asp Leu Ala Ala 
                1010                1015                1020 

Ser Thr Pro Ser Asp Ser Leu Ile Tyr Asp Asp Gly Leu Ser Glu 
                1025                1030                1035 

Glu Glu Thr Pro Leu Val Asp Cys Asn Asn Ala Pro Leu Pro Arg 
                1040                1045                1050 

Ala Leu Pro Ser Thr Trp Ile Glu Asn Lys Leu Tyr Gly Met Ser 
                1055                1060                1065 

Asp Pro Asn Trp Pro Gly Glu Ser Pro Val Pro Leu Thr Arg Ala 
                1070                1075                1080 

Asp Gly Thr Asn Thr Gly Phe Pro Arg Tyr Pro Asn Asp Ser Val 
                1085                1090                1095 

Tyr Ala Asn Trp Met Leu Ser Pro Ser Ala Ala Lys Leu Met Asp 
                1100                1105                1110 

Thr Phe Asp Ser 

 
           
             20  
             567  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7483117CD1  
             
           
            20 

Met Asp Asp Lys Asp Ile Asp Lys Glu Leu Arg Gln Lys Leu Asn 
1               5                   10                  15 

Phe Ser Tyr Cys Glu Glu Thr Glu Ile Glu Gly Gln Lys Lys Val 
                20                  25                  30 

Glu Glu Ser Arg Glu Ala Ser Ser Gln Thr Pro Glu Lys Gly Glu 
                35                  40                  45 

Val Gln Asp Ser Glu Ala Lys Gly Thr Pro Pro Trp Thr Pro Leu 
                50                  55                  60 

Ser Asn Val His Glu Leu Asp Thr Ser Ser Glu Lys Asp Lys Glu 
                65                  70                  75 

Ser Pro Asp Gln Ile Leu Arg Thr Pro Val Ser His Pro Leu Lys 
                80                  85                  90 

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

Pro Ser Asp Ser Pro Ser Thr Pro Lys Thr Met Leu Ser Arg Leu 
                110                 115                 120 

Val Ile Ser Pro Thr Gly Lys Leu Pro Ser Arg Gly Pro Lys His 
                125                 130                 135 

Leu Lys Leu Thr Pro Ala Pro Leu Lys Asp Glu Met Thr Ser Leu 
                140                 145                 150 

Ala Leu Val Asn Ile Asn Pro Phe Thr Pro Glu Ser Tyr Lys Lys 
                155                 160                 165 

Leu Phe Leu Gln Ser Gly Gly Lys Arg Lys Ile Arg Gly Asp Leu 
                170                 175                 180 

Glu Glu Ala Gly Pro Glu Glu Gly Lys Gly Gly Leu Pro Ala Lys 
                185                 190                 195 

Arg Cys Val Leu Arg Glu Thr Asn Met Ala Ser Arg Tyr Glu Lys 
                200                 205                 210 

Glu Phe Leu Glu Val Glu Lys Ile Gly Val Gly Glu Phe Gly Thr 
                215                 220                 225 

Val Tyr Lys Cys Ile Lys Arg Leu Asp Gly Cys Val Tyr Ala Ile 
                230                 235                 240 

Lys Arg Ser Met Lys Thr Phe Thr Glu Leu Ser Asn Glu Asn Ser 
                245                 250                 255 

Ala Leu His Glu Val Tyr Ala His Ala Val Leu Gly His His Pro 
                260                 265                 270 

His Val Val Arg Tyr Tyr Ser Ser Trp Ala Glu Asp Asp His Met 
                275                 280                 285 

Ile Ile Gln Asn Glu Tyr Cys Asn Gly Gly Ser Leu Gln Ala Ala 
                290                 295                 300 

Ile Ser Glu Asn Thr Lys Ser Gly Asn His Phe Glu Glu Pro Lys 
                305                 310                 315 

Leu Lys Asp Ile Leu Leu Gln Ile Ser Leu Gly Leu Asn Tyr Ile 
                320                 325                 330 

His Asn Ser Ser Met Val His Leu Asp Ile Lys Pro Ser Asn Ile 
                335                 340                 345 

Phe Ile Cys His Lys Met Gln Ser Glu Ser Ser Gly Val Ile Glu 
                350                 355                 360 

Glu Val Glu Asn Glu Ala Asp Trp Phe Leu Ser Ala Asn Val Met 
                365                 370                 375 

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

Lys Val Glu Glu Gly Asp Ser Arg Phe Leu Ala Asn Glu Ile Leu 
                395                 400                 405 

Gln Glu Asp Tyr Arg His Leu Pro Lys Ala Asp Ile Phe Ala Leu 
                410                 415                 420 

Gly Leu Thr Ile Ala Val Ala Ala Gly Ala Glu Ser Leu Pro Thr 
                425                 430                 435 

Asn Gly Ala Ala Trp His His Ile Arg Lys Gly Asn Phe Pro Asp 
                440                 445                 450 

Val Pro Gln Glu Leu Ser Glu Ser Phe Ser Ser Leu Leu Lys Asn 
                455                 460                 465 

Met Ile Gln Pro Asp Ala Glu Gln Arg Pro Ser Ala Ala Ala Leu 
                470                 475                 480 

Ala Arg Asn Thr Val Leu Arg Pro Ser Leu Gly Lys Thr Glu Glu 
                485                 490                 495 

Leu Gln Gln Gln Leu Asn Leu Glu Lys Phe Lys Thr Ala Thr Leu 
                500                 505                 510 

Glu Arg Glu Leu Arg Glu Ala Gln Gln Ala Gln Ser Pro Gln Gly 
                515                 520                 525 

Tyr Thr His His Gly Asp Thr Gly Val Ser Gly Thr His Thr Gly 
                530                 535                 540 

Ser Arg Ser Thr Lys Arg Leu Val Gly Gly Lys Ser Ala Arg Ser 
                545                 550                 555 

Ser Ser Phe Thr Ser Gly Glu Arg Glu Pro Leu His 
                560                 565 

 
           
             21  
             2054  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7484498CD1  
             
           
            21 

Met Leu Lys Phe Lys Tyr Gly Ala Arg Asn Pro Leu Asp Ala Gly 
1               5                   10                  15 

Ala Ala Glu Pro Ile Ala Ser Arg Ala Ser Arg Leu Asn Leu Phe 
                20                  25                  30 

Phe Gln Gly Lys Pro Pro Phe Met Thr Gln Gln Gln Met Ser Pro 
                35                  40                  45 

Leu Ser Arg Glu Gly Ile Leu Asp Ala Leu Phe Val Leu Phe Glu 
                50                  55                  60 

Glu Cys Ser Gln Pro Ala Leu Met Lys Ile Lys His Val Ser Asn 
                65                  70                  75 

Phe Val Arg Lys Tyr Ser Asp Thr Ile Ala Glu Leu Gln Glu Leu 
                80                  85                  90 

Gln Pro Ser Ala Lys Asp Phe Glu Val Arg Ser Leu Val Gly Cys 
                95                  100                 105 

Gly His Phe Ala Glu Val Gln Val Val Arg Glu Lys Ala Thr Gly 
                110                 115                 120 

Asp Ile Tyr Ala Met Lys Val Met Lys Lys Lys Ala Leu Leu Ala 
                125                 130                 135 

Gln Glu Gln Val Ser Phe Phe Glu Glu Glu Arg Asn Ile Leu Ser 
                140                 145                 150 

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

Asp Lys Asn His Leu Tyr Leu Val Met Glu Tyr Gln Pro Gly Gly 
                170                 175                 180 

Asp Leu Leu Ser Leu Leu Asn Arg Tyr Glu Asp Gln Leu Asp Glu 
                185                 190                 195 

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

Ser Val His Leu Met Gly Tyr Val His Arg Asp Ile Lys Pro Glu 
                215                 220                 225 

Asn Ile Leu Val Asp Arg Thr Gly His Ile Lys Leu Val Asp Phe 
                230                 235                 240 

Gly Ser Ala Ala Lys Met Asn Ser Asn Lys Met Val Asn Ala Lys 
                245                 250                 255 

Leu Pro Ile Gly Thr Pro Asp Tyr Met Ala Pro Glu Val Leu Thr 
                260                 265                 270 

Val Met Asn Gly Asp Gly Lys Gly Thr Tyr Gly Leu Asp Cys Asp 
                275                 280                 285 

Trp Trp Ser Val Gly Val Ile Ala Tyr Glu Met Ile Tyr Gly Arg 
                290                 295                 300 

Ser Pro Phe Ala Glu Gly Thr Ser Ala Arg Thr Phe Asn Asn Ile 
                305                 310                 315 

Met Asn Phe Gln Arg Phe Leu Lys Phe Pro Asp Asp Pro Lys Val 
                320                 325                 330 

Ser Ser Asp Phe Leu Asp Leu Ile Gln Ser Leu Leu Cys Gly Gln 
                335                 340                 345 

Lys Glu Arg Leu Lys Phe Glu Gly Leu Cys Cys His Pro Phe Phe 
                350                 355                 360 

Ser Lys Ile Asp Trp Asn Asn Ile Arg Asn Ser Pro Pro Pro Phe 
                365                 370                 375 

Val Pro Thr Leu Lys Ser Asp Asp Asp Thr Ser Asn Phe Asp Glu 
                380                 385                 390 

Pro Glu Lys Asn Ser Trp Val Ser Ser Ser Pro Cys Gln Leu Ser 
                395                 400                 405 

Pro Ser Gly Phe Ser Gly Glu Glu Leu Pro Phe Val Gly Phe Ser 
                410                 415                 420 

Tyr Ser Lys Ala Leu Gly Ile Leu Gly Arg Ser Glu Ser Val Val 
                425                 430                 435 

Ser Gly Leu Asp Ser Pro Ala Lys Thr Ser Ser Met Glu Lys Lys 
                440                 445                 450 

Leu Leu Ile Lys Ser Lys Glu Leu Gln Asp Ser Gln Asp Lys Cys 
                455                 460                 465 

His Lys Met Glu Gln Glu Met Thr Arg Leu His Arg Arg Val Ser 
                470                 475                 480 

Glu Val Glu Ala Val Leu Ser Gln Lys Glu Val Glu Leu Lys Ala 
                485                 490                 495 

Ser Glu Thr Gln Arg Ser Leu Leu Glu Gln Asp Leu Ala Thr Tyr 
                500                 505                 510 

Ile Thr Glu Cys Ser Ser Leu Lys Arg Ser Leu Glu Gln Ala Arg 
                515                 520                 525 

Met Glu Val Ser Gln Glu Asp Asp Lys Ala Leu Gln Leu Leu His 
                530                 535                 540 

Asp Ile Arg Glu Gln Ser Arg Lys Leu Gln Glu Ile Lys Glu Gln 
                545                 550                 555 

Glu Tyr Gln Ala Gln Val Glu Glu Met Arg Leu Met Met Asn Gln 
                560                 565                 570 

Leu Glu Glu Asp Leu Val Ser Ala Arg Arg Arg Ser Asp Leu Tyr 
                575                 580                 585 

Glu Ser Glu Leu Arg Glu Ser Arg Leu Ala Ala Glu Glu Phe Lys 
                590                 595                 600 

Arg Lys Ala Thr Glu Cys Gln His Lys Leu Leu Lys Ala Lys Asp 
                605                 610                 615 

Gln Gly Lys Pro Glu Val Gly Glu Tyr Ala Lys Leu Glu Lys Ile 
                620                 625                 630 

Asn Ala Glu Gln Gln Leu Lys Ile Gln Glu Leu Gln Glu Lys Leu 
                635                 640                 645 

Glu Lys Ala Val Lys Ala Ser Thr Glu Ala Thr Glu Leu Leu Gln 
                650                 655                 660 

Asn Ile Arg Gln Ala Lys Glu Arg Ala Glu Arg Glu Leu Glu Lys 
                665                 670                 675 

Leu Gln Asn Arg Glu Asp Ser Ser Glu Gly Ile Arg Lys Lys Leu 
                680                 685                 690 

Val Glu Ala Glu Glu Arg Arg His Ser Leu Glu Asn Lys Val Lys 
                695                 700                 705 

Arg Leu Glu Thr Met Glu Arg Arg Glu Asn Arg Leu Lys Asp Asp 
                710                 715                 720 

Ile Gln Thr Lys Ser Gln Gln Ile Gln Gln Met Ala Asp Lys Ile 
                725                 730                 735 

Leu Glu Leu Glu Glu Lys His Arg Glu Ala Gln Val Ser Ala Gln 
                740                 745                 750 

His Leu Glu Val His Leu Lys Gln Lys Glu Gln His Tyr Glu Glu 
                755                 760                 765 

Lys Ile Lys Val Leu Asp Asn Gln Ile Lys Lys Asp Leu Ala Asp 
                770                 775                 780 

Lys Glu Thr Leu Glu Asn Met Met Gln Arg His Glu Glu Glu Ala 
                785                 790                 795 

His Glu Lys Gly Lys Ile Leu Ser Glu Gln Lys Ala Met Ile Asn 
                800                 805                 810 

Ala Met Asp Ser Lys Ile Arg Ser Leu Glu Gln Arg Ile Val Glu 
                815                 820                 825 

Leu Ser Glu Ala Asn Lys Leu Ala Ala Asn Ser Ser Leu Phe Thr 
                830                 835                 840 

Gln Arg Asn Met Lys Ala Gln Glu Glu Met Ile Ser Glu Leu Arg 
                845                 850                 855 

Gln Gln Lys Phe Tyr Leu Glu Thr Gln Ala Gly Lys Leu Glu Ala 
                860                 865                 870 

Gln Asn Arg Lys Leu Glu Glu Gln Leu Glu Lys Ile Ser His Gln 
                875                 880                 885 

Asp His Ser Asp Lys Asn Arg Leu Leu Glu Leu Glu Thr Arg Leu 
                890                 895                 900 

Arg Glu Val Ser Leu Glu His Glu Glu Gln Lys Leu Glu Leu Lys 
                905                 910                 915 

Arg Gln Leu Thr Glu Leu Gln Leu Ser Leu Gln Glu Arg Glu Ser 
                920                 925                 930 

Gln Leu Thr Ala Leu Gln Ala Ala Arg Ala Ala Leu Glu Ser Gln 
                935                 940                 945 

Leu Arg Gln Ala Lys Thr Glu Leu Glu Glu Thr Thr Ala Glu Ala 
                950                 955                 960 

Glu Glu Glu Ile Gln Ala Leu Thr Ala His Arg Asp Glu Ile Gln 
                965                 970                 975 

Arg Lys Phe Asp Ala Leu Arg Asn Ser Cys Thr Val Ile Thr Asp 
                980                 985                 990 

Leu Glu Glu Gln Leu Asn Gln Leu Thr Glu Asp Asn Ala Glu Leu 
                995                 1000                1005 

Asn Asn Gln Asn Phe Tyr Leu Ser Lys Gln Leu Asp Glu Ala Ser 
                1010                1015                1020 

Gly Ala Asn Asp Glu Ile Val Gln Leu Arg Ser Glu Val Asp His 
                1025                1030                1035 

Leu Arg Arg Glu Ile Thr Glu Arg Glu Met Gln Leu Thr Ser Gln 
                1040                1045                1050 

Lys Gln Thr Met Glu Ala Leu Lys Thr Thr Cys Thr Met Leu Glu 
                1055                1060                1065 

Glu Gln Val Met Asp Leu Glu Ala Leu Asn Asp Glu Leu Leu Glu 
                1070                1075                1080 

Lys Glu Arg Gln Trp Glu Ala Trp Arg Ser Val Leu Gly Asp Glu 
                1085                1090                1095 

Lys Ser Gln Phe Glu Cys Arg Val Arg Glu Leu Gln Arg Met Leu 
                1100                1105                1110 

Asp Thr Glu Lys Gln Ser Arg Ala Arg Ala Asp Gln Arg Ile Thr 
                1115                1120                1125 

Glu Ser Arg Gln Val Val Glu Leu Ala Val Lys Glu His Lys Ala 
                1130                1135                1140 

Glu Ile Leu Ala Leu Gln Gln Ala Leu Lys Glu Gln Lys Leu Lys 
                1145                1150                1155 

Ala Glu Ser Leu Ser Asp Lys Leu Asn Asp Leu Glu Lys Lys His 
                1160                1165                1170 

Ala Met Leu Glu Met Asn Ala Arg Ser Leu Gln Gln Lys Leu Glu 
                1175                1180                1185 

Thr Glu Arg Glu Leu Lys Gln Arg Leu Leu Glu Glu Gln Ala Lys 
                1190                1195                1200 

Leu Gln Gln Gln Met Asp Leu Gln Lys Asn His Ile Phe Arg Leu 
                1205                1210                1215 

Thr Gln Gly Leu Gln Glu Ala Leu Asp Arg Ala Asp Leu Leu Lys 
                1220                1225                1230 

Thr Glu Arg Ser Asp Leu Glu Tyr Gln Leu Glu Asn Ile Gln Val 
                1235                1240                1245 

Leu Tyr Ser His Glu Lys Val Lys Met Glu Gly Thr Ile Ser Gln 
                1250                1255                1260 

Gln Thr Lys Leu Ile Asp Phe Leu Gln Ala Lys Met Asp Gln Pro 
                1265                1270                1275 

Ala Lys Lys Lys Lys Val Pro Leu Gln Tyr Asn Glu Leu Lys Leu 
                1280                1285                1290 

Ala Leu Glu Lys Glu Lys Ala Arg Cys Ala Glu Leu Glu Glu Ala 
                1295                1300                1305 

Leu Gln Lys Thr Arg Ile Glu Leu Arg Ser Ala Arg Glu Glu Ala 
                1310                1315                1320 

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

Thr Ala Arg Gln Gln Ile Ala Met Ser Ala Ile Val Arg Ser Pro 
                1340                1345                1350 

Glu His Gln Pro Ser Ala Met Ser Leu Leu Ala Pro Pro Ser Ser 
                1355                1360                1365 

Arg Arg Lys Glu Ser Ser Thr Pro Glu Glu Phe Ser Arg Arg Leu 
                1370                1375                1380 

Lys Glu Arg Met His His Asn Ile Pro His Arg Phe Asn Val Gly 
                1385                1390                1395 

Leu Asn Met Arg Ala Thr Lys Cys Ala Val Cys Leu Asp Thr Val 
                1400                1405                1410 

His Phe Gly Arg Gln Ala Ser Lys Cys Leu Glu Cys Gln Val Met 
                1415                1420                1425 

Cys His Pro Lys Cys Ser Thr Cys Leu Pro Ala Thr Cys Gly Leu 
                1430                1435                1440 

Pro Ala Glu Tyr Ala Thr His Phe Thr Glu Ala Phe Cys Arg Asp 
                1445                1450                1455 

Lys Met Asn Ser Pro Gly Leu Gln Thr Lys Glu Pro Ser Ser Ser 
                1460                1465                1470 

Leu His Leu Glu Gly Trp Met Lys Val Pro Arg Asn Asn Lys Arg 
                1475                1480                1485 

Gly Gln Gln Gly Trp Asp Arg Lys Tyr Ile Val Leu Glu Gly Ser 
                1490                1495                1500 

Lys Val Leu Ile Tyr Asp Asn Glu Ala Arg Glu Ala Gly Gln Arg 
                1505                1510                1515 

Pro Val Glu Glu Phe Glu Leu Cys Leu Pro Asp Gly Asp Val Ser 
                1520                1525                1530 

Ile His Gly Ala Val Gly Ala Ser Glu Leu Ala Asn Thr Ala Lys 
                1535                1540                1545 

Ala Asp Val Pro Tyr Ile Leu Lys Met Glu Ser His Pro His Thr 
                1550                1555                1560 

Thr Cys Trp Pro Gly Arg Thr Leu Tyr Leu Leu Ala Pro Ser Phe 
                1565                1570                1575 

Pro Asp Lys Gln Arg Trp Val Thr Ala Leu Glu Ser Val Val Ala 
                1580                1585                1590 

Gly Gly Arg Val Ser Arg Glu Lys Ala Glu Ala Asp Ala Lys Leu 
                1595                1600                1605 

Leu Gly Asn Ser Leu Leu Lys Leu Glu Gly Asp Asp Arg Leu Asp 
                1610                1615                1620 

Met Asn Cys Thr Leu Pro Phe Ser Asp Gln Val Val Leu Val Gly 
                1625                1630                1635 

Thr Glu Glu Gly Leu Tyr Ala Leu Asn Val Leu Lys Asn Ser Leu 
                1640                1645                1650 

Thr His Val Pro Gly Ile Gly Ala Val Phe Gln Ile Tyr Ile Ile 
                1655                1660                1665 

