Patent Publication Number: US-2004044184-A1

Title: Cytoskeleton-associated proteins

Description:
TECHNICAL FIELD  
       [0001] This invention relates to nucleic acid and amino acid sequences of cytoskeleton-associated proteins and to the use of these sequences in the diagnosis, treatment, and prevention of cell proliferative disorders, viral infections, and neurological disorders, and in the assessment of the effects of exogenous compounds on the expression of nucleic acid and amino acid sequences of cytoskeleton-associated proteins.  
       BACKGROUND OF THE INVENTION  
       [0002] The cytoskeleton is a cytoplasmic network of protein fibers that mediate cell shape, structure, and movement. The cytoskeleton supports the cell membrane and forms tracks along which organelles and other elements move in the cytosol. The cytoskeleton is a dynamic structure that allows cells to adopt various shapes and to carry out directed movements. Major cytoskeletal fibers include the microtubules, the microfilaments, and the intermediate filaments. Motor proteins, including myosin, dynein, and kinesin, drive movement of or along the fibers. The motor protein dynamin drives the formation of membrane vesicles. Accessory or associated proteins modify the structure or activity of the fibers while cytoskeletal membrane anchors connect the fibers to the cell membrane.  
       [0003] Microtubules and Associated Proteins  
       [0004] Tubulins  
       [0005] Microtubules, cytoskeletal fibers with a diameter of about 24 nm, have multiple roles in the cell. Bundles of microtubules form cilia and flagella, which are whip-like extensions of the cell membrane that are necessary for sweeping materials across an epithelium and for swimming of sperm, respectively. Marginal bands of microtubules in red blood cells and platelets are important for these cells&#39; pliability. Organelles, membrane vesicles, and proteins are transported in the cell along tracks of microtubules. For example, microtubules run through nerve cell axons, allowing bi-directional transport of materials and membrane vesicles between the cell body and the nerve terminal. Failure to supply the nerve terminal with these vesicles blocks the transmission of neural signals. Microtubules are also critical to chromosomal movement during cell division. Both stable and short-lived populations of microtubules exist in the cell.  
       [0006] Microtubules are polymers of GTP-binding tubulin protein subunits. Each subunit is a heterodimer of α- and β-tubulin, multiple isoforms of which exist. The hydrolysis of GTP is linked to the addition of tubulin subunits at the end of a microtubule. The subunits interact head to tail to form protofilaments; the protofilaments interact side to side to form a microtubule. A microtubule is polarized, one end ringed with a-tubulin and the other with β-tubulin, and the two ends differ in their rates of assembly. Generally, each microtubule is composed of 13 protofilaments although 11 or 15 protofilament-microtubules are sometimes found. Cilia and flagella contain doublet microtubules. Microtubules grow from specialized structures known as centrosomes or microtubule-organizing centers (MTOCs). MTOCs may contain one or two centrioles, which are pinwheel arrays of triplet microtubules. The basal body, the organizing center located at the base of a cilium or flagellum, contains one centriole. Gamma tubulin present in the MTOC is important for nucleating the polymerization of α- and β-tubulin heterodimers but does not polymerize into microtubules.  
       [0007] Microtubule-Associated Proteins  
       [0008] Microtubule-associated proteins (MAPs) have roles in the assembly and stabilization of microtubules. One major family of MAPs, assembly MAPs, can be identified in neurons as well as non-neuronal cells. Assembly MAPs are responsible for cross-linking microtubules in the cytosol. These MAPs are organized into two domains: a basic microtubule-binding domain and an acidic projection domain. The projection domain is the binding site for membranes, intermediate filaments, or other microtubules. Based on sequence analysis, assembly MAPs can be further grouped into two types: Type I and Type II. Type I MAPs, which include MAP1A and MAP1B, are large, filamentous molecules that co-purify with microtubules and are abundantly expressed in brain and testes. Type I MAPs contain several repeats of a positively-charged amino acid sequence motif that binds and neutralizes negatively charged tubulin, leading to stabilization of microtubules. MAP1A and MAP1B are each derived from a single precursor polypeptide that is subsequently proteolytically processed to generate one heavy chain and one light chain.  
       [0009] Another light chain, LC3, is a 16.4 kDa molecule that binds MAP1A, MAP1B, and microtubules. It is suggested that LC3 is synthesized from a source other than the MAP1A or MAP1B transcripts, and that the expression of LC3 maybe important in regulating the microtubule binding activity of MAP1A and MAP1B during cell proliferation (Mann, S. S. et al. (1994) J. Biol. Chem. 269:11492-11497).  
       [0010] Type II MAPs, which include MAP2a, MAP2b, MAP2c, MAP4, and Tau, are characterized by three to four copies of an 18-residue sequence in the microtubule-binding domain. MAP2a, MAP2b, and MAP2c are found only in dendrites, MAP4 is found in non-neuronal cells, and Tau is found in axons and dendrites of nerve cells. Alternative splicing of the Tau MRNA leads to the existence of multiple forms of Tau protein. Tau phosphorylation is altered in neurodegenerative disorders such as Alzheimer&#39;s disease, Pick&#39;s disease, progressive supranuclear palsy, corticobasal degeneration, and familial frontotemporal dementia and Parkinsonism linked to chromosome 17. The altered Tau phosphorylation leads to a collapse of the microtubule network and the formation of intraneuronal Tau aggregates (Spillantini, M. G. and M. Goedert (1998) Trends Neurosci. 21:428-433).  
       [0011] The protein pericentrin is found in the MTOC and has a role in microtubule assembly.  
       [0012] Another microtubule associated protein, STOP (stable tubule only polypeptide), is a calmodulin-regulated protein that regulates stability (Denarier, E. et al. (1998) Biochem. Biophys. Res. Commun. 24:791-796). In order for neurons to maintain conductive connections over great distances, they rely upon axodendritic extensions, which in turn are supported by microtubules. STOP proteins function to stabilize the microtubular network. STOP proteins are associated with axonal microtubules, and are also abundant in neurons (Guillaud, L. et al. (1998) J. Cell Biol. 142:167-179). STOP proteins are necessary for normal neurite formation, and have been observed to stabilize microtubules, in vitro, against cold-, calcium-, or drug-induced dissassembly (Margolis, R. L. et al. (1990) EMBO 9:4095-502).  
       [0013] Microfilaments and Associated Proteins  
       [0014] Actins  
       [0015] Microfilaments, cytoskeletal filaments with a diameter of about 7-9 nm, are vital to cell locomotion, cell shape, cell adhesion, cell division, and muscle contraction. Assembly and disassembly of the microfilaments allow cells to change their morphology. Microfilaments are the polymerized form of actin, the most abundant intracellular protein in the eukaryotic cell. Human cells contain six isoforms of actin. The three α-actins are found in different kinds of muscle, nonmuscle β-actin and nonmuscle γ-actin are found in nonmuscle cells, and another γ-actin is found in intestinal smooth muscle cells. G-actin, the monomeric form of actin, polymerizes into polarized, helical F-actin filaments, accompanied by the hydrolysis of ATP to ADP. Actin filaments associate to form bundles and networks, providing a framework to support the plasma membrane and determine cell shape. These bundles and networks are connected to the cell membrane. In muscle cells, thin filaments containing actin slide past thick filaments containing the motor protein myosin during contraction. A family of actin-related proteins exist that are not part of the actin cytoskeleton, but rather associate with microtubules and dynein.  
       [0016] Actin-Associated Proteins  
       [0017] Actin-associated proteins have roles in cross-linking, severing, and stabilization of actin filaments and in sequestering actin monomers. Several of the actin-associated proteins have multiple functions. Bundles and networks of actin filaments are held together by actin cross-linking proteins. These proteins have two actin-binding sites, one for each filament. Short cross-linking proteins promote bundle formation while longer, more flexible cross-linking proteins promote network formation. Actin-interacting proteins (AIPs) participate in the regulation of actin filament organization.  
       [0018] Other actin-associated proteins such as TARA, a novel F-actin binding protein, function in a similar capacity by regulating actin cytoskeletal organization. Calmodulin-like calcium-binding domains in actin cross-linking proteins allow calcium regulation of cross-linking. Group I cross-linking proteins have unique actin-binding domains and include the 30 kD protein, EF-1a, fascin, and scruin. Group III cross-linking proteins have a 7,000-MW actin-binding domain and include villin and dematin. Group m cross-linking proteins have pairs of a 26,000-MW actin-binding domain and include fimbrin, spectrin, dystrophin, ABP 120, and filamin.  
       [0019] The Rho family of low molecular weight GTP-binding proteins regulates actin organization, and controls signal transduction pathways that link extracellular and intracellular signals to the rearrangement of the actin cytoskeleton. This affects such diverse processes as cell shape and motility, cell adhesion, and proliferation. LMW GTP-binding proteins cycle between the active GTP-bound form and the inactive GDP-bound form, and this cycling is regulated by additional proteins. The intrinsic rate of GTP hydrolysis of the LMW GTP-binding proteins is typically very slow, but it can be stimulated by several orders of magnitude by GTPase-activating proteins (GAPs) (Geyer, M. and Wittinghofer, A. (1997) Curr. Opin. Struct. Biol. 7:786-792) while guanine-nucleotide exchange factors (GEFs) promote GDP dissociation and facilitate GTP binding. In the active GTP-bound state, Rho proteins interact with and activate downstream effectors to control the assembly of actin filaments (for a review, see Schmidt A. and Hall, M. N. (1998) Annu. Rev. Cell. Dev. Biol 14:305-38).  
       [0020] Severing proteins regulate the length of actin filaments by breaking them into short pieces or by blocking their ends. Severing proteins include gCAP39, severin (fragmin), gelsolin, and villin. Capping proteins can cap the ends of actin filaments, but cannot break filaments. Capping proteins include CapZ and tropomodulin. The proteins thymosin and profilin sequester actin monomers in the cytosol, allowing a pool of unpolymerized actin to exist. The actin-associated proteins tropomyosin, troponin, and caldesmon regulate muscle contraction in response to calcium.  
       [0021] Microtubule and actin filament networks cooperate in processes such as vesicle and organelle transport, cleavage furrow placement, directed cell migration, spindle rotation, and nuclear migration. Microtubules and actin may coordinate to transport vesicles, organelles, and cell fate determinants, or transport may involve targeting and capture of microtubule ends at cortical actin sites. These cytoskeletal systems may be bridged by myosin-kinesin complexes, myosin-CLIP170 complexes, formin-homology (FH) proteins, dynein, the dynactin complex, Kar9p, coronin, ERM proteins, and kelch repeat-containing proteins (for a review, see Goode, B. L. et al. (2000) Curr. Opin. Cell Biol. 12:63-71). The kelch repeat is a motif originally observed in the kelch protein, which is involved in formation of cytoplasmic bridges called ring canals. A variety of mammalian and other kelch family proteins have been identified. The kelch repeat domain is believed to mediate interaction with actin (Robinson, D. N. and L. Cooley (1997) J. Cell Biol. 138:799-810).  
       [0022] ADF/cofilins are a family of conserved 15-18 kDa actin-binding proteins that play a role in cytokinesis, endocytosis, and in development of embryonic tissues, as well as in tissue regeneration and in pathologies such as ischemia, oxidative or osmotic stress. LIM kinase 1 downregulates ADF (Carlier, M. F. et al. (1999) J. Biol. Chem. 274:33827-33830).  
       [0023] LIM is an acronym of three transcription factors, Lin-11, Isl-1, and Mec-3, in which the motif was first identified. The LIM domain is a double zinc-finger motif that mediates the protein-protein interactions of transcription factors, signaling, and cytoskeleton-associated proteins (Roof, D. J. et al. (1997) J. Cell Biol. 138:575-588). These proteins are distributed in the nucleus, cytoplasm, or both (Brown, S. et al. (1999) J. Biol. Chem. 274:27083-27091). Recently, ALP (actinin-associated LIM protein) has been shown to bind alpha-actinin-2 (Bouju, S. et al. (1999) Neuromuscul. Disord. 9:3-10).  
       [0024] The Frabin protein is another example of an actin-filament binding protein (Obaishi, H. et al. (1998) J. Biol. Chem. 273:18697-18700). Frabin FGD1-related F-actin-binding protein) possesses one actin-filament binding (FAB) domain, one Dbl homology (DH) domain, two pleckstrin homology (PH) domains, and a single cysteine-rich FYVE (Fab1p, YOTB, Vac1p, and EEA1 (early endosomal antigen 1)) domain. Frabin has shown GDP/GTP exchange activity for Cdc42 small G protein (Cdc42), and indirectly induces activation of Rac small G protein (Rac) in intact cells. Through the activation of Cdc42 and Rac, Frabin is able to induce formation of both filopodia- and lamelipodia-like processes (Ono, Y. et al. (2000) Oncogene 19:3050-3058). The Rho family small GTP-binding proteins are important regulators of actin-dependent cell functions including cell shape change, adhesion, and motility. The Rho family consists of three major subfamilies: Cdc42, Rac, and Rho. Rho family members cycle between GDP-bound inactive and GTP-bound active forms by means of a GDP/GTP exchange factor (GEF) (Umikawa, M. et al. (1999) J. Biol. Chem. 274:25197-25200). The Rho GEF family is crucial for microfilament organization.  
       [0025] Intermediate Filaments and Associated Proteins  
       [0026] Intermediate filaments (IFs) are cytoskeletal fibers with a diameter of about 10 nm, intermediate between that of microfilaments and microtubules. IFs serve structural roles in the cell, reinforcing cells and organizing cells into tissues. IFs are particularly abundant in epidermal cells and in neurons. IFs are extremely stable, and, in contrast to microfilaments and microtubules, do not function in cell motility.  
       [0027] Five types of IF proteins are known in mammals. Type I and Type II proteins are the acidic and basic keratins, respectively. Heterodimers of the acidic and basic keratins are the building blocks of keratin IFs. Keratins are abundant in soft epithelia such as skin and cornea, hard epithelia such as nails and hair, and in epithelia that line internal body cavities. Mutations in keratin genes lead to epithelial diseases including epidermolysis bullosa simplex, bullous congenital ichthyosiform erythroderma (epidermolytic hyperkeratosis), non-epidermolytic and epidermolytic palmoplantar keratoderma, ichthyosis bullosa of Siemens, pachyonychia congenita, and white sponge nevus. Some of these diseases result in severe skin blistering. (See, e.g., Wawersik, M. et al. (1997) J. Biol. Chem. 272:32557-32565; and Corden L. D. and W. H. McLean (1996) Exp. Dermatol. 5:297-307.)  
       [0028] Type III IF proteins include desmin, glial fibrillary acidic protein, vimentin, and peripherin. Desmin filaments in muscle cells link myofibrils into bundles and stabilize sarcomeres in contracting muscle. Glial fibrillary acidic protein filaments are found in the glial cells that surround neurons and astrocytes. Vimentin filaments are found in blood vessel endothelial cells, some epithelial cells, and mesenchymal cells such as fibroblasts, and are commonly associated with microtubules. Vimentin filaments may have roles in keeping the nucleus and other organelles in place in the cell. Type IV IFs include the neurofilaments and nestin. Neurofilaments, composed of three polypeptides NF-L, NF-M, and NF-H, are frequently associated with microtubules in axons. Neurofilaments are responsible for the radial growth and diameter of an axon, and ultimately for the speed of nerve impulse transmission. Changes in phosphorylation and metabolism of neurofilaments are observed in neurodegenerative diseases including amyotrophic lateral sclerosis, Parkinson&#39;s disease, and Alzheimer&#39;s disease (Julien, J. P. and W. E. Mushynski (1998) Prog. Nucleic Acid Res. Mol. Biol. 61:1-23). Type V IFs, the lamins, are found in the nucleus where they support the nuclear membrane.  
       [0029] IFs have a central a-helical rod region interrupted by short nonhelical linker segments. The rod region is bracketed, in most cases, by non-helical head and tail domains. The rod regions of intermediate filament proteins associate to form a coiled-coil dimer. A highly ordered assembly process leads from the dimers to the IFs. Neither ATP nor GTP is needed for IF assembly, unlike that of microfilaments and microtubules.  
       [0030] IF-associated proteins (IFAPs) mediate the interactions of IFs with one another and with other cell structures. IFAPs cross-link IFs into a bundle, into a network, or to the plasma membrane, and may cross-link IFs to the microfilament and microtubule cytoskeleton. Microtubules and IFs are particularly closely associated. IFAPs include BPAG1, plakoglobin, desmoplakin I, desmoplakin II, plectin, ankyrin, filaggrin, and lamin B receptor.  
       [0031] Cytoskeletal-Membrane Anchors  
       [0032] Cytoskeletal fibers are attached to the plasma membrane by specific proteins. These attachments are important for maintaining cell shape and for muscle contraction. In erythrocytes, the spectrin-actin cytoskeleton is attached to the cell membrane by three proteins, band 4.1, ankyrin, and adducin. Defects in this attachment result in abnormally shaped cells which are more rapidly degraded by the spleen, leading to anemia. In platelets, the spectrin-actin cytoskeleton is also linked to the membrane by ankyrin; a second actin network is anchored to the membrane by filamin. In muscle cells the protein dystrophin links actin filaments to the plasma membrane; mutations in the dystrophin gene lead to Duchenne muscular dystrophy. In adherens junctions and adhesion plaques the peripheral membrane proteins a-actinin and vinculin attach actin filaments to the cell membrane.  
       [0033] Focal Adhesions  
       [0034] Focal adhesions are specialized structures in the plasma membrane involved in the adhesion of a cell to a substrate, such as the extracellular matrix. Focal adhesions form the connection between an extracellular substrate and the cytoskeleton, and affect such functions as cell shape, cell motility and cell proliferation. Transmembrane integrin molecules form the basis of focal adhesions. Upon ligand binding, integrins cluster in the plane of the plasma membrane. Cytoskeletal linker proteins such as the actin binding proteins α-actinin, talin, tensin, vinculin, paxillin, and filamin are recruited to the clustering site. Key regulatory proteins, such as Rho and Ras family proteins, focal adhesion kinase, and Src family members are also recruited. These events lead to the reorganization of actin filaments and the formation of stress fibers. These intracellular rearrangements promote further integrin-ECM interactions and integrin clustering. Thus, integrins mediate aggregation of protein complexes on both the cytosolic and extracellular faces of the plasma membrane, leading to the assembly of the focal adhesion. Many signal transduction responses are mediated via various adhesion complex proteins, including Src, FAK, paxillin, and tensin. (For a review, see Yamada, K. M. and B. Geiger, (1997) Curr. Opin. Cell Biol. 9:76-85.)  
       [0035] IFs are also attached to membranes by cytoskeletal-membrane anchors. The nuclear lamina is attached to the inner surface of the nuclear membrane by the lamin B receptor. Vimentin IFs are attached to the plasma membrane by ankyrin and plectin. Desmosome and hemidesmosome membrane junctions hold together epithelial cells of organs and skin. These membrane junctions allow shear forces to be distributed across the entire epithelial cell layer, thus providing strength and rigidity to the epithelium. IFs in epithelial cells are attached to the desmosome by plakoglobin and desmoplakins. The proteins that link IFs to hemidesmosomes are not known. Desmin IFs surround the sarcomere in muscle and are linked to the plasma membrane by paranemin, synemin, and ankyrin.  
       [0036] Motor Proteins  
       [0037] Myosin-Related Motor Proteins  
       [0038] Myosins are actin-activated ATPases, found in eukaryotic cells, that couple hydrolysis of ATP with motion. Myosin provides the motor function for muscle contraction and intracellular movements such as phagocytosis and rearrangement of cell contents during mitotic cell division (cytokinesis). The contractile unit of skeletal muscle, termed the sarcomere, consists of highly ordered arrays of thin actin-containing filaments and thick myosin-containing filaments. Crossbridges form between the thick and thin filaments, and the ATP-dependent movement of myosin heads within the thick filaments pulls the thin filaments, shortening the sarcomere and thus the muscle fiber.  
       [0039] Myosins are composed of one or two heavy chains and associated light chains. Myosin heavy chains contain an amino-terminal motor or head domain, a neck that is the site of light-chain binding, and a carboxy-terminal tail domain. The tail domains may associate to form an α-helical coiled coil. Conventional myosins, such as those found in muscle tissue, are composed of two myosin heavy-chain subunits, each associated with two light-chain subunits that bind at the neck region and play a regulatory role. Unconventional myosins, believed to function in intracellular motion, may contain either one or two heavy chains and associated light chains. There is evidence for about 25 myosin heavy chain genes in vertebrates, more than half of them unconventional.  
       [0040] Dynein-Related Motor Proteins  
       [0041] Dyneins are (−) end-directed motor proteins which act on microtubules. Two classes of dyneins, cytosolic and axonemal, have been identified. Cytosolic dyneins are responsible for translocation of materials along cytoplasmic microtubules, for example, transport from the nerve terminal to the cell body and transport of endocytic vesicles to lysosomes. As well, viruses often take advantage of cytoplasmic dyneins to be transported to the nucleus and establish a successful infection (Sodeik, B. et al. (1997) J. Cell Biol. 136:1007-1021). Virion proteins of herpes simplex virus 1, for example, interact with the cytoplasmic dynein intermediate chain (Ye, G. J. et al. (2000) J. Virol. 74:1355-1363). Cytoplasmic dyneins are also reported to play a role in mitosis. Axonemal dyneins are responsible for the beating of flagella and cilia. Dynein on one microtubule doublet walks along the adjacent microtubule doublet. This sliding force produces bending that causes the flagellum or cilium to beat. Dyneins have a native mass between 1000 and 2000 kDa and contain either two or three force-producing heads driven by the hydrolysis of ATP. The heads are linked via stalks to a basal domain which is composed of a highly variable number of accessory intermediate and light chains. Cytoplasmic dynein is the largest and most complex of the motor proteins.  
       [0042] Kinesin-Related Motor Proteins  
       [0043] Kinesins are (+) end-directed motor proteins which act on microtubules. The prototypical kinesin molecule is involved in the transport of membrane-bound vesicles and organelles. This function is particularly important for axonal transport in neurons. Kinesin is also important in all cell types for the transport of vesicles from the Golgi complex to the endoplasmic reticulum. This role is critical for maintaining the identity and functionality of these secretory organelles.  
       [0044] Kinesins define a ubiquitous, conserved family of over 50 proteins that can be classified into at least 8 subfamilies based on primary amino acid sequence, domain structure, velocity of movement, and cellular function. (Reviewed in Moore, J. D. and S. A. Endow (1996) Bioessays 18:207-219; and Hoyt, A. M. (1994) Curr. Opin. Cell Biol. 6:63-68.) The prototypical kinesin molecule is a heterotetramer comprised of two heavy polypeptide chains (KHCs) and two light polypeptide chains (KLCs). The KHC subunits are typically referred to as “kinesin.” KHC is about 1000 amino acids in length, and KLC is about 550 amino acids in length. Two KHCs dimerize to form a rod-shaped molecule with three distinct regions of secondary structure. At one end of the molecule is a globular motor domain that functions in ATP hydrolysis and microtubule binding. Kinesin motor domains are highly conserved and share over 70% identity. Beyond the motor domain is an a-helical coiled-coil region which mediates dimerization. At the other end of the molecule is a fan-shaped tail that associates with molecular cargo. The tail is formed by the interaction of the KHC C-termini with the two KLCs.  
       [0045] Members of the more divergent subfamilies of kinesins are called kinesin-related proteins (KRPs), many of which function during mitosis in eukaryotes (Hoyt, supra). Some KRPs are required for assembly of the mitotic spindle. In vivo and in vitro analyses suggest that these KRPs exert force on microtubules that comprise the mitotic spindle, resulting in the separation of spindle poles. Phosphorylation of KRP is required for this activity. Failure to assemble the mitotic spindle results in abortive mitosis and chromosomal aneuploidy, the latter condition being characteristic of cancer cells. In addition, a unique KRP, centromere protein E, localizes to the kinetochore of human mitotic chromosomes and may play a role in their segregation to opposite spindle poles.  
       [0046] Dynamin-Related Motor Proteins  
       [0047] Dynamin is a large GTPase motor protein that functions as a “molecular pinchase,” generating a mechanochemical force used to sever membranes. This activity is important in forming clathrin-coated vesicles from coated pits in endocytosis and in the biogenesis of synaptic vesicles in neurons. Binding of dynamin to a membrane leads to dynamin&#39;s self-assembly into spirals that may act to constrict a flat membrane surface into a tubule. GTP hydrolysis induces a change in conformation of the dynamin polymer that pinches the membrane tubule, leading to severing of the membrane tubule and formation of a membrane vesicle. Release of GDP and inorganic phosphate leads to dynamin disassembly. Following disassembly the dynamin may either dissociate from the membrane or remain associated to the vesicle and be transported to another region of the cell. Three homologous dynamin genes have been discovered, in addition to several dynamin-related proteins. Conserved dynamin regions are the N-terminal GTP-binding domain, a central pleckstrin homology domain that binds membranes, a central coiled-coil region that may activate dynamin&#39;s GTPase activity, and a C-terminal proline-rich domain that contains several motifs that bind SH3 domains on other proteins. Some dynamin-related proteins do not contain the pleckstrin homology domain or the proline-rich domain. (See McNiven, M. A. (1998) Cell 94:151-154; Scaife, R. M. and R. L. Margolis (1997) Cell. Signal. 9:395-401.)  
       [0048] The cytoskeleton is reviewed in Lodish, H. et al. (1995)  Molecular Cell Biology,  Scientific American Books, New York N.Y.  
       [0049] The discovery of new cytoskeleton-associated proteins, and the polynucleotides encoding them, satisfies a need in the art by providing new compositions which are useful in the diagnosis, prevention, and treatment of cell proliferative disorders, viral infections, and neurological disorders, and in the assessment of the effects of exogenous compounds on the expression of nucleic acid and amino acid sequences of cytoskeleton-associated proteins.  
       SUMMARY OF THE INVENTION  
       [0050] The invention features purified polypeptides, cytoskeleton-associated proteins, referred to collectively as “CSAP” and individually as “CSAP-1,” “CSAP-2,” “CSAP-3,” “CSAP-4,” “CSAP-5,” “CSAP-6,” “CSAP-7,” “CSAP-8,” “CSAP-9,” “CSAP-10,” “CSAP-11,” “CSAP-12,” “CSAP-13,” and “CSAP-14.” 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:1-14, 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:1-14, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-14, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-14. In one alternative, the invention provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO:1-14.  
       [0051] 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:1-14, 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: 1-14, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-14, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-14. In one alternative, the polynucleotide encodes a polypeptide selected from the group consisting of SEQ ID NO:1-14. In another alternative, the polynucleotide is selected from the group consisting of SEQ ID NO:15-28.  
       [0052] 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:1-14, 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:1-14, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-14, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 1-14. 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.  
       [0053] 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:1-14, 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:1-14, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-14, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-14. 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.  
       [0054] 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: 1-14, 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:1-14, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-14, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-14.  
       [0055] The invention further provides an isolated polynucleotide selected from the group consisting of a) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:15-28, 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:15-28, 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.  
       [0056] 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:15-28, 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:15-28, 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.  
       [0057] 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: 15-28, 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:15-28, 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.  
       [0058] The invention further provides a composition comprising an effective amount of a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-14, 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:1-14, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-14, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-14, and a pharmaceutically acceptable excipient. In one embodiment, the composition comprises an amino acid sequence selected from the group consisting of SEQ ID NO:1-14. The invention additionally provides a method of treating a disease or condition associated with decreased expression of functional CSAP, comprising administering to a patient in need of such treatment the composition.  
       [0059] 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:1-14, 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:1-14, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-14, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-14. 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 CSAP, comprising administering to a patient in need of such treatment the composition.  
       [0060] 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:1-14, 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:1-14, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-14, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-14. 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 CSAP, comprising administering to a patient in need of such treatment the composition.  
       [0061] 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:1-14, 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:1-14, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-14, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-14. 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.  
       [0062] 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:1-14, 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:1-14, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-14, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-14. 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.  
       [0063] 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:15-28, the method comprising a) exposing a sample comprising the target polynucleotide to a compound, and b) detecting altered expression of the target polynucleotide.  
       [0064] 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:15-28, 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:15-28, iii) a polynucleotide having a sequence complementary to i), iv) a polynucleotide complementary to the polynucleotide of ii), and v) an RNA equivalent of i)-iv). Hybridization occurs under conditions whereby a specific hybridization complex is formed between said probe and a target polynucleotide in the biological sample, said target polynucleotide selected from the group consisting of i) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:15-28, 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:15-28, 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  
       [0065] Table 1 summarizes the nomenclature for the full length polynucleotide and polypeptide sequences of the present invention.  
       [0066] Table 2 shows the GenBank identification number and annotation of the nearest GenBank homolog for polypeptides of the invention. The probability scores for the matches between each polypeptide and its homolog(s) are also shown.  
       [0067] 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.  
       [0068] Table 4 lists the cDNA and/or genomic DNA fragments which were used to assemble polynucleotide sequences of the invention, along with selected fragments of the polynucleotide sequences.  
       [0069] Table 5 shows the representative cDNA library for polynucleotides of the invention.  
       [0070] Table 6 provides an appendix which describes the tissues and vectors used for construction of the cDNA libraries shown in Table 5.  
       [0071] 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  
       [0072] 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.  
       [0073] 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.  
       [0074] 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.  
       [0075] Definitions  
       [0076] “CSAP” refers to the amino acid sequences of substantially purified CSAP 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.  
       [0077] The term “agonist” refers to a molecule which intensifies or mimics the biological activity of CSAP. Agonists may include proteins, nucleic acids, carbohydrates, small molecules, or any other compound or composition which modulates the activity of CSAP either by directly interacting with CSAP or by acting on components of the biological pathway in which CSAP participates.  
       [0078] An “allelic variant” is an alternative form of the gene encoding CSAP. 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.  
       [0079] “Altered” nucleic acid sequences encoding CSAP include those sequences with deletions, insertions, or substitutions of different nucleotides, resulting in a polypeptide the same as CSAP or a polypeptide with at least one functional characteristic of CSAP. Included within this definition are polymorphisms which may or may not be readily detectable using a particular oligonucleotide probe of the polynucleotide encoding CSAP, and improper or unexpected hybridization to allelic variants, with a locus other than the normal chromosomal locus for the polynucleotide sequence encoding CSAP. 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 CSAP. 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 CSAP 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.  
       [0080] 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.  
       [0081] “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.  
       [0082] The term “antagonist” refers to a molecule which inhibits or attenuates the biological activity of CSAP. Antagonists may include proteins such as antibodies, nucleic acids, carbohydrates, small molecules, or any other compound or composition which modulates the activity of CSAP either by directly interacting with CSAP or by acting on components of the biological pathway in which CSAP participates.  
       [0083] 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 CSAP polypeptides can be prepared using intact polypeptides or using fragments containing small peptides of interest as the immunizing antigen. The polypeptide or oligopeptide used to immunize an animal (e.g., a mouse, a rat, or a rabbit) can be derived from the translation of RNA, or synthesized chemically, and can be conjugated to a carrier protein if desired. Commonly used carriers that are chemically coupled to peptides include bovine serum albumin, thyroglobulin, and keyhole limpet hemocyanin (KLH). The coupled peptide is then used to immunize the animal.  
       [0084] 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.  
       [0085] 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 maybe 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.)  
       [0086] 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).  
       [0087] The term “spiegelmer” refers to an aptamer which includes L-DNA, L-RNA, or other left-handed nucleotide derivatives or nucleotide-like molecules. Aptamers containing left-handed nucleotides are resistant to degradation by naturally occurring enzymes, which normally act on substrates containing right-handed nucleotides.  
       [0088] 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.  
       [0089] 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 CSAP, or of any oligopeptide thereof, to induce a specific immune response in appropriate animals or cells and to bind with specific antibodies.  
       [0090] “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′.  
       [0091] 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 CSAP or fragments of CSAP 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.).  
       [0092] “Consensus sequence” refers to a nucleic acid sequence which has been subjected to repeated DNA sequence analysis to resolve uncalled bases, extended using the XL-PCR kit (Applied Biosystems, Foster City Calif.) in the 5′ and/or the 3′ direction, and resequenced, or which has been assembled from one or more overlapping cDNA, EST, or genomic DNA fragments using a computer program for fragment assembly, such as the GELVIEW fragment assembly system (GCG, Madison Wis.) or Phrap (University of Washington, Seattle Wash.). Some sequences have been both extended and assembled to produce the consensus sequence.  
       [0093] “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                  
 
       [0094] 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.  
       [0095] 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.  
       [0096] The term “derivativ” refers to a chemically modified polynucleotide or polypeptide. Chemical modifications of a polynucleotide can include, for example, replacement of hydrogen by an alkyl, acyl, hydroxyl, or amino group. A derivative polynucleotide encodes a polypeptide which retains at least one biological or immunological function of the natural molecule. A derivative polypeptide is one modified by glycosylation, pegylation, or any similar process that retains at least one biological or immunological function of the polypeptide from which it was derived.  
       [0097] 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.  
       [0098] “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.  
       [0099] “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.  
       [0100] A “fragment” is a unique portion of CSAP or the polynucleotide encoding CSAP 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, maybe 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, maybe encompassed by the present embodiments.  
       [0101] A fragment of SEQ ID NO:15-28 comprises a region of unique polynucleotide sequence that specifically identifies SEQ ID NO: 15-28, for example, as distinct from any other sequence in the genome from which the fragment was obtained. A fragment of SEQ ID NO:15-28 is useful, for example, in hybridization and amplification technologies and in analogous methods that distinguish SEQ ID NO:15-28 from related polynucleotide sequences. The precise length of a fragment of SEQ ID NO:15-28 and the region of SEQ ID NO: 15-28 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 fragment of SEQ ID NO:1-14 is encoded by a fragment of SEQ ID NO:15-28. A fragment of SEQ ID NO:1-14 comprises a region of unique amino acid sequence that specifically identifies SEQ ID NO:1-14. For example, a fragment of SEQ ID NO:1-14 is useful as an immunogenic peptide for the development of antibodies that specifically recognize SEQ ID NO:1-14. The precise length of a fragment of SEQ ID NO:1-14 and the region of SEQ ID NO:1-14 to which the fragment corresponds are routinely determinable by one of ordinary skill in the art based on the intended purpose for the fragment.  
       [0103] 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.  
       [0104] “Homology” refers to sequence similarity or, interchangeably, sequence identity, between two or more polynucleotide sequences or two or more polypeptide sequences.  
       [0105] 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.  
       [0106] 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.  
       [0107] Alternatively, a suite of commonly used and freely available sequence comparison algorithms is provided by the National Center for Biotechnology Information (NCBI) Basic Local Alignment Search Tool (BLAST) (Altschul, S. F. et al. (1990) J. Mol. Biol. 215:403-410), which is available from several sources, including the NCBI, Bethesda, Md., and on the Internet at http://www.ncbi.nlm.nih.gov/BLAST/. The BLAST software suite includes various sequence analysis programs including “blastn,” that is used to align a known polynucleotide sequence with other polynucleotide sequences from a variety of databases. Also available is a tool called “BLAST 2 Sequences” that is used for direct pairwise comparison of two nucleotide sequences. “BLAST 2 Sequences” can be accessed and used interactively at http://www.ncbi.nlm.nih.gov/gorf/bl2.html. The “BLAST 2 Sequences” tool can be used for both blastn and blastp (discussed below). BLAST programs are commonly used with gap and other parameters set to default settings. For example, to compare two nucleotide sequences, one may use blastn with the “BLAST 2 Sequences” tool Version 2.0.12 (Apr. 21, 2000) set at default parameters. Such default parameters may be, for example:  
       [0108] Matrix: BLOSUM62  
       [0109] Reward for match: 1  
       [0110] Penalty for mismatch: −2  
       [0111] Open Gap: 5 and Extension Gap: 2 penalties  
       [0112] Gap x drop-off: 50  
       [0113] Expect: 10  
       [0114] Word Size: 11  
       [0115] Filter: on  
       [0116] 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 maybe measured.  
       [0117] 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.  
       [0118] 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.  
       [0119] Percent identity between polypeptide sequences may be determined using the default parameters of the CLUSTAL V algorithm as incorporated into the MGALIGN version 3.12e sequence alignment program (described and referenced above). For pairwise alignments of polypeptide sequences using CLUSTAL V, the default parameters are set as follows: Ktuple=1, gap penalty=3, window=5, and “diagonals saved”=5. The PAM250 matrix is selected as the default residue weight table. As with polynucleotide alignments, the percent identity is reported by CLUSTAL V as the “percent similarity” between aligned polypeptide sequence pairs.  
       [0120] 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:  
       [0121] Matrix: BLOSUM62  
       [0122] Open Gap: 11 and Extension Gap: 1 penalties  
       [0123] Gap x drop-off: 50  
       [0124] Expect: 10  
       [0125] Word Size: 3  
       [0126] Filter: on  
       [0127] 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.  
       [0128] “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.  
       [0129] 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.  
       [0130] “Hybridization” refers to the process by which a polynucleotide strand anneals with a complementary strand through base pairing under defined hybridization conditions. Specific hybridization is an indication that two nucleic acid sequences share a high degree of complementarity. Specific hybridization complexes form under permissive annealing conditions and remain hybridized after the “washing” step(s). The washing step(s) is particularly important in determining the stringency of the hybridization process, with more stringent conditions allowing less non-specific binding, i.e., binding between pairs of nucleic acid strands that are not perfectly matched. Permissive conditions for annealing of nucleic acid sequences are routinely determinable by one of ordinary skill in the art and may be consistent among hybridization experiments, whereas wash conditions may be varied among experiments to achieve the desired stringency, and therefore hybridization specificity. Permissive annealing conditions occur, for example, at 68° C. in the presence of about 6×SSC, about 1% (w/v) SDS, and about 100 μg/ml sheared, denatured salmon sperm DNA.  
       [0131] Generally, stringency of hybridization is expressed, in part, with reference to the temperature under which the wash step is carried out. Such wash temperatures are typically selected to be about 5° C. to 20° C. lower than the thermal melting point (T m ) for the specific sequence at a defined ionic strength and pH. The T m  is the temperature (under defined ionic strength and pH) at which 50% of the target sequence hybridizes to a perfectly matched probe. An equation for calculating T m  and conditions for nucleic acid hybridization are well known and can be found in Sambrook, J. et al. (1989)  Molecular Cloning: A Laboratory Manual,  2 nd  ed., vol. 1-3, Cold Spring Harbor Press, Plainview N.Y.; specifically see volume 2, chapter 9.  
       [0132] 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.  
       [0133] 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).  
       [0134] 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.  
       [0135] “Immune respons” can refer to conditions associated with inflammation, trauma, immune disorders, or infectious or genetic disease, etc. These conditions can be characterized by expression of various factors, e.g., cytokines, chemokines, and other signaling molecules, which may affect cellular and systemic defense systems.  
       [0136] An “immunogenic fragment” is a polypeptide or oligopeptide fragment of CSAP 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 CSAP which is useful in any of the antibody production methods disclosed herein or known in the art.  
       [0137] The term “microarray” refers to an arrangement of a plurality of polynucleotides, polypeptides, or other chemical compounds on a substrate.  
       [0138] The terms “element” and “array element” refer to a polynucleotide, polypeptide, or other chemical compound having a unique and defined position on a microarray.  
       [0139] The term “modulate” refers to a change in the activity of CSAP. For example, modulation may cause an increase or a decrease in protein activity, binding characteristics, or any other biological, functional, or immunological properties of CSAP.  
       [0140] 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.  
       [0141] “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.  
       [0142] “Peptide nucleic acid” (PNA) refers to an antisense molecule or anti-gene agent which comprises an oligonucleotide of at least about 5 nucleotides in length linked to a peptide backbone of amino acid residues ending in lysine. The terminal lysine confers solubility to the composition. PNAs preferentially bind complementary single stranded DNA or RNA and stop transcript elongation, and may be pegylated to extend their lifespan in the cell.  
       [0143] “Post-translational modification” of an CSAP may involve lipidation, glycosylation, phosphorylation, acetylation, racemization, proteolytic cleavage, and other modifications known in the art. These processes may occur synthetically or biochemically. Biochemical modifications will vary by cell type depending on the enzymatic milieu of CSAP.  
       [0144] “Probe” refers to nucleic acid sequences encoding CSAP, their complements, or fragments thereof, which are used to detect identical, allelic or related nucleic acid sequences. Probes are isolated oligonucleotides or polynucleotides attached to a detectable label or reporter molecule. Typical labels include radioactive isotopes, ligands, chemiluminescent agents, and enzymes. “Primers” are short nucleic acids, usually DNA oligonucleotides, which may be annealed to a target polynucleotide by complementary base-pairing. The primer may then be extended along the target DNA strand by a DNA polymerase enzyme. Primer pairs can be used for amplification (and identification) of a nucleic acid sequence, e.g., by the polymerase chain reaction (PCR).  
       [0145] 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.  
       [0146] 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.).  
       [0147] Oligonucleotides for use as primers are selected using software known in the art for such purpose. For example, OLIGO 4.06 software is useful for the selection of PCR primer pairs of up to 100 nucleotides each, and for the analysis of oligonucleotides and larger polynucleotides of up to 5,000 nucleotides from an input polynucleotide sequence of up to 32 kilobases. Similar primer selection programs have incorporated additional features for expanded capabilities. For example, the PrimOU primer selection program (available to the public from the Genome Center at University of Texas South West Medical Center, Dallas Tex.) is capable of choosing specific primers from megabase sequences and is thus useful for designing primers on a genome-wide scope. The Primer3 primer selection program (available to the public from the Whitehead Institute/MIT Center for Genome Research, Cambridge Mass.) allows the user to input a “mispriming library,” in which sequences to avoid as primer binding sites are user-specified. Primer3 is useful, in particular, for the selection of oligonucleotides for microarrays. (The source code for the latter two primer selection programs may also be obtained from their respective sources and modified to meet the user&#39;s specific needs.) The PrimeGen program (available to the public from the UK Human Genome Mapping Project Resource Centre, Cambridge UK) designs primers based on multiple sequence alignments, thereby allowing selection of primers that hybridize to either the most conserved or least conserved regions of aligned nucleic acid sequences. Hence, this program is useful for identification of both unique and 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, micro array 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.  
       [0148] 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.  
       [0149] 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.  
       [0150] 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.  
       [0151] “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.  
       [0152] An “RNA equivalent,” in reference to a DNA sequence, is composed of the same linear sequence of nucleotides as the reference DNA sequence with the exception that all occurrences of the nitrogenous base thymine are replaced with uracil, and the sugar backbone is composed of ribose instead of deoxyribose.  
       [0153] The term “sample” is used in its broadest sense. A sample suspected of containing CSAP, nucleic acids encoding CSAP, 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.  
       [0154] 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.  
       [0155] 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.  
       [0156] A “substitution” refers to the replacement of one or more amino acid residues or nucleotides by different amino acid residues or nucleotides, respectively.  
       [0157] “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.  
       [0158] A “transcript image” or “expression profile” refers to the collective pattern of gene expression by a particular cell type or tissue under given conditions at a given time.  
       [0159] “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.  
       [0160] 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.  
       [0161] A “variant” of a particular nucleic acid sequence is defined as a nucleic acid sequence having at least 40% sequence identity to the particular nucleic acid sequence over a certain length of one of the nucleic acid sequences using blastn with the “BLAST 2 Sequences” tool Version 2.0.9 (May 7, 1999) set at default parameters. Such a pair of nucleic acids may show, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% or greater sequence identity over a certain defined length. A variant 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.  
       [0162] A “variant” of a particular polypeptide sequence is defined as a polypeptide sequence having at least 40% sequence identity to the particular polypeptide sequence over a certain length of one of the polypeptide sequences using blastp with the “BLAST 2 Sequences” tool Version 2.0.9 (May 7, 1999) set at default parameters. Such a pair of polypeptides may show, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% or greater sequence identity over a certain defined length of one of the polypeptides.  
       [0163] The Invention  
       [0164] The invention is based on the discovery of new human cytoskeleton-associated proteins (CSAP), the polynucleotides encoding CSAP, and the use of these compositions for the diagnosis, treatment, or prevention of cell proliferative disorders, viral infections, and neurological disorders.  
       [0165] 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.  
       [0166] Table 2 shows sequences with homology to the polypeptides of the invention as identified by BLAST analysis against the GenBank protein (genpept) database. Columns 1 and 2 show the polypeptide sequence identification number (Polypeptide SEQ ID NO:) and the corresponding Incyte polypeptide sequence number (Incyte Polypeptide ID) for polypeptides of the invention. Column 3 shows the GenBank identification number (GenBank ID NO:) of the nearest GenBank homolog. Column 4 shows the probability scores for the matches between each polypeptide and its homolog(s). Column 5 shows the annotation of the GenBankhomolog(s) along with relevant citations where applicable, all of which are expressly incorporated by reference herein.  
       [0167] Table 3 shows various structural features of the polypeptides of the invention. Columns 1 and 2 show the polypeptide sequence identification number (SEQ ID NO:) and the corresponding Incyte polypeptide sequence number (Incyte Polypeptide ID) for each polypeptide of the invention. Column 3 shows the number of amino acid residues in each polypeptide. Column 4 shows potential phosphorylation sites, and column 5 shows potential glycosylation sites, as determined by the MOTIFS program of the GCG sequence analysis software package (Genetics Computer Group, Madison Wis.). Column 6 shows amino acid residues comprising signature sequences, domains, and motifs. Column 7 shows analytical methods for protein structure/function analysis and in some cases, searchable databases to which the analytical methods were applied.  
       [0168] Together, Tables 2 and 3 summarize the properties of polypeptides of the invention, and these properties establish that the claimed polypeptides are cytoskeleton-associated proteins. For example, SEQ ID NO:1 is 93% identical to mouse NBIA, a Band 4.1 family cytoskeletal protein (GenBank ID g466548) as determined by the Basic Local Alignment Search Tool (BLAST). (See Table 2.) The BLAST probability score is 1.5e-287, which indicates the probability of obtaining the observed polypeptide sequence alignment by chance. SEQ ID NO:1 also contains a FERM/Band 4.1 family 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:1 is an Band 4.1 family cytoskeletal protein. In an alternative example, SEQ ID NO:8 is 84% identical to  Rattus norvegicus  nadrin, an actin-filament regulating protein (GenBank ID g9971185) 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:8 also contains a Rho-GAP (GTPase activating) site 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 MOTIIFS analyses provide further corroborative evidence that SEQ ID NO:8 is a nadrin. In an alternative example, SEQ ID NO:11 is 68% identical to sea urchin dynein, intermediate chain (GenBank ID g927639) as determined by the Basic Local Alignment Search Tool (BLAST). (See Table 2.) The BLAST probability score is 1.5e-222, which indicates the probability of obtaining the observed polypeptide sequence alignment by chance. SEQ ID NO:11 also contains a WD repeat domain characteristic of dynein intermediate chains, 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:11 is a cytoplasmic dynein intermediate chain. SEQ ID NO:2-7, SEQ ID NO:9-10, and SEQ ID NO:12-14 were analyzed and annotated in a similar manner. The algorithms and parameters for the analysis of SEQ ID NO:1-14 are described in Table 7.  
       [0169] As shown in Table 4, the full length polynucleotide sequences of the present invention were assembled using cDNA sequences or coding (exon) sequences derived from genomic DNA, or any combination of these two types of sequences. Columns 1 and 2 list the polynucleotide sequence identification number (Polynucleotide SEQ ID NO:) and the corresponding Incyte polynucleotide consensus sequence number (Incyte Polynucleotide ID) for each polynucleotide of the invention. Column 3 shows the length of each polynucleotide sequence in basepairs. Column 4 lists fragments of the polynucleotide sequences which are useful, for example, in hybridization or amplification technologies that identify SEQ ID NO:15-28 or that distinguish between SEQ ID NO:15-28 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.  
       [0170] 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, 7011045F8 is the identification number of an Incyte cDNA sequence, and KIDNNOC01 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., 71108830V1). Alternatively, the identification numbers in column 5 may refer to GenBank cDNAs or ESTs (e.g., g1548017) 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 maybe derived from the NCBI RefSeq Nucleotide Sequence Records Database (i.e., those sequences including the designation “NM” or “NT”) or the NCBI RefSeq Protein Sequence Records (i.e., those sequences including the designation “NP”). Alternatively, the identification numbers in column 5 may refer to assemblages of both cDNA and Genscan-predicted exons brought together by an “exon stitching” algorithm. For example, FL_XXXXXX_N 1— N 2— YYYYY_N 3— N 4  represents a “stitched” sequence in which XXXXXX is the identification number of the cluster of sequences to which the algorithm was applied, and YYYYY is the number of the prediction generated by the algorithm, and N 1,2,3 . . .  , if present, represent specific exons that may have been manually edited during analysis (See Example V). Alternatively, the identification numbers in column 5 may refer to assemblages of exons brought together by an “exon-stretching” algorithm. For example, FLXXXXXX_gAAAAA_gBBBBB — 1_N is the identification number of a “stretched” sequence, with XXXXXX being the Incyte project identification number, gAAAAA being the GenBank identification number of the human genomic sequence to which the “exon-stretching” algorithm was applied, gBBBBB being the GenBank identification number or NCBI RefSeq identification number of the nearest GenBank protein homolog, and N referring to specific exons (See Example V). In instances where a RefSeq sequence was used as a protein homolog for the “exon-stretching” algorithm, a RefSeq identifier (denoted by “NM,” “NP,” or “NT”) may be used in place of the GenBank identifier (i.e., gBBBBB).  
       [0171] 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.                  
 
