CA2359701A1 - Nucleic-acid binding proteins - Google Patents

Abstract

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

Description

NUCLEIC-ACID BINDING PROTEINS
TECHNICAL FIELD
This invention relates to nucleic acid and amino acid sequences of nucleic-acid binding proteins and to the use of these sequences in the diagnosis, treatment, and prevention of reproductive, immune, and neurological disorders, and cell proliferative disorders including cancer.
BACKGROUND OF THE INVENTION
Multicellular organisms are comprised of diverse cell types that differ dramatically both in structure and function. The identity of a cell is determined by its characteristic pattern of gene expression, and different cell types express overlapping but distinct sets of genes throughout development. Spatial and temporal regulation of gene expression is critical for the control of cell proliferation, cell differentiation, apoptosis, and other processes that contribute to organismal development. Furthermore, gene expression is regulated in response to extracellular signals that mediate cell-cell communication and coordinate the activities of different cell types. Appropriate gene regulation also ensures that cells function efficiently by expressing only those genes whose functions are required at a given time.
Transcriptional regulatory proteins are essential for the control of gene expression. Some of these proteins function as transcription factors that initiate, activate, repress, or terminate gene transcription. Transcription factors generally bind to promoter, enhancer, or upstream regulatory regions of a gene in a sequence-specific manner, although some factors bind regulatory elements within or downstream of the coding region. Transcription factors may bind to a specific region of DNA singly or as a complex with other accessory factors. (Reviewed in Lewin, B. (1990) Genes IV, Oxford University Press, New York, NY, pp. 554-570.) The double helix structure and repeated sequences of DNA create topological and chemical features which can be recognized by transcription factors. These features include hydrogen bond donor and acceptor groups, hydrophobic patches, major and minor grooves, and regular repeated stretches of sequence which induce distinct bends in the helix. Typically, transcription factors recognize specific DNA sequence motifs of about 20 nucleotides in length.
Multiple adjacent transcription factor-binding motifs may be required for gene regulation.
Many transcription factors incorporate DNA-binding structural motifs which comprise either a helices or f3 sheets that bind to the major groove of DNA. Four well-characterized structural motifs are helix-turn-helix, zinc finger, leucine zipper, and helix-loop-helix.
Proteins containing these motifs may act alone as monomers or form homo- or heterodimers that interact with DNA.
The helix-turn-helix motif consists of two a helices connected at a fixed angle by a short chain of amino acids. One of the helices binds to the major groove. Helix-turn-helix motifs are exemplified by the homeobox motif which is present in homeodomain proteins.
These proteins are critical for specifying the anterior-posterior body axis during development and are conserved throughout the animal kingdom. The Antennapedia and Ultrabithorax proteins of Drosophila S melano ag~ster are prototypical homeodomain proteins. (Pabo, C.O. and R.T.
Sauer (1992) Ann. Rev.
Biochem. 61:1053-1095.) The zinc finger motif, which binds zinc ions, generally contains tandem repeats of about 30 amino acids consisting of periodically spaced cysteine and histidine residues.
Examples of this sequence pattern include the C2H2-type and the C3HC4-type zinc fingers, and the PHD domain.
(Lewin, su ra ; Aasland, R., et al. ( 1995) Trends Biochem. Sci 20:56 - 59.) Zinc finger proteins each contain an a helix and an antiparallel (3 sheet whose proximity and conformation are maintained by the zinc ion. Contact with DNA is made by the arginine preceding the a helix and by the second, third, and sixth residues of the a helix. Variants of the zinc finger motif include poorly defined cysteine-rich motifs which bind zinc or other metal ions. These motifs may not contain histidine residues and are generally nonrepetitive.
The leucine zipper motif comprises a stretch of amino acids rich in leucine which can form an amphipathic a helix. This structure provides the basis for dimerization of two leucine zipper proteins.
The region adjacent to the leucine zipper is usually basic, and upon protein dimerization, is optimally positioned for binding to the major groove. Proteins containing such motifs are generally referred to as bZIP transcription factors.
The helix-loop-helix motif (HLH) consists of a short a helix connected by a loop to a longer a helix. The loop is flexible and allows the two helices to fold back against each other and to bind to DNA. The transcription factor Myc contains a prototypical HLH motif.
Most transcription factors contain characteristic DNA binding motifs, and variations on the above motifs and new motifs have been and are currently being characterized.
(Faisst, S. and S.
Meyer (1992) Nucl. Acids Res. 20:3-26.) Mutations in transcription factors contribute to oncogenesis. This is likely due to the role of transcription factors in the expression of genes involved in cell proliferation. For example, mutations in transcription factors encoded by proto-oncogenes, such as Fos, Jun, Myc, Rel, and Spil, may be oncogenic due to increased stimulation of cell proliferation. Conversely, mutations in transcription factors encoded by tumor suppressor genes, such as p53, RBI, and WTI, may be oncogenic due to decreased inhibition of cell proliferation. (Latchman, D. (1995) Gene Regulation: A Eukaryotic Pers~,ective, Chapman and Hall, London, UK, pp 242-255.) Gene expression is also affected by chromatin-associated proteins. In the nucleus, DNA is packaged into chromatin, the compact organization of which limits the accessibility of DNA to transcription factors and plays a key role in gene regulation. (Lewin, supra, pp. 409-410.) The compact structure of chromatin is determined and influenced by chromatin-associated proteins such as histones, high mobility group (HMG) proteins, helicases, and chromodomain proteins. There are five classes of histones, H 1, H2A, H2B, H3, and H4, all of which are highly basic, low molecular weight proteins. The fundamental unit of chromatin, the nucleosome, consists of 200 base pairs of DNA
associated with two copies each of H2A, H2B, H3, and H4. H1 links adjacent nucleosomes. HMG
proteins are low molecular weight, non-histone proteins that may play a role in unwinding DNA and stabilizing single-stranded DNA. Helicases, which are DNA-dependent ATPases, unwind DNA, allowing access for transcription factors. Chromodomain proteins play a key role in the formation of highly-compacted, transcriptionally silent heterochromatin.
Much of the regulation of gene expression in eucaryotic cells occurs at the posttranscriptional level. Messenger RNAs (mRNA), which are produced in the cell nucleus from primary transcripts of protein-encoding genes, are processed and transported to the cytoplasm where the protein synthesis machinery is located. RNA-binding proteins are a group of proteins that participate in the processing, editing, transport, localization, and posttranscriptional regulation of mRNAs, and comprise the protein component of ribosomes as well. The RNA-binding activity of many of these proteins is mediated by a series of RNA-binding motifs identified within them. These domains include the RNP motif, the arginine-rich motif, the RGG box, and the KH motif. (Reviewed in Burd, C. G.
and Dreyfuss, G.
(1994) Science 265:615 - 621.) The RNP motif is the most widely found and best characterized of these motifs. The RNP motif is composed of 90-100 amino acids which form an RNA-binding domain and is found in one or more copies in proteins that bind pre-mRNA, mRNA, pre-ribosomal RNA, and small nuclear RNAs. The RNP motif is composed of two short sequences (RNP-1 and RNP-2) and a number of other mostly hydrophobic, conserved amino acids interspersed throughout the motif. (Burd, supra; ExPASy PROSITE document PDOC0030.) Many neoplastic disorders in humans can be attributed to inappropriate gene expression.
Malignant cell growth may result from either excessive expression of tumor promoting genes or insufficient expression of tumor suppressor genes. (Cleary, M.L. (1992) Cancer Surv. 15:89-104.) Chromosomal translocations may also produce chimeric loci which fuse the coding sequence of one gene with the regulatory regions of a second unrelated gene. Such an arrangement often results in inappropriate gene transcription. The Wilms tumor suppressor gene product, WT1, is a protein containing a DNA-binding domain consisting of four zinc fingers and a proline-glutamine rich region capable of regulating transcription. (ExPASy PROSITE document PR00049.) Deletions of the WTl gene, or point mutations which destroy the DNA-binding activity of the protein are associated with development of the pediatric nephroblastoma, Wilms tumor, and Denys-Drash syndrome. (Rauscher, F.J. (1993) FASEB J. 7:896-903.) Certain proteins enriched in glutamine are associated with various neurological disorders including spinocerebellar ataxia, bipolar effective disorder, schizophrenia, and autism. (Margolis, R.L. et al. (1997) Human Genetics 100:114-122.) These proteins contain regions with as many as 15 or more consecutive glutamine residues and may function as transcription factors with a potential role in regulation of neurodevelopment or neuroplasticity.
The immune system responds to infection or trauma by activating a cascade of events that coordinate the progressive selection, amplification, and mobilization of cellular defense mechanisms.
A complex and balanced program of gene activation and repression is involved in this process.
However, hyperactivity of the immune system as a result of improper or insufficient regulation of gene expression may result in considerable tissue or organ damage. This damage is well documented in immunological responses associated with arthritis, allergens, heart attack, stroke, and infections.
(Harrison's Principles of Internal Medicine, 13/e, McGraw Hill, Inc. and Teton Data Systems Software, 1996.) In particular, a zinc finger protein termed Staf50 (for Stimulated trans-acting factor of 50 kDa) is a transcriptional regulator and is induced in various cell lines by interferon-I and -II.
Staf50 appears to mediate the antiviral activity of interferon by down-regulating the viral transcription directed by the long terminal repeat promoter region of human immunodeficiency virus type-1 in transfected cells. (Tissot, C. (1995) J. Biol. Chem. 270:14891-14898.) Furthermore, the generation of multicellular organisms is based upon the induction and coordination of cell differentiation at the appropriate stages of development.
Central to this process is differential gene expression, which confers the distinct identities of cells and tissues throughout the body. Failure to regulate gene expression during development could result in developmental disorders.
The discovery of new nucleic-acid binding proteins and the polynucleotides encoding them satisfies a need in the art by providing new compositions which are useful in the diagnosis, prevention, and treatment of reproductive, immune, and neurological disorders, and cell proliferative disorders including cancer.
SUMMARY OF THE INVENTION
The invention features purified polypeptides, protnames, referred to collectively as "ABBR"
and individually as "NuABP-1," "NuABP-2," "NuABP-3," "NuABP-4," "NuABP-5,"
"NuABP-6,"
"NuABP-7," "NuABP-8," "NuABP-9," "NuABP-10" "NuABP-11," "NuABP-12," "NuABP-13,"
"NuABP-14," "NuABP-15," "NuABP-16," "NuABP-17," "NuABP-18," "NuABP-19," "NuABP-20,"
"NuABP-21," ''NuABP-22," "NuABP-23," "NuABP-24," "NuABP-25," "NuABP-26,"
"NuABP-27," "NuABP-28," "NuABP-29," "NuABP-30," "NuABP-31," "NuABP-32," "NuABP-33,"

"NuABP-34," "NuABP-35," "NuABP-36," "NuABP-37," "NuABP-38," "NuABP-39," "NuABP-40" "NuABP-41," "NuABP-42," "NuABP-43," "NuABP-44," ''NuABP-45," "NuABP-46,"
"NuABP-47," "IVuABP-48," "NuABP-49," "NuABP-50" "NuABP-51," ''NuABP-52," "NuABP-53,"
"NuABP-54," and "NuABP-55." In one aspect, the invention provides an isolated polypeptide comprising a) an amino acid sequence selected from the group consisting of SEQ ID NO:1-55, b) a naturally occurring amino acid sequence having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO:1-55, c) a biologically active fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1-55, or d) an immunogenic fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1-55. In one alternative, the invention provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO:1-55.
The invention further provides an isolated polynucleotide encoding a polypeptide comprising a) an amino acid sequence selected from the group consisting of SEQ ID NO:1-55, b) a naturally occurring amino acid sequence having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO:1-55, c) a biologically active fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1-55, or d) an immunogenic fragment of an amino acid sequence selected from the group consisting of SEQ
ID NO:1-55. In one alternative, the polynucleotide is selected from the group consisting of SEQ
ID N0:56-110.
Additionally, the invention provides a recombinant polynucleotide comprising a promoter sequence operably linked to a polynucleotide encoding a polypeptide comprising a) an amino acid sequence selected from the group consisting of SEQ ID NO:1-55, b) a naturally occurring amino acid sequence having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO:1-55, c) a biologically active fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1-55, or d) an immunogenic fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:I-55. 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.
The invention also provides a method for producing a polypeptide comprising a) an amino acid sequence selected from the group consisting of SEQ ID NO:1-55, b) a naturally occurring amino acid sequence having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO:1-55, c) a biologically active fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1-55, or d) an immunogenic fragment of an amino acid sequence selected from the group consisting of SEQ ID NO: l-55. The method comprises a) culturing a cell under conditions suitable for expression of the polypeptide, wherein said cell is transformed with a recombinant polynucleotide comprising a promoter sequence operably linked to a polynucleotide encoding the polypeptide, and b) recovering the polypeptide so expressed.

Additionally, the invention provides an isolated antibody which specifically binds to a polypeptide comprising a) an amino acid sequence selected from the group consisting of SEQ ID
NO:1-55, b) a naturally occurring amino acid sequence having at least 90%
sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO:1-55, c) a biologically active fragment of an amino acid sequence selected from the group consisting of SEQ
ID NO:1-55, or d) an immunogenic fragment of an amino acid sequence selected from the group consisting of SEQ ID
NO:1-55.
The invention further provides an isolated polynucleotide comprising a) a polynucleotide sequence selected from the group consisting of SEQ ID N0:56-110, b) a naturally occurring polynucleotide sequence having at least 90% sequence identity to a polynucleotide sequence selected from the group consisting of SEQ ID N0:56-110, c) a polynucleotide sequence complementary to a), or d) a polynucleotide sequence complementary to b). In one alternative, the polynucleotide comprises at least 60 contiguous nucleotides.
Additionally, the invention provides a method for detecting a target polynucleotide in a sample, said target polynucleotide having a sequence of a polynucleotide comprising a) a polynucleotide sequence selected from the group consisting of SEQ ID N0:56-110, b) a naturally occurring polynucleotide sequence having at least 90% sequence identity to a polynucleotide sequence selected from the group consisting of SEQ ID N0:56-110, c) a polynucleotide sequence complementary to a), or d) a polynucleotide sequence complementary to b). The method comprises a) hybridizing the sample with a probe comprising at least 16 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, 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 30 contiguous nucleotides. In another alternative, the probe comprises at least 60 contiguous nucleotides.
The invention further provides a pharmaceutical composition comprising an effective amount of a polypeptide comprising a) an amino acid sequence selected from the group consisting of SEQ ID
NO:I-55, b) a naturally occurring amino acid sequence having at least 90%
sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO:1-55, c) a biologically active fragment of an amino acid sequence selected from the group consisting of SEQ
ID NO:1-55, or d) an immunogenic fragment of an amino acid sequence selected from the group consisting of SEQ ID
NO:1-S5, and a pharmaceutically acceptable excipient. The invention additionally provides a method of treating a disease or condition associated with decreased expression of functional NuABP, comprising administering to a patient in need of such treatment the pharmaceutical composition.