Lys Asp Leu Glu Lys Leu Leu Met Ile Ala Gly Glu Glu Arg Ala 
                1670                1675                1680 

Leu Cys Leu Val Asp Val Lys Lys Val Lys Gln Ser Leu Ala Gln 
                1685                1690                1695 

Ser His Leu Pro Ala Gln Pro Asp Ile Ser Pro Asn Ile Phe Glu 
                1700                1705                1710 

Ala Val Lys Gly Cys His Leu Phe Gly Ala Gly Lys Ile Glu Asn 
                1715                1720                1725 

Gly Leu Cys Ile Cys Ala Ala Met Pro Ser Lys Val Val Ile Leu 
                1730                1735                1740 

Arg Tyr Asn Glu Asn Leu Ser Lys Tyr Cys Ile Arg Lys Glu Ile 
                1745                1750                1755 

Glu Thr Ser Glu Pro Cys Ser Cys Ile His Phe Thr Asn Tyr Ser 
                1760                1765                1770 

Ile Leu Ile Gly Thr Asn Lys Phe Tyr Glu Ile Asp Met Lys Gln 
                1775                1780                1785 

Tyr Thr Leu Glu Glu Phe Leu Asp Lys Asn Asp His Ser Leu Ala 
                1790                1795                1800 

Pro Ala Val Phe Ala Ala Ser Ser Asn Ser Phe Pro Val Ser Ile 
                1805                1810                1815 

Val Gln Val Asn Ser Ala Gly Gln Arg Glu Glu Tyr Leu Leu Cys 
                1820                1825                1830 

Phe His Glu Phe Gly Val Phe Val Asp Ser Tyr Gly Arg Arg Ser 
                1835                1840                1845 

Arg Thr Asp Asp Leu Lys Trp Ser Arg Leu Pro Leu Ala Phe Ala 
                1850                1855                1860 

Tyr Arg Glu Pro Tyr Leu Phe Val Thr His Phe Asn Ser Leu Glu 
                1865                1870                1875 

Val Ile Glu Ile Gln Ala Arg Ser Ser Ala Gly Thr Pro Ala Arg 
                1880                1885                1890 

Ala Tyr Leu Asp Ile Pro Asn Pro Arg Tyr Leu Gly Pro Ala Ile 
                1895                1900                1905 

Ser Ser Gly Ala Ile Tyr Leu Ala Ser Ser Tyr Gln Asp Lys Leu 
                1910                1915                1920 

Arg Val Ile Cys Cys Lys Gly Asn Leu Val Lys Glu Ser Gly Thr 
                1925                1930                1935 

Glu His His Arg Gly Pro Ser Thr Ser Arg Ser Ser Pro Asn Lys 
                1940                1945                1950 

Arg Gly Pro Pro Thr Tyr Asn Glu His Ile Thr Lys Arg Val Ala 
                1955                1960                1965 

Ser Ser Pro Ala Pro Pro Glu Gly Pro Ser His Pro Arg Glu Pro 
                1970                1975                1980 

Ser Thr Pro His Arg Tyr Arg Glu Gly Arg Thr Glu Leu Arg Arg 
                1985                1990                1995 

Asp Lys Ser Pro Gly Arg Pro Leu Glu Arg Glu Lys Ser Pro Gly 
                2000                2005                2010 

Arg Met Leu Ser Thr Arg Arg Glu Arg Ser Pro Gly Arg Leu Phe 
                2015                2020                2025 

Glu Asp Ser Ser Arg Gly Arg Leu Pro Ala Gly Ala Val Arg Thr 
                2030                2035                2040 

Pro Leu Ser Gln Val Asn Lys Val Trp Asp Gln Ser Ser Val 
                2045                2050 

 
           
             22  
             1665  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7638121CD1  
             
           
            22 

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

Ser Val Ser Gln Gly Leu Thr Asn His Pro Ser Met Val Gly Cys 
                20                  25                  30 

Gly Trp His Pro Gly Leu Cys Gly Trp Gly Gly Gly Leu His Ser 
                35                  40                  45 

Ser Leu Pro Ala Leu Pro Gly Pro Pro Ser Met Gln Val Thr Ile 
                50                  55                  60 

Glu Asp Val Gln Ala Gln Thr Gly Gly Thr Ala Gln Phe Glu Ala 
                65                  70                  75 

Ile Ile Glu Gly Asp Pro Gln Pro Ser Val Thr Trp Tyr Lys Asp 
                80                  85                  90 

Ser Val Gln Leu Val Asp Ser Thr Arg Leu Ser Gln Gln Gln Glu 
                95                  100                 105 

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

Ala Gly Val Tyr Thr Cys Leu Ala Gln Asn Thr Gly Gly Gln Val 
                125                 130                 135 

Leu Cys Lys Ala Glu Leu Leu Val Leu Gly Gly Asp Asn Glu Pro 
                140                 145                 150 

Asp Ser Glu Lys Gln Ser His Arg Arg Lys Leu His Ser Phe Tyr 
                155                 160                 165 

Glu Val Lys Glu Glu Ile Gly Arg Gly Val Phe Gly Phe Val Lys 
                170                 175                 180 

Arg Val Gln His Lys Gly Asn Lys Ile Leu Cys Ala Ala Lys Phe 
                185                 190                 195 

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

Asp Ile Leu Ala Ala Leu Ser His Pro Leu Val Thr Gly Leu Leu 
                215                 220                 225 

Asp Gln Phe Glu Thr Arg Lys Thr Leu Ile Leu Ile Leu Glu Leu 
                230                 235                 240 

Cys Ser Ser Glu Glu Leu Leu Asp Arg Leu Tyr Arg Lys Gly Val 
                245                 250                 255 

Val Thr Glu Ala Glu Val Lys Val Tyr Ile Gln Gln Leu Val Glu 
                260                 265                 270 

Gly Leu His Tyr Leu His Ser His Gly Val Leu His Leu Asp Ile 
                275                 280                 285 

Lys Pro Ser Asn Ile Leu Met Val His Pro Ala Arg Glu Asp Ile 
                290                 295                 300 

Lys Ile Cys Asp Phe Gly Phe Ala Gln Asn Ile Thr Pro Ala Glu 
                305                 310                 315 

Leu Gln Phe Ser Gln Tyr Gly Ser Pro Glu Phe Val Ser Pro Glu 
                320                 325                 330 

Ile Ile Gln Gln Asn Pro Val Ser Glu Ala Ser Asp Ile Trp Ala 
                335                 340                 345 

Met Gly Val Ile Ser Tyr Leu Ser Leu Thr Cys Ser Ser Pro Phe 
                350                 355                 360 

Ala Gly Glu Ser Asp Arg Ala Thr Leu Leu Asn Val Leu Glu Gly 
                365                 370                 375 

Arg Val Ser Trp Ser Ser Pro Met Ala Ala His Leu Ser Glu Asp 
                380                 385                 390 

Ala Lys Asp Phe Ile Lys Ala Thr Leu Gln Arg Ala Pro Gln Ala 
                395                 400                 405 

Arg Pro Ser Ala Ala Gln Cys Leu Ser His Pro Trp Phe Leu Lys 
                410                 415                 420 

Ser Met Pro Ala Glu Glu Ala His Phe Ile Asn Thr Lys Gln Leu 
                425                 430                 435 

Lys Phe Leu Leu Ala Arg Ser Arg Trp Gln Arg Ser Leu Met Ser 
                440                 445                 450 

Tyr Lys Ser Ile Leu Val Met Arg Ser Ile Pro Glu Leu Leu Arg 
                455                 460                 465 

Gly Pro Pro Asp Ser Pro Ser Leu Gly Val Ala Arg His Leu Cys 
                470                 475                 480 

Arg Asp Thr Gly Gly Ser Ser Ser Ser Ser Ser Ser Ser Asp Asn 
                485                 490                 495 

Glu Leu Ala Pro Phe Ala Arg Ala Lys Ser Leu Pro Pro Ser Pro 
                500                 505                 510 

Val Thr His Ser Pro Leu Leu His Pro Arg Gly Phe Leu Arg Pro 
                515                 520                 525 

Ser Ala Ser Leu Pro Glu Glu Ala Glu Ala Ser Glu Arg Ser Thr 
                530                 535                 540 

Glu Ala Pro Ala Pro Pro Ala Ser Pro Glu Gly Ala Gly Pro Pro 
                545                 550                 555 

Ala Ala Gln Gly Cys Val Pro Arg His Ser Val Ile Arg Ser Leu 
                560                 565                 570 

Phe Tyr His Gln Ala Gly Glu Ser Pro Glu His Gly Ala Leu Ala 
                575                 580                 585 

Pro Gly Ser Arg Arg His Pro Ala Arg Arg Arg His Leu Leu Lys 
                590                 595                 600 

Gly Gly Tyr Ile Ala Gly Ala Leu Pro Gly Leu Arg Glu Pro Leu 
                605                 610                 615 

Met Glu His Arg Val Leu Glu Glu Glu Ala Ala Arg Glu Glu Gln 
                620                 625                 630 

Ala Thr Leu Leu Ala Lys Ala Pro Ser Phe Glu Thr Ala Leu Arg 
                635                 640                 645 

Leu Pro Ala Ser Gly Thr His Leu Ala Pro Gly His Ser His Ser 
                650                 655                 660 

Leu Glu His Asp Ser Pro Ser Thr Pro Arg Pro Ser Ser Glu Ala 
                665                 670                 675 

Cys Gly Glu Ala Gln Arg Leu Pro Ser Ala Pro Ser Gly Gly Ala 
                680                 685                 690 

Pro Ile Arg Asp Met Gly His Pro Gln Gly Ser Lys Gln Leu Pro 
                695                 700                 705 

Ser Thr Gly Gly His Pro Gly Thr Ala Gln Pro Glu Arg Pro Ser 
                710                 715                 720 

Pro Asp Ser Pro Trp Gly Gln Pro Ala Pro Phe Cys His Pro Lys 
                725                 730                 735 

Gln Gly Ser Ala Pro Gln Glu Gly Cys Ser Pro His Pro Ala Val 
                740                 745                 750 

Ala Pro Cys Pro Pro Gly Ser Phe Pro Pro Gly Ser Cys Lys Glu 
                755                 760                 765 

Ala Pro Leu Val Pro Ser Ser Pro Phe Leu Gly Gln Pro Gln Ala 
                770                 775                 780 

Pro Leu Ala Pro Ala Lys Ala Ser Pro Pro Leu Asp Ser Lys Met 
                785                 790                 795 

Gly Pro Gly Asp Ile Ser Leu Pro Gly Arg Pro Lys Pro Gly Pro 
                800                 805                 810 

Cys Ser Ser Pro Gly Ser Ala Ser Gln Ala Ser Ser Ser Gln Val 
                815                 820                 825 

Ser Ser Leu Arg Val Gly Ser Ser Gln Val Gly Thr Glu Pro Gly 
                830                 835                 840 

Pro Ser Leu Asp Ala Glu Gly Trp Thr Gln Glu Ala Glu Asp Leu 
                845                 850                 855 

Ser Asp Ser Thr Pro Thr Leu Gln Arg Pro Gln Glu Gln Val Thr 
                860                 865                 870 

Met Arg Lys Phe Ser Leu Gly Gly Arg Gly Gly Tyr Ala Gly Val 
                875                 880                 885 

Ala Gly Tyr Gly Thr Phe Ala Phe Gly Gly Asp Ala Gly Gly Met 
                890                 895                 900 

Leu Gly Gln Gly Pro Met Trp Ala Arg Ile Ala Trp Ala Val Ser 
                905                 910                 915 

Gln Ser Glu Glu Glu Glu Gln Glu Glu Ala Arg Ala Glu Ser Gln 
                920                 925                 930 

Ser Glu Glu Gln Gln Glu Ala Arg Ala Glu Ser Pro Leu Pro Gln 
                935                 940                 945 

Val Ser Ala Arg Pro Val Pro Glu Val Gly Arg Ala Pro Thr Arg 
                950                 955                 960 

Ser Ser Pro Glu Pro Thr Pro Trp Glu Asp Ile Gly Gln Val Ser 
                965                 970                 975 

Leu Val Gln Ile Arg Asp Leu Ser Gly Asp Ala Glu Ala Ala Asp 
                980                 985                 990 

Thr Ile Ser Leu Asp Ile Ser Glu Val Asp Pro Ala Tyr Leu Asn 
                995                 1000                1005 

Leu Ser Asp Leu Tyr Asp Ile Lys Tyr Leu Pro Phe Glu Phe Met 
                1010                1015                1020 

Ile Phe Arg Lys Val Pro Lys Ser Ala Gln Pro Glu Pro Pro Ser 
                1025                1030                1035 

Pro Met Ala Glu Glu Glu Leu Ala Glu Phe Pro Glu Pro Thr Trp 
                1040                1045                1050 

Pro Trp Pro Gly Glu Leu Gly Pro His Ala Gly Leu Glu Ile Thr 
                1055                1060                1065 

Glu Glu Ser Glu Asp Val Asp Ala Leu Leu Ala Glu Ala Ala Val 
                1070                1075                1080 

Gly Arg Lys Arg Lys Trp Ser Ser Pro Ser Arg Ser Leu Phe His 
                1085                1090                1095 

Phe Pro Gly Arg His Leu Pro Leu Asp Glu Pro Ala Glu Leu Gly 
                1100                1105                1110 

Leu Arg Glu Arg Val Lys Ala Ser Val Glu His Ile Ser Arg Ile 
                1115                1120                1125 

Leu Lys Gly Arg Pro Glu Gly Leu Glu Lys Glu Gly Pro Pro Arg 
                1130                1135                1140 

Lys Lys Pro Gly Leu Ala Ser Phe Arg Leu Ser Gly Leu Lys Ser 
                1145                1150                1155 

Trp Asp Arg Ala Pro Thr Phe Leu Arg Glu Leu Ser Asp Glu Thr 
                1160                1165                1170 

Val Val Leu Gly Gln Ser Val Thr Leu Ala Cys Gln Val Ser Ala 
                1175                1180                1185 

Gln Pro Ala Ala Gln Ala Thr Trp Ser Lys Asp Gly Ala Pro Leu 
                1190                1195                1200 

Glu Ser Ser Ser Arg Val Leu Ile Ser Ala Thr Leu Lys Asn Phe 
                1205                1210                1215 

Gln Leu Leu Thr Ile Leu Val Val Val Ala Glu Asp Leu Gly Val 
                1220                1225                1230 

Tyr Thr Cys Ser Val Ser Asn Ala Leu Gly Thr Val Thr Thr Thr 
                1235                1240                1245 

Gly Val Leu Arg Lys Ala Glu Arg Pro Ser Ser Ser Pro Cys Pro 
                1250                1255                1260 

Asp Ile Gly Glu Val Tyr Ala Asp Gly Val Leu Leu Val Trp Lys 
                1265                1270                1275 

Pro Val Glu Ser Tyr Gly Pro Val Thr Tyr Ile Val Gln Cys Ser 
                1280                1285                1290 

Leu Glu Gly Gly Ser Trp Thr Thr Leu Ala Ser Asp Ile Phe Asp 
                1295                1300                1305 

Cys Cys Tyr Leu Thr Ser Lys Leu Ser Arg Gly Gly Thr Tyr Thr 
                1310                1315                1320 

Phe Arg Thr Ala Cys Val Ser Lys Ala Gly Met Gly Pro Tyr Ser 
                1325                1330                1335 

Ser Pro Ser Glu Gln Val Leu Leu Gly Gly Pro Ser His Leu Ala 
                1340                1345                1350 

Ser Glu Glu Glu Ser Gln Gly Arg Ser Ala Gln Pro Leu Pro Ser 
                1355                1360                1365 

Thr Lys Thr Phe Ala Phe Gln Thr Gln Ile Gln Arg Gly Arg Phe 
                1370                1375                1380 

Ser Val Val Arg Gln Cys Trp Glu Lys Ala Ser Gly Arg Ala Leu 
                1385                1390                1395 

Ala Ala Lys Ile Ile Pro Tyr His Pro Lys Asp Lys Thr Ala Val 
                1400                1405                1410 

Leu Arg Glu Tyr Glu Ala Leu Lys Gly Leu Arg His Pro His Leu 
                1415                1420                1425 

Ala Gln Leu His Ala Ala Tyr Leu Ser Pro Arg His Leu Val Leu 
                1430                1435                1440 

Ile Leu Glu Leu Cys Ser Gly Pro Glu Leu Leu Pro Cys Leu Ala 
                1445                1450                1455 

Glu Arg Ala Ser Tyr Ser Glu Ser Glu Val Lys Asp Tyr Leu Trp 
                1460                1465                1470 

Gln Met Leu Ser Ala Thr Gln Tyr Leu His Asn Gln His Ile Leu 
                1475                1480                1485 

His Leu Asp Leu Arg Ser Glu Asn Met Ile Ile Thr Glu Tyr Asn 
                1490                1495                1500 

Leu Leu Lys Val Val Asp Leu Gly Asn Ala Gln Ser Leu Ser Gln 
                1505                1510                1515 

Glu Lys Val Leu Pro Ser Asp Lys Phe Lys Asp Tyr Leu Glu Thr 
                1520                1525                1530 

Met Ala Pro Glu Leu Leu Glu Gly Gln Gly Ala Val Pro Gln Thr 
                1535                1540                1545 

Asp Ile Trp Ala Ile Gly Val Thr Ala Phe Ile Met Leu Ser Ala 
                1550                1555                1560 

Glu Tyr Pro Val Ser Ser Glu Gly Ala Arg Asp Leu Gln Arg Gly 
                1565                1570                1575 

Leu Arg Lys Gly Leu Val Arg Leu Ser Arg Cys Tyr Ala Gly Leu 
                1580                1585                1590 

Ser Gly Gly Ala Val Ala Phe Leu Arg Ser Thr Leu Cys Ala Gln 
                1595                1600                1605 

Pro Trp Gly Arg Pro Cys Ala Ser Ser Cys Leu Gln Cys Pro Trp 
                1610                1615                1620 

Leu Thr Glu Glu Gly Pro Ala Cys Ser Arg Pro Ala Pro Val Thr 
                1625                1630                1635 

Phe Pro Thr Ala Arg Leu Arg Val Phe Val Arg Asn Arg Glu Lys 
                1640                1645                1650 

Arg Arg Ala Leu Leu Tyr Lys Arg His Asn Leu Ala Gln Val Arg 
                1655                1660                1665 

 
           
             23  
             1014  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7482896CB1  
             
           
            23 

atgacaaaca acagcggctc caaagccgaa ctcgttgtgg gagggaaata caaactggtg     60 

cggaagatcg ggtctggctc ctttggagac gtttatctgg gcatcaccac caccaacggc    120 

gaggacgtag cagtgaagct ggaatctcag aaggtcaagc acccccagtt gctgtatgag    180 

agcaaactct acacgattct tcaaggtggg gttggcatcc cccacatgca ctggtatggt    240 

caggaaaaag acaacaatgt gctagtcatg gaccttctgg gacccagcct cgaagacctc    300 

tttaatttct gttcaagaag gttcaccatg aaaactgtac ttatgttagc cgaccagatg    360 

atcagcagaa ttgaatacgt gcatacaaag aattttctac accgagacat taaaccagat    420 

aacttcctga tgggtactgg gcgtcactgt aataagttgt tccttattga ttttggtttg    480 

gccaaaaagt acagagacaa caggaccagg caacacatac cgtacagaga agataaacac    540 

ctcattggca ctgtccgata tgccagcatc aatgcacatc ttggtattga gcagagccgc    600 

cgagatgaca tggaatcctt aggctacgtt ttcatgtatt ttaatagaac cagcctgccg    660 

tggcaaggac taagggctat gacaaaaaaa caaaaatatg aaaagattag tgagaagaag    720 

atgtccaccc ctgttgaagt tttatgtaag gggtttcctg cagaattcgc catgtacttg    780 

aactactgtc gtgggctgcg ctttgaggaa gtcccagatt acatgtatct gaggcagcta    840 

ttccgcattc ttttcaggac cctgaaccac caatatgact acacatttga ttggacgatg    900 

ttaaagcaga aagcagcaca gcaggcagcc tcttccagtg ggcagggtca gcaggcccaa    960 

acccagacag gcaagcaaac tgaaaaaaac aagaataatg tgaaagataa ctaa         1014 

 
           
             24  
             1530  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7483046CB1  
             