       [0172] 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.  
       [0173] 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.  
       [0174] The invention also encompasses CSAP variants. A preferred CSAP 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 CSAP amino acid sequence, and which contains at least one functional or structural characteristic of CSAP.  
       [0175] The invention also encompasses polynucleotides which encode CSAP. In a particular embodiment, the invention encompasses a polynucleotide sequence comprising a sequence selected from the group consisting of SEQ ID NO:15-28, which encodes CSAP. The polynucleotide sequences of SEQ ID NO: 15-28, as presented in the Sequence Listing, embrace the equivalent RNA sequences, wherein occurrences of the nitrogenous base thymine are replaced with uracil, and the sugar backbone is composed of ribose instead of deoxyribose.  
       [0176] The invention also encompasses a variant of a polynucleotide sequence encoding CSAP. 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 CSAP. 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:15-28 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: 15-28. Any one of the polynucleotide variants described above can encode an amino acid sequence which contains at least one functional or structural characteristic of CSAP.  
       [0177] In addition, or in the alternative, a polynucleotide variant of the invention is a splice variant of a polynucleotide sequence encoding CSAP. A splice variant may have portions which have significant sequence identity to the polynucleotide sequence encoding CSAP, but will generally have a greater or lesser number of polynucleotides due to additions or deletions of blocks of sequence arising from alternate splicing of exons during mRNA processing. A splice variant may have less than about 70%, or alternatively less than about 60%, or alternatively less than about 50% polynucleotide sequence identity to the polynucleotide sequence encoding CSAP over its entire length; however, portions of the splice variant will have at least about 70%, or alternatively at least about 85%, or alternatively at least about 95%, or alternatively 100% polynucleotide sequence identity to portions of the polynucleotide sequence encoding CSAP. Any one of the splice variants described above can encode an amino acid sequence which contains at least one functional or structural characteristic of CSAP.  
       [0178] 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 CSAP, 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 CSAP, and all such variations are to be considered as being specifically disclosed.  
       [0179] Although nucleotide sequences which encode CSAP and its variants are generally capable of hybridizing to the nucleotide sequence of the naturally occurring CSAP under appropriately selected conditions of stringency, it may be advantageous to produce nucleotide sequences encoding CSAP 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 CSAP 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.  
       [0180] The invention also encompasses production of DNA sequences which encode CSAP and CSAP 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 CSAP or any fragment thereof.  
       [0181] 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:15-28 and fragments thereof under various conditions of stringency. (See, e.g., Wahl, G. M. and S. L. Berger (1987) Methods Enzymol. 152:399-407; Kimmel, A. R. (1987) Methods Enzymol. 152:507-511.) Hybridization conditions, including annealing and wash conditions, are described in “Definitions.” 
       [0182] Methods for DNA sequencing are well known in the art and may be used to practice any of the embodiments of the invention. The methods may employ such enzymes as the Klenow fragment of DNA polymerase I, SEQUENASE (US Biochemical, Cleveland Ohio), Taq polymerase (Applied Biosystems), thermostable T7 polymerase (Amersham Pharmacia Biotech, Piscataway N.J.), or combinations of polymerases and proofreading exonucleases such as those found in the ELONGASE amplification system (Life Technologies, Gaithersburg Md.). Preferably, sequence preparation is automated with machines such as the MICROLAB 2200 liquid transfer system (Hamilton, Reno Nev.), PTC200 thermal cycler (MJ Research, Watertown Mass.) and ABI CATALYST 800 thermal cycler (Applied Biosystems). Sequencing is then carried out using either the ABI 373 or 377 DNA sequencing system (Applied Biosystems), the MEGABACE 1000 DNA sequencing system (Molecular Dynamics, Sunnyvale Calif.), or other systems known in the art. The resulting sequences are analyzed using a variety of algorithms which are well known in the art. (See, e.g., Ausubel, F. M. (1997)  Short Protocols in Molecular Biology,  John Wiley &amp; Sons, New York N.Y., unit 7.7; Meyers, R. A. (1995)  Molecular Biology and Biotechnology,  Wiley VCH, New York N.Y., pp. 856-853.)  
       [0183] The nucleic acid sequences encoding CSAP may be extended utilizing a partial nucleotide sequence and employing various PCR-based methods known in the art to detect upstream sequences, such as promoters and regulatory elements. For example, one method which may be employed, restriction-site PCR, uses universal and nested primers to amplify unknown sequence from genomic DNA within a cloning vector. (See, e.g., Sarkar, G. (1993) PCR Methods Applic. 2:318-322.) Another method, inverse PCR, uses primers that extend in divergent directions to amplify unknown sequence from a circularized template. The template is derived from restriction fragments comprising a known genomic locus and surrounding sequences. (See, e.g., Triglia, T. et al. (1988) Nucleic Acids Res. 16:8186.) A third method, capture PCR, involves PCR amplification of DNA fragments adjacent to known sequences inhuman and yeast artificial chromosome DNA. (See, e.g., Lagerstrom, M. et al. (1991) PCR Methods Applic. 1:111-119.) In this method, multiple restriction enzyme digestions and ligations may be used to insert an engineered double-stranded sequence into a region of unknown sequence before performing PCR. Other methods which may be used to retrieve unknown sequences are known in the art. (See, e.g., Parker, J. D. et al. (1991) Nucleic Acids Res. 19:3055-3060). Additionally, one may use PCR, nested primers, and PROMOTERFINDER libraries (Clontech, Palo Alto Calif.) to walk genomic DNA. This procedure avoids the need to screen libraries and is useful in finding intron/exon junctions. For all PCR-based methods, primers may be designed using commercially available software, such as OLIGO 4.06 primer analysis software (National Biosciences, Plymouth Minn.) or another appropriate program, to be about 22 to 30 nucleotides in length, to have a GC content of about 50% or more, and to anneal to the template at temperatures of about 68° C. to 72° C.  
       [0184] 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.  
       [0185] 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. Outputlight 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.  
       [0186] In another embodiment of the invention, polynucleotide sequences or fragments thereof which encode CSAP may be cloned in recombinant DNA molecules that direct expression of CSAP, 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 CSAP.  
       [0187] The nucleotide sequences of the present invention can be engineered using methods generally known in the art in order to alter CSAP-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.  
       [0188] 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 CSAP, such as its biological or enzymatic activity or its ability to bind to other molecules or compounds. DNA shuffling is a process by which a library of gene variants is produced using PCR-mediated recombination of gene fragments. The library is then subjected to selection or screening procedures that identify those gene variants with the desired properties. These preferred variants may then be pooled and further subjected to recursive rounds of DNA shuffling and selection/screening. Thus, genetic diversity is created through “artificial” breeding and rapid molecular evolution. For example, fragments of a single gene containing random point mutations may be recombined, screened, and then reshuffled until the desired properties are optimized. Alternatively, fragments of a given gene may be recombined with fragments of homologous genes in the same gene family, either from the same or different species, thereby maximizing the genetic diversity of multiple naturally occurring genes in a directed and controllable manner.  
       [0189] In another embodiment, sequences encoding CSAP 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, CSAP itself or a fragment thereof may be synthesized using chemical methods. For example, peptide synthesis can be performed using various solution-phase or solid-phase techniques. (See, e.g., Creighton, T. (1984)  Proteins, Structures and Molecular Properties,  W H Freeman, New York N. Y., pp. 55-60; and Roberge, J. Y. et al. (1995) Science 269:202-204.) Automated synthesis may be achieved using the ABI 431A peptide synthesizer (Applied Biosystems). Additionally, the amino acid sequence of CSAP, 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.  
       [0190] 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.)  
       [0191] In order to express a biologically active CSAP, the nucleotide sequences encoding CSAP or derivatives thereof may be inserted into an appropriate expression vector, i.e., a vector which contains the necessary elements for transcriptional and translational control of the inserted coding sequence in a suitable host. These elements include regulatory sequences, such as enhancers, constitutive and inducible promoters, and 5′ and 3′ untranslated regions in the vector and in polynucleotide sequences encoding CSAP. Such elements may vary in their strength and specificity. Specific initiation signals may also be used to achieve more efficient translation of sequences encoding CSAP. Such signals include the ATG initiation codon and adjacent sequences, e.g. the Kozak sequence. In cases where sequences encoding CSAP 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.)  
       [0192] Methods which are well known to those skilled in the art may be used to construct expression vectors containing sequences encoding CSAP 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.)  
       [0193] A variety of expression vector/host systems may be utilized to contain and express sequences encoding CSAP. 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, maybe used for delivery of nucleotide sequences to the targeted organ, tissue, or cell population. (See, e.g., Di Nicola, M. et al. (1998) Cancer Gen. Ther. 5(6):350-356; Yu, M. et al. (1993) Proc. Natl. Acad. Sci. USA 90(13):6340-6344; Buller, R. M. et al. (1985) Nature 317(6040):813-815; McGregor, D. P. et al. (1994) Mol. Immunol. 31(3):219-226; and Verma, I. M. and N. Somia (1997) Nature 389:239-242.) The invention is not limited by the host cell employed.  
       [0194] In bacterial systems, a number of cloning and expression vectors may be selected depending upon the use intended for polynucleotide sequences encoding CSAP. For example, routine cloning, subcloning, and propagation of polynucleotide sequences encoding CSAP 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 CSAP 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 CSAP are needed, e.g. for the production of antibodies, vectors which direct high level expression of CSAP may be used. For example, vectors containing the strong, inducible SP6 or T7 bacteriophage promoter may be used.  
       [0195] Yeast expression systems may be used for production of CSAP. 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.)  
       [0196] Plant systems may also be used for expression of CSAP. Transcription of sequences encoding CSAP may be driven by viral promoters, e.g., the 35S and 19S promoters of CaMV used alone or in combination with the omega leader sequence from TMV (Takamatsu, N. (1987) EMBO J. 6:307-311). Alternatively, plant promoters such as the small subunit of RUBISCO or heat shock promoters maybe used. (See, e.g., Coruzzi, G. et al. (1984) EMBO J. 3:1671-1680; Broglie, R. et al. (1984) Science 224:838-843; and Winter, J. et al. (1991) Results Probl. Cell Differ. 17:85-105.) These constructs can be introduced into plant cells by direct DNA transformation or pathogen-mediated transfection. (See, e.g.,  The McGraw Hill Yearbook of Science and Technology  (1992) McGraw Hill, New York N.Y., pp. 191-196.)  
       [0197] 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 CSAP may be ligated into an adenovirus transcription/translation complex consisting of the late promoter and tripartite leader sequence. Insertion in a non-essential E1 or E3 region of the viral genome may be used to obtain infective virus which expresses CSAP 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.  
       [0198] 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.)  
       [0199] For long term production of recombinant proteins in mammalian systems, stable expression of CSAP in cell lines is preferred. For example, sequences encoding CSAP 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.  
       [0200] Any number of selection systems may be used to recover transformed cell lines. These include, but are not limited to, the herpes simplex virus thymidine kinase and adenine phosphoribosyltransferase genes, for use in tk and apr cells, respectively. (See, e.g., Wigler, M. et al. (1977) Cell 11:223-232; Lowy, I. et al. (1980) Cell 22:817-823.) Also, antimetabolite, antibiotic, or herbicide resistance can be used as the basis for selection. For example, dhfr confers resistance to methotrexate; neo confers resistance to the aminoglycosides neomycin and G-418; and als and pat confer resistance to chlorsulfuron and phosphinotricin acetyltransferase, respectively. (See, e.g., Wigler, M. et al. (1980) Proc. Natl. Acad. Sci. USA 77:3567-3570; Colbere-Garapin, F. et al. (1981) J. Mol. Biol. 150:1-14.) Additional selectable genes have been described, e.g., tipB and hisD, which alter cellular requirements for metabolites. (See, e.g., Hartman, S. C. and R. C. Mulligan (1988) Proc. Natl. Acad. Sci. USA 85:8047-8051.) Visible markers, e.g., anthocyanins, green fluorescent proteins (GFP; Clontech), B glucuronidase and its substrate B-glucuronide, or luciferase and its substrate luciferin may be used. These markers can be used not only to identify transformants, but also to quantify the amount of transient or stable protein expression attributable to a specific vector system. (See, e.g., Rhodes, C. A. (1995) Methods Mol. Biol. 55:121-131.)  
       [0201] 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 CSAP is inserted within a marker gene sequence, transformed cells containing sequences encoding CSAP can be identified by the absence of marker gene function. Alternatively, a marker gene can be placed in tandem with a sequence encoding CSAP 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.  
       [0202] In general, host cells that contain the nucleic acid sequence encoding CSAP and that express CSAP 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.  
       [0203] Immunological methods for detecting and measuring the expression of CSAP 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 CSAP is preferred, but a competitive binding assay may be employed. These and other assays are well known in the art. (See, e.g., Hampton, R. et al. (1990)  Serological Methods, a Laboratory Manual,  APS Press, St. Paul Minn., Sect. IV; Coligan, J. E. et al. (1997)  Current Protocols in Immunology,  Greene Pub. Associates and Wiley-Interscience, New York N.Y.; and Pound, J. D. (1998)  Immunochemical Protocols,  Humana Press, Totowa N.J.)  
       [0204] 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 CSAP include oligolabeling, nick translation, end-labeling, or PCR amplification using a labeled nucleotide. Alternatively, the sequences encoding CSAP, 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 maybe 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.  
       [0205] Host cells transformed with nucleotide sequences encoding CSAP 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 CSAP maybe designed to contain signal sequences which direct secretion of CSAP through a prokaryotic or eukaryotic cell membrane.  
       [0206] 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.  
       [0207] In another embodiment of the invention, natural, modified, or recombinant nucleic acid sequences encoding CSAP 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 CSAP protein containing a heterologous moiety that can be recognized by a commercially available antibody may facilitate the screening of peptide libraries for inhibitors of CSAP activity. Heterologous protein and peptide moieties may also facilitate purification of fusion proteins using commercially available affinity matrices. Such moieties include, but are not limited to, glutathione S-transferase (GST), maltose binding protein (MBP), thioredoxin (Trx), calmodulin binding peptide (CBP), 6-His, FLAG, c-myc, and hemagglutinin (HA). GST, MBP, Trx, CBP, and 6-His enable purification of their cognate fusion proteins on immobilized glutathione, maltose, phenylarsine oxide, calmodulin, and metal-chelate resins, respectively. FLAG; c-myc, and hemagglutinin (HA) enable immunoaffinity purification of fusion proteins using commercially available monoclonal and polyclonal antibodies that specifically recognize these epitope tags. A fusion protein may also be engineered to contain a proteolytic cleavage site located between the CSAP encoding sequence and the heterologous protein sequence, so that CSAP may be cleaved away from the heterologous moiety following purification. Methods for fusion protein expression and purification are discussed in Ausubel (1995, supra, ch. 10). A variety of commercially available kits may also be used to facilitate expression and purification of fusion proteins.  
       [0208] In a further embodiment of the invention, synthesis of radiolabeled CSAP 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.  
       [0209] CSAP of the present invention or fragments thereof may be used to screen for compounds that specifically bind to CSAP. At least one and up to a plurality of test compounds may be screened for specific binding to CSAP. Examples of test compounds include antibodies, oligonucleotides, proteins (e.g., receptors), or small molecules.  
       [0210] In one embodiment, the compound thus identified is closely related to the natural ligand of CSAP, 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 CSAP 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 CSAP, either as a secreted protein or on the cell membrane. Preferred cells include cells from mammals, yeast, Drosophila, or  E. coli.  Cells expressing CSAP or cell membrane fractions which contain CSAP are then contacted with a test compound and binding, stimulation, or inhibition of activity of either CSAP or the compound is analyzed.  
       [0211] An assay may simply test binding of a test compound to the polypeptide, wherein binding is detected by a fluorophore, radioisotope, enzyme conjugate, or other detectable label. For example, the assay may comprise the steps of combining at least one test compound with CSAP, either in solution or affixed to a solid support, and detecting the binding of CSAP to the compound. Alternatively, the assay may detect or measure binding of a test compound in the presence of a labeled competitor. Additionally, the assay may be carried out using cell-free preparations, chemical libraries, or natural product mixtures, and the test compound(s) may be free in solution or affixed to a solid support.  
       [0212] CSAP of the present invention or fragments thereof may be used to screen for compounds that modulate the activity of CSAP. Such compounds may include agonists, antagonists, or partial or inverse agonists. In one embodiment, an assay is performed under conditions permissive for CSAP activity, wherein CSAP is combined with at least one test compound, and the activity of CSAP in the presence of a test compound is compared with the activity of CSAP in the absence of the test compound. A change in the activity of CSAP in the presence of the test compound is indicative of a compound that modulates the activity of CSAP. Alternatively, a test compound is combined with an in vitro or cell-free system comprising CSAP under conditions suitable for CSAP activity, and the assay is performed. In either of these assays, a test compound which modulates the activity of CSAP 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.  
       [0213] In another embodiment, polynucleotides encoding CSAP or their mammalian homologs may be “knocked out” in an animal model system using homologous recombination in embryonic stem (ES) cells. Such techniques are well known in the art and are useful for the generation of animal models of human disease. (See, e.g., U.S. Pat. No. 5,175,383 and U.S. Pat. No. 5,767,337.) For example, mouse ES cells, such as the mouse 129/SvJ cell line, are derived from the early mouse embryo and grown in culture. The ES cells are transformed with a vector containing the gene of interest disrupted by a marker gene, e.g., the neomycin phosphotransferase gene (neo; Capecchi, M. R. (1989) Science 244:1288-1292). The vector integrates into the corresponding region of the host genome by homologous recombination. Alternatively, homologous recombination takes place using the Cre-loxP system to knockout a gene of interest in a tissue- or developmental stage-specific manner (Marth, J. D. (1996) Clin. Invest. 97:1999-2002; Wagner, K. U. et al. (1997) Nucleic Acids Res. 25:4323-4330). Transformed ES cells are identified and microinjected into mouse cell blastocysts such as those from the C57BL/6 mouse strain. The blastocysts are surgically transferred to pseudopregnant dams, and the resulting chimeric progeny are genotyped and bred to produce heterozygous or homozygous strains. Transgenic animals thus generated may be tested with potential therapeutic or toxic agents.  
       [0214] Polynucleotides encoding CSAP 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).  
       [0215] Polynucleotides encoding CSAP 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 CSAP is injected into animal ES cells, and the injected sequence integrates into the animal cell genome. Transformed cells are injected into blastulae, and the blastulae are implanted as described above. Transgenic progeny or inbred lines are studied and treated with potential pharmaceutical agents to obtain information on treatment of a human disease. Alternatively, a mammal inbred to overexpress CSAP, e.g., by secreting CSAP in its milk, may also serve as a convenient source of that protein (Janne, J. et al. (1998) Biotechnol. Annu. Rev. 4:55-74).  
       [0216] Therapeutics  
       [0217] Chemical and structural similarity, e.g., in the context of sequences and motifs, exists between regions of CSAP and cytoskeleton-associated proteins. In addition, the expression of CSAP is closely associated with brain and neurological tissues, cardiovascular tissues, digestive tissues, and endocrine tissues. Therefore, CSAP appears to play a role in cell proliferative disorders, viral infections, and neurological disorders. In the treatment of disorders associated with increased CSAP expression or activity, it is desirable to decrease the expression or activity of CSAP. In the treatment of disorders associated with decreased CSAP expression or activity, it is desirable to increase the expression or activity of CSAP.  
       [0218] Therefore, in one embodiment, CSAP 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 CSAP. Examples of such disorders include, but are not limited to, a cell proliferative disorder such as actinic keratosis, arteriosclerosis, atherosclerosis, bursitis, cirrhosis, hepatitis, mixed connective tissue disease (MCID), myelofibrosis, paroxysmal nocturnal hemoglobinuria, polycythemia vera, psoriasis, primary thrombocythemia, and a cancer including adenocarcinoma, leukemia, lymphoma, melanoma, myeloma, sarcoma, teratocarcinoma, and, in particular, a cancer of the adrenal gland, bladder, bone, bone marrow, brain, breast, cervix, gall bladder, ganglia, gastrointestinal tract, heart, kidney, liver, lung, muscle, ovary, pancreas, parathyroid, penis, prostate, salivary glands, skin, spleen, testis, thymus, thyroid, and uterus; a viral infection such as those caused by adenoviruses (acute respiratory disease, pneumonia), arenaviruses (lymphocytic choriomeningitis), bunyaviruses (Hantavirus), coronaviruses (pneumonia, chronic bronchitis), hepadnaviruses (hepatitis), herpesviruses (herpes simplex virus, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus), flaviviruses (yellow fever), orthomyxoviruses (influenza), papillomaviruses (cancer), paramyxoviruses (measles, mumps), picornoviruses (rhinovirus, poliovirus, coxsackie-virus), polyomaviruses (BK virus, JC virus), poxviruses (smallpox), reovirus (Colorado tick fever), retroviruses (human immunodeficiency virus, human T lymphotropic virus), rhabdoviruses (rabies), rotaviruses (gastroenteritis), and togaviruses (encephalitis, rubella); and a neurological disorder such as epilepsy, ischemic cerebrovascular disease, stroke, cerebral neoplasms, Alzheimer&#39;s disease, Pick&#39;s disease, Huntington&#39;s disease, dementia, Parkinson&#39;s disease and other extrapyramidal disorders, amyotrophic lateral sclerosis and other motor neuron disorders, progressive neural muscular atrophy, retinitis pigmentosa, hereditary ataxias, multiple sclerosis and other demyelinating diseases, bacterial and viral meningitis, brain abscess, subdural empyema, epidural abscess, suppurative intracranial thrombophlebitis, myelitis and radiculitis, viral central nervous system disease, a prion disease including kuru, Creutzfeldt-Jakob disease, and Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, nutritional and metabolic diseases of the nervous system, neurofibromatosis, tuberous sclerosis, cerebelloretinal hemangioblastomatosis, encephalotrigeminal syndrome, mental retardation and other developmental disorders of the central nervous system, cerebral palsy, neuroskeletal disorders, autonomic nervous system disorders, cranial nerve disorders, spinal cord diseases, muscular dystrophy and other neuromuscular disorders, peripheral nervous system disorders, dermatomyositis and polymyositis; inherited, metabolic, endocrine, and toxic myopathies; myasthenia gravis, periodic paralysis, mental disorders including mood, anxiety, and schizophrenic disorders, seasonal affective disorder (SAD), akathesia, amnesia, catatonia, diabetic neuropathy, tardive dyskinesia, dystonias, paranoid psychoses, postherpetic neuralgia, and Tourette&#39;s disorder.  
       [0219] In another embodiment, a vector capable of expressing CSAP 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 CSAP including, but not limited to, those described above.  
       [0220] In a further embodiment, a composition comprising a substantially purified CSAP 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 CSAP including, but not limited to, those provided above.  
       [0221] In still another embodiment, an agonist which modulates the activity of CSAP may be administered to a subject to treat or prevent a disorder associated with decreased expression or activity of CSAP including, but not limited to, those listed above.  
       [0222] In a further embodiment, an antagonist of CSAP may be administered to a subject to treat or prevent a disorder associated with increased expression or activity of CSAP. Examples of such disorders include, but are not limited to, those cell proliferative disorders, viral infections, and neurological disorders described above. In one aspect, an antibody which specifically binds CSAP 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 CSAP.  
       [0223] In an additional embodiment, a vector expressing the complement of the polynucleotide encoding CSAP may be administered to a subject to treat or prevent a disorder associated with increased expression or activity of CSAP including, but not limited to, those described above.  
       [0224] In other embodiments, any of the proteins, antagonists, antibodies, agonists, complementary sequences, or vectors of the invention may be administered in combination with other appropriate therapeutic agents. Selection of the appropriate agents for use in combination therapy may be made by one of ordinary skill in the art, according to conventional pharmaceutical principles. The combination of therapeutic agents may act synergistically to effect the treatment or prevention of the various disorders described above. Using this approach, one may be able to achieve therapeutic efficacy with lower dosages of each agent, thus reducing the potential for adverse side effects.  
       [0225] An antagonist of CSAP may be produced using methods which are generally known in the art. In particular, purified CSAP may be used to produce antibodies or to screen libraries of pharmaceutical agents to identify those which specifically bind CSAP. Antibodies to CSAP 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.  
       [0226] For the production of antibodies, various hosts including goats, rabbits, rats, mice, humans, and others may be immunized by injection with CSAP 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.  
       [0227] It is preferred that the oligopeptides, peptides, or fragments used to induce antibodies to CSAP 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 CSAP amino acids maybe fused with those of another protein, such as KLH, and antibodies to the chimeric molecule may be produced.  
       [0228] Monoclonal antibodies to CSAP 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.)  
       [0229] In addition, techniques developed for the production of “chimeric antibodies,” such as the splicing of mouse antibody genes to human antibody genes to obtain a molecule with appropriate antigen specificity and biological activity, can be used. (See, e.g., Morrison, S. L. et al. (1984) Proc. Natl. Acad. Sci. USA 81:6851-6855; Neuberger, M. S. et al. (1984) Nature 312:604-608; and Takeda, S. et al. (1985) Nature 314:452-454.) Alternatively, techniques described for the production of single chain antibodies may be adapted, using methods known in the art, to produce CSAP-specific single chain antibodies. Antibodies with related specificity, but of distinct idiotypic composition, maybe generated by chain shuffling from random combinatorial immunoglobulin libraries. (See, e.g., Burton, D. R. (1991) Proc. Natl. Acad. Sci. USA 88:10134-10137.)  
       [0230] Antibodies may also be produced by inducing in vivo production in the lymphocyte population or by screening immunoglobulin libraries or panels of highly specific binding reagents as disclosed in the literature. (See, e.g., Orlandi, R. et al. (1989) Proc. Natl. Acad. Sci. USA 86:3833-3837; Winter, G. et al. (1991) Nature 349:293-299.)  
       [0231] Antibody fragments which contain specific binding sites for CSAP may also be generated. For example, such fragments include, but are not limited to, F(ab′) 2  fragments produced by pepsin digestion of the antibody molecule and Fab fragments generated by reducing the disulfide bridges of the F(ab′)2 fragments. Alternatively, Fab expression libraries may be constructed to allow rapid and easy identification of monoclonal Fab fragments with the desired specificity. (See, e.g., Huse, W. D. et al. (1989) Science 246:1275-1281.)  
       [0232] 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 CSAP and its specific antibody. A two-site, monoclonal-based immunoassay utilizing monoclonal antibodies reactive to two non-interfering CSAP epitopes is generally used, but a competitive binding assay may also be employed (Pound, supra).  
       [0233] Various methods such as Scatchard analysis in conjunction with radioimmunoassay techniques may be used to assess the affinity of antibodies for CSAP. Affinity is expressed as an association constant, K a , which is defined as the molar concentration of CSAP-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 CSAP epitopes, represents the average affinity, or avidity, of the antibodies for CSAP. The K a  determined for a preparation of monoclonal antibodies, which are monospecific for a particular CSAP 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 CSAP-antibody complex must withstand rigorous manipulations. Low-affinity antibody preparations with K a  ranging from about 10 6  to 10 7  L/mole are preferred for use in immunopurification and similar procedures which ultimately require dissociation of CSAP, 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.).  
       [0234] 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 CSAP-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.)  
       [0235] In another embodiment of the invention, the polynucleotides encoding CSAP, 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 CSAP. 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 CSAP. (See, e.g., Agrawal, S., ed. (1996)  Antisense Therapeutics,  Humana Press Inc., Totawa N.J.)  
       [0236] In therapeutic use, any gene delivery system suitable for introduction of the antisense sequences into appropriate target cells can be used. Antisense sequences can be delivered intracellularly in the form of an expression plasmid which, upon transcription, produces a sequence complementary to at least a portion of the cellular sequence encoding the target protein. (See, e.g., Slater, J. E. et al. (1998) J. Allergy Clin. Immunol. 102(3):469-475; and Scanlon, K. J. et al. (1995) 9(13):1288-1296.) Antisense sequences can also be introduced intracellularly through the use of viral vectors, such as retrovirus and adeno-associated virus vectors. (See, e.g., Miller, A. D. (1990) Blood 76:271; Ausubel, supra; Uclert, 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.)  
       [0237] In another embodiment of the invention, polynucleotides encoding CSAP may be used for somatic or germline gene therapy. Gene therapy may be performed to (i) correct a genetic deficiency (e.g., in the cases of severe combined immunodeficiency (SCID)-X1 disease characterized by X-linked inheritance (Cavazzana-Calvo, M. et al. (2000) Science 288:669-672), severe combined immunodeficiency syndrome associated with an inherited adenosine deaminase (ADA) deficiency (Blaese, R. M. et al. (1995) Science 270:475-480; Bordignon, C. et al. (1995) Science 270:470-475), cystic fibrosis (Zabner, J. et al. (1993) Cell 75:207-216; Crystal, R. G. et al. (1995) Hum. Gene Therapy 6:643-666; Crystal, R. G. et al. (1995) Hum. Gene Therapy 6:667-703), thalassamias, familial hypercholesterolemia, and hemophilia resulting from Factor VIII or Factor IX deficiencies (Crystal, R. G. (1995) Science 270:404-410; Verma, I. M. and N. Somia (1997) Nature 389:239-242)), (ii) express a conditionally lethal gene 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 CSAP expression or regulation causes disease, the expression of CSAP from an appropriate population of transduced cells may alleviate the clinical manifestations caused by the genetic deficiency.  
       [0238] In a further embodiment of the invention, diseases or disorders caused by deficiencies in CSAP are treated by constructing mammalian expression vectors encoding CSAP and introducing these vectors by mechanical means into CSAP-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. Recipon (1998) Curr. Opin. Biotechnol. 9:445-450).  
       [0239] Expression vectors that may be effective for the expression of CSAP include, but are not limited to, the PCDNA 3.1, EPITAG, PRCCMV2, PREP, PVAX, PCR2-TOPOTA vectors (Invitrogen, Carlsbad Calif.), PCMV-SCRIPT, PCMV-TAG, PEGSH/PERV (Stratagene, La Jolla Calif.), and PTET-OFF, PTET-ON, PTRE2, PTRE2-LUC, PIK-HYG (Clontech, Palo Alto Calif.). CSAP may be expressed using (i) a constitutively active promoter, (e.g., from cytomegalovirus (CMV), Rous sarcoma virus (RSV), SV40 virus, thymidine kinase (TK), or β-actin genes), (ii) an inducible promoter (e.g., the tetracycline-regulated promoter (Gossen, M. and H. Bujard (1992) Proc. Natl. Acad. Sci. USA 89:5547-5551; Gossen, M. et al. (1995) Science 268:1766-1769; Rossi, F. M. V. and H. M. Blau (1998) Curr. Opin. Biotechnol. 9:451-456), commercially available in the T-REX plasmid (Invitrogen)); the ecdysone-inducible promoter (available in the plasmids PVGRXR and PIND; Invitrogen); the FK506/rapamycin inducible promoter; or the RU486/mifepristone inducible promoter (Rossi, F. M. V. and H. M. Blau, supra)), or (iii) a tissue-specific promoter or the native promoter of the endogenous gene encoding CSAP from a normal individual.  
       [0240] 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.  
       [0241] In another embodiment of the invention, diseases or disorders caused by genetic defects with respect to CSAP expression are treated by constructing a retrovirus vector consisting of (i) the polynucleotide encoding CSAP 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., PEB and PFBNEO) are commercially available (Stratagene) and are based on published data (Riviere, I. et al. (1995) Proc. Natl. Acad. Sci. USA 92:6733-6737), incorporated by reference herein. The vector is propagated in an appropriate vector producing cell line (VPCL) that expresses an envelope gene with a tropism for receptors on the target cells or a promiscuous envelope protein such as VSVg (Armentano, D. et al. (1987) J. Virol. 61:1647-1650; Bender, M. A. et al. (1987) J. Virol. 61:1639-1646; Adam, M. A. and A. D. Miller (1988) J. Virol. 62:3802-3806; Dull, T. et al. (1998) J. Virol. 72:8463-8471; Zufferey, R. et al. (1998) J. Virol. 72:9873-9880). U.S. Pat. No. 5,910,434 to Rigg (“Method for obtaining retrovirus packaging cell lines producing high transducing efficiency retroviral supernatant”) discloses a method for obtaining retrovirus packaging cell lines and is hereby incorporated by reference. Propagation of retrovirus vectors, transduction of a population of cells (e.g., CD4 +  T-cells), and the return of transduced cells to a patient are procedures well known to persons skilled in the art of gene therapy and have been well documented (Ranga, U. et al. (1997) J. Virol. 71:7020-7029; Bauer, G. et al. (1997) Blood 89:2259-2267; Bonyhadi, M. L. (1997) J. Virol. 71:4707-4716; Ranga, U. et al. (1998) Proc. Natl. Acad. Sci. USA 95:1201-1206; Su, L. (1997) Blood 89:2283-2290).  
       [0242] In the alternative, an adenovirus-based gene therapy delivery system is used to deliver polynucleotides encoding CSAP to cells which have one or more genetic abnormalities with respect to the expression of CSAP. 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.  
       [0243] In another alternative, a herpes-based, gene therapy delivery system is used to deliver polynucleotides encoding CSAP to target cells which have one or more genetic abnormalities with respect to the expression of CSAP. The use of herpes simplex virus (HSV)-based vectors may be especially valuable for introducing CSAP 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.  
       [0244] In another alternative, an alphavirus (positive, single-stranded RNA virus) vector is used to deliver polynucleotides encoding CSAP 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 CSAP into the alphavirus genome in place of the capsid-coding region results in the production of a large number of CSAP-coding RNAs and the synthesis of high levels of CSAP 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 CSAP 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.  
       [0245] 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.  
       [0246] Ribozymes, enzymatic RNA molecules, may also be used to catalyze the specific cleavage of RNA. The mechanism of ribozyme action involves sequence-specific hybridization of the ribozyme molecule to complementary target RNA, followed by endonucleolytic cleavage. For example, engineered hammerhead motif ribozyme molecules may specifically and efficiently catalyze endonucleolytic cleavage of sequences encoding CSAP.  
       [0247] Specific ribozyme cleavage sites within any potential RNA target are initially identified by scanning the target molecule for ribozyme cleavage sites, including the following sequences: GUA, GUU, and GUC. Once identified, short RNA sequences of between 15 and 20 ribonucleotides, corresponding to the region of the target gene containing the cleavage site, may be evaluated for secondary structural features which may render the oligonucleotide inoperable. The suitability of candidate targets may also be evaluated by testing accessibility to hybridization with complementary oligonucleotides using ribonuclease protection assays.  
       [0248] 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 CSAP. Such DNA sequences maybe incorporated into a wide variety of vectors with suitable RNA polymerase promoters such as T7 or SP6. Alternatively, these cDNA constructs that synthesize complementary RNA, constitutively or inducibly, can be introduced into cell lines, cells, or tissues.  
       [0249] 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.  
       [0250] An additional embodiment of the invention encompasses a method for screening for a compound which is effective in altering expression of a polynucleotide encoding CSAP. 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 CSAP expression or activity, a compound which specifically inhibits expression of the polynucleotide encoding CSAP maybe therapeutically useful, and in the treatment of disorders associated with decreased CSAP expression or activity, a compound which specifically promotes expression of the polynucleotide encoding CSAP may be therapeutically useful.  
       [0251] At least one, and up to a plurality, of test compounds may be screened for effectiveness in altering expression of a specific polynucleotide. A test compound may be obtained by any method commonly known in the art, including chemical modification of a compound known to be effective in altering polynucleotide expression; selection from an existing, commercially-available or proprietary library of naturally-occurring or non-natural chemical compounds; rational design of a compound based on chemical and/or structural properties of the target polynucleotide; and selection from a library of chemical compounds created combinatorially or randomly. A sample comprising a polynucleotide encoding CSAP 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 CSAP 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 CSAP. The amount of hybridization may be quantified, thus forming the basis for a comparison of the expression of the polynucleotide both with and without exposure to one or more test compounds. Detection of a change in the expression of a polynucleotide exposed to a test compound indicates that the test compound is effective in altering the expression of the polynucleotide. A screen for a compound effective in altering expression of a specific polynucleotide can be carried out, for example, using a  Schizosaccharomyces pombe  gene expression system (Atkins, D. et al. (1999) U.S. Pat. No. 5,932,435; Arndt, G. M. et al. (2000) Nucleic Acids Res. 28:E15) or a human cell line such as HeLa cell (Clarke, M. L. et al. (2000) Biochem. Biophys. Res. Commun. 268:8-13). A particular embodiment of the present invention involves screening a combinatorial library of oligonucleotides (such as deoxyribonucleotides, ribonucleotides, peptide nucleic acids, and modified oligonucleotides) for antisense activity against a specific polynucleotide sequence (Bruice, T. W. et al. (1997) U.S. Pat. No. 5,686,242; Bruice, T. W. et al. (2000) U.S. Pat. No. 6,022,691).  
       [0252] 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.)  
       [0253] 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.  
       [0254] An additional embodiment of the invention relates to the administration of a composition which generally comprises an active ingredient formulated with a pharmaceutically acceptable excipient. Excipients may include, for example, sugars, starches, celluloses, gums, and proteins. Various formulations are commonly known and are thoroughly discussed in the latest edition of  Rermington&#39;s Pharmaceutical Sciences  (Maack Publishing, Easton Pa.). Such compositions may consist of CSAP, antibodies to CSAP, and mimetics, agonists, antagonists, or inhibitors of CSAP.  
       [0255] 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.  
       [0256] Compositions for pulmonary administration maybe 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.  
       [0257] 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.  
       [0258] Specialized forms of compositions may be prepared for direct intracellular delivery of macromolecules comprising CSAP or fragments thereof. For example, liposome preparations containing a cell-impermeable macromolecule may promote cell fusion and intracellular delivery of the macromolecule. Alternatively, CSAP 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).  
       [0259] 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.  
       [0260] A therapeutically effective dose refers to that amount of active ingredient, for example CSAP or fragments thereof, antibodies of CSAP, and agonists, antagonists or inhibitors of CSAP, which ameliorates the symptoms or condition. Therapeutic efficacy and toxicity may be determined by standard pharmaceutical procedures in cell cultures or with experimental animals, such as by calculating the ED 50  (the dose therapeutically effective in 50% of the population) or LD 50  (the dose lethal to 50% of the population) statistics. The dose ratio of toxic to therapeutic effects is the therapeutic index, which can be expressed as the LD 50 /ED 50  ratio. Compositions which exhibit large therapeutic indices are preferred. The data obtained from cell culture assays and animal studies are used to formulate a range of dosage for human use. The dosage contained in such compositions is preferably within a range of circulating concentrations that includes the ED 50  with little or no toxicity. The dosage varies within this range depending upon the dosage form employed, the sensitivity of the patient, and the route of administration.  
       [0261] 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.  
       [0262] 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.  
       [0263] Diagnostics  
       [0264] In another embodiment, antibodies which specifically bind CSAP may be used for the diagnosis of disorders characterized by expression of CSAP, or in assays to monitor patients being treated with CSAP or agonists, antagonists, or inhibitors of CSAP. Antibodies useful for diagnostic purposes may be prepared in the same manner as described above for therapeutics. Diagnostic assays for CSAP include methods which utilize the antibody and a label to detect CSAP 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.  
       [0265] A variety of protocols for measuring CSAP, including ELISAs, RIAs, and FACS, are known in the art and provide a basis for diagnosing altered or abnormal levels of CSAP expression. Normal or standard values for CSAP expression are established by combining body fluids or cell extracts taken from normal mammalian subjects, for example, human subjects, with antibodies to CSAP under conditions suitable for complex formation. The amount of standard complex formation may be quantitated by various methods, such as photometric means. Quantities of CSAP 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.  
       [0266] In another embodiment of the invention, the polynucleotides encoding CSAP may be used for diagnostic purposes. The polynucleotides which may be used include oligonucleotide sequences, complementary RNA and DNA molecules, and PNAs. The polynucleotides may be used to detect and quantify gene expression in biopsied tissues in which expression of CSAP may be correlated with disease. The diagnostic assay may be used to determine absence, presence, and excess expression of CSAP, and to monitor regulation of CSAP levels during therapeutic intervention.  
       [0267] In one aspect, hybridization with PCR probes which are capable of detecting polynucleotide sequences, including genomic sequences, encoding CSAP or closely related molecules maybe used to identify nucleic acid sequences which encode CSAP. 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 CSAP, allelic variants, or related sequences.  
       [0268] Probes may also be used for the detection of related sequences, and may have at least 50% sequence identity to any of the CSAP 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: 15-28 or from genomic sequences including promoters, enhancers, and introns of the CSAP gene.  
       [0269] Means for producing specific hybridization probes for DNAs encoding CSAP include the cloning of polynucleotide sequences encoding CSAP or CSAP derivatives into vectors for the production of mRNA probes. Such vectors are known in the art, are commercially available, and may be used to synthesize RNA probes in vitro by means of the addition of the appropriate RNA polymerases and the appropriate labeled nucleotides. Hybridization probes may be labeled by a variety of reporter groups, for example, by radionuclides such as  32 P or  35 S, or by enzymatic labels, such as alkaline phosphatase coupled to the probe via avidin/biotin coupling systems, and the like.  
       [0270] Polynucleotide sequences encoding CSAP may be used for the diagnosis of disorders associated with expression of CSAP. Examples of such disorders include, but are not limited to, a cell proliferative disorder such as actinic keratosis, arteriosclerosis, atherosclerosis, bursitis, cirrhosis, hepatitis, mixed connective tissue disease (MCTD), myelofibrosis, paroxysmal nocturnal hemoglobinuria, polycythemia vera, psoriasis, primary thrombocythemia, and a cancer including adenocarcinoma, leukemia, lymphoma, melanoma, myeloma, sarcoma, teratocarcinoma, and, in particular, a cancer of the adrenal gland, bladder, bone, bone marrow, brain, breast, cervix, gall bladder, ganglia, gastrointestinal tract, heart, kidney, liver, lung, muscle, ovary, pancreas, parathyroid, penis, prostate, salivary glands, skin, spleen, testis, thymus, thyroid, and uterus; a viral infection such as those caused by adenoviruses (acute respiratory disease, pneumonia), arenaviruses (lymphocytic choriomeningitis), bunyaviruses (Hantavirus), coronaviruses (pneumonia, chronic bronchitis), hepadnaviruses (hepatitis), herpesviruses (herpes simplex virus, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus), flaviviruses (yellow fever), orthomyxoviruses (influenza), papillomaviruses (cancer), paramyxoviruses (measles, mumps), picornoviruses (rhinovirus, poliovirus, coxsackie-virus), polyomaviruses (BK virus, JC virus), poxviruses (smallpox), reovirus (Colorado tick fever), retroviruses (human immunodeficiency virus, human T lymphotropic virus), rhabdoviruses (rabies), rotaviruses (gastroenteritis), and togaviruses (encephalitis, rubella); and a neurological disorder such as epilepsy, ischemic cerebrovascular disease, stroke, cerebral neoplasms, Alzheimer&#39;s disease, Pick&#39;s disease, Huntington&#39;s disease, dementia, Parkinson&#39;s disease and other extrapyramidal disorders, amyotrophic lateral sclerosis and other motor neuron disorders, progressive neural muscular atrophy, retinitis pigmentosa, hereditary ataxias, multiple sclerosis and other demyelinating diseases, bacterial and viral meningitis, brain abscess, subdural empyema, epidural abscess, suppurative intracranial thrombophlebitis, myelitis and radiculitis, viral central nervous system disease, a prion disease including kuru, Creutzfeldt-Jakob disease, and Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, nutritional and metabolic diseases of the nervous system, neurofibromatosis, tuberous sclerosis, cerebelloretinal hemangioblastomatosis, encephalotrigeminal syndrome, mental retardation and other developmental disorders of the central nervous system, cerebral palsy, neuroskeletal disorders, autonomic nervous system disorders, cranial nerve disorders, spinal cord diseases, muscular dystrophy and other neuromuscular disorders, peripheral nervous system disorders, dermatomyositis and polymyositis; inherited, metabolic, endocrine, and toxic myopathies; myasthenia gravis, periodic paralysis, mental disorders including mood, anxiety, and schizophrenic disorders, seasonal affective disorder (SAD), akathesia, amnesia, catatonia, diabetic neuropathy, tardive dyskinesia, dystonias, paranoid psychoses, postherpetic neuralgia, and Tourette&#39;s disorder. The polynucleotide sequences encoding CSAP 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 CSAP expression. Such qualitative or quantitative methods are well known in the art.  
       [0271] In a particular aspect, the nucleotide sequences encoding CSAP may be useful in assays that detect the presence of associated disorders, particularly those mentioned above. The nucleotide sequences encoding CSAP may be labeled by standard methods and added to a fluid or tissue sample from a patient under conditions suitable for the formation of hybridization complexes. After a suitable incubation period, the sample is washed and the signal is quantified and compared with a standard value. If the amount of signal in the patient sample is significantly altered in comparison to a control sample then the presence of altered levels of nucleotide sequences encoding CSAP 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.  
       [0272] In order to provide a basis for the diagnosis of a disorder associated with expression of CSAP, a normal or standard profile for expression is established. This maybe accomplished by combining body fluids or cell extracts taken from normal subjects, either animal or human, with a sequence, or a fragment thereof, encoding CSAP, 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.  
       [0273] 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.  
       [0274] 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.  
       [0275] Additional diagnostic uses for oligonucleotides designed from the sequences encoding CSAP 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 CSAP, or a fragment of a polynucleotide complementary to the polynucleotide encoding CSAP, and will be employed under optimized conditions for identification of a specific gene or condition. Oligomers may also be employed under less stringent conditions for detection or quantification of closely related DNA or RNA sequences.  
       [0276] In a particular aspect, oligonucleotide primers derived from the polynucleotide sequences encoding CSAP 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 CSAP 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.).  
       [0277] Methods which may also be used to quantify the expression of CSAP 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.  
       [0278] In further embodiments, oligonucleotides or longer fragments derived from any of the polynucleotide sequences described herein may be used as elements on a microarray. The microarray can be used in transcript imaging techniques which monitor the relative expression levels of large numbers of genes simultaneously as described below. The microarray may also be used to identify genetic variants, mutations, and polymorphisms. This information may be used to determine gene function, to understand the genetic basis of a disorder, to diagnose a disorder, to monitor progression/regression of disease as a function of gene expression, and to develop and monitor the activities of therapeutic agents in the treatment of disease. In particular, this information may be used to develop a pharmacogenomic profile of a patient in order to select the most appropriate and effective treatment regimen for that patient. For example, therapeutic agents which are highly effective and display the fewest side effects may be selected for a patient based on his/her pharmacogenomic profile.  
       [0279] In another embodiment, CSAP, fragments of CSAP, or antibodies specific for CSAP 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.  
       [0280] A particular embodiment relates to the use of the polynucleotides of the present invention to generate a transcript image of a tissue or cell type. A transcript image represents the global pattern of gene expression by a particular tissue or cell type. Global gene expression patterns are analyzed by quantifying the number of expressed genes and their relative abundance under given conditions and at a given time. (See Seilhamer et al., “Comparative Gene Transcript Analysis,” U.S. Pat. No. 5,840,484, expressly incorporated by reference herein.) Thus a transcript image may be generated by hybridizing the polynucleotides of the present invention or their complements to the totality of transcripts or reverse transcripts of a particular tissue or cell type. In one embodiment, the hybridization takes place in high-throughput format, wherein the polynucleotides of the present invention or their complements comprise a subset of a plurality of elements on a microarray. The resultant transcript image would provide a profile of gene activity.  
       [0281] 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.  
       [0282] Transcript images which profile the expression of the polynucleotides of the present invention may also be used in conjunction with in vitro model systems and preclinical evaluation of pharmaceuticals, as well as toxicological testing of industrial and naturally-occurring environmental compounds. All compounds induce characteristic gene expression patterns, frequently termed molecular fingerprints or toxicant signatures, which are indicative of mechanisms of action and toxicity (Nuwaysir, E. F. et al. (1999) Mol. Carcinog. 24:153-159; Steiner, S. and N. L. Anderson (2000) Toxicol. Lett. 112-113:467-471, expressly incorporated by reference herein). If a test compound has a signature similar to that of a compound with known toxicity, it is likely to share those toxic properties. These fingerprints or signatures are most useful and refined when they contain expression information from a large number of genes and gene families. Ideally, a genome-wide measurement of expression provides the highest quality signature. Even genes whose expression is not altered by any tested compounds are important as well, as the levels of expression of these genes are used to normalize the rest of the expression data. The normalization procedure is useful for comparison of expression data after treatment with different compounds. While the assignment of gene function to elements of a toxicant signature aids in interpretation of toxicity mechanisms, knowledge of gene function is not necessary for the statistical matching of signatures which leads to prediction of toxicity. (See, for example, Press Release 00-02 from the National Institute of Environmental Health Sciences, released Feb. 29, 2000, available at http://www.niehs.nih.gov/oc/news/toxchip.htm.) Therefore, it is important and desirable in toxicological screening using toxicant signatures to include all expressed gene sequences.  
       [0283] 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.  
       [0284] Another particular embodiment relates to the use of the polypeptide sequences of the present invention to analyze the proteome of a tissue or cell type. The term proteome refers to the global pattern of protein expression in a particular tissue or cell type. Each protein component of a proteome can be subjected individually to further analysis. Proteome expression patterns, or profiles, are analyzed by quantifying the number of expressed proteins and their relative abundance under given conditions and at a given time. A profile of a cell&#39;s proteome may thus be generated by separating and analyzing the polypeptides of a particular tissue or cell type. In one embodiment, the separation is achieved using two-dimensional gel electrophoresis, in which proteins from a sample are separated by isoelectric focusing in the first dimension, and then according to molecular weight by sodium dodecyl sulfate slab gel electrophoresis in the second dimension (Steiner and Anderson, supra). The proteins are visualized in the gel as discrete and uniquely positioned spots, typically by staining the gel with an agent such as Coomassie Blue or silver or fluorescent stains. The optical density of each protein spot is generally proportional to the level of the protein in the sample. The optical densities of equivalently positioned protein spots from different samples, for example, from biological samples either treated or untreated with a test compound or therapeutic agent, are compared to identify any changes in protein spot density related to the treatment. The proteins in the spots are partially sequenced using, for example, standard methods employing chemical or enzymatic cleavage followed by mass spectrometry. The identity of the protein in a spot may be determined by comparing its partial sequence, preferably of at least 5 contiguous amino acid residues, to the polypeptide sequences of the present invention. In some cases, further sequence data may be obtained for definitive protein identification.  
       [0285] A proteomic profile may also be generated using antibodies specific for CSAP to quantify the levels of CSAP expression. In one embodiment, the antibodies are used as elements on a microarray, and protein expression levels are quantified by exposing the microarray to the sample and detecting the levels of protein bound to each array element (Lueking, A. et al. (1999) Anal. Biochem. 270:103-111; Mendoze, L. G. et al. (1999) Biotechniques 27:778-788). Detection may be performed by a variety of methods known in the art, for example, by reacting the proteins in the sample with a thiol- or amino-reactive fluorescent compound and detecting the amount of fluorescence bound at each array element.  
       [0286] Toxicant signatures at the proteome level are also useful for toxicological screening, and should be analyzed in parallel with toxicant signatures at the transcript level. There is a poor correlation between transcript and protein abundances for some proteins in some tissues (Anderson, N. L. and J. Seilhamer (1997) Electrophoresis 18:533-537), so proteome toxicant signatures maybe 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.  
       [0287] 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.  
       [0288] In another embodiment, the toxicity of a test compound is assessed by treating a biological sample containing proteins with the test compound. Proteins from the biological sample are incubated with antibodies specific to the polypeptides of the present invention. The amount of protein recognized by the antibodies is quantified. The amount of protein in the treated biological sample is compared with the amount in an untreated biological sample. A difference in the amount of protein between the two samples is indicative of a toxic response to the test compound in the treated sample.  
       [0289] Microarrays may be prepared, used, and analyzed using methods known in the art. (See, e.g., Brennan, T. M. et al. (1995) U.S. Pat. No. 5,474,796; Schena, M. et al. (1996) Proc. Natl. Acad. Sci. USA 93:10614-10619; Baldeschweiler et al. (1995) PCT application WO95/251116; Shalon, D. et al. (1995) PCT application WO95/35505; Heller, R. A. et al. (1997) Proc. Natl. Acad. Sci. USA 94:2150-2155; and Heller, M. J. et al. (1997) U.S. Pat. No. 5,605,662.) Various types of microarrays are well known and thoroughly described in DNA Microarrays: A Practical Approach, M. Schena, ed. (1999) Oxford University Press, London, hereby expressly incorporated by reference.  
       [0290] In another embodiment of the invention, nucleic acid sequences encoding CSAP 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.)  
       [0291] 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 CSAP 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.  
       [0292] 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.  
       [0293] In another embodiment of the invention, CSAP, 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 CSAP and the agent being tested may be measured.  
       [0294] 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 CSAP, or fragments thereof, and washed. Bound CSAP is then detected by methods well known in the art. Purified CSAP 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.  
       [0295] In another embodiment, one may use competitive drug screening assays in which neutralizing antibodies capable of binding CSAP specifically compete with a test compound for binding CSAP. In this manner, antibodies can be used to detect the presence of any peptide which shares one or more antigenic determinants with CSAP.  
       [0296] In additional embodiments, the nucleotide sequences which encode CSAP maybe 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.  
       [0297] 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.  
       [0298] The disclosures of all patents, applications, and publications mentioned above and below, including U.S. Ser. No. 60/244,022, U.S. Ser. No. 60/247,370, and U.S. Ser. No. 60/251,831, are hereby expressly incorporated by reference. 
     