The invention also provides a method for screening a compound for effectiveness as an agonist of a polypeptide comprising a) an amino acid sequence selected from the group consisting of SEQ ID NO: l-55, b) a naturally occurring amino acid sequence having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO:I-S5, c) a biologically active fragment of an amino acid sequence selected from the group consisting of SEQ ID NO: l-S5, or d) an immunogenic fragment of an amino acid sequence selected from the group consisting of SEQ
ID NO: I-55. 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 pharmaceutical 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 NuABP, comprising administering to a patient in need of such treatment the pharmaceutical composition.
Additionally, the invention provides a method for screening a compound for effectiveness as an antagonist of a polypeptide comprising a) an amino acid sequence selected from the group consisting of SEQ ID NO:I-55, b) a naturally occurring amino acid sequence having at least 90%
sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO:I-S5, c) a biologically active fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1-55, or d) an immunogenic fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1-55. 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 pharmaceutical 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 NuABP, comprising administering to a patient in need of such treatment the pharmaceutical composition.
The invention further provides a method for screening a compound for effectiveness in altering expression of a target polynucleotide, wherein said target polynucleotide comprises a sequence selected from the group consisting of SEQ ID N0:56-110, the method comprising a) exposing a sample comprising the target polynucleotide to a compound, and b) detecting altered expression of the target polynucleotide.
BRIEF DESCRIPTION OF THE TABLES
Table 1 shows polypeptide and nucleotide sequence identification numbers (SEQ
ID NOs), clone identification numbers (clone IDs), cDNA libraries, and cDNA fragments used to assemble full-length sequences encoding NuABP.

Table 2 shows features of each polypeptide sequence, including potential motifs. homologous sequences, and methods, algorithms. and searchable databases used for analysis of NuABP.
Table 3 shows selected fragments of each nucleic acid sequence: the tissue-specific expression patterns of each nucleic acid sequence as determined by northern analysis; diseases, disorders, or conditions associated with these tissues; and the vector into which each cDNA was cloned.
Table 4 describes the tissues used to construct the cDNA libraries from which cDNA clones encoding NuABP were isolated.
Table 5 shows the tools, programs, and algorithms used to analyze NuABP, along with applicable descriptions, references, and threshold parameters.
DESCRIPTION OF THE INVENTION
Before the present proteins, nucleotide sequences, and methods are described, it is understood that this invention is not limited to the particular machines, materials and methods described, as these IS may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention which will be limited only by the appended claims.
It must be noted that as used herein and in the appended claims, the singular forms "a," "an,"
and "the" include plural reference unless the context clearly dictates otherwise. Thus, for example, a reference to "a host cell" includes a plurality of such host cells, and a reference to ''an antibody" is a reference to one or more antibodies and equivalents thereof known to those skilled in the art, and so forth.
Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which this invention belongs.
Although any machines, materials, and methods similar or equivalent to those described herein can be used to practice or test the present invention, the preferred machines, materials and methods are now described. All publications mentioned herein are cited for the purpose of describing and disclosing the cell lines, protocols, reagents and vectors which are reported in the publications and which might be used in connection with the invention. Nothing herein is to be construed as an admission that the invention is not entitled to antedate such disclosure by virtue of prior invention.
DEFINITIONS
"NuABP" refers to the amino acid sequences of substantially purified NuABP
obtained from any species, particularly a mammalian species, including bovine, ovine, porcine, murine, equine, and human, and from any source, whether natural, synthetic, semi-synthetic, or recombinant.
The term "agonist" refers to a molecule which intensifies or mimics the biological activity of NuABP. Agonists may include proteins, nucleic acids. carbohydrates, small molecules, or any other compound or composition which modulates the activity of NuABP either by directly interacting with NuABP or by acting on components of the biological pathway in which NuABP
participates.
An "allelic variant" is an alternative form of the gene encoding NuABP.
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.
"Altered" nucleic acid sequences encoding NuABP include those sequences with deletions, insertions, or substitutions of different nucleotides, resulting in a polypeptide the same as NuABP or a polypeptide with at least one functional characteristic of NuABP. Included within this definition are polymorphisms which may or may not be readily detectable using a particular oligonucleotide probe of the polynucleotide encoding NuABP, and improper or unexpected hybridization to allelic variants, with a locus other than the normal chromosomal locus for the polynucleotide sequence encoding NuABP. 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 NuABP. 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 NuABP is retained. For example, negatively charged amino acids may include aspartic acid and glutamic acid, and positively charged amino acids may include lysine and arginine. Amino acids with uncharged polar side chains having similar hydrophilicity values may include: asparagine and glutamine; and serine and threonine.
Amino acids with uncharged side chains having similar hydrophilicity values may include: leucine, isoleucine, and valine; glycine and alanine; and phenylalanine and tyrosine.
The terms "amino acid" and "amino acid sequence" refer to an oligopeptide, peptide, polypeptide, or protein sequence, or a fragment of any of these, and to naturally occurring or synthetic molecules. Where "amino acid sequence" is recited to refer to an amino acid sequence of a naturally occurring protein molecule, "amino acid sequence" and like terms are not meant to limit the amino acid sequence to the complete native amino acid sequence associated with the recited protein molecule.
"Amplification" relates to the production of additional copies of a nucleic acid sequence.
Amplification is generally carried out using polymerase chain reaction (PCR) technologies well known in the art.

The term "antagonist" refers to a molecule which inhibits or attenuates the biological activity ofNuABP. Antagonists may include proteins such as antibodies, nucleic acids, carbohydrates, small molecules, or any other compound or composition which modulates the activity of NuABP either by directly interacting with NuABP or by acting on components of the biological pathway in which NuABP participates.
The term ''antibody' refers to intact immunoglobulin molecules as well as to fragments thereof, such as Fab, F(ab')=, and Fv fragments, which are capable of binding an epitopic determinant.
Antibodies that bind NuABP polypeptides can be prepared using intact polypeptides or using fragments containing small peptides of interest as the immunizing antigen. The polypeptide or oligopeptide used to immunize an animal (e.g., a mouse, a rat, or a rabbit) can be derived from the translation of RNA, or synthesized chemically, and can be conjugated to a carrier protein if desired.
Commonly used carriers that are chemically coupled to peptides include bovine serum albumin, thyroglobulin, and keyhole limpet hemocyanin (KLH). The coupled peptide is then used to immunize the animal.
The term "antigenic determinant" refers to that region of a molecule (i.e., an epitope) that makes contact with a particular antibody. When a protein or a fragment of a protein is used to immunize a host animal, numerous regions of the protein may induce the production of antibodies which bind specifically to antigenic determinants (particular regions or three-dimensional structures on the protein). An antigenic determinant may compete with the intact antigen (i.e., the immunogen used to elicit the immune response) for binding to an antibody.
The term ''antisense" refers to any composition containing a nucleic acid sequence which is complementary to the "sense" strand of a specific nucleic acid sequence.
Antisense molecules may be produced by any method including synthesis or transcription. Once introduced into a cell, the complementary nucleotides combine with natural sequences produced by the cell to form duplexes and to 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.
The term "biologically active" refers to a protein having structural, regulatory, or biochemical functions of a naturally occurring molecule. Likewise, "immunologically active" refers to the capability of the natural, recombinant, or synthetic NuABP, or of any oligopeptide thereof, to induce a specific immune response in appropriate animals or cells and to bind with specific antibodies.
The terms "complementary" and "complementarity" refer to the natural binding of polynucleotides by base pairing. For example, the sequence "5' A-G-T 3"' bonds to the complementary sequence "3' T-C-A 5'." Complementarity between two single-stranded molecules may be "partial," such that only some of the nucleic acids bind, or it may be "complete," such that total eomplementarity exists between the single stranded molecules. The degree of complementarity between nucleic acid strands has significant effects on the efficiency and strength of the hybridization between the nucleic acid strands. This is of particular importance in amplification reactions, which depend upon binding between nucleic acid strands, and in the design and use of peptide nucleic acid (PNA) molecules.
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 NuABP or fragments of NuABP 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., NaCI), detergents (e.g., sodium dodecyl sulfate; SDS), and other components (e.g., Denhardt's solution, dry milk, salmon sperm DNA, etc.).
"Consensus sequence" refers to a nucleic acid sequence which has been resequenced to resolve uncalled bases, extended using the XL-PCR kit (Perkin-Elmer, Norwalk CT) in the ~' and/or the 3' direction, and resequenced, or which has been assembled from the overlapping sequences of one or more Incyte Clones and, in some cases, one or more public domain ESTs, using a computer program for fragment assembly, such as the GELVIEW fragment assembly system (GCG, Madison WI). Some sequences have been both extended and assembled to produce the consensus sequence.
"Conservative amino acid substitutions'' are those substitutions that, when made, 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 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.
A "deletion" refers to a change in the amino acid or nucleotide sequence that results in the absence of one or more amino acid residues or nucleotides.
The term "derivative" refers to the chemical modification of a polypeptide sequence, or a polynucleotide sequence. Chemical modifications of a polynucleotide sequence can include, for example, replacement of hydrogen by an alkyl, acyl, hydroxyl, or amino group.
A derivative polynucleotide encodes a polypeptide which retains at least one biological or immunological function of the natural molecule. A derivative polypeptide is one modified by glycosylation, pegylation, or any similar process that retains at least one biological or immunological function of the polypeptide from which it was derived.
A "fragment" is a unique portion of NuABP or the polynucleotide encoding NuABP
which is identical in sequence to but shorter in length than the parent sequence. A
fragment may comprise up to the entire length of the defined sequence, minus one nucleotide/amino acid residue. For example, a fragment may comprise from 5 to 1000 contiguous nucleotides or amino acid residues. A fragment used as a probe, primer, antigen, therapeutic molecule, or for other purposes, may be at least 5, 10, 15, 20, 25, 30, 40, 50, 60, 75, 100, 150, 250 or at least 500 contiguous nucleotides or amino acid residues in length. Fragments may be preferentially selected from certain regions of a molecule. For example, a polypeptide fragment may comprise a certain length of contiguous amino acids selected from the first 250 or 500 amino acids (or first 25% or 50% of a polypeptide) as shown in a certain defined sequence. Clearly these lengths are exemplary, and any length that is supported by the specification, including the Sequence Listing, tables, and figures, may be encompassed by the present embodiments.
A fragment of SEQ ID N0:56-1 10 comprises a region of unique polynucleotide sequence that specifically identifies SEQ ID N0:56-110, for example, as distinct from any other sequence in the same genome. A fragment of SEQ ID N0:56-1 10 is useful, for example, in hybridization and amplification technologies and in analogous methods that distinguish SEQ ID
N0:56-110 from related polynucleotide sequences. The precise length of a fragment of SEQ ID
N0:56-110 and the region of SEQ ID N0:56-110 to which the fragment corresponds are routinely determinable by one of ordinary skill in the art based on the intended purpose for the fragment.
A fragment of SEQ ID NO:I-55 is encoded by a fragment of SEQ ID N0:56-110. A

fragment of SEQ ID NO:1-55 comprises a region of unique amino acid sequence that specifically identifies SEQ ID NO:1-55. For example, a fragment of SEQ ID NO:1-5~ is useful as an immunogenic peptide for the development of antibodies that specifically recognize SEQ ID NO: I-55.
The precise length of a fragment of SEQ ID NO:I-55 and the region of SEQ ID
NO:1-SS to which the fragment corresponds are routinely determinable by one of ordinary skill in the art based on the intended purpose for the fragment.
The term "similarity" refers to a degree of complementarity. There may be partial similarity or complete similarity. The word "identity" may substitute for the word "similarity." A partially complementary sequence that at least partially inhibits an identical sequence from hybridizing to a target nucleic acid is referred to as "substantially similar." The inhibition of hybridization of the completely complementary sequence to the target sequence may be examined using a hybridization assay (Southern or northern blot, solution hybridization, and the like) under conditions of reduced stringency. A substantially similar sequence or hybridization probe will compete for and inhibit the binding of a completely similar (identical) sequence to the target sequence under conditions of IS reduced stringency. This is not to say that conditions of reduced stringency are such that non-specific binding is permitted, as reduced stringency conditions require that the binding of two sequences to one another be a specific (i.e., a selective) interaction. The absence of non-specific binding may be tested by the use of a second target sequence which lacks even a partial degree of complementarity (e.g., less than about 30% similarity or identity). In the absence of non-specific binding, the substantially similar sequence or probe will not hybridize to the second non-complementary target sequence.
The phrases "percent identity" and "% identity," as applied to polynucleotide sequences, refer to the percentage of residue matches between at least two polynucleotide sequences aligned using a standardized algorithm. Such an algorithm may insert, in a standardized and reproducible way, gaps in the sequences being compared in order to optimize alignment between two sequences, and therefore achieve a more meaningful comparison of the two sequences.
Percent identity between polynucleotide sequences may be determined using the default parameters of the CLUSTAL V algorithm as incorporated into the MEGALIGN
version 3.12e sequence alignment program. This program is part of the LASERGENE software package, a suite of molecular biological analysis programs (DNASTAR, Madison WI). CLUSTAL V is described in Higgins, D.G. and P.M. Sharp (1989) CABIOS 5:151-153 and in Higgins, D.G. et al. (1992) CABIOS
8:189-191. For pairwise alignments of polynucleotide sequences, the default parameters are set as follows: Ktuple=2, gap penalty=5, window=4, and "diagonals saved"=4. The "weighted" residue weight table is selected as the default. Percent identity is reported by CLUSTAL V as the ''percent similarity" between aligned polynucleotide sequence pairs.