           
            24 

cggcctgaca ggcgggcatg cgggcggcca gactgtagcc gagcagcgag gctccggccg     60 

cagccatgga gcggcggctg cgcgcgctgg agcagctggc gcggggcgag gccggcggct    120 

gcccggggct cgacggcctc ctagatctgc tgctggcgct gcaccacgag ctcagcagcg    180 

gccccctacg gcgggagcgc agcgtggcgc agttcctgag ctgggccagc cccttcgtat    240 

caaaggtgaa agaactgcgt ctgcagagag atgactttga gatcttgaag gtgatcggcc    300 

gaggagcctt tggggaggtc accgtggtga ggcagaggga cactgggcag atttttgcca    360 

tgaaaatgct gcacaagtgg gagatgctga agagggctga gacagcctgt ttccgggagg    420 

agcgggatgt gctcgtgaaa ggggacagcc gttgggtgac cactctgcac tatgccttcc    480 

aagacgagga gtacctgtac cttgtgatgg actactatgc tggtggggac ctcctgacgc    540 

tgctgagccg cttcgaggac cgtctcccgc ccgagctggc ccagttctac ctggctgaga    600 

tggtgctggc catccactcg ctgcaccagc tgggttatgt ccacagggat gtcaagccag    660 

acaacgtcct gctggatgtg aacgggcaca ttcgcctggc tgacttcggc tcctgcctgc    720 

gtctcaacac caacggcatg gtggattcat cagtggcagt agggacgccg gactatatct    780 

cccctgagat cctgcaggcc atggaggagg gcaagggcca ctacggccca cagtgtgact    840 

ggtggtcgct tggagtctgc gcctatgagc tgctctttgg ggagacgccc ttctatgctg    900 

agtccttggt ggaaacctac ggcaagatca tgaaccacga ggaccacctg cagttccccc    960 

cggacgtgcc tgacgtgcca gccagcgccc aagacctgat ccgccagctg ctgtgtcgcc   1020 

aggaagagcg gctaggccgt ggtgggctgg atgacttccg gaaccatcct ttcttcgaag   1080 

gcgtggactg ggagcggctg gcgagcagca cggcccccta tattcctgag ctgcgggggc   1140 

ccatggacac ctccaacttt gatgtggatg acgacaccct caaccatcca gggaccctgc   1200 

caccgccctc ccacggggcc ttctccggcc atcacctgcc attcgtgggc ttcacctaca   1260 

cctcaggcag tcacagtcct gagagcagct ctgaggcttg ggctgccctg gagcggaagc   1320 

tccagtgtct ggagcaggag aaggtggagc tgagcaggaa gcaccaagag gccctgcacg   1380 

cccccacaga ccatcgggag ctggagcagc tacggaagga agtgcagact ctgcgggaca   1440 

ggctgccagg tatcccttcc gcccaccccc accctctcct tgagtttctg tgaattaaaa   1500 

tatttgcaaa tccaaaaaaa aaaaaaaagg                                    1530 

 
           
             25  
             3150  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 71636374CB1  
             
           
            25 

attggcttat aggaaaaatt gatttataaa aagtggtaca ggttttcata gataaccatg     60 

acaacatccc atatgaatgg gcatgttaca gaggaatcag acagcgaagt aaaaaatgtt    120 

gatcttgcat caccagagga acatcagaag caccgagaga tggctgttga ctgccctgga    180 

gatttgggca ccaggatgat gccaatacgt cgaagtgcac agttggagcg tattcggcaa    240 

caacaggagg acatgaggcg taggagagag gaagaaggga aaaagcaaga acttgacctt    300 

aattcttcca tgagacttaa gaaactagcc caaattcctc caaagaccgg aatagataac    360 

cctatgtttg atacagagga aggaattgtc ttagaaagtc ctcattatgc tgtgaaaata    420 

ttagaaatag aagacttgtt ttcttcactt aaacatatcc aacatacttt ggtagattct    480 

cagagccagg aggatatttc actgctttta caacttgttc aaaataagga tttccagaat    540 

gcatttaaga tacacaatgc catcacagta cacatgaaca aggccagtcc tccatttcct    600 

cttatctcca acgcacaaga tcttgctcaa gaggtacaaa ctgttttgaa gccagttcat    660 

cataaggaag gacaagaact aactgctttg ctgaatactc cacatattca ggcactttta    720 

ctggcccacg ataaggttgc tgagcaggaa atgcagctag agcccattac agatgagaga    780 

gtttatgaaa gtattggcca gtatggagga gaaactgtaa aaatagttcg tatagaaaag    840 

gctcgtgata ttccgttggg tgctacagtt cgtaatgaaa tggactctgt catcattagc    900 

cggatagtaa aagggggtgc tgcagagaaa agtggtctgt tgcatgaagg agatgaagtt    960 

ctagagatta atggcattga aattcggggg aaagatgtca atgaggtttt tgacttgttg   1020 

tctgatatgc atggtacttt gacttttgtc ctgattccca gtcaacagat caagccgcct   1080 

cctgccaagg aaacagtaat ccatgtaaaa gctcattttg actatgaccc ctcagatgac   1140 

ccttatgttc catgtcgaga gttaggtctg tcttttcaaa aaggtgatat acttcatgtg   1200 

atcagtcaag aagatccaaa ctggtggcag gcctacaggg aaggggacga agataatcaa   1260 

cctctagccg ggcttgttcc agggaaaagc tttcagcagc aaagggaagc catgaaacaa   1320 

accatagaag aagataagga gccagaaaaa tcaggaaaac tgtggtgtgc aaagaagaat   1380 

aaaaagaaga ggaaaaaggt tttatataat gccaataaaa atgatgatta tgacaacgag   1440 

gagatcttaa cctatgagga aatgtcactt tatcatcagc cagcaaatag gaagagacct   1500 

atcatcttga ttggtccaca gaactgtggc cagaatgaat tgcgtcagag gctcatgaac   1560 

aaagaaaagg accgctttgc atctgcagtt cctcatacaa cccggagtag gcgagaccaa   1620 

gaagtagccg gtagagatta ccactttgtt tcgcggcaag cattcgaggc agacatagca   1680 

gctggaaagt tcattgagca tggtgaattt gagaagaatt tgtatggaac tagcatagat   1740 

tctgtacggc aagtgatcaa ctctggcaaa atatgtcttt taagtcttcg tacacagtca   1800 

ttgaagactc tccggaattc agatttgaaa ccatatatta tcttcattgc acccccttca   1860 

caagaaagac ttcgggcatt attggccaaa gaaggcaaga atccaaagcc tgaagagttg   1920 

agagaaatca ttgagaagac aagagagatg gagcagaaca atggccacta ctttgatacg   1980 

gcaattgtga attccgatct tgataaagcc tatcaggaat tgcttaggtt aattaacaaa   2040 

cttgatactg aacctcagtg ggtaccatcc acttggctga ggtgaaagaa acatccattc   2100 

tgtggcatgt tggacttgat ctggcaaaaa ctgccaatag gaggactgcc cgacactgca   2160 

gcaagattga ggataagatg gaaggcagca gtataagctg tagatctgtt cttagatctc   2220 

ttgaattagt gagacgacag ttcccttagg cagtttgtgc atggcatcct ttattctcta   2280 

tacatggctt tagcggttct tgcctcattt tgggattcta aatggaagct ttcaacagag   2340 

cattccattt tgtcctgtta aaaccttttg ttttcaccta aaccctttct gcttagttgt   2400 

atctctgtga aaaacttgta tacacaagcg tccatgtctc acacaaatat tgatgtgatt   2460 

attcttaagt gttaaatcat taacacttaa atgacttcat tgggaatatt gagcagaggg   2520 

actgtgcttc tatgcactgg gcaaggcagt atttgcttag gaaactaatt tagtcatcag   2580 

agatactttc ctaaaaagga aaaataaaaa acaaaatggt gccactttgg gttgaagcta   2640 

ctttgttagg cttgaattca tttatatgtc ttttgattct taaaaaaaca aaaaacattc   2700 

cattagaagc accagttttt ttgctcagac tttgtggatc agactctaca ctcaacacac   2760 

tctaatctac ttaaaggtat acaaaatatg ctgatctttt ttaaattatg atttcctgaa   2820 

tttttttctt aagtcgtctc aactgattta ctcacttagc ttcccttccc tcatcagcat   2880 

agtataatag aatgtatgtt acatttttat gaatggcagg tgttcattat aatctgtatt   2940 

gacttaaaaa gtttcttcct catgatgcta atagtttttt gtatacatgg gaggatagca   3000 

catttgacag tttttgcatt tttatgtatg agcacagtat cctatgactg tgctacgtat   3060 

atataggtaa taaactggaa ttctgttgat gaatatagct gctgtactgt atattaatat   3120 

ttaatagatc aacaaatggt cattgaaaac                                    3150 

 
           
             26  
             2901  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7480597CB1  
             
           
            26 

atggcggaag gcaaggaagg gcaagtccca tcttacatgg atggcagcag gcaaagagag     60 

aatgaggaag atgcaaaagc ggaaacccct gatgtaacca tcagatctta tgagatttat    120 

tcactaccat ggaacagaca gcaaggccta tgtgaccatt ctctaaaata tttaagctcg    180 

agaatcacag agcggaagct gcaaggctcc tggctgcctg ccagccgagg gaatctggag    240 

aaaccattcc tggggccgcg tggccccgtc gtgcccttgt tctgccctcg gaatggcctt    300 

cactcagcac atcctgagaa cagccctctg aagcccaggg tcgtgaccgt agtgaagctg    360 

ggtgggcagc gcccccgaaa gatcactctg ctcctcaaca ggcgatcagt gcagacgttc    420 

gagcagctct tagctgacat ctcagaagcc ttgggctctc ccagatggaa gaatgaccgt    480 

gtgaggaaac tgtttaacct caagggcagg gaaatcagga gcgtctctga tttcttcagg    540 

gaaggggatg ctttcatagc tatgggcaaa gaaccactga cactgaagag cattcaggtg    600 

gctgtagaag aactgtaccc caacaaagcc cgggccctga cactggccca gcacagccgt    660 

gccccttctc caaggctgag gagcaggctg tttagcaagg ctctgaaagg agaccaccgc    720 

tgtggggaga ccgagacccc caagagctgc agcgaagttg caggatgcaa ggcagccatg    780 

aggcaccagg ggaagatccc cgaggagctt tcactagatg acagagcgag gacccagaag    840 

aagtggggga gggggaaatg ggagccagaa cccagtagca agccccccag ggaagccact    900 

ctggaagaga ggcacgcaag gggagagaag catcttgggg tggagattga aaagacctcg    960 

ggtgaaatta tcagatgcga gaagtgcaag agagagaggg agctccagca gagcctggag   1020 

cgtgagaggc tttctctggg gaccagtgag ctggatatgg ggaagggccc aatgtatgat   1080 

gtggagaagc tggtgaggac cagaagctgc aggaggtctc ccgaggcaaa tcctgcaagt   1140 

ggggaggaag ggtggaaggg tgacagccac aggagcagcc ccaggaatcc cactcaagag   1200 

ctgaggagac ccagcaagag catggacaag aaagaggaca gaggcccaga ggatcaagaa   1260 

agccatgctc agggagcagc caaggccaag aaggaccttg tggaagttct tcctgtcaca   1320 

gaggaggggc tgagggaggt gaagaaggac accaggccca tgagcaggag caaacatggt   1380 

ggctggctcc tgagagagca ccaggcgggc tttgagaagc tccgcaggac ccgaggagaa   1440 

gagaaggagg cagagaagga gaaaaagcca tgtatgtctg gaggcagaag gatgactctc   1500 

agagatgacc aacctgcaaa gctagaaaag gagcccaaga cgaggccaga agagaacaag   1560 

ccagagcggc ccagcggtcg gaagccacgg cccatgggca tcattgccgc caatgtggaa   1620 

aagcattatg agactggccg ggtcattggg gatgggaact ttgctgtcgt gaaggagtgc   1680 

agacaccgcg agaccaggca ggcctatgcg atgaagatca ttgacaagtc cagactcaag   1740 

ggcaaggagg acatggtgga cagtgagatc ttgatcatcc agagcctctc tcaccccaac   1800 

atcgtgaaat tgcatgaagt ctacgaaaca gacatggaaa tctacctgat cctggagtac   1860 

gtgcagggag gagacctttt tgacgccatc atagaaagtg tgaagttccc ggagcccgat   1920 

gctgccctca tgatcatgga cttatgcaaa gccctcgtcc acatgcacga caagagcatt   1980 

gtccaccggg acctcaagcc ggaaaacctt ttggttcagc gaaatgagga caaatctact   2040 

accttgaaat tggctgattt tggacttgca aagcatgtgg tgagacctat atttactgtg   2100 

tgtgggaccc caacttacgt agctcccgaa attctttctg agaaaggtta tggactggag   2160 

gtggacatgt gggctgctgg cgtgatcctc tatatcctgc tgtgtggctt tcccccattc   2220 

cgcagccctg agagggacca ggacgagctc tttaacatca tccagctggg ccactttgag   2280 

ttcctccccc cttactggga caatatctct gatgctgcta aagatctggt gagccggttg   2340 

ctggtggtag accccaaaaa gcgctacaca gctcatcagg ttcttcagca cccctggatc   2400 

gaaacagctg gcaagaccaa tacagtgaaa cgacagaagc aggtgtcccc cagcagcgag   2460 

ggtcacttcc ggagccagca caagagggtt gtggagcagg tatcatagtc accaccttgg   2520 

gaatctgtcc agcccccagt tctgctcaag gacagagaaa aggatagaag tttgagagaa   2580 

aaacaatgaa agaggcttct tcacataatt ggtgaatcag agggagagac actgagtata   2640 

ttttaaagca tattaaaaaa attaagtcaa tgttaaatgt cacaacatat ttttagattt   2700 

gtatatttaa agcctttaat acatttttgg ggggtaagca ttgtcatcag tgaggaattt   2760 

tggtaataat gatgtgtttt gcttcccctt tgtaaccaag tttattctgt actacaggag   2820 

tggtgcttac cagggtctaa actccccctg tgagattaat aaggtgcatt gtggtctttc   2880 

tgtgttaata aaatgtggtc c                                             2901 

 
           
             27  
             1671  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 3227248CB1  
             
           
            27 

atgaagctta taaatggcaa aaagcaaaca ttcccatggt ttggcatgga catcggtgga     60 

acgctggtta aattggtgta tttcgagccg aaggatatta cagccgaaga ggagcaagag    120 

gaagtggaga acctgaagag catccggaag tatttgactt ctaatactgc ttatgggaaa    180 

actgggatcc gagacgtcca cctggaactg aaaaacctga ccatgtgtgg acgcaaaggg    240 

aacctgcact tcatccgctt tcccagctgt gctatgcaca ggttcattca gatgggcagc    300 

gagaagaact tctctagcct tcacaccacc ctctgtgcca caggaggcgg ggctttcaaa    360 

ttcgaagagg acttcagaat gattgctgac ctgcagctgc ataaactgga tgaactggac    420 

tgtctgattc agggcctgct ttatgtcgac tctgttggct tcaacggcaa gccagaatgt    480 

tactattttg aaaatcccac aaatcctgaa ttgtgtcaaa aaaagccgta ctgccttgat    540 

aacccatacc ctatgttgct ggttaacatg ggctcaggtg tcagcattct agccgtgtac    600 

tccaaggaca actataaaag agttacaggg accagtcttg gaggtggaac attcctaggc    660 

ctatgttgct tgctgactgg ttgtgagacc tttgaagaag ctctggaaat ggcagctaaa    720 

ggcgacagca ccaatgttga taaactggtg aaggacattt acggaggaga ctatgaacga    780 

tttggccttc aaggatctgc tgtagcatca agctttggca acatgatgag taaagaaaag    840 

cgagattcca tcagcaagga agacctcgcc cgggccacat tggtcaccat caccaacaac    900 

attggctcca ttgctcggat gtgtgcgttg aatgagaaca tagacagagt tgtgtttgtt    960 

ggaaattttc tcagaatcaa tatggtctcc atgaagctgc tggcatatgc catggatttt   1020 

tggtccaaag gacaactgaa agctctgttt ttggaacatg agggttattt tggagccgtt   1080 

ggggcactgt tggaactgtt caaaatgact gatgataagt agagacgagc agtggaggaa   1140 

acagcctccc aaaaggacag agaactaaaa aattgctgct ggagaaggtg aaagtcgctt   1200 

tgggacggaa gccaagccat tatggcagat gaacctgctg gatttgtaaa taatttaaaa   1260 

tccttccaga tgatctttta ctcttaggtt ttgagctaat gattcaaaac gggggaatat   1320 

aaaaggtttt ttttctgtat actgtatttt tttaaaaaaa tggtgcagcg tggccaaacc   1380 

taccaattgt atgcattaac tttgaaaagt tgtttgatgt ttaagaagga cctgatatgt   1440 

aagcgctggt catttttctt ctggggttta ctgatcagtg tggtgatttt aacttcattt   1500 

agtaattact ctaggagatt ttaccttgac ttatattttt catgacgttt catgatttgc   1560 

tgttggtttc aaatgaaact acaaatctgg catgttttac tgtgaacact tttgttattt   1620 

gttttgtacc ctttttgtct tgtttttctg ttttagttgt cttctgaaaa a            1671 

 
           
             28  
             2577  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 4207273CB1  
             
           
            28 

atgccacaga tagcaaagaa gcaatcaact caccggactc agaaacctaa aaagcaatca     60 

tttccttgca tctgtaaaaa tccaggaaca cagaagtcat gtgttcctct ctctgttcaa    120 

ccgacagagc caagactaaa ttacctagat cttaagtata gtgatatgtt caaagaaatc    180 

aattcaactg ctaatggacc tggaatctat gaaatgtttg ggacccctgt ttattgtcat    240 

gtgcgagaga ctgaaaggga tgaaaacacg tattaccgtg agatatgttc ggctccatca    300 

ggcagacgta tcaccaataa atgtcgatct tcacacagtg agaggaagag caatatcaga    360 

acaagacttt ctcagaaaaa aacacatatg aaatgcccaa agacttcatt tggcattaaa    420 

caagagcaca aagtcttaat ttctaaagaa aagagttcca aggctgtaca tagcaaccta    480 

catgacattg aaaatggtga tggtatttca gaaccagact ggcagataaa gtcttcagga    540 

aatgagtttc tatcttccaa agatgaaatt catcccatga acttggctca gacacctgag    600 

cagtccatga aacagaatga attccctcct gtctcagatt tatccattgt tgaagaagtt    660 

tctatggaag agtctactgg tgatagagac atttctaaca atcaaatact caccacaagc    720 

ctcagagatc tgcaagaact tgaagagcta catcaccaga tcccatttat cccttcagaa    780 

gacagctggg cagtgcccag tgagaagaat tctaacaagt atgtacagca agaaaagcag    840 

aatacagcat ctcttagtaa agtaaatgcc agccgaattt taactaatga tctagagttt    900 

gatagtgttt cagatcactc taaaacactt acaaatttct ctttccaagc aaaacaagaa    960 

agtgcatctt cccagacata tcaatattgg gtacattatt tggatcatga tagtttagca   1020 

aataagtcaa tcacatatca aatgtttgga aaaaccttaa gtggcacaaa ttcaatttcc   1080 

caagaaatta tggactctgt aaataatgaa gaattgacag atgaactatt aggttgtcta   1140 

gctgcagaat tattagctct tgatgagaaa gataacaact cttgccaaaa aatggcaaat   1200 

gaaacagatc ctgaaaacct aaatcttgtc ctcagatgga gaggaagtac cccaaaagaa   1260 

atgggcagag agacaacaaa agtcaaaata cagaggcata gtagtgggct caggatatat   1320 

gacagggagg agaaatttct catctcaaat gaaaagaaga tattttctga aaatagttta   1380 

aagtctgaag aacctatcct atggaccaag ggtgagattc ttggaaaggg agcctacggc   1440 

acagtatact gtggtctcac tagtcaagga cagctaatag ctgtaaaaca ggtggctttg   1500 

gatacctcta ataaattagc tgctgaaaag gaataccgga aactacagga agaagtagat   1560 

ttgctcaaag cactgaaaca tgtcaacatt gtggcctatt tggggacatg cttgcaagag   1620 

aacactgtga gcattttcat ggagtttgtt cctggtggct caatctctag tattataaac   1680 

cgttttgggc cattgcctga gatggtgttc tgtaaatata cgaaacaaat acttcaaggt   1740 

gttgcttatc tccatgagaa ctgtgtggta catcgcgata tcaaaggaaa taatgttatg   1800 

ctcatgccaa ctggaataat aaagctgatt gactttggct gtgccaggcg tttggcctgg   1860 

gcaggtttaa atggcaccca cagtgacatg cttaagtcca tgcatgggac tccatattgg   1920 

atggccccag aagtcatcaa tgagtctggc tatggacgga aatcagatat ctggagcatt   1980 

ggttgtactg tgtttgagat ggctacaggg aagcctccac tggcttccat ggacaggatg   2040 

gccgccatgt tttacatcgg agcacaccga gggctgatgc ctcctttacc agaccacttc   2100 

tcagaaaatg cagcagactt tgtgcgcatg tgcctgacca gggaccagca tgagcgacct   2160 

tctgctctcc agctcctgaa gcactccttc ttggagagaa gtcactgaat atacatcaag   2220 

actttcttcc cagttccact gcagatgctc ccttgcttaa ttgtggggaa tgatggctaa   2280 

gggatctttg tttccccact gaaaattcag tctaacccag tttaagcaga tcctatggag   2340 

tcattaactg aaagttgcag ttacatatta gcctcctcaa gtgtcagaca ttattactca   2400 

tagtatcaga aaacatgttc ttaataacaa caaaaaacta tttcagtgtt tacagttttg   2460 

attgtccagg aactacattc tctagtgttt tatatgacat ttctttttat ttttggcctg   2520 

tcctgtcaat tttaatgttg ttagtttaaa ataaattgta aaaacaaaaa aaaaaaa      2577 

 
           