    
    
     EXAMPLES  
     [0299] I. Construction of cDNA Libraries  
     [0300] 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.  
     [0301] 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.).  
     [0302] In some cases, Stratagene was provided with RNA and constructed the corresponding cDNA libraries. Otherwise, cDNA was synthesized and cDNA libraries were constructed with the UNIZAP vector system (Stratagene) or SUPERSCRIPT plasmid system (Life Technologies), using the recommended procedures or similar methods known in the art. (See, e.g., Ausubel, 1997, supra, units 5.1-6.6.) Reverse transcription was initiated using oligo d(T) or random primers. Synthetic oligonucleotide adapters were ligated to double stranded cDNA, and the cDNA was digested with the appropriate restriction enzyme or enzymes. For most libraries, the cDNA was size-selected (300-1000 bp) using SEPHACRYL S1000, SEPHAROSE CL2B, or SEPHAROSE CL4B column chromatography (Amersham Pharmacia Biotech) or preparative agarose gel electrophoresis. cDNAs were ligated into compatible restriction enzyme sites of the polylinker of a suitable plasmid, e.g., PBLUESCRIPT plasmid (Stratagene), PSPORT1 plasmid (Life Technologies), PCDNA2.1 plasmid (Invitrogen, Carlsbad Calif.), PBK-CMV plasmid (Stratagene), PCR2-TOPOTA plasmid (Invitrogen), PCMV-ICIS plasmid (Stratagene), pIGEN (Incyte Genomics, Palo Alto Calif.), or pINCY (Incyte Genomics), or derivatives thereof. Recombinant plasmids were transformed into competent  E. coli  cells including XL1-Blue, XL1-BlueMRF, or SOLR from Stratagene or DH5a, DH10B, or ElectroMAX DH10B from Life Technologies.  
     [0303] II. Isolation of cDNA Clones  
     [0304] Plasmids obtained as described in Example I were recovered from host cells by in vivo excision using the UNIZAP vector system (Stratagene) or by cell lysis. Plasmids were purified using at least one of the following: a Magic or WIZARD Minipreps DNA purification system (Promega); an AGTC Miniprep purification kit (Edge Biosystems, Gaithersburg Md.); and QIAWELL 8 Plasmid, QIAWELL 8 Plus Plasmid, QIAWELL 8 Ultra Plasmid purification systems or the R.E.A.L. PREP 96 plasmid purification kit from QIAGEN. Following precipitation, plasmids were resuspended in 0.1 ml of distilled water and stored, with or without lyophilization, at 4° C.  
     [0305] 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).  
     [0306] III. Sequencing and Analysis  
     [0307] Incyte cDNA recovered in plasmids as described in Example II were sequenced as follows. Sequencing reactions were processed using standard methods or high-throughput instrumentation such as the ABI CATALYST 800 (Applied Biosystems) thermal cycler or the PTC-200 thermal cycler (MJ Research) in conjunction with the HYDRA microdispenser (Robbins Scientific) or the MICROLAB 2200 (Hamilton) liquid transfer system. cDNA sequencing reactions were prepared sing 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.  
     [0308] The polynucleotide sequences derived from Incyte cDNAs were validated by removing vector, linker, and poly(A) sequences and by masking ambiguous bases, using algorithms and programs based on BLAST, dynamic programming, and dinucleotide nearest neighbor analysis. The Incyte cDNA sequences or translations thereof were then queried against a selection of public databases such as the GenBank primate, rodent, mammalian, vertebrate, and eukaryote databases, and BLOCKS, PRINTS, DOMO, PRODOM; PROTEOME databases with sequences from  Homo sapiens, Rattus norvegicus, Mus musculus, Caenorhabditis elegans, Saccharomyces cerevisiae, Schizosaccharomyces pombe , and  Candida albicans  (Incyte Genomics, Palo Alto Calif.); and hidden Markov model (HMM)-based protein family databases such as PFAM. (HMM is a probabilistic approach which analyzes consensus primary structures of gene families. See, for example, Eddy, S. R. (1996) Curr. Opin. Struct. Biol. 6:361-365.) The queries were performed using programs based on BLAST, FASTA, BLIMPS, and HMMER. The Incyte cDNA sequences were assembled to produce full length polynucleotide sequences. Alternatively, GenBank cDNAs, GenBank ESTs, stitched sequences, stretched sequences, or Genscan-predicted coding sequences (see Examples IV and V) were used to extend Incyte cDNA assemblages to full length. Assembly was performed using programs based on Phred, Phrap, and Consed, and cDNA assemblages were screened for open reading frames using programs based on GeneMark, BLAST, and FASTA. The full length polynucleotide sequences were translated to derive the corresponding full length polypeptide sequences. Alternatively, a polypeptide of the invention may begin at any of the methionine residues of the full length translated polypeptide. Full length polypeptide sequences were subsequently analyzed by querying against databases such as the GenBank protein databases (genpept), SwissProt, the PROTEOME databases, BLOCKS, PRINTS, DOMO, PRODOM, Prosite, and hidden Markov model (H)-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.  
     [0309] 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 value, the greater the identity between two sequences).  
     [0310] The programs described above for the assembly and analysis of full length polynucleotide and polypeptide sequences were also used to identify polynucleotide sequence fragments from SEQ ID NO:15-28. Fragments from about 20 to about 4000 nucleotides which are useful in hybridization and amplification technologies are described in Table 4, column 4.  
     [0311] IV. Identification and Editing of Coding Sequences from Genomic DNA  
     [0312] Putative cytoskeleton-associated proteins were initially identified by running the Genscan gene identification program against public genomic sequence databases (e.g., gbpri and gbhtg). Genscan is a general-purpose gene identification program which analyzes genomic DNA sequences from a variety of organisms (See Burge, C. and S. Karlin (1997) J. Mol. Biol. 268:78-94, and Burge, C. and S. Karlin (1998) Curr. Opin Struct. Biol. 8:346-354). The program concatenates predicted exons to form an assembled cDNA sequence extending from a methionine to a stop codon. The output of Genscan is a FASTA database of polynucleotide and polypeptide sequences. The maximum range of sequence for Genscan to analyze at once was set to 30 kb. To determine which of these Genscan predicted cDNA sequences encode cytoskeleton-associated proteins, the encoded polypeptides were analyzed by querying against PFAM models for cytoskeleton-associated proteins. Potential cytoskeleton-associated proteins were also identified by homology to Incyte cDNA sequences that had been annotated as cytoskeleton-associated proteins. These selected-Genscan-predicted sequences were then compared by BLAST analysis to the genpept and gbpri public databases. Where necessary, the Genscan-predicted sequences were then edited by comparison to the top BLAST hit from genpept to correct errors in the sequence predicted by Genscan, such as extra or omitted exons. BLAST analysis was also used to find any Incyte cDNA or public cDNA coverage of the Genscan-predicted sequences, thus providing evidence for transcription. When Incyte cDNA coverage was available, this information was used to correct or confirm the Genscan predicted sequence. Full length polynucleotide sequences were obtained by assembling Genscan-predicted coding sequences with Incyte cDNA sequences and/or public cDNA sequences using the assembly process described in Example III. Alternatively, full length polynucleotide sequences were derived entirely from edited or unedited Genscan-predicted coding sequences.  
     [0313] V. Assembly of Genomic Sequence Data with cDNA Sequence Data  
     [0314] “Stitched” Sequences  
     [0315] 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 m 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.  
     [0316] “Stretched” Sequences  
     [0317] Partial DNA sequences were extended to full length with an algorithm based on BLAST analysis. First, partial cDNAs assembled as described in Example m 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.  
     [0318] VI. Chromosomal Mapping of CSAP Encoding Polynucleotides  
     [0319] The sequences which were used to assemble SEQ ID NO:15-28 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:15-28 were assembled into clusters of contiguous and overlapping sequences using assembly algorithms such as Phrap (Table 7). Radiation hybrid and genetic mapping data available from public resources such as the Stanford Human Genome Center (SHGC), Whitehead Institute for Genome Research (WIGR), and Généthon were used to determine if any of the clustered sequences had been previously mapped. Inclusion of a mapped sequence in a cluster resulted in the assignment of all sequences of that cluster, including its particular SEQ ID NO, to that map location.  
     [0320] 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.  
     [0321] VII. Analysis of Polynucleotide Expression  
     [0322] 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.)  
     [0323] 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     )         }                     
 
     [0324] 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.  
     [0325] Alternatively, polynucleotide sequences encoding CSAP 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 CSAP. cDNA sequences and cDNA library/tissue information are found in the LIFESEQ GOLD database (Incyte Genomics, Palo Alto Calif.).  
     [0326] VIII. Extension of CSAP Encoding Polynucleotides  
     [0327] Full length polynucleotide sequences were also produced by extension of an appropriate fragment of the full length molecule using oligonucleotide primers designed from this fragment. One primer was synthesized to initiate 5′ extension of the known fragment, and the other primer was synthesized to initiate 3′ extension of the known fragment. The initial primers were designed using OLIGO 4.06 software (National Biosciences), or another appropriate program, to be about 22 to 30 nucleotides in length, to have a GC content of about 50% or more, and to anneal to the target sequence at temperatures of about 68° C. to about 72° C. Any stretch of nucleotides which would result in hairpin structures and primer-primer dimerizations was avoided.  
     [0328] 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.  
     [0329] 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.  
     [0330] 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.  
     [0331] The extended nucleotides were desalted and concentrated, transferred to 384-well plates, digested with CviJI cholera virus endonuclease (Molecular Biology Research, Madison Wis.), and sonicated or sheared prior to religation into pUC 18 vector (Amersham Pharmacia Biotech). For shotgun sequencing, the digested nucleotides were separated on low concentration (0.6 to 0.8%) agarose gels, fragments were excised, and agar digested with Agar ACE (Promega). Extended clones were religated using T4 ligase (New England Biolabs, Beverly Mass.) into pUC 18 vector (Amersham Pharmacia Biotech), treated with Pfu DNA polymerase (Stratagene) to fill-in restriction site overhangs, and transfected into competent E. coli cells. Transformed cells were selected on antibiotic-containing media, and individual colonies were picked and cultured overnight at 37° C. in 384-well plates in LB/2×carb liquid media.  
     [0332] 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).  
     [0333] 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.  
     [0334] IX. Labeling and Use of Individual Hybridization Probes  
     [0335] Hybridization probes derived from SEQ ID NO:15-28 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 μmol 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).  
     [0336] 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.  
     [0337] X. Microarrays  
     [0338] 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.)  
     [0339] 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.  
     [0340] 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.  
     [0341] Tissue or Cell Sample Preparation  
     [0342] 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 dTTP, 40 μM dCTP, 40 μM dCTP-Cy3 (BDS) or dCTP-Cy5 (Amersham Pharmacia Biotech). The reverse transcription reaction is performed in a 25 ml volume containing 200 ng poly(A) +  RNA with GEMBRIGHT kits (Incyte). Specific control poly(A)+RNAs are synthesized by in vitro transcription from non-coding yeast genomic DNA. After incubation at 37° C. for 2 hr, each reaction sample (one with Cy3 and another with Cy5 labeling) is treated with 2.5 ml of 0.5M sodium hydroxide and incubated for 20 minutes at 85° C. to the stop the reaction and degrade the RNA. Samples are purified using two successive CHROMA SPIN 30 gel filtration spin columns (CLONTECH Laboratories, 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.  
     [0343] Microarray Preparation  
     [0344] 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).  
     [0345] 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.  
     [0346] 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.  
     [0347] 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.  
     [0348] Hybridization  
     [0349] Hybridization reactions contain 9 μl of sample mixture consisting of 0.2 μg each of Cy3 and Cy5 labeled cDNA synthesis products in 5×SSC, 0.2% SDS hybridization buffer. The sample mixture is heated to 65° C. for 5 minutes and is aliquoted onto the microarray surface and covered with an 1.8 cm 2  coverslip. The arrays are transferred to a waterproof chamber having a cavity just slightly larger than a microscope slide. The chamber is kept at 100% humidity internally by the addition of 140 μl of 5×SSC in a corner of the chamber. The chamber containing the arrays is incubated for about 6.5 hours at 60° C. The arrays are washed for 10 min at 45° C. in a first washbuffer (1×SSC, 0.1% SDS), three times for 10 minutes each at 45° C. in a second wash buffer (0.1×SSC), and dried.  
     [0350] Detection  
     [0351] 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.  
     [0352] 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.  
     [0353] 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.  
     [0354] 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 two different fluorophores are excited and measured simultaneously, the data are first corrected for optical crosstalk (due to overlapping emission spectra) between the fluorophores using each fluorophore&#39;s emission spectrum.  
     [0355] A grid is superimposed over the fluorescence signal image such that the signal from each spot is centered in each element of the grid. The fluorescence signal within each element is then integrated to obtain a numerical value corresponding to the average intensity of the signal. The software used for signal analysis is the GEMTOOLS gene expression analysis program (Incyte).  
     [0356] XI. Complementary Polynucleotides  
     [0357] Sequences complementary to the CSAP-encoding sequences, or any parts thereof, are used to detect, decrease, or inhibit expression of naturally occurring CSAP. 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 CSAP. 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 CSAP-encoding transcript.  
     [0358] XII. Expression of CSAP  
     [0359] Expression and purification of CSAP is achieved using bacterial or virus-based expression systems. For expression of CSAP 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 CSAP upon induction with isopropyl beta-D-thiogalactopyranoside (IPTG). Expression of CSAP 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 CSAP by either homologous recombination or bacterial-mediated transposition involving transfer plasmid intermediates. Viral infectivity is maintained and the strong polyhedrin promoter drives high levels of cDNA transcription. Recombinant baculovirus is used to infect  Spodoptera frugiperda  (Sf9) insect cells in most cases, or human hepatocytes, in some cases. Infection of the latter requires additional genetic modifications to baculovirus. (See Engelhard, E. K. et al. (1994) Proc. Natl. Acad. Sci. USA 91:3224-3227; Sandig, V. et al. (1996) Hum. Gene Ther. 7:1937-1945.)  
     [0360] In most expression systems, CSAP is synthesized as a fusion protein with, e.g., glutathione S-transferase (GST) or a peptide epitope tag, such as FLAG or 6-His, permitting rapid, single-step, affinity-based purification of recombinant fusion protein from crude cell lysates. GST, a 26-kilodalton enzyme from  Schistosoma japonicum,  enables the purification of fusion proteins on immobilized glutathione under conditions that maintain protein activity and antigenicity (Amersham Pharmacia Biotech). Following purification, the GST moiety can be proteolytically cleaved from CSAP 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 CSAP obtained by these methods can be used directly in the assays shown in Examples XVI and XVII, etc. where applicable.  
     [0361] XIII. Functional Assays  
     [0362] CSAP function is assessed by expressing the sequences encoding CSAP at physiologically elevated levels in mammalian cell culture systems. cDNA is subcloned into a mammalian expression vector containing a strong promoter that drives high levels of cDNA expression. Vectors of choice include PCMV SPORT (Life Technologies) and PCR3.1 Invitrogen, Carlsbad Calif.), both of which contain the cytomegalovirus promoter. 5-10 μg of recombinant vector are transiently transfected into a human cell line, for example, an endothelial or hematopoietic cell line, using either liposome formulations or electroporation. 1-2 μg of an additional plasmid containing sequences encoding a marker protein are co-transfected. Expression of a marker protein provides a means to distinguish transfected cells from nontransfected cells and is a reliable predictor of cDNA expression from the recombinant vector. Marker proteins of choice include, e.g., Green Fluorescent Protein (GFP; Clontech), CD64, or a CD64-GFP fusion protein. Flow cytometry (FCM), an automated, laser optics-based technique, is used to identify transfected cells expressing GFP or CD64-GFP and to evaluate the apoptotic state of the cells and other cellular properties. FCM detects and quantifies the uptake of fluorescent molecules that diagnose events preceding or coincident with cell death. These events include changes in nuclear DNA content as measured by staining of DNA with propidium iodide; changes in cell size and granularity as measured by forward light scatter and 90 degree side light scatter; down-regulation of DNA synthesis as measured by decrease in bromodeoxyuridine uptake; alterations in expression of cell surface and intracellular proteins as measured by reactivity with specific antibodies; and alterations in plasma membrane composition as measured by the binding of fluorescein-conjugated Annexin V protein to the cell surface. Methods in flow cytometry are discussed in Ormerod, M. G. (1994)  Flow Cytometry,  Oxford, New York N.Y.  
     [0363] The influence of CSAP on gene expression can be assessed using highly purified populations of cells transfected with sequences encoding CSAP 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 CSAP and other genes of interest can be analyzed by northern analysis or microarray techniques.  
     [0364] XIV. Production of CSAP Specific Antibodies  
     [0365] CSAP 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.  
     [0366] Alternatively, the CSAP 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.)  
     [0367] 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-CSAP activity by, for example, binding the peptide or CSAP to a substrate, blocking with 1% BSA, reacting with rabbit antisera, washing, and reacting with radio-iodinated goat anti-rabbit IgG.  
     [0368] XV. Purification of Naturally Occurring CSAP Using Specific Antibodies  
     [0369] Naturally occurring or recombinant CSAP is substantially purified by immunoaffinity chromatography using antibodies specific for CSAP. An immunoaffinity column is constructed by covalently coupling anti-CSAP 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.  
     [0370] Media containing CSAP are passed over the immunoaffinity column, and the column is washed under conditions that allow the preferential absorbance of CSAP (e.g., high ionic strength buffers in the presence of detergent). The column is eluted under conditions that disrupt antibody/CSAP binding (e.g., a buffer of pH 2 to pH 3, or a high concentration of a chaotrope, such as urea or thiocyanate ion), and CSAP is collected.  
     [0371] XVI. Identification of Molecules Which Interact with CSAP  
     [0372] CSAP, 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 CSAP, washed, and any wells with labeled CSAP complex are assayed. Data obtained using different concentrations of CSAP are used to calculate values for the number, affinity, and association of CSAP with the candidate molecules.  
     [0373] Alternatively, molecules interacting with CSAP 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).  
     [0374] CSAP 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).  
     [0375] XVII. Demonstration of CSAP Activity  
     [0376] A microtubule motility assay for CSAP measures motor protein activity. In this assay, recombinant CSAP is immobilized onto a glass slide or similar substrate. Taxol-stabilized bovine brain microtubules (commercially available) in a solution containing ATP and cytosolic extract are perfused onto the slide. Movement of microtubules as driven by CSAP motor activity can be visualized and quantified using video-enhanced light microscopy and image analysis techniques. CSAP activity is directly proportional to the frequency and velocity of microtubule movement.  
     [0377] Alternatively, an assay for CSAP measures the formation of protein filaments in vitro. A solution of CSAP at a concentration greater than the “critical concentration” for polymer assembly is applied to carbon-coated grids. Appropriate nucleation sites maybe supplied in the solution. The grids are negative stained with 0.7% (w/v) aqueous uranyl acetate and examined by electron microscopy. The appearance of filaments of approximately 25 nm (microtubules), 8 nm (actin), or 10 nm (intermediate filaments) is a demonstration of protein activity.  
     [0378] In another alternative, CSAP activity is measured by the binding of CSAP to protein filaments.  35 S-Met labeled CSAP sample is incubated with the appropriate filament protein (actin, tubulin, or intermediate filament protein) and complexed protein is collected by immunoprecipitation using an antibody against the filament protein. The immunoprecipitate is then run out on SDS-PAGE and the amount of CSAP bound is measured by autoradiography.  
     [0379] CSAP activity is demonstrated by measuring the effect of CSAP on the activity of a GTPase such as rac or rho. The GTPase is combined with ( γ32 P)GTP for 30 min at 30° C. in the presence and in the absence of CSAP (+CSAP and −CSAP). Aliquots are removed from the +CSAP and −CSAP reaction solutions at intervals, until the reactions are stopped by addition of Norit activated charcoal in NaH 2 PO 4  and charcoal is removed by centrifugation.  γ32 P i  release in both +CSAP and −CSAP solutions is monitored by scintillation count, and the difference is proportional to CSAP activity (Ogier-Denis, E. et al. (2000) J. Biol. Chem. 275:39090-39095).  
     [0380] Various modifications and variations of the described methods and systems of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with certain embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention which are obvious to those skilled in molecular biology or related fields are intended to be within the scope of the following claims.  
                               TABLE 1                               Incyte       Incyte       Incyte   Polypeptide   Polypeptide   Polynucleotide   Polynucleotide       Project ID   SEQ ID NO:   ID   SEQ ID NO:   ID                                                    1806450   1   1806450CD1   15   1806450CB1       959690   2    959690CD1   16    959690CB1       7091536   3   7091536CD1   17   7091536CB1       7472724   4   7472724CD1   18   7472724CB1       5844189   5   5844189CD1   19   5844189CB1       7472720   6   7472720CD1   20   7472720CB1       7583990   7   7583990CD1   21   7583990CB1       2058182   8   2058182CD1   22   2058182CB1       3564377   9   3564377CD1   23   3564377CB1       1568689   10   1568689CD1   24   1568689CB1       1393767   11   1393767CD1   25   1393767CB1       3029343   12   3029343CD1   26   3029343CB1       5507629   13   5507629CD1   27   5507629CB1       5607780   14   5607780CD1   28   5607780CB1                  
 