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 2Ø9 (May-07-1999) set at default parameters. Such default parameters may be, for example:
Matrix: BLOSUM62 I 5 Reward for match: I
Penalty for mismatch: -2 Open Gap: 5 and Extension Gap: 2 penalties Gap x drop-ofj.~ 50 Expect. 10 Word Size: Il Filter: on Percent identity may be measured over the length of an entire defined sequence, for example, as defined by a particular SEQ ID number, or may be measured over a shorter length, for example, over the length of a fragment taken from a larger, defined sequence, for instance, a fragment of at least 20, at least 30, at least 40, at least 50, at least 70, at least 100, or at least 200 contiguous nucleotides. Such lengths are exemplary only, and it is understood that any fragment length supported by the sequences shown herein, in the tables, figures, or Sequence Listing, may be used to describe a length over which percentage identity may be measured.
Nucleic acid sequences that do not show a high degree of identity may nevertheless encode similar amino acid sequences due to the degeneracy of the genetic code. It is understood that changes in a nucleic acid sequence can be made using this degeneracy to produce multiple nucleic acid sequences that all encode substantially the same protein.
The phrases "percent identity" and "% identity," as applied to polypeptide sequences, refer to the percentage of residue matches between at least two polypeptide sequences aligned using a standardized algorithm. Methods of polypeptide sequence alignment are well-known. Some alignment methods take into account conservative amino acid substitutions.
Such conservative substitutions, explained in more detail above, generally preserve the hydrophobicity and acidity at the site of substitution, thus preserving the structure (and therefore function) of the polypeptide.
Percent identity between polypeptide sequences may be determined using the default parameters of the CLUSTAL V algorithm as incorporated into the MEGALIGN
version 3.12e sequence alignment program (described and referenced above). For pairwise alignments of polypeptide sequences using CLUSTAL V, the default parameters are set as follows: Ktuple=l, gap penalty=3, window=5, and "diagonals saved"=5. The PAM250 matrix is selected as the default residue weight table. As with polynucleotide alignments, the percent identity is reported by CLUSTAL V as the "percent similarity" between aligned polypeptide sequence pairs.
Alternatively the NCBI BLAST software suite may be used. For example. for a pairwise comparison of two polypeptide sequences, one may use the "BLAST 2 Sequences"
tool Version 2Ø9 (May-07-1999) with blastp set at default parameters. Such default parameters may be, for example:
Matrix: BLOSUM62 Open Gap: 11 and Extension Gap: I penalties Gap x drop-off. 50 Expect: 10 Word Size: 3 Filter.' on Percent identity may be measured over the length of an entire defined polypeptide sequence, for example, as defined by a particular SEQ ID number, or may be measured over a shorter length, for example, over the length of a fragment taken from a larger, defined polypeptide sequence, for instance, a fragment of at least I 5, at least 20, at least 30, at least 40, at least S0, at least 70 or at least 150 contiguous residues. Such lengths are exemplary only, and it is understood that any fragment length supported by the sequences shown herein, in the tables, figures or Sequence Listing, may be used to describe a length over which percentage identity may be measured.
"Human artificial chromosomes" (HACs) are linear microchromosomes which may contain DNA sequences of about 6 kb to 10 Mb in size, and which contain all of the elements required for stable mitotic chromosome segregation and maintenance.
The term "humanized antibody" refers to antibody molecules in which the amino acid sequence in the non-antigen binding regions has been altered so that the antibody more closely resembles a human antibody, and still retains its original binding ability.
"Hybridization" refers to the process by which a polynucleotide strand anneals with a complementary strand through base pairing under defined hybridization conditions. Specific hybridization is an indication that two nucleic acid sequences share a high degree of identity. Specific hybridization complexes form under permissive annealing conditions and remain hybridized after the "washing" step(s). The washing steps) is particularly important in determining the stringency of the hybridization process, with more stringent conditions allowing less non-specific binding, i.e., binding between pairs of nucleic acid strands that are not perfectly matched.
Permissive conditions for annealing of nucleic acid sequences are routinely determinable by one of ordinary skill in the art and may be consistent among hybridization experiments, whereas wash conditions may be varied among experiments to achieve the desired stringency, and therefore hybridization specificity. Permissive annealing conditions occur, for example, at 68°C in the presence of about 6 x SSC, about 1 % (w/v) SDS, and about 100 pg/ml denatured salmon sperm DNA.
Generally, stringency of hybridization is expressed, in part, with reference to the temperature under which the wash step is carried out. Generally, such wash temperatures are selected to be about 5°C to 20°C lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength and pH. The Tm is the temperature (under defined ionic strength and pH) at which 50% of the target sequence hybridizes to a perfectly matched probe. An equation for calculating Tm and conditions for nucleic acid hybridization are well known and can be found in Sambrook et al., 1989, Molecular Cloning: A Laboratory Manual, 2"d ed., vol. 1-3, Cold Spring Harbor Press, Plainview NY;
specifically see volume 2, chapter 9.
High stringency conditions for hybridization between polynucleotides of the present invention include wash conditions of 68°C in the presence of about 0.2 x SSC and about 0.1 % SDS, for 1 hour.
Alternatively, temperatures of about 65°C, 60°C, 55°C, or 42°C may be used. SSC concentration may be varied from about 0.1 to 2 x SSC, with SDS being present at about 0.1%.
Typically, blocking reagents are used to block non-specific hybridization. Such blocking reagents include, for instance, denatured salmon sperm DNA at about 100-200 pg/ml. Organic solvent, such as formamide at a concentration of about 35-50% v/v, may also be used under particular circumstances, such as for RNA:DNA hybridizations. Useful variations on these wash conditions will be readily apparent to those of ordinary skill in the art. Hybridization, particularly under high stringency conditions, may be suggestive of evolutionary similarity between the nucleotides. Such similarity is strongly indicative of a similar role for the nucleotides and their encoded polypeptides.
The term "hybridization complex" refers to a complex formed between two nucleic acid sequences by virtue of the formation of hydrogen bonds between complementary bases. A
hybridization complex may be formed in solution (e.g., C°t or R°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).
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.
"Immune response'' can refer to conditions associated with inflammation, trauma, immune disorders, or infectious or genetic disease, etc. These conditions can be characterized by expression of various factors, e.g., cytokines, chemokines, and other signaling molecules, which may affect cellular and systemic defense systems.
The term "microarray" refers to an arrangement of distinct polynucleotides on a substrate.
The terms "element" and "array element" in a microarray context, refer to hybridizable polynucleotides arranged on the surface of a substrate.
The term "modulate" refers to a change in the activity of NuABP. For example, modulation may cause an increase or a decrease in protein activity, binding characteristics, or any other biological, functional, or immunological properties of NuABP.
The phrases "nucleic acid" and "nucleic acid sequence" refer to a nucleotide, oligonucleotide, polynucleotide, or any fragment thereof. These phrases also refer to DNA or RNA of genomic or synthetic origin which may be single-stranded or double-stranded and may represent the sense or the antisense strand, to peptide nucleic acid (PNA), or to any DNA-like or RNA-like material.
"Operably linked" refers to the situation in which a first nucleic acid sequence is placed in a functional relationship with the 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. Generally, operably linked DNA sequences may be in close proximity or contiguous and, where necessary to join two protein coding regions, in the same reading frame.
"Peptide nucleic acid" (PNA) refers to an antisense molecule or anti-gene agent which comprises an oligonucleotide of at least about 5 nucleotides in length linked to a peptide backbone of amino acid residues ending in lysine. The terminal lysine confers solubility to the composition.
PNAs preferentially bind complementary single stranded DNA or RNA and stop transcript elongation, and may be pegylated to extend their lifespan in the cell.
"Probe" refers to nucleic acid sequences encoding NuABP, 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).
Probes and primers as used in the present invention typically comprise at least I S 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 1 SO consecutive nucleotides of the disclosed nucleic acid sequences. Probes and primers may be considerably longer than these examples. and it is understood that any length supported by the specification, including the tables, figures, and Sequence Listing, may be used.
Methods for preparing and using probes and primers are described in the references, for example Sambrook et al., 1989, Molecular Cloning: A Laboratory Manual, 2"d ed., vol. 1-3, Cold Spring Harbor Press, Plainview NY; Ausubel et al.,1987, Current Protocols in Molecular Biolo~y, Greene Publ. Assoc. & Wiley-Intersciences, New York NY; Innis et al., 1990, PCR Protocols. A
Guide to Methods and Applications, Academic Press, San Diego CA. PCR primer pairs can be derived from a known sequence, for example, by using computer programs intended for that purpose such as Primer (Version 0.5, 1991, Whitehead Institute for Biomedical Research, Cambridge MA).
Oligonucleotides for use as primers are selected using software known in the art for such purpose. For example, OLIGO 4.06 software is useful for the selection of PCR
primer pairs of up to 100 nucleotides each, and for the analysis of oligonucleotides and larger polynucleotides of up to l5 5,000 nucleotides from an input polynucleotide sequence of up to 32 kilobases. Similar primer selection programs have incorporated additional features for expanded capabilities. For example, the PrimOU primer selection program (available to the public from the Genome Center at University of Texas South West Medical Center, Dallas TX) is capable of choosing specific primers from megabase sequences and is thus useful for designing primers on a genome-wide scope. The Primer3 primer selection program (available to the public from the Whitehead Institute/MIT
Center for Genome Research, Cambridge MA) allows the user to input a "mispriming library," in which sequences to avoid as primer binding sites are user-specified. Primer3 is useful, in particular, for the selection of oligonucleotides for microarrays. (The source code for the latter two primer selection programs may also be obtained from their respective sources and modified to meet the user's specific needs.) The PrimeGen program (available to the public from the UK Human Genome Mapping Project Resource Centre, Cambridge UK) designs primers based on multiple sequence alignments, thereby allowing selection of primers that hybridize to either the most conserved or least conserved regions of aligned nucleic acid sequences. Hence, this program is useful for identification of both unique and conserved oligonucleotides and polynucleotide fragments. The oligonucleotides and polynucleotide fragments identified by any of the above selection methods are useful in hybridization technologies, for example, as PCR or sequencing primers, microarray elements, or specific probes to identify fully or partially complementary polynucleotides in a sample of nucleic acids. Methods of oligonucleotide selection are not limited to those described above.
A "recombinant nucleic acid" is a sequence that is not naturally occurring or has a sequence that is made by an artificial combination of two or more otherwise separated segments of sequence.

This artificial combination is often accomplished by chemical synthesis or, more commonly, by the artificial manipulation of isolated segments of nucleic acids, e.g., by genetic engineering techniques such as those described in Sambrook, 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.
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.
The term "sample" is used in its broadest sense. A sample suspected of containing nucleic acids encoding NuABP, or fragments thereof, or NuABP itself, 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.
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 containing the epitope A, or the presence of free unlabeled A, in a reaction containing free labeled A
and the antibody will reduce the amount of labeled A that binds to the antibody.
The term ''substantially purified" refers to nucleic acid or amino acid sequences that are removed from their natural environment and are isolated or separated, and are at least 60% free, preferably at least 75% free, and most preferably at least 90% free from other components with which they are naturally associated.
A "substitution" refers to the replacement of one or more amino acids or nucleotides by different amino acids or nucleotides, respectively.
"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.
"Transformation" describes a process by which exogenous DNA enters and changes 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, viral infection, electroporation, heat shock, lipofection, and particle bombardment. The term "transformed" cells includes stably transformed cells in which the inserted DNA is capable of replication either as an autonomously replicating plasmid or as part of the host chromosome, as well as transiently transformed cells which express the inserted DNA or RNA for limited periods of time.
A "variant" of a particular nucleic acid sequence is defined as a nucleic acid sequence having at least 40% sequence identity to the particular nucleic acid sequence over a certain length of one of the nucleic acid sequences using blastn with the "BLAST 2 Sequences" tool Version 2Ø9 (May-07-1999) set at default parameters. Such a pair of nucleic acids may show, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95% or at least 98% or greater sequence identity over a certain defined length. A variant may be described as, for example, an "allelic" (as defined above), ''splice," "species," or "polymorphic"
variant. A splice variant may have significant identity to a reference molecule, but will generally have a greater or lesser number of polynucleotides 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 generally will have significant amino acid identity relative to each other. A polymorphic variant is a variation in the polynucleotide sequence of a particular gene between individuals of a given species. Polymorphic variants also may encompass "single nucleotide polymorphisms" (SNPs) in which the polynucleotide sequence varies by one nucleotide base. The presence of SNPs may be indicative of, for example, a certain population, a disease state, or a propensity for a disease state.
A "variant" of a particular polypeptide sequence is defined as a polypeptide sequence having at least 40% sequence identity to the particular polypeptide sequence over a certain length of one of the polypeptide sequences using blastp with the "BLAST 2 Sequences" tool Version 2Ø9 (May-07-1999) set at default parameters. Such a pair of polypeptides may show, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98% or greater sequence identity over a certain defined length of one of the polypeptides.
THE INVENTION
The invention is based on the discovery of new human nucleic-acid binding proteins (NuABP), the polynucleotides encoding NuABP, and the use of these compositions for the diagnosis, treatment, or prevention of reproductive, immune, and neurological disorders, and cell proliferative disorders including cancer.
Table 1 lists the Incyte clones used to assemble full length nucleotide sequences encoding NuABP. Columns I and 2 show the sequence identification numbers (SEQ ID NOs) of the polypeptide and nucleotide sequences, respectively. Column 3 shows the clone IDs of the Incyte clones in which nucleic acids encoding each NuABP were identified, and column 4 shows the cDNA
libraries from which these clones were isolated. Column 5 shows Incyte clones and their corresponding cDNA libraries. Clones for which cDNA libraries are not indicated were derived from pooled cDNA libraries. The Incyte clones in column 5 were used to assemble the consensus nucleotide sequence of each NuABP and are useful as fragments in hybridization technologies.
The columns of Table 2 show various properties of each of the polypeptides of the invention:
column 1 references the SEQ ID NO; column 2 shows the number of amino acid residues in each polypeptide; column 3 shows potential phosphorylation sites; column 4 shows potential glycosylation sites; column S shows the amino acid residues comprising signature sequences and motifs; column 6 shows identification or homologous sequences as identified by BLAST analysis;
and column 7 shows analytical methods and in some cases, searchable databases to which the analytical methods were applied. The methods of column 7 were used to characterize each polypeptide through sequence homology and protein motifs.
The columns of Table 3 show the tissue-specificity and diseases, disorders, or conditions associated with nucleotide sequences encoding NuABP. The first column of Table 3 lists the nucleotide SEQ ID NOs. Column 2 lists fragments of the nucleotide sequences of column 1. These fragments are useful, for example, in hybridization or amplification technologies to identify SEQ ID
N0:56-I 10 and to distinguish between SEQ ID N0:56-I 10 and related polynucleotide sequences.
The polypeptides encoded by these fragments are useful, for example, as immunogenic peptides.
Column 3 lists tissue categories which express NuABP as a fraction of total tissues expressing NuABP. Column 4 lists diseases, disorders, or conditions associated with those tissues expressing NuABP as a fraction of total tissues expressing NuABP. Of particular note is the expression of SEQ
ID N0:83 and SEQ ID NO:I 10 in neurological tissue. About 53% of the cDNA
libraries expressing SEQ ID N0:83 are derived from neurological tissue. Furthermore, SEQ ID NO:1 10 expression is detected exclusively in a cDNA library derived from brain tissue afflicted with Huntington's disease.
Column 5 lists the vectors used to subclone each cDNA library.
The columns of Table 4 show descriptions of the tissues used to construct the cDNA libraries from which eDNA clones encoding NuABP were isolated. Column I references the nucleotide SEQ
ID NOs, column 2 shows the cDNA libraries from which these clones were isolated, and column 3 shows the tissue origins and other descriptive information relevant to the cDNA libraries in column 2.
Fragments of the nucleotide sequences encoding NuABP are useful, for example, in hybridization or amplification technologies to identify SEQ ID NOS:56-I 10 and to distinguish between SEQ ID NOS:56-I 10 and related polynucleotide sequences. The polypeptides encoded by these fragments are useful, for example, as immunogenic peptides.
The invention also encompasses NuABP variants. A preferred NuABP variant is one which has at least about 80%, or alternatively at least about 90%, or even at least about 9~% amino acid sequence identity to the NuABP amino acid sequence, and which contains at least one functional or structural characteristic of NuABP.
The invention also encompasses polynucleotides which encode NuABP. In a particular embodiment, the invention encompasses a polynucleotide sequence comprising a sequence selected from the group consisting of SEQ ID N0:56-110, which encodes NuABP.
The invention also encompasses a variant of a polynucleotide sequence encoding NuABP. 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 NuABP. A particular aspect of the invention encompasses a variant of a polynucleotide sequence comprising a sequence selected from the group consisting of SEQ ID
N0:56-1 10 which has at least about 70%, or alternatively at least about 85%, or even at least about IS 95% polynucleotide sequence identity to a nucleic acid sequence selected from the group consisting of SEQ ID N0:56-1 10. Any one of the polynucleotide variants described above can encode an amino acid sequence which contains at least one functional or structural characteristic of NuABP.
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 NuABP, 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 NuABP, and all such variations are to be considered as being specifically disclosed.
Although nucleotide sequences which encode NuABP and its variants are generally capable of hybridizing to the nucleotide sequence of the naturally occurring NuABP
under appropriately selected conditions of stringency, it may be advantageous to produce nucleotide sequences encoding NuABP 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 NuABP and its derivatives without altering the encoded amino acid sequences include the production of RNA transcripts having more desirable properties, such as a greater half life, than transcripts produced from the naturally occurring sequence.