             29  
             2110  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7483334CB1  
             
           
            29 

ctagggtcgc cggggaagcg gtttgggaga gcccatggtg actgcgtgag tggagcccag     60 

ctgtgtggat gccccagcat ggatgactac atggtcctga gaatgattgg ggagggctcc    120 

ttcggcagag ctcttttggt tcagcttgaa agcagtaatc agatgtttgc catgaaagaa    180 

ataaggcttc ccaagtcttt ctctaataca cagaattcta ggaaggaggc tgttctttta    240 

gccaaaatga aacaccctaa tattgttgcc ttcaaagaat catttgaagc tgaaggacac    300 

ttgtatattg tgatggaata ctgtgatgga ggggatctaa tgcaaaagat taaacagcag    360 

aaaggaaagt tatttcctga agacatgata cttaattggt ttacccaaat gtgccttgga    420 

gtaaatcaca ttcacaagaa acgtgtgcta cacagagata tcaagtccaa gaatatcttc    480 

ctcactcaga atggaaaagt gaaattggga gactttggat ctgcccgtct tctctccaat    540 

ccgatggcat ttgcttgtac ctatgtggga actccttatt atgtgcctcc agaaatttgg    600 

gaaaacctgc cttataacaa taaaagtgac atctggtcct tgggttgcat cctgtatgaa    660 

ctctgtaccc ttaagcatcc atttcaggca aatagttgga aaaatcttat cctcaaagta    720 

tgtcaagggt gcatcagtcc actgccgtct cattactcct atgaacttca gttcctagtc    780 

aagcagatgt ttaaaaggaa tccctcacat cgcccctcgg ctacaacgct tctctctcga    840 

ggcatcgtag ctcggcttgt ccagaagtgc ttaccccccg agatcatcat ggaatatggt    900 

gaggaagtat tagaagaaat aaaaaattcg aagcataaca caccaagaaa aaaaacaaac    960 

cccagcagaa tcaggatagc tttgggaaat gaagcaagca cagtgcaaga ggaagaacaa   1020 

gatagaaagg gtagccatac tgatttggaa agcattaatg aaaatttagt tgaaagtgca   1080 

ttgagaagag taaacagaga agaaaaaggt aataagtcag tccatctgag gaaagccagt   1140 

tcaccaaatc ttcatagacg acagtgggag aaaaatgtac ccaatacagc tcttacagct   1200 

ttggaaaatg catccatact cacctccagt ttaacagcag aggacgatag aggtggttct   1260 

gtaataaagt acagcaaaaa tactactcgt aagcagtggc tcaaagagac ccctgacact   1320 

ttgttgaaca tccttaagaa tgctgatctc agcttggctt ttcaaacata cacaatatat   1380 

agaccaggtt cagaagggtt cttgaaaggc cccctgtctg aagaaacaga agcatcggac   1440 

agtgttgatg gaggtcacga ttctgtcatt ttggatccag agcgacttga gcctgggcta   1500 

gatgaggagg acacggactt tgaggaggaa gatgacaacc ccgactgggt gtcagagctg   1560 

aagaagcgag ctggatggca aggcctgtgc gacagataat gcctgaggaa atgttcctga   1620 

gtcacgctga ggagagcctt cactcaggag ttcatgctga gatgatcatg agttcatgcg   1680 

acgtatattt tcctttggaa acagaatgaa gcagaggaaa ctcttaatac ttaaaatcgt   1740 

tcttgattag tatcgtgagt ttgaaaagtc tagaactcct gtaagttttt gaactcaagg   1800 

gagaaggtat agtggaatga gtgtgagcat cgggctttgc agtcccatag aacagaaatg   1860 

ggatgctagc gtgccactac ctacttgtgt gattgtggga aattacttaa cctcttcaag   1920 

ccccaatttc ctcaaccata aaatgaagat aataatgcct acctcagagg gatgctgacc   1980 

acagaccttt atagcagccc gtatgatatt attcacatta tgatatgtgt ttattattat   2040 

gtgactcttt ttacatttcc taaaggtttg agaattaaat atatttaatt atgatttaaa   2100 

aaaaaaaaaa                                                          2110 

 
           
             30  
             7093  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7483337CB1  
             
           
            30 

cgaggggacg cctcgcgacg gttcctggga gagctggcgg cggccttgct ctgcgcgctc     60 

ttcgcgccgc cctccccgcc cgcccgcctc aggattgagg aagtgcgtct gggcccggcc    120 

ccggcgcggg gggcagacgg cggtgggacg gccaggcccc ggccccgcca gtgtgtccgc    180 

ccggccccgc gtcccggagg agtcagctgt gtgtccagaa cgtgccatgg agacgcttaa    240 

cggtgccggg gacacgggcg gcaagccgtc cacgcggggc ggtgaccctg cagcgcggtc    300 

ccgcaggacg gaaggcatcc gcgccgcgta caggcgggga gaccgcggcg gcgcccggga    360 

cctgctggag gaggcctgcg accagtgcgc gtcccagctg gaaaagggcc agcttctgag    420 

catcccggca gcctatgggg atctggagat ggtccgctac ctactcagca agagactggt    480 

ggagctgccc accgagccca cggatgacaa cccagccgtg gtggcagcgt attttggaca    540 

cacggcagtt gtgcaaaata cgctgcccac cgagcccacg gatgacaacc cagccgtggt    600 

ggcagcgtat tttggacaca cggcagttgt gcaggaattg cttgagtcct taccaggtcc    660 

ctgcagtccc cagcggcttc tgaactggat gctggccttg gcttgccagc gagggcacct    720 

gggggttgtg aagctcctgg tcctgacgca cggggctgac ccggagagct acgctgtcag    780 

gaagaatgag ttccctgtca tcgtgcgctt gcccctgtat gcggccatca agtcagggaa    840 

tgaagacatt gcaatattcc tgcttcggca tggggcctat ttctgttcct acatcttgct    900 

ggatagtcct gaccccagca aacatctgct gagaaagtac ttcattgaag ccagtccctt    960 

gcccagcagt tatccgggaa aaacagctct ccgtgtgaaa tggtcccatc tcagactgcc   1020 

ctgggtagac ctagactggc tcatagacat ctcctgccag atcacggagc tcgacctttc   1080 

tgccaactgc ctggcgaccc tcccctcggt tatcccctgg ggcctcatca atctccggaa   1140 

gctgaacctc tccgacaacc acctggggga gctgcctggc gtgcagtcat cggacgaaat   1200 

catctgttcc aggctacttg aaattgacat ttccagcaac aagttgtccc acctccctcc   1260 

tggattcttg cacctctcaa aacttcaaaa actgacagct tcaaaaaatt gtttagaaaa   1320 

attgttcgaa gaagaaaatg ccactaactg gataggttta cggaagctac aggaacttga   1380 

tatatctgac aataaattga cagaactccc tgccctgttc cttcactctt tcaagtccct   1440 

caattctctg aatgtctcca gaaacaacct gaaggtgttt ccagatccct gggcctgccc   1500 

tttgaaatgt tgtaaagctt ccagaaatgc cctggaatgt ctgccagaca aaatggctgt   1560 

cttttggaaa aatcacctga aggatgtgga tttctcagaa aacgcactca aagaagttcc   1620 

cctgggactt ttccagcttg atgccctcat gttcttgagg ttacagggga accagctggc   1680 

ggcacttcca cctcaagaga agtggacctg caggcagctc aaaaccctgg atctctccag   1740 

aaaccaactt ggcaaaaatg aagatggact gaaaacgaag cgtattgcct ttttcaccac   1800 

cagaggtcgc cagcgctccg ggactgaggc agagacaact atggagttca gtgcatctct   1860 

ggtaaccatt gtgttcctgt ctaacaactg taacctctgt gcatacacat gtgcagcaag   1920 

tgtgctggaa tttccggcct tcctaagtga gtctttggaa gtcctttgcc tgaacgacaa   1980 

ccacctcgac acagtccctc cctcggtttg cctactgaag agcttatcag agctctactt   2040 

gggaaacaac cctggcctcc gggagctccc tcctgagctg gggcagctgg gcaacctctg   2100 

gcagctggac actgaagacc tgaccatcag caatgtgcct gcagaaatcc aaaaagaagg   2160 

ccccaaagca atgctgtctt acctgcgtgc tcagctgcgg aaagcggaaa agtgcaagct   2220 

gatgaagatg atcatcgtgg gtcccccgcg ccagggcaag tccaccctcc tggagatctt   2280 

acagacgggg agggcccccc aggtggtgca tggagaggcc accatcagga ccaccaagtg   2340 

ggagctccag aggccggctg gctcgagagc caaggtcaag gatggtctgc gtgcagagtc   2400 

cctgtgggtt gagtccgtgg agttcaacgt ctgggacatc gggggaccgg ccagcatggc   2460 

cactgtcaac cagtgcttct tcacggacaa ggccctgtac gtggtggtct ggaacctggc   2520 

gctgggggag gaggccgtgg ccaacctcca gttctggctg ctcaacatcg aggccaaggc   2580 

cccaaacgcc gtggtgctgg tggtcgggac gcacctggat ttaattgaag ccaagttccg   2640 

tgtggaaagg attgcaacgc tgcgtgccta tgtgctggca ctctgccgct ccccctccgg   2700 

ctccagggcc acaggcttcc cagacatcac cttcaaacac ttacatgaga tttcctgcaa   2760 

gagcctggaa ggtcaggaag ggctgcgaca gctgattttc cacgtcacgt gcagcatgaa   2820 

ggacgtcggc agcaccatcg gctgccagcg actggcaggg cggctgatcc ccaggagcta   2880 

cctgagcctg caggaggccg tgctggcaga gcagcagcgc cgcagccggg acgacgacgt   2940 

gcagtacctg acggacaggc agctggagca gctggtggag cagacgcccg acaacgacat   3000 

caaggactac gaggacctgc agtcagccat cagcttcctc atagaaaccg gcaccctgct   3060 

ccatttcccg gacaccagcc acggcctgag gaacctctac ttcctcgacc ctatttggct   3120 

ctccgaatgt ctgcagagga tctttaatat taagggctct cggtcagtgg ccaagaatgg   3180 

ggtgatcaga gcagaagacc tcaggatgct gctggtgggg actggcttca cgcagcagac   3240 

ggaagagcag tacttccagt tcctggccaa gtttgagatc gccctgcccg tcgccaatga   3300 

cagctacctc ctgccccatc tccttccatc taaacctggc ctggacaccc acggtatgcg   3360 

gcaccccaca gccaacacca ttcagagggt atttaagatg agcttcgttc ccgttggctt   3420 

ctggcaaagg tttatagcac ggatgctgat cagcctggcg gagatggacc tgcagctttt   3480 

tgaaaacaag aagaatacta aaagcaggaa caggaaagtc accatttaca gttttacagg   3540 

aaaccagaga aatcgctgta gcacattcag agtgaaaaga aatcagacca tctattggca   3600 

ggaagggctc ctggtcactt ttgatggggg ctacctcagt gtggaatctt ccgacgtgaa   3660 

ctggaaaaag aagaaaagcg gaggaatgaa aattgtttgc caatcagaag tgagggactt   3720 

ctcagccatg gctttcatca cggaccacgt caattccttg attgatcagt ggtttcccgc   3780 

cctgacagcc acagagagcg acgggacgcc actcatggag cagtacgtgc cctgcccggt   3840 

ctgcgagaca gcctgggccc agcacacgga ccccagtgag aaatcagagg atgtgcagta   3900 

cttcgacatg gaagactgtg tcctgacggc catcgagcgg gacttcatct cctgccccag   3960 

acacccggac ctccccgtgc cgctgcagga gctggtccct gaactgttca tgaccgactt   4020 

cccggccagg ctcttcctgg agaacagcaa gctggagcac agcgaggacg agggcagcgt   4080 

cctgggccag ggcggcagtg gcaccgtcat ctaccgggcc cggtaccagg gccagcctgt   4140 

ggccgtcaag cgcttccaca tcaaaaaatt caagaacttt gctaacgtac cggcagacac   4200 

catgctgagg cacctgcggg ccaccgatgc catgaagaac ttctccgagt tccggcagga   4260 

ggccagcatg ctgcacgcgc tgcagcaccc ctgcatcgtg gcgctcatcg gcatcagcat   4320 

ccacccgctc tgcttcgccc tggagctcgc gccgctcagc agcctcaaca ccgtgctgtc   4380 

cgagaacgcc agagattctt cctttatacc cctgggacac atgctcaccc aaaaaatagc   4440 

ctaccagatc gcctcgggcc tggcctacct gcacaagaaa aacatcatct tctgtgacct   4500 

gaagtcggac aacattctgg tgtggtccct tgacgtcaag gagcacatca acatcaagct   4560 

atctgactac gggatttcga ggcagtcatt ccatgagggc gccctaggcg tggagggcac   4620 

tcctggctac caggccccag agatcaggcc tcgcattgta tatgatgaga aggtagatat   4680 

gttctcctat ggaatggtgc tctacgagtt gctgtcagga cagcgccctg cactgggcca   4740 

ccaccagctc cagattgcca agaagctgtc caagggcatc cgcccggttc tggggcagcc   4800 

ggaggaagtg cagttccggc gactgcaggc gctcatgatg gagtgctggg acactaagcc   4860 

agagaagcga ccgctggccc tgtcggtggt gagccagatg aaggacccga cttttgccac   4920 

cttcatgtat gaactgtgct gtgggaagca gacagccttc ttctcatccc agggccagga   4980 

gtacaccgtg gtgttttggg atggaaaaga ggagtccagg aactacacgg tggtgaacac   5040 

agagaagggc ctcatggagg tgcagaggat gtgctgccct gggatgaagg tgagctgcca   5100 

gctccaggtc cagagatccc tgtggacagc caccgagaat tcctacctgg tcttagcggg   5160 

cctcgccgat gggcttgtgg ctgtgtttcc cgtggtgcgg ggcaccccaa aggacagctg   5220 

ctcctacctg tgctcacaca cagccaacag gtccaagttc agcatcgcgg atgaagacgc   5280 

acggcagaac ccctacccag tgaaggccat ggaggtggtc aacagcggct ctgaggtctg   5340 

gtacagcaat gggccgggcc tccttgtcat cgactgtgcc tccctggaga tctgcaggcg   5400 

gctggagccc tacatggccc cctccatggt tacgtcagtc gtgtgcagct ctgagggcag   5460 

aggggaggag gtcgtctggt gcctggatga caaggccaac tccttggtga tgtaccactc   5520 

caccacctac cagctgtgtg cccggtactt ctgcggggtc cccagccccc tcagggacat   5580 

gtttcccgtg cggcccttgg acacggaacc cccggcagcc agccacacgg ccaacccaaa   5640 

ggtgcctgag ggggactcca tcgcggacgt gagcatcatg tacagtgagg agctgggcac   5700 

gcagatcctg atccaccagg aatcactcac tgactactgc tccatgtcct cctactcctc   5760 

atccccaccc cgccaggctg ccaggtcccc ctcaagcctc cccagctccc cagcaagttc   5820 

ttccagtgtg cctttctcca ccgactgcga ggactcagac atgctacata cgcccggtgc   5880 

tgcctccgac aggtctgagc atgacctgac ccccatggac ggggagacct tcagccagca   5940 

cctgcaggcc gtgaagatcc tcgccgtcag agacctcatt tgggtcccca ggcgcggtgg   6000 

agatgttatc gtcattggcc tggagaagga ttctggcgcc cagcggggcc gagtcattgc   6060 

cgtcttaaaa gcccgagagc tgactccgca tggggtgctg gtggatgctg ccgtggtggc   6120 

aaaggacact gttgtgtgca cctttgaaaa tgaaaacaca gagtggtgcc tggccgtctg   6180 

gaggggctgg ggcgccaggg agttcgacat tttctaccag tcctacgagg agctgggccg   6240 

gctggaggct tgcactcgca agagaaggta attcctgtgg aatgactgtc acacatcaga   6300 

gctggctggc ccggggctgc agcctgactc ctctgccatc ggcctctagt tctccaagga   6360 

cctagaagac agatggagtt ctcccctgaa ctccttgctg ctaagaagtg ctgagaagtt   6420 

actcgcctgg cggtggctcc agggttctct ggttctctgg agcagagttc tctgaatacc   6480 

ccatccccca actgctgatt ttacagcccc agggaagaca gtggtatcag gctgggagcg   6540 

gcctcctctg gcctccccca tcagtttgca ggagcagggg tgcaggatcc tgttctgagc   6600 

tgggtcaaac aaagcagggc cgggccttcc tgccatcccc aggtctcaga tggaattaca   6660 

ctagaggccc tccgctggga agcacttgag gtagggcagg aggggggctg tgacccctgc   6720 

cctttccccg ccagagacct caggctctca gcacattcca caggctcctg agtccccgag   6780 

gcctgggcca gcttgggcaa gccaagatca gatgtctctg tgttcgggaa ggtctccgtg   6840 

tgggaaagcc cttgggggat cccgggtgag gagtgttgcc ccatccagag aatgaatgag   6900 

ttcctttaag tgccaccgcc agcaagccca gaggcacaca ttctgagtgc acccgcttag   6960 

cctttacatt cctctccacc gacaaaagga aggggaaact caatcagcag gacttcagaa   7020 

agggccttgt gtttatagct ttgtcaagta aatttggacg cagctggaaa cacaggcctg   7080 

tttgttgcac ata                                                      7093 

 
           
             31  
             1800  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 6035509CB1  
             
           
            31 

gctgcagagt gctttacttt caacaagatg gagtcttgct ctgtttccca gcctgtagtg     60 

cagtgacaca gtcttggctc actgtaacct ctgcctcctg ggttcaagtg attctcctgc    120 

ctcagcctcc tgagtagctg ggattacagg aaacatctgt atggattatt tcactataat    180 

cctatgatgc ttggacttga atcacttcca gatcccacag acacctggga aattatagag    240 

accattggta aaggcaccta tggcaaagtc tacaaggtaa ctaacaagag agatgggagc    300 

ctggctgcag tgaaaattct ggatccagtc agtgatatgg atgaagaaat tgaggcagaa    360 

tacaacattt tgcagttcct tcctaatcat cccaatgttg taaagtttta tgggatgttt    420 

tacaaagcgg atcactgtgt agggggacag ctgtggctgg tcctggagct gtgtaatggg    480 

ggctcagtca ctgagcttgt caaaggtcta ctcagatgtg gccagcggtt ggatgaagca    540 

atgatctcat acatcttgta cggggccctc ttgggccttc agcatttgca caacaaccga    600 

atcatccacc gtgatgtgaa ggggaataac attcttctga caacagaagg aggagttaag    660 

ctcgttgact ttggtgtttc agctcaactc accagtacac gtctgcggag aaacacatct    720 

gttggcaccc cgttctggat ggcccctgag gtcattgcct gtgagcagca gtatgactct    780 

tcctatgacg ctcgctgtga cgtctggtcc ttggggatca cagctattga actgggggat    840 

ggagaccctc ccctctttga catgcatcct gtgaaaacac tctttaagat tccaagaaat    900 

cctccaccta ctttacttca tccagaaaaa tggtgtgaag aattcaacca ctttatttca    960 

cagtgtctta ttaaggattt tgaaaggcga ccttccgtca cacatctcct tgaccaccca   1020 

tttattaaag gagtacatgg aaaagttctg tttctgcaaa aacagctggc caaggttctc   1080 

caagaccaga agcatcaaaa tcctgttgct aaaaccaggc atgagaggat gcataccaga   1140 

agaccttatc atgtggaaga tgctgaaaaa tactgccttg aggatgattt ggtcaaccta   1200 

gaggttctgg atgaggtact aaatatttag tagacaattc tcattgaaga catttgtttc   1260 

atgtgaatgg tctgaacttt ctgttgtaga ccatgtcctc ctaaggtcat ttgaaaattt   1320 

aattgtttgt gtagctatgg gatgaagttc agggagcatt cagttgctgt gactatgatc   1380 

ctgtgctgtg tttatttaga tagcccctag aatgatgaag agaaaaggat ttggattttt   1440 

gcaataaagc tctttatatt gtagccttaa tgatggatta tatcagctga aaatattttg   1500 

tttgataaaa tttgataaaa tatttcaatt aacccttaag aagttgtttg ttcttcataa   1560 

gaaagagctt catttaggga aatagtgaag ttaatatagc ttgaattcta aatttgaagt   1620 

ctgtgataat ccccatttaa aatatgcatg tttaatagag ctgttaattg cactggacct   1680 

gtttatgctg agtctaactc tggggattgt taccttcaat gtctaaatca ctaaagtgta   1740 

atacaaagtg gttaattctg tatttatgcc acctaggttt taagtgcagt gctttgagaa   1800 

 
           