     [0381]                               TABLE 2                           Incyte                   Polypeptide   Polypeptide   GenBank   Probability       SEQ ID NO:   ID   ID NO:   Score   GenBank Homolog                                                    1   1806450CD1   g466548   1.5e−287   NBL4 [ Mus musculus ] (Takeuchi, K. et al. (1994) J. Cell.                       Sci. 107: 1921-1928)       2    959690CD1   g3885834   2.2e−11   lin-7-C [ Rattus norvegicus ] (Irie, M. et al. (1999)                       Oncogene 18: 2811-2817)       3   7091536CD1   g2739096   3.0e−64   Protein 4.1-G [ Homo sapiens ] (Parra, M. et al. (1998)                       Genomics 49: 298-306)       4   7472724CD1   g6624055   1.9e−19   Similar to ankyrin motif [ Homo sapiens ]       5   5844189CD1   g1790878   0.0   [ Homo sapiens ] microtubule-associated protein 1a                       Fink, J. K. et al. (1996) Genomics 35: 577-585       6   7472720CD1   g7274242   1.0e−26   [ Homo sapiens ] novel retinal pigment epithelial-cell                       cytoskeletal thread protein                       Kutty, R. K. et al. J. Biol. Chem. published October 19,                       2000 as 10.1074/jbc.M007421200       7   7583990CD1   g3108195   6.4e−57   [ Homo sapiens ] Duo (binds huntingtin-associated protein 1)                       Colomer, V. et al. (1997) Hum. Mol. Genet. 6: 1519-1525       8   2058182CD1   g9971185   0.0   [ Rattus norvegicus ] Nadrin, actin-filament regulating                       protein                       Harada, A. et al. J. Biol. Chem. published Aug. 30, 2000                       as 10.1074/jbc.M004069200       9   3564377CD1   g4826478   0.0   [ Homo sapiens ] SH3 domain binding protein 1, a Rac GTPase                       activating protein                       Cicchetti, P. (1995) EMBO J. 14: 3127-3135       10   1568689CD1   g4742003   2.5e−17   [ Takifugu rubripes ] kelch (associated with protein-protein                       interaction) actin organizing protein                       Adams, S. et al. (2000) Trends Cell Biol. 10: 17-24       11   1393767CD1   g927639   1.5e−222   dynein intermediate chain 3 [ Anthocidaris crassispina ]                       (Ye, GJ. et al. (2000) J. Virol. 74: 1355-1363)               g11493148   0   [ Homo sapiens ] intermediate dynein chain                       Bartoloni, L. et al.                       No deleterious mutations were found in three genes (HFH4,                       LC8, DNAI2) on human chromosome 17q in patients with Primary                       Ciliary Dyskinesia                       Eur. J. Hum. Genet. 8, 126-126 (2000)       12   3029343CD1   g29865   1.6e−14   CENP-E [ Homo sapiens ]                       (Yen, T. J. et al. (1992) Nature 359: 536-539)       13   5507629CD1   g1098579   4.4e−104   actin [ Diphyllobothrium dendriticum ]       14   5607780CD1   g11275669   0   [ Homo sapiens ] (AF225896) tensin                       Chen, H. et al.                       Molecular characterization of human tensin                       Biochem. J. 351 (Pt 2), 403-411 (2000)               g212752   6.3e−263   tensin [ Gallus gallus ]                       (Katz, B. Z. et al. (2000) Biochem. Biophys. Res. Commun.                       272: 717-720)                    
     [0382]                                       TABLE 3                       SEQ   Incyte   Amino   Potential   Potential       Analytical       ID   Polypeptide   Acid   Phosphorylation   Glycosylation   Signature Sequences,   Methods and       NO:   ID   Residues   Sites   Sites   Domains and Motifs   Databases                                                            1   1806450CD1   580   S190 S306 S310   N217 N267   FERM domain (Band 4.1 family):   HMMER_PFAM                   S314 S322 S35   N300 N343   C13-H211                   S393 S426 S428   N450 N481   Band 4.1 family motif: H181-L210   MOTIFS                   S433 S448 S464       Band 4.1 family domain   ProfileScan                   S476 S484 S486       signatures:                   S491 S532 T199       A78-D122, G186-K234                   T255 T36 T382       Band 4.1 family domains:   BLIMPS_BLOCKS                   T405 T439 T577       BL00660A: L25-L77                   T76 Y113       BL00660B: R112-D151                           BL00660C: E191-K234                           BL00660D: Y242-D265                           BL00660E: F273-F295                           Band 4.1 protein family PR00935:   BLIMPS_PRINTS                           V49-Y61, L117-C130, C130-Y150,                           E191-G207                           ERM family signature   BLIMPS_PRINTS                           PR00661: L83-D102, G126-L147                           Band 4   BLAST_DOMO                           DM00609|P52963|2-423: G2-S426                           DM00609|P29074|19-463: E10-S368                           DM00609|P11171|200-623: Y12-Q406                           DM00609|P11434|183-612: C13-K435                           NBL4, structural cytoskelton,   BLAST_PRODOM                           Band 4.1-like                           PD040496: S402-N531                           Cytoskeleton structural protein,   BLAST_PRODOM                           phosphatase, protein tyrosine                           phosphorylation, Moesin, Band                           PD000961: F11-D209                           Cytoskeleton structural protein,   BLAST_PRODOM                           phosphatase, protein tyrosine                           phosphorylation, Band PD014063:                           L210-D404                           Band 4.1-like protein 4   BLAS_PRODOM                           PD129254: R533-E580       2   959690CD1   541   S153 S194 S226   N213 N294   PDZ domain (Also known as DHR or   HMMER_PFAM                   S248 S263 S273   N345   GLGF):                   S295 S436 T113       V43-V135                   T158 T288 T356       PX domain: D156-S265   HMMER_PFAM                   T363 T364 T479       PDZ domain protein: V95-N105   BLIMPS_PFAM                   Y400       GLGF domain DM00224|A54971|1358-1454;   BLAST_DOMO                           V44-R122                           (P-value = 8.2e−10)                           F25H2.2 protein PD136546:   BLAST_PRODOM                           D274-T541       3   7091536CD1   570   S150 S158 S168       Transmembrane domains:   HMMER                   S261 S320 S331       S216-Q233, L504-L522                   S375 S382 S396       FERM domain (Band 4.1 family):   HMMER_PFAM                   S407 S408 S425       C19-H210                   S455 S487 S525       Band 4.1 family motif: W71-D100   MOTIFS                   T367 T468 T470       Band 4.1 family domain   ProfileScan                   T523 Y17 Y29       signatures:                   T20 S9       K76-D120, G185-Q233                           Band 4.1 family domain:   BLIMPS_BLOCKS                           BL00660A: D26-V78                           BL00660B: R110-D149                           BL00660C: T190-Q233                           BL00660D: I241-E264                           BL00660E: Y272-Y294                           Band 4.1 protein family   BLIMPS_PRINTS                           PR00935: L50-F62, L115-C128, C128-                           Y148, T190-G206                           ERM family signature   BLIMPS_PRINTS                           PR00661: T30-H49, Q81-D100, G124-                           I145                           Band 4   BLAST_DOMO                           DM00609|p11171|200-623: R15-G379                           Band 4   BLAST_DOMO                           DM00609|P52963|2-423: S12-V327                           Band 4   BLAST_DOMO                           DM00609|p11434|183-612: C19-G345                           Band 4   BLAST_DOMO                           DM00609|P29074|19-463: E16-E337                           Cytoskeleton structural protein,   BLAST_PRODOM                           phosphatase, protein tyrosine                           phosphorylation, Moesin, Band                           PD000961: Y17-D208                           Cytoskeleton structural protein,   BLAST_PRODOM                           phosphatase, protein tyrosine                           phosphorylation, Band                           PD014063: H210-P339       4   7472724CD1   163   S145 S86 T11   N125   Ank repeat:   HMMER_PFAM                   T155 T54       Y31-R63, K64-R96, E97-F129, F130-                           K162                           Ank repeat proteins   BLIMPS_PFAM                           PF00023: L69-L84, G131-Y140       5   5844189CD1   2803   S1013 S1029   N1245 N2010   Leucine_Zipper   MOTIFS                   S1146 S119       L1408-L1429                   S1190 S1198       L1415-L1436                   S1213 S1254       L1422-L1443                   S1311 S149       L1457-L1478                   S1544 S155       L1464-L1485                   S1791 S1801 S19       L1551-L1572                   S1931 S2001       MICROTUBULE; 1A; MAP1B; 1B;   BLAST_DOMO                   S2022 S2092       DM03993                   S2096 S2099       P34926|1-652: M1-E654                   S2104 S2106       NEURAXIN AND MAP1B PROTEINS   BLAST_DOMO                   S2108 S2182       REPEATED REGION                   S2259 S2270       DM04499|P34926|2393-2773: S2419-                   S2299 S2400       F2803                   S2401 S2460                   S2467 S2502                   T1514 T1526                   T1033 T1048                   T1169 T1208                   T1270 T1310                   S831 S844 S877                   S878 S899 S900                   S921 S951 S986                   S2509 S2511       MICROTUBULE ASSOCIATED PROTEIN 1A   BLAST_PRODOM                   S2533 S2589       CONTAINS: MAP1 LIGHT CHAIN LC2                   S2682 S2703       MICROTUBULES REPEAT                   S2723 S322 S367       PD043025: T452-V938                   S410 S460 S526       PD042764: V948-Y1388                   S527 S612 S644       PD040324: R2158-E2470                   T1944 T1949       PD014346: M1-S410                   T2011 T2212                   T2344 T259                   T2655 T295 T326                   T359 T452 T563                   T616 T622 T675                   T692 T749 T833                   T862 T991 Y1640                   Y291                   S66 S667 S744                   S751 S771 S798                   T1590 T1656                   T1674 T1728                   T1420 T1462       6   7472720CD1   1029   S147 S268 S311   N388 N391   Ank repeat ank:   HMMER_PFAM                   S333 S367 S377   N720 N721   Q66-K98, E99-I131,Y132-K164,                   S393 S597 S622   N949 N997   D165-R197, L198-M230                   S683 S688 S770       Ank repeat proteins   BLIMPS_PRODOM                   S781 S8 S823       PD00078B: D130-Y142                   S953 S959 S967       Ank repeat proteins   BLIMPS_PFAM                   T338 T356 T390       PF00023: L71-L86, G133-Y142                   T440 T491 T529       TRICHOHYALIN   BLAST_DOMO                   T625 T672 T723       DM03839|P22793|921-1475: A359-Q898                   T913 T926 T933                   T957 T986 Y608                   Y892       7   7583990CD1   696   S172 S184 S235   N182 N226   Signal_cleavage: M1-M40   SPSCAN                   S253 S269 S305       DBL; ONCOGENE; TRANSFORMING;   BLAST_DOMO                   S368 S55 S550       DM05391|S51620|1-290: V124-Q388                   S568 S575 S609       GUANINE NUCLEOTIDE EXCHANGE   BLAST_PRODOM                   S640 S661 S667       FACTOR                   T109 T212 T272       PD006893: P89-Q279                   T38 T416 T572       PD009732: M1-Q85       8   2058182CD1   803   S109 S150 S171   N13 N449 N463   Signal_cleavage: M1-A62   SPSCAN                   S261 S308 S349   N470 N515   RhoGAP GTPase activator domain   HMMER_PFAM                   S46 S497 S589   N796   RhoGAP:                   S624 S742 T175       A266-T415                   T214 T233 T252       Rho-GAP PF00620B: D316-P332   BLIMPS_PFAM                   T38 T415 T468       PH (pleckstrin homology) DOMAIN   BLAST_DOMO                   T550 T60 T83       DM00470                   T96 Y124       P55194|113-387: E178-D439                           P11274|973-1254: F250-L408, H541-                           P568, E118-T175                           A49307|566-842: F250-H437, E118-                           T175                           P98171|405-693: F250-L408                           GTPASE ACTIVATION   BLAST_PRODOM                           PD109560: D87-P248 PD000780:                           I265-L408                           GTPASE DOMAIN AC PD00930B:   BLIMPS_PRODOM                           L367-L407       9   3564377CD1   701   S131 S243 S333   N395 N476   RhoGAP: A290-Q441   HMMER_PFAM                   S373 S491 S544       Rho-GAP GTPase activator   BLIMPS_PFAM                   S550 S61 S613       PF00620B: D316-P332                           GTPASE DOMAIN AC   BLIMPS_PRODOM                           PD00930A: L391-L431       9           S635 S84 T154       GTPASE ACTIVATION   BLAST_PRODOM                   T190 T218 T485       PD109561: Q441-G680,                   T489 T534 T565       PD109560: L88-P292,                   T80       PD000780: I289-D440                           PH (pleckstrin homology) DOMAIN   BLAST_DOMO                           DM00470                           P55194|113-387: E193-T467                           A49307|566-842: V273-I462                           P15882|109-331: H269-D466                           A43953|74-296: H269-D466       10   1568689CD1   354   T112 T190 T19       Kelch motif Kelch:   HMMER_PFAM                   T67 S210 S264       C20-P66, A68-P114, A116-P162,                   T317       P164-P209, R211-L265, K270-P316                           Kelch repeat signature PR00501   BLIMPS_PRINTS                           P313-L325, G174-L187, T247-L261       11   1393767CD1   605   S12 S21 S56 S58   N19   WD domain, G-beta repeat:   HMMER_PFAM                   S64 S115 S148       A164-D202, P209-D245, L255-D293,                   S183 S250 S256       I356-S392, S399-D436                   S261 S298 S447       WD-40 repeat proteins   BLIMPS_BLOCKS                   S498 S546 S578       BL00678: S282-W292                   T93 T246 T276       G-PROTEIN BETA WD-40 REPEAT   BLIMPS_BLOCKS                   T309 T351 T382       PR00320A: C280-I294                   T387 T425 T426       BETA H-PROTEIN TRANSDUCIN   BLIMPS_PRINTS                   T477 T504 T533       PR00319B: C280-I294                   Y106       DYNEIN INTERMEDIATE CHAIN MOTOR   BLAST_PRODOM                           PROTEIN MICROTUBULES FLAGELLA                           REPEAT WD CILIARY                           PD040521: E354-F553                           PD018332: S12-E315                           PD037574: M1-W81                           do DYNEIN; CYTOSOLIC;   BLAST_DOMO                           INTERMEDIATE; 74 K;                           DM08083|P54703|101-535: D84-R347       12   3029343CD1   1179   S117 S124 S133   N591 N655       MOTIFS                   S218 S221 S223   N695 N899                   S266 S299 S309   N1083 N1139                   S424 S438 S593   N1146                   S608 S641 S694                   S706 S832 S839                   S931 S939 S986                   S1014 S959 S83                   S1125 T131 T138                   T219 S1132 T240                   T250 T481 T657                   T841 T901 T914                   T1011 S77 T1030                   T1107 T1148       13   5507629CD1   372   S77 S201 S203   N12   Actin: M1-F372   HMMER_PFAM                   S253 S335 T76       Actin proteins   BLIMPS_BLOCKS                   T355       BL00406: P7-Q41, E82-Q136, L141-                           H195, L266-A320, A323-F372                           Actins signatures   PROFILESCAN                           actins_2.prf: K333-F372                           Actin signature   BLIMPS_PRINTS                           PR00190: I83-P101, N114-G127,                           L139-V158, L233-D249, G48-D59,                           W60-E82                           PROTEIN STRUCTURAL ACTIN MULTIGENE   BLAST_PRODOM                           FAMILY ACETYLATION MUSCLE                           CYTOSKELETON CYTOPLASMIC PD000056:                           V8-F372                           ACTINS AND ACTIN-RELATED PROTEINS   BLAST_DOMO                           DM00167|A03001|1-269: V8-L266                           DM00167|P02578|1-268: V8-L266                           DM00167|P12432|1-268: Q5-L266                           DM00167|P14883|1-269: M1-P261                           Actins &amp; actin-related proteins   MOTIFS                           signature: L103-R115       14   5607780CD1   1561   S63 S171 S271   N169 N242   Phorbol esters/diacylglycerol   HMMER_PFAM                   S286 S399 S477   N397 N438   binding domain: H37-C83                   S478 S515 S534   N451 N844   Src homology domain 2: W1288-H1383   HMMER_PFAM                   S556 S613 S687       Phorbol esters/DAG binding domain   BLIMPS_BLOCKS                   S754 S859 S878       proteins BL00479: H37-G59, Q60-C75                   S892 S927 S952       Phorbol esters/DAG binding domain   PROFILESCAN                   S982 S1003       dag_pe_binding_domain.prf:                   S1057 S1059       C50-P110                   S1069 S1079       TENSIN ACTIN BINDING CYTOSKELETON   BLAST_PRODOM                   S1098 S1119       SH2 DOMAIN                   S1221 S1270       PD148069: E457-P1212, Y361-E457                   S1317 S1416       PD034457: S1416-I1555                   S1512 S1525       PD147924: T1188-F1287                   S1557 T116 T129       PROTEIN PHOSPHORYLATION AUXILIN   BLAST_PRODOM                   T518 T529 T873       COAT REPEAT CYCLIN GASSOCIATED                   T1094 T1284       KINASE TRANSFERASE                   T1358 T1475       PD025411: S171-C360                           SRC HOMOLOGY 2 (SH2) DOMAIN   BLAST_DOMO                           DM00048|Q04205|1455-1573: Q1282-                           L1402                           Phorbol esters/DAG binding domain:   MOTIFS                           H37-C83                    
     [0383]                                       TABLE 4                           Incyte                           Polynucleotide   Polynucleotide   Sequence   Selected                   SEQ ID NO:   ID   Length   Fragment (s)   Sequence Fragments   5′ Position   3′ Position                                                            15   1806450CB1   2066   1-53, 914-980   7011045F8 (KIDNNOC01)   397   975                       4334891T6 (KIDCTMT01)   1504   2066                       934453T6 (CERVNOT01)   1   424                       6898687R9 (LIVRTMR01)   905   1659                       6768027J1 (BRAUNOR01)   449   1155       16   959690CB1   1912   1532-1912,   6618442H1 (BRAUTDR04)   720   1226                   65-127                       959690T6 (BRSTTUT03)   1092   1698                       6618442J1 (BRAUTDR04)   1242   1912                       5603145T6 (MONOTXN03)   663   1212                       7758631H1 (THYMNOE02)   69   689                       GNN.g9188381_000026_002   1   312       17   7091536CB1   2846   1-83, 2277-2846,   7190549T9 (BRATDIC01)   1858   2475                   2197-2224                       5970463H1 (BRAZNOT01)   2322   2846                       7274095H1 (PROSUNJ01)   672   1260                       5972128H1 (BRAZNOT01)   233   897                       7190549H1 (BRATDIC01)   1   588                       5899281F6 (BRAYDIN03)   1040   1619                       6055275H1 (BRAENOT04)   1461   2059       18   7472724CB1   1200   1-119   6577872H1 (BRANDIT04)   676   1200                       71989128V1   578   1200                       7651017H1 (STOMTDE01)   1   610                       8008388H2 (NOSEDIC02)   866   1200       19   5844189CB1   10253   1-737   3450803H1 (UTRSNON03)   8896   9160                       6435007H1 (LUNGNON07)   1151   1719                       3825305H1 (BRAIHCT01)   9385   9667                       702684R6 (SYNORAT03)   8605   9118                       7226621H1 (BRAXTDR15)   4608   5235                       71108830V1   1700   2266                       1412637F6 (BRAINOT12)   9965   10253                       3470805H1 (BRAIDIT01)   8546   8818                       1290463F6 (BRAINOT11)   9109   9655                       7231177H1 (BRAXTDR15)   5266   5828                       70837321V1   1197   1729                       71105936V1   2226   2809                       70484333V1   551   1173                       6438073H1 (BRAENOT02)   7710   8269                       2492760F6 (ADRETUT05)   1   560                       3147658H1 (PENCNOT05)   8386   8699                       6983064H1 (BRAIFER05)   2974   3510                       6762815J1 (BRAUNOR01)   6048   6610                       70485476V1   468   1133                       6950596H1 (BRAITDR02)   7485   8068                       6885353J1 (BRAHTDR03)   7282   7924                       6774466H1 (OVARDIR01)   3835   4509                       7628765H1 (GBLADIE01)   4768   5274                       1290463T6 (BRAINOT11)   9551   10232                       6985284H1 (BRAIFER05)   3295   3911                       6894193J1 (BRAITDR03)   5058   5669                       6463879H2 (OSTEUNC01)   8071   8466                       6887148J1 (BRAITDR03)   2357   3056                       6908894H1 (PITUDIR01)   4241   4709                       6870888H1 (BRAGNON02)   5734   6143                       6888951J1 (BRAITDR03)   6675   7305                       6992849H1 (BRAQTDR02)   6439   7061                       71262033V1   1725   2293       20   7472720CB1   3851   165-225,   55136611T1   1388   1849                   1040-1205,                   2715-2955,                   1662-1724                       7948427H1 (BRABNOE02)   1994   2535                       3071429H1 (UTRSNOR01)   2421   2714                       7117454H1 (BRAHNOE01)   1719   1873                       4110728F9 (PROSBPT07)   1   509                       71996691V1   3226   3851                       71998563V1   2974   3633                       6394784F8 (UTRENOT10)   242   971                       5963992T9 (BRATNOT05)   934   1430                       71722971V1   1757   2433                       GNN.g6425557_010.edit   1610   3386       21   7583990CB1   3100   1-300, 2838-3100   5948913H1 (LIVRTUN04)   2802   3100                       6401188T8 (UTRENOT10)   1763   2526                       7153096H1 (BONEUNR01)   431   956                       3728642H1 (SMCCNON03)   2574   2858                       5632906R8 (PLACFER01)   1133   1558                       1458392T6 (COLNFET02)   1974   2558                       6808658H1 (SKIRNOR01)   627   1212                       7430535H1 (UTRMTMR02)   1   566                       412504F1 (BRSTNOT01)   2250   2833                       7076127H1 (BRAUTDR04)   1241   1823       22   2058182CB1   3248   1-313   g1548017   2790   3248                       70790685V1   2155   2752                       3853541F6 (BRAITUT12)   625   1155                       7977047H1 (LSUBDMC01)   1   644                       6936022H1 (SINTTMR02)   1206   1783                       70791096V1   1952   2567                       8013460H1 (HEARNOC04)   2688   3247                       70789630V1   1402   2003                       7039568H1 (UTRSTMR02)   772   1261       23   3564377CB1   2592   1-216, 1741-2592   1807042F6 (SINTNOT13)   2257   2592                       7083969H1 (STOMTMR02)   1461   1994                       996489R6 (KIDNTUT01)   283   776                       1390744T6 (EOSINOT01)   1823   2469                       7720436J1 (THYRDIE01)   97   625                       6821354J1 (SINTNOR01)   1020   1719                       6178475H1 (BMARUNT02)   1   270                       7765524J1 (URETTUE01)   702   1359       24   1568689CB1   2004   1-51   7665791H1 (SPLNFEC01)   1   547                       1863491F6 (PROSNOT19)   1188   1758                       71955811V1   505   1093                       2782052F6 (OVARTUT03)   1685   2004                       71952924V1   658   1312                       1831510F6 (THP1AZT01)   1320   1927       25   1393767CB1   2250   1776-1842,   6318344F6 (LUNGDIN02)   1888   2249                   418-538                       71413002V1   1266   1900                       3679624F9 (LUNGNOT33)   1   608                       6431635H1 (LUNGNON07)   2003   2250                       71412762V1   1193   1784                       7674549J1 (NOSETUE01)   666   1230                       1849430T6 (LUNGFET03)   1621   2228       25   1393767CB1   2250   1776-1842,   71411963V1   575   1172                   418-538       26   3029343CB1   3728   1807-1863,   GBI.g8072612_000002_000007 —     1   1481                   2618-2675, 1-76,   000006.regenscan                   1614-1694,                   247-912,                   1510-1554                       7594615F8 (LIVRNOC07)   1901   2790                       72435607D1   2796   3343                       72435382D1   2662   3317                       7594495F8 (LIVRNOC07)   1602   2444                       72435855D1   3255   3728                       GNN.g8072612_000006_004.edit   595   1581                       6427666H1 (LUNGNON07)   1212   1807       27   5507629CB1   2241   968-1091   4138803H1 (ADRENOT15)   1   282                       8133382H1 (SCOMDIC01)   1277   1989                       4249162F6 (BRADDIR01)   1934   2241                       8031936J1 (TESTNOF01)   615   1324                       4919304F6 (TESTNOT11)   878   1492                       5508394R6 (BRADDIR01)   1705   2226                       g6569543   1   442                       3595464H1 (FIBPNOT01)   319   636       28   5607780CB1   5203   3850-3946, 1-305,   55148770J1   4451   5203                   976-1733,                   2409-3166                       6430080F8 (LUNGNON07)   3124   3882                       71136406V1   546   1194                       8246406H1 (BONEUNR01)   4205   4816                       71135385V1   704   1221                       7199141H1 (LUNGFER04)   2787   3349                       6916264H1 (PLACFER06)   1   631                       55105469H1   1613   2516                       5626906R8 (PLACFER01)   2037   2542                       7724527J1 (THYRDIE01)   3967   4785                       5626906F6 (PLACFER01)   1432   2034                       7714385J1 (SINTFEE02)   2383   3015                       8080767J1 (BONMTUE02)   3370   4094                       7722890J2 (THYRDIE01)   1095   1816                    
     [0384]                       TABLE 5                       Polynucleotide   Incyte           SEQ ID NO:   Project ID   Representative Library                  15   1806450CB1   KIDCTMT01       16    959690CB1   THYMNOE02       17   7091536CB1   BRAIFER05       18   7472724CB1   PROSNON01       19   5844189CB1   BRAYDIN03       20   7472720CB1   UTRENOT10       21   7583990CB1   BRSTNOT01       22   2058182CB1   CORPNOT02       23   3564377CB1   EOSINOT01       24   1568689CB1   BRAITUT21       25   1393767CB1   LUNGDIN02       26   3029343CB1   LIVRNOC07       27   5507629CB1   BRADDIR01       28   5607780CB1   THYRDIE01                    
     [0385]                       TABLE 6                       Library   Vector   Library Description                  BRADDIR01   pINCY   Library was constructed using RNA isolated from diseased choroid plexus tissue of the               lateral ventricle, removed from the brain of a 57-year-old Caucasian male, who died from               a cerebrovascular accident.       BRAIFER05   pINCY   Library was constructed using RNA isolated from brain tissue removed from a Caucasian               male fetus who was stillborn with a hypoplastic left heart at 23 weeks&#39; gestation.       BRAITUT21   pINCY   Library was constructed using RNA isolated from brain tumor tissue removed from the               midline frontal lobe of a 61-year-old Caucasian female during excision of a cerebral               meningeal lesion. Pathology indicated subfrontal meningothelial meningioma with no               atypia. One ethmoid and mucosal tissue sample indicated meningioma. Family history               included cerebrovascular disease, senile dementia, hyperlipidemia, benign hypertension,               atherosclerotic coronary artery disease, congestive heart failure, and breast cancer.       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.       BRSTNOT01   PBLUESCRIPT   Library was constructed using RNA isolated from the breast tissue of a 56-year-old               Caucasian female who died in a motor vehicle accident.       CORPNOT02   pINCY   Library was constructed using RNA isolated from diseased corpus callosum tissue removed               from the brain of a 74-year-old Caucasian male who died from Alzheimer&#39;s disease.       EOSINOT01   pINCY   Library was constructed using RNA isolated from microscopically normal eosinophils from               31 non-allergic donors. Donors abstained from prescription and over- the-counter drug               use for at least one week prior to donating 200 ml of peripheral venous blood.       KIDCTMT01   pINCY   Library was constructed using RNA isolated from kidney cortex tissue removed from a 65-               year-old male during nephroureterectomy. Pathology for the associated tumor tissue               indicated grade 3 renal cell carcinoma within the mid-portion of the kidney and the               renal capsule.       LIVRNOC07   pINCY   Library was constructed using pooled cDNA from two different donors. cDNA was generated               using RNA isolated from liver tissue removed from a 20-week-old Caucasian male fetus who               died from Patauas Syndrome (donor A) and a 16-week-old Caucasian female fetus who died               from anencephaly (donor B). Family history included mitral valve prolapse in donor B.       LUNGDIN02   pINCY   This normalized lung tissue library was constructed from 7.6 × 10e5 independent clones               from a diseased lung tissue library. Starting RNA was made from RNA isolated from               diseased lung tissue. Pathology indicated ideopathic pulmonary disease. The library               was normalized in 2 rounds using conditions adapted from Soares et al., PNAS (1994)               91: 9228-9232 and Bonaldo et al., Genome Research 6 (1996): 791, except that a               significantly longer (48 hours/round) reannealing hybridization was used.       PROSNON01   PSPORT1   This normalized prostate library was constructed from 4.4 M independent clones from a               prostate library. Starting RNA was made from prostate tissue removed from a 28-year-old               Caucasian male who died from a self-inflicted gunshot wound. The normalization and               hybridization conditions were adapted from Soares, M.B. et al. (1994) Proc. Natl. Acad.               Sci. USA 91: 9228-9232, using a longer (19 hour) reannealing hybridization period.       THYMNOE02   PCDNA2.1   This 5′ biased random primed library was constructed using RNA isolated from thymus               tissue removed from a 3-year-old Hispanic male during a thymectomy and closure of a               patent ductus arteriosus. The patient presented with severe pulmonary stenosis and               cyanosis. Patient history included a cardiac catheterization and echocardiogram.               Previous surgeries included Blalock-Taussig shunt and pulmonary valvotomy. The patient               was not taking any medications. Family history included benign hypertension,               osteoarthritis, depressive disorder, and extrinsic asthma in the grandparent(s).       THYRDIE01   PCDNA2.1   This 5′ biased random primed library was constructed using RNA isolated from diseased               thyroid tissue removed from a 22-year-old Caucasian female during closed thyroid biopsy,               partial thyroidectomy, and regional lymph node excision. Pathology indicated adenomatous               hyperplasia. The patient presented with malignant neoplasm of the thyroid. Patient               history included normal delivery, alcohol abuse, and tobacco abuse. Previous surgeries               included myringotomy. Patient medications included an unspecified type of birth control               pills. Family history included hyperlipidemia and depressive disorder in the mother; and               benign hypertension, congestive heart failure, and chronic leukemia in the               grandparent(s).       UTRENOT10   pINCY   Library was constructed using RNA isolated from pooled uterine endometiral tissue               removed from three adult females during endometrial biopsy. Pathology indicated normal               endometrium. All three patients were positive for Beta-3 integrin.                    
     [0386]                           TABLE 7                       Program   Description   Reference   Parameter Threshold                  ABI   A program that removes vector sequences and   Applied Biosystems, Foster City, CA.           FACTURA   masks ambiguous bases in nucleic acid sequences.       ABI/   A Fast Data Finder useful in comparing and   Applied Biosystems, Foster City, CA;   Mismatch &lt; 50%       PARACEL       FDF   annotating amino acid or nucleic acid sequences.   Paracel Inc., Pasadena, CA.       ABI Auto-   A program that assembles nucleic acid sequences.   Applied Biosystems, Foster City, CA.       Assembler       BLAST   A Basic Local Alignment Search Tool useful in   Altschul, S.F. et al. (1990) J. Mol. Biol.   ESTs: Probability           sequence similarity search for amino acid and   215: 403-410; Altschul, S.F. et al. (1997)   value = 1.0E−8 or less           nucleic acid sequences. BLAST includes five   Nucleic Acids Res. 25: 3389-3402.   Full Length sequences:           functions: blastp, blastn, blastx, tblastn, and tblastx.       Probability value = 1.0                   E−10 or less       FASTA   A Pearson and Lipman algorithm that searches for   Pearson, W. R. and D. J. Lipman (1988) Proc.   ESTs: fasta E value =           similarity between a query sequence and a group of   Natl. Acad Sci. USA 85: 2444-2448; Pearson,   1.06E−6 Assembled           sequences of the same type. FASTA comprises as   W. R. (1990) Methods Enzymol. 183: 63-98;   ESTs: fasta Identity =           least five functions: fasta, tfasta, fastx, tfastx, and   and Smith, T. F. and M. S. Waterman (1981)   95% or greater and           ssearch.   Adv. Appl. Math. 2: 482-489.   Match length = 200                   bases or greater; fastx E                   value = 1.0E−8 or less                   Full Length sequences:                   fastx score = 100 or                   greater       BLIMPS   A BLocks IMProved Searcher that matches a   Henikoff, S. and J. G. Henikoff (1991) Nucleic   Probability value =           sequence against those in BLOCKS, PRINTS,   Acids Res. 19: 6565-6572; Henikoff, J. G. and   1.0E−3 or less           DOMO, PRODOM, and PFAM databases to search   S. Henikoff (1996) Methods Enzymol.           for gene families, sequence homology, and   266: 88-105; and Attwood, T. K. et al. (1997)           structural fingerprint regions.   J. Chem. Inf. Comput. Sci. 37: 417-424.       HMMER   An algorithm for searching a query sequence against   Krogh, A. et al. (1994) J. Mol. Biol.   PFAM hits: Probability           hidden Markov model (HMM)-based databases of   235: 1501-1531; Sonnhammer, E. L. L. et al.   value = 1.0E−3 or less           protein family consensus sequences, such as PFAM.   (1988) Nucleic Acids Res. 26: 320-322;   Signal peptide hits:               Durbin, R. et al. (1998) Our World View, in a   Score = 0 or greater               Nutshell, Cambridge Univ. Press, pp. 1-350.       ProfileScan   An algorithm that searches for structural and sequence   Gribskov, M. et al. (1988) CABIOS 4: 61-66;   Normalized quality           motifs in protein sequences that match sequence   Gribskov, M. et al. (1989) Methods Enzymol.   score ≧ GCG-           patterns defined in Prosite.   183: 146-159; Bairoch, A. et al. (1997)   specified “HIGH” value               Nucleic Acids Res. 25: 217-221.   for that particular Prosite                   motif. Generally, score =                   1.4-2.1.       Phred   A base-calling algorithm that examines automated   Ewing, B. et al. (1998) Genome Res.           sequencer traces with high sensitivity and probability.   8: 175-185; Ewing, B. and P. Green               (1998) Genome Res. 8: 186-194.       Phrap   A Phils Revised Assembly Program including SWAT   Smith, T. F. and M. S. Waterman (1981) Adv.   Score = 120 or greater;           and CrossMatch, programs based on efficient   Appl. Math. 2: 482-489; Smith, T. F. and M. S.   Match length = 56           implementation of the Smith-Waterman algorithm,   Waterman (1981) J. Mol. Biol. 147: 195-197;   or greater           useful in searching sequence homology and   and Green, P., University of Washington,           assembling DNA sequences.   Seattle, WA.       Consed   A graphical tool for viewing and editing Phrap   Gordon, D. et al. (1998) Genome Res. 8: 195-202.           assemblies.       SPScan   A weight matrix analysis program that scans protein   Nielson, H. et al. (1997) Protein Engineering   Score = 3.5 or greater           sequences for the presence of secretory signal peptides.   10: 1-6; Claverie, J. M. and S. Audic (1997)               CABIOS 12: 431-439.       TMAP   A program that uses weight matrices to delineate   Persson, B. and P. Argos (1994) J. Mol. Biol.           transmembrane segments on protein sequences and   237: 182-192; Persson, B. and P. Argos (1996)           determine orientation.   Protein Sci. 5: 363-371.       TMHMMER   A program that uses a hidden Markov model (HMM)   Sonnhammer, E. L. et al. (1998) Proc. Sixth Intl.           to delineate transmembrane segments on protein   Conf. on Intelligent Systems for Mol. Biol.,           sequences and determine orientation.   Glasgow et al., eds., The Am. Assoc. for Artificial               Intelligence Press, Menlo Park, CA, pp. 175-182.       Motifs   A program that searches amino acid sequences for   Bairoch, A. et al. (1997) Nucleic Acids Res. 25: 217-           patterns that matched those defined in Prosite.   221; Wisconsin Package Program Manual, version 9,               page M51-59, Genetics Computer Group,               Madison, WI.                    
     [0387] 
    
     
       
         1 
         
           
             28  
           
           
             1  
             580  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 1806450CD1  
             
           
            1 

Met Gly Cys Phe Cys Ala Val Pro Glu Glu Phe Tyr Cys Glu Val 
  1               5                  10                  15 

Leu Leu Leu Asp Glu Ser Lys Leu Thr Leu Thr Thr Gln Gln Gln 
                 20                  25                  30 

Gly Ile Lys Lys Ser Thr Lys Gly Ser Val Val Leu Asp His Val 
                 35                  40                  45 

Phe His His Val Asn Leu Val Glu Ile Asp Tyr Phe Gly Leu Arg 
                 50                  55                  60 

Tyr Cys Asp Arg Ser His Gln Thr Tyr Trp Leu Asp Pro Ala Lys 
                 65                  70                  75 

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

Thr Leu Tyr Phe Gly Ile Lys Phe Tyr Ala Glu Asp Pro Cys Lys 
                 95                 100                 105 

Leu Lys Glu Glu Ile Thr Arg Tyr Gln Phe Phe Leu Gln Val Lys 
                110                 115                 120 

Gln Asp Val Leu Gln Gly Arg Leu Pro Cys Pro Val Asn Thr Ala 
                125                 130                 135 

Ala Gln Leu Gly Ala Tyr Ala Ile Gln Ser Glu Leu Gly Asp Tyr 
                140                 145                 150 

Asp Pro Tyr Lys His Thr Ala Gly Tyr Val Ser Glu Tyr Arg Phe 
                155                 160                 165 

Val Pro Asp Gln Lys Glu Glu Leu Glu Glu Ala Ile Glu Arg Ile 
                170                 175                 180 

His Lys Thr Leu Met Gly Gln Ile Pro Ser Glu Ala Glu Leu Asn 
                185                 190                 195 

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

His Pro Val Tyr Gly Glu Asn Lys Ser Glu Tyr Phe Leu Gly Leu 
                215                 220                 225 

Thr Pro Val Gly Val Val Val Tyr Lys Asn Lys Lys Gln Val Gly 
                230                 235                 240 

Lys Tyr Phe Trp Pro Arg Ile Thr Lys Val His Phe Lys Glu Thr 
                245                 250                 255 

Gln Phe Glu Leu Arg Val Leu Gly Lys Asp Cys Asn Glu Thr Ser 
                260                 265                 270 

Phe Phe Phe Glu Ala Arg Ser Lys Thr Ala Cys Lys His Leu Trp 
                275                 280                 285 

Lys Cys Ser Val Glu His His Thr Phe Phe Arg Met Pro Glu Asn 
                290                 295                 300 

Glu Ser Asn Ser Leu Ser Arg Lys Leu Ser Lys Phe Gly Ser Ile 
                305                 310                 315 

Arg Tyr Lys His Arg Tyr Ser Gly Arg Thr Ala Leu Gln Met Ser 
                320                 325                 330 

Arg Asp Leu Ser Ile Gln Leu Pro Arg Pro Asp Gln Asn Val Thr 
                335                 340                 345 

Arg Ser Arg Ser Lys Thr Tyr Pro Lys Arg Ile Ala Gln Thr Gln 
                350                 355                 360 

Pro Ala Glu Ser Asn Thr Ile Ser Arg Ile Thr Ala Asn Met Glu 
                365                 370                 375 

Asn Gly Glu Asn Glu Gly Thr Ile Lys Ile Ile Ala Pro Ser Pro 
                380                 385                 390 

Val Lys Ser Phe Lys Lys Ala Lys Asn Glu Asn Ser Pro Asp Thr 
                395                 400                 405 

Gln Arg Ser Lys Ser His Ala Pro Trp Glu Glu Asn Gly Pro Gln 
                410                 415                 420 

Ser Gly Leu Tyr Asn Ser Pro Ser Asp Arg Thr Lys Ser Pro Lys 
                425                 430                 435 

Phe Pro Tyr Thr Arg Arg Arg Asn Pro Ser Cys Gly Ser Asp Asn 
                440                 445                 450 

Asp Ser Val Gln Pro Val Arg Arg Arg Lys Ala His Asn Ser Gly 
                455                 460                 465 

Glu Asp Ser Asp Leu Lys Gln Arg Arg Arg Ser Arg Ser Arg Cys 
                470                 475                 480 

Asn Thr Ser Ser Gly Ser Glu Ser Glu Asn Ser Asn Arg Glu His 
                485                 490                 495 

Arg Lys Lys Arg Asn Arg Ile Arg Gln Glu Asn Asp Met Val Asp 
                500                 505                 510 

Ser Ala Pro Gln Trp Glu Ala Val Leu Arg Arg Gln Lys Glu Lys 
                515                 520                 525 

Asn His Ala Asp Pro Asn Ser Arg Arg Ser Arg His Arg Ser Arg 
                530                 535                 540 

Ser Arg Ser Pro Asp Ile Gln Ala Lys Glu Glu Leu Trp Lys His 
                545                 550                 555 

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

Leu Lys Glu Ile Pro Tyr Thr Lys Ile Glu 
                575                 580 

 
           
             2  
             541  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 959690CD1  
             
           
            2 

Met Ala Asp Glu Asp Gly Glu Gly Ile His Pro Ser Ala Pro His 
  1               5                  10                  15 

Arg Asn Gly Gly Gly Gly Gly Gly Gly Gly Ser Gly Leu His Cys 
                 20                  25                  30 

Ala Gly Asn Gly Gly Gly Gly Gly Gly Gly Pro Arg Val Val Arg 
                 35                  40                  45 

Ile Val Lys Ser Glu Ser Gly Tyr Gly Phe Asn Val Arg Gly Gln 
                 50                  55                  60 

Val Ser Glu Gly Gly Gln Leu Arg Ser Ile Asn Gly Glu Leu Tyr 
                 65                  70                  75 

Ala Pro Leu Gln His Val Ser Ala Val Leu Pro Gly Gly Ala Ala 
                 80                  85                  90 

Asp Arg Ala Gly Val Arg Lys Gly Asp Arg Ile Leu Glu Val Asn 
                 95                 100                 105 

His Val Asn Val Glu Gly Ala Thr His Lys Gln Val Val Asp Leu 
                110                 115                 120 

Ile Arg Ala Gly Glu Lys Glu Leu Ile Leu Thr Val Leu Ser Val 
                125                 130                 135 

Pro Pro His Glu Ala Asp Asn Leu Asp Pro Ser Asp Asp Ser Leu 
                140                 145                 150 

Gly Gln Ser Phe Tyr Asp Tyr Thr Glu Lys Gln Ala Val Pro Ile 
                155                 160                 165 

Ser Val Pro Arg Tyr Lys His Val Glu Gln Asn Gly Glu Lys Phe 
                170                 175                 180 

Val Val Tyr Asn Val Tyr Met Ala Gly Arg Gln Leu Cys Ser Lys 
                185                 190                 195 

Arg Tyr Arg Glu Phe Ala Ile Leu His Gln Asn Leu Lys Arg Glu 
                200                 205                 210 

Phe Ala Asn Phe Thr Phe Pro Arg Leu Pro Gly Lys Trp Pro Phe 
                215                 220                 225 

Ser Leu Ser Glu Gln Gln Leu Asp Ala Arg Arg Arg Gly Leu Glu 
                230                 235                 240 

Glu Tyr Leu Glu Lys Val Cys Ser Ile Arg Val Ile Gly Glu Ser 
                245                 250                 255 

Asp Ile Met Gln Glu Phe Leu Ser Glu Ser Asp Glu Asn Tyr Asn 
                260                 265                 270 

Gly Val Ser Asp Val Glu Leu Arg Val Ala Leu Pro Asp Gly Thr 
                275                 280                 285 

Thr Val Thr Val Arg Val Lys Lys Asn Ser Thr Thr Asp Gln Val 
                290                 295                 300 

Tyr Gln Ala Ile Ala Ala Lys Val Gly Met Asp Ser Thr Thr Val 
                305                 310                 315 

Asn Tyr Phe Ala Leu Phe Glu Val Ile Ser His Ser Phe Val Arg 
                320                 325                 330 

Lys Leu Ala Pro Asn Glu Phe Pro His Lys Leu Tyr Ile Gln Asn 
                335                 340                 345 

Tyr Thr Ser Ala Val Pro Gly Thr Cys Leu Thr Ile Arg Lys Trp 
                350                 355                 360 

Leu Phe Thr Thr Glu Glu Glu Ile Leu Leu Asn Asp Asn Asp Leu 
                365                 370                 375 

Ala Val Thr Tyr Phe Phe His Gln Ala Val Asp Asp Val Lys Lys 
                380                 385                 390 

Gly Tyr Ile Lys Ala Glu Glu Lys Ser Tyr Gln Leu Gln Lys Leu 
                395                 400                 405 

Tyr Glu Gln Arg Lys Met Val Met Tyr Leu Asn Met Leu Arg Thr 
                410                 415                 420 

Cys Glu Gly Tyr Asn Glu Ile Ile Phe Pro His Cys Ala Cys Asp 
                425                 430                 435 

Ser Arg Arg Lys Gly His Val Ile Thr Ala Ile Ser Ile Thr His 
                440                 445                 450 

Phe Lys Leu His Ala Cys Thr Glu Glu Gly Gln Leu Glu Asn Gln 
                455                 460                 465 

Val Ile Ala Phe Glu Trp Asp Glu Met Gln Arg Trp Asp Thr Asp 
                470                 475                 480 

Glu Glu Gly Met Ala Phe Cys Phe Glu Tyr Ala Arg Gly Glu Lys 
                485                 490                 495 

Lys Pro Arg Trp Val Lys Ile Phe Thr Pro Tyr Phe Asn Tyr Met 
                500                 505                 510 

His Glu Cys Phe Glu Arg Val Phe Cys Glu Leu Lys Trp Arg Lys 
                515                 520                 525 

Glu Asn Ile Phe Gln Met Ala Arg Ser Gln Gln Arg Asp Val Ala 
                530                 535                 540 

Thr 

 
           
             3  
             570  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7091536CD1  
             
           
            3 

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

Glu Tyr Ser Cys Thr Val Arg Leu Leu Asp Asp Ser Glu Tyr Thr 
                 20                  25                  30 

Cys Thr Ile Gln Arg Asp Ala Lys Gly Gln Tyr Leu Phe Asp Leu 
                 35                  40                  45 

Leu Cys His His Leu Asn Leu Leu Glu Lys Asp Tyr Phe Gly Ile 
                 50                  55                  60 

Arg Phe Val Asp Pro Asp Lys Gln Arg His Trp Leu Glu Phe Thr 
                 65                  70                  75 

Lys Ser Val Val Lys Gln Leu Arg Ser Gln Pro Pro Phe Thr Met 
                 80                  85                  90 

Cys Phe Arg Val Lys Phe Tyr Pro Ala Asp Pro Ala Ala Leu Lys 
                 95                 100                 105 

Glu Glu Ile Thr Arg Tyr Leu Val Phe Leu Gln Ile Lys Arg Asp 
                110                 115                 120 

Leu Tyr His Gly Arg Leu Leu Cys Lys Thr Ser Asp Ala Ala Leu 
                125                 130                 135 

Leu Ala Ala Tyr Ile Leu Gln Ala Glu Ile Gly Asp Tyr Asp Ser 
                140                 145                 150 

Val Lys His Pro Glu Gly Tyr Ser Ser Lys Phe Gln Phe Phe Pro 
                155                 160                 165 

Lys His Ser Glu Lys Leu Glu Arg Lys Ile Ala Glu Ile His Lys 
                170                 175                 180 

Thr Glu Leu Ser Gly Gln Thr Pro Ala Thr Ser Glu Leu Asn Phe 
                185                 190                 195 

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

Pro Cys Lys Asp Val Ser Gly Asn Ala Ala Phe Leu Ala Phe Thr 
                215                 220                 225 

Pro Phe Gly Phe Val Val Leu Gln Gly Asn Lys Arg Val His Phe 
                230                 235                 240 

Ile Lys Trp Asn Glu Val Thr Lys Leu Lys Phe Glu Gly Lys Thr 
                245                 250                 255 

Phe Tyr Leu Tyr Val Ser Gln Lys Glu Glu Lys Lys Ile Ile Leu 
                260                 265                 270 

Thr Tyr Phe Ala Pro Thr Pro Glu Ala Cys Lys His Leu Trp Lys 
                275                 280                 285 

Cys Gly Ile Glu Asn Gln Ala Phe Tyr Lys Leu Glu Lys Ser Ser 
                290                 295                 300 

Gln Val Arg Thr Val Ser Ser Ser Asn Leu Phe Phe Lys Gly Ser 
                305                 310                 315 

Arg Phe Arg Tyr Ser Gly Arg Val Ala Lys Glu Val Met Glu Ser 
                320                 325                 330 

Ser Ala Lys Ile Lys Arg Glu Pro Pro Glu Ile His Arg Ala Gly 
                335                 340                 345 

Met Val Pro Ser Arg Ser Cys Pro Ser Ile Thr His Gly Pro Arg 
                350                 355                 360 

Leu Ser Ser Val Pro Arg Thr Arg Arg Arg Ala Val His Ile Ser 
                365                 370                 375 

Ile Met Glu Gly Leu Glu Ser Leu Arg Asp Ser Ala His Ser Thr 
                380                 385                 390 

Pro Val Arg Ser Thr Ser His Gly Asp Thr Phe Leu Pro His Val 
                395                 400                 405 

Arg Ser Ser Arg Thr Asp Ser Asn Glu Arg Val Ala Val Ile Ala 
                410                 415                 420 

Asp Glu Ala Tyr Ser Pro Ala Asp Ser Val Leu Pro Thr Pro Val 
                425                 430                 435 

Ala Glu His Ser Leu Glu Leu Met Leu Leu Ser Arg Gln Ile Asn 
                440                 445                 450 

Gly Ala Thr Cys Ser Ile Glu Glu Glu Lys Glu Ser Glu Ala Ser 
                455                 460                 465 

Thr Pro Thr Ala Thr Glu Val Glu Ala Leu Gly Gly Glu Leu Arg 
                470                 475                 480 

Ala Leu Cys Gln Gly His Ser Gly Pro Glu Glu Glu Gln Val Asn 
                485                 490                 495 

Lys Phe Val Leu Ser Val Leu Arg Leu Leu Leu Val Thr Met Gly 
                500                 505                 510 

Leu Leu Phe Val Leu Leu Leu Leu Leu Ile Ile Leu Thr Glu Ser 
                515                 520                 525 

Asp Leu Asp Ile Ala Phe Phe Arg Asp Ile Arg Gln Thr Pro Glu 
                530                 535                 540 

Phe Glu Gln Phe His Tyr Gln Tyr Phe Cys Pro Leu Arg Arg Trp 
                545                 550                 555 

Phe Ala Cys Lys Ile Arg Ser Val Val Ser Leu Leu Ile Asp Thr 
                560                 565                 570 

 
           
             4  
             163  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7472724CD1  
             
           
            4 

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

Leu Cys Ser Asp Gly Phe Ala Phe Pro Gln Tyr Pro Ile Lys Pro 
                 20                  25                  30 

Tyr His Leu Lys Arg Ile His Arg Ala Val Leu His Gly Asn Leu 
                 35                  40                  45 

Glu Lys Leu Lys Tyr Leu Leu Leu Thr Tyr Tyr Asp Ala Asn Lys 
                 50                  55                  60 

Arg Asp Arg Lys Glu Arg Thr Ala Leu His Leu Ala Cys Ala Thr 
                 65                  70                  75 