The invention also encompasses production of DNA sequences which encode NuABP
and NuABP 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 NuABP or any fragment thereof.
Also encompassed by the invention are polynucleotide sequences that are capable of hybridizing to the claimed polynucleotide sequences, and, in particular, to those shown in SEQ ID
N0:56-110 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."
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 OH), Taq polymerase (Perkin-IS Elmer), thermostable T7 polymerase (Amersham Pharmacia Biotech, Piscataway NJ), 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 NV), PTC200 thermal cycler (MJ Research, Watertown MA) and ABI CATALYST 800 thermal cycler (Perkin-Elmer). Sequencing is then carried out using either the ABI 373 or 377 DNA sequencing system (Perkin-Elmer), the MEGABACE 1000 DNA sequencing system (Molecular Dynamics, Sunnyvale CA), or other systems known in the art. The resulting sequences are analyzed using a variety of algorithms which are well known in the art. (See, e.g., Ausubel, F.M. ( 1997) Short Protocols in Molecular Biolo~y, John Wiley & Sons, New York NY, unit 7.7;
Meyers, R.A. (1995) Molecular Biology and Biotechnolo~y, Wiley VCH, New York NY, pp. 856-853.) The nucleic acid sequences encoding NuABP may be extended utilizing a partial nucleotide sequence and employing various PCR-based methods known in the art to detect upstream sequences, such as promoters and regulatory elements. For example, one method which may be employed, restriction-site PCR, uses universal and nested primers to amplify unknown sequence from genomic DNA within a cloning vector. (See, e.g., Sarkar, G. (1993) PCR Methods Applic.
2:318-322.) Another method, inverse PCR, uses primers that extend in divergent directions to amplify unknown sequence from a circularized template. The template is derived from restriction fragments comprising a known genomic locus and surrounding sequences. (See, e.g., Triglia, T. et al. (1988) Nucleic Acids Res. 16:8186.) A third method, capture PCR, involves PCR amplification of DNA
fragments adjacent to known sequences in human and yeast artificial chromosome DNA. (See, e.g., Lagerstrom, M. et al.

(1991 ) PCR Methods Applic. 1:1 1 1-119.) In this method, multiple restriction enzyme digestions and ligations may be used to insert an engineered double-stranded sequence into a region of unknown sequence before performing PCR. Other methods which may be used to retrieve unknown sequences are known in the art. (See, e.g., Parker, J.D. et al. (1991) Nucleic Acids Res. 19:3055-3060).
Additionally, one may use PCR, nested primers, and PROMOTERFINDER libraries (Clontech, Palo Alto CA) to walk genomic DNA. This procedure avoids the need to screen libraries and is useful in finding intron/exon junctions. For all PCR-based methods, primers may be designed using commercially available software, such as OLIGO 4.06 Primer Analysis software (National Biosciences, Plymouth MN) or another appropriate program, to be about 22 to 30 nucleotides in length, to have a GC content of about 50% or more, and to anneal to the template at temperatures of about 68°C to 72°C.
When screening for full-length cDNAs, it is preferable to use libraries that have been size-selected to include larger cDNAs. In addition, random-primed libraries, which often include sequences containing the 5' regions of genes, are preferable for situations in which an oligo d(T) library does not yield a full-length cDNA. Genomic libraries may be useful for extension of sequence into S' non-transcribed regulatory regions.
Capillary electrophoresis systems which are commercially available may be used to analyze the size or confirm the nucleotide sequence of sequencing or PCR products. In particular, capillary sequencing may employ flowable polymers for electrophoretic separation, four different nucleotide-specific, laser-stimulated fluorescent dyes, and a charge coupled device camera for detection of the emitted wavelengths. Output/light intensity may be converted to electrical signal using appropriate software (e.g., GENOTYPER and SEQUENCE NAVIGATOR, Perkin-Elmer), and the entire process from loading of samples to computer analysis and electronic data display may be computer controlled.
Capillary electrophoresis is especially preferable for sequencing small DNA
fragments which may be present in limited amounts in a particular sample.
In another embodiment of the invention, polynucleotide sequences or fragments thereof which encode NuABP may be cloned in recombinant DNA molecules that direct expression of NuABP, 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 NuABP.
The nucleotide sequences of the present invention can be engineered using methods generally known in the art in order to alter NuABP-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.
In another embodiment. sequences encoding NuABP 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, NuABP itself or a fragment thereof may be synthesized using chemical methods. For example, peptide synthesis can be performed using various solid-phase techniques. (See, e.g., Roberge, J.Y. et al. ( 1995) Science 269:202-204.) Automated synthesis may be achieved using the ABI 431A peptide synthesizer (Perkin-Elmer). Additionally, the amino acid sequence ofNuABP, 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.
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, T. (1984) Proteins, Structures and Molecular Properties, WH Freeman, New York NY.) In order to express a biologically active NuABP, the nucleotide sequences encoding NuABP
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 NuABP. Such elements may vary in their strength and specificity. Specific initiation signals may also be used to achieve more efficient translation of sequences encoding NuABP. Such signals include the ATG initiation codon and adjacent sequences, e.g. the Kozak sequence. In cases where sequences encoding NuABP 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.) Methods which are well known to those skilled in the art may be used to construct expression vectors containing sequences encoding NuABP and appropriate transcriptional and translational control elements. These methods include in vitro recombinant DNA techniques, synthetic techniques, and in vivo genetic recombination. (See, e.g., Sambrook, J. et al. (1989) Molecular Cloning, A
Laboratory Manual, Cold Spring Harbor Press, Plainview NY, ch. 4, 8, and 16-17; Ausubel, F.M. et al. (1995) Current Protocols in Molecular Biolo~v, John Wiley & Sons, New York NY, ch. 9, 13, and 16.) A variety of expression vector/host systems may be utilized to contain and express sequences encoding NuABP. 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. The invention is not limited by the host cell employed.
In bacterial systems, a number of cloning and expression vectors may be selected depending upon the use intended for polynucleotide sequences encoding NuABP. For example, routine cloning, subcloning, and propagation of polynucleotide sequences encoding NuABP can be achieved using a IS multifunctional E. coli vector such as PBLUESCRIPT (Stratagene, La Jolla CA) or PSPORTI
plasmid (Life Technologies). Ligation of sequences encoding NuABP into the vector's multiple cloning site disrupts the lacZ gene, allowing a colorimetric screening procedure for identification of transformed bacteria containing recombinant molecules. In addition, these vectors may be useful for in vitro transcription, dideoxy sequencing, single strand rescue with helper phage, and creation of nested deletions in the cloned sequence. (See, e.g., Van Heeke, G. and S.M.
Schuster ( 1989) J. Biol.
Chem. 264:5503-5509.) When large quantities of NuABP are needed, e.g. for the production of antibodies, vectors which direct high level expression of NuABP may be used.
For example, vectors containing the strong, inducible TS or T7 bacteriophage promoter may be used.
Yeast expression systems may be used for production of NuABP. A number of vectors containing constitutive or inducible promoters, such as alpha factor, alcohol oxidase, and PGH
promoters, may be used in the yeast Saccharomvces 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. I 53:516-544; and Scorer, C.A. et al. ( 1994) Bio/Technology 12:181-184.) Plant systems may also be used for expression of NuABP. Transcription of sequences encoding NuABP may be driven viral promoters, e.g., the 35S and 19S promoters of CaMV used alone or in combination with the omega leader sequence from TMV (Takamatsu, N.
( 1987) EMBO J.
6:307-311 ). Alternatively, plant promoters such as the small subunit of RUBISCO or heat shock promoters may be used. (See, e.g., Coruzzi, 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 Technoloey (1992) McGraw Hill, New York NY, pp. 191-196.) In mammalian cells, a number of viral-based expression systems may be utilized. In cases where an adenovirus is used as an expression vector, sequences encoding NuABP
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 NuABP in host cells. (See, e.g., Logan, J. and T. Shenk ( 1984) Proc.
Natl. Acad. Sci. USA 81:3655-3659.) In addition, transcription enhancers, such as the Rous sarcoma virus (RSV) enhancer, may be used to increase expression in mammalian host cells. SV40 or EBV-based vectors may also be used for high-level protein expression.
Human artificial chromosomes (HACs) may also be employed to deliver larger fragments of DNA than can be contained in and expressed 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.) For long term production of recombinant proteins in mammalian systems, stable expression of NuABP in cell lines is preferred. For example, sequences encoding NuABP can be transformed into cell lines using expression vectors which may contain viral origins of replication and/or endogenous expression elements and a selectable marker gene on the same or on a separate vector. Following the introduction of the vector, cells may be allowed to grow for about 1 to 2 days in enriched media before being switched to selective media. The purpose of the selectable marker is to confer resistance to a selective agent, and its presence allows growth and recovery of cells which successfully express the introduced sequences. Resistant clones of stably transformed cells may be propagated using tissue culture techniques appropriate to the cell type.
Any number of selection systems may be used to recover transformed cell lines.
These include, but are not limited to, the herpes simplex virus thymidine kinase and adenine phosphoribosyltransferase genes, for use in tk' and apr cells, respectively.
(See, e.g., Wigler, M. et al. (1977) Cell 11:223-232; Lowy, I. et al. (1980) Cell 22:817-823.) Also, antimetabolite, antibiotic, or herbicide resistance can be used as the basis for selection. For example, dhfr confers resistance to methotrexate; neo confers resistance to the aminoglycosides neomycin and G-418; and als and pat confer resistance to chlorsulfuron and phosphinotricin acetyltransferase, respectively. (See, e.g., Wigler, M. et al. (1980) Proc. Natl. Acad. Sci. USA 77:3567-3570; Colbere-Garapin, F. et al. (1981) J. Mol. Biol. 150:1-14.) Additional selectable genes have been described, e.g., trpB and hisD, which alter cellular requirements for metabolites. (See, e.g., Hartman, S.C. and R.C. Mulligan ( 1988) Proc.
Natl. Acad. Sci. USA 85:8047-8051.) Visible markers, e.g., anthocyanins, green fluorescent proteins (GFP; Clontech), f3 glucuronidase and its substrate f3-glucuronide. or luciferase and its substrate luciferin may be used. These markers can be used not only to identify transformants, but also to quantify the amount of transient or stable protein expression attributable to a specific vector system.
(See, e.g., Rhodes, C.A. (1995) Methods Mol. Biol. 55:121-131.) Although the presence/absence of marker gene expression suggests that the gene of interest is also present, the presence and expression of the gene may need to be confirmed. For example, if the sequence encoding NuABP is inserted within a marker gene sequence, transformed cells containing sequences encoding NuABP can be identified by the absence of marker gene function. Alternatively, a marker gene can be placed in tandem with a sequence encoding NuABP under the control of a single promoter. Expression of the marker gene in response to induction or selection usually indicates expression of the tandem gene as well.
In general, host cells that contain the nucleic acid sequence encoding NuABP
and that express NuABP 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.
Immunological methods for detecting and measuring the expression of NuABP
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 NuABP is preferred, but a competitive binding assay may be employed. These and other assays are well known in the art. (See, e.g., Hampton, R. et al. (1990) Seroloeical Methods, a Laboratory Manual, APS
Press, St. Paul MN, Sect. IV; Coligan, J.E. et al. (1997) Current Protocols in Immunoloey, Greene Pub. Associates and Wiley-Interscience, New York NY; and Pound, J.D. (1998) Immunochemical Protocols, Humana Press, Totowa NJ.) A wide variety of labels and conjugation techniques are known by those skilled in the art and may be used in various nucleic acid and amino acid assays. Means for producing labeled hybridization or PCR probes for detecting sequences related to polynucleotides encoding NuABP
include oligolabeling, nick translation, end-labeling, or PCR amplification using a labeled nucleotide.
Alternatively, the sequences encoding NuABP, or any fragments thereof, may be cloned into a vector for the production of an mRNA probe. Such vectors are known in the art, are commercially available, and may be used to synthesize RNA probes in vitro by addition of an appropriate RNA polymerase such as T7, T3, or SP6 and labeled nucleotides. These procedures may be conducted using a variety of commercially available kits, such as those provided by Amersham Pharmacia Biotech, Promega (Madison WI), and US Biochemical. Suitable reporter molecules or labels which may be used for ease of detection include radionuclides, enzymes. fluorescent.
chemiluminescent, or chromogenic agents, as well as substrates, cofactors, inhibitors, magnetic particles, and the like.
Host cells transformed with nucleotide sequences encoding NuABP 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 NuABP may be designed to contain signal sequences which direct secretion of NuABP through a prokaryotic or eukaryotic cell membrane.
In addition, a host cell strain may be chosen for its ability to modulate expression of the inserted sequences or to process the expressed protein in the desired fashion.
Such modifications of the polypeptide include, but are not limited to, acetylation, carboxylation, glycosylation, phosphorylation, lipidation, and acylation. Post-translational processing which cleaves a "prepro" or "pro" form of the protein may also be used to specify protein targeting, folding, and/or activity.
Different host cells which have specific cellular machinery and characteristic mechanisms for post-translational activities (e.g., CHO, HeLa, MDCK, HEK293, and WI38) are available from the American Type Culture Collection (ATCC, Manassas VA) and may be chosen to ensure the correct modification and processing of the foreign protein.
In another embodiment of the invention, natural, modified, or recombinant nucleic acid sequences encoding NuABP 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 NuABP protein containing a heterologous moiety that can be recognized by a commercially available antibody may facilitate the screening of peptide libraries for inhibitors of NuABP
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 NuABP encoding sequence and the heterologous protein sequence, so that NuABP 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.
In a further embodiment of the invention, synthesis of radiolabeled NuABP 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, 'SS-methionine.
Fragments of NuABP may be produced not only by recombinant means, but also by direct peptide synthesis using solid-phase techniques. (See, e.g., Creighton, su ra pp. ~5-60.) Protein synthesis may be performed by manual techniques or by automation. Automated synthesis may be achieved, for example, using the ABI 43 I A peptide synthesizer (Perkin-Elmer). Various fragments of NuABP may be synthesized separately and then combined to produce the full length molecule.
THERAPEUTICS
Chemical and structural similarity, e.g., in the context of sequences and motifs, exists between regions of NuABP and nucleic-acid binding proteins. In addition, the expression of NuABP is closely associated with proliferative, neuronal, inflamed, and cancerous tissues and tissues of the reproductive system. Therefore, NuABP appears to play a role in reproductive, immune, and neurological disorders, and cell proliferative disorders including cancer. In the treatment of disorders associated with increased NuABP expression or activity, it is desirable to decrease the expression or activity of NuABP. In the treatment of disorders associated with decreased NuABP
expression or activity, it is desirable to increase the expression or activity of NuABP.
Therefore, in one embodiment, NuABP 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 NuABP. Examples of such disorders include, but are not limited to, a reproductive disorder such as disorders of prolactin production, infertility, including tubal disease, ovulatory defects, and endometriosis, disruptions of the estrous cycle, disruptions of the menstrual cycle, polycystic ovary syndrome, ovarian hyperstimulation syndrome, endometrial and ovarian tumors, uterine fibroids, autoimmune disorders, ectopic pregnancies, and teratogenesis; cancer of the breast, fibrocystic breast disease, and galactorrhea; disruptions of spermatogenesis, abnormal sperm physiology, cancer of the testis, cancer of the prostate, benign prostatic hyperplasia, prostatitis, Peyronie's disease, impotence, carcinoma of the male breast, and gynecomastia; an immune disorder such as inflammation, actinic keratosis, acquired immunodeficiency syndrome (AIDS), Addison's disease, adult respiratory distress syndrome, allergies, ankylosing spondylitis, amyloidosis, anemia, arteriosclerosis, asthma, atherosclerosis, autoimmune hemolytic anemia, autoimmune thyroiditis, bronchitis, bursitis, WO 00/44900 PCT/US00lD2237 cholecystitis, cirrhosis, contact dermatitis, Crohn's disease, atopic dermatitis, dermatomyositis, diabetes mellitus, emphysema, erythroblastosis fetalis, erythema nodosum, atrophic gastritis, glomerulonephritis. Goodpasture's syndrome, gout, Graves' disease. Hashimoto's thyroiditis, paroxysmal nocturnal hemoglobinuria, hepatitis, hypereosinophilia, irritable bowel syndrome, episodic lymphopenia with lymphocytotoxins, mixed connective tissue disease (MCTD), multiple sclerosis, myasthenia gravis, myocardial or pericardial inflammation, myelofibrosis, osteoarthritis, osteoporosis, pancreatitis, polycythemia vera, polymyositis, psoriasis, Reiter's syndrome, rheumatoid arthritis. scleroderma, Sjogren's syndrome, systemic anaphylaxis, systemic lupus erythematosus, systemic sclerosis, primary thrombocythemia, thrombocytopenic purpura, ulcerative colitis, uveitis, Werner syndrome, complications of cancer, hemodialysis, and extracorporeal circulation, trauma, and hematopoietic cancer including lymphoma, leukemia, and myeloma; a neurological disorder such as epilepsy, ischemic cerebrovascular disease, stroke, cerebral neoplasms, Alzheimer's disease, Pick's disease, Huntington's disease, dementia, Parkinson's disease and other extrapyramidal disorders, amyotrophic lateral sclerosis and other motor neuron disorders, progressive neural muscular atrophy, retinitis pigmentosa, hereditary ataxias, multiple sclerosis and other demyelinating diseases, bacterial and viral meningitis, brain abscess, subdural empyema, epidural abscess, suppurative intracranial thrombophlebitis, myelitis and radiculitis, viral central nervous system disease, prion diseases including kuru, Creutzfeldt-Jakob disease, and Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, nutritional and metabolic diseases of the nervous system, neurofibromatosis, tuberous sclerosis, cerebelloretinal hemangioblastomatosis, encephalotrigeminal syndrome, mental retardation and other developmental disorders of the central nervous system, cerebral palsy, neuroskeleta) disorders, autonomic nervous system disorders, cranial nerve disorders, spinal cord diseases, muscular dystrophy and other neuromuscular disorders, peripheral nervous system disorders. dermatomyositis and polymyositis, inherited, metabolic, endocrine, and toxic myopathies, myasthenia gravis, periodic paralysis, mental disorders including mood, anxiety, and schizophrenic disorders. akathesia, amnesia, catatonia, diabetic neuropathy, tardive dyskinesia, dystonias, paranoid psychoses, postherpetic neuralgia, and Tourette's disorder; and a cell proliferative disorder such as actinic keratosis, arteriosclerosis, atherosclerosis, bursitis, cirrhosis, hepatitis, mixed connective tissue disease (MCTD), myelofibrosis, paroxysmal nocturnal hemoglobinuria, polycythemia vera, psoriasis, primary thrombocythemia, and cancers including adenocarcinoma, leukemia, lymphoma, melanoma, myeloma, sarcoma, teratocarcinoma, and, in particular, cancers of the adrenal gland, bladder, bone, bone marrow, brain, breast, cervix, gall bladder, ganglia, gastrointestinal tract, heart, kidney, liver, lung, muscle, ovary, pancreas, parathyroid, penis, prostate, salivary glands, skin, spleen, testis, thymus, thyroid, and uterus.
In another embodiment, a vector capable of expressing NuABP 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 NuABP including, but not limited to. those described above.
In a further embodiment, a pharmaceutical composition comprising a substantially purified NuABP 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 NuABP including, but not limited to, those provided above.
In still another embodiment, an agonist which modulates the activity of NuABP
may be administered to a subject to treat or prevent a disorder associated with decreased expression or activity of NuABP including, but not limited to, those listed above.
t0 In a further embodiment, an antagonist of NuABP may be administered to a subject to treat or prevent a disorder associated with increased expression or activity of NuABP.
Examples of such disorders include, but are not limited to, those reproductive, immune, and neurological disorders, and cell proliferative disorders including cancer, described above. In one aspect, an antibody which specifically binds NuABP 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 NuABP.
In an additional embodiment, a vector expressing the complement of the polynucleotide encoding NuABP may be administered to a subject to treat or prevent a disorder associated with increased expression or activity of NuABP including, but not limited to, those described above.
In other embodiments, any of the proteins, antagonists, antibodies, agonists, complementary sequences, or vectors of the invention may be administered in combination with other appropriate therapeutic agents. Selection of the appropriate agents for use in combination therapy may be made by one of ordinary skill in the art, according to conventional pharmaceutical principles. The combination of therapeutic agents may act synergistically to effect the treatment or prevention of the various disorders described above. Using this approach, one may be able to achieve therapeutic efficacy with lower dosages of each agent, thus reducing the potential for adverse side effects.
An antagonist of NuABP may be produced using methods which are generally known in the art. In particular, purified NuABP may be used to produce antibodies or to screen libraries of pharmaceutical agents to identify those which specifically bind NuABP.
Antibodies to NuABP may also be generated using methods that are well known in the art. Such antibodies may include, but are not limited to, polyclonal, monoclonal, chimeric, and single chain antibodies, Fab fragments, and fragments produced by a Fab expression library. Neutralizing antibodies (i.e., those which inhibit dimer formation) are generally preferred for therapeutic use.
For the production of antibodies, various hosts including goats, rabbits, rats, mice, humans, and others may be immunized by injection with NuABP or with any fragment or oligopeptide thereof which has immunogenic properties. Depending on the host species, various adjuvants may be used to increase immunological response. Such adjuvants include, but are not limited to, Freund's, mineral gels such as aluminum hydroxide, and surface active substances such as lysolecithin, pluronic polyols, polyanions. peptides, oil emulsions, KLH, and dinitrophenol. Among adjuvants used in humans. BCG
(bacilli Calmette-Guerin) and Corynebacteriumparvum are especially preferable.
It is preferred that the oligopeptides, peptides, or fragments used to induce antibodies to NuABP 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 and contain the entire amino acid sequence of a small, naturally occurring molecule. Short stretches of NuABP amino acids may be fused with those of another protein, such as KLH, and antibodies to the chimeric molecule may be produced.
Monoclonal antibodies to NuABP 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.) 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 NuABP-specific single chain antibodies. Antibodies with related specificity, but of distinct idiotypic composition, may be generated by chain shuffling from random combinatorial immunoglobulin libraries. (See, e.g., Burton, D.R. (1991) Proc. Natl. Acad. Sci. USA 88:10134-10137.) Antibodies may also be produced by inducing in vivo production in the lymphocyte population or by screening immunoglobulin libraries or panels of highly specific binding reagents as disclosed in the literature. (See, e.g., Orlandi, R. et al. (1989) Proc. Natl.
Acad. Sci. USA
86:3833-3837; Winter, G. et al. (1991) Nature 349:293-299.) Antibody fragments which contain specific binding sites for NuABP may also be generated.
For example, such fragments include, but are not limited to, F(ab'), fragments produced by pepsin digestion of the antibody molecule and Fab fragments generated by reducing the disulfide bridges of the F(ab')2 fragments. Alternatively, Fab expression libraries may be constructed to allow rapid and easy identification of monoclonal Fab fragments with the desired specificity.
(See, e.g., Huse, W.D.