             32  
             6347  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7373485CB1  
             
           
            32 

ggaagcgaga agccgcatca accatgtaag cagcttcgct tcctgccgca accgtccgcg     60 

gcctgaggag cccaccgccg ctctcggggg ccgacttccg ggggctgagc cgttgaagcg    120 

gaggctgggg cggggggcag ccggcgcggc cggggcagga ggcgcagact catgaaatgg    180 

ccacagatga taagacgtcc ccaacactgg actctgctaa tgatttgcct cgatctccta    240 

ctagtccttc tcatctcaca cactttaaac ctttgactcc tgatcaagat gagccccctt    300 

ttaaatcagc ttatagttct tttgtaaatc tctttcgttt taacaaagag agagcagaag    360 

gaggccaggg agaacagcag cctttgagtg gaagttggac cagccctcag ctcccttcga    420 

ggacacagtc tgttaggtca cccacacctt ataaaaagca gcttaatgag gaactccagc    480 

ggcgctcttc agcattagac acaagaagga aagcagaacc tacctttgga ggtcatgacc    540 

ctcgtacagc tgttcagctt cgaagcctca gcacagtatt aaaacgcctc aaggaaatca    600 

tggaggggaa aagccaggat agtgacctga aacaatactg gatgccagat agccaatgta    660 

aagagtgcta tgactgtagt gagaaattta caacctttag gcgcagacac cattgccgac    720 

tatgtgggca gattttctgc agtcgttgct gtaatcaaga aatccctgga aaatttatgg    780 

gctatacagg agacctccga gcttgcacat attgtagaaa aatagcctta agttatgctc    840 

attccacaga cagtaattct attggggaag acttgaatgc tctttcagat tctgcttgct    900 

ctgtgtctgt gcttgatcca agtgaacccc gaacacctgt tgggagtagg aaagccagcc    960 

gtaacatatt tttagaggat gatttggcct ggcaaagttt gattcatcca gattcctcaa   1020 

atactcctct ttcaacaaga cttgtatctg tgcaagagga tgctgggaaa tctcctgctc   1080 

gaaatagatc agccagcatt actaacctgt cactggatag atctggttct cctatggtac   1140 

cttcatatga gacatctgtc agtccccagg ctaaccgaac atatgttagg acagagacca   1200 

ctgaggatga acgcaaaatt cttctggaca gtgtgcagtt aaaagacctg tggaaaaaaa   1260 

tctgccatca cagcagtgga atggagtttc aggatcaccg ctactggttg agaacgcatc   1320 

ccaactgcat tgtaggaaag gaattagtca actggctaat ccgaaatggg catattgcca   1380 

caagggcaca agctatagca attggacaag caatggttga tggacgttgg ctggattgtg   1440 

ttagtcatca cgaccagctt ttcagagatg agtatgcgct gtatagacca ctgcagagta   1500 

cagaattttc tgagacgcct tctcccgaca gtgactcagt gaactccgtg gaaggacact   1560 

ctgagccatc ctggtttaaa gacataaagt ttgatgacag tgacacagaa cagatagctg   1620 

aagaaggtga cgataatttg gctaagtatt tgatttctga cactggagga caacagctct   1680 

caataagtga cgctttcatc aaagaatcct tatttaatcg ccgagtagag gaaaaatcca   1740 

aagagctgcc tttcacacct ttgggctggc atcataacaa cctggagctc ctgagggagg   1800 

agaatgggga gaaacaagcc atggagaggt tgctttcagc taatcataac cacatgatgg   1860 

cactactcca gcagttgctc catagtgact cactgtcatc atcttggagg gacatcatcg   1920 

tgtcattggt ctgccaggtt gttcagacag tccgacctga tgtcaagaac caggatgatg   1980 

acatggatat ccgtcagttt gtccacatca aaaaaatccc aggtggaaag aagtttgatt   2040 

ctgtggttgt caatggcttt gtttgtacca agaacattgc acataaaaag atgaattctt   2100 

gtattaaaaa ccctaaaatt cttctgttga agtgttccat tgagtatctc tacagagaag   2160 

aaactaagtt tacttgcatt gatcctattg tgcttcagga aagggaattc ttgaagaatt   2220 

atgtccagcg aatagttgat gttcgaccca ccttggttct tgttgagaaa acagtgtctc   2280 

ggattgccca ggacatgtta ttggaacatg gcattacttt ggtcattaat gtaaagtcac   2340 

aagttttgga acgaatcagt cgaatgaccc aaggtgattt agtgatgtca atggaccagc   2400 

tgcttacgaa accacgcctg ggcacttgtc acaaatttta tatgcagata tttcagttgc   2460 

ctaatgaaca aaccaagaca ctgatgtttt ttgaaggttg tccacagcac ctaggctgta   2520 

caatcaagct aagaggaggc tctgattatg agctggctcg agttaaggag atcctaatat   2580 

ttatgatctg tgttgcttat cattctcaac tagaaatatc ctttctcatg gatgaatttg   2640 

ctatgcctcc cacattaatg caaaaccctt cattccattc cctgattgag ggacgagggc   2700 

atgagggggc tgtccaagag cagtacggtg gaggttccat cccctgggat cctgacatcc   2760 

ctcctgagtc tctgccctgt gatgatagca gtttgctgga atcgaggatt gtgtttgaga   2820 

agggtgagca ggaaaataaa aatcttccgc aggctgttgc ctctgtgaag catcaagaac   2880 

atagcacaac agcttgcccg gcgggtctcc cttgtgcttt ctttgcacct gtaccggaat   2940 

cattgttgcc actccctgtg gatgaccaac aagatgcttt aggcagcgag ctgccagaga   3000 

gtttgcagca aacagttgtg ctgcaggatc ccaaaagcca gataagagcc tttagagacc   3060 

ctctacagga tgacactgga ttatatgtta ctgaggaagt cacctcctct gaagataaac   3120 

gaaagactta ttctttggcc tttaagcagg aattaaaaga tgtgatcctc tgtatctccc   3180 

cagtaatcac attccgagaa ccctttcttt taactgaaaa ggggatgaga tgctctaccc   3240 

gagattattt tgcagagcag gtttactggt ctcctctcct caataaagaa ttcaaagaaa   3300 

tggagaacag gaggaagaaa cagctgctca gggatctctc tggacttcag ggcatgaatg   3360 

gaagtattca ggccaagtct attcaagtct taccctcaca tgagctagtg agcactagaa   3420 

ttgctgagca tctgggcgat agccagagct tgggtagaat gctggccgat tatcgagcca   3480 

gaggaggaag aattcagccc aaaaattcag acccttttgc tcattcaaag gatgcatcaa   3540 

gtacttcaag tggcaaatca ggaagcaaaa acgagggtga tgaagagaga gggcttattc   3600 

tgagtgatgc tgtgtggtca acaaaggtgg actgtctgaa tcccattaat caccagagac   3660 

tttgtgtgct cttcagcagc tcttctgccc agtccagcaa tgctcctagt gcctgtgtca   3720 

gtccttggat tgtaacaatg gaattttatg gaaagaatga tcttacatta ggaatatttt   3780 

tagagagata ctgtttcagg ccttcttatc agtgtccaag catgttctgt gataccccca   3840 

tggtacatca tattcggcgc tttgttcatg gccaaggctg tgtgcagata atcctgaagg   3900 

agttggattc tccagtacct ggatatcagc atacaattct tacatattcc tggtgtagaa   3960 

tctgcaaaca ggtaacacca gttgttgctc tttccaatga gtcctggtct atgtcatttg   4020 

caaaatacct tgaacttagg ttttatgggc accagtatac tcgcagagcc aacgctgagc   4080 

cctgtggtca ctccatccat catgattatc accagtattt ctcctataac cagatggtgg   4140 

cgtctttcag ttattctccc attcggcttc ttgaagtatg tgttccactc cccaaaatat   4200 

tcattaagcg tcaggcccca ttaaaagtgt cccttcttca ggatctgaag gacttctttc   4260 

aaaaagtttc acaggtatat gttgccattg atgaaagact tgcatctttg aaaactgata   4320 

catttagtaa aacaagagag gaaaaaatgg aagatatttt tgcacagaaa gagatggaag   4380 

aaggtgagtt caagaactgg attgagaaga tgcaagcaag gctcatgtct tcctctgtag   4440 

atacccctca gcaactgcag tcggtctttg agtcactcat tgccaagaaa caaagtctct   4500 

gtgaagtgct gcaagcttgg aataacaggt tgcaggacct tttccaacag gaaaagggta   4560 

gaaagagacc ttcagttcct ccaagtcctg gaagactgag acaaggggaa gaaagcaaga   4620 

taagtgcgat ggatgcatct ccacggaata tttctccagg acttcagaat ggagaaaaag   4680 

aggatcgctt cttaacaact ttgtccagcc agagctccac cagttctact catctccaat   4740 

tgcctacgcc acctgaagtc atgtctgaac agtcagtggg agggccccct gagctagata   4800 

cagccagcag ttccgaagat gtgtttgatg ggcatttgct gggatccaca gacagccaag   4860 

tgaaggaaaa gtcaaccatg aaagccatct ttgcaaattt gcttccagga aatagctata   4920 

atcctattcc atttcctttt gatccagata aacactactt aatgtatgaa catgaacgag   4980 

tgcccattgc agtctgcgag aaggaaccca gctccatcat tgcttttgct ctcagttgta   5040 

aagaataccg aaatgcctta gaggaattgt ctaaagcgac tcagtggaac agtgccgaag   5100 

aagggcttcc aacaaatagt acttcagata gcagaccaaa gagtagcagc cctatcagat   5160 

tacctgaaat gagtggagga cagacaaatc gtacaacaga aacagaacca caaccaacca   5220 

aaaaggcttc tggaatgctg tccttcttca gagggacagc agggaaaagc cccgatctct   5280 

cttcccagaa gagagagacc ttacgtggag cagatagtgc ttactaccag gttgggcaga   5340 

caggcaagga ggggaccgag aatcaaggcg ttgagcctca agatgaagta gatggaggag   5400 

atacgcaaaa gaagcaactc ataaatcctc atgtggaact tcaattttca gatgctaatg   5460 

ccaagtttta ctgtcggctc tactatgcgg gagagtttca taagatgcgt gaagtgattc   5520 

tggacagcag tgaggaagat ttcattcgtt ccctctccca ctcatcaccc tggcaggccc   5580 

ggggaggcaa atcaggagct gccttctatg caactgagga tgatagattt attttgaagc   5640 

aaatgcctcg tctggaagtc cagtccttcc tcgactttgc accacattac ttcaattata   5700 

ttacaaatgc tgttcaacaa aagaggccca cggcgttggc caaaattctt ggagtttaca   5760 

gaattggtta taagaactct cagaacaaca ctgagaagaa gttagatctc cttgtcatgg   5820 

aaaatctttt ctacgggaga aagatggcac aggtttttga tttgaagggc tctcttagga   5880 

atcggaatgt aaaaactgac actggaaaag agagttgtga tgtggtcctg ctagatgaaa   5940 

atctcctaaa gatggttcga gacaaccctc tatatattcg ttctcattcc aaagctgtgc   6000 

tgagaacctc gatccatagt gactcccatt tcctttctag ccacctcatt atagattatt   6060 

ctttgctggt tgggcgagat gatactagca atgagctagt agttggaatt atagattata   6120 

ttcgaacatt tacatgggac aaaaagcttg agatggttgt gaaatcaaca ggaattttag   6180 

gtggacaagg taaaatgcca acagtggtgt ctccggagtt gtacaggact aggttttgtg   6240 

aggcaatgga caagtatttc ctaatggtac cagaccactg gacaggcttg ggtctgaatt   6300 

gctgaaatca agacatattt gaaatggact gtgaggaaaa ggggaac                 6347 

 
           
             33  
             1876  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 5734965CB1  
             
           
            33 

tggggttcgg cgcggctacg tgcagaatcc gtctagctaa aatgtaattt cagattggac     60 

aagtactgtg gaggaactgc aatgtctggt ggagaacaga aaccagagag gtactatgtg    120 

ggtgtggacg ttggaacagg cagtgtccgt gcagctctgg tggaccagag tggggtcctg    180 

ttggcttttg cagaccagcc aattaagaat tgggagcccc agttcaacca ccatgagcag    240 

tcctccgagg acatctgggc tgcgtgctgt gttgtcacaa agaaagttgt acaagggatt    300 

gatttaaacc aaattcgagg acttgggttt gatgccacgt gttctctggt tgttttggat    360 

aagcagtttc acccattacc agtcaaccag gaaggggatt cccatcgaaa cgtcatcatg    420 

tggctggacc atcgagcagt cagtcaagtt aacaggatca atgagaccaa gcacagtgtc    480 

ctccagtacg tcgggggggt gatgtctgtg gaaatgcagg ccccgaaact tctgtggctg    540 

aaagagaact tgagagagat ttgctgggat aaggcgggac atttctttga tctcccggac    600 

ttcttatcgt ggaaggcaac aggtgtcaca gcacggtctc tctgctccct ggtgtgtaag    660 

tggacatatt cagcagagaa aggctgggac gacagtttct ggaaaatgat tggtttggaa    720 

gactttgttg cagataatta cagcaaaata ggaaaccaag tgctacctcc tggagcttct    780 

cttggaaatg ggctcacacc agaggcagca agagaccttg gccttctccc tgggattgcg    840 

gtcgcagctt cactcattga tgcccatgca ggaggactag gagtgattgg ggcagatgtg    900 

agagggcacg gcctcatctg tgaggggcag ccagtgacgt cacggctggc tgtcatctgt    960 

ggaacgtctt cttgtcacat ggggatcagc aaagacccga tttttgtacc aggcgtctgg   1020 

gggccttatt tctcagccat ggtacctggg ttctggctga atgaaggtgg tcagagcgtt   1080 

actggaaaat tgatagacca catggtacaa ggccatgctg cttttccaga actacaagta   1140 

aaggccacag ccagatgcca gagtatatat gcatatttga acagtcacct ggatctgatt   1200 

aagaaggctc agcctgtggg tttccttact gttgatttac atgtttggcc agatttccat   1260 

ggcaaccggt ctcccttagc agatctgaca ctaaagggca tggtcaccgg attgaaactg   1320 

tctcaggacc ttgatgatct tgccattctc tacctggcca cagttcaagc cattgctttg   1380 

gggactcgct tcattataga agccatggag gcagcagggc actcaatcag tactcttttc   1440 

ctatgtggag gcctcagcaa gaatcccctt tttgtgcaaa tgcatgcgga cattactggc   1500 

atgcctgtgg tcctgtcgca agaggtggag tccgttcttg tgggtgctgc tgttctgggt   1560 

gcctgtgcct caggggattt cgcttctgta caggaagcaa tggcaaaaat gagcaaagtt   1620 

gggaaagttg tgttcccgag actacaggat aaaaaatact atgataagaa ataccaagta   1680 

ttcctgaagc tggttgaaca ccagaaggag tatttggcga tcatgaatga tgactgaaca   1740 

gggcttgcag gtgctgatgc cagaagcttc tgtgccattg cattaaagac ttctgtcatt   1800 

tgatccatgt tcaagaccct tgaggtattg tttcatcatt tctgtattgt ctttcaataa   1860 

agaatacaaa catgtg                                                   1876 

 
           
             34  
             1487  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7473788CB1  
             
           
            34 

atgaggagtg gcgccgaacg caggggcagc agcgccgcgg cgtccccggg ctcgccgccc     60 

cccggccgcg cgcgccccgc cggctccgac gcgccctcgg ccctgccgcc gcccgctgct    120 

ggccagcccc gggcccggga ctcgggcgat gtccgctcgc agccgcgccc cctgtttcag    180 

tggagcaagt ggaagaagag gatgggctcg tccatgtcgg cggccaccgc gcggaggccg    240 

gtgtttgacg acaaggagga cgtgaacttc gaccacttcc agatccttcg ggccattggg    300 

aagggcagct ttggcaaggt gtgcattgtg cagaagcggg acacggagaa gatgtacgcc    360 

atgaagtaca tgaacaagca gcagtgcatc gagcgcgacg aggtccgcaa cgtcttccgg    420 

gagctggaga tcctgcagga gatcgagcac gtcttcctgg tgaacctctg gtactccttc    480 

caggacgagg aggacatgtt catggtcgtg gacctgctac tgggcgggga cctgcgctac    540 

cacctgcagc agaacgtgca gttctccgag gacacggtga ggctgtacat ctgcgagatg    600 

gcactggctc tggactacct gcgcggccag cacatcatcc acagagatgt caagcctgac    660 

aacattctcc tggatgagag aggacatgca cacctgaccg acttcaacat tgccaccatc    720 

atcaaggacg gggagcgggc gacggcatta gcaggcacca agccgtacat ggctccggag    780 

atcttccact cttttgtcaa cggcgggacc ggctactcct tcgaggtgga ctggtggtcg    840 

gtgggggtga tggcctatga gctgctgcga ggatggaggc cctatgacat ccactccagc    900 

aacgccgtgg agtccctggt gcagctgttc agcaccgtga gcgtccagta tgtccccacg    960 

tggtccaagg agatggtggc cttgctgcgg aagctcctca ctgtgaaccc cgagcaccgg   1020 

ctctccagcc tccaggacgt gcaggcagcc ccggcgctgg ccggcgtgct gtgggaccac   1080 

ctgagcgaga agagggtgga gccgggcttc gtgcccaaca aaggccgtct gcactgcgac   1140 

cccacctttg agctggagga gatgatcctg gagtccaggc ccctgcacaa gaagaagaag   1200 

cgcctggcca agaacaagtc ccgggacaac agcagggaca gctcccagtc cgagaatgac   1260 

tatcttcaag actgcctcga tgccatccag caagacttcg tgatttttaa cagagaaaag   1320 

ctgaagagga gccaggacct cccgagggag cctctccccg ccctgagtcc agggatgctg   1380 

cggagcctgt ggaggacgag gcggacgctc cgcctgccca tgtgcggccc catttgcccc   1440 

tcggccggga gcggctaggc cgggacgccc gtggtcctca ccccttg                 1487 

 
           
             35  
             1884  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 3107989CB1  
             