Gly Gln Pro Glu Met Val His Leu Leu Val Ser Arg Arg Cys Glu 
                 80                  85                  90 

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

Val Gln Leu Arg Gln Glu Ala Cys Ala Thr Leu Leu Leu Gln Asn 
                110                 115                 120 

Gly Ala Asn Pro Asn Ile Thr Asp Phe Phe Gly Arg Thr Ala Leu 
                125                 130                 135 

His Tyr Ala Val Tyr Asn Glu Asp Thr Ser Met Ile Glu Lys Leu 
                140                 145                 150 

Leu Ser His Gly Thr Asn Ile Glu Glu Cys Ser Lys Val 
                155                 160 

 
           
             5  
             2803  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 5844189CD1  
             
           
            5 

Met Asp Gly Val Ala Glu Phe Ser Glu Tyr Val Ser Glu Thr Val 
  1               5                  10                  15 

Asp Val Pro Ser Pro Phe Asp Leu Leu Glu Pro Pro Thr Ser Gly 
                 20                  25                  30 

Gly Phe Leu Lys Leu Ser Lys Pro Cys Cys Tyr Ile Phe Pro Gly 
                 35                  40                  45 

Gly Arg Gly Asp Ser Ala Leu Phe Ala Val Asn Gly Phe Asn Ile 
                 50                  55                  60 

Leu Val Asp Gly Gly Ser Asp Arg Lys Ser Cys Phe Trp Lys Leu 
                 65                  70                  75 

Val Arg His Leu Asp Arg Ile Asp Ser Val Leu Leu Thr His Ile 
                 80                  85                  90 

Gly Ala Asp Asn Leu Pro Gly Ile Asn Gly Leu Leu Gln Arg Lys 
                 95                 100                 105 

Val Ala Glu Leu Glu Glu Glu Gln Ser Gln Gly Ser Ser Ser Tyr 
                110                 115                 120 

Ser Asp Trp Val Lys Asn Leu Ile Ser Pro Glu Leu Gly Val Val 
                125                 130                 135 

Phe Phe Asn Val Pro Glu Lys Leu Arg Leu Pro Asp Ala Ser Arg 
                140                 145                 150 

Lys Ala Lys Arg Ser Ile Glu Glu Ala Cys Leu Thr Leu Gln His 
                155                 160                 165 

Leu Asn Arg Leu Gly Ile Gln Ala Glu Pro Leu Tyr Arg Val Val 
                170                 175                 180 

Ser Asn Thr Ile Glu Pro Leu Thr Leu Phe His Lys Met Gly Val 
                185                 190                 195 

Gly Arg Leu Asp Met Tyr Val Leu Asn Pro Val Lys Asp Ser Lys 
                200                 205                 210 

Glu Met Gln Phe Leu Met Gln Lys Trp Ala Gly Asn Ser Lys Ala 
                215                 220                 225 

Lys Thr Gly Ile Val Leu Pro Asn Gly Lys Glu Ala Glu Ile Ser 
                230                 235                 240 

Val Pro Tyr Leu Thr Ser Ile Thr Ala Leu Val Val Trp Leu Pro 
                245                 250                 255 

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

Ala Pro Gln Asn Lys Ile Leu Glu Gly Leu Glu Lys Leu Arg His 
                275                 280                 285 

Leu Asp Phe Leu Arg Tyr Pro Val Ala Thr Gln Lys Asp Leu Ala 
                290                 295                 300 

Ser Gly Ala Val Pro Thr Asn Leu Lys Pro Ser Lys Ile Lys Gln 
                305                 310                 315 

Arg Ala Asp Ser Lys Glu Ser Leu Lys Ala Thr Thr Lys Thr Ala 
                320                 325                 330 

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

Lys Glu Ala Arg Ser Glu Leu Ala Lys Glu Leu Ala Lys Thr Glu 
                350                 355                 360 

Lys Lys Ala Lys Glu Ser Ser Glu Lys Pro Pro Glu Lys Pro Ala 
                365                 370                 375 

Lys Pro Glu Arg Val Lys Thr Glu Ser Ser Glu Ala Leu Lys Ala 
                380                 385                 390 

Glu Lys Arg Lys Leu Ile Lys Asp Lys Val Gly Lys Lys His Leu 
                395                 400                 405 

Lys Glu Lys Ile Ser Lys Leu Glu Glu Lys Lys Asp Lys Glu Lys 
                410                 415                 420 

Lys Glu Ile Lys Lys Glu Arg Lys Glu Leu Lys Lys Asp Glu Gly 
                425                 430                 435 

Arg Lys Glu Glu Lys Lys Asp Ala Lys Lys Glu Glu Lys Arg Lys 
                440                 445                 450 

Asp Thr Lys Pro Glu Leu Lys Lys Ile Ser Lys Pro Asp Leu Lys 
                455                 460                 465 

Pro Phe Thr Pro Glu Val Arg Lys Thr Leu Tyr Lys Ala Lys Val 
                470                 475                 480 

Pro Gly Arg Val Lys Ile Asp Arg Ser Arg Ala Ile Arg Gly Glu 
                485                 490                 495 

Lys Glu Leu Ser Ser Glu Pro Gln Thr Pro Pro Ala Gln Lys Gly 
                500                 505                 510 

Thr Val Pro Leu Pro Thr Ile Ser Gly His Arg Glu Leu Val Leu 
                515                 520                 525 

Ser Ser Pro Glu Asp Leu Thr Gln Asp Phe Glu Glu Met Lys Arg 
                530                 535                 540 

Glu Glu Arg Ala Leu Leu Ala Glu Gln Arg Asp Thr Gly Leu Gly 
                545                 550                 555 

Asp Lys Pro Phe Pro Leu Asp Thr Ala Glu Glu Gly Pro Pro Ser 
                560                 565                 570 

Thr Ala Ile Gln Gly Thr Pro Pro Ser Val Pro Gly Leu Gly Gln 
                575                 580                 585 

Glu Glu His Val Met Lys Glu Lys Glu Leu Val Pro Glu Val Pro 
                590                 595                 600 

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

Thr Glu Glu Glu Lys Asp Thr Trp Glu Glu Lys Lys Gln Arg Glu 
                620                 625                 630 

Ala Glu Arg Leu Pro Asp Arg Thr Glu Ala Arg Glu Glu Ser Glu 
                635                 640                 645 

Pro Glu Val Lys Glu Asp Val Ile Glu Lys Ala Glu Leu Glu Glu 
                650                 655                 660 

Met Glu Glu Val His Pro Ser Asp Glu Glu Glu Glu Asp Ala Thr 
                665                 670                 675 

Lys Ala Glu Gly Phe Tyr Gln Lys His Met Gln Glu Pro Leu Lys 
                680                 685                 690 

Val Thr Pro Arg Ser Arg Glu Ala Phe Gly Gly Arg Glu Leu Gly 
                695                 700                 705 

Leu Gln Gly Lys Ala Pro Glu Lys Glu Thr Ser Leu Phe Leu Ser 
                710                 715                 720 

Ser Leu Thr Thr Pro Ala Gly Ala Thr Glu His Val Ser Tyr Ile 
                725                 730                 735 

Gln Asp Glu Thr Ile Pro Gly Tyr Ser Glu Thr Glu Gln Thr Ile 
                740                 745                 750 

Ser Asp Glu Glu Ile His Asp Glu Pro Glu Glu Arg Pro Ala Pro 
                755                 760                 765 

Pro Arg Phe His Thr Ser Thr Tyr Asp Leu Pro Gly Pro Glu Gly 
                770                 775                 780 

Ala Gly Pro Phe Glu Ala Ser Gln Pro Ala Asp Ser Ala Val Pro 
                785                 790                 795 

Ala Thr Ser Gly Lys Val Tyr Gly Thr Pro Glu Thr Glu Leu Thr 
                800                 805                 810 

Tyr Pro Thr Asn Ile Val Ala Ala Pro Leu Ala Glu Glu Glu His 
                815                 820                 825 

Val Ser Ser Ala Thr Ser Ile Thr Glu Cys Asp Lys Leu Ser Ser 
                830                 835                 840 

Phe Ala Thr Ser Val Ala Glu Asp Gln Ser Val Ala Ser Leu Thr 
                845                 850                 855 

Ala Pro Gln Thr Glu Glu Thr Gly Lys Ser Ser Leu Leu Leu Asp 
                860                 865                 870 

Thr Val Thr Ser Ile Pro Ser Ser Arg Thr Glu Ala Thr Gln Gly 
                875                 880                 885 

Leu Asp Tyr Val Pro Ser Ala Gly Thr Ile Ser Pro Thr Ser Ser 
                890                 895                 900 

Leu Glu Glu Asp Lys Gly Phe Lys Ser Pro Pro Cys Glu Asp Phe 
                905                 910                 915 

Ser Val Thr Gly Glu Ser Glu Lys Arg Gly Glu Ile Ile Gly Lys 
                920                 925                 930 

Gly Leu Ser Gly Glu Arg Ala Val Glu Glu Glu Glu Glu Glu Thr 
                935                 940                 945 

Ala Asn Val Glu Met Ser Glu Lys Leu Cys Ser Gln Tyr Gly Thr 
                950                 955                 960 

Pro Val Phe Ser Ala Pro Gly His Ala Leu His Pro Gly Glu Pro 
                965                 970                 975 

Ala Leu Gly Glu Ala Glu Glu Arg Cys Leu Ser Pro Asp Asp Ser 
                980                 985                 990 

Thr Val Lys Met Ala Ser Pro Pro Pro Ser Gly Pro Pro Ser Ala 
                995                1000                1005 

Thr His Thr Pro Phe His Gln Ser Pro Val Glu Glu Lys Ser Glu 
               1010                1015                1020 

Pro Gln Asp Phe Gln Glu Ala Asp Ser Trp Gly Asp Thr Lys Arg 
               1025                1030                1035 

Thr Pro Gly Val Gly Lys Glu Asp Ala Ala Glu Glu Thr Val Lys 
               1040                1045                1050 

Pro Gly Pro Glu Glu Gly Thr Leu Glu Lys Glu Glu Lys Val Pro 
               1055                1060                1065 

Pro Pro Arg Ser Pro Gln Ala Gln Glu Ala Pro Val Asn Ile Asp 
               1070                1075                1080 

Glu Gly Leu Thr Gly Cys Thr Ile Gln Leu Leu Pro Ala Gln Asp 
               1085                1090                1095 

Lys Ala Ile Val Phe Glu Ile Met Glu Ala Gly Glu Pro Thr Gly 
               1100                1105                1110 

Pro Ile Leu Gly Ala Glu Ala Leu Pro Gly Gly Leu Arg Thr Leu 
               1115                1120                1125 

Pro Gln Glu Pro Gly Lys Pro Gln Lys Asp Glu Val Leu Arg Tyr 
               1130                1135                1140 

Pro Asp Arg Ser Leu Ser Pro Glu Asp Ala Glu Ser Leu Ser Val 
               1145                1150                1155 

Leu Ser Val Pro Ser Pro Asp Thr Ala Asn Gln Glu Pro Thr Pro 
               1160                1165                1170 

Lys Ser Pro Cys Gly Leu Thr Glu Gln Tyr Leu His Lys Asp Arg 
               1175                1180                1185 

Trp Pro Glu Val Ser Pro Glu Asp Thr Gln Ser Leu Ser Leu Ser 
               1190                1195                1200 

Glu Glu Ser Pro Ser Lys Glu Thr Ser Leu Asp Val Ser Ser Lys 
               1205                1210                1215 

Gln Leu Ser Pro Glu Ser Leu Gly Thr Leu Gln Phe Gly Glu Leu 
               1220                1225                1230 

Asn Leu Gly Lys Glu Glu Met Gly His Leu Met Gln Ala Glu Asn 
               1235                1240                1245 

Thr Ser His His Thr Ala Pro Met Ser Val Pro Glu Pro His Ala 
               1250                1255                1260 

Ala Thr Ala Ser Pro Pro Thr Asp Gly Thr Thr Arg Tyr Ser Ala 
               1265                1270                1275 

Gln Thr Asp Ile Thr Asp Asp Ser Leu Asp Arg Lys Ser Pro Ala 
               1280                1285                1290 

Ser Ser Phe Ser His Ser Thr Pro Ser Gly Asn Gly Lys Tyr Leu 
               1295                1300                1305 

Pro Gly Ala Ile Thr Ser Pro Asp Glu His Ile Leu Thr Pro Asp 
               1310                1315                1320 

Ser Ser Phe Ser Lys Ser Pro Glu Ser Leu Pro Gly Pro Ala Leu 
               1325                1330                1335 

Glu Asp Ile Ala Ile Lys Trp Glu Asp Lys Val Pro Gly Leu Lys 
               1340                1345                1350 

Asp Arg Thr Ser Glu Gln Lys Lys Glu Pro Glu Pro Lys Asp Glu 
               1355                1360                1365 

Val Leu Gln Gln Lys Asp Lys Thr Leu Glu His Lys Glu Val Val 
               1370                1375                1380 

Glu Pro Lys Asp Thr Ala Ile Tyr Gln Lys Asp Glu Ala Leu His 
               1385                1390                1395 

Val Lys Asn Glu Ala Val Lys Gln Gln Asp Lys Ala Leu Glu Gln 
               1400                1405                1410 

Lys Gly Arg Asp Leu Glu Gln Lys Asp Thr Ala Leu Glu Gln Lys 
               1415                1420                1425 

Asp Lys Ala Leu Glu Pro Lys Asp Lys Asp Leu Glu Glu Lys Asp 
               1430                1435                1440 

Lys Ala Leu Glu Gln Lys Asp Lys Ile Pro Glu Glu Lys Asp Lys 
               1445                1450                1455 

Ala Leu Glu Gln Lys Asp Thr Ala Leu Glu Gln Lys Asp Lys Ala 
               1460                1465                1470 

Leu Glu Pro Lys Asp Lys Asp Leu Glu Gln Lys Asp Arg Val Leu 
               1475                1480                1485 

Glu Gln Lys Glu Lys Ile Pro Glu Glu Lys Asp Lys Ala Leu Asp 
               1490                1495                1500 

Gln Lys Val Arg Ser Val Glu His Lys Ala Pro Glu Asp Thr Val 
               1505                1510                1515 

Ala Glu Met Lys Asp Arg Asp Leu Glu Gln Thr Asp Lys Ala Pro 
               1520                1525                1530 

Glu Gln Lys His Gln Ala Gln Glu Gln Lys Asp Lys Val Ser Glu 
               1535                1540                1545 

Lys Lys Asp Gln Ala Leu Glu Gln Lys Tyr Trp Ala Leu Gly Gln 
               1550                1555                1560 

Lys Asp Glu Ala Leu Glu Gln Asn Ile Gln Ala Leu Glu Glu Asn 
               1565                1570                1575 

His Gln Thr Gln Glu Gln Glu Ser Leu Val Gln Glu Asp Lys Thr 
               1580                1585                1590 

Arg Lys Pro Lys Met Leu Glu Glu Lys Ser Pro Glu Lys Val Lys 
               1595                1600                1605 

Ala Met Glu Glu Lys Leu Glu Ala Leu Leu Glu Lys Thr Lys Ala 
               1610                1615                1620 

Leu Gly Leu Glu Glu Ser Leu Val Gln Glu Gly Arg Ala Arg Glu 
               1625                1630                1635 

Gln Glu Glu Lys Tyr Trp Arg Gly Gln Asp Val Val Gln Glu Trp 
               1640                1645                1650 

Gln Glu Thr Ser Pro Thr Arg Glu Glu Pro Ala Gly Glu Gln Lys 
               1655                1660                1665 

Glu Leu Ala Pro Ala Trp Glu Asp Thr Ser Pro Glu Gln Asp Asn 
               1670                1675                1680 

Arg Tyr Trp Arg Gly Arg Glu Asp Val Ala Leu Glu Gln Asp Thr 
               1685                1690                1695 

Tyr Trp Arg Glu Leu Ser Cys Glu Arg Lys Val Trp Phe Pro His 
               1700                1705                1710 

Glu Leu Asp Gly Gln Gly Ala Arg Pro His Tyr Thr Glu Glu Arg 
               1715                1720                1725 

Glu Ser Thr Phe Leu Asp Glu Gly Pro Asp Asp Glu Gln Glu Val 
               1730                1735                1740 

Pro Leu Arg Glu His Ala Thr Arg Ser Pro Trp Ala Ser Asp Phe 
               1745                1750                1755 

Lys Asp Phe Gln Glu Ser Ser Pro Gln Lys Gly Leu Glu Val Glu 
               1760                1765                1770 

Arg Trp Leu Ala Glu Ser Pro Val Gly Leu Pro Pro Glu Glu Glu 
               1775                1780                1785 

Asp Lys Leu Thr Arg Ser Pro Phe Glu Ile Ile Ser Pro Pro Ala 
               1790                1795                1800 

Ser Pro Pro Glu Met Val Gly Gln Arg Val Pro Ser Ala Pro Gly 
               1805                1810                1815 

Gln Glu Ser Pro Ile Pro Asp Pro Lys Leu Met Pro His Met Lys 
               1820                1825                1830 

Asn Glu Pro Thr Thr Pro Ser Trp Leu Ala Asp Ile Pro Pro Trp 
               1835                1840                1845 

Val Pro Lys Asp Arg Pro Leu Pro Pro Ala Pro Leu Ser Pro Ala 
               1850                1855                1860 

Pro Gly Pro Pro Thr Pro Ala Pro Glu Ser His Thr Pro Ala Pro 
               1865                1870                1875 

Phe Ser Trp Gly Thr Ala Glu Tyr Asp Ser Val Val Ala Ala Val 
               1880                1885                1890 

Gln Glu Gly Ala Ala Glu Leu Glu Gly Gly Pro Tyr Ser Pro Leu 
               1895                1900                1905 

Gly Lys Asp Tyr Arg Lys Ala Glu Gly Glu Arg Glu Glu Glu Gly 
               1910                1915                1920 

Arg Ala Glu Ala Pro Asp Lys Ser Ser His Ser Ser Lys Val Pro 
               1925                1930                1935 

Glu Ala Ser Lys Ser His Ala Thr Thr Glu Pro Glu Gln Thr Glu 
               1940                1945                1950 

Pro Glu Gln Arg Glu Pro Thr Pro Tyr Pro Asp Glu Arg Ser Phe 
               1955                1960                1965 

Gln Tyr Ala Asp Ile Tyr Glu Gln Met Met Leu Thr Gly Leu Gly 
               1970                1975                1980 

Pro Ala Cys Pro Thr Arg Glu Pro Pro Leu Gly Ala Ala Gly Asp 
               1985                1990                1995 

Trp Pro Pro Cys Leu Ser Thr Lys Glu Ala Ala Ala Gly Arg Asn 
               2000                2005                2010 

Thr Ser Ala Glu Lys Glu Leu Ser Ser Pro Ile Ser Pro Lys Ser 
               2015                2020                2025 

Leu Gln Ser Asp Thr Pro Thr Phe Ser Tyr Ala Ala Leu Ala Gly 
               2030                2035                2040 

Pro Thr Val Pro Pro Arg Pro Glu Pro Gly Pro Ser Met Glu Pro 
               2045                2050                2055 

Ser Leu Thr Pro Pro Ala Val Pro Pro Arg Ala Pro Ile Leu Ser 
               2060                2065                2070 

Lys Gly Pro Ser Pro Pro Leu Asn Gly Asn Ile Leu Ser Cys Ser 
               2075                2080                2085 

Pro Asp Arg Arg Ser Pro Ser Pro Lys Glu Ser Gly Arg Ser His 
               2090                2095                2100 

Trp Asp Asp Ser Thr Ser Asp Ser Glu Leu Glu Lys Gly Ala Arg 
               2105                2110                2115 

Glu Gln Pro Glu Lys Glu Ala Gln Ser Pro Ser Pro Pro His Pro 
               2120                2125                2130 

Ile Pro Met Gly Ser Pro Thr Leu Trp Pro Glu Thr Glu Ala His 
               2135                2140                2145 

Val Ser Pro Pro Leu Asp Ser His Leu Gly Pro Ala Arg Pro Ser 
               2150                2155                2160 

Leu Asp Phe Pro Ala Ser Ala Phe Gly Phe Ser Ser Leu Gln Pro 
               2165                2170                2175 

Ala Pro Pro Gln Leu Pro Ser Pro Ala Glu Pro Arg Ser Ala Pro 
               2180                2185                2190 

Cys Gly Ser Leu Ala Phe Ser Gly Asp Arg Ala Leu Ala Leu Ala 
               2195                2200                2205 

Pro Gly Pro Pro Thr Arg Thr Arg His Asp Glu Tyr Leu Glu Val 
               2210                2215                2220 

Thr Lys Ala Pro Ser Leu Asp Ser Ser Leu Pro Gln Leu Pro Ser 
               2225                2230                2235 

Pro Ser Ser Pro Gly Ala Pro Leu Leu Ser Asn Leu Pro Arg Pro 
               2240                2245                2250 

Ala Ser Pro Ala Leu Ser Glu Gly Ser Ser Ser Glu Ala Thr Thr 
               2255                2260                2265 

Pro Val Ile Ser Ser Val Ala Glu Arg Phe Ser Pro Ser Leu Glu 
               2270                2275                2280 

Ala Ala Glu Gln Glu Ser Gly Glu Leu Asp Pro Gly Met Glu Pro 
               2285                2290                2295 

Ala Ala His Ser Leu Trp Asp Leu Thr Pro Leu Ser Pro Ala Pro 
               2300                2305                2310 

Pro Ala Ser Leu Asp Leu Ala Leu Ala Pro Ala Pro Ser Leu Pro 
               2315                2320                2325 

Gly Asp Met Gly Asp Gly Ile Leu Pro Cys His Leu Glu Cys Ser 
               2330                2335                2340 

Glu Ala Ala Thr Glu Lys Pro Ser Pro Phe Gln Val Pro Ser Glu 
               2345                2350                2355 

Asp Cys Ala Ala Asn Gly Pro Thr Glu Thr Ser Pro Asn Pro Pro 
               2360                2365                2370 

Gly Pro Ala Pro Ala Lys Ala Glu Asn Glu Glu Ala Ala Ala Cys 
               2375                2380                2385 

Pro Ala Trp Glu Arg Gly Ala Trp Pro Glu Gly Ala Glu Arg Ser 
               2390                2395                2400 

Ser Arg Pro Asp Thr Leu Leu Ser Pro Glu Gln Pro Val Cys Pro 
               2405                2410                2415 

Ala Gly Gly Ser Gly Gly Pro Pro Ser Ser Ala Ser Pro Glu Val 
               2420                2425                2430 

Glu Ala Gly Pro Gln Gly Cys Ala Thr Glu Pro Arg Pro His Arg 
               2435                2440                2445 

Gly Glu Leu Ser Pro Ser Phe Leu Asn Pro Pro Leu Pro Pro Ser 
               2450                2455                2460 

Ile Asp Asp Arg Asp Leu Ser Thr Glu Glu Val Arg Leu Val Gly 
               2465                2470                2475 

Arg Gly Gly Arg Arg Arg Val Gly Gly Pro Gly Thr Thr Gly Gly 
               2480                2485                2490 

Pro Cys Pro Val Thr Asp Glu Thr Pro Pro Thr Ser Ala Ser Asp 
               2495                2500                2505 

Ser Gly Ser Ser Gln Ser Asp Ser Asp Val Pro Pro Glu Thr Glu 
               2510                2515                2520 

Glu Cys Pro Ser Ile Thr Ala Glu Ala Ala Leu Asp Ser Asp Glu 
               2525                2530                2535 

Asp Gly Asp Phe Leu Pro Val Asp Lys Ala Gly Gly Val Ser Gly 
               2540                2545                2550 

Thr His His Pro Arg Pro Gly His Asp Pro Pro Pro Leu Pro Gln 
               2555                2560                2565 

Pro Asp Pro Arg Pro Ser Pro Pro Arg Pro Asp Val Cys Met Ala 
               2570                2575                2580 

Asp Pro Glu Gly Leu Ser Ser Glu Ser Gly Arg Val Glu Arg Leu 
               2585                2590                2595 

Arg Glu Lys Glu Lys Val Gln Gly Arg Val Gly Arg Arg Ala Pro 
               2600                2605                2610 

Gly Lys Ala Lys Pro Ala Ser Pro Ala Arg Arg Leu Asp Leu Arg 
               2615                2620                2625 

Gly Lys Arg Ser Pro Thr Pro Gly Lys Gly Pro Ala Asp Arg Ala 
               2630                2635                2640 

Ser Arg Ala Pro Pro Arg Pro Arg Ser Thr Thr Ser Gln Val Thr 
               2645                2650                2655 

Pro Ala Glu Glu Lys Asp Gly His Ser Pro Met Ser Lys Gly Leu 
               2660                2665                2670 

Val Asn Gly Leu Lys Ala Gly Pro Met Ala Leu Ser Ser Lys Gly 
               2675                2680                2685 

Ser Ser Gly Ala Pro Val Tyr Val Asp Leu Ala Tyr Ile Pro Asn 
               2690                2695                2700 

His Cys Ser Gly Lys Thr Ala Asp Leu Asp Phe Phe Arg Arg Val 
               2705                2710                2715 

Arg Ala Ser Tyr Tyr Val Val Ser Gly Asn Asp Pro Ala Asn Gly 
               2720                2725                2730 

Glu Pro Ser Arg Ala Val Leu Asp Ala Leu Leu Glu Gly Lys Ala 
               2735                2740                2745 

Gln Trp Gly Glu Asn Leu Gln Val Thr Leu Ile Pro Thr His Asp 
               2750                2755                2760 

Thr Glu Val Thr Arg Glu Trp Tyr Gln Gln Thr His Glu Gln Gln 
               2765                2770                2775 

Gln Gln Leu Asn Val Leu Val Leu Ala Ser Ser Ser Thr Val Val 
               2780                2785                2790 

Met Gln Asp Glu Ser Phe Pro Ala Cys Lys Ile Glu Phe 
               2795                2800 

 
           
             6  
             1029  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7472720CD1  
             
           
            6 

Met Lys Leu Phe Gly Phe Gly Ser Arg Arg Gly Gln Thr Ala Gln 
  1               5                  10                  15 

Gly Ser Ile Asp His Val Tyr Thr Gly Ser Gly Tyr Arg Ile Arg 
                 20                  25                  30 

Asp Ser Glu Leu Gln Lys Ile His Arg Ala Ala Val Lys Gly Asp 
                 35                  40                  45 

Ala Ala Glu Val Glu Arg Cys Leu Ala Arg Arg Ser Gly Asp Leu 
                 50                  55                  60 

Asp Ala Leu Asp Lys Gln His Arg Thr Ala Leu His Leu Ala Cys 
                 65                  70                  75 

Ala Ser Gly His Val Gln Val Val Thr Leu Leu Val Asn Arg Lys 
                 80                  85                  90 

Cys Gln Ile Asp Val Cys Asp Lys Glu Asn Arg Thr Pro Leu Ile 
                 95                 100                 105 

Gln Ala Val His Cys Gln Glu Glu Ala Cys Ala Val Ile Leu Leu 
                110                 115                 120 

Glu His Gly Ala Asn Pro Asn Leu Lys Asp Ile Tyr Gly Asn Thr 
                125                 130                 135 

Ala Leu His Tyr Ala Val Tyr Ser Glu Ser Thr Ser Leu Ala Glu 
                140                 145                 150 

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

Asn Asn Thr Pro Leu Leu Phe Ala Ile Ile Cys Lys Lys Glu Lys 
                170                 175                 180 

Met Val Glu Phe Leu Leu Lys Lys Lys Ala Val His Asn Ala Val 
                185                 190                 195 

Asp Arg Leu Arg Arg Ser Ala Leu Ile Leu Ala Val Tyr Tyr Asp 
                200                 205                 210 

Ser Pro Gly Ile Val Asn Ile Leu Leu Lys Gln Asn Ile Asp Val 
                215                 220                 225 

Phe Ala Gln Asp Met Cys Gly Arg Asp Ala Glu Asp Tyr Ala Ile 
                230                 235                 240 

Ser His His Leu Thr Lys Ile Gln Gln Gln Ile Leu Glu His Lys 
                245                 250                 255 

Lys Lys Ile Leu Lys Lys Glu Lys Ser Asp Val Gly Ser Ser Asp 
                260                 265                 270 

Glu Ser Ala Val Ser Ile Phe His Glu Leu Arg Val Asp Ser Leu 
                275                 280                 285 

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

Pro Glu Lys Val Ser Glu Pro Leu Pro Gly Ser Ser His Glu Lys 
                305                 310                 315 

Gly Asn Arg Ile Val Asn Gly Gln Gly Glu Gly Pro Pro Ala Lys 
                320                 325                 330 

His Pro Ser Leu Lys Pro Ser Thr Glu Val Glu Asp Pro Ala Val 
                335                 340                 345 

Lys Gly Ala Val Gln Arg Lys Asn Val Gln Thr Leu Arg Ala Glu 
                350                 355                 360 

Gln Ala Leu Pro Val Ala Ser Glu Glu Glu Gln Gln Arg His Glu 
                365                 370                 375 

Arg Ser Glu Lys Lys Gln Pro Gln Val Lys Glu Gly Asn Asn Thr 
                380                 385                 390 

Asn Lys Ser Glu Lys Ile Gln Leu Ser Glu Asn Ile Cys Asp Ser 
                395                 400                 405 

Thr Ser Ser Ala Ala Ala Gly Arg Leu Thr Gln Gln Arg Lys Ile 
                410                 415                 420 

Gly Lys Thr Tyr Pro Gln Gln Phe Pro Lys Lys Leu Lys Glu Glu 
                425                 430                 435 

His Asp Arg Cys Thr Leu Lys Gln Glu Asn Glu Glu Lys Thr Asn 
                440                 445                 450 

Val Asn Met Leu Tyr Lys Lys Asn Arg Glu Glu Leu Glu Arg Lys 
                455                 460                 465 

Glu Lys Gln Tyr Lys Lys Glu Val Glu Ala Lys Gln Leu Glu Pro 
                470                 475                 480 

Thr Val Gln Ser Leu Glu Met Lys Ser Lys Thr Ala Arg Asn Thr 
                485                 490                 495 

Pro Asn Arg Asp Phe His Asn His Glu Glu Met Lys Gly Leu Met 
                500                 505                 510 

Asp Glu Asn Cys Ile Leu Lys Ala Asp Ile Ala Ile Leu Arg Gln 
                515                 520                 525 

Glu Ile Cys Thr Met Lys Asn Asp Asn Leu Glu Lys Glu Asn Lys 
                530                 535                 540 

Tyr Leu Lys Asp Ile Lys Ile Val Lys Glu Thr Asn Ala Ala Leu 
                545                 550                 555 

Glu Lys Tyr Ile Lys Leu Asn Glu Glu Met Ile Thr Glu Thr Ala 
                560                 565                 570 

Phe Arg Tyr Gln Gln Glu Leu Asn Asp Leu Lys Ala Glu Asn Thr 
                575                 580                 585 

Arg Leu Asn Ala Glu Leu Leu Lys Glu Lys Glu Ser Lys Lys Arg 
                590                 595                 600 

Leu Glu Ala Asp Ile Glu Ser Tyr Gln Ser Arg Leu Ala Ala Ala 
                605                 610                 615 

Ile Ser Lys His Ser Glu Ser Val Lys Thr Glu Arg Asn Leu Lys 
                620                 625                 630 

Leu Ala Leu Glu Arg Thr Gln Asp Val Ser Val Gln Val Glu Met 
                635                 640                 645 

Ser Ser Ala Ile Ser Lys Val Lys Ala Glu Asn Glu Phe Leu Thr 
                650                 655                 660 

Glu Gln Leu Ser Glu Thr Gln Ile Lys Phe Asn Thr Leu Lys Asp 
                665                 670                 675 

Lys Phe Arg Lys Thr Arg Asp Ser Leu Arg Lys Lys Ser Leu Ala 
                680                 685                 690 

Leu Glu Thr Val Gln Asn Asp Leu Ser Gln Thr Gln Gln Gln Thr 
                695                 700                 705 

Gln Glu Met Lys Glu Met Tyr Gln Asn Ala Glu Ala Lys Val Asn 
                710                 715                 720 

Asn Ser Thr Gly Lys Trp Asn Cys Val Glu Glu Arg Ile Cys His 
                725                 730                 735 

Leu Gln Arg Glu Asn Ala Trp Leu Val Gln Gln Leu Asp Asp Val 
                740                 745                 750 

His Gln Lys Glu Asp His Lys Glu Thr Val Thr Asn Ile Gln Arg 
                755                 760                 765 

Gly Phe Ile Glu Ser Gly Lys Lys Asp Leu Val Leu Glu Glu Lys 
                770                 775                 780 

Ser Lys Lys Leu Met Asn Glu Cys Asp His Leu Lys Glu Ser Leu 
                785                 790                 795 

Phe Gln Tyr Glu Arg Glu Lys Ala Glu Gly Val Pro Lys Lys Glu 
                800                 805                 810 

Asn Glu Glu Leu Arg Lys Leu Phe Glu Leu Ile Ser Ser Leu Lys 
                815                 820                 825 

Tyr Asn Val Asn Arg Ile Arg Lys Lys Asn Asp Glu Leu Glu Glu 
                830                 835                 840 

Glu Ala Thr Gly Tyr Lys Lys Leu Leu Glu Met Thr Ile Asn Met 
                845                 850                 855 

Leu Asn Val Phe Gly Asn Glu Asp Phe Asp Cys His Gly Asp Leu 
                860                 865                 870 

Lys Thr Asp Gln Leu Lys Met Asp Ile Leu Ile Lys Lys Leu Lys 
                875                 880                 885 

Gln Lys Glu Gln Ala Gln Tyr Glu Lys Gln Leu Glu Gln Leu Asn 
                890                 895                 900 

Lys Asp Asn Met Ala Ser Leu Asn Lys Lys Glu Leu Thr Leu Lys 
                905                 910                 915 

Asp Val Glu Cys Lys Phe Ser Glu Met Lys Thr Ala Tyr Glu Glu 
                920                 925                 930 

Val Thr Thr Glu Leu Glu Glu Tyr Lys Glu Ala Phe Ala Ala Ala 
                935                 940                 945 

Leu Lys Ala Asn Asn Ser Met Ser Lys Lys Leu Thr Lys Ser Asn 
                950                 955                 960 

Lys Lys Ile Ala Val Ile Ser Met Lys Leu Leu Met Glu Lys Glu 
                965                 970                 975 

Gln Met Lys Tyr Phe Leu Ser Ala Leu Pro Thr Arg Arg Asp Pro 
                980                 985                 990 

Glu Ser Pro Cys Val Glu Asn Leu Thr Ser Ile Gly Leu Asn Arg 
                995                1000                1005 

Lys Tyr Ile Pro Gln Thr Pro Ile Arg Ile Pro Ile Ser Ser Pro 
               1010                1015                1020 

Gln Thr Ser Asn Asn Cys Lys Asn Ser 
               1025 

 
           
             7  
             696  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7583990CD1  
             
           
            7 

Met Glu Ala Ser Val Ile Leu Pro Ile Leu Lys Lys Lys Leu Ala 
  1               5                  10                  15 

Phe Leu Ser Gly Gly Lys Asp Arg Arg Ser Gly Leu Ile Leu Thr 
                 20                  25                  30 

Ile Pro Leu Cys Leu Glu Gln Thr Asn Met Asp Glu Leu Ser Val 
                 35                  40                  45 

Thr Leu Asp Tyr Leu Leu Ser Ile Pro Ser Glu Lys Cys Lys Ala 
                 50                  55                  60 

Arg Gly Phe Thr Val Ile Val Asp Gly Arg Lys Ser Gln Trp Asn 
                 65                  70                  75 

Val Val Lys Thr Val Val Val Met Leu Gln Asn Val Val Pro Ala 
                 80                  85                  90 

Glu Val Ser Leu Val Cys Val Val Lys Pro Asp Glu Phe Trp Asp 
                 95                 100                 105 

Lys Lys Val Thr His Phe Cys Phe Trp Lys Glu Lys Asp Arg Leu 
                110                 115                 120 

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

Ile Glu Pro Cys Gln Leu Thr Glu Asp Phe Gly Gly Ser Leu Thr 
                140                 145                 150 

Tyr Asp His Met Asp Trp Leu Asn Lys Arg Leu Val Phe Glu Lys 
                155                 160                 165 

Phe Thr Lys Glu Ser Thr Ser Leu Leu Asp Glu Leu Ala Leu Ile 
                170                 175                 180 

Asn Asn Gly Ser Asp Lys Gly Asn Gln Gln Glu Lys Glu Arg Ser 
                185                 190                 195 

Val Asp Leu Asn Phe Leu Pro Ser Val Asp Pro Glu Thr Val Leu 
                200                 205                 210 

Gln Thr Gly His Glu Leu Leu Ser Glu Leu Gln Gln Arg Arg Phe 
                215                 220                 225 

Asn Gly Ser Asp Gly Gly Val Ser Trp Ser Pro Met Asp Asp Glu 
                230                 235                 240 

Leu Leu Ala Gln Pro Gln Val Met Lys Leu Leu Asp Ser Leu Arg 
                245                 250                 255 

Glu Gln Tyr Thr Arg Tyr Gln Glu Val Cys Arg Gln Arg Ser Lys 
                260                 265                 270 

Arg Thr Gln Leu Glu Glu Ile Gln Gln Lys Val Met Gln Val Val 
                275                 280                 285 

Asn Trp Leu Glu Gly Pro Gly Ser Glu Gln Leu Arg Ala Gln Trp 
                290                 295                 300 

Gly Ile Gly Asp Ser Ile Arg Ala Ser Gln Ala Leu Gln Gln Lys 
                305                 310                 315 

His Glu Glu Ile Glu Ser Gln His Ser Glu Trp Phe Ala Val Tyr 
                320                 325                 330 

Val Glu Leu Asn Gln Gln Ile Ala Ala Leu Leu Asn Ala Gly Asp 
                335                 340                 345 

Glu Glu Asp Leu Val Glu Leu Lys Ser Leu Gln Gln Gln Leu Ser 
                350                 355                 360 

Asp Val Cys Tyr Arg Gln Ala Ser Gln Leu Glu Phe Arg Gln Asn 
                365                 370                 375 

Leu Leu Gln Ala Ala Leu Glu Phe His Gly Val Ala Gln Asp Leu 
                380                 385                 390 

Ser Gln Gln Leu Asp Gly Leu Leu Gly Met Leu Cys Val Asp Val 
                395                 400                 405 

Ala Pro Ala Asp Gly Ala Ser Ile Gln Gln Thr Leu Lys Leu Leu 
                410                 415                 420 

Glu Glu Lys Leu Lys Ser Val Asp Val Gly Leu Gln Gly Leu Arg 
                425                 430                 435 

Glu Lys Gly Gln Gly Leu Leu Asp Gln Ile Ser Asn Gln Ala Ser 
                440                 445                 450 

Trp Ala Tyr Gly Lys Asp Val Thr Ile Glu Asn Lys Glu Asn Val 
                455                 460                 465 

Asp His Ile Gln Gly Val Met Glu Asp Met Gln Leu Arg Lys Gln 
                470                 475                 480 

Arg Cys Glu Asp Met Val Asp Val Arg Arg Leu Lys Met Leu Gln 
                485                 490                 495 

Met Val Gln Leu Phe Lys Cys Glu Glu Asp Ala Ala Gln Ala Val 
                500                 505                 510 

Glu Trp Leu Ser Glu Leu Leu Asp Ala Leu Leu Lys Thr His Ile 
                515                 520                 525 

Arg Leu Gly Asp Asp Ala Gln Glu Thr Lys Val Leu Leu Glu Lys 
                530                 535                 540 

His Arg Lys Phe Val Asp Val Ala Gln Ser Thr Tyr Asp Tyr Gly 
                545                 550                 555 

Arg Gln Leu Leu Gln Ala Thr Val Val Leu Cys Gln Ser Leu Arg 
                560                 565                 570 

Cys Thr Ser Arg Ser Ser Gly Asp Thr Leu Pro Arg Leu Asn Arg 
                575                 580                 585 

Val Trp Lys Gln Phe Thr Ile Ala Ser Glu Glu Arg Val His Arg 
                590                 595                 600 

Leu Glu Met Ala Ile Ala Phe His Ser Asn Ala Glu Lys Ile Leu 
                605                 610                 615 

Gln Asp Cys Pro Glu Glu Pro Glu Ala Ile Asn Asp Glu Glu Gln 
                620                 625                 630 

Phe Asp Glu Ile Glu Ala Val Gly Lys Ser Leu Leu Asp Arg Leu 
                635                 640                 645 

Thr Val Pro Val Val Tyr Pro Asp Gly Thr Glu Gln Tyr Phe Gly 
                650                 655                 660 

Ser Pro Ser Asp Met Ala Ser Thr Ala Glu Asn Ile Arg Asp Arg 
                665                 670                 675 

Met Lys Leu Val Asn Leu Lys Arg Gln Gln Leu Arg His Pro Glu 
                680                 685                 690 

Met Val Thr Thr Glu Ser 
                695 

 
           
             8  
             803  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 2058182CD1  
             
           
            8 

Met Lys Lys Gln Phe Asn Arg Met Lys Gln Leu Ala Asn Gln Thr 
  1               5                  10                  15 

Val Gly Arg Ala Glu Lys Thr Glu Val Leu Ser Glu Asp Leu Leu 
                 20                  25                  30 

Gln Ile Glu Arg Arg Leu Asp Thr Val Arg Ser Ile Cys His His 
                 35                  40                  45 

Ser His Lys Arg Leu Val Ala Cys Phe Gln Gly Gln His Gly Thr 
                 50                  55                  60 

Asp Ala Glu Arg Arg His Lys Lys Leu Pro Leu Thr Ala Leu Ala 
                 65                  70                  75 

Gln Asn Met Gln Glu Ala Ser Thr Gln Leu Glu Asp Ser Leu Leu 
                 80                  85                  90 

Gly Lys Met Leu Glu Thr Cys Gly Asp Ala Glu Asn Gln Leu Ala 
                 95                 100                 105 

Leu Glu Leu Ser Gln His Glu Val Phe Val Glu Lys Glu Ile Val 
                110                 115                 120 

Asp Pro Leu Tyr Gly Ile Ala Glu Val Glu Ile Pro Asn Ile Gln 
                125                 130                 135 

Lys Gln Arg Lys Gln Leu Ala Arg Leu Val Leu Asp Trp Asp Ser 
                140                 145                 150 

Val Arg Ala Arg Trp Asn Gln Ala His Lys Ser Ser Gly Thr Asn 
                155                 160                 165 

Phe Gln Gly Leu Pro Ser Lys Ile Asp Thr Leu Lys Glu Glu Met 
                170                 175                 180 

Asp Glu Ala Gly Asn Lys Val Glu Gln Cys Lys Asp Gln Leu Ala 
                185                 190                 195 

Ala Asp Met Tyr Asn Phe Met Ala Lys Glu Gly Glu Tyr Gly Lys 
                200                 205                 210 

Phe Phe Val Thr Leu Leu Glu Ala Gln Ala Asp Tyr His Arg Lys 
                215                 220                 225 

Ala Leu Ala Val Leu Glu Lys Thr Leu Pro Glu Met Arg Ala His 
                230                 235                 240 

Gln Asp Lys Trp Ala Glu Lys Pro Ala Phe Gly Thr Pro Leu Glu 
                245                 250                 255 

Glu His Leu Lys Arg Ser Gly Arg Glu Ile Ala Leu Pro Ile Glu 
                260                 265                 270 

Ala Cys Val Met Leu Leu Leu Glu Thr Gly Met Lys Glu Glu Gly 
                275                 280                 285 

Leu Phe Arg Ile Gly Ala Gly Ala Ser Lys Leu Lys Lys Leu Lys 
                290                 295                 300 

Ala Ala Leu Asp Cys Ser Thr Ser His Leu Asp Glu Phe Tyr Ser 
                305                 310                 315 