et al. ( 1989) Science 246:1275-1281.) Various immunoassays may be used for screening to identify antibodies having the desired specificity. Numerous protocols for competitive binding or immunoradiometric assays using either polyclonal or monoclonal antibodies with established specificities are well known in the art. Such immunoassays typically involve the measurement of complex formation between NuABP and its specific antibody. A two-site, monoclonal-based immunoassay utilizing monoclonal antibodies reactive to two non-interfering NuABP epitopes is generally used, but a competitive binding assay may also be employed (Pound, supra).
Various methods such as Scatchard analysis in conjunction with radioimmunoassay techniques may be used to assess the affinity of antibodies for NuABP.
Affinity is expressed as an association constant, Ka, which is defined as the molar concentration of NuABP-antibody complex divided by the molar concentrations of free antigen and free antibody under equilibrium conditions.
The Ka determined for a preparation of polyclonal antibodies, which are heterogeneous in their affinities for multiple NuABP epitopes, represents the average affinity, or avidity, of the antibodies l5 for NuABP. The K~ determined for a preparation of monoclonal antibodies, which are monospecific for a particular NuABP epitope, represents a true measure of affinity. High-affinity antibody preparations with Ka ranging from about 109 to 10'-'' L/mole are preferred for use in immunoassays in which the NuABP-antibody complex must withstand rigorous manipulations. Low-affinity antibody preparations with Ka ranging from about 106 to 10' L/mole are preferred for use in immunopurification and similar procedures which ultimately require dissociation of NuABP, preferably in active form, from the antibody (Catty, D. (1988) Antibodies, Volume I: A Practical Approach, IRL Press, Washington, DC; Liddell, J.E. and Cryer, A. (1991) A
Practical Guide to Monoclonal Antibodies, John Wiley & Sons, New York NY).
The titer and avidity of polyclonal antibody preparations may be further evaluated to determine the quality and suitability of such preparations for certain downstream applications. For example, a polyclonal antibody preparation containing at least 1-2 mg specific antibody/ml, preferably 5-10 mg specific antibody/ml, is generally employed in procedures requiring precipitation ofNuABP-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. su ra.) In another embodiment of the invention, the polynucleotides encoding NuABP, or any fragment or complement thereof, may be used for therapeutic purposes. In one aspect, the complement of the polynucleotide encoding NuABP may be used in situations in which it would be desirable to block the transcription of the mRNA. In particular, cells may be transformed with sequences complementary to polynucleotides encoding NuABP. Thus, complementary molecules or fragments may be used to modulate NuABP activity, or to achieve regulation of gene function. Such technology is now well known in the art, and sense or antisense oligonucleotides or larger fragments can be designed from various locations along the coding or control regions of sequences encoding NuABP.
Expression vectors derived from retroviruses, adenoviruses, or herpes or vaccinia viruses, or from various bacterial plasmids, may be used for delivery of nucleotide sequences to the targeted organ, tissue, or cell population. Methods which are well known to those skilled in the art can be used to construct vectors to express nucleic acid sequences complementary to the polynucleotides encoding NuABP. (See, e.g., Sambrook, supra; Ausubel, 1995, supra.) Genes encoding NuABP can be turned off by transforming a cell or tissue with expression vectors which express high levels of a polynucleotide, or fragment thereof, encoding NuABP. Such constructs may be used to introduce untranslatable sense or antisense sequences into a cell. Even in the absence of integration into the DNA, such vectors may continue to transcribe RNA molecules until they are disabled by endogenous nucleases. Transient expression may last for a month or more with a non-replicating vector, and may last even longer if appropriate replication elements are part of the vector system.
As mentioned above, modifications of gene expression can be obtained by designing complementary sequences or antisense molecules (DNA, RNA, or PNA) to the control, S', or regulatory regions of the gene encoding NuABP. Oligonucleotides derived from the transcription initiation site, e.g., between about positions -10 and +10 from the start site, may be employed.
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 triplet DNA have been described in the literature. (See, e.g., Gee, J.E.
et al. (1994) in Huber, B.E. and B.I. Carr, Molecular and Immunolo~ic Approaches, Futura Publishing, Mt. Kisco NY, pp.
163-177.) A complementary sequence or antisense molecule may also be designed to block translation of mRNA by preventing the transcript from binding to ribosomes.
Ribozymes, enzymatic RNA molecules, may also be used to catalyze the specific cleavage of RNA. The mechanism of ribozyme action involves sequence-specific hybridization of the ribozyme molecule to complementary target RNA, followed by endonucleolytic cleavage.
For example, engineered hammerhead motif ribozyme molecules may specifically and efficiently catalyze endonucleolytic cleavage of sequences encoding NuABP.
Specific ribozyme cleavage sites within any potential RNA target are initially identified by scanning the target molecule for ribozyme cleavage sites, including the following sequences: GUA, GUU, and GUC. Once identified, short RNA sequences of between 15 and 20 ribonucleotides, corresponding to the region of the target gene containing the cleavage site, may be evaluated for secondary structural features which may render the oligonucleotide inoperable.
The suitability of candidate targets may also be evaluated by testing accessibility to hybridization with complementary oligonucleotides using ribonuclease protection assays.
Complementary ribonucleic acid molecules and ribozymes of the invention may be prepared by any method known in the art for the synthesis of nucleic acid molecules.
These include techniques for chemically synthesizing oligonucleotides such as solid phase phosphoramidite chemical synthesis.
Alternatively, RNA molecules may be generated by in vitro and in vivo transcription of DNA
sequences encoding NuABP. Such DNA sequences may be incorporated into a wide variety of vectors with suitable RNA polymerase promoters such as T7 or SP6.
Alternatively, these cDNA
constructs that synthesize complementary RNA, constitutively or inducibly, can be introduced into cell lines, cells, or tissues.
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.
Many methods for introducing vectors into cells or tissues are available and equally suitable for use in vivo, in vitro, and ex vivo. For ex vivo therapy, vectors may be introduced into stem cells taken from the patient and clonally propagated for autologous transplant back into that same patient.
Delivery by transfection, by liposome injections, or by polycationic amino polymers may be achieved using methods which are well known in the art. (See, e.g., Goldman, C.K. et al. ( 1997) Nat.
Biotechnol.15:462-466.) Any of the therapeutic methods described above may be applied to any subject in need of such therapy, including, for example, mammals such as humans, dogs, cats, cows, horses, rabbits, and monkeys.
An additional embodiment of the invention relates to the administration of a pharmaceutical or sterile composition, in conjunction with a pharmaceutically acceptable carrier, for any of the therapeutic effects discussed above. Such pharmaceutical compositions may consist ofNuABP, antibodies to NuABP, and mimetics, agonists, antagonists, or inhibitors of NuABP. The compositions may be administered alone or in combination with at least one other agent, such as a stabilizing compound, which may be administered in any sterile, biocompatible pharmaceutical carrier including, but not limited to, saline, buffered saline, dextrose, and water. The compositions may be administered to a patient alone, or in combination with other agents. drugs, or hormones.
The pharmaceutical 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, transdermal, subcutaneous, intraperitoneal, intranasal, enteral, topical, sublingual, or rectal means.
In addition to the active ingredients, these pharmaceutical compositions may contain suitable pharmaceutically-acceptable carriers comprising excipients and auxiliaries which facilitate processing of the active compounds into preparations which can be used pharmaceutically.
Further details on techniques for formulation and administration may be found in the latest edition of Remineton's Pharmaceutical Sciences (Maack Publishing, Easton PA).
Pharmaceutical compositions for oral administration can be formulated using pharmaceutically acceptable carriers well known in the art in dosages suitable for oral administration.
Such carriers enable the pharmaceutical compositions to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions, and the like, for ingestion by the patient.
Pharmaceutical preparations for oral use can be obtained through combining active compounds with solid excipient and processing the resultant mixture of granules (optionally, after grinding) to obtain tablets or dragee cores. Suitable auxiliaries can be added, if desired. Suitable excipients include carbohydrate or protein fillers, such as sugars, including lactose, sucrose, mannitol, and sorbitol; starch from corn, wheat, rice, potato, or other plants;
cellulose, such as methyl cellulose, hydroxypropylmethyl-cellulose, or sodium carboxymethylcellulose; gums, including arabic and tragacanth; and proteins, such as gelatin and collagen. 1f desired, disintegrating or solubilizing agents may be added, such as the cross-linked polyvinyl pyrrolidone, agar, and alginic acid or a salt thereof, such as sodium alginate.
Dragee cores may be used in conjunction with suitable coatings, such as concentrated sugar solutions, which may also contain gum arabic, talc, polyvinylpyrrolidone, carbopol gel, polyethylene glycol, and/or titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures.
Dyestuffs or pigments may be added to the tablets or dragee coatings for product identification or to characterize the quantity of active compound, i.e., dosage.
Pharmaceutical preparations which can be used orally include push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a coating, such as glycerol or sorbitol.
Push-fit capsules can contain active ingredients mixed with fillers or binders, such as lactose or starches, lubricants, such as talc or magnesium stearate, and, optionally, stabilizers. In soft capsules, the active compounds may be dissolved or suspended in suitable liquids, such as fatty oils, liquid, or liquid polyethylene glycol with or without stabilizers.
Pharmaceutical formulations suitable for parenteral administration may be formulated in aqueous solutions, preferably in physiologically compatible buffers such as Hanks' solution, Ringer's solution, or physiologically buffered saline. Aqueous injection suspensions may contain substances which increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Additionally, suspensions of the active compounds may be prepared as appropriate oily injection suspensions. Suitable lipophilic solvents or vehicles include fatty oils, such as sesame oil, or synthetic fatty acid esters, such as ethyl oleate, triglycerides, or liposomes. Non-lipid polycationic amino polymers may also be used for delivery. Optionally, the suspension may also contain suitable stabilizers or agents to increase the solubility of the compounds and allow for the preparation of highly concentrated solutions.
For topical or nasal administration, penetrants appropriate to the particular barrier to be permeated are used in the formulation. Such penetrants are generally known in the art.
The pharmaceutical compositions of the present invention may be manufactured in a manner that is known in the art, e.g., by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping, or lyophilizing processes.
IS The pharmaceutical composition may be provided as a salt and can be formed with many acids, including but not limited to, hydrochloric, sulfuric, acetic, lactic, tartaric, malic, and succinic acids. Salts tend to be more soluble in aqueous or other protonic solvents than are the corresponding free base forms. In other cases, the preparation may be a lyophilized powder which may contain any or all of the following: I mM to 50 mM histidine, 0.1% to 2% sucrose, and 2%
to 7% mannitol, at a pH range of 4.5 to 5.5, that is combined with buffer prior to use.
After pharmaceutical compositions have been prepared, they can be placed in an appropriate container and labeled for treatment of an indicated condition. For administration of NuABP, such labeling would include amount, frequency, and method of administration.
Pharmaceutical compositions suitable for use in the invention include compositions wherein the active ingredients are contained in an effective amount to achieve the intended purpose. The determination of an effective dose is well within the capability of those skilled in the art.
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, or pigs.
An animal model may also be used to determine the appropriate concentration range and route of administration. Such information can then be used to determine useful doses and routes for administration in humans.
A therapeutically effective dose refers to that amount of active ingredient, for example NuABP or fragments thereof, antibodies of NuABP, and agonists, antagonists or inhibitors of NuABP, 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 EDS° (the dose therapeutically effective in 50%
of the population) or LDS° (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 LDS°/EDS°
ratio. Pharmaceutical compositions which exhibit large therapeutic indices are preferred. The data obtained from cell culture assays and animal studies are used to formulate a range of dosage for human use. The dosage contained in such compositions is preferably within a range of circulating concentrations that includes the EDS° with little or no toxicity. The dosage varies within this range depending upon the dosage form employed, the sensitivity of the patient, and the route of administration.
The exact dosage will be determined by the practitioner, in light of factors related to the subject requiring treatment. Dosage and administration are adjusted to provide sufficient levels of the active moiety or to maintain the desired effect. Factors which may be taken into account include the severity of the disease state, the general health of the subject, the age, weight, and gender of the subject, time and frequency of administration, drug combination(s), reaction sensitivities, and response to therapy. Long-acting pharmaceutical compositions may be administered every 3 to 4 I S days, every week, or biweekly depending on the half life and clearance rate of the particular formulation.
Normal dosage amounts may vary from about 0.1 ~cg to 100,000 ,ug, up to a total dose of about I gram, depending upon the route of administration. Guidance as to particular dosages and methods of delivery is provided in the literature and generally available to practitioners in the art.
Those skilled in the art will employ different formulations for nucleotides than for proteins or their inhibitors. Similarly, delivery of polynucleotides or polypeptides will be specific to particular cells, conditions, locations, etc.
DIAGNOSTICS
In another embodiment, antibodies which specifically bind NuABP may be used for the diagnosis of disorders characterized by expression of NuABP, or in assays to monitor patients being treated with NuABP or agonists, antagonists, or inhibitors of NuABP.
Antibodies useful for diagnostic purposes may be prepared in the same manner as described above for therapeutics.
Diagnostic assays for NuABP include methods which utilize the antibody and a label to detect NuABP in human body fluids or in extracts of cells or tissues. The antibodies may be used with or without modification, and may be labeled by covalent or non-covalent attachment of a reporter molecule. A wide variety of reporter molecules, several of which are described above, are known in the art and may be used.
A variety of protocols for measuring NuABP, including ELISAs, RIAs, and FACS, are known in the art and provide a basis for diagnosing altered or abnormal levels of NuABP expression.
Normal or standard values for NuABP expression are established by combining body fluids or cell extracts taken from normal mammalian subjects, for example. human subjects, with antibody to NuABP under conditions suitable for complex formation. The amount of standard complex formation may be quantitated by various methods, such as photometric means. Quantities of NuABP expressed in subject, control, and disease samples from biopsied tissues are compared with the standard values.
Deviation between standard and subject values establishes the parameters for diagnosing disease.
In another embodiment of the invention, the polynucleotides encoding NuABP 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 ofNuABP
may be correlated with disease. The diagnostic assay may be used to determine absence, presence, and excess expression of NuABP, and to monitor regulation of NuABP levels during therapeutic intervention.
In one aspect, hybridization with PCR probes which are capable of detecting polynueleotide sequences, including genomic sequences, encoding NuABP or closely related molecules may be used to identify nucleic acid sequences which encode NuABP. The specificity of the probe, whether it is 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 NuABP, allelic variants, or related sequences.
Probes may also be used for the detection of related sequences, and may have at least 50%
sequence identity to any of the NuABP encoding sequences. The hybridization probes of the subject invention may be DNA or RNA and may be derived from the sequence of SEQ ID
N0:56-I 10 or from genomic sequences including promoters, enhancers, and introns of the NuABP gene.
Means for producing specific hybridization probes for DNAs encoding NuABP
include the cloning of polynucleotide sequences encoding NuABP or NuABP 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 3'-P or 35S, or by enzymatic labels, such as alkaline phosphatase coupled to the probe via avidin/biotin coupling systems, and the like.
Polynucleotide sequences encoding NuABP may be used for the diagnosis of disorders associated with expression ofNuABP. Examples of such disorders include, but are not limited to, a reproductive disorder such as disorders of prolactin production, infertility, including tubal disease, ovulatory defects, and endometriosis, disruptions of the estrous cycle, disruptions of the menstrual cycle, polycystic ovary syndrome, ovarian hyperstimulation syndrome, endometrial and ovarian tumors, uterine fibroids, autoimmune disorders, ectopie pregnancies, and teratogenesis; cancer of the breast, fibrocystic breast disease, and galactorrhea; disruptions of spermatogenesis, abnormal sperm physiology, cancer of the testis, cancer of the prostate, benign prostatic hyperplasia, prostatitis, Peyronie's disease, impotence, carcinoma of the male breast, and gynecomastia;
an immune disorder such as inflammation, actinic keratosis, acquired immunodeficiency syndrome (AIDS), Addison's disease. adult respiratory distress syndrome, allergies, ankylosing spondylitis, amyloidosis, anemia, arteriosclerosis, asthma, atherosclerosis, autoimmune hemolytic anemia, autoimmune thyroiditis, bronchitis, bursitis, cholecystitis, cirrhosis, contact dermatitis, Crohn's disease, atopic dermatitis, dermatomyositis, diabetes mellitus, emphysema, erythroblastosis fetalis, erythema nodosum, atrophic gastritis, glomerulonephritis, Goodpasture's syndrome, gout, Graves' disease, Hashimoto's thyroiditis, paroxysmal nocturnal hemoglobinuria, hepatitis, hypereosinophilia, irritable bowel syndrome, episodic lymphopenia with lymphocytotoxins, mixed connective tissue disease (MCTD), multiple sclerosis, myasthenia gravis, myocardial or pericardial inflammation, myelofibrosis, osteoarthritis, osteoporosis, pancreatitis, polycythemia vera, polymyositis, psoriasis, Reiter's syndrome, rheumatoid arthritis, scleroderma, Sjogren's syndrome, systemic anaphylaxis, systemic lupus erythematosus, systemic sclerosis, primary thrombocythemia, thrombocytopenic purpura, ulcerative colitis, uveitis, Werner syndrome, complications of cancer, hemodialysis, and extracorporeal circulation, trauma, and hematopoietic cancer including lymphoma, leukemia, and myeloma; a neurological disorder such as epilepsy, ischemic cerebrovascular disease, stroke, cerebral neoplasms, Alzheimer's disease, Pick's disease, Huntington's disease, dementia, Parkinson's disease and other extrapyramidal disorders, amyotrophic lateral sclerosis and other motor neuron disorders, progressive neural muscular atrophy, retinitis pigmentosa, hereditary ataxias, multiple sclerosis and other demyelinating diseases, bacterial and viral meningitis, brain abscess, subdural empyema, epidural abscess, suppurative intracranial thrombophlebitis, myelitis and radiculitis, viral central nervous system disease, prion diseases including kuru, Creutzfeldt-Jakob disease, and Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, nutritional and metabolic diseases of the nervous system, neuroftbromatosis, tuberous sclerosis, cerebelloretinal hemangioblastomatosis, encephalotrigeminal syndrome, mental retardation and other developmental disorders of the central nervous system, cerebral palsy, neuroskeletal disorders, autonomic nervous system disorders, cranial nerve disorders, spinal cord diseases, muscular dystrophy and other neuromuscular disorders, peripheral nervous system disorders, dermatomyositis and polymyositis, inherited, metabolic, endocrine, and toxic myopathies, myasthenia gravis, periodic paralysis, mental disorders including mood, anxiety, and schizophrenic disorders, akathesia, amnesia, catatonia, diabetic neuropathy, tardive dyskinesia, dystonias, paranoid psychoses, postherpetic neuralgia, and Tourette's disorder; and a cell proliferative disorder such as actinic keratosis, arteriosclerosis, atherosclerosis, bursitis, cirrhosis, hepatitis, mixed connective tissue disease (MCTD), myelofibrosis, paroxysmal nocturnal hemoglobinuria, polycvthemia vera, psoriasis, primary thrombocythemia, and cancers including, adenocarcinoma; leukemia, lymphoma, melanoma, myeloma, sarcoma, teratocarcinoma, and, in particular, cancers of the adrenal gland. bladder, bone, bone marrow, brain, breast. cervix, gall bladder, ganglia, gastrointestinal tract, heart, kidney, liver, lung, muscle, ovary, pancreas, parathyroid, penis, prostate, salivary glands, skin, spleen, testis, thymus, thyroid, and uterus. The polynucleotide sequences encoding NuABP 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 NuABP
expression. Such qualitative or quantitative methods are well known in the art.
In a particular aspect, the nucleotide sequences encoding NuABP may be useful in assays that detect the presence of associated disorders, particularly those mentioned above. The nucleotide sequences encoding NuABP 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 NuABP in the sample indicates the presence of the associated disorder. Such assays may also be used to evaluate the efficacy of a particular therapeutic treatment regimen in animal studies, in clinical trials, or to monitor the treatment of an individual patient.
In order to provide a basis for the diagnosis of a disorder associated with expression of NuABP, a normal or standard profile for expression is established. This may be accomplished by combining body fluids or cell extracts taken from normal subjects, either animal or human, with a sequence, or a fragment thereof, encoding NuABP, under conditions suitable for hybridization or amplification. Standard hybridization may be quantified by comparing the values obtained from normal subjects with values from an experiment in which a known amount of a substantially purified polynucleotide is used. Standard values obtained in this manner may be compared with values obtained from samples from patients who are symptomatic for a disorder.
Deviation from standard values is used to establish the presence of a disorder.
Once the presence of a disorder is established and a treatment protocol is initiated, hybridization assays may be repeated on a regular basis to determine if the level of expression in the patient begins to approximate that which is observed in the normal subject.
The results obtained from successive assays may be used to show the efficacy of treatment over a period ranging from several days to months.
With respect to cancer, the presence of an abnormal amount of transcript (either under- or overexpressed) in biopsied tissue from an individual may indicate a predisposition for the development of the disease, or may provide a means for detecting the disease prior to the appearance of actual clinical symptoms. A more definitive diagnosis of this type may allow health professionals to employ preventative measures or aggressive treatment earlier thereby preventing the development or further progression of the cancer.
Additional diagnostic uses for oligonucleotides designed from the sequences encoding NuABP may involve the use of PCR. These oligomers may be chemically synthesized, generated enzymatically, or produced in vitro. Oligomers wilt preferably contain a fragment of a polynucleotide encoding NuABP, or a fragment of a polynucleotide complementary to the polynucleotide encoding NuABP, 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.
Methods which may also be used to quantify the expression of NuABP include radiolabeling or biotinylating nucleotides, coamplification of a control nucleic acid, and interpolating results from standard curves. (See, e.g., Melby, P.C. et al. (1993) J. Immunol. Methods 159:235-244; Duplaa, C.
et al. (1993) Anal. Biochem. 212:229-236.) The speed of quantitation of multiple samples may be accelerated by running the assay in a high-throughput format where the oligomer of interest is presented in various dilutions and a spectrophotometric or colorimetric response gives rapid quantitation.
In further embodiments, oligonucleotides or longer fragments derived from any of the polynucleotide sequences described herein may be used as targets in a microarray. The microarray can be used to monitor the expression level of large numbers of genes simultaneously and 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, and to develop and monitor the activities of therapeutic agents.
Microarrays may be prepared, used, and analyzed using methods known in the art. (See, e.g., Brennan, T.M. et al. ( 1995) U.S. Patent No. 5,474,796; Schena, M. et al. ( 1996) Proc. Natl. Acad. Sci.
USA 93:10614-10619; Baldeschweiler et al. (1995) PCT application W095/251 I
16; Shalom D. et al.
(1995) PCT application W095/35505; Heller, R.A. et al. (1997) Proc. Natl.
Acad. Sci. USA 94:2150-2155; and Heller, M.J. et al. (1997) U.S. Patent No. 5,605,662.) In another embodiment of the invention, nucleic acid sequences encoding NuABP
may be used to generate hybridization probes useful in mapping the naturally occurring genomic sequence.
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.) Fluorescent in situ hybridization (FISH) may be correlated with other physical chromosome mapping techniques 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 NuABP on a physical chromosomal map and a specific disorder, or a predisposition to a specific disorder, may help define the region of DNA
associated with that disorder.
The nucleotide sequences of the invention may be used to detect differences in gene sequences among normal, carrier, and affected individuals.
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 number or arm of a particular human chromosome is not known. New sequences can be assigned to chromosomal arms by physical mapping.
This provides IS valuable information to investigators searching for disease genes using positional cloning or other gene discovery techniques. Once the disease or syndrome has been crudely localized by genetic linkage to a particular genomic region, e.g., ataxia-telangiectasia to 1 Iq22-23, 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 subject invention may also be used to detect differences in the chromosomal location due to translocation, inversion, etc., among normal, carrier, or affected individuals.
In another embodiment of the invention, NuABP, 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 NuABP and the agent being tested may be measured.
Another technique for drug screening provides for high throughput screening of compounds having suitable binding affinity to the protein of interest. (See, e.g., Geysen, et al. ( 1984) PCT
application W084/03564.) In this method, large numbers of different small test compounds are synthesized on a solid substrate. The test compounds are reacted with NuABP, or fragments thereof, and washed. Bound NuABP is then detected by methods well known in the art.
Purified NuABP can also be coated directly onto plates for use in the aforementioned drug screening techniques.
Alternatively, non-neutralizing antibodies can be used to capture the peptide and immobilize it on a solid support.
In another embodiment, one may use competitive drug screening assays in which neutralizing WO 00/44900 ' PCT/US00/02237 antibodies capable of binding NuABP specifically compete with a test compound for binding NuABP.
In this manner, antibodies can be used to detect the presence of any peptide which shares one or more antigenic determinants with NuABP.
In additional embodiments, the nucleotide sequences which encode NuABP may be used in any molecular biology techniques that have yet to be developed, provided the new techniques rely on properties of nucleotide sequences that are currently known, including, but not limited to, such properties as the triplet genetic code and specific base pair interactions.
Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. The following embodiments are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.
Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. The following preferred specific embodiments are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.
The disclosures of all patents, applications, and publications mentioned above and below, in particular U.S. Ser. No. 60/117,905 and U.S. Ser. No. 60/117,904, are hereby expressly incorporated by reference.
EXAMPLES
I. Construction of cDNA Libraries RNA was purchased from Clontech or isolated from tissues described in Table 4.
Some tissues were homogenized and lysed in guanidinium isothiocyanate, while others were homogenized and lysed in phenol or in a suitable mixture of denaturants, such as TRIZOL
(Life Technologies), a monophasic solution of phenol and guanidine isothiocyanate. The resulting lysates were centrifuged over CsCI cushions or extracted with chloroform. RNA was precipitated from the lysates with either isopropanol or sodium acetate and ethanol, or by other routine methods.
Phenol extraction and precipitation of RNA were repeated as necessary to increase RNA
purity. In some cases, RNA was treated with DNase. For most libraries, poly(A+) RNA was isolated using oligo d(T)-coupled paramagnetic particles (Promega), OLIGOTEX latex particles (QIAGEN, Chatsworth CA), or an OLIGOTEX mRNA purification kit (QIAGEN). Alternatively, RNA was isolated directly from tissue lysates using other RNA isolation kits, e.g., the POLY(A)PURE mRNA
purification kit (Ambion, Austin TX).
In some cases, Stratagene was provided with RNA and constructed the corresponding cDNA
libraries. Otherwise, cDNA was synthesized and cDNA libraries were constructed with the UNIZAP