           
            35 

gaggtgacca attttctctc caaaagagaa aggaagttga ttaaaaaaag aatccatgct     60 

ccaaagcggc agccaaatcc atctatggcc cccaatgcat cacccagaaa ggggttccag    120 

actctcctgc aaaaggccaa ctctacttcc cggctcccac ttcccctcct tcgccacagg    180 

agggtggcga aggatttata acccacctct ttctttcagt tgccatggag acaagcccca    240 

gtcctttcat tccttctggt acctctctct ccaacgcagg cggaaaggag gcggcttagc    300 

ccaaacatgc tgggggaggg gctggcggcc tcgacggcag ctgcggaact aggccgaggg    360 

acaaaggcta agtttttcca tggtttggac tggatatcgg tggaactctg gtcaagctgg    420 

tatattttga acccaaagac atcactgctg aagaagaaga ggaagaagtg gaaagtctta    480 

aaagcattcg gaagtacctg acctccaatg tggcttatgg gtctacaggc attcgggacg    540 

tgcacctcga gctgaaggac ctgactctgt gtggacgcaa aggcaatctg cactttatac    600 

gctttcccac tcatgacatg cctgctttta ttcaaatggg cagagataaa aacttctcga    660 

gtctccacac tgtcttttgt gccactggag gtggagcgta caaatttgag caggattttc    720 

tcacaatagg tgatcttcag ctttgcaaac tggatgaact agattgcttg atcaaaggaa    780 

ttttatacat tgactcagtc ggattcaatg gacggtcaca gtgctattac tttgaaaacc    840 

ctgctgattc tgaaaagtgt cagaagttac catttgattt gaaaaatccg tatcctctgc    900 

ttctggtgaa cattggctca ggggttagca tcttagcagt atattccaaa gataattaca    960 

aacgggtcac aggtactagt cttggaggag gaactttttt tggtctctgc tgtcttctta   1020 

ctggctgtac cacttttgaa gaagctcttg aaatggcatc tcgtggagat agcaccaaag   1080 

tggataaact agtacgagat atttatggag gggactatga gaggtttgga ctgccaggct   1140 

gggctgtggc ttcaagcttt ggaaacatga tgagcaagga aaagcgagat tccatcagca   1200 

aggaagacct cgcccgggcc acattggtca ccatcaccaa caacattggc tccattgctc   1260 

ggatgtgtgc gttgaatgag aacatagaca gagttgtgtt tgttggaaat tttctcagaa   1320 

tcaatatggt ctccatgaag ctgctggcat atgccatgga tttttggtcc aaaggacaac   1380 

tgaaagctct gtttttggaa catgagggtt attttggagc cgttggggca ctgttggaac   1440 

tgttcaaaat gactgatgac aagtagagac gagcagtgga ggaaacagcc tcccaaaagg   1500 

acagagaact aaaaaattgc tgctggagaa ggtgaaagtc gctttgggac ggaagccaag   1560 

ccattatggc agatgaacct gctggatttg taaataattt aaaatccttc cagatgatct   1620 

tttactctta ggttttgagc taatgattca aaacggggga atataaaagg ttttttttct   1680 

gtatactgta tttttttaaa aaaatggtgc agcgtggcca aacctaccaa ttgtatgcat   1740 

taactttgaa aagttgtttg atgtttaaga aggacctgat atgtaagcgc tggtcatttt   1800 

tcttctgggg tttactgatc agtgtggtga ttttaacttc atttagtaat tactctagga   1860 

gattttacct tgacttatat tttc                                          1884 

 
           
             36  
             1070  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7482887CB1  
             
           
            36 

gcaaatcaca cagcatggca gctcccagtc ctcctgcctc ttctgcattc cagacctgct     60 

ctttaaaaac ctgggcattc cctccacaaa ttgaagagtg gaattttttt tcacctgctc    120 

ttcctcttgc tggcacagat cataaagtct tgctctcttt ctatcacatc tcattattat    180 

tttggcttct ttctacaagc aaggagcagc aggccctttt acattaccat tagtgaaggc    240 

acttgagtta aatccgcaca acgaatctta ctcttgcctg taatcccagc actttggaaa    300 

gccaaggcgg gtggatcacc tgaggtcagg agttcgagac cagcctggcc aatgtggtaa    360 

aacctatctc tactaaaaat acaaaaaatt ggccaggtgt ggtggtgggg gcctgtaatc    420 

tcagctactt gggaggctaa ggcaggagaa ttgcttgaat ctgggagaca gaggttgcgg    480 

tgggccaaga tagcgccact gcactccagc cttagcaaca agagcacaac tccatctcaa    540 

aataataata ataatttctt ggctccaagt ctcagctccc gcaccacctg acactgtcag    600 

atcctcaggc catggccaac actgagagca tcattatcaa tccgagtgct gttcagcaca    660 

gcctggtggg tgaaatcatc aaatactctg agcagaaggg attctacctg gtgaccatga    720 

agttccttcg ggcctctgag aaacccctga agccgcacta cactaacctg aaagaccacc    780 

cattcttccc ggaccttgtg aagtacatga actcagggca ggttgtggcc atggtcctgg    840 

aggggctgaa tgtggcaaag acagggctaa ggatgcttgg ggagaccaat tcattgggct    900 

ctatgctaga gactattatt cgcagggact tctgcgctaa aataggcggg aacgtcattg    960 

gtggcagtga ttcattacaa agtgctgaaa aagaaatcag cctatggttt aagcccaaag   1020 

aaccagttga ctacagatct tgtgcttatg actgggtcta tgcatgatag              1070 

 
           
             37  
             2890  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 2963414CB1  
             
           
            37 

gtgacccttc cctccccagg ccacggcagc ccggccctcc cgggcagacc tcccgcacca     60 

gggctctggt gaacagcaaa tgctccacgc tgggacgggc cattgcctga tgcctgtaca    120 

tggtgggcac tgagagacaa gattcctggg ccctgccttc catacactcc ccacgatctc    180 

ggaggaagct ctgaggaccc cgctgagaac ccacagacag gaggacaact gcgctatgac    240 

agcaataaag gccaagaagg agaaagttga ggaccgctga cagccccgtg tgctgttggg    300 

agctgccctt tctacttcaa accttcctct agcagactgt gcagggaccc cccaccacca    360 

ccatctgccg ccatggttgt gcaaaacagc gcagacgccg gggacatgag ggcaggcgtg    420 

cagctggagc ccttcctgca ccaggtcggg gggcacatga gcgtgatgaa gtatgacgag    480 

catacggtgt gcaagcccct cgtctcccgg gagcagaggt tctatgaatc cctgccgctg    540 

gccatgaagc ggttcacccc acagtacaaa ggtaccgtca cagtgcacct ctggaaagac    600 

agcacaggcc atctcagctt ggttgccaac ccagtgaagg agagccagga gcccttcaag    660 

gtctccacag agtcggcggc ggtggccata tggcagacgc tccagcagac caccggcagc    720 

aatggcagcg actgcaccct tgcccagtgg ccgcatgccc agctggcacg ctcacccaag    780 

gagagcccgg ccaaggctct tctgaggtcc gagccccacc tcaacactcc agccttctcg    840 

ctggtggaag acaccaacgg aaaccaggtt gagaggaaga gcttcaaccc gtggggcctg    900 

caatgccacc aggcccacct gacccgcctg tgctccgagt acccagagaa caagcggcat    960 

cggttcttgt tgctggaaaa tgtagtgtca cagtacacgc atccctgtgt cctggatctg   1020 

aagatgggga cccggcagca cggcgatgat gcatcggagg agaagaaggc ccgccacatg   1080 

aggaagtgtg cgcagagcac ctcagcctgc ctgggtgtgc gcatctgcgg catgcaggtt   1140 

tatcaaacag ataagaagta ctttctctgc aaagacaagt actatggaag aaaactctca   1200 

gtggaggggt tcagacaagc cctctatcag ttcctacata atggaagcca cctccggagg   1260 

gagctcctgg agcccatcct gcaccagctc cgggccctcc tctccatcat taggagccag   1320 

agttcatacc gcttctattc cagctctctc cttgtcatct atgatgggca ggaaccacca   1380 

gaaagagccc caggcagccc gcatcctcac gaggctcccc aggcagccca cggtagctct   1440 

cccggtggtc tcaccaaggt tgacatccgc atgattgact ttgctcatac cacatacaag   1500 

ggctactgga atgagcacac cacctacgat ggaccagacc ctggctatat ttttggcctg   1560 

gaaaacctca tcaggatcct gcaggatatc caagagggag aatgaaactt cctgggctta   1620 

tctggattct tctgggctat agatctcaaa tagagacctg ttggttgcta gggtagtcca   1680 

gacacccctt agatgtcttc ataatagtcc tatctacctt caaaaaccat ctctatatat   1740 

ggcagactat attaacagct gctgaacaaa tcagctctgg aggtgattcc acatcccctg   1800 

gcattatgct ctaatgctgc tcatcggaga acagacagcc aggataaagt ggcaccttct   1860 

ggagtacact ggagggggca gcccaagtta gaggccagca ttgctgacat tctggaatat   1920 

ttgcatctaa aaatgtttac tcgttgccat gctgcagtcc gcacaagctg tgaggcagaa   1980 

aacttgactt gaagcagcct tgaagagtga gttcatgagc tcatggtttt tctccttgta   2040 

tggactgctc gctccaaggg caggcagagc tcatgaatgc ctcttatctt cctaagcgga   2100 

gttttaggtg acacaggatg aagcagaaga gatctaccca tctcacctgc tctgcaccca   2160 

gcttctaagt ggacaaagcc aagcccaggc atgagctctg gcaaagcaag accccagatt   2220 

ctccattttt gcctgtggaa aggagggtcc ctttacaggc ttttttttcc tttttttccc   2280 

ccaaaatctc ttaaaatgag gaatctctta gcagactttg gagttcccca ttctgccaca   2340 

ttctgaccat gagacgcggc ttgcagtggg ggtgaacgca cataaaaagg gaccactgac   2400 

gtcctgctct actctctgct ttctatttat ttattttggg ggtgggttgg ggagtcagaa   2460 

gaacctggag gacggaggaa accaggggca atgtttacaa gactggtgga caagtgtaaa   2520 

tatggaataa gaacaaacag ttctaattaa ttccttcttc tgcagtacgg aaacctatta   2580 

caatgccctt gagtcaagca ctgagatacg ttacccaatt agggaaataa atttgttaat   2640 

aaaattgctg aggtcaccag tgattattgg tgtgccttat taccctttcc atttgtttat   2700 

tctgatcaca ctgtgtggta gttccaattt atgagcgact agcatatacc acaagaacag   2760 

ttcactgatt tcctacaatc cttcagggaa ctcgggtgga aatggtggct aataaaatat   2820 

ttgcatgtat ctgcaaggga ggcaccagac ctgagaagtg gtccttttat ttgaatctca   2880 

tacaatgtac                                                          2890 

 
           
             38  
             5198  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7477139CB1  
             
           
            38 

cgacacggag cacccttcta gcttcttcgt ctccaggact gacgctcagg ctcctctctc     60 

gccttagccc aacttgcttt cccgcctcgc aaactccggt ttccctccac tcccaactct    120 

tttcactaca cgtttcccct cctctatctc ccacgccacg aaccccgatc cccagactcc    180 

tctctcccgc cctcctcctt cctctctcct cccttcaact cttcatccgc ttccacctca    240 

gactctgcgc gcacccaatt cagtcgcccg ctcccgttcg gctcctcgaa gccatggcgg    300 

gacctggggg ctggagggac agggaggtca cggatctggg ccacctgccg gatccaactg    360 

gaatattctc actagataaa accattggcc ttggtactta tggcagaatc tatttgggac    420 

ttcatgagaa gactggtgca tttacagctg ttaaagtgat gaacgctcgt aagacccctt    480 

tacctgaaat aggaaggcga gtgagagtga ataaatatca aaaatctgtt gggtggagat    540 

acagtgatga ggaagaggat ctcaggactg aactcaacct tctgaggaag tactctttcc    600 

acaaaaacat tgtgtccttc tatggagcat ttttcaagct gagtccccct ggtcagcggc    660 

accaactttg gatggtgatg gagttatgtg cagcaggttc ggtcactgat gtagtgagaa    720 

tgaccagtaa tcagagttta aaagaagatt ggattgctta tatctgccga gaaatccttc    780 

agggcttagc tcaccttcac gcacaccgag taattcaccg ggacatcaaa ggtcagaatg    840 

tgctgctgac tcataatgct gaagtaaaac tggttgattt tggagtgagt gcccaggtga    900 

gcagaactaa tggaagaagg aatagtttca ttgggacacc atactggatg gcacctgagg    960 

tgattgactg tgatgaggac ccaagacgct cctatgatta cagaagtgat gtgtggtctg   1020 

tgggaattac tgccattgaa atggctgaag gagcccctcc tctgtgtaac cttcaaccct   1080 

tggaagctct cttcgttatt ttgcgggaat ctgctcccac agtcaaatcc agcggatggt   1140 

cccgtaagtt ccacaatttc atggaaaagt gtacgataaa aaatttcctg tttcgtccta   1200 

cttctgcaaa catgcttcaa cacccatttg ttcgggatat aaaaaatgaa cgacatgttg   1260 

ttgagtcatt aacaaggcat cttactggaa tcattaaaaa aagacagaaa aaaggaatac   1320 

ctttgatctt tgaaagagaa gaagctatta aggaacagta caccgtgaga agattcagag   1380 

gaccctcttg cactcacgag cttctgagat tgccaaccag cagcagatgc agaccactta   1440 

gagtcctgca tggggaaccc tctcagccaa ggtggctacc tgatcgagaa gagccacagg   1500 

tccaggcact tcagcagcta cagggagcag ccagggtatt catgccactg caggctctgg   1560 

acagtgcacc taagcctcta aaggggcagg ctcaggcacc tcaacgacta caaggggcag   1620 

ctcgggtgtt catgccacta caggctcagg tgaaggctaa agcctctaaa cctctacaaa   1680 

tgcagattaa ggcacctcca cgactacgga gggcagccag ggtgctcatg ccactacagg   1740 

cacaggttag ggcacctagg cttctgcagg tacagtccca ggtatccaaa aagcagcagg   1800 

cccagaccca gacatcagaa ccacaagatt tggaccaggt accagaggaa tttcagggtc   1860 

aagatcaggt acccgaacaa caaaggcagg gccaggcccc tgaacaacag cagaggcaca   1920 

accaggtgcc tgaacaagag ctggagcaga accaggcacc tgaacagcca gaggtacagg   1980 

aacaggctgc cgagcctgca caggcagaga ctgaggcaga ggaacctgag tcattacgag   2040 

taaatgccca ggtatttctg cccctgctat cacaagatca ccatgtgctg ttgccactac   2100 

atttggatac tcaggtgctc attccagtag aggggcaaac tgaaggatca cctcaggcac   2160 

aggcttggac actagaaccc ccacaggcaa ttggctcagt tcaagcactg atagagggac   2220 

tatcaagaga cttgcttcgg gcaccaaact caaataactc aaagccactt ggtccgttgc   2280 

aaaccctgat ggaaaatctg tcatcaaata ggttttactc acaaccagaa caggcacggg   2340 

agaaaaaatc aaaagtttct actctgaggc aagcactggc aaaaagacta tcaccaaaga   2400 

ggttcagggc aaagtcatca tggagacctg aaaagcttga actctcggat ttagaagccc   2460 

gcaggcaaag gcgccaacgc agatgggaag atatctttaa tcagcatgag gaagaattga   2520 

gacaagttga taaaaccagt tggcgtcagt ggggtccttc agaccagttg attgacaata   2580 

gtttcactgg tatgcaagac ctgaagaaat atctcaaagg aaaaacaaca tttcataatg   2640 

ttcaagttgt tatctacaga gcagttaagg ggaatgatga tgttgcaaca aggtctaccg   2700 

ttcctcagcg gtctcttttg gaacaagctc agaagcccat tgacatcaga caaaggagtt   2760 

cgcaaaatcg tcaaaattgg ctggcagcat caggtgattc aaagcacaaa attttagcag   2820 

gcaaaacaca gagctactgt ttaacaattt atatttcaga agtcaagaaa gaagaatttc   2880 

aagaaggaat gaatcaaaag tgtcagggag cccaagtagg attaggacct gaaggccatt   2940 

gtatttggca attgggtgaa tcttcttctg aggaagaaag tcctgtgact ggaaggaggt   3000 

ctcagtcatc accaccttat tctactattg atcagaagtt gctggttgac atccatgttc   3060 

cagatggatt taaagtagga aaaatatcac cccctgtata cttgacaaac gaatgggtag   3120 

gctataatgc actctctgaa atcttccgga atgattggtt aactccggca cctgtcattc   3180 

agccacctga agaggatggt gattatgttg aactctatga tgccagtgct gatactgatg   3240 

gtgatgatga tgatgagtct aatgatactt ttgaagatac ctatgatcat gccaatggca   3300 

atgatgactt ggataaccag gttgatcagg ctaatgatgt ttgtaaagac catgatgatg   3360 

acaacaataa gtttgttgat gatgtaaata ataattatta tgaggcgcct agttgtccaa   3420 

gcttgttgtc agggcaagct atggcagaga tggaagctgc aagcaagatg gttatgatgg   3480 

aagtcgtgga aaagaggaag cctacagagg ctatggaagc catacagcca atagaagcca   3540 

tggaggaagt gcagccagtg agggacaatg cagccattgg agatcaggaa gaacatgcag   3600 

ccaatatagg cagtgaaaga agaggcagtg agggtgatgg aggtaaggga gtcgttcgaa   3660 

ccagtgaaga gagtggagcc cttggactca atggagaaga aaattgctca gagacagatg   3720 

gtccaggatt gaagagacct gcgtctcagg actttgaata tctacaggag gagccaggtg   3780 

gtggaaatga ggcctcaaat gccattgact caggtgctgc accgtcagca cctgatcatg   3840 

agagtgacaa taaggacata tcagaatcat caacacaatc agatttttct gccaatcact   3900 

catctccttc caaaggttct gggatgtctg ctgatgctaa ctttgccagt gccatcttat   3960 

acgctggatt cgtagaagta cctgaggaat cacctaagca accctctgaa gtcaatgtta   4020 

acccactcta tgtctctcct gcatgtaaaa aaccactaat ccacatgtat gaaaaggagt   4080 

tcacttctga gatctgctgt ggttctttgt ggggagtcaa tttgctgttg ggaacccgat   4140 

ctaatctata tctgatggac agaagtggaa aggctgacat tactaaactt ataaggcgaa   4200 

gaccattccg ccagattcaa gtcttagagc cactcaattt gctgattacc atctcaggtc   4260 

ataagaacag acttcgggtg tatcatctga cctggttgag gaacaagatt ttgaataatg   4320 

atccagaaag taaaagaagg caagaagaaa tgctgaagac agaggaagcc tgcaaagcta   4380 

ttgataagtt aacaggctgt gaacacttca gtgtcctcca acatgaagaa acaacatata   4440 

ttgcaattgc tttgaaatca tcaattcacc tttatgcatg ggcaccaaag tcctttgatg   4500 

aaagcactgc tattaaagta tttccaacac ttgatcataa gccagtgaca gttgacctgg   4560 

ctattggttc tgaaaaaaga ctaaagattt tcttcagctc agcagatgga tatcacctca   4620 

tcgatgcaga atctgaggtt atgtctgatg tgaccctgcc aaagaataat atcatcattt   4680 

tacctgattg cttgggaatt ggcatgatgc tcaccttcaa tgctgaagcc ctctctgtgg   4740 

aagcaaatga acaactcttc aagaagatcc ttgaaatgtg gaaagacata ccatcttcta   4800 

tagcttttga atgtacacag cgaaccacag gatggggcca aaaggccatt gaagtgcgct   4860 

ctttgcaatc cagggttctg gaaagtgagc tgaagcgcag gtcaattaag aagctgagat   4920 

tcctgtgcac ccggggtgac aagctgttct ttacctctac cctgcgcaat caccacagcc   4980 

gggtttactt catgacactt ggaaaacttg aagagctcca aagcaattat gatgtctaaa   5040 

agtttccagt gatttattac cacattataa acatcatgta taggcagtct gcatcttcag   5100 

atttcagaga ttaaatgagt attcagtttt atttttagta aagattaaat ccaaaacttt   5160 

acttttaatg tagcacagaa tagttttaat gagaaatg                           5198 

 
           
             39  
             3969  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 55009053CB1  
             