Asp Pro His Ala Val Ala Gly Ala Leu Lys Ser Tyr Leu Arg Glu 
                320                 325                 330 

Leu Pro Glu Pro Leu Met Thr Phe Asn Leu Tyr Glu Glu Trp Thr 
                335                 340                 345 

Gln Val Ala Ser Val Gln Asp Gln Asp Lys Lys Leu Gln Asp Leu 
                350                 355                 360 

Trp Arg Thr Cys Gln Lys Leu Pro Pro Gln Asn Phe Val Asn Phe 
                365                 370                 375 

Arg Tyr Leu Ile Lys Phe Leu Ala Lys Leu Ala Gln Thr Ser Asp 
                380                 385                 390 

Val Asn Lys Met Thr Pro Ser Asn Ile Ala Ile Val Leu Gly Pro 
                395                 400                 405 

Asn Leu Leu Trp Ala Arg Asn Glu Gly Thr Leu Ala Glu Met Ala 
                410                 415                 420 

Ala Ala Thr Ser Val His Val Val Ala Val Ile Glu Pro Ile Ile 
                425                 430                 435 

Gln His Ala Asp Trp Phe Phe Pro Glu Glu Val Glu Phe Asn Val 
                440                 445                 450 

Ser Glu Ala Phe Val Pro Leu Thr Thr Pro Ser Ser Asn His Ser 
                455                 460                 465 

Phe His Thr Gly Asn Asp Ser Asp Ser Gly Thr Leu Glu Arg Lys 
                470                 475                 480 

Arg Pro Ala Ser Met Ala Val Met Glu Gly Asp Leu Val Lys Lys 
                485                 490                 495 

Glu Ser Pro Pro Lys Pro Lys Asp Pro Val Ser Ala Ala Val Pro 
                500                 505                 510 

Ala Pro Gly Arg Asn Asn Ser Gln Ile Ala Ser Gly Gln Asn Gln 
                515                 520                 525 

Pro Gln Ala Ala Ala Gly Ser His Gln Leu Ser Met Gly Gln Pro 
                530                 535                 540 

His Asn Ala Ala Gly Pro Ser Pro His Thr Leu Arg Arg Ala Val 
                545                 550                 555 

Lys Lys Pro Ala Pro Ala Pro Pro Lys Pro Gly Asn Pro Pro Pro 
                560                 565                 570 

Gly His Pro Gly Gly Gln Ser Ser Ser Gly Thr Ser Gln His Pro 
                575                 580                 585 

Pro Ser Leu Ser Pro Lys Pro Pro Thr Arg Ser Pro Ser Pro Pro 
                590                 595                 600 

Thr Gln His Thr Gly Gln Pro Pro Gly Gln Pro Ser Ala Pro Ser 
                605                 610                 615 

Gln Leu Ser Ala Pro Arg Arg Tyr Ser Ser Ser Leu Ser Pro Ile 
                620                 625                 630 

Gln Ala Pro Asn His Pro Pro Pro Gln Pro Pro Thr Gln Ala Thr 
                635                 640                 645 

Pro Leu Met His Thr Lys Pro Asn Ser Gln Gly Pro Pro Asn Pro 
                650                 655                 660 

Met Ala Leu Pro Ser Glu His Gly Leu Glu Gln Pro Ser His Thr 
                665                 670                 675 

Pro Pro Gln Thr Pro Thr Pro Pro Ser Thr Pro Pro Leu Gly Lys 
                680                 685                 690 

Gln Asn Pro Ser Leu Pro Ala Pro Gln Thr Leu Ala Gly Gly Asn 
                695                 700                 705 

Pro Glu Thr Ala Gln Pro His Ala Gly Thr Leu Pro Arg Pro Arg 
                710                 715                 720 

Pro Val Pro Lys Pro Arg Asn Arg Pro Ser Val Pro Pro Pro Pro 
                725                 730                 735 

Gln Pro Pro Gly Val His Ser Ala Gly Asp Ser Ser Leu Thr Asn 
                740                 745                 750 

Thr Ala Pro Thr Ala Ser Lys Ile Val Thr Asp Ser Asn Ser Arg 
                755                 760                 765 

Val Ser Glu Pro His Arg Ser Ile Phe Pro Glu Met His Ser Asp 
                770                 775                 780 

Ser Ala Ser Lys Asp Val Pro Gly Arg Ile Leu Leu Asp Ile Asp 
                785                 790                 795 

Asn Asp Thr Glu Ser Thr Ala Leu 
                800 

 
           
             9  
             701  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 3564377CD1  
             
           
            9 

Met Met Lys Arg Gln Leu His Arg Met Arg Gln Leu Ala Gln Thr 
  1               5                  10                  15 

Gly Ser Leu Gly Arg Thr Pro Glu Thr Ala Glu Phe Leu Gly Glu 
                 20                  25                  30 

Asp Leu Leu Gln Val Glu Gln Arg Leu Glu Pro Ala Lys Arg Ala 
                 35                  40                  45 

Ala His Asn Ile His Lys Arg Leu Gln Ala Cys Leu Gln Gly Gln 
                 50                  55                  60 

Ser Gly Ala Asp Met Asp Lys Arg Val Lys Lys Leu Pro Leu Met 
                 65                  70                  75 

Ala Leu Ser Thr Thr Met Ala Glu Ser Phe Lys Glu Leu Asp Pro 
                 80                  85                  90 

Asp Ser Ser Met Gly Lys Ala Leu Glu Met Ser Cys Ala Ile Gln 
                 95                 100                 105 

Asn Gln Leu Ala Arg Ile Leu Ala Glu Phe Glu Met Thr Leu Glu 
                110                 115                 120 

Arg Asp Val Leu Gln Pro Leu Ser Arg Leu Ser Glu Glu Glu Leu 
                125                 130                 135 

Pro Ala Ile Leu Lys His Lys Lys Ser Leu Gln Lys Leu Val Ser 
                140                 145                 150 

Asp Trp Asn Thr Leu Lys Ser Arg Leu Ser Gln Ala Thr Lys Asn 
                155                 160                 165 

Ser Gly Ser Ser Gln Gly Leu Gly Gly Ser Pro Gly Ser His Ser 
                170                 175                 180 

His Thr Thr Met Ala Asn Lys Val Glu Thr Leu Lys Glu Glu Glu 
                185                 190                 195 

Glu Glu Leu Lys Arg Lys Val Glu Gln Cys Arg Asp Glu Tyr Leu 
                200                 205                 210 

Ala Asp Leu Tyr His Phe Val Thr Lys Glu Asp Ser Tyr Ala Asn 
                215                 220                 225 

Tyr Phe Ile Arg Leu Leu Glu Ile Gln Ala Asp Tyr His Arg Arg 
                230                 235                 240 

Ser Leu Ser Ser Leu Asp Thr Ala Leu Ala Glu Leu Arg Glu Asn 
                245                 250                 255 

His Gly Gln Ala Asp His Ser Pro Ser Met Thr Ala Thr His Phe 
                260                 265                 270 

Pro Arg Val Tyr Gly Val Ser Leu Ala Thr His Leu Gln Glu Leu 
                275                 280                 285 

Gly Arg Glu Ile Ala Leu Pro Ile Glu Ala Cys Val Met Met Leu 
                290                 295                 300 

Leu Ser Glu Gly Met Lys Glu Glu Gly Leu Phe Arg Leu Ala Ala 
                305                 310                 315 

Gly Ala Ser Val Leu Lys Arg Leu Lys Gln Thr Met Ala Ser Asp 
                320                 325                 330 

Pro His Ser Leu Glu Glu Phe Cys Ser Asp Pro His Ala Val Ala 
                335                 340                 345 

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

Thr Phe Asp Leu Tyr Asp Asp Trp Met Arg Ala Ala Ser Leu Lys 
                365                 370                 375 

Glu Pro Gly Ala Arg Leu Gln Ala Leu Gln Glu Val Cys Ser Arg 
                380                 385                 390 

Leu Pro Pro Glu Asn Leu Ser Asn Leu Arg Tyr Leu Met Lys Phe 
                395                 400                 405 

Leu Ala Arg Leu Ala Glu Glu Gln Glu Val Asn Lys Met Thr Pro 
                410                 415                 420 

Ser Asn Ile Ala Ile Val Leu Gly Pro Asn Leu Leu Trp Pro Pro 
                425                 430                 435 

Glu Lys Glu Gly Asp Gln Ala Gln Leu Asp Ala Ala Ser Val Ser 
                440                 445                 450 

Ser Ile Gln Val Val Gly Val Val Glu Ala Leu Ile Gln Ser Ala 
                455                 460                 465 

Asp Thr Leu Phe Pro Gly Asp Ile Asn Phe Asn Val Ser Gly Leu 
                470                 475                 480 

Phe Ser Ala Val Thr Leu Gln Asp Thr Val Ser Asp Arg Leu Ala 
                485                 490                 495 

Ser Glu Glu Leu Pro Ser Thr Ala Val Pro Thr Pro Ala Thr Thr 
                500                 505                 510 

Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Leu 
                515                 520                 525 

Ala Ser Ala Ala Thr Lys Glu Arg Thr Glu Ser Glu Val Pro Pro 
                530                 535                 540 

Arg Pro Ala Ser Pro Lys Val Thr Arg Ser Pro Pro Glu Thr Ala 
                545                 550                 555 

Ala Pro Val Glu Asp Met Ala Arg Arg Thr Lys Arg Pro Ala Pro 
                560                 565                 570 

Ala Arg Pro Thr Met Pro Pro Pro Gln Val Ser Gly Ser Arg Ser 
                575                 580                 585 

Ser Pro Pro Ala Pro Pro Leu Pro Pro Gly Ser Gly Ser Pro Gly 
                590                 595                 600 

Thr Pro Gln Ala Leu Pro Arg Arg Leu Val Gly Ser Ser Leu Arg 
                605                 610                 615 

Ala Pro Thr Val Pro Pro Pro Leu Pro Pro Thr Pro Pro Gln Pro 
                620                 625                 630 

Ala Arg Arg Gln Ser Arg Arg Ser Pro Ala Ser Pro Ser Pro Ala 
                635                 640                 645 

Ser Pro Gly Pro Ala Ser Pro Ser Pro Val Ser Leu Ser Asn Pro 
                650                 655                 660 

Ala Gln Val Asp Leu Gly Ala Ala Thr Ala Glu Gly Gly Ala Pro 
                665                 670                 675 

Glu Ala Ile Ser Gly Val Pro Thr Pro Pro Ala Ile Pro Pro Gln 
                680                 685                 690 

Pro Arg Pro Arg Ser Leu Ala Ser Glu Thr Asn 
                695                 700 

 
           
             10  
             354  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 1568689CD1  
             
           
            10 

Met Ser Ala Gly Gly Gly Arg Ala Phe Ala Trp Gln Val Phe Pro 
  1               5                  10                  15 

Pro Met Pro Thr Cys Arg Val Tyr Gly Thr Val Ala His Gln Asp 
                 20                  25                  30 

Gly His Leu Leu Val Leu Gly Gly Cys Gly Arg Ala Gly Leu Pro 
                 35                  40                  45 

Leu Asp Thr Ala Glu Thr Leu Asp Met Ala Ser His Thr Trp Leu 
                 50                  55                  60 

Ala Leu Ala Pro Leu Pro Thr Ala Arg Ala Gly Ala Ala Ala Val 
                 65                  70                  75 

Val Leu Gly Lys Gln Val Leu Val Val Gly Gly Val Asp Glu Val 
                 80                  85                  90 

Gln Ser Pro Val Ala Ala Val Glu Ala Phe Leu Met Asp Glu Gly 
                 95                 100                 105 

Arg Trp Glu Arg Arg Ala Thr Leu Pro Gln Ala Ala Met Gly Val 
                110                 115                 120 

Ala Thr Val Glu Arg Asp Gly Met Val Tyr Ala Leu Gly Gly Met 
                125                 130                 135 

Gly Pro Asp Thr Ala Pro Gln Ala Gln Val Arg Val Tyr Glu Pro 
                140                 145                 150 

Arg Arg Asp Cys Trp Leu Ser Leu Pro Ser Met Pro Thr Pro Cys 
                155                 160                 165 

Tyr Gly Ala Ser Thr Phe Leu His Gly Asn Lys Ile Tyr Val Leu 
                170                 175                 180 

Gly Gly Arg Gln Gly Lys Leu Pro Val Thr Ala Phe Glu Ala Phe 
                185                 190                 195 

Asp Leu Glu Ala Arg Thr Trp Thr Arg His Pro Ser Leu Pro Ser 
                200                 205                 210 

Arg Arg Ala Phe Ala Gly Cys Ala Met Ala Glu Gly Ser Val Phe 
                215                 220                 225 

Ser Leu Gly Gly Leu Gln Gln Pro Gly Pro His Asn Phe Tyr Ser 
                230                 235                 240 

Arg Pro His Phe Val Asn Thr Val Glu Met Phe Asp Leu Glu His 
                245                 250                 255 

Gly Ser Trp Thr Lys Leu Pro Arg Ser Leu Arg Met Arg Asp Lys 
                260                 265                 270 

Arg Ala Asp Phe Val Val Gly Ser Leu Gly Gly His Ile Val Ala 
                275                 280                 285 

Ile Gly Gly Leu Gly Asn Gln Pro Cys Pro Leu Gly Ser Val Glu 
                290                 295                 300 

Ser Phe Ser Leu Ala Arg Arg Arg Trp Glu Ala Leu Pro Ala Met 
                305                 310                 315 

Pro Thr Ala Arg Cys Ser Cys Ser Ser Leu Gln Ala Gly Pro Arg 
                320                 325                 330 

Leu Phe Val Ile Gly Gly Val Ala Gln Gly Pro Ser Gln Ala Val 
                335                 340                 345 

Glu Ala Leu Cys Leu Arg Asp Gly Val 
                350 

 
           
             11  
             605  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 1393767CD1  
             
           
            11 

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

Lys Gln Cys Asn Phe Ser Asp Arg Gln Ala Glu Leu Asn Ile Asp 
                 20                  25                  30 

Ile Met Pro Asn Pro Glu Leu Ala Glu Gln Phe Val Glu Arg Asn 
                 35                  40                  45 

Pro Val Asp Thr Gly Ile Gln Cys Ser Ile Ser Met Ser Glu His 
                 50                  55                  60 

Glu Ala Asn Ser Glu Arg Phe Glu Met Glu Thr Arg Gly Val Asn 
                 65                  70                  75 

His Val Glu Gly Gly Trp Pro Lys Asp Val Asn Pro Leu Glu Leu 
                 80                  85                  90 

Glu Gln Thr Ile Arg Phe Arg Lys Lys Val Glu Lys Asp Glu Asn 
                 95                 100                 105 

Tyr Val Asn Ala Ile Met Gln Leu Gly Ser Ile Met Glu His Cys 
                110                 115                 120 

Ile Lys Gln Asn Asn Ala Ile Asp Ile Tyr Glu Glu Tyr Phe Asn 
                125                 130                 135 

Asp Glu Glu Ala Met Glu Val Met Glu Glu Asp Pro Ser Ala Lys 
                140                 145                 150 

Thr Ile Asn Val Phe Arg Asp Pro Gln Glu Ile Lys Arg Ala Ala 
                155                 160                 165 

Thr His Leu Ser Trp His Pro Asp Gly Asn Arg Lys Leu Ala Val 
                170                 175                 180 

Ala Tyr Ser Cys Leu Asp Phe Gln Arg Ala Pro Val Gly Met Ser 
                185                 190                 195 

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

Leu Ala Leu Lys Pro Ser Ser Pro Leu Val Thr Leu Glu Phe Asn 
                215                 220                 225 

Pro Lys Asp Ser His Val Leu Leu Gly Gly Cys Tyr Asn Gly Gln 
                230                 235                 240 

Ile Ala Cys Trp Asp Thr Arg Lys Gly Ser Leu Val Ala Glu Leu 
                245                 250                 255 

Ser Thr Ile Glu Ser Ser His Arg Asp Pro Val Tyr Gly Thr Ile 
                260                 265                 270 

Trp Leu Gln Ser Lys Thr Gly Thr Glu Cys Phe Ser Ala Ser Thr 
                275                 280                 285 

Asp Gly Gln Val Met Trp Trp Asp Ile Arg Lys Met Ser Glu Pro 
                290                 295                 300 

Thr Glu Val Val Ile Leu Asp Ile Thr Lys Lys Glu Gln Leu Glu 
                305                 310                 315 

Asn Ala Leu Gly Ala Ile Ser Leu Glu Phe Glu Ser Thr Leu Pro 
                320                 325                 330 

Thr Lys Phe Met Val Gly Thr Glu Gln Gly Ile Val Ile Ser Cys 
                335                 340                 345 

Asn Arg Lys Ala Lys Thr Ser Ala Glu Lys Ile Val Cys Thr Phe 
                350                 355                 360 

Pro Gly His His Gly Pro Ile Tyr Ala Leu Gln Arg Asn Pro Phe 
                365                 370                 375 

Tyr Pro Lys Asn Phe Leu Thr Val Gly Asp Trp Thr Ala Arg Ile 
                380                 385                 390 

Trp Ser Glu Asp Ser Arg Glu Ser Ser Ile Met Trp Thr Lys Tyr 
                395                 400                 405 

His Met Ala Tyr Leu Thr Asp Ala Ala Trp Ser Pro Val Arg Pro 
                410                 415                 420 

Thr Val Phe Phe Thr Thr Arg Met Asp Gly Thr Leu Asp Ile Trp 
                425                 430                 435 

Asp Phe Met Phe Glu Gln Cys Asp Pro Thr Leu Ser Leu Lys Val 
                440                 445                 450 

Cys Asp Glu Ala Leu Phe Cys Leu Arg Val Gln Asp Asn Gly Cys 
                455                 460                 465 

Leu Ile Ala Cys Gly Ser Gln Leu Gly Thr Thr Thr Leu Leu Glu 
                470                 475                 480 

Val Ser Pro Gly Leu Ser Thr Leu Gln Arg Asn Glu Lys Asn Val 
                485                 490                 495 

Ala Ser Ser Met Phe Glu Arg Glu Thr Arg Arg Glu Lys Ile Leu 
                500                 505                 510 

Glu Ala Arg His Arg Glu Met Arg Leu Lys Glu Lys Gly Lys Ala 
                515                 520                 525 

Glu Gly Arg Asp Glu Glu Gln Thr Asp Glu Glu Leu Ala Val Asp 
                530                 535                 540 

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

Ile Phe Thr Glu Leu Lys Lys Lys Glu Ala Asp Ala Ile Lys Leu 
                560                 565                 570 

Thr Pro Val Pro Gln Gln Pro Ser Pro Glu Glu Asp Gln Val Val 
                575                 580                 585 

Glu Glu Gly Glu Glu Ala Ala Gly Glu Glu Gly Asp Glu Glu Val 
                590                 595                 600 

Glu Glu Asp Leu Ala 
                605 

 
           
             12  
             1179  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 3029343CD1  
             
           
            12 

Met Asp Tyr Glu His His Glu Arg Trp Pro Arg Phe Asn Arg Met 
  1               5                  10                  15 

Phe Leu Asp Lys Ser Gly Ala Gln Ser Lys Ala Phe Asp Val Leu 
                 20                  25                  30 

Gly Arg Val Glu Ala Tyr Leu Lys Leu Leu Lys Ser Glu Gly Leu 
                 35                  40                  45 

Ser Leu Ala Val Leu Ala Val Arg His Glu Glu Leu His Arg Lys 
                 50                  55                  60 

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

Ile Ser Gln Val Asp Ser Cys Ser Thr Arg Pro Gln Gly Gln Ser 
                 80                  85                  90 

Lys Pro Tyr Lys Thr Asp Pro Lys Ser Pro Glu Pro Val Pro Arg 
                 95                 100                 105 

Pro Val Arg Glu Leu His Ile Lys Glu Val Cys Ser Arg His Glu 
                110                 115                 120 

Gly Pro Met Ser Thr Val Asp Val Ala Val Thr Ser Ser Glu Lys 
                125                 130                 135 

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

Gly Ser Gln Val Ser Gly Ile His Glu Met Met Gly Cys Ile Lys 
                155                 160                 165 

Arg Arg Val Asp His Leu Thr Glu Gln Cys Ser Ala His Lys Glu 
                170                 175                 180 

Tyr Ala Leu Lys Lys Gln Gln Leu Thr Ala Ser Val Glu Gly Tyr 
                185                 190                 195 

Leu Arg Lys Val Glu Met Ser Ile Gln Lys Ile Ser Pro Val Leu 
                200                 205                 210 

Ser Asn Ala Met Asp Val Gly Ser Thr Arg Ser Glu Ser Glu Lys 
                215                 220                 225 

Ile Leu Asn Lys Tyr Leu Glu Leu Asp Ile Gln Ala Lys Glu Thr 
                230                 235                 240 

Ser His Glu Leu Glu Ala Ala Ala Lys Thr Met Met Glu Lys Asn 
                245                 250                 255 

Glu Phe Val Ser Asp Glu Met Val Ser Leu Ser Ser Lys Ala Arg 
                260                 265                 270 

Trp Leu Ala Glu Glu Leu Asn Leu Phe Gly Gln Ser Ile Asp Tyr 
                275                 280                 285 

Arg Ser Gln Val Leu Gln Thr Tyr Val Ala Phe Leu Lys Ser Ser 
                290                 295                 300 

Glu Glu Val Glu Met Gln Phe Gln Ser Leu Lys Glu Phe Tyr Glu 
                305                 310                 315 

Thr Glu Ile Pro Gln Lys Glu Gln Asp Asp Ala Lys Ala Lys His 
                320                 325                 330 

Cys Ser Asp Ser Ala Glu Lys Gln Trp Gln Leu Phe Leu Lys Lys 
                335                 340                 345 

Ser Phe Ile Thr Gln Asp Leu Gly Leu Glu Phe Leu Asn Leu Ile 
                350                 355                 360 

Asn Met Ala Lys Glu Asn Glu Ile Leu Asp Val Lys Asn Glu Val 
                365                 370                 375 

Tyr Leu Met Lys Asn Thr Met Glu Asn Gln Lys Ala Glu Arg Glu 
                380                 385                 390 

Glu Leu Ser Leu Leu Arg Leu Ala Trp Gln Leu Lys Ala Thr Glu 
                395                 400                 405 

Ser Lys Pro Gly Lys Gln Gln Trp Ala Ala Phe Lys Glu Gln Leu 
                410                 415                 420 

Lys Lys Thr Ser His Asn Leu Lys Leu Leu Gln Glu Ala Leu Met 
                425                 430                 435 

Pro Val Ser Ala Leu Asp Leu Gly Gly Ser Leu Gln Phe Ile Leu 
                440                 445                 450 

Asp Leu Arg Gln Lys Trp Asn Asp Met Lys Pro Gln Phe Gln Gln 
                455                 460                 465 

Leu Asn Asp Glu Val Gln Tyr Ile Met Lys Glu Ser Glu Glu Leu 
                470                 475                 480 

Thr Gly Arg Gly Ala Pro Val Lys Glu Lys Ser Gln Gln Leu Lys 
                485                 490                 495 

Asp Leu Ile His Phe His Gln Lys Gln Lys Glu Arg Ile Gln Asp 
                500                 505                 510 

Tyr Glu Asp Ile Leu Tyr Lys Val Val Gln Phe His Gln Val Lys 
                515                 520                 525 

Glu Glu Leu Gly Arg Leu Ile Lys Ser Arg Glu Leu Glu Phe Val 
                530                 535                 540 

Glu Gln Pro Lys Glu Leu Gly Asp Ala His Asp Val Gln Ile His 
                545                 550                 555 

Leu Arg Cys Ser Gln Glu Lys Gln Ala Arg Val Asp His Leu His 
                560                 565                 570 

Arg Leu Ala Leu Ser Leu Gly Val Asp Ile Ile Ser Ser Val Gln 
                575                 580                 585 

Arg Pro His Cys Ser Asn Val Ser Ala Lys Asn Leu Gln Gln Gln 
                590                 595                 600 

Leu Glu Leu Leu Glu Glu Asp Ser Met Lys Trp Arg Ala Lys Ala 
                605                 610                 615 

Glu Glu Tyr Gly Arg Thr Leu Ser Arg Ser Val Glu Tyr Cys Ala 
                620                 625                 630 

Met Arg Asp Glu Ile Asn Glu Leu Lys Asp Ser Phe Lys Asp Ile 
                635                 640                 645 

Lys Lys Lys Phe Asn Asn Leu Lys Phe Asn Tyr Thr Lys Lys Asn 
                650                 655                 660 

Glu Lys Ser Arg Asn Leu Lys Ala Leu Lys Tyr Gln Ile Gln Gln 
                665                 670                 675 

Val Asp Met Tyr Ala Glu Lys Met Gln Ala Leu Lys Arg Lys Met 
                680                 685                 690 

Glu Lys Val Ser Asn Lys Thr Ser Asp Ser Phe Leu Asn Tyr Pro 
                695                 700                 705 

Ser Asp Lys Val Asn Val Leu Leu Glu Val Met Lys Asp Leu Gln 
                710                 715                 720 

Lys His Val Asp Asp Phe Asp Lys Val Val Thr Asp Tyr Lys Lys 
                725                 730                 735 

Asn Leu Asp Leu Thr Glu His Phe Gln Glu Val Ile Glu Glu Cys 
                740                 745                 750 

His Phe Trp Tyr Glu Asp Ala Ser Ala Thr Val Val Arg Val Gly 
                755                 760                 765 

Lys Tyr Ser Thr Glu Cys Lys Thr Lys Glu Ala Val Lys Ile Leu 
                770                 775                 780 

His Gln Gln Phe Asn Lys Phe Ile Ala Pro Ser Val Pro Gln Gln 
                785                 790                 795 

Glu Glu Arg Ile Gln Glu Ala Thr Asp Leu Ala Gln His Leu Tyr 
                800                 805                 810 

Gly Leu Glu Glu Gly Gln Lys Tyr Ile Glu Lys Ile Val Thr Lys 
                815                 820                 825 

His Lys Glu Val Leu Glu Ser Val Thr Glu Leu Cys Glu Ser Arg 
                830                 835                 840 

Thr Glu Leu Glu Glu Lys Leu Lys Gln Gly Asp Val Leu Lys Met 
                845                 850                 855 

Asn Pro Asn Leu Glu Asp Phe His Tyr Asp Tyr Ile Asp Leu Leu 
                860                 865                 870 

Lys Glu Pro Ala Lys Asn Lys Gln Thr Ile Phe Asn Glu Glu Arg 
                875                 880                 885 

Asn Lys Gly Gln Val Gln Val Ala Asp Leu Leu Gly Ile Asn Gly 
                890                 895                 900 

Thr Gly Glu Glu Arg Leu Pro Gln Asp Leu Lys Val Ser Thr Asp 
                905                 910                 915 

Lys Glu Gly Gly Val Gln Asp Leu Leu Leu Pro Glu Asp Met Leu 
                920                 925                 930 

Ser Gly Glu Glu Tyr Glu Cys Val Ser Pro Asp Asp Ile Ser Leu 
                935                 940                 945 

Pro Pro Leu Pro Gly Ser Pro Glu Ser Pro Leu Ala Pro Ser Asp 
                950                 955                 960 

Met Glu Val Glu Glu Pro Val Ser Ser Ser Leu Ser Leu His Ile 
                965                 970                 975 

Ser Ser Tyr Gly Val Gln Ala Gly Thr Ser Ser Pro Gly Asp Ala 
                980                 985                 990 

Gln Glu Ser Val Leu Pro Pro Pro Val Ala Phe Ala Asp Ala Cys 
                995                1000                1005 

Asn Asp Lys Arg Glu Thr Phe Ser Ser His Phe Glu Arg Pro Tyr 
               1010                1015                1020 

Leu Gln Phe Lys Ala Glu Pro Pro Leu Thr Ser Arg Gly Phe Val 
               1025                1030                1035 

Glu Lys Ser Thr Ala Leu His Arg Ile Ser Ala Glu His Pro Glu 
               1040                1045                1050 

Ser Met Met Ser Glu Val His Glu Arg Ala Leu Gln Gln His Pro 
               1055                1060                1065 

Gln Ala Gln Gly Gly Leu Leu Glu Thr Arg Glu Lys Met His Ala 
               1070                1075                1080 

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

Asp Ala Phe Ser Gly Leu Arg Phe Gln Ser Gly Thr Ser Arg Gly 
               1100                1105                1110 

Tyr Gln Arg Gln Met Val Pro Arg Glu Glu Ile Lys Ser Thr Ser 
               1115                1120                1125 

Ala Lys Ser Ser Val Val Ser Leu Ala Asp Gln Ala Pro Asn Phe 
               1130                1135                1140 

Ser Arg Leu Leu Ser Asn Val Thr Val Met Glu Gly Ser Pro Val 
               1145                1150                1155 

Thr Leu Glu Val Glu Val Thr Gly Phe Pro Glu Pro Thr Leu Thr 
               1160                1165                1170 

Trp Trp Val Ala Tyr Asn Asp Lys Pro 
               1175 

 
           
             13  
             372  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 5507629CD1  
             
           
            13 

Met Asn His Cys Gln Leu Pro Val Val Ile Asp Asn Gly Ser Gly 
  1               5                  10                  15 

Met Ile Lys Ala Gly Val Ala Gly Cys Arg Glu Pro Gln Phe Ile 
                 20                  25                  30 

Tyr Pro Asn Ile Ile Gly Arg Ala Lys Gly Gln Ser Arg Ala Ala 
                 35                  40                  45 

Gln Gly Gly Leu Glu Leu Cys Val Gly Asp Gln Ala Gln Asp Trp 
                 50                  55                  60 

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

Thr Ser Trp Glu Asp Met Glu Ile Met Trp Lys His Ile Tyr Asp 
                 80                  85                  90 

Tyr Asn Leu Lys Leu Lys Pro Cys Asp Gly Pro Val Leu Ile Thr 
                 95                 100                 105 

Glu Pro Ala Leu Asn Pro Leu Ala Asn Arg Gln Gln Ile Thr Glu 
                110                 115                 120 

Met Phe Phe Glu His Leu Gly Val Pro Ala Phe Tyr Met Ser Ile 
                125                 130                 135 

Gln Ala Val Leu Ala Leu Phe Ala Ala Gly Phe Thr Thr Gly Leu 
                140                 145                 150 

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

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

Gly Leu Asp Leu Thr Asn Tyr Leu Met Val Leu Met Lys Asn His 
                185                 190                 195 

Gly Ile Met Leu Leu Ser Ala Ser Asp Arg Lys Ile Val Glu Asp 
                200                 205                 210 

Ile Lys Glu Ser Phe Cys Tyr Val Ala Met Asn Tyr Glu Glu Glu 
                215                 220                 225 

Met Ala Lys Lys Pro Asp Cys Leu Glu Lys Val Tyr Gln Leu Pro 
                230                 235                 240 

Asp Gly Lys Val Ile Gln Leu His Asp Gln Leu Phe Ser Cys Pro 
                245                 250                 255 

Glu Ala Leu Phe Ser Pro Cys His Met Asn Leu Glu Ala Pro Gly 
                260                 265                 270 

Ile Asp Lys Ile Cys Phe Ser Ser Ile Met Lys Cys Asp Thr Gly 
                275                 280                 285 

Leu Arg Asn Ser Phe Phe Ser Asn Ile Ile Leu Ala Gly Gly Ser 
                290                 295                 300 

Thr Ser Phe Pro Gly Leu Asp Lys Arg Leu Val Lys Asp Ile Ala 
                305                 310                 315 

Lys Val Ala Pro Ala Asn Thr Ala Val Gln Val Ile Ala Pro Pro 
                320                 325                 330 

Glu Arg Lys Ile Ser Val Trp Met Gly Gly Ser Ile Leu Ala Ser 
                335                 340                 345 

Leu Ser Ala Phe Gln Asp Met Trp Ile Thr Ala Ala Glu Phe Lys 
                350                 355                 360 

Glu Val Gly Pro Asn Ile Val His Gln Arg Cys Phe 
                365                 370 

 
           
             14  
             1561  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 5607780CD1  
             
           
            14 

Met Cys Ser Arg Gln Arg Ser Gly Phe Gly Cys Ile Thr Asn Trp 
  1               5                  10                  15 

Trp Lys Met Gly Thr Arg His Pro Ala His Pro Ala Gln Pro Glu 
                 20                  25                  30 

Glu Leu Thr Ser Ser Leu His Ala Phe Lys Asn Lys Ala Phe Lys 
                 35                  40                  45 

Lys Ser Lys Val Cys Gly Val Cys Lys Gln Ile Ile Asp Gly Gln 
                 50                  55                  60 

Gly Ile Ser Cys Arg Ala Cys Lys Tyr Ser Cys His Lys Lys Cys 
                 65                  70                  75 

Glu Ala Lys Val Val Ile Pro Cys Gly Val Gln Val Arg Leu Glu 
                 80                  85                  90 

Gln Ala Pro Gly Ser Ser Thr Leu Ser Ser Ser Leu Cys Arg Asp 
                 95                 100                 105 

Lys Pro Leu Arg Pro Val Ile Leu Ser Pro Thr Met Glu Glu Gly 
                110                 115                 120 

His Gly Leu Asp Leu Thr Tyr Ile Thr Glu Arg Ile Ile Ala Val 
                125                 130                 135 

Ser Phe Pro Ala Gly Cys Ser Glu Glu Ser Tyr Leu His Asn Leu 
                140                 145                 150 

Gln Glu Val Thr Arg Met Leu Lys Ser Lys His Gly Asp Asn Tyr 
                155                 160                 165 

Leu Val Leu Asn Leu Ser Glu Lys Arg Tyr Asp Leu Thr Lys Leu 
                170                 175                 180 

Asn Pro Lys Ile Met Asp Val Gly Trp Pro Glu Leu His Ala Pro 
                185                 190                 195 

Pro Leu Asp Lys Met Cys Thr Ile Cys Lys Ala Gln Glu Ser Trp 
                200                 205                 210 

Leu Asn Ser Asn Leu Gln His Val Val Val Ile His Cys Arg Gly 
                215                 220                 225 

Gly Lys Gly Arg Ile Gly Val Val Ile Ser Ser Tyr Met His Phe 
                230                 235                 240 

Thr Asn Val Ser Ala Ser Ala Asp Gln Ala Leu Asp Arg Phe Ala 
                245                 250                 255 

Met Lys Lys Phe Tyr Asp Asp Lys Val Ser Ala Leu Met Gln Pro 
                260                 265                 270 

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

Ser Val Lys Met Asn Ala Ser Pro Leu Phe Leu His Phe Val Ile 
                290                 295                 300 

Leu His Gly Thr Pro Asn Phe Asp Thr Gly Gly Val Cys Arg Pro 
                305                 310                 315 

Phe Leu Lys Leu Tyr Gln Ala Met Gln Pro Val Tyr Thr Ser Gly 
                320                 325                 330 

Ile Tyr Asn Val Gly Pro Glu Asn Pro Ser Arg Ile Cys Ile Val 
                335                 340                 345 

Ile Glu Pro Ala Gln Leu Leu Lys Gly Asp Val Met Val Lys Cys 
                350                 355                 360 

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

Leu Gln Phe His Thr Gly Ala Val Gln Gly Tyr Gly Leu Val Phe 
                380                 385                 390 

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

Asp Tyr Gly Lys Val Glu Leu Val Phe Ser Ala Thr Pro Glu Lys 
                410                 415                 420 

Ile Gln Gly Ser Glu His Leu Tyr Asn Asp His Gly Val Ile Val 
                425                 430                 435 

Asp Tyr Asn Thr Thr Asp Pro Leu Ile Arg Trp Asp Ser Tyr Glu 
                440                 445                 450 

Asn Leu Ser Ala Asp Gly Glu Val Leu His Thr Gln Gly Pro Val 
                455                 460                 465 

Asp Gly Ser Leu Tyr Ala Lys Val Arg Lys Lys Ser Ser Ser Asp 
                470                 475                 480 

Pro Gly Ile Pro Gly Gly Pro Gln Ala Ile Pro Ala Thr Asn Ser 
                485                 490                 495 

Pro Asp His Ser Asp His Thr Leu Ser Val Ser Ser Asp Ser Gly 
                500                 505                 510 

His Ser Thr Ala Ser Ala Arg Thr Asp Lys Thr Glu Glu Arg Leu 
                515                 520                 525 

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

Leu Asp Gln Leu Leu Ser Gly Phe Gly Leu Glu Asp Pro Gly Ser 
                545                 550                 555 

Ser Leu Lys Glu Met Thr Asp Ala Arg Ser Lys Tyr Ser Gly Thr 
                560                 565                 570 

Arg His Val Val Pro Ala Gln Val His Val Asn Gly Asp Ala Ala 
                575                 580                 585 

Leu Lys Asp Arg Glu Thr Asp Ile Leu Asp Asp Glu Met Pro His 
                590                 595                 600 

His Asp Leu His Ser Val Asp Ser Leu Gly Thr Leu Ser Ser Ser 
                605                 610                 615 

Glu Gly Pro Gln Ser Ala His Leu Gly Pro Phe Thr Cys His Lys 
                620                 625                 630 

Ser Ser Gln Asn Ser Leu Leu Ser Asp Gly Phe Gly Ser Asn Val 
                635                 640                 645 

Gly Glu Asp Pro Gln Gly Thr Leu Val Pro Asp Leu Gly Leu Gly 
                650                 655                 660 

Met Asp Gly Pro Tyr Glu Arg Glu Arg Thr Phe Gly Ser Arg Glu 
                665                 670                 675 

Pro Lys Gln Pro Gln Pro Leu Leu Arg Lys Pro Ser Val Ser Ala 
                680                 685                 690 

Gln Met Gln Ala Tyr Gly Gln Ser Ser Tyr Ser Thr Gln Thr Trp 
                695                 700                 705 

Val Arg Gln Gln Gln Met Val Val Ala His Gln Tyr Ser Phe Ala 
                710                 715                 720 

Pro Asp Gly Glu Ala Arg Leu Val Ser Arg Cys Pro Ala Asp Asn 
                725                 730                 735 

Pro Gly Leu Val Gln Ala Gln Pro Arg Val Pro Leu Thr Pro Thr 
                740                 745                 750 

Arg Gly Thr Ser Ser Arg Val Ala Val Gln Arg Gly Val Gly Ser 
                755                 760                 765 

Gly Pro His Pro Pro Asp Thr Gln Gln Pro Ser Pro Ser Lys Ala 
                770                 775                 780 

Phe Lys Pro Arg Phe Pro Gly Asp Gln Val Val Asn Gly Ala Gly 
                785                 790                 795 

Pro Glu Leu Ser Thr Gly Pro Ser Pro Gly Ser Pro Thr Leu Asp 
                800                 805                 810 

Ile Asp Gln Ser Ile Glu Gln Leu Asn Arg Leu Ile Leu Glu Leu 
                815                 820                 825 

Asp Pro Thr Phe Glu Pro Ile Pro Thr His Met Asn Ala Leu Gly 
                830                 835                 840 

Ser Gln Ala Asn Gly Ser Val Ser Pro Asp Ser Val Gly Gly Gly 
                845                 850                 855 

Leu Arg Ala Ser Ser Arg Leu Pro Asp Thr Gly Glu Gly Pro Ser 
                860                 865                 870 

Arg Ala Thr Gly Arg Gln Gly Ser Ser Ala Glu Gln Pro Leu Gly 
                875                 880                 885 

Gly Arg Leu Arg Lys Leu Ser Leu Gly Gln Tyr Asp Asn Asp Ala 
                890                 895                 900 

Gly Gly Gln Leu Pro Phe Ser Lys Cys Ala Trp Gly Lys Ala Gly 
                905                 910                 915 

Val Asp Tyr Ala Pro Asn Leu Pro Pro Phe Pro Ser Pro Ala Asp 
                920                 925                 930 

Val Lys Glu Thr Met Thr Pro Gly Tyr Pro Gln Asp Leu Asp Ile 
                935                 940                 945 

Ile Asp Gly Arg Ile Leu Ser Ser Lys Glu Ser Met Cys Ser Thr 
                950                 955                 960 

Pro Ala Phe Pro Val Ser Pro Glu Thr Pro Tyr Val Lys Thr Ala 
                965                 970                 975 

Leu Arg His Pro Pro Phe Ser Pro Pro Glu Pro Pro Leu Ser Ser 
                980                 985                 990 

Pro Ala Ser Gln His Lys Gly Gly Arg Glu Pro Arg Ser Cys Pro 
                995                1000                1005 

Glu Thr Leu Thr His Ala Val Gly Met Ser Glu Ser Pro Ile Gly 
               1010                1015                1020 

Pro Lys Ser Thr Met Leu Arg Ala Asp Ala Ser Ser Thr Pro Ser 
               1025                1030                1035 

Phe Gln Gln Ala Phe Ala Ser Ser Cys Thr Ile Ser Ser Asn Gly 
               1040                1045                1050 

Pro Gly Gln Arg Arg Glu Ser Ser Ser Ser Ala Glu Arg Gln Trp 
               1055                1060                1065 

Val Glu Ser Ser Pro Lys Pro Met Val Ser Leu Leu Gly Ser Gly 
               1070                1075                1080 

Arg Pro Thr Gly Ser Pro Leu Ser Ala Glu Phe Ser Gly Thr Arg 
               1085                1090                1095 

Lys Asp Ser Pro Val Leu Ser Cys Phe Pro Pro Ser Glu Leu Gln 
               1100                1105                1110 

Ala Pro Phe His Ser His Glu Leu Ser Leu Ala Glu Pro Pro Asp 
               1115                1120                1125 

Ser Leu Ala Pro Pro Ser Ser Gln Ala Phe Leu Gly Phe Gly Thr 
               1130                1135                1140 

Ala Pro Val Gly Ser Gly Leu Pro Pro Glu Glu Asp Leu Gly Ala 
               1145                1150                1155 

Leu Leu Ala Asn Ser His Gly Ala Ser Pro Thr Pro Ser Ile Pro 
               1160                1165                1170 

Leu Thr Ala Thr Gly Ala Ala Asp Asn Gly Phe Leu Ser His Asn 
               1175                1180                1185 

Phe Leu Thr Val Ala Pro Gly His Ser Ser His His Ser Pro Gly 
               1190                1195                1200 

Leu Gln Gly Gln Gly Val Thr Leu Pro Gly Gln Pro Pro Leu Pro 
               1205                1210                1215 

Glu Lys Lys Arg Ala Ser Glu Gly Asp Arg Ser Leu Gly Ser Val 
               1220                1225                1230 

Ser Pro Ser Ser Ser Gly Phe Ser Ser Pro His Ser Gly Ser Thr 
               1235                1240                1245 

Ile Ser Ile Pro Phe Pro Asn Val Leu Pro Asp Phe Ser Lys Ala 
               1250                1255                1260 

Ser Glu Ala Ala Ser Pro Leu Pro Asp Ser Pro Gly Asp Lys Leu 
               1265                1270                1275 

Val Ile Val Lys Phe Val Gln Asp Thr Ser Lys Phe Trp Tyr Lys 
               1280                1285                1290 

Ala Asp Ile Ser Arg Glu Gln Ala Ile Ala Met Leu Lys Asp Lys 
               1295                1300                1305 

Glu Pro Gly Ser Phe Ile Val Arg Asp Ser His Ser Phe Arg Gly 
               1310                1315                1320 

Ala Tyr Gly Leu Ala Met Lys Val Ala Thr Pro Pro Pro Ser Val 
               1325                1330                1335 

Leu Gln Leu Asn Lys Lys Ala Gly Asp Leu Ala Asn Glu Leu Val 
               1340                1345                1350 

Arg His Phe Leu Ile Glu Cys Thr Pro Lys Gly Val Arg Leu Lys 
               1355                1360                1365 