vector system (Stratagene) or SUPERSCRIPT plasmid system (Life Technologies), using the recommended procedures or similar methods known in the art. (See, e.g., Ausubel, 1997, supra, units 5.1-6.6.) Reverse transcription was initiated using oligo d(T) or random primers. Synthetic oligonucleotide adapters were ligated to double stranded cDNA, and the cDNA
was digested with the appropriate restriction enzyme or enzymes. For most libraries, the cDNA was size-selected (300-1000 bp) using SEPHACRYL S 1000, SEPHAROSE CL2B, or SEPHAROSE CL4B column chromatography (Amersham Pharmacia Biotech) or preparative agarose gel electrophoresis. cDNAs were ligated into compatible restriction enzyme sites of the polylinker of a suitable plasmid, e.g., PBLUESCRIPT plasmid (Stratagene), PSPORTI plasmid (Life Technologies), or pINCY (Incyte Pharmaceuticals, Palo Alto CA). Recombinant plasmids were transformed into competent E. coli cells including XL1-Blue, XL1-BIueMRF, or SOLR from Stratagene or DHSa, DH10B, or ElectroMAX DH l OB from Life Technologies.
II. Isolation of cDNA Clones Plasmids 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, Ultra Plasmid purification systems or the R.E.A.L. PREP 96 plasmid purification kit from QIAGEN.
Following precipitation, plasmids were resuspended in 0.1 ml of distilled water and stored, with or without lyophilization, at 4°C.
Alternatively, plasmid DNA was amplified from host cell lysates using direct link PCR in a high-throughput format (Rao, V.B. (1994) Anal. Biochem. 216:1-14). Host cell lysis and thermal cycling steps were carried out in a single reaction mixture. Samples were processed and stored in 384-well plates, and the concentration of amplified plasmid DNA was quantified fluorometrically using PICOGREEN dye (Molecular Probes, Eugene OR) and a FLUOROSKAN II
fluorescence scanner (Labsystems Oy, Helsinki, Finland).
III. Sequencing and Analysis cDNA sequencing reactions were processed using standard methods or high-throughput instrumentation such as the ABI CATALYST 800 (Perkin-Elmer) thermal cycler or the PTC-200 thermal cycler (MJ Research) in conjunction with the HYDRA microdispenser (Robbins Scientific) or the MICROLAB 2200 (Hamilton) liquid transfer system. cDNA sequencing reactions were prepared using reagents provided by Amersham Pharmacia Biotech or supplied in ABI
sequencing kits such as the ABI PRISM BIGDYE Terminator cycle sequencing ready reaction kit (Perkin-Elmer).
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 (Perkin-Elmer) 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 V.
The polynucleotide sequences derived from cDNA sequencing were assembled and analyzed using a combination of software programs which utilize algorithms well known to those skilled in the art. Table 5 summarizes the tools, programs, and algorithms used and provides applicable descriptions, references. and threshold parameters. The first column of Table 5 shows the tools, programs, and algorithms used, the second column provides brief descriptions thereof, the third column presents appropriate references, all of which are incorporated by reference herein in their entirety, and the fourth column presents, where applicable, the scores, probability values, and other parameters used to evaluate the strength of a match between two sequences (the higher the score, the greater the homology between two sequences). Sequences were analyzed using MACDNASIS PRO
l5 software (Hitachi Software Engineering, South San Francisco CA) and LASERGENE software (DNASTAR). Polynucleotide and polypeptide sequence alignments were generated using the default parameters specified by the clustal algorithm as incorporated into the MEGALIGN multisequence alignment program (DNASTAR), which also calculates the percent identity between aligned sequences.
The polynucleotide sequences were validated by removing vector, linker, and polyA
sequences and by masking ambiguous bases, using algorithms and programs based on BLAST, dynamic programing, and dinucleotide nearest neighbor analysis. The sequences were then queried against a selection of public databases such as the GenBank primate, rodent, mammalian, vertebrate, and eukaryote databases. and BLOCKS, PRINTS, DOMO, PRODOM, and PFAM to acquire annotation using programs based on BLAST, FASTA, and BLIMPS. The sequences were assembled into full length polynucleotide sequences using programs based on Phred, Phrap, and Consed, and were screened for open reading frames using programs based on GeneMark, BLAST, and FASTA.
The full length polynucleotide sequences were~translated to derive the corresponding full length amino acid sequences, and these full length sequences were subsequently analyzed by querying against databases such as the GenBank databases (described above), SwissProt, BLOCKS, PRINTS, DOMO, PRODOM, Prosite, and Hidden Markov Model (HMM)-based protein family databases such as PFAM. HMM is a probabilistic approach which analyzes consensus primary structures of gene families. (See, e.g., Eddy, S.R. (1996) Curr. Opin. Struct. Biol. 6:361-365.) The programs described above for the assembly and analysis of full length polynucleotide and amino acid sequences were also used to identify polynucleotide sequence fragments from SEQ ID