           
            39 

cttttttcct ttcagtgtgc ttcaaatgtc acgacacagg ttagctcagt cgacttgggg     60 

ctgctgagct ctggtccctg ccagcctcac cgctcggacc cccccgatcc tccggactcc    120 

gctggtcctg gccacgcgag gagcccacgc tagctccaaa gaatcccccg agggcacgtg    180 

gaccgaggga gcccctgtga aggctgcgga agactccgcg cgtcccgagc tcccggactc    240 

tgcagtgggc ccggggtcca gggagccgct aagggtccct gaagctgtgg ccctagagcg    300 

gcggcgggag caggaagaaa aggaggacat ggagacccag gctgtggcaa cgtcccccga    360 

tggccgatac ctcaagtttg acatcgagat tggacgtggc tccttcaaga cggtgtatcg    420 

agggctagac accgacacca cagtggaggt ggcctggtgt gagctgcaga ctcggaaact    480 

gtctagagct gagcggcagc gcttctcaga ggaggtggag atgctcaagg ggctgcagca    540 

ccccaacatc gtccgcttct atgattcgtg gaagtcggtg ctgaggggcc aggtttgcat    600 

cgtgctggtc accgaactca tgacctcggg cacgctcaag acgtacctga ggcggttccg    660 

ggagatgaag ccgcgggtcc ttcagcgctg gagccgccaa atcctgcggg gacttcattt    720 

cctacactcc cgggttcctc ccatcctgca ccgggatctc aagtgcgaca atgtctttat    780 

cacgggacct tctggctctg tcaaaatcgg ggacctgggc ctggccacgc tcaagcgcgc    840 

ctcctttgcc aagagtgtca tcgggacccc ggaattcatg gcccccgaga tgtacgagga    900 

aaagtacgat gaggccgtgg acgtgtacgc gttcggcatg tgcatgctgg agatggccac    960 

ctctgagtac ccgtactccg agtgccagaa tgccgcgcaa atctaccgca aggtcacttc   1020 

gggcagaaag ccgaacagct tccacaaggt gaagataccc gaggtgaagg agatcattga   1080 

aggctgcatc cgcacggata agaacgagag gttcaccatc caggacctcc tggcccacgc   1140 

cttcttccgc gaggagcgcg gtgtgcacgt ggaactagcg gaggaggacg acggcgagaa   1200 

gccgggcctc aagctctggc tgcgcatgga ggacgcgcgg cgcggggggc gcccacggga   1260 

caaccaggcc atcgagttcc tgttccagct gggccgggac gcggccgagg aggtggcaca   1320 

ggagatggtg gctctgggct tggtctgtga agccgattac cagccagtgg cccgtgcagt   1380 

acgtgaacgg gttgctgcca tccagcgaaa gcgtgagaag ctgcgtaaag caagggaatt   1440 

ggaggcactc ccaccagagc caggacctcc accagcaact gtgcccatgg cccccggtcc   1500 

ccccagtgtc ttcccccctg agcctgagga gccagaggca gaccagcacc agcccttcct   1560 

tttccgccac gccagctact catctaccac ttcggattgc gagactgatg gctacctcag   1620 

ctcctccggc ttcctggatg cctcagaccc tgcccttcag ccccctgggg gggtgccatc   1680 

cagcctggct gagtcccatc tctgcctgcc ctcggctttt gccctatcca ttccacgttc   1740 

tggccctgga agtgactttt cccccgggga cagctatgcc tcagatgcag cttcaggcct   1800 

tagcgatgtg ggagaaggga tgggacaaat gaggagaccc ccagggagga atctccggcg   1860 

cagaccccga tcccggctgc gggtcactag tgtctcagac cagaatgaca gagtggttga   1920 

gtgccagcta cagacccata acagcaagat ggtgaccttc cgatttgatc tggatgggga   1980 

cagcccggaa gagattgcag ctgccatggt atataacgag ttcattctgc cttcggagcg   2040 

agatggattt ctcagacgga ttcgggagat tatccagcga gtggagaccc tgttgaagag   2100 

agacactggc cccatggagg ctgctgaaga caccctaagc ccccaggagg agccagcacc   2160 

attacctgcc ctgcccgtcc ccctcccaga cccatccaat gaagagctcc agagcagcac   2220 

ctccctggag cacaggagct ggacagcctt ctccacctcc tcatcttctc ctggaactcc   2280 

tttgtctcct ggaaacccat tttcccctgg aacccccatt tccccaggtc ccatcttccc   2340 

catcacttct cccccatgtc atcccagccc ctccccattc tcccccattt cttcccaggt   2400 

ctcctcaaat ccctctccac accccaccag ctctccactt ccattctcct ccagcacacc   2460 

cgagtttccg gtcccactct ctcagtgtcc ctggagttct ctccccacga cttctccacc   2520 

tacgttctct cccacttgtt ctcaggtcac tcttagttcc cctttctttc ctccgtgccc   2580 

ctccacttct tccttcccct ccaccacagc agcccctctc ctttctctgg ctagtgcctt   2640 

ctcactggct gtgatgactg tggcccagtc cctgctgtcc ccctcacctg ggctcctttc   2700 

ccagtctcct ccagcccctc ctagtcccct ccctagcctg ccccttcccc ctcccgttgc   2760 

tcctggtggc caggaaagcc cttcacccca cacagctgag gtggagagtg aggcctcacc   2820 

acctcctgct cggcccctcc caggggaagc caggctggcg cccatctctg aagagggaaa   2880 

gccgcagctt gttgggcgtt tccaagtgac ttcatccaag gaaccggctg agcctcttcc   2940 

cttgcagcca acatccccca ctctctctgg ttctccaaaa ccttcaaccc ctcagctcac   3000 

ttcagagagc tcagatacag aggacagtgc tggaggcggg ccagagacca gggaagctct   3060 

ggctgagagc gaccgtgcag ctgagggtct gggggctgga gttgaggagg aaggagatga   3120 

tgggaaggaa ccccaagttg ggggcagccc ccaacccctg agccatccca gcccagtgtg   3180 

gatgaactac tcctacagca gcctgtgttt gagcagcgag gagtcagaaa gcagtgggga   3240 

agatgaggag ttctgggctg agctgcagag tcttcggcag aagcacttgt cagaggtgga   3300 

aacactacag acactacaga aaaaagaaat tgaagatttg tacagccggc tggggaagca   3360 

gcccccaccg ggtattgtgg ccccagctgc tatgctgtcc agccgccagc gccgcctctc   3420 

caagggcagc ttccccacct cccgccgcaa cagcctacag cgctctgagc ccccaggccc   3480 

tggcatcatg cgaaggaact ctctgagtgg cagcagcacc ggctcccagg agcagcgggc   3540 

aagcaagggg gtgacattcg ccggggatgt tggcaggatg tgaattcaga acagaagcca   3600 

tgtatctccc ccacaccagg gcccaccatg gagcttgtgt tctcagaatc tgatgctttc   3660 

tgatcaacaa aactgagcaa ggaagatccc aacactgaag gggtagaagg ccaggggggc   3720 

atggagagtg cagctccatt atagtgaaga gccaaacata tgtgaactgt ttgctgtgtg   3780 

gaggtgttag ttctgctgcc taccatcttc atctctagca cctcccctgc caagagtcaa   3840 

ccactaagca atcccaccca agcctggatg cttctagagg ggcccactcc cagctgggag   3900 

agtgtagggg atatgctcac accacattag cagcaaccaa taaaaatgct ggaaacaaga   3960 

aaaaaaaaa                                                           3969 

 
           
             40  
             1803  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7474648CB1  
             
           
            40 

atgggtgaaa gtggaaacca tcattttcag caaactaaca caggaacaga aaaccaaaca     60 

gcacatgttc tcactcataa gtgggagttg gacaatgaaa acatatgggc acagggaggg    120 

gaacatcaca aactgggacc tgtcatgggt tggaaggcta ggagtgggaa aacattagga    180 

gaaataccta acgtaggcac actcacactc ctcactggct atgggggatg ccagctgcca    240 

tgctgcaagg acactcaggc agcctatgga gaaacccacg tggtgcggag tggaggcctt    300 

ctgccaacag ccagctggga actgaggcct gctgacagtc acacggtgac cagcgatgat    360 

ccaggcgtct cggtcgttag cgggtatcct gggggctgtc tccctgacca cgacccccca    420 

gtggggtttc tttccgaggg tcccgcccct cgcagctgct ctttgataaa gggcggagga    480 

acggggctgg ctgcttcccg agtccccagg tcccgcgagc ggcgggcgtg ttgcgggtat    540 

ggggtgcggc gccagcagga aggtggtccc ggggccacca gcgctggctt gggccaagca    600 

cgaaggtcaa aaccaagccg gcgtcggagg cgcggggcct gggcccgagg cggcggccca    660 

ggcggcgcag aggatacagg tggctcgctt ccgagccaag ttcgaccccc gggtccttgc    720 

cagtgcccag tacaatttct ctttgacatc tctgaacagg gagttcagag gatgggaaaa    780 

aagagagcag gagcagcagc aaacaaggga aggaattcct atcttcggag atatgacatc    840 

aaagctctta ttgggacagg cagtttcagc agggttgtca gggtagagca gaagaccacc    900 

aagaaacctt ttgcaataaa agtgatggaa accagagaga gggaaggtag agaagcgtgc    960 

gtgtctgagc tgagcgtcct gcggcgggtt agccatcgtt acattgtcca gctcatggag   1020 

atctttgaga ctgaggatca agtttacatg gtaatggagc tggctaccgg aggggagctc   1080 

tttgatcgac tcattgctca gggatccttt acagagcggg atgccgtcag gatcctccag   1140 

atggttgctg atgggattag gtatttgcat gcgctgcaga taactcatag gaatctaaag   1200 

cctgaaaacc tcttatacta tcatccaggt gaagagtcga aaattttaat tacagatttt   1260 

ggtttggcat actccgggaa aaaaagtggt gactggacaa tgaagacact ctgtgggacc   1320 

ccagagtaca tagctcctga ggttttgcta aggaagcctt ataccagtgc agtggacatg   1380 

tgggctcttg gtgtgatcac atatgcttta cttagcggat tcctgccttt tgatgatgaa   1440 

agccagacaa ggctttacag gaagattctg aaaggcaaat ataattatac aggagagcct   1500 

tggccaagca tttcccactt ggcgaaggac tttatagaca aactactgat tttggaggct   1560 

ggtcatcgca tgtcagctgg ccaggccctg gaccatccct gggtgatcac catggctgca   1620 

gggtcttcca tgaagaatct ccagagggcc atatcccgaa acctcatgca gagggcctct   1680 

ccccactctc agagtcctgg atctgcacag tcttctaagt cacattattc tcacaaatcc   1740 

aggcatatgt ggagcaagag aaacttaagg atagtagaat cgccactgtc tgcgcttttg   1800 

taa                                                                 1803 

 
           
             41  
             3472  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7483053CB1  
             
           
            41 

atggcgaagg cgacgtccgg tgccgcgggg ctgcgtctgc tgttgctgct gctgctgccg     60 

ctgctaggca aagtggcatt gggcctctac ttctcgaggg atgcttactg ggagaagctg    120 

tatgtggacc aggcagccgg cacgcccttg ctgtacgtcc atgccctgcg ggacgcccct    180 

gaggaggtgc ccagcttccg cctgggccag catctctacg gcacgtaccg aacacggctg    240 

catgagaaca actggatctg catccaggag gacaccggcc tcctctacct taaccggagc    300 

ctggaccata gctcctggga gaagctcagt gtccgcaacc gcggctttcc cctgctcacc    360 

gtctacctca aggtcttcct gtcacccaca tcccttcgtg agggcgagtg ccagtggcca    420 

ggctgtgccc gcgtatactt ctccttcttc aacacctcct ttccagcctg cagctccctc    480 

aagccccggg agctctgctt cccagagaca aggccctcct tccgcattcg ggagaaccga    540 

cccccaggca ccttccacca gttccgcctg ctgcctgtgc agttcttgtg ccccaacatc    600 

agcgtggcct acaggctcct ggagggtgag ggtctgccct tccgctgcgc cccggacagc    660 

ctggaggtga gcacgcgctg ggccctggac cgcgagcagc gggagaagta cgagctggtg    720 

gccgtgtgca ccgtgcacgc cggcgcgcgc gaggaggtgg tgatggtgcc cttcccggtg    780 

accgtgtacg acgaggacga ctcggcgccc accttccccg cgggcgtcga caccgccagc    840 

gccgtggtgg agttcaagcg gaaggaggac accgtggtgg ccacgctgcg tgtcttcgat    900 

gcagacgtgg tacctgcatc aggggagctg gtgaggcggt acacaagcac gctgctcccc    960 

ggggacacct gggcccagca gaccttccgg gtggaacact ggcccaacga gacctcggtc   1020 

caggccaacg gcagcttcgt gcgggcgacc gtacatgact ataggctggt tctcaaccgg   1080 

aacctctcca tctcggagaa ccgcaccatg cagctggcgg tgctggtcaa tgactcagac   1140 

ttccagggcc caggagcggg cgtcctcttg ctccacttca acgtgtcggt gctgccggtc   1200 

agcctgcacc tgcccagtac ctactccctc tccgtgagca ggagggctcg ccgatttgcc   1260 

cagatcggga aagtctgtgt ggaaaactgc caggcgttca gtggcatcaa cgtccagtac   1320 

aagctgcatt cctctggtgc caactgcagc acgctagggg tggtcacctc agccgaggac   1380 

acctcgggga tcctgtttgt gaatgacacc aaggccctgc ggcggcccaa gtgtgccgaa   1440 

cttcactaca tggtggtggc caccgaccag cagacctcta ggcaggccca ggcccagctg   1500 

cttgtaacag tggaggggtc atatgtggcc gaggaggcgg gctgccccct gtcctgtgca   1560 

gtcagcaaga gacggctgga gtgtgaggag tgtggcggcc tgggctcccc aacaggcagg   1620 

tgtgagtgga ggcaaggaga tggcaaaggg atcaccagga acttctccac ctgctctccc   1680 

agcaccaaga cctgccccga cggccactgc gatgttgtgg agacccaaga catcaacatt   1740 

tgccctcagg actgcctccg gggcagcatt gttgggggac acgagcctgg ggagccccgg   1800 

gggattaaag ctggctatgg cacctgcaac tgcttccctg aggaggagaa gtgcttctgc   1860 

gagcccgaag acatccagga tccactgtgc gacgagctgt gccgcacggt gatcgcagcc   1920 

gctgtcctct tctccttcat cgtctcggtg ctgctgtctg ccttctgcat ccactgctac   1980 

cacaagtttg cccacaagcc acccatctcc tcagctgaga tgaccttccg gaggcccgcc   2040 

caggccttcc cggtcagcta ctcctcttcc agtgcccgcc ggccctcgct ggactccatg   2100 

gagaaccagg tctccgtgga tgccttcaag atcctggagg atccaaagtg ggaattccct   2160 

cggaagaact tggttcttgg aaaaactcta ggagaaggcg aatttggaaa agtggtcaag   2220 

gcaacggcct tccatctgaa aggcagagca gggtacacca cggtggccgt gaagatgctg   2280 

aaagagaacg cctccccgag tgagcttcga gacctgctgt cagagttcaa cgtcctgaag   2340 

caggtcaacc acccacatgt catcaaattg tatggggcct gcagccagga tggcccgctc   2400 

ctcctcatcg tggagtacgc caaatacggc tccctgcggg gcttcctccg cgagagccgc   2460 

aaagtggggc ctggctacct gggcagtgga ggcagccgca actccagctc cctggaccac   2520 

ccggatgagc gggccctcac catgggcgac ctcatctcat ttgcctggca gatctcacag   2580 

gggatgcagt atctggccga gatgaagctc gttcatcggg acttggcagc cagaaacatc   2640 

ctggtagctg aggggcggaa gatgaagatt tcggatttcg gcttgtcccg agatgtttat   2700 

gaagaggatt cgtacgtgaa gaggagccag ggtcggattc cagttaaatg gatggcaatt   2760 

gaatcccttt ttgatcatat ctacaccacg caaagtgatg tatggtcttt tggtgtcctg   2820 

ctgtgggaga tcgtgaccct agggggaaac ccctatcctg ggattcctcc tgagcggctc   2880 

ttcaaccttc tgaagaccgg ccaccggatg gagaggccag acaactgcag cgaggagatg   2940 

taccgcctga tgctgcaatg ctggaagcag gagccggaca aaaggccggt gtttgcggac   3000 

atcagcaaag acctggagaa gatgatggtt aagaggagag actacttgga ccttgcggcg   3060 

tccactccat ctgactccct gatttatgac gacggcctct cagaggagga gacaccgctg   3120 

gtggactgta ataatgcccc cctccctcga gccctccctt ccacatggat tgaaaacaaa   3180 

ctctatggca tgtcagaccc gaactggcct ggagagagtc ctgtaccact cacgagagct   3240 

gatggcacta acactgggtt tccaagatat ccaaatgata gtgtatatgc taactggatg   3300 

ctttcaccct cagcggcaaa attaatggac acgtttgata gttaacattt ctttgtgaaa   3360 

ggtaatggac tcacaagggg aagaaacatg ctgagaatgg aaagtctacc ggccctttct   3420 

ttgtgaacgt cacattggcc gagccgtgtt cagttcccag gtggcagact cg           3472 

 
           
             42  
             1704  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7483117CB1  
             
           
            42 

atggatgaca aagatattga caaagaacta aggcagaaat taaacttttc ctattgtgag     60 

gagactgaga ttgaagggca gaagaaagta gaagaaagca gggaggcttc gagccaaacc    120 

ccagagaagg gtgaagtgca ggattcagag gcaaagggta caccaccttg gactcccctt    180 

agcaacgtgc atgagctcga cacatcttcg gaaaaagaca aagaaagtcc agatcagatt    240 

ttgaggactc cagtgtcaca ccctctcaaa tgtcctgaga caccagccca accagacagc    300 

aggagcaagc tgctgcccag tgacagcccc tctactccca aaaccatgct gagccggttg    360 

gtgatttctc caacagggaa gcttccttcc agaggcccta agcatttgaa gctcacacct    420 

gctcccctca aggatgagat gacctcattg gctctggtca atattaatcc cttcactcca    480 

gagtcctata aaaaattatt tcttcaatct ggtggcaaga ggaaaataag aggagatctt    540 

gaggaagctg gtccagagga aggcaaggga gggctgcctg ccaagagatg tgttttacga    600 

gaaaccaaca tggcttcccg ctatgaaaaa gaattcttgg aggttgaaaa aattggggtt    660 

ggcgaatttg gtacagtcta caagtgcatt aagaggctgg atggatgtgt ttatgcaata    720 

aagcgctcta tgaaaacttt tacagaatta tcaaatgaga attcggcttt gcatgaagtt    780 

tatgctcacg cagtgcttgg gcatcacccc catgtggtac gttactattc ctcatgggca    840 

gaagatgacc acatgatcat tcagaatgaa tactgcaatg gtgggagttt gcaagctgct    900 

atatctgaaa acactaagtc tggcaatcat tttgaagagc caaaactcaa ggacatcctt    960 

ctacagattt cccttggcct taattacatc cacaactcta gcatggtaca cctggacatc   1020 

aaacctagta atatattcat ttgtcacaag atgcaaagtg aatcctctgg agtcatagaa   1080 

gaagttgaaa atgaagctga ttggtttctc tctgccaatg tgatgtataa aattggtgac   1140 

ctgggccacg caacatcaat aaacaaaccc aaagtggaag aaggagatag tcgcttcctg   1200 

gctaatgaga ttttgcaaga ggattaccgg caccttccca aagcagacat atttgccttg   1260 

ggattaacaa ttgcagtggc tgcaggagca gagtcattgc ccaccaatgg tgctgcatgg   1320 

caccatatcc gcaagggtaa ctttccggac gttcctcagg agctctcaga aagcttttcc   1380 

agtctgctca agaacatgat ccaacctgat gccgaacaga gaccttctgc agcagctctg   1440 

gccagaaata cagttctccg gccttccctg ggaaaaacag aagagctcca acagcagctg   1500 

aatttggaaa agttcaagac tgccacactg gaaagggaac tgagagaagc ccagcaggcc   1560 

cagtcacccc agggatatac ccatcatggt gacactgggg tctctgggac ccacacagga   1620 

tcaagaagca caaaacgcct ggtgggagga aagagtgcaa ggtcttcaag ctttacctca   1680 

ggagagcgtg agcctctgca ttaa                                          1704 

 
           
             43  
             6298  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7484498CB1  
             