Gly Cys Ser Asn Glu Pro Tyr Phe Gly Ser Leu Thr Ala Leu Val 
               1370                1375                1380 

Cys Gln His Ser Ile Thr Pro Leu Ala Leu Pro Cys Lys Leu Leu 
               1385                1390                1395 

Ile Pro Glu Arg Asp Pro Leu Glu Glu Ile Ala Glu Ser Ser Pro 
               1400                1405                1410 

Gln Thr Ala Ala Asn Ser Ala Ala Glu Leu Leu Lys Gln Gly Ala 
               1415                1420                1425 

Ala Cys Asn Val Trp Tyr Leu Asn Ser Val Glu Met Glu Ser Leu 
               1430                1435                1440 

Thr Gly His Gln Ala Ile Gln Lys Ala Leu Ser Ile Thr Leu Val 
               1445                1450                1455 

Gln Glu Pro Pro Pro Val Ser Thr Val Val His Phe Lys Val Ser 
               1460                1465                1470 

Ala Gln Gly Ile Thr Leu Thr Asp Asn Gln Arg Lys Leu Phe Phe 
               1475                1480                1485 

Arg Arg His Tyr Pro Val Asn Ser Val Ile Phe Cys Ala Leu Asp 
               1490                1495                1500 

Pro Gln Asp Arg Lys Trp Ile Lys Asp Gly Pro Ser Ser Lys Val 
               1505                1510                1515 

Phe Gly Phe Val Ala Arg Lys Gln Gly Ser Ala Thr Asp Asn Val 
               1520                1525                1530 

Cys His Leu Phe Ala Glu His Asp Pro Glu Gln Pro Ala Ser Ala 
               1535                1540                1545 

Ile Val Asn Phe Val Ser Lys Val Met Ile Gly Ser Pro Lys Lys 
               1550                1555                1560 

Val 

 
           
             15  
             2066  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 1806450CB1  
             
           
            15 

ggcggctggg cgcctcggtg gtagctttct ctcctggctg gagacgacca caaccgacat     60 

gggctgtttc tgcgctgttc cggaagaatt ttactgcgaa gttttgctcc tggatgaatc    120 

caagttaacc cttaccaccc agcagcaggg catcaagaag tcaacgaaag gttccgttgt    180 

ccttgaccac gtattccatc acgtaaacct tgtggagata gattattttg ggctacgtta    240 

ctgtgacaga agccatcaga cgtattggct ggatcctgca aaaacccttg ctgaacacaa    300 

agaactgatc aacactggac ctccatatac tttgtatttt ggtattaaat tctatgctga    360 

agatccatgt aaacttaaag aagaaataac cagatatcag tttttcttgc aggtgaagca    420 

agatgtcctt cagggccgtc tgccctgtcc cgtcaacact gctgctcagc tgggagcgta    480 

tgccatccag tcggagcttg gagattatga cccatataaa catactgcag gatatgtatc    540 

tgagtaccgg tttgttcctg atcagaagga agaacttgaa gaagccatag aaaggattca    600 

taaaactcta atgggtcaga ttccttctga ggctgagctg aattacttga ggactgccaa    660 

atccctggag atgtatggcg ttgacctcca tcccgtctat ggagaaaaca agtctgagta    720 

tttcttagga ttaactccgg ttggtgttgt tgtgtacaag aataaaaagc aagtggggaa    780 

gtatttctgg cctcggatta caaaggttca cttcaaggag actcaatttg aactcagagt    840 

actgggaaaa gattgtaacg aaacctcatt cttttttgaa gctcggagta aaactgcttg    900 

caagcacctc tggaagtgca gtgtggaaca tcatacattt tttagaatgc cagaaaatga    960 

atccaattca ctgtcaagaa aactcagcaa gtttggatcc atacgttata agcaccgcta   1020 

cagtggcagg acagctttgc aaatgagccg agatctttct attcagcttc cccggcctga   1080 

tcagaatgtg acaagaagtc gaagcaagac ttaccctaag cgaatagcac aaacacagcc   1140 

agctgaatca aacaccatca gtaggataac tgcaaacatg gaaaatggag aaaatgaagg   1200 

aacaattaaa attattgcac cttcaccagt aaaaagcttt aagaaagcaa agaatgaaaa   1260 

tagccctgat acccaaagaa gcaaatctca tgcaccgtgg gaagaaaatg gcccccagag   1320 

tggactctac aattctccca gtgatcgcac taagtcgcca aagttccctt acacgcgtcg   1380 

ccgaaacccc tcctgtggaa gtgacaatga ttctgtacag cctgtgagga ggaggaaagc   1440 

ccataacagt ggtgaagatt cagatcttaa gcaaaggagg aggtcacgtt cacgctgtaa   1500 

caccagcagt ggtagtgaat cagaaaattc taatagagaa caccggaaaa agagaaacag   1560 

aatacggcag gagaatgata tggttgattc agcgcctcag tgggaagctg tattaaggag   1620 

acaaaaggaa aaaaaccacg ccgaccccaa cagcaggcga tccagacaca gatctcgttc   1680 

gagaagcccc gatatccaag caaaagaaga gttatggaag cacattcaaa aagaacttgt   1740 

ggatccatcc ggattgtccg aagaacaatt aaaagagatt ccatacacta aaatagagtg   1800 

agtgcctttc agaatcttct caccaaagct ttattagtgc ttgtgagtaa tccattctaa   1860 

ttcttcaatt gtgttccaga cagtgcttta atttgtcttt acattttaac caaaactagg   1920 

tgacagtagc gaaagaggaa gaaaagtgtg cattaaagct acttattcta cactataatc   1980 

actatcatct cttattagcc acctctttgt acttggtagg tacaaggggg cttttcctga   2040 

ttaatgtcag ttttaaaata gagtat                                        2066 

 
           
             16  
             1912  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 959690CB1  
             
           
            16 

atggcggacg aggacgggga agggattcat ccctcagccc ctcacaggaa cggaggtggc     60 

ggcggcggcg gggggtctgg gctccactgc gccgggaacg gcggcggggg aggcggcggc    120 

ccgcgggtcg tgcgcatcgt caagtccgag tccggctacg gcttcaacgt gcggggccaa    180 

gtgagcgagg gcgggcaact gcggagcatc aacggggagc tgtacgcgcc gctgcagcat    240 

gtgagcgccg tgctgcccgg gggggcggcc gatcgggccg gggtgcgcaa gggggaccgc    300 

atcctggagg tgaaccacgt gaatgttgag ggggcgacac acaagcaggt ggtggacctg    360 

attcgagcag gcgagaagga attgatcttg acagtgttat ctgtacctcc tcatgaggca    420 

gataacctag atcccagtga cgactcgttg ggacaatcat tttatgatta cacagaaaag    480 

caagcagtgc ccatatcggt ccccagatac aaacatgtgg agcagaatgg tgagaagttt    540 

gtggtatata atgtttacat ggcagggagg cagctgtgtt ctaagcggta ccgggagttt    600 

gctatcctac accagaacct gaagagagag tttgccaact ttacatttcc tcgactccca    660 

gggaagtggc cattttcatt atcagaacaa caattagatg cccgacgtcg gggattggaa    720 

gaatatctag aaaaagtgtg ttcaatacga gtaattggtg agagtgacat catgcaggaa    780 

ttcctatcag aatccgatga gaactacaat ggtgtgtccg acgtagagct gagagtagca    840 

ttaccagatg gaacaacggt tacagtcagg gttaaaaaga acagtactac agaccaagta    900 

tatcaggcta tcgcagcaaa ggttggcatg gacagtacga cagtgaatta ctttgcctta    960 

tttgaagtga tcagtcactc ctttgtacgt aaattggcac ctaatgagtt tcctcacaaa   1020 

ctctacattc agaattatac atcagctgtg ccaggcacct gcttgaccat tcgaaagtgg   1080 

ctttttacaa cagaagaaga aattctctta aatgacaatg accttgctgt tacctacttc   1140 

tttcatcagg cagtcgatga tgtgaagaaa ggttacatca aagcagaaga aaagtcctat   1200 

caattacaga agctatacga acaaagaaaa atggtcatgt acctcaacat gctaaggact   1260 

tgtgagggct acaatgaaat catctttccc cactgtgcct gtgactccag gaggaagggg   1320 

cacgttatca cagccatcag catcacgcac tttaaactgc atgcctgcac tgaagaagga   1380 

cagctggaga accaggtaat tgcatttgaa tgggatgaga tgcagcgatg ggacacagat   1440 

gaagaaggga tggccttctg tttcgaatat gcacgaggag agaagaagcc ccgatgggtt   1500 

aaaatcttca cgccatattt caattacatg catgagtgct tcgagagggt gttctgcgag   1560 

ctcaagtgga gaaaagagaa cattttccag atggcgaggt cacagcagag agatgtggcc   1620 

acctagcctt tccttatccc cttcccttcc cttcaccccc atcctcttac tcctttcatg   1680 

tcccatttca gacagagtaa ccattaacaa aaaagaagag aaaaagttaa agtcgttata   1740 

ttcaaaagcc ctaaactaaa tattattaat aaccccctct gaatttcatg tctctggaat   1800 

tgaggtggta gtgaacagca gatcggtcag caccagaagt caactgagtt aaggcaggaa   1860 

aagaaataag ccctttccag cacactgcgc cgtaactagt gtgccggctc ga           1912 

 
           
             17  
             2846  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7091536CB1  
             
           
            17 

cggctcgaga tctgggctgg ggggaggcgg tggcggctga gggaaggagg aggataagga     60 

ggaggaacga ggccagcagg aggcaacggc agcgacgggg ccggggtgat ggtgcaggtg    120 

cctggggtcg gtgcggagct gccgggctga gggacgcctg gtccagggtc cgcagcgccg    180 

ccgcgtcgct cccgggcggg cgggcgggaa gatgctgagc aggttgatga gcggcagcag    240 

caggagcctg gagcgcgagt acagctgcac cgtgcggctg ctggacgaca gcgagtacac    300 

ctgcaccatc cagagagatg ccaaaggcca gtacctgttt gaccttcttt gccaccatct    360 

gaacctactt gagaaagact attttggtat ccgctttgta gacccagata agcagcggca    420 

ttggctggaa tttacaaagt ctgtggtgaa acaattgaga tcccagcctc cattcaccat    480 

gtgcttccgt gtgaagtttt atcctgcaga ccctgctgct ctgaaagaag aaataaccag    540 

gtatttagtc ttcctgcaga tcaaaaggga tctctaccat ggccgactcc tctgtaaaac    600 

atcggatgct gccttgttag cagcttacat ccttcaagcg gagattgggg attatgactc    660 

agtgaaacac cctgaaggct acagctccaa gttccagttt ttccctaaac attcagagaa    720 

gctggaaagg aaaattgctg agattcacaa gacggaactg agtggtcaaa caccagcaac    780 

atcagagctg aacttcttaa gaaaagcaca gacattggaa acatatggag tggatcctca    840 

cccatgtaag gacgtgtcag gaaatgctgc atttctggcc ttcactcctt ttgggtttgt    900 

tgttcttcaa ggaaacaaga gggtccactt cattaaatgg aatgaggtga ccaagctgaa    960 

atttgaagga aagactttct atttatacgt aagtcagaaa gaggaaaaga aaattattct   1020 

tacatatttt gctccaactc ctgaagcgtg taagcacctc tggaaatgtg gaatcgagaa   1080 

ccaagccttc tacaagctgg agaagtcaag ccaagtccgc acagtgtcca gcagcaattt   1140 

attctttaaa gggagccggt tccgatacag tggccgagtt gcaaaggaag tcatggaatc   1200 

aagtgctaag atcaaacggg agccaccgga aatacacaga gcagggatgg ttcccagccg   1260 

gagctgtccc tccataaccc atggcccaag gctgagcagc gtccccagga cccgcagaag   1320 

agctgttcac atctccatca tggaaggcct agagtcctta cgggacagtg cccattccac   1380 

accagtgcgt tccacttccc atggggacac cttcctgcct cacgtgagaa gcagccggac   1440 

agatagcaat gagcgagtag ctgtgattgc agacgaggcc tacagccctg cagacagcgt   1500 

gctgcccacc cctgtggctg agcacagcct ggagctgatg ttgctttccc ggcagatcaa   1560 

tggagccacc tgcagcattg aggaggagaa ggaatctgaa gccagcaccc caactgctac   1620 

agaggtggag gcccttgggg gagagctgag ggccctgtgt caggggcaca gcgggcccga   1680 

ggaggaacag gtgaataagt ttgttctaag tgtcctccgt ttgctccttg tgaccatggg   1740 

actcctcttt gttttgctcc tcctcctgat catccttacc gagtctgacc ttgacattgc   1800 

ctttttccgt gatatccgcc agacccccga gtttgaacaa ttccactatc aatacttttg   1860 

tcccctcagg cgatggtttg cctgcaaaat ccgctcagtg gtgagcctgc tcattgacac   1920 

ctgagaaggc atgactcctc ccaaaaacta gccaggtgga ccaaggaacc cggctaccca   1980 

ttcccagcaa tgggacccat cgcggaacca tcggcacata taccaagtcc tcctctcatg   2040 

actcaaagtc cactgcagcc taggagggtg tttcccagaa gaagaaaggg ataggctcat   2100 

gccctgtcta aacaaactgg gaaaactcat tttcttcaga agttatttca agaaaggctc   2160 

agcgactctg tttctcatct ttccaatttg caggataatt tttgggtttt gaattttgat   2220 

ttttcataga tgtatattat tttgaagtat caaataaaaa taatttattt tactattact   2280 

gattattgca gctagtactc acctagcaga ggggacacta gttgaaaact agagagctgc   2340 

tgtcctctgt attctgcagg agcttttcct gctggtgcca ctgggttcca gtagactcat   2400 

cactgcagcc tcagcagggc aggccaggat ctggacaatg gggactgttt agttttttgt   2460 

ttgttttttt tgccagccag aacttttaaa aaagtaaaca tccatgtaga atgattaaat   2520 

ggaaagttgc ttcttatgat ggtctgagtt ggattttctt ttccttttgt tttttcaaat   2580 

ctgagcagag tgggcatctg aagggaccac cgctacagca acagcagcat caggggtggg   2640 

gtaagtctgt ccccttagtc tagagcctag tgggcatcac catagttttg tataatgaaa   2700 

ctagacttaa cgtgattttt tttttccgaa gaacctcaag acttttatag tgctccaggg   2760 

gcgttaaacg aattcagggg taccagagat agatagttct gtcagaattg tgggacaaag   2820 

tgtagttaag agaaagcaga gttaag                                        2846 

 
           
             18  
             1200  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7472724CB1  
             
           
            18 

gggcgacagt taaacaggcc ctggggcagg gcgcgcctcg cgctccaggg agccccgccc     60 

tcccgcggca cctccgcagc aaccgccgcc tgcactgggc gcgcgagagc tgctagggcg    120 

gtttctctgc ctcgggcctg ttgggcaggg ccggctaagg tgcgcgtgct cgctggttct    180 

aacccttctg ttgggcgttt ctgctgagag gcgggaggcg ctgagagtct gtgcggaggt    240 

ccgtggacag actgctttgc tcgttgttgc tcttcggagg cggcgatccc cgaaggcgag    300 

ctgaaatacg gctgcaggct acaatttgca gccgacgatt atggaagacg gcaagcggga    360 

gaggtggccc accctcatgg agcgcttgtg ctcggatggc ttcgcatttc cccaataccc    420 

cattaaaccg tatcatctga agaggatcca cagagctgtc ttacatggta atctagagaa    480 

actgaagtac cttctgctca cgtattatga cgccaataag agagacagga aggaaaggac    540 

cgccctacat ttggcctgtg ccactggcca accggaaatg gtacatctcc tggtgtccag    600 

aagatgtgag cttaacctct gcgaccgtga agacaggaca cctctgatca aggctgtaca    660 

actgaggcag gaggcttgtg caactcttct gctgcaaaat ggcgccaatc caaatattac    720 

ggatttcttt ggaaggactg ctctgcacta cgctgtgtat aatgaagata catccatgat    780 

agaaaaactt ctttcacatg gtacaaatat tgaagaatgc agcaaggtat aggtcaacca    840 

atgttatttt caaactatct gaaatgaatt tattttaaca ttgacacatg taagggtcaa    900 

tttttcatat ttggaagctc aaacattcct tgaatgaaaa tattttgaaa tgccttaact    960 

gtctaagatt ttactttaaa tattggaact tttaaagaag cattataggg aacagccttt   1020 

tttcatgcac ttatggtaaa taactataaa aacaaatgaa ttacaataaa tttataattc   1080 

atgacaactg aatttgggaa aggtaatagt taagtgtttt tccactaaat tacttttttt   1140 

ctaatcagtg tgaagtgaca caggaaagta aaattgtccc ttataaatag gctttatttt   1200 

 
           
             19  
             10253  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 5844189CB1  
             
           
            19 

ttccctgaag ctgccggctg aggccggagc tgccgcctcc atgagaggct tcctcctaca     60 

ccccagggcc agaggaccct ttgccaccag agtgagatcc tagagaccat catcctggta    120 

aatcccagtg cagacagcat cagctctgag gttcatcatc ttcttagcag ctcatcagct    180 

tataaactac taatcttgag tgggcaaagt ttagagcctg ggggagacct catcctacag    240 

agtggcacct actcatatga aaactttgcc caggtccttc acaaccccga gatttcccaa    300 

ttgctcagca atagagaccc tgggatacgg gccttcctta ccgtgtcctg cttaggggaa    360 

ggtgattgga gccacctggg attatccagt tcccaagaga ccctgcacct ccggctaaac    420 

cctgagccca ctctgcccac catggacggc gtggctgagt tctccgagta tgtctctgag    480 

actgtggacg tgccatcccc atttgaccta ctagagcccc ccacctcagg gggcttcctc    540 

aagctctcca agccttgttg ctacatcttc ccaggtggtc gtggggactc tgccctcttt    600 

gctgtcaatg gtttcaacat cctggtggat ggtggctctg atcgcaagtc ctgtttttgg    660 

aagctggtac ggcacttgga ccgcattgac tcggtgctac tcacacacat tggggcagac    720 

aacctgccag gcatcaatgg actactgcag cgcaaagtgg cagagctaga ggaggagcag    780 

tcccagggct ctagcagtta cagcgactgg gtgaagaacc ttatctctcc tgagcttgga    840 

gttgtctttt tcaacgtgcc tgagaagctg cggcttcctg atgcctcccg gaaagccaag    900 

cgtagcattg aggaggcctg cctcactctg cagcacttaa accgcctggg catccaggct    960 

gagcctctat atcgtgtggt cagcaatacc attgagccac tgaccctctt ccacaaaatg   1020 

ggtgtgggcc ggctggacat gtatgtcctc aaccctgtca aggacagcaa ggagatgcag   1080 

ttcctcatgc aaaagtgggc aggcaatagt aaagccaaga caggcatcgt gctgcccaat   1140 

gggaaggagg ctgagatctc cgtgccctac cttacctcta tcactgctct ggtggtctgg   1200 

ctaccagcca atcccactga gaagattgtg cgtgtgcttt ttccaggaaa tgctccccaa   1260 

aacaagatct tggagggcct agaaaagctt cggcatctgg acttcctgcg ttaccctgtg   1320 

gccacgcaga aggacctggc ttctggggct gtgcctacca acctcaagcc cagcaaaatc   1380 

aaacagcggg ctgatagcaa ggagagcctc aaagccacta ccaagacggc cgtgagcaag   1440 

ttggccaaac gggaggaggt ggtagaagag ggagccaagg aggcacgttc agagctggcc   1500 

aaggagttag ccaagacaga gaagaaggca aaagagtcat ctgagaagcc cccagagaag   1560 

cctgccaagc ctgagagggt gaagacagag tcaagtgagg cactgaaggc agagaagcga   1620 

aagctgatca aagacaaggt agggaaaaag caccttaaag aaaagatatc aaagctggaa   1680 

gaaaaaaaag acaaggagaa aaaagagatc aaaaaggaga ggaaagagct caagaaggat   1740 

gaaggaagga aggaggagaa gaaggatgcc aagaaggagg agaagaggaa agataccaaa   1800 

cctgagctca agaagatttc caagccagac ctaaagccct ttactcctga ggtacgtaag   1860 

accctctata aagccaaggt ccctggaaga gtcaaaatag acaggagccg tgctatccgt   1920 

ggggagaagg agctgtcttc tgagccccag acacccccag cccagaaggg aactgtacca   1980 

ctcccaacca tcagtgggca cagggagctg gtcctatcct caccagagga cctcacacag   2040 

gactttgagg agatgaagcg tgaggagagg gctttgctgg ctgaacaaag ggacacagga   2100 

ctaggagata agccattccc tctagacact gcagaggagg gacccccaag tacagctatc   2160 

cagggaacac caccctctgt tccagggctg ggacaagaag aacatgtgat gaaggagaaa   2220 

gagcttgtcc cagaggtccc tgaggaacaa ggcagcaagg acagaggcct agactctggg   2280 

gctgaaacag aggaagagaa agatacctgg gaggaaaaga agcagaggga agcagagagg   2340 

ctcccagaca gaacagaagc cagagaggaa agtgaacctg aagtaaagga ggatgtgata   2400 

gaaaaggctg agttagaaga aatggaggag gtacaccctt cagatgagga ggaagaggac   2460 

gcgacaaaag ctgagggttt ttaccaaaaa catatgcagg aacccttgaa ggtaactcca   2520 

aggagccggg aggcttttgg gggtcgggaa ttgggactcc agggcaaggc ccctgagaag   2580 

gagacctcgt tattcctaag cagcctgacc acacctgcag gagccactga gcatgtctct   2640 

tacatccagg atgagacaat ccctggctac tcagagactg agcagaccat ctcagatgag   2700 

gagatccatg atgagccgga ggagcgccca gctccaccca gatttcatac aagtacatat   2760 

gacctgcccg ggcctgaagg tgctggccca ttcgaagcca gccaacctgc cgatagtgct   2820 

gttcctgcta cctctggcaa agtctatgga acgccagaga ctgaactcac ctaccccact   2880 

aacatagtgg ctgccccttt ggctgaagag gaacatgtgt cctcggccac ttcaatcact   2940 

gagtgtgaca aactttcttc ctttgccaca tcagtggctg aggaccaatc tgtggcctca   3000 

cttacagctc cccagacaga ggagacaggc aagagctccc tgctgcttga cacagtcaca   3060 

agcatccctt cctcccgtac tgaagctacg cagggcttgg actatgtgcc atcagctggt   3120 

accatctcac ccacctcctc actggaagaa gacaagggct tcaaatcacc accctgtgag   3180 

gacttctctg tgactgggga gtcagagaag agaggagaga tcatagggaa aggcttgtct   3240 

ggagagagag ctgtggaaga ggaagaggag gagacagcaa acgtagagat gtctgagaaa   3300 

ctttgcagtc aatatggaac tccagtgttt agtgcccctg ggcatgccct acatccagga   3360 

gaaccagccc ttggagaagc agaggagcgg tgccttagcc cagatgacag cacagtgaag   3420 

atggcttctc ctccaccatc tggcccaccc agtgccaccc acacaccctt tcatcagtcc   3480 

ccagtggaag aaaagtctga gccccaagac tttcaggagg cagactcctg gggagacact   3540 

aagcgcacac caggtgtggg caaagaagat gctgctgagg agacagtcaa gccagggcct   3600 

gaagagggca cactagagaa ggaagagaaa gttcctcctc ccaggagccc ccaggcccag   3660 

gaagcacctg tcaacattga tgaggggctt acaggctgta ccattcaact gttgccagca   3720 

caggataaag caatagtctt tgagattatg gaggcaggag agcccacagg cccaattctg   3780 

ggagcagaag cccttcccgg aggtttgagg actttacccc aagaacctgg caaacctcag   3840 

aaagatgagg tgctcagata tcctgaccga agcctctctc ctgaagatgc agaatccctc   3900 

tctgtcctca gcgtgccctc cccagacact gccaaccaag agcctacccc caagtctccc   3960 

tgtggcctga cagaacagta cctacacaaa gaccgttggc cagaggtatc tccagaagac   4020 

acccagtcac tttctctgtc agaagagagt cccagcaagg agacctccct ggatgtctct   4080 

tctaagcagc tctctccaga aagccttggc accctccagt ttggggaact aaaccttggg   4140 

aaggaagaaa tggggcatct gatgcaggcc gagaacacct ctcaccacac agctcccatg   4200 

tctgttccag agccccatgc agccacagcg tcacctccca cagatgggac aactcgatac   4260 

tctgcacaga cagacatcac agatgacagc cttgacagga agtcacctgc cagctcattc   4320 

tctcactcta caccttcagg aaatgggaag tacttacctg gggcgatcac aagccctgat   4380 

gaacacattc tgacacctga tagctccttc tccaagagtc ctgagtcttt gccaggccct   4440 

gccttggagg acattgccat aaagtgggaa gataaagttc cagggttgaa agacagaacc   4500 

tcagaacaga agaaggaacc tgagccaaag gatgaagttt tacagcagaa agacaaaact   4560 

ctggagcaca aggaggtggt agagccgaag gatacagcca tctatcagaa agatgaggct   4620 

ctgcatgtaa agaatgaggc tgtgaaacag caggataagg ctttagaaca aaagggcaga   4680 

gacttagagc aaaaagacac agccctagaa cagaaggaca aggccctgga accaaaagac   4740 

aaagacttag aagaaaaaga caaggccctg gaacagaagg ataagattcc agaagagaaa   4800 

gacaaagcct tagaacaaaa ggatacagcc ctggaacaga aggacaaggc cctggaacca   4860 

aaagataaag acttggaaca aaaggacagg gtcctagaac agaaggagaa gatcccagaa   4920 

gagaaagaca aagccttaga tcaaaaagtc agaagtgttg aacataaggc tccggaggac   4980 

acggtcgctg aaatgaagga cagagaccta gaacagacag acaaagcccc tgaacagaaa   5040 

caccaggccc aggaacaaaa ggataaagtc tcagaaaaga aggatcaggc cttagaacaa   5100 

aaatactggg ctttgggaca gaaggatgaa gccctggaac aaaacattca ggctctggaa   5160 

gagaaccacc aaactcagga gcaggagagc ctagtgcagg aggataaaac caggaaacca   5220 

aagatgctag aggaaaaatc cccagaaaag gtcaaggcca tggaagagaa gttagaagct   5280 

cttctggaga agaccaaagc tctgggcctg gaagagagcc tagtgcagga gggcagggcc   5340 

agagagcagg aagaaaagta ctggaggggg caggatgtgg tccaggagtg gcaagaaaca   5400 

tctcctacca gagaggagcc ggctggagaa cagaaagagc ttgccccggc atgggaggac   5460 

acatctcctg agcaggacaa taggtattgg aggggcagag aggatgtggc cttggaacag   5520 

gacacatact ggagggagct aagctgtgag cggaaggtct ggttccctca cgagctggat   5580 

ggccaggggg cccgcccaca ctacactgag gaacgggaaa gcactttcct agatgagggc   5640 

ccagatgatg agcaagaagt acccctgcgg gaacacgcaa cccggagccc ctgggcctca   5700 

gacttcaagg atttccagga atcctcacca cagaaggggc tagaggtgga gcgctggctt   5760 

gctgaatcac cagttgggtt gccaccagag gaagaggaca aactgacccg ctctcccttt   5820 

gagatcatct cccctccagc ttccccacct gagatggttg gacaaagggt tccttcagcc   5880 

ccaggacaag agagtcctat cccagaccct aagctcatgc cacacatgaa gaatgaaccc   5940 

actactccct catggctggc tgacatccca ccctgggtgc ccaaggacag acccctcccc   6000 

cctgcacccc tctccccagc tcctggtccc cccacacctg ccccggaatc ccatactcct   6060 

gcacccttct cttggggcac agccgagtat gacagtgtgg tggctgcagt gcaggagggg   6120 

gcagctgagt tggaaggtgg gccatactcc cccctgggga aggactaccg caaggctgaa   6180 

ggggaaaggg aagaagaagg tagggctgag gctcctgaca aaagctcaca cagctcaaag   6240 

gtaccagagg ccagcaaaag ccatgccacc acggagcctg agcagactga gccggagcag   6300 

agagagccca caccctatcc tgatgagaga agctttcagt atgcagacat ctatgagcag   6360 

atgatgctta ctgggcttgg ccctgcatgc cccactagag agcctccact tggagcagct   6420 

ggggattggc ccccatgcct ctcaaccaag gaggcagctg ccggccgaaa cacatctgca   6480 

gagaaggagc tttcatctcc tatctcaccc aagagcctcc agtctgacac tccaaccttc   6540 

agctatgcag ccctggcagg acccactgta cccccaaggc cagagccagg gccaagtatg   6600 

gagcccagcc tcaccccacc tgcagttccc ccccgtgctc ctatcctgag caaaggccca   6660 

agcccccctc ttaatggtaa catcctgagc tgcagcccag ataggaggtc cccatccccc   6720 

aaggaatcag gccggagtca ctgggatgac agcactagtg actcagaact ggagaagggg   6780 

gctcgggaac agccagaaaa agaggcccaa tccccaagtc ctcctcaccc cattcctatg   6840 

gggtccccca cattatggcc agaaactgag gcacatgtta gccctccctt ggactcacac   6900 

ctggggcctg cccgacccag tctggacttc cctgcttcag cctttggctt ctcctcattg   6960 

cagccagctc ccccacagct gccctctcca gctgaacccc gctcggcacc ctgtggctcc   7020 

cttgccttct ctggggatcg agctctggct ctggctccag gaccccccac cagaacccgg   7080 

catgatgaat acctggaagt gaccaaggcc cccagcctgg attcctcact gccccagctc   7140 

ccatcaccca gttctcctgg ggcccctctc ctctccaatc tgccacgacc tgcctcacca   7200 

gccctgtctg agggctcctc ctctgaggct accacgcctg tgatttcaag tgtggcggag   7260 

cgcttctctc caagccttga ggctgcagaa caggagtctg gagagctgga cccaggaatg   7320 

gaaccagctg cccacagcct ctgggacctc actcctctga gcccagcacc cccagcttca   7380 

ctggacttgg ccctagctcc agctccaagc ctgcctggag acatgggtga tggcatcctg   7440 

ccgtgccacc tggagtgctc agaggcagcc acggagaagc caagcccctt ccaggttccc   7500 

tctgaggatt gtgcagccaa tggcccaact gaaaccagcc ctaacccccc aggccctgcc   7560 

ccagccaagg ctgaaaatga agaggctgcg gcttgccctg cctgggaacg tggggcctgg   7620 

cctgaaggag ctgagaggag ctcccggcct gacacattgc tctcccctga gcagccagtg   7680 

tgtcctgcag ggggctccgg gggcccaccc agcagtgcct ctcctgaggt cgaagctggg   7740 

ccccagggat gtgccactga gcctcggccc catcgtgggg agctctcccc atccttcctg   7800 

aacccacctc tgcccccatc catagatgat agggacctct caactgagga agttcggcta   7860 

gtaggaagag gggggcggcg ccgggtaggg gggccaggga ccactggggg cccatgccct   7920 

gtgactgatg agacaccccc tacatcagcc agtgactcag gctcctcaca gtcagattct   7980 

gatgtcccgc cagaaactga ggagtgtccg tccatcacag ctgaggcagc cctcgactca   8040 

gatgaagatg gagacttcct acctgtggac aaagctgggg gtgtcagtgg tactcaccac   8100 

cccaggcctg gccatgaccc acctcctctc ccacagccag acccccgccc atcccctccc   8160 

cgccctgatg tgtgcatggc tgaccccgag gggctcagct cagagtctgg gagagtagag   8220 

aggctacggg agaaggaaaa ggttcagggg cgagtagggc gcagggcccc aggcaaggcc   8280 

aagccagcgt cccctgcacg gcgtctggat cttcggggaa aacgctcacc cacccctggt   8340 

aaagggcctg cagatcgagc atcccgggcc ccacctcgac cacgcagcac cacaagccag   8400 

gtcaccccag cagaggaaaa ggatggacac agccccatgt ccaaaggcct agtcaatgga   8460 

ctcaaggcag gaccaatggc cttgagttcc aagggcagct ctggtgcccc tgtatatgtg   8520 

gatctcgcct acatcccgaa tcattgcagt ggcaagactg ctgaccttga cttcttccgt   8580 

cgagtgcgtg catcctacta tgtggtcagt gggaatgacc ctgccaatgg cgagccaagc   8640 

cgggctgtgc tggatgccct gctggagggc aaggcccagt ggggggagaa tcttcaggtg   8700 

actctgatcc ctactcatga cacggaggtg actcgtgagt ggtaccaaca aactcatgag   8760 

cagcagcaac aactgaatgt cctggtcctg gctagcagca gcaccgtggt gatgcaggat   8820 

gagtccttcc ctgcctgcaa gattgagttc tgaaagagcc gccctccctt ccccaaggat   8880 

ccactccccc agctccttta gagaatggct actgctgagt cctttggggt tgagggagat   8940 

gggagctagg gggaggggag ggagatgtct tgttgtgggg acttgggctg ggctaaatgg   9000 

gaggggttgt ccctccccat catccattcc tgtgaggtgt ctcaaaccaa agttaacagg   9060 

gagaggatgg gggaggggac aaattagaat aggatagcat ctgatgcctg agaaccctct   9120 

cctagcactg tcaaatgctg gtattgaatg gggactgagg atgggtctca gagagcaacc   9180 

tcctccctcg tagagggaga ttatatcccc aactccaggg acctctttat ctcaatctat   9240 

ttatttggca tcctgggaag gatttccaat agtaatttat gtgacctggg gcaggatacc   9300 

gtcagtgagg tgcccagagc tgcacccttt cctccatttc ccatccccca tctcctcaac   9360 

caccagggtc tgagttctag cagggtcctg ggggtatccc actgctatac tgttctactg   9420 

cttccctcag tatctgaatg tctcaattta aaacttgaag ctctttagac caatagactg   9480 

gtgagaggag aaaggagctt atcccccaga ccctgcttta taccattcac atcccagggc   9540 

tgtgtccaga cagcacaaaa cggcaaggag agcccaagcc ccaatgccag aattcttcca   9600 

aactccctga ctctttgaag tttttactca ccccatttca attatcctga tcccttctca   9660 

tcccctgctt ggcttctctg catgtggtca tctgctgtgg cttggtgttt aatgggttaa   9720 

aaataagcca ctgcctgaca tcccaacatt tgacacccca gcaatgtgtg actcccccaa   9780 

cattccacta tgccatcctg cagctgaaat gggaacactg gctgcctctc caaacccgct   9840 

cttggacaga ggatctggga ggtggaagcc aggccagagg acttggggaa aatgagatgg   9900 

aggaaggaaa aagggagaag ctgagccaca gcttaactcc tacagagtga aatgaaaacg   9960 

ggctgaaaat accaccccag gagaggacct cgccccaagc aagccagtga gcagccctgc  10020 

cagactactg ccagactgag aaacccagaa gctggtagtc atgtgggctt gccttctctg  10080 

ccaaacgact gggaaaccaa aatgagccca ccttgtgttc ttcctagctc caccctcccc  10140 

gtgctgctgt gttctgctcc tccccacgct tccctgctat agttcccagc tgctgtaacg  10200 

gagccacctc caactctaac aataaaccaa gttcattgca gaaaaaaaaa aaa         10253 

 
           
             20  
             3851  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7472720CB1  
             
           
            20 

cggcagcaac tgccgtgcag gcgcgcgccc aacggctttg cgaggctcac tcggtctgag     60 

aggtcggagg ctgcgagtgt cgctgctgaa ggctgtggtg gaccgggctg gatcgcggat    120 

tgtggagtag attatagatt tgaaatagcg gagttggggt tggatcgggg cttggggttg    180 

gataggggat ttggggctgg gtcggccggg gtcggggagg ggggtggtga aaaggtgaca    240 

gggagctgcc ctcgctcaag agccggtggt tgggggtctg agaagaagtc accaatatga    300 

agttattcgg cttcgggagc cgcaggggcc agacggccca gggctccata gaccacgtct    360 

acacgggttc cggataccga atccgggact ccgaactgca gaagatccac agggcagctg    420 

tcaaaggcga tgccgcggag gtggagcgct gcttggcgcg caggagcgga gacctggacg    480 

ccctggacaa gcagcacaga actgctctac acttggcctg tgccagtggc catgtgcaag    540 

tggtcactct cctggttaac agaaaatgcc agattgatgt ctgtgacaaa gaaaacagaa    600 

cgcctttgat acaggctgtc cattgccagg aagaggcttg tgccgttatt ctgctggaac    660 

atggcgccaa tccaaacctt aaggatatct acggcaacac tgctctccat tatgccgtgt    720 

atagtgagag cacctcactg gcagaaaaac tgctttccca tggtgcacat attgaagcac    780 

tggacaagga caataatacc ccacttttat tcgctataat ttgcaagaaa gagaaaatgg    840 

tggaattttt attgaaaaag aaagcagtgc acaatgccgt tgataggctg agacggtcag    900 

ctctcatact tgctgtatac tatgactcac caggtattgt caatatcctt cttaagcaaa    960 

atattgatgt cttcgctcaa gacatgtgtg gacgagatgc agaagattat gctatttctc   1020 

atcatttgac aaaaattcaa caacaaattt tggaacataa aaagaagata cttaaaaagg   1080 

agaaatcaga tgttggaagt tctgatgaat ctgcagtcag cattttccat gaactgcgtg   1140 

tggattcatt gcctgcatcg gatgacaaag acttgaatgt tgctactaag tgtgtccccg   1200 

agaaagtgtc agagccttta cctggatctt cgcatgaaaa aggaaacaga atagtcaatg   1260 

gacaaggaga agggcctcct gcaaaacatc cttccttgaa gcctagcact gaagtggaag   1320 

atcctgctgt gaaaggagca gtacaaagaa agaatgtaca gacattgaga gcagaacaag   1380 

ccttaccagt ggcttcagag gaagagcaac aaaggcatga aagaagtgaa aagaagcaac   1440 

cacaggtcaa agaaggaaat aatacaaaca aaagtgaaaa aatacaactt tcagaaaata   1500 

tatgtgatag tacatcttct gctgctgctg gcagattaac ccaacaaaga aagattggga   1560 

aaacgtatcc tcagcaattt cccaagaagc tgaaggaaga gcatgataga tgcaccttaa   1620 

aacaagaaaa tgaagaaaaa acaaatgtta atatgctgta caaaaaaaat agagaagaat   1680 

tagaaaggaa agagaaacaa tataagaaag aagttgaagc aaaacaactt gaaccaactg   1740 

ttcagtcact agagatgaaa tcaaagactg caagaaatac tccaaatcgg gattttcata   1800 

atcatgaaga aatgaaaggt ctgatggatg aaaattgcat tttgaaggca gatattgcta   1860 

tactcagaca ggaaatatgt acaatgaaaa atgacaactt ggaaaaagaa aataaatatc   1920 

ttaaggacat taaaattgtt aaagaaacaa atgctgccct tgaaaagtat ataaaactca   1980 

atgaggaaat gataacagaa acagcattcc ggtatcaaca agagcttaat gatctcaagg   2040 

ctgagaatac aaggctcaat gccgaactgt tgaaggaaaa agaaagcaag aaaagactgg   2100 

aagctgacat tgaatcttat cagtctagac tggctgctgc tataagcaaa cacagtgaaa   2160 

gtgtgaaaac agaaagaaac ctaaaacttg ctttagagag aacacaagat gtttctgtac   2220 

aagtagaaat gagttctgct atttccaaag taaaagctga gaatgagttt cttactgaac   2280 

aactttctga aacacaaatt aaattcaata ccttaaaaga taagttccgt aagacaagag   2340 

atagtctcag aaaaaagtca ttggctttag aaactgtaca aaacgaccta agccaaacac   2400 

agcagcaaac acaggaaatg aaagagatgt atcaaaatgc agaagctaaa gtgaataatt   2460 

ccactggaaa gtggaactgt gtagaagaga ggatatgtca cctccaacgt gaaaatgcgt   2520 

ggcttgtaca gcaactagat gacgttcatc agaaagagga tcataaagag acagtaacta   2580 

atatccaaag aggctttatt gagagtggaa agaaagacct cgtgctagaa gagaaaagta   2640 

agaagctaat gaatgaatgt gatcatttaa aagaaagtct ctttcagtat gagagagaga   2700 

aagcagaagg agtacctaaa aaagaaaatg aagaattaag aaaacttttt gagttaatat   2760 

catcactgaa atataatgtg aatcgaataa gaaagaaaaa tgatgaatta gaagaagagg   2820 

caactggata taagaaactc ctggaaatga caataaatat gttaaatgta tttggaaatg   2880 

aagactttga ttgccatgga gacttaaaaa cagatcaact gaaaatggat attctgatta   2940 

agaagctaaa acagaaggaa caagcacaat atgaaaaaca attagagcag ttaaacaagg   3000 

ataatatggc ttcactaaat aaaaaggaac tcacacttaa agatgtggaa tgtaaattct   3060 

cagaaatgaa aactgcttat gaagaggtta caaccgaatt agaagaatat aaggaagcct   3120 

ttgcagcagc attgaaagct aacaattcca tgtcaaaaaa gttaacaaaa tcaaataaga   3180 

aaatagcagt gattagcatg aagctcctca tggagaaaga gcagatgaaa tattttctca   3240 

gtgctcttcc tacaaggcga gacccagagt caccttgtgt tgaaaatctt actagtatag   3300 

gactcaacag aaaatatatt ccccaaacac ccataagaat tcctatttca agcccacaga   3360 

cttcaaataa ctgcaagaac tcctagactg tgatggagct ggactgtgta gaacaaataa   3420 

ctagagaaac aaagagaatt gttgctgtgt tgaacacttg ctcccgtcta cttacttctc   3480 

tataatccac tgccatggaa tgagtgattt ttcttagaag cagaggtgga gccactgagg   3540 

aagcacaggc gagccctccc cagcacgtgc tcactggtcc ccaacagaac aaccgctgcc   3600 

gcatccatga ggctcccatt gtggtgggtt gtgtcacccc acaatgtcac tgttgctgag   3660 

cccccatcgc ctctgtgttg tggagcagtt agagacacac tgtggtgtct gagtggctct   3720 

gtgtgaagga ccgttttcta ggtgagaggc acatctcaac acagctgact gatcagactc   3780 

agccgttttg cacaccctgg tcagaatgaa acattccttg gggaactcgg gccgtgagaa   3840 

gcatcctccc g                                                        3851 

 
           
             21  
             3100  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7583990CB1  
             