WO 00/44900 PCT/US00/~2237 N0:56-110. Fragments from about 20 to about 4000 nucleotides which are useful in hybridization and amplification technologies were described in The Invention section above.
IV. Northern Analysis 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, s_u~ra, ch. 4 and 16.) Analogous computer techniques applying BLAST were used to search for identical or related molecules in nucleotide databases such as GenBank or LIFESEQ (Incyte Pharmaceuticals). 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:
sequence identity x % maximum BLAST score The product score takes into account both the degree of similarity between two sequences and the length of the sequence match. For example, with a product score of 40, the match will be exact within a 1% to 2% error, and, with a product score of 70, the match will be exact.
Similar molecules are usually identified by selecting those which show product scores between 15 and 40, although lower scores may identify related molecules.
The results of northern analyses are reported as a percentage distribution of libraries in which the transcript encoding NuABP occurred. Analysis involved the categorization of cDNA libraries by organ/tissue and disease. The organ/tissue categories included cardiovascular, dermatologic, developmental, endocrine, gastrointestinal, hematopoietic/immune, musculoskeletal, nervous, reproductive, and urologic. The disease/condition categories included cancer, inflammation, trauma, cell proliferation, neurological, and pooled. For each category, the number of libraries expressing the sequence of interest was counted and divided by the total number of libraries across all categories.
Percentage values of tissue-specific and disease- or condition-specific expression are reported in Table 3.
V. Extension of NuABP Encoding Polynucleotides The full length nucleic acid sequences of SEQ ID N0:56-110 were produced by extension of an appropriate fragment ofthe 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, to initiate 3' extension of the known fragment. The initial primers were designed using OLIGO 4.06 software (National Biosciences), or another appropriate program, to be about 22 to 30 nucleotides in length, to have a GC content of about 50% or more, and to anneal to the target sequence at temperatures of about 68°C to about 72°C. Any stretch of nucleotides which would result in hairpin structures and primer-primer dimerizations was avoided.
Selected human cDNA libraries were used to extend the sequence. If more than one extension was necessary or desired. additional or nested sets of primers were designed.
High fidelity amplification was obtained by PCR using methods well known in the art. PCR
was performed in 96-well plates using the PTC-200 thermal cycler (MJ Research, Inc.). The reaction mix contained DNA template, 200 nmol of each primer, reaction buffer containing Mg=-. (NHa)ZSO,, and ~i-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, S
min; Step 7: storage at 4°C. In the alternative, the parameters for primer pair T7 and SK+ were as follows: Step 1: 94°C, 3 min; Step 2:
94°C, 15 sec; Step 3: 57°C, 1 min; Step 4: 68°C, 2 min;
Step 5: Steps 2, 3, and 4 repeated 20 times;
Step 6: 68°C, 5 min; Step 7: storage at 4°C.
The concentration of DNA in each well was determined by dispensing 100 pl PICOGREEN
quantitation reagent (0.25% (v/v) PICOGREEN; Molecular Probes, Eugene OR) dissolved in 1 X TE
and 0.5 pl of undiluted PCR product into each well of an opaque fluorimeter plate (Corning Costar, Acton MA), allowing the DNA to bind to the reagent. The plate was scanned in a Fluoroskan II
(Labsystems Oy, Helsinki, Finland) to measure the fluorescence of the sample and to quantify the concentration of DNA. A 5 ~l to 10 ~l aliquot of the reaction mixture was analyzed by electrophoresis on a 1 % agarose mini-gel to determine which reactions were successful in extending the sequence.
The extended nucleotides were desalted and concentrated, transferred to 384-well plates, digested with CviJI cholera virus endonuclease (Molecular Biology Research, Madison WI), and sonicated or sheared prior to relegation 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 relegated using T4 ligase (New England Biolabs, Beverly MA) 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, individual colonies were picked and cultured overnight at 37°C in 384-well plates in LB/2x carb liquid media.
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; Step3:
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 ( I :2, v/v), and sequenced using DYENAMIC energy transfer sequencing S primers and the DYENAMIC DIRECT kit (Amersham Pharmacia Biotech) or the ABI
PRISM
BIGDYE Terminator cycle sequencing ready reaction kit (Perkin-Elmer).
In like manner, the nucleotide sequences of SEQ ID N0:56-I 10 are used to obtain 5' regulatory sequences using the procedure above, oligonucleotides designed for such extension, and an appropriate genomic library.
VI. Labeling and Use of Individual Hybridization Probes Hybridization probes derived from SEQ ID N0:56-1 10 are employed to screen cDNAs, genomie DNAs, or mRNAs. Although the labeling of oligonucleotides, consisting of about 20 base pairs, is specifically described, essentially the same procedure is used with larger nucleotide fragments. Oligonucleotides are designed using state-of the-art software such as OLIGO 4.06 software (National Biosciences) and labeled by combining 50 pmol of each oligomer, 250 ~cCi of [y-3-'P] adenosine triphosphate (Amersham Pharmacia Biotech), and T4 polynucleotide kinase (DuPont NEN, Boston MA). The labeled oligonucleotides are substantially purified using a SEPHADEX G-25 superfine size exclusion dextran bead column (Amersham Pharmacia Biotech).
An aliquot containing 10' counts per minute of the labeled probe is used in a typical membrane-based hybridization analysis of human genomic DNA digested with one of the following endonucleases:
Ase I, Bgl II, Eco RI, Pst I, Xba I, or Pvu II (DuPont NEN).
The DNA from each digest is fractionated on a 0.7% agarose gel and transferred to nylon membranes (Nytran Plus, Schleicher & Schuell, Durham NH). Hybridization is carried out for 16 hours at 40°C. To remove nonspecific signals, blots are sequentially washed at room temperature under conditions of up to, for example, 0.1 x saline sodium citrate and 0.5%
sodium dodeeyl sulfate.
Hybridization patterns are visualized using autoradiography or an alternative imaging means and compared.
VII. Microarrays A chemical coupling procedure and an ink jet device can be used to synthesize array elements on the surface of a substrate. (See, e.g., Baldeschweiler, supra.) An array 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 by hand or using available methods and machines and contain any appropriate number of elements.
After hybridization, nonhybridized probes are removed and a scanner used to determine the levels and patterns of fluorescence. The degree of complementarity and the relative abundance of each probe SO

which hybridizes to an element on the microarray may be assessed through analysis of the scanned images.
Full-length cDNAs, Expressed Sequence Tags (ESTs). or fragments thereof may comprise the elements of the microarray. Fragments suitable for hybridization can be selected using software well known in the art such as LASERGENE software (DNASTAR). Full-length cDNAs, ESTs, or fragments thereof corresponding to one of the nucleotide sequences of the present invention, or selected at random from a cDNA library relevant to the present invention, are arranged on an appropriate substrate, e.g., a glass slide. The cDNA is fixed to the slide using, e.g., UV cross-linking followed by thermal and chemical treatments and subsequent drying. (See, e.g., Schena, M. et al.
( 1995) Science 270:467-470; Shalom D. et al. ( 1996) Genome Res. 6:639-645.) Fluorescent probes are prepared and used for hybridization to the elements on the substrate. The substrate is analyzed by procedures described above.
VIII. Complementary Polynucleotides Sequences complementary to the NuABP-encoding sequences, or any parts thereof, are used to detect, decrease, or inhibit expression of naturally occurring NuABP.
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 NuABP. 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 NuABP-encoding transcript.
IX. Expression of NuABP
Expression and purification of NuABP is achieved using bacterial or virus-based expression systems. For expression of NuABP 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 TS or T7 bacteriophage promoter in conjunction with the lac operator regulatory element. Recombinant vectors are transformed into suitable bacterial hosts, e.g., BL21 (DE3).
Antibiotic resistant bacteria express NuABP upon induction with isopropyl beta-D-thiogalactopyranoside (IPTG). Expression ofNuABP in eukaryotic cells is achieved by infecting insect or mammalian cell lines with recombinant Auto raphica californica nuclear polyhedrosis virus (AcMNPV), commonly known as baculovirus. The nonessential polyhedrin gene of baculovirus is replaced with cDNA encoding NuABP 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 (Sfi7) 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.
7:193 7-1945. ) In most expression systems, NuABP 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 NuABP 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, l5 supra, ch. 10 and 16). Purified NuABP obtained by these methods can be used directly in the following activity assay.
X. Demonstration of NuABP Activity NuABP activity is measured by its ability to stimulate transcription of a reporter gene (Liu, H.Y. et al. ( 1997) EMBO J. 16( 17):5289-5298.) The assay entails the use of a well characterized reporter gene construct, LexAoP LacZ, that consists of LexA DNA
transcriptional control elements (LexAoP) fused to sequences encoding the E. coli LacZ enzyme. The methods for constructing and expressing fusions genes, introducing them into cells, and measuring LacZ
enzyme activity, are well known to those skilled in the art. Sequences encoding NuABP are cloned into a plasmid that directs the synthesis of a fusion protein, LexA-NuABP, consisting of NuABP and a DNA
binding domain derived from the LexA transcription factor. The resulting plasmid, encoding a LexA-NuABP fusion protein, is introduced into yeast cells along with a plasmid containing the LexAoP LacZ reporter gene.
The amount of LacZ enzyme activity associated with LexA-NuABP transfected cells, relative to control cells, is proportional to the amount of transcription stimulated by the NuABP.
XI. Functional Assays NuABP function is assessed by expressing the sequences encoding NuABP 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 CA), both of which contain the cytomegalovirus promoter. 5-10 ~g of recombinant vector are transiently transfected into a human cell line, for example, an endothelial or hematopoietic cell line, using either liposome formulations or electroporation. 1-2 ~g of an additional plasmid containing sequences encoding a marker protein are co-transfected. Expression of a marker protein provides a means to distinguish transfeeted 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 NY.
The influence ofNuABP on gene expression can be assessed using highly purified populations of cells transfeeted with sequences encoding NuABP 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 NY). mRNA can be purified from the cells using methods well known by those of skill in the art. Expression of mRNA encoding NuABP and other genes of interest can be analyzed by northern analysis or microarray techniques.
XII. Production of NuABP Specific Antibodies NuABP substantially purified using polyacrylamide gel electrophoresis (PAGE;
see, e.g., Harrington, M.G. ( 1990) Methods Enzymol. 182:488-495), or other purification techniques, is used to immunize rabbits and to produce antibodies using standard protocols.
Alternatively, the NuABP 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. I l.) Typically, oligopeptides of about 1 S residues in length are synthesized using an ABI 431 A
peptide synthesizer (Perkin-Elmer) using fmoc-chemistry and coupled to KLH
(Sigma-Aldrich, St.
Louis MO) by reaction with N-maleimidobenzoyl-N-hydroxysuecinimide ester (MBS) to increase immunogenicity. (See. e.g., Ausubel, 1995, supra.) Rabbits are immunized with the oligopeptide-KLH complex in complete Freund's adjuvant. Resulting antisera are tested for antipeptide and anti-NuABP activity by, for example, binding the peptide or NuABP to a substrate, blocking with 1 BSA, reacting with rabbit antisera, washing, and reacting with radio-iodinated goat anti-rabbit IgG.
XIII. Purification of Naturally Occurring NuABP Using Specific Antibodies Naturally occurring or recombinant NuABP is substantially purified by immunoaffinity chromatography using antibodies specific for NuABP. An immunoaffinity column is constructed by covalently coupling anti-NuABP antibody to an activated chromatographic resin, such as CNBr-activated SEPHAROSE (Amersham Pharmacia Biotech). After the coupling, the resin is blocked and washed according to the manufacturer's instructions.
Media containing NuABP are passed over the immunoaffinity column, and the column is washed under conditions that allow the preferential absorbance of NuABP (e.g., high ionic strength buffers in the presence of detergent). The column is eluted under conditions that disrupt antibodylNuABP 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 NuABP is collected.
XIV. Identification of Molecules Which Interact with NuABP
NuABP, or biologically active fragments thereof, are labeled with '-'SI 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 NuABP, washed, and any wells with labeled NuABP complex are assayed. Data obtained using different concentrations of NuABP are used to calculate values for the number, affinity, and association of NuABP with the candidate molecules.
Various modifications and variations of the described methods and systems of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention.
Although the invention has been described in connection with certain embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments.
Indeed, various modifications of the described modes for carrying out the invention which are obvious to those skilled in molecular biology or related fields are intended to be within the scope of the following claims.

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d ~ v tr a> R a v7 o~. a' 2 4 U rr SUBSTITUTE SHEET (RULE 26) SEQUENCE LISTING
<110> INCYTE PHARMACEUTICALS, INC.
TANG, Y. Tom LAL, Preeti HILLMAN, Jennifer L.
YUE, Henry AZIMZAI, Yalda LU, Aina M.D.
BAUGHN, Mariah R.
TRAN, Bao SHIH, Leo L.
AU-YOUNG, Janice <120> NUCLEIC ACID-BINDING PROTEINS
<130> PF-0662 PCT
<140> To Be Assigned <141> Herewith <150> 60/117,905; 60/117,904 <151> 1999-01-29; 1999-01-29 <160> 110 <170> PERL Program <210> 1 <211> 754 <212> PRT
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 025733CD1 <400> 1 Met Ala Ala Ala Gly Ser Arg Lys Arg Arg Leu Ala Glu Leu Thr Val Asp Glu Phe Leu Ala Ser Gly Phe Asp Ser Glu Ser Glu Ser Glu Ser Glu Asn Ser Pro Gln Ala Glu Thr Arg Glu Ala Arg Glu Ala Ala Arg Ser Pro Asp Lys Pro Gly Gly Ser Pro Ser Ala Ser Arg Arg Lys Gly Arg Ala Ser Glu His Lys Asp Gln Leu Ser Arg Leu Lys Asp Arg Asp Pro Glu Phe Tyr Lys Phe Leu Gln Glu Asn Asp Gln Ser Leu Leu Asn Phe Ser Asp Ser Asp Ser Ser Glu Glu Glu Glu Gly Pro Phe His Ser Leu Pro Asp Val Leu Glu Glu Ala Ser Glu Glu Glu Asp Gly Ala Glu Glu Gly Glu Asp Gly Asp Arg Val Pro Arg Gly Leu Lys Gly Lys Lys Asn Ser Val Pro Val Thr Val Ala Met Val Glu Arg Trp Lys Gln Aia Ala Lys Gln Arg Leu SUBSTITUTE SHEET (RULE 26) Thr Pro Lys Leu Phe His Glu Val Val Gln Ala Phe Arg Ala Ala Val Ala Thr Thr Arg Gly Asp Gln Glu Ser Ala Glu Ala Asn Lys Phe Gln Val Thr Asp Ser Ala Ala Phe Asn Ala Leu Val Thr Phe Cys Ile Arg Asp Leu Ile Gly Cys Leu Gln Lys Leu Leu Phe Gly Lys Val Ala Lys Asp Ser Ser Arg Met Leu Gln Pro Ser Ser Ser Pro Leu Trp Gly Lys Leu Arg Val Asp Ile Lys Ala Tyr Leu Gly Ser Ala Ile Gln Leu Val Ser Cys Leu Ser Glu Thr Thr Val Leu Ala Ala Val Leu Arg His Ile Ser Val Leu Val Pro Cys Phe Leu Thr Phe Pro Lys Gln Cys Arg Met Leu Leu Lys Arg Met Val Val Val Trp Ser Thr Gly Glu Glu Ser Leu Arg Val Leu Ala Phe Leu Val Leu Ser Arg Val Cys Arg His Lys Lys Asp Thr Phe Leu Gly Pro Val Leu Lys Gln Met Tyr Ile Thr Tyr Val Arg Asn Cys Lys Phe Thr Ser Pro Gly Ala Leu Pro Phe Ile Ser Phe Met Gln Trp Thr Leu Thr Glu Leu Leu Ala Leu Glu Pro Gly Val Ala Tyr Gln His Ala Phe Leu Tyr Ile Arg Gln Leu Ala Ile His Leu Arg Asn Ala Met Thr Thr Arg Lys Lys Glu Thr Tyr Gln Ser Val Tyr Asn Trp Gln Tyr Val His Cys Leu Phe Leu Trp Cys Arg Val Leu Ser Thr Ala Gly Pro Ser Glu Ala Leu Gln Pro Leu Val Tyr Pro Leu Ala Gln Val Ile Ile Gly Cys Ile Lys Leu Ile Pro Thr Ala Arg Phe Tyr Pro Leu Arg Met His Cys Ile Arg Ala Leu Thr Leu Leu Ser Gly Ser Ser Gly Ala Phe Ile Pro Val Leu Pro Phe Ile Leu Glu Met Phe Gln Gln Val Asp Phe Asn Arg Lys Pro Gly Arg Met Ser Ser Lys Pro Ile Asn Phe Ser Val Ile Leu Lys Leu Ser Asn Val Asn Leu Gln Glu Lys Ala Tyr Arg Asp Gly Leu Val Glu Gln Leu Tyr Asp Leu Thr Leu Glu Tyr Leu His Ser Gln Ala His Cys Ile Gly Phe Pro Glu Leu Val Leu Pro Val Val Leu Gln Leu Lys Ser Phe Leu Arg Glu Cys Lys Val Ala Asn Tyr Cys Arg Gln Val Gln Gln Leu Leu Gly Lys Val Gln Glu Asn Ser Ala Tyr Ile Cys Ser Arg Arg Gln Arg Val Ser Phe Gly Val Ser Glu Gln Gln Ala Val Glu Ala Trp Glu Lys Leu Thr Arg Glu Glu Gly Thr Pro Leu SUBSTITUTE SHEET (RULE 26) Thr Leu Tyr Tyr Ser His Trp Arg Lys Leu Arg Asp Arg Glu Ile Gln Leu Glu Ile Ser Gly Lys Glu Arg Leu Glu Asp Leu Asn Phe Pro Glu Ile Lys Arg Arg Lys Met Ala Asp Arg Lys Asp Glu Asp Arg Lys Gln Phe Lys Asp Leu Phe Asp Leu Asn Ser Ser Glu Glu Asp Asp Thr Glu Gly Phe Ser Glu Arg Gly Ile Leu Arg Pro Leu Ser Thr Arg His Gly Val Glu Asp Asp Glu Glu Asp Glu Glu Glu 695 700 . 705 Gly Glu Glu Asp Ser Ser Asn Ser Glu Gly Glu Trp Ser Trp Asp Gly Asp Pro Asp Ala Glu Ala Gly Leu Ala Pro Gly Glu Leu Gln Gln Leu Ala Gln Gly Pro Glu Asp Glu Leu Glu Asp Leu Gln Leu Ser Glu Asp Asp <210> 2 <211> 593 <212> PRT
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 079702CD1 <400> 2 Met Arg Asp Ser Thr Gly Ala Gly Asn Ser Leu Val His Lys Arg Ser Pro Leu Arg Arg Asn Gln Lys Thr Pro Thr Ser Leu Thr Lys Leu Ser Leu Gln Asp Gly His Lys Ala Lys Lys Pro Ala Cys Lys Phe Glu Glu Gly Gln Asp Val Leu Ala Arg Trp Ser Asp Gly Leu Phe Tyr Leu Gly Thr Ile Lys Lys Ile Asn Ile Leu Lys Gln Ser Cys Phe Ile Ile Phe Glu Asp Ser Ser Lys Ser Trp Val Leu Trp Lys Asp Ile Gln Thr Gly Ala Thr Gly Ser Gly Glu Met Val Cys Thr Ile Cys Gln Glu Glu Tyr Ser Glu Ala Pro Asn Glu Met Val Ile Cys Asp Lys Cys Gly Gln Gly Tyr His Gln Leu Cys His Thr Pro His Ile Asp Ser Ser Val Ile Asp Ser Asp Glu Lys Trp Leu Cys Arg Gln Cys Val Phe Ala Thr Thr Thr Lys Arg Gly Gly Ala Leu Lys Lys Gly Pro Asn Ala Lys Ala Leu Gln Val Met Lys Gln Thr Leu Pro Tyr Ser Val Ala Asp Leu Glu Trp Asp Ala Gly His Lys Thr Asn Val Gln Gln Cys Tyr Cys Tyr Cys Gly Gly Pro Gly Asp Trp Tyr Leu Lys Met Leu Gln Cys Cys Lys Cys Lys Gln Trp SUBSTITUTE SHEET (RULE 26) Phe His Glu Ala Cys Val Gln Cys Leu Gln Lys Pro Met Leu