           
            43 

cgcggggcgg aacagatcgc agacctgggg gttcgcagag ccgccagtgg ggagatgttg     60 

aagttcaaat atggagcgcg gaatcctttg gatgctggtg ctgctgaacc cattgccagc    120 

cgggcctcca ggctgaatct gttcttccag gggaaaccac cctttatgac tcaacagcag    180 

atgtctcctc tttcccgaga agggatatta gatgccctct ttgttctctt tgaagaatgc    240 

agtcagcctg ctctgatgaa gattaagcac gtgagcaact ttgtccggaa gtattccgac    300 

accatagctg agttacagga gctccagcct tcggcaaagg acttcgaagt cagaagtctt    360 

gtaggttgtg gtcactttgc tgaagtgcag gtggtaagag agaaagcaac cggggacatc    420 

tatgctatga aagtgatgaa gaagaaggct ttattggccc aggagcaggt ttcatttttt    480 

gaggaagagc ggaacatatt atctcgaagc acaagcccgt ggatccccca attacagtat    540 

gcctttcagg acaaaaatca cctttatctg gtcatggaat atcagcctgg aggggacttg    600 

ctgtcacttt tgaatagata tgaggaccag ttagatgaaa acctgataca gttttaccta    660 

gctgagctga ttttggctgt tcacagcgtt catctgatgg gatacgtgca tcgagacatc    720 

aagcctgaga acattctcgt tgaccgcaca ggacacatca agctggtgga ttttggatct    780 

gccgcgaaaa tgaattcaaa caagatggtg aatgccaaac tcccgattgg gaccccagat    840 

tacatggctc ctgaagtgct gactgtgatg aacggggatg gaaaaggcac ctacggcctg    900 

gactgtgact ggtggtcagt gggcgtgatt gcctatgaga tgatttatgg gagatccccc    960 

ttcgcagagg gaacctctgc cagaaccttc aataacatta tgaatttcca gcggtttttg   1020 

aaatttccag atgaccccaa agtgagcagt gactttcttg atctgattca aagcttgttg   1080 

tgcggccaga aagagagact gaagtttgaa ggtctttgct gccatccttt cttctctaaa   1140 

attgactgga acaacattcg taactctcct ccccccttcg ttcccaccct caagtctgac   1200 

gatgacacct ccaattttga tgaaccagag aagaattcgt gggtttcatc ctctccgtgc   1260 

cagctgagcc cctcaggctt ctcgggtgaa gaactgccgt ttgtggggtt ttcgtacagc   1320 

aaggcactgg ggattcttgg tagatctgag tctgttgtgt cgggtctgga ctcccctgcc   1380 

aagactagct ccatggaaaa gaaacttctc atcaaaagca aagagctaca agactctcag   1440 

gacaagtgtc acaagatgga gcaggaaatg acccggttac atcggagagt gtcagaggtg   1500 

gaggctgtgc ttagtcagaa ggaggtggag ctgaaggcct ctgagactca gagatccctc   1560 

ctggagcagg accttgctac ctacatcaca gaatgcagta gcttaaagcg aagtttggag   1620 

caagcacgga tggaggtgtc ccaggaggat gacaaagcac tgcagcttct ccatgatatc   1680 

agagagcaga gccggaagct ccaagaaatc aaagagcagg agtaccaggc tcaagtggaa   1740 

gaaatgaggt tgatgatgaa tcagttggaa gaggatcttg tctcagcaag aagacggagt   1800 

gatctctacg aatctgagct gagagagtct cggcttgctg ctgaagaatt caagcggaaa   1860 

gcgacagaat gtcagcataa actgttgaag gctaaggatc aagggaagcc tgaagtggga   1920 

gaatatgcga aactggagaa gatcaatgct gagcagcagc tcaaaattca ggagctccaa   1980 

gagaaactgg agaaggctgt aaaagccagc acggaggcca ccgagctgct gcagaatatc   2040 

cgccaggcaa aggagcgagc cgagagggag ctggagaagc tgcagaaccg agaggattct   2100 

tctgaaggca tcagaaagaa gctggtggaa gctgaggaac gccgccattc tctggagaac   2160 

aaggtaaaga gactagagac catggagcgt agagaaaaca gactgaagga tgacatccag   2220 

acaaaatccc aacagatcca gcagatggct gataaaattc tggagctcga agagaaacat   2280 

cgggaggccc aagtctcagc ccagcaccta gaagtgcacc tgaaacagaa agagcagcac   2340 

tatgaggaaa agattaaagt gttggacaat cagataaaga aagacctggc tgacaaggag   2400 

acactggaga acatgatgca gagacacgag gaggaggccc atgagaaggg caaaattctc   2460 

agcgaacaga aggcgatgat caatgctatg gattccaaga tcagatccct ggaacagagg   2520 

attgtggaac tgtctgaagc caataaactt gcagcaaata gcagtctttt tacccaaagg   2580 

aacatgaagg cccaagaaga gatgatttct gaactcaggc aacagaaatt ttacctggag   2640 

acacaggctg ggaagttgga ggcccagaac cgaaaactgg aggagcagct ggagaagatc   2700 

agccaccaag accacagtga caagaatcgg ctgctggaac tggagacaag attgcgggag   2760 

gtcagtctag agcacgagga gcagaaactg gagctcaagc gccagctcac agagctacag   2820 

ctctccctgc aggagcgcga gtcacagttg acagccctgc aggctgcacg ggcggccctg   2880 

gagagccagc ttcgccaggc gaagacagag ctggaagaga ccacagcaga agctgaagag   2940 

gagatccagg cactcacggc acatagagat gaaatccagc gcaaatttga tgctcttcgt   3000 

aacagctgta ctgtaatcac agacctggag gagcagctaa accagctgac cgaggacaac   3060 

gctgaactca acaaccaaaa cttctacttg tccaaacaac tcgatgaggc ttctggcgcc   3120 

aacgacgaga ttgtacaact gcgaagtgaa gtggaccatc tccgccggga gatcacggaa   3180 

cgagagatgc agcttaccag ccagaagcaa acgatggagg ctctgaagac cacgtgcacc   3240 

atgctggagg aacaggtcat ggatttggag gccctaaacg atgagctgct agaaaaagag   3300 

cggcagtggg aggcctggag gagcgtcctg ggtgatgaga aatcccagtt tgagtgtcgg   3360 

gttcgagagc tgcagaggat gctggacacc gagaaacaga gcagggcgag agccgatcag   3420 

cggatcaccg agtctcgcca ggtggtggag ctggcagtga aggagcacaa ggctgagatt   3480 

ctcgctctgc agcaggctct caaagagcag aagctgaagg ccgagagcct ctctgacaag   3540 

ctcaatgacc tggagaagaa gcatgctatg cttgaaatga atgcccgaag cttacagcag   3600 

aagctggaga ctgaacgaga gctcaaacag aggcttctgg aagagcaagc caaattacag   3660 

cagcagatgg acctgcagaa aaatcacatt ttccgtctga ctcaaggact gcaagaagct   3720 

ctagatcggg ctgatctact gaagacagaa agaagtgact tggagtatca gctggaaaac   3780 

attcaggttc tctattctca tgaaaaggtg aaaatggaag gcactatttc tcaacaaacc   3840 

aaactcattg attttctgca agccaaaatg gaccaacctg ctaaaaagaa aaaggttcct   3900 

ctgcagtaca atgagctgaa gctggccctg gagaaggaga aagctcgctg tgcagagcta   3960 

gaggaagccc ttcagaagac ccgcatcgag ctccggtccg cccgggagga agctgcccac   4020 

cgcaaagcaa cggaccaccc acacccatcc acgccagcca ccgcgaggca gcagatcgcc   4080 

atgtccgcca tcgtgcggtc gccagagcac cagcccagtg ccatgagcct gctggccccg   4140 

ccatccagcc gcagaaagga gtcttcaact ccagaggaat ttagtcggcg tcttaaggaa   4200 

cgcatgcacc acaatattcc tcaccgattc aacgtaggac tgaacatgcg agccacaaag   4260 

tgtgctgtgt gtctggatac cgtgcacttt ggacgccagg catccaaatg tctcgaatgt   4320 

caggtgatgt gtcaccccaa gtgctccacg tgcttgccag ccacctgcgg cttgcctgct   4380 

gaatatgcca cacacttcac cgaggccttc tgccgtgaca aaatgaactc cccaggtctc   4440 

cagaccaagg agcccagcag cagcttgcac ctggaagggt ggatgaaggt gcccaggaat   4500 

aacaaacgag gacagcaagg ctgggacagg aagtacattg tcctggaggg atcaaaagtc   4560 

ctcatttatg acaatgaagc cagagaagct ggacagaggc cggtggaaga atttgagctg   4620 

tgccttcccg acggggatgt atctattcat ggtgccgttg gtgcttccga actcgcaaat   4680 

acagccaaag cagatgtccc atacatactg aagatggaat ctcacccgca caccacctgc   4740 

tggcccggga gaaccctcta cttgctagct cccagcttcc ctgacaaaca gcgctgggtc   4800 

accgccttag aatcagttgt cgcaggtggg agagtttcta gggaaaaagc agaagctgat   4860 

gctaaactgc ttggaaactc cctgctgaaa ctggaaggtg atgaccgtct agacatgaac   4920 

tgcacgctgc ccttcagtga ccaggtggtg ttggtgggca ccgaggaagg gctctacgcc   4980 

ctgaatgtct tgaaaaactc cctaacccat gtcccaggaa ttggagcagt cttccaaatt   5040 

tatattatca aggacctgga gaagctactc atgatagcag gagaagagcg ggcactgtgt   5100 

cttgtggacg tgaagaaagt gaaacagtcc ctggcccagt cccacctgcc tgcccagccc   5160 

gacatctcac ccaacatttt tgaagctgtc aagggctgcc acttgtttgg ggcaggcaag   5220 

attgagaacg ggctctgcat ctgtgcagcc atgcccagca aagtcgtcat tctccgctac   5280 

aacgaaaacc tcagcaaata ctgcatccgg aaagagatag agacctcaga gccctgcagc   5340 

tgtatccact tcaccaatta cagtatcctc attggaacca ataaattcta cgaaatcgac   5400 

atgaagcagt acacgctcga ggaattcctg gataagaatg accattcctt ggcacctgct   5460 

gtgtttgccg cctcttccaa cagcttccct gtctcaatcg tgcaggtgaa cagcgcaggg   5520 

cagcgagagg agtacttgct gtgtttccac gaatttggag tgttcgtgga ttcttacgga   5580 

agacgtagcc gcacagacga tctcaagtgg agtcgcttac ctttggcctt tgcctacaga   5640 

gaaccctatc tgtttgtgac ccacttcaac tcactcgaag taattgagat ccaggcacgc   5700 

tcctcagcag ggacccctgc ccgagcgtac ctggacatcc cgaacccgcg ctacctgggc   5760 

cctgccattt cctcaggagc gatttacttg gcgtcctcat accaggataa attaagggtc   5820 

atttgctgca agggaaacct cgtgaaggag tccggcactg aacaccaccg gggcccgtcc   5880 

acctcccgca gcagccccaa caagcgaggc ccacccacgt acaacgagca catcaccaag   5940 

cgcgtggcct ccagcccagc gccgcccgaa ggccccagcc acccgcgaga gccaagcaca   6000 

ccccaccgct accgcgaggg gcggaccgag ctgcgcaggg acaagtctcc tggccgcccc   6060 

ctggagcgag agaagtcccc cggccggatg ctcagcacgc ggagagagcg gtcccccggg   6120 

aggctgtttg aagacagcag caggggccgg ctgcctgcgg gagccgtgag gaccccgctg   6180 

tcccaggtga acaaggtctg ggaccagtct tcagtataaa tctcagccag aaaaaccaac   6240 

tcctcatctt gatctgcagg aaaacaccaa acacactatg gaactctgct gatgggga     6298 

 
           
             44  
             5454  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7638121CB1  
             
           
            44 

cacgcacacc gcacgtacgg ggttgggccc agctgggtta taagcgtgat ccccatgccc     60 

cctgcccagg ctggggggca tttgcacatc tgcaaaggcc tcccagcctg tcccagccct    120 

gccccagcct gggaccccca cattctactc accgtgtctc ctcagagggg ccagaaccct    180 

ccactgggga gaggcaagtg gcggtgaact tggtgtccat aggaccctgt ccctgagagc    240 

gacagctgag ttagtgagct ccactggccc caccaactcc ttctgatcac ctggccagct    300 

gaggtcagag tgggagaggc agtggttcca ttgaaggagt actcctaact gtcagaagcc    360 

tgggcggtca ggatggggtg ctgtcgcttg ggctgcgggg ggtgttcagt tgcccacagt    420 

gtatctcagg gtctcaccaa ccatccaagc atggtaggct gtggctggca cccagggttg    480 

tgtggctggg gaggtggtct ccacagttcc ctccctgccc tcccagggcc cccatccatg    540 

caggtaacca tcgaggatgt gcaggcacag acaggcggaa cggcccaatt cgaggctatc    600 

attgagggcg acccacagcc ctcggtgacc tggtacaagg acagcgtcca gctggtggac    660 

agcacccggc ttagccagca gcaagaaggc accacatact ccctggtgct gaggcatatg    720 

gcctcgaagg atgccggcgt ttacacctgc ctggcccaaa acactggtgg ccaggtgctc    780 

tgcaaggcag agctgctggt gcttgggggg gacaatgagc cggactcaga gaagcaaagc    840 

caccggagga agctgcactc cttctatgag gtcaaggagg agattggaag gggcgtgttt    900 

ggcttcgtaa aaagagtgca gcacaaagga aacaagatct tgtgcgctgc caagttcatc    960 

cccctacgga gcagaactcg ggcccaggca tacagggagc gagacatcct ggccgcgctg   1020 

agccacccgc tggtcacggg gctgctggac cagtttgaga cccgcaagac cctcatcctc   1080 

atcctggagc tgtgctcatc cgaggagctg ctggaccgcc tgtacaggaa gggcgtggtg   1140 

acggaggccg aggtcaaggt ctacatccag cagctggtgg aggggctgca ctacctgcac   1200 

agccatggcg ttctccacct ggacataaag ccctctaaca tcctgatggt gcatcctgcc   1260 

cgggaagaca ttaaaatctg cgactttggc tttgcccaga acatcacccc agcagagctg   1320 

cagttcagcc agtacggctc ccctgagttc gtctcccccg agatcatcca gcagaaccct   1380 

gtgagcgaag cctccgacat ttgggccatg ggtgtcatct cctacctcag cctgacctgc   1440 

tcatccccat ttgccggcga gagtgaccgt gccaccctcc tgaacgtcct ggaggggcgc   1500 

gtgtcatgga gcagccccat ggctgcccac ctcagcgaag acgccaaaga cttcatcaag   1560 

gctacgctgc agagagcccc tcaggcccgg cctagtgcgg cccagtgcct ctcccacccc   1620 

tggttcctga aatccatgcc tgcggaggag gcccacttca tcaacaccaa gcagctcaag   1680 

ttcctcctgg cccgaagtcg ctggcagcgt tccctgatga gctacaagtc catcctggtg   1740 

atgcgctcca tccctgagct gctgcggggc ccacccgaca gcccctccct cggcgtagcc   1800 

cggcacctct gcagggacac tggtggctcc tccagttcct cctcctcctc tgacaacgag   1860 

ctcgccccat ttgcccgggc taagtcactg ccaccctccc cggtgacaca ctcaccactg   1920 

ctgcaccccc ggggcttcct gcggccctcg gccagcctgc ctgaggaagc cgaggccagt   1980 

gagcgctcca ccgaggcccc agctccgcct gcatctcccg agggtgccgg gccaccggcc   2040 

gcccagggct gcgtgccccg gcacagcgtc atccgcagcc tgttctacca ccaggcgggt   2100 

gagagccctg agcacggggc cctggccccg gggagcaggc ggcacccggc ccggcggcgg   2160 

cacctgctga agggcgggta cattgcgggg gcgctgccag gcctgcgcga gccactgatg   2220 

gagcaccgcg tgctggagga ggaggccgcc agggaggagc aggccaccct cctggccaaa   2280 

gccccctcat tcgagactgc cctccggctg cctgcctctg gcacccactt ggcccctggc   2340 

cacagccact ccctggaaca tgactctccg agcacccccc gcccctcctc ggaggcctgc   2400 

ggtgaggcac agcgactgcc ttcagccccc tccggggggg cccctatcag ggacatgggg   2460 

caccctcagg gctccaagca gcttccatcc actggtggcc acccaggcac tgctcagcca   2520 

gagaggccat ccccggacag cccttggggg cagccagccc ctttctgcca ccccaagcag   2580 

ggttctgccc cccaggaggg ctgcagcccc cacccagcag ttgccccatg ccctcctggc   2640 

tccttccctc caggatcttg caaagaggcc cccttagtac cctcaagccc cttcttggga   2700 

cagccccagg caccccttgc ccctgccaaa gcaagccccc cattggactc taagatgggg   2760 

cctggagaca tctctcttcc tgggaggcca aaacccggcc cctgcagttc cccagggtca   2820 

gcctcccagg cgagctcttc ccaagtgagc tccctcaggg tgggctcctc ccaggtgggc   2880 

acagagcctg gcccctccct ggatgcggag ggctggaccc aggaggctga ggatctgtcc   2940 

gactccacac ccaccttgca gcggcctcag gaacaggtga ccatgcgcaa gttctccctg   3000 

ggtggtcgcg ggggctacgc aggcgtggct ggctatggca cctttgcctt tggtggagat   3060 

gcagggggca tgctggggca ggggcccatg tgggccagga tagcctgggc tgtgtcccag   3120 

tcggaggagg aggagcagga ggaggccagg gctgagtccc agtcggagga gcagcaggag   3180 

gccagggctg agagcccact gccccaggtc agtgcaaggc ctgtgcctga ggtcggcagg   3240 

gctcccacca ggagctctcc agagcccacc ccatgggagg acatcgggca ggtctccctg   3300 

gtgcagatcc gggacctgtc aggtgatgcg gaggcggccg acacaatatc cctggacatt   3360 

tccgaggtgg accccgccta cctcaacctc tcagacctgt acgatatcaa gtacctccca   3420 

ttcgagttta tgatcttcag gaaagtcccc aagtccgctc agccagagcc gccctccccc   3480 

atggctgagg aggagctggc cgagttcccg gagcccacgt ggccctggcc aggtgaactg   3540 

ggcccccacg caggcctgga gatcacagag gagtcagagg atgtggacgc gctgctggca   3600 

gaggctgccg tgggcaggaa gcgcaagtgg tcctcgccgt cacgcagcct cttccacttc   3660 

cctgggaggc acctgccgct ggacgagcct gcagagctgg ggctgcgtga gagagtgaag   3720 

gcctccgtgg agcacatctc ccggatcctg aagggcaggc cggaaggtct ggagaaggag   3780 

gggcccccca ggaagaagcc aggccttgct tccttccggc tctcaggtct gaagagctgg   3840 

gaccgagcgc cgacattcct aagggagctc tcagatgaga ctgtggtcct gggccagtca   3900 

gtgacactgg cctgccaggt gtcagcccag ccagctgccc aggccacctg gagcaaagac   3960 

ggagcccccc tggagagcag cagccgtgtc ctcatctctg ccaccctcaa gaacttccag   4020 

cttctgacca tcctggtggt ggtggctgag gacctgggtg tgtacacctg cagcgtgagc   4080 

aatgcgctgg ggacagtgac caccacgggc gtcctccgga aggcagagcg cccctcatct   4140 

tcgccatgcc cggatatcgg ggaggtgtac gcggatgggg tgctgctggt ctggaagccc   4200 

gtggaatcct acggccctgt gacctacatt gtgcagtgca gcctagaagg cggcagctgg   4260 

accacactgg cctccgacat ctttgactgc tgctacctga ccagcaagct ctcccggggt   4320 

ggcacctaca ccttccgcac ggcatgtgtc agcaaggcag gaatgggtcc ctacagcagc   4380 

ccctcggagc aagtcctcct gggagggccc agccacctgg cctctgagga ggagagccag   4440 

gggcggtcag cccaacccct gcccagcaca aagaccttcg cattccagac acagatccag   4500 

aggggccgct tcagcgtggt gcggcaatgc tgggagaagg ccagcgggcg ggcgctggcc   4560 

gccaagatca tcccctacca ccccaaggac aagacagcag tgctgcgcga atacgaggcc   4620 

ctcaagggcc tgcgccaccc gcacctggcc cagctgcacg cagcctacct cagcccccgg   4680 

cacctggtgc tcatcttgga gctgtgctct gggcccgagc tgctcccctg cctggccgag   4740 

agggcctcct actcagaatc cgaggtgaag gactacctgt ggcagatgtt gagtgccacc   4800 

cagtacctgc acaaccagca catcctgcac ctggacctga ggtccgagaa catgatcatc   4860 

accgaataca acctgctcaa ggtcgtggac ctgggcaatg cacagagcct cagccaggag   4920 

aaggtgctgc cctcagacaa gttcaaggac tacctagaga ccatggctcc agagctcctg   4980 

gagggccagg gggctgttcc acagacagac atctgggcca tcggtgtgac agccttcatc   5040 

atgctgagcg ccgagtaccc ggtgagcagc gagggtgcac gcgacctgca gagaggactg   5100 

cgcaaggggc tggtccggct gagccgctgc tacgcggggc tgtccggggg cgccgtggcc   5160 

ttcctgcgca gcactctgtg cgcccagccc tggggccggc cctgcgcgtc cagctgcctg   5220 

cagtgcccgt ggctaacaga ggagggcccg gcctgttcgc ggcccgcgcc cgtgaccttc   5280 

cctaccgcgc ggctgcgcgt cttcgtgcgc aatcgcgaga agagacgcgc gctgctgtac   5340 

aagaggcaca acctggccca ggtgcgctga gggtcgcccc ggccacaccc ttggtctccc   5400 

cgctgggggt cgctgcagac gcgccaataa aaacgcacag ccgggcgaga aaaa         5454