           
            21 

ccgcccccag cccgccttcc tcccgccgcg ccctccgcct ccgcccgcac ctcgctagcg     60 

ttcccctgtc ttccccaacg ccccggagcc gccggccgct agcgtcagcg ccagccagaa    120 

ttaaggaagt tcactggagt aaaatggagg cctcagtaat attacccatt ctgaagaaaa    180 

aactagcctt cctttcagga ggaaaggaca gacggagtgg cctcattttg acaattccat    240 

tatgcctcga acagacaaat atggatgagc tgagtgtcac cttagactac ctactcagca    300 

ttccaagtga gaagtgtaag gctagaggat ttaccgtgat tgtggatggc agaaaatcac    360 

agtggaatgt ggtgaaaaca gtagtcgtaa tgctacagaa tgttgttcca gctgaggtgt    420 

cccttgtttg tgtggtaaag ccagatgaat tctgggataa gaaagtaacg catttttgtt    480 

tttggaagga gaaggataga cttggctttg aggttatttt agtgtccgcc aacaaattga    540 

ctcgttatat agaaccatgc caattaacag aagattttgg tgggagtctc acctatgatc    600 

acatggactg gttaaataag aggctggttt ttgagaagtt tacaaaggaa tctacatcat    660 

tattagatga acttgctttg attaacaatg gaagtgataa aggaaatcag caagagaaag    720 

aaaggtctgt ggatttaaac tttcttccat cggttgatcc tgaaacagtt cttcagacag    780 

ggcatgaatt gttgtccgaa ttacagcagc gtcgatttaa tggctcagac ggaggggttt    840 

catggtctcc tatggatgat gaacttcttg cacagccaca ggttatgaaa ttattagatt    900 

cactccgaga gcaatatacc cgctaccagg aagtttgtag gcaacgtagc aagcgcacac    960 

agttagaaga gattcaacag aaggtaatgc aggtggtgaa ctggctagaa gggcctggat   1020 

cagaacaact aagagcccag tggggcattg gagactccat tagggcctcc caggccctac   1080 

agcagaaaca cgaagagatt gagagccagc acagtgaatg gtttgcagtg tatgtggaac   1140 

ttaatcagca aattgcagca ctcttgaatg ctggcgatga ggaagatctt gtggaactaa   1200 

agtcactgca gcaacaactt agtgatgttt gttatcgaca ggccagtcag ctggaattta   1260 

ggcaaaatct cttacaagca gctcttgaat ttcatggtgt tgcccaagat ttgtctcagc   1320 

agttggatgg cttattaggg atgttgtgcg tagatgtagc accagctgat ggagcatcga   1380 

ttcagcaaac tttaaaactg cttgaagaga agctgaaaag tgttgatgtg ggattgcaag   1440 

gtttgcgtga aaaaggtcaa ggtctcctgg atcagatctc caatcaggca tcctgggcct   1500 

atggaaagga tgtaaccatt gaaaataaag aaaatgtgga ccacatacaa ggagtgatgg   1560 

aagatatgca gcttagaaaa caaagatgtg aagacatggt agatgtgcga aggttaaaga   1620 

tgcttcagat ggtgcagttg tttaaatgtg aagaagatgc tgcccaggca gtagaatggc   1680 

taagtgaact tctggatgct ctgcttaaga ctcacatcag attgggcgat gatgctcaag   1740 

aaacgaaagt tttgctggaa aagcatagaa aatttgttga tgttgcacag agcacttatg   1800 

actatggcag gcagttgcta caggccacag ttgtgttatg ccaatctttg cgctgcactt   1860 

ctcggtcatc tggggataca cttcctcgac tgaacagagt atggaaacaa tttacaatag   1920 

catctgaaga gagagtacat agattggaaa tggctattgc atttcactca aatgctgaaa   1980 

agattttgca ggactgtcca gaagagcctg aagctattaa tgatgaggag caatttgatg   2040 

aaattgaagc agttgggaaa tcacttttgg atagattaac tgttccagta gtttatcctg   2100 

atggaaccga acaatatttt gggagtccaa gtgacatggc ttctactgca gaaaacatca   2160 

gagacaggat gaaactagtt aatctcaaaa ggcagcagct gagacatcct gaaatggtga   2220 

ccacagagag ctaatagcta ccagctacct acagatttgc agttcataat cccgcatgtt   2280 

gtcaacatac tacagcatta gccaccacac cttaagatgc atttcacagc caaaataagt   2340 

ctcatttctt ttcatgacac atttctcttt acatgttaac accttgctac taccaaggca   2400 

taattactta acatgcttcg aggctgtaga ttccaagtat cttaaaagaa ggaactataa   2460 

acattgcact gaaaacttgc tttaaagctt tacctgacct gtcagtttgt agacaaacaa   2520 

ctgataataa gctttgaatg gtgctaataa gagtaggaat tctctctatt aaaaagaaaa   2580 

aaaaaagttg cccttcctcc acaggtgatt tagtaaattt agacagtagt taaactcttg   2640 

ttagtagaca gtggtgtcct caaaatttta ctttgtaatt cttcagaatt gattattttt   2700 

attgtgtcaa tacagagaaa gcctttcaga tctttgatat atcatagtca ttaaaagacc   2760 

ttttcctatt tgtattgata atgtattaaa agttgtttgt gcttaataaa agacttcttt   2820 

aaacatctta tttaatttag tagttacatc ctatttccaa acatgagtgc cttatttaaa   2880 

agggcattct taggactgtg aggatggttt aatatttgtt ttttcatggt ggttgcatgt   2940 

attttagaca ggaaatacat atgtaagcat gtgtatataa taaataagca tgttttatca   3000 

tgaaaaatta ttgtgaacaa tttagatctt taagaactta ttaataatgg aatactattt   3060 

ctaatttttc tctttttcaa cttgaaaaat attctcaaaa                         3100 

 
           
             22  
             3248  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 2058182CB1  
             
           
            22 

gcgggaagcg atgtagtagc tgccaggctg tcccccgccc tgcccggccc gagccccgcg     60 

ggccgccgcc gccaccgccg ccatgaagaa gcagttcaac cgcatgaagc agctggctaa    120 

ccagaccgtg ggcagagctg agaaaacaga agtccttagt gaagatctat tacagattga    180 

gagacgcctg gacacggtgc ggtcaatatg ccaccattcc cataagcgct tggtggcatg    240 

tttccagggc cagcatggca ccgatgccga gaggagacac aaaaaactgc ctctgacagc    300 

tcttgctcaa aatatgcaag aagcatcgac tcagctggaa gactctctcc tggggaagat    360 

gctggagacg tgtggagatg ctgagaatca gctggctctc gagctctccc agcacgaagt    420 

ctttgttgag aaggagatcg tggaccctct gtacggcata gctgaggtgg agattcccaa    480 

catccagaag cagaggaagc agcttgcaag attggtgtta gactgggatt cagtcagagc    540 

caggtggaac caagctcaca aatcctcagg aaccaacttt caggggcttc catcaaaaat    600 

agatactcta aaggaagaga tggatgaagc tggaaataaa gtagaacagt gcaaggatca    660 

acttgcagca gacatgtaca actttatggc caaagaaggg gagtatggca aattctttgt    720 

tacgttatta gaagcccaag cagattacca tagaaaagca ttagcagtct tagaaaagac    780 

cctccccgaa atgcgagccc atcaagataa gtgggcggaa aaaccagcct ttgggactcc    840 

cctagaagaa cacctgaaga ggagcgggcg cgagattgcg ctgcccattg aagcctgtgt    900 

catgctgctt ctggagacag gcatgaagga ggagggcctt ttccgaattg gggctggggc    960 

ctccaagtta aagaagctga aagctgcttt ggactgttct acttctcacc tggatgagtt   1020 

ctattcagac ccccatgctg tagcaggtgc tttaaaatcc tatttacggg aattgcctga   1080 

acctttgatg acttttaatc tgtatgaaga atggacacaa gttgcaagtg tgcaggatca   1140 

agacaaaaaa cttcaagact tgtggagaac atgtcagaag ttgccaccac aaaattttgt   1200 

taactttaga tatttgatca agttccttgc aaagcttgct cagaccagcg atgtgaataa   1260 

aatgactccc agcaacattg cgattgtgtt aggccctaac ttgttatggg ccagaaatga   1320 

aggaacactt gctgaaatgg cagcagccac atccgtccat gtggttgcag tgattgaacc   1380 

catcattcag catgccgact ggttcttccc tgaagaggtg gaatttaatg tatcagaagc   1440 

atttgtacct ctcaccaccc cgagttctaa tcactcattc cacactggaa acgactctga   1500 

ctcggggacc ctggagagga agcggcctgc tagcatggcg gtgatggaag gagacttggt   1560 

gaagaaggaa agtcctccca aaccgaagga ccctgtatct gcagctgtgc cagcaccagg   1620 

gagaaacaac agtcagatag catctggcca aaatcagccc caggcagctg ctggctccca   1680 

ccagctctcc atgggccaac ctcacaatgc tgcagggccc agcccgcata cactgcgccg   1740 

agctgttaaa aaacccgctc cagcaccccc gaaaccgggc aacccacctc ctggccaccc   1800 

cgggggccag agttcttcag gaacatctca gcatccaccc agtctgtcac caaagccacc   1860 

cacccgaagc ccctctcctc ccacccagca cacgggccag cctccaggcc agccctccgc   1920 

cccctcccag ctctcagcac cccggaggta ctccagcagc ttgtctccaa tccaagctcc   1980 

caatcaccca ccgccgcagc cccctacgca ggccacgcca ctgatgcaca ccaaacccaa   2040 

tagccagggc cctcccaacc ccatggcatt gcccagtgag catggacttg agcagccatc   2100 

tcacacccct ccccagactc caacgccccc cagtactccg cccctaggaa aacagaaccc   2160 

cagtctgcca gctcctcaga ccctggcagg gggtaaccct gaaactgcac agccacatgc   2220 

tggaacctta ccgagaccga gaccagtacc aaagccaagg aaccggccca gcgtgccccc   2280 

acccccccaa cctcctggtg tccactcagc tggggacagc agcctcacca acacagcacc   2340 

aacagcttcc aagatagtaa cagactccaa ttccagggtt tcagaaccgc atcgcagcat   2400 

ctttcctgaa atgcactcag actcagccag caaagacgtg cctggccgca tcctgctgga   2460 

tatagacaat gataccgaga gcactgccct gtgaagaaag ccctttccca gccctccacc   2520 

acttccaccc tggcgagtgg agcaggggca ggcgaacctc tttctttgca gaccgaacag   2580 

tgaaaagctt tcagtggagg acaaaggagg gcctcactgt gcgggacctg gccttctgca   2640 

cggcccaagg agaacctgga ggccaccact aaagctgaat gacctgtgtc ttgaagaagt   2700 

tggctttctt tacatgggaa ggaaatcatg ccaaaaaaat ccaaaacaaa gaagtacctg   2760 

gagtggagag agtattcctg ctgaaacgcg cataggaagc ttttgtccct gctgttaatg   2820 

cgggcagcac ctacagcaac ttggaatgag taagaagcag tgcgttaact atctatttaa   2880 

taaaatgcgc tcattatgca agtcgcctac tctctgctac ctggacgttc attcttatgt   2940 

attaggaggg aggctgcgct ccttcagact tgctgcagaa tcattttgta tcatgtatgg   3000 

tctgtgtctc cccagtcccc tcagaaccat gcccatggat ggtgactgct ggctctgtca   3060 

cctcatcaaa ctggatgtga cccatgccgc ctcgttggat tgtcggaatg tagacagaaa   3120 

tgtactgttc tttttttttt ttttaaacaa tgtaattgct acttgataag gaccgaacat   3180 

tattctagtt tcatgtttaa tttgaattaa atatattctg tggtttatat gaaaaaaaaa   3240 

aaaaaaaa                                                            3248 

 
           
             23  
             2592  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 3564377CB1  
             
           
            23 

gcgagagcgc cgcccaccca tccggggcaa gagccgcgcc gcaggagagg caggctggac     60 

cgggggctcc ccgggcccgc gacccccgcc gtgaccccgc agcccccagc tcgcccccaa    120 

gatgatgaag aggcagctgc accgcatgcg gcagctggcc cagacgggca gcttgggacg    180 

caccccggag accgctgagt tcctgggtga ggacctgctg caggtagaac agcggctgga    240 

gccggccaag cgggcagccc acaacatcca caagcggctg caggcctgtc tgcagggcca    300 

gagcggggca gacatggaca agcgggtgaa gaagcttccc ctcatggctc tgtccaccac    360 

gatggctgag agcttcaagg agctggaccc tgattccagc atggggaagg ccttggagat    420 

gagctgtgcc atccagaatc agctggcccg catcctggcc gagtttgaga tgaccctgga    480 

gagggacgtc ctgcagccac tcagcaggct gagtgaggag gagctgccag ccatcctcaa    540 

acacaagaaa agcctccaga agctcgtgtc cgactggaac acactcaaga gcaggctcag    600 

tcaggcaacc aagaattcag gcagcagtca aggcctagga ggcagcccgg gtagtcacag    660 

ccatacgacc atggccaaca aggtggagac gctgaaggag gaggaggagg agctgaagag    720 

gaaagtggag caatgcaggg acgagtactt ggctgacctg taccactttg ttaccaagga    780 

ggactcctat gccaactact tcattcgtct cctggagatt caggccgatt accatcgcag    840 

gtcactgagc tcgctggaca cagccctggc tgagctgagg gagaaccacg gccaagcaga    900 

ccactcccct tcgatgacag ccacccactt ccccagggtg tatggggtgt cgctggcaac    960 

ccacctgcaa gagctgggcc gggagattgc cctgcccatc gaggcctgcg tcatgatgct   1020 

gctttctgag ggcatgaagg aagagggtct cttccgtctg gctgctgggg cctcggtgct   1080 

gaagcgtctc aagcagacaa tggcctcgga cccccacagc ctggaggagt tctgctccga   1140 

cccgcacgct gtggcaggtg ccctcaagtc ctatctgcgg gagctgccag agcctctgat   1200 

gaccttcgac ctctatgatg actggatgag ggcagccagc ctgaaggagc caggggcccg   1260 

gctgcaggcc ctccaagagg tgtgcagccg cctacccccc gagaacctca gcaacctcag   1320 

gtacctgatg aagttcctgg cacggctggc cgaggagcag gaggtgaaca agatgacacc   1380 

cagcaacatc gccatagtcc tgggacccaa cttgctgtgg ccacctgaga aagaagggga   1440 

ccaggcccag ctggatgcag cctccgtgtc ttccatccag gtggtgggcg tcgtcgaggc   1500 

gctgatccag agcgcagaca ccctcttccc tggagacatc aacttcaacg tgtcaggcct   1560 

cttctcagct gttaccctcc aggacacagt cagtgacagg ctggcctctg aggaacttcc   1620 

gtccactgcc gtgcccaccc cagccaccac cccggctccg gctccggctc cagctccagc   1680 

tccggcccca gccttggctt cagcggctac caaggaaagg acagagtctg aggtgcctcc   1740 

cagaccagcc tcccccaagg tcaccaggag tcccccggag acagctgccc cagtggagga   1800 

catggctcgg aggaccaagc gcccggcgcc agcccggccc accatgccgc ccccccaggt   1860 

ctccggctcc cgctcctccc ctccagcccc gcccttgccc cctggctctg gcagccctgg   1920 

gaccccccaa gccctgcccc gacgtctggt tggcagcagc ctccgagccc ccacagtgcc   1980 

acccccgtta ccccccacac cccctcagcc tgcccggcgc caaagccggc gttcaccagc   2040 

ctcccccagc ccggcctccc caggtccagc ctcccccagc ccagtctctt tgagtaaccc   2100 

tgcacaggtg gacctggggg ctgccacagc agagggagga gcccctgagg ctatcagtgg   2160 

ggtccccact cccccagcta tcccccctca gccccgcccc aggagccttg cctcagagac   2220 

caactgagtg gctggtttct ccctaagcag ccctcagcac cccctccctc cccacctggc   2280 

cctcccagga cagctctcgc cccccacaaa ggggcatggg cctccagcct ttgcccacaa   2340 

gtgcctcagt gcccactggg tcggccccca tggccaggag ggctcaggac aatcctctat   2400 

ttcctgacct tttcctcgtc caccctgggc ttggggaccc ccccaccgga ctctccactc   2460 

tccggcaggt cctaggggag ccaccggaag gaaggagagg tttgcctgct cctacgggac   2520 

tgattcttct cttgccgaca tgttttttgt aaggctggta aataaattat tttggacaaa   2580 

aaaaaaaaaa aa                                                       2592 

 
           
             24  
             2004  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 1568689CB1  
             
           
            24 

ggccccgcgc cggagcagtg ccggagcccc gccagagccc gacttcagcc ccagccagat     60 

cccgcgtcaa cggaggcgga acggcggacc ccgtaccctg gcagcatcgg agcaccggcg    120 

ggtgaaggca aggtccctgg actggtcata tacctcttgt ggccctggca gaatcaagat    180 

gaggccctgt catgcctccc cagtgaggcc tacagtctga gcagacagca tggcctgcca    240 

ctggcagtga acaccatgtc tgcaggaggt ggccgggcct ttgcttggca agtgttcccc    300 

cccatgccca cttgccgggt ctatggcaca gtggcacacc aagatgggca cctgctggtg    360 

ttggggggtt gtggccgggc tggactgccc ctggacactg ctgagacact ggacatggcc    420 

tcgcacacat ggctggcact ggcacccctg cccactgccc gggctggtgc agctgcggta    480 

gttctgggca agcaggtgct agtggtgggt ggtgtggatg aggtccagag cccggtagct    540 

gctgtagagg ccttcctgat ggatgagggc cgctgggagc gtcgggccac cctccctcaa    600 

gcagccatgg gggttgcaac tgtggagaga gatggtatgg tgtatgctct ggggggaatg    660 

ggccctgaca cggcccccca ggcccaggta cgtgtgtatg agccccgtcg ggactgctgg    720 

ctttcgctac cctccatgcc cacaccctgc tatggggcct ccaccttcct gcacgggaac    780 

aagatctatg tcctgggggg ccgccagggc aagctcccgg tgactgcttt tgaagccttt    840 

gatctggagg cccgtacatg gacccggcat ccaagcctac ccagccgtcg ggcctttgct    900 

ggctgcgcca tggctgaagg cagcgtcttt agcctgggtg gcctgcagca gcctgggccc    960 

cacaacttct actctcgccc acactttgtc aacactgtgg agatgtttga cctggagcat   1020 

gggtcctgga ccaaattgcc ccgcagcctg cgcatgaggg ataagagggc agactttgtg   1080 

gttgggtccc ttgggggcca cattgtggcc attgggggcc ttggaaacca gccatgtcct   1140 

ttgggctctg tggagagctt tagccttgca cggcggcgct gggaggcatt gcctgccatg   1200 

cccactgccc gctgctcctg ctctagtctg caggctgggc cccggctgtt tgttattggg   1260 

ggtgtggccc agggccccag tcaagccgtg gaggcactgt gtctgcgtga tggggtctga   1320 

aggcttggtg ggagctgtcc actggagcag ctcattgcca gaggcagcta tttctatggc   1380 

tccttttgct gctgaggaca ctcactgtgg ctctgtggga tgagagaggc atgggggtga   1440 

gcacttgaaa cactgccttg gggccttggg ttaggggagc ctttgtcttt agtgcaggac   1500 

acacatatgc ttacacctac ctttatcacc attcgttcat gaatcatgcc tagctccatc   1560 

cttgccctgg gacctactag gccttccatc caactgggaa atggggagaa gcaaagctgg   1620 

cctcatgctc ttcagggtca gttcctatct ggagttgacc aggcctaccc cagttgccat   1680 

tcctgaaaaa tctcagctgc caggctgcct ttagggtccc tgtagaccca ggagagttga   1740 

gagggtgggg gacacagaga gaatagagag gatgtgggaa ctgccagagg gccggagcgc   1800 

aggagttcaa gtggaggaat gctggctttg agccctctac actgctggtt gtatgacctt   1860 

ggacaagtca cttcacctct ctgtgcctca gcatcctcat ctataaatgg ggatctctga   1920 

aaccttccta ccctacctac ctcacagggc tgttgtgagg acccagggag tttggatgtg   1980 

gaagtaaaag tgctgctaaa aaaa                                          2004 

 
           
             25  
             2250  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 1393767CB1  
             
           
            25 

ggagcaccgg gtggattgga cgcttcccca gagacccaga agcagaagga gcggacccag     60 

gcagccggca ccatggagat tgtgtacgtg tacgtcaaga agcgcagcga gttcgggaag    120 

cagtgcaatt tctcggaccg ccaggccgag ctgaacatcg acatcatgcc caaccctgag    180 

ctggccgagc agttcgtgga gcggaaccca gtggacacgg gcatccagtg ctcgatcagc    240 

atgtcggaac acgaggccaa ctcagagcgg tttgagatgg agacccgggg agttaaccat    300 

gtcgaggggg gctggcccaa ggacgtgaac cccctggagc tggagcagac catccgtttc    360 

cggaagaaag tggagaaaga tgagaactac gttaacgcca tcatgcagct cggctctatc    420 

atggagcact gcatcaagca gaacaatgcc attgacatct atgaagagta tttcaatgac    480 

gaggaggcca tggaagtgat ggaggaggac ccttcagcta aaaccatcaa tgtgttcagg    540 

gacccccagg aaatcaagag ggctgccaca cacctctcct ggcaccccga tggcaacagg    600 

aagttggcag tggcatactc ctgcttggat tttcagcggg cacctgtggg catgagcagc    660 

gattcataca tctgggacct ggaaaacccc aacaagcctg aacttgctct gaagccatcg    720 

tctccactcg tgacgttgga gttcaacccc aaagattccc acgtactcct gggtggctgc    780 

tacaatggac agatagcctg ctgggacacc cgaaagggca gcctggtggc ggagctatcc    840 

accattgagt ccagccaccg agaccctgtg tatggcacca tctggctgca gtcgaagacg    900 

ggcaccgagt gcttctcagc ttccacggat gggcaggtca tgtggtggga catccgaaag    960 

atgagcgagc ccactgaagt tgtgatcttg gacatcacca agaaggaaca gttggaaaat   1020 

gccttggggg ccatctccct ggagttcgaa tctactttgc ccaccaagtt catggtgggg   1080 

accgagcagg gcatcgtcat ctcctgcaac cgcaaggcca agacgtcagc tgaaaagatt   1140 

gtgtgcacct tcccgggcca tcatggcccc atctacgccc tccagagaaa ccccttctac   1200 

ccgaagaact tcctgacggt tggcgactgg acagcccgca tttggtctga agacagccgg   1260 

gaatcgtcca tcatgtggac caagtaccac atggcttacc tcactgatgc tgcctggagc   1320 

cccgtgaggc cgaccgtttt ctttaccacc aggatggacg gaaccctgga tatctgggac   1380 

ttcatgttcg agcagtgcga tcccaccctc agcttgaagg tgtgtgacga ggccctcttc   1440 

tgcctccggg tgcaggacaa tgggtgtctc atcgcctgcg gctcccagct ggggacaacc   1500 

accctgctgg aggtctcgcc tgggctctct accctccaga ggaatgagaa gaacgtagcc   1560 

tcttccatgt ttgagcgtga gacccggcga gagaagatcc tggaggccag gcaccgggag   1620 

atgcggctga aggagaaggg taaggcggag ggcagggatg aggagcagac cgatgaggag   1680 

ctggccgtag acctggaggc gctggtcagc aaggccgagg aggagttctt cgacatcatc   1740 

ttcacagagc tgaagaagaa ggaggcagac gccataaagc tgacgccagt gcctcagcaa   1800 

ccaagtccag aagaagacca ggtggtggag gagggagagg aagcagcggg ggaagaaggg   1860 

gatgaagaag tggaagaaga cttagcctag aagtcagcct tcgactgcgg cgctatccct   1920 

gtgtgccttc ctttcccacc tcttgaccct caaccagact tgcatggcca tggcagggcc   1980 

tcgggaagac cttcaggagt ggggaagggt ttctcctcca tgatcgaccc tcctcgtcca   2040 

cctacaaatc aggaacagaa agtctgtcca ctttgaaaat acctttccag gcagctccct   2100 

gaccatttgg acacattgcc acgacaggag cctccaagta tgtgggaggg gacgggcggg   2160 

acgagcttgg ctgttctgct gcacctgaat gctttctgtt atcctaattc ttgtaaaatt   2220 

aaatgaatcg taacaataaa aaaaaaaaaa                                    2250 

 
           
             26  
             3728  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 3029343CB1  
             
           
            26 

atggattatg aacaccatga aagatggccc aggtttaaca ggatgttcct ggacaagtca     60 

ggagcacagt ctaaggcatt tgatgtactt ggaagagttg aagcttacct taagctcctt    120 

aaatcagagg gtttaagtct ggctgttttg gcagtgaggc atgaggaatt acacagaaaa    180 

attaaagact gcacaactga tgctttgcaa aagggacaaa ccttaatcag ccaagtagac    240 

tcctgcagca ccaggcctca gggacaatca aagccatata aaactgaccc caaatcccca    300 

gaacctgtcc cgcgtccagt cagggagctg cacatcaagg aagtgtgctc caggcacgag    360 

gggcccatga gtacagtgga tgttgcggtc acttcttcag agaagggaga cacaatccga    420 

aagtctgaga tcaagacagg ccaaatgaaa ggctctcagg tgtccggcat ccatgagatg    480 

atggggtgca ttaagagacg agtggatcat ctgaccgaac agtgttcagc gcacaaggaa    540 

tatgctctta agaaacaaca actaacagcc tcagtggagg gttacctacg gaaggtggaa    600 

atgtcaattc agaaaatcag tccagtactt tctaatgcaa tggatgttgg ttctacccgt    660 

tctgaatcag agaagatttt gaataaatat ctggaactag atatccaagc taaggagaca    720 

tcacatgaat tagaagcagc tgcaaaaacc atgatggaga aaaatgaatt tgtatctgat    780 

gaaatggtat cactttcctc taaagctaga tggctagcag aagaattaaa cctatttggc    840 

caaagcattg actatagatc gcaagtcctg caaacttacg tggcatttct gaagtcatca    900 

gaggaggtag agatgcagtt tcagagctta aaagaatttt atgaaaccga aatccctcag    960 

aaggagcagg atgatgctaa agccaagcat tgttctgact cggctgagaa gcagtggcag   1020 

ctatttttaa agaagagttt tataacacaa gatctagggc ttgagttcct taatttaata   1080 

aatatggcaa aagagaacga gatattagat gtgaaaaatg aagtgtacct catgaagaac   1140 

accatggaaa accagaaagc agaacgggaa gaacttagcc tccttcggct ggcatggcag   1200 

cttaaagcca cggaaagcaa gcctggaaaa cagcagtggg cggcattcaa agagcaactt   1260 

aaaaagactt ctcacaactt aaaacttctt caggaagcac ttatgcctgt gtctgcactt   1320 

gacctcggag ggagcctcca gttcatttta gatctacgac aaaaatggaa tgacatgaag   1380 

cctcagttcc agcaattgaa tgatgaggtt cagtacatta tgaaagaatc agaggagtta   1440 

actggcagag gagcccctgt aaaagaaaag tctcaacaac tgaaggacct tattcacttc   1500 

catcaaaaac agaaagagag aatccaggat tacgaggata tcctgtacaa ggtggtccag   1560 

ttccatcaag tcaaggaaga gctgggacgt ctcatcaaat caagagagct ggagtttgta   1620 

gagcagccga aggaactggg tgatgcccat gatgtgcaga ttcacctccg gtgctctcag   1680 

gaaaagcaag cccgtgtaga ccatctccac agactggccc tttccttagg agtcgacatc   1740 

atctcatcag tgcagcggcc tcactgctct aatgtttctg caaagaacct acagcagcag   1800 

ctggagctcc ttgaggagga cagcatgaag tggcgtgcca aagctgagga gtatggacgg   1860 

accctgtccc gtagtgtgga gtactgcgcc atgagagacg agataaatga gctcaaagac   1920 

tcattcaaag atatcaaaaa gaaattcaat aatttgaagt ttaattacac taagaaaaat   1980 

gaaaaatctc ggaatctgaa ggcgcttaaa tatcaaattc agcaagttga tatgtatgct   2040 

gaaaaaatgc aggctttgaa aaggaaaatg gaaaaagtta gtaataaaac ctctgattct   2100 

ttcttaaatt atccaagtga taaagttaat gtccttttgg aagtcatgaa ggatttgcaa   2160 

aaacatgtgg atgactttga caaagttgtg acagattaca agaagaattt ggacctgact   2220 

gagcatttcc aggaggtgat agaagagtgt catttttggt acgaagatgc aagtgccaca   2280 

gttgtaagag ttggaaaata ttccacagag tgcaagacaa aggaagctgt gaaaattctc   2340 

caccagcagt ttaataagtt tattgcaccc tcagtgccgc agcaagaaga aaggattcag   2400 

gaggccactg accttgctca gcacttatat ggtttggaag aaggacagaa atatattgag   2460 

aaaatagtga caaaacacaa agaggttctt gaatctgtga ctgaattatg tgagtcccgc   2520 

acagagctcg aagaaaaact gaagcaggga gatgttttaa agatgaatcc gaatttggaa   2580 

gacttccatt atgattacat tgacttgcta aaggaaccag caaaaaataa gcagacaata   2640 

ttcaatgaag aaaggaataa ggggcaggtg caggtggcag atcttttggg catcaatgga   2700 

acaggggaag agcgactacc acaagacctg aaggtgtcca ctgacaagga gggtggcgtc   2760 

caggacctgc tcctgcctga agacatgctc tcaggggaag aatatgagtg tgtctcacct   2820 

gatgacatct ccttgcctcc tctcccagga agccctgagt ccccccttgc accatctgac   2880 

atggaggtgg aagagcctgt cagctcctcc ctcagccttc acataagcag ctatggggtg   2940 

caggctggga ccagcagccc aggggatgcc caggaatctg ttcttccacc acctgttgcc   3000 

tttgcggatg catgcaatga taagagagaa acattttcaa gtcattttga gaggccttac   3060 

ctccagttca aagctgagcc cccactaacc tccagaggat tcgtggaaaa gagtactgcc   3120 

ttacacagaa tcagtgctga acatccagag agcatgatga gtgaagtgca tgagagagct   3180 

ttacagcagc accctcaggc tcagggtggt ttgctagaaa cacgggagaa aatgcatgct   3240 

gataataact tcactaaaac ccaagatagg ctgcatgctt cctctgatgc attctcgggc   3300 

ctcaggtttc aatcaggcac cagcaggggc tatcagaggc aaatggttcc tcgagaagag   3360 

attaaaagca catcagcaaa gagcagcgtg gtcagcctag ctgaccaggc acctaatttc   3420 

tccaggctcc tgtctaatgt aactgtcatg gaaggttctc cagtgacttt ggaagttgaa   3480 

gtaacaggat ttccagagcc tacactgaca tggtgggtag cctataatga caagccataa   3540 

atggaaacaa attcaatcac agagaaaaat cattctgtga gcactaactg aaaggtttag   3600 

ggctagctga ttaatattct atgacactgc aactctgcat gattcaatct cacatcagac   3660 

ccctctcatt ttagtagcag catagttaat acctttaaga aaaataaaag gtaaccatat   3720 

aaagtact                                                            3728 

 
           
             27  
             2241  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 5507629CB1  
             
           
            27 

taattgcgta cattttgctt ggaaatcaca ggaagaaaca caacaaagca ttgcccaagg     60 

tacagaaaca ataataaacg tacttaaaac tcatttaaat tccagcattt ttctccttat    120 

tttagaagtt taacatttca gaagcagaca ctgcctccct tcctgcaaca actttctcct    180 

cttaagtctc atttttcccc agtttcaagg gcgaattcta gaactccccg gaaccgccac    240 

cagttaacca gaattccgtg gctttggaaa taaaactgct gttatagctc ttctgggtat    300 

ttgagaaatg cacttgtgaa gggttagagt tgaatctttt gatgcgaaag tcgggttttc    360 

ctgatactgg gattccggga ttccaggtgt tggggtggcc caattcctgc gagaagcaat    420 

agcgggcggt aacatgagga gcacggtgcg tccagcgagt ccttccgcct ggggccctgc    480 

cgaccccctg cctgtgcccc caggactctg gcctcacccg gccgtgccgg ggcctctgtg    540 

acgcggcgtt ccaggcactc ggccccggcc gagcccgtag ctagagcggc tcagagacag    600 

gaggcggcgg cagcagcggc ggcatgaacc actgccagct accggtggtg atcgacaacg    660 

gctcgggaat gatcaaggcg ggcgtggctg ggtgccggga gccccagttt atctacccga    720 

acattatcgg ccgcgccaag ggccagagcc gcgcggccca gggcgggcta gaactctgcg    780 

tgggcgacca agctcaggac tggaggagct cgctgttcat cagttaccca gtggagcgtg    840 

gtctcattac ttcatgggag gacatggaga tcatgtggaa gcatatctat gactataacc    900 

taaagctgaa gccgtgtgat ggcccagtct tgattactga gccagcgctg aacccactgg    960 

ccaaccggca acagatcacg gaaatgtttt ttgagcatct gggtgttcct gccttctata   1020 

tgtccatcca ggctgtgctg gctctctttg ctgctggctt cactactggc cttgtgctga   1080 

attcaggtgc tggggttacc cagagtgtgc ccatctttga gggttactgt ctgcctcatg   1140 

gtgtgcagca actggatctg gcaggccttg acctcaccaa ctacctcatg gtgctaatga   1200 

agaaccatgg tatcatgttg ctcagtgctt cagacagaaa gattgttgaa gacatcaagg   1260 

agagcttttg ttatgtggca atgaactacg aagaggaaat ggccaagaaa cccgattgtc   1320 

tagagaaagt ttaccaacta cctgatggga aggtcatcca gctccatgac cagctctttt   1380 

cttgtccaga ggccctcttc tctccgtgtc atatgaacct tgaggcccct ggcattgata   1440 

agatatgctt cagcagcata atgaaatgtg atacaggcct gaggaattcc ttcttttcca   1500 

atattatcct tgccggggga tcaacctctt tccctggttt agacaagcgg ttagttaagg   1560 

atatagcaaa ggtggctcct gccaacaccg ctgtgcaagt tatagctcct ccagaaagga   1620 

aaatatcagt gtggatggga ggttctattc ttgcatcctt gtctgccttc caggacatgt   1680 

ggatcactgc tgcagaattt aaagaagttg gacccaacat agtacaccaa agatgcttct   1740 

gaaatacaga taaaatggtt ggaagaaaat gttttgagta tatgtgacag aaaactttgg   1800 

atattatatg tttctgggag aagagaaaat acttcaccta ttgggatgcc aatatttctg   1860 

ttgtatttct ataatgggtt tgggggataa taatggtgaa gctcaagaac agatgtctat   1920 

tgagtagaac caagttaaaa taatgtttcc catagtgttt cttctataac ttgacgttgg   1980 

tgagcttata tttcccttgg aagagagcat ttgtggtaca atatgctatg tgccaaatga   2040 

gtgataagat ttaagcttat tgaagtttag ggaaagaagg ttgctgtggt gaggaacgag   2100 

actccatagc agaggtatgc catcatggaa ggggtggcat tgggatggag cgcagatatc   2160 

caggcaagca tactaaaatg aacaagttgc taaagatgag aatgaacaaa gcatattcag   2220 

ggcatgttta atagactgat t                                             2241 

 
           
             28  
             5203  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 5607780CB1  
             
           
            28 

ggtttgatgg tcctggtgga agtagccttg gcggctgctg gttttcaaag cctctgacaa     60 

agctgtgcat atcacccgtg actgcaccct gaggaaagac gaaaagtcag cctctccctt    120 

acgtaggacg cttgtaaact ttcccagacg cactgttggt cttaagaatt gttctgaccc    180 

tggacatttg caggacttgt ccaaggtgga tctgagcctc ctcatgtgct ccaggcagag    240 

atcaggattc ggatgcatca ccaactggtg gaagatgggg actaggcacc ctgcacaccc    300 

tgcacagccg gaagaattaa cctcgagtct gcacgctttt aagaacaagg cctttaaaaa    360 

atccaaagtg tgtggagttt gcaaacaaat tattgacggt caaggtattt catgccgagc    420 

ctgcaagtat tcctgccaca agaaatgtga agccaaggtg gtgattccct gcggtgtgca    480 

agtccgactg gaacaggctc cagggagttc cacgctgtcc agttctctct gccgtgataa    540 

acctctgcgg cccgtcatcc tgagtcccac catggaggag ggccatgggc tggacctcac    600 

ttacatcacg gagcgcatca tcgctgtgtc cttccctgcc ggctgctctg aggagtccta    660 

cctgcacaac ctacaggagg tcacgcgcat gctcaagtcc aagcacgggg acaactacct    720 

ggtattaaac ctttcagaaa agagatatga ccttacgaag cttaacccaa agatcatgga    780 

tgtgggctgg ccagagctcc acgcaccgcc cctggataag atgtgtacca tatgcaaggc    840 

gcaggagtcc tggctgaaca gcaacctcca gcatgtggtc gtcattcact gcaggggcgg    900 

gaaaggacgc ataggagtgg tcatatcatc ctacatgcat ttcaccaacg tctcagccag    960 

cgccgaccag gcccttgaca ggtttgcaat gaagaagttt tatgatgaca aagtttcagc   1020 

tttaatgcag ccttcccaaa aacggtatgt tcagttcctc agtgggctcc tgtccggatc   1080 

ggtgaaaatg aatgcctctc ccctgttcct gcattttgtc atcctccacg gcacccccaa   1140 

cttcgacaca ggtggagtgt gccggccctt tctgaagctc taccaagcca tgcagcctgt   1200 

gtacacctcc gggatctaca acgttggccc agaaaacccc agcaggatct gcatcgtcat   1260 

cgagccggcc cagcttctga agggagatgt catggtgaaa tgctaccaca agaaataccg   1320 

ctcggccacc cgtgacgtca ttttccgcct gcagtttcac actggggctg tgcagggcta   1380 

cgggctggtg tttgggaagg aggatctgga caatgccagc aaagatgacc gttttcctga   1440 

ctatgggaag gttgaattag tcttctctgc cacgcctgag aagattcaag ggtccgaaca   1500 

cttgtacaac gaccacggtg tgattgtgga ctacaacaca acagacccac tgatacgctg   1560 

ggactcgtac gagaacctca gtgcagatgg agaagtgcta cacacgcagg gccctgtcga   1620 

tggcagcctt tacgcgaagg tgaggaagaa aagctcctcg gatcctggca tcccaggtgg   1680 

cccccaggca atcccggcca ccaacagccc agaccacagt gaccacacct tgtctgtcag   1740 

cagtgactcc ggccactcta cagcctctgc caggacggat aagacggaag agcgcctggc   1800 

cccaggaacc aggaggggcc tgagtgccca ggagaaggct gagttggacc agctgctcag   1860 

tggctttggc ctggaagatc ctggaagctc cctcaaggaa atgactgatg ctcgaagcaa   1920 

gtacagtggg acccgccacg tggtgccagc ccaggttcac gtgaatggag acgctgctct   1980 

gaaggatcgg gagacagaca ttctggatga cgagatgccc caccacgacc tgcacagtgt   2040 

ggacagcctt gggaccctgt cctcctcgga agggcctcag tcggcccacc tgggtccctt   2100 

cacctgccac aagagcagcc agaactcact cctatctgac ggttttggca gcaacgttgg   2160 

tgaagatccg cagggcaccc tcgttccgga cctgggcctt ggcatggacg gcccctatga   2220 

gcgggagcgg acttttggga gtcgagagcc caagcagccc cagcccctgc tgagaaagcc   2280 

ctcagtgtcc gcccagatgc aggcctatgg gcagagcagc tactccacac agacctgggt   2340 

gcgccagcag cagatggttg tagctcacca gtatagcttc gccccagatg gggaggcccg   2400 

gctggtgagc cgctgccctg cagacaatcc tggcctcgtc caggcccagc ccagagtgcc   2460 

actcaccccc acccgaggga ccagcagtag ggtggctgtc cagaggggtg taggcagtgg   2520 

gccacatccc cctgacacac agcagccctc tcccagcaaa gcgttcaaac ccaggtttcc   2580 

aggagaccag gttgtgaatg gagccggccc agagctgagc acaggcccct ccccaggctc   2640 

gcccaccctg gacatcgacc agtccatcga gcagctcaac aggctgatcc tggagctgga   2700 

tcccaccttc gagcccatcc ctacccacat gaacgccctc ggtagccagg ccaatggctc   2760 

tgtgtctcca gacagcgtgg gaggcgggct ccgggcaagc agcaggctgc ctgacacagg   2820 

agagggcccc agcagggcca ccgggcggca aggctcctct gctgaacagc ccctgggcgg   2880 

gagactcagg aagctgagcc tggggcagta cgacaacgat gctggggggc agctgccctt   2940 

ctccaaatgt gcatggggaa aggctggtgt ggactatgcc ccaaacctgc cgccattccc   3000 

ctcaccagcg gacgtcaaag agacgatgac ccctggctat ccccaggacc tcgatattat   3060 

cgatggcaga attttaagta gcaaggagtc catgtgttca actccagcat ttcctgtgtc   3120 

tccagagaca ccttatgtga aaacagcgct gcgccatcct ccgttcagcc cacctgagcc   3180 

cccgctgagc agcccagcca gtcagcacaa aggaggacgt gaaccacgaa gctgccctga   3240 

gacgctcact cacgctgtgg ggatgtcaga gagccccatc ggacccaaat ccacgatgct   3300 

ccgggctgat gcgtcctcga cgccctcctt tcagcaggct tttgcttctt cctgcaccat   3360 

ttccagcaac ggccctgggc agaggagaga gagctcctct tctgcagaac gccagtgggt   3420 

ggagagcagc cccaagccca tggtttccct gctggggagc ggccggccca ccggaagtcc   3480 

cctcagcgct gagttctccg gtaccaggaa ggactcccca gtgctgtcct gcttcccgcc   3540 

gtcagagctc caggctcctt tccacagcca tgagctgtcc ctagcagagc caccggactc   3600 

cctggcgcct cccagcagcc aggccttcct gggcttcggc accgccccag tgggaagtgg   3660 

ccttccgccc gaggaggacc tgggggcctt gctggccaat tctcatggag cgtcaccgac   3720 

ccccagcatc ccgctgacag cgacaggggc tgccgacaat ggcttcctgt cccacaactt   3780 

tctcacggtg gcgcctggac acagcagcca ccacagtcca ggcctgcagg gccagggtgt   3840 

gaccctgccc gggcagccac ccctccctga gaagaagcgg gcctcggagg gggatcgttc   3900 

tttgggctca gtctctccct cctccagtgg cttctccagc ccgcacagcg ggagcaccat   3960 

cagtatcccc ttcccaaatg tccttcccga cttttccaag gcttcagaag cggcctcacc   4020 

tctgccagat agtccaggtg ataaacttgt gatcgtgaaa tttgttcaag acacttccaa   4080 

gttctggtac aaggcggata tttcaagaga acaagccatc gccatgttga aggacaagga   4140 

gccgggctca ttcattgttc gagacagcca ttccttccga ggggcctatg gcctggccat   4200 

gaaggtggcc acgcccccac cttcagtcct gcagctgaac aagaaagctg gagatttggc   4260 

caatgaactc gtccggcact ttttgatcga gtgtaccccg aagggagtgc ggttgaaagg   4320 

gtgctcgaat gaaccatatt tcgggagcct gacggccttg gtgtgccagc attccatcac   4380 

gcccttggcc ttgccgtgca agctgcttat cccagagaga gatccattgg aggaaatagc   4440 

agaaagttct ccccagacgg cagccaattc agcagctgag ctgttgaagc agggggcagc   4500 

ctgcaacgtg tggtacttga actctgtgga gatggagtcc ctcaccggcc accaggcgat   4560 

ccagaaggcc ctgagcatca ccctggtcca ggagcctcca cctgtgtcca cagttgtgca   4620 

cttcaaggtg tcagcccagg gcatcaccct gacagacaat cagaggaagc tcttcttccg   4680 

gaggcattac cccgtgaaca gtgtgatttt ctgtgccttg gacccacaag acaggaagtg   4740 

gatcaaagat ggcccttcct caaaagtctt tggatttgtg gcccggaagc agggcagtgc   4800 

cacggataat gtgtgccacc tgtttgcaga gcatgaccct gagcagcctg ccagtgccat   4860 

tgtcaacttc gtatcaaagg tcatgattgg ttccccaaag aaggtctgag aactcccctc   4920 

cctccctgga cccaccgatg cctctcgaag ccctggagac agccgttggg tgagggtggg   4980 

gcccccactt tttaccaaac tagtaaacct gacattccag gcccatgagg ggaaagagga   5040 

tcttccagct ctgcaaaaac aagaacaaac aacatcaccg tgaattggcc tttcctgaaa   5100 

gtgacttatc tgacacatct ctgtagccac atgctttttg ggtagaagaa gctgggcatg   5160 

ggtgcacccc accccctagg gtccccatgg gaaagggaca tgc                     5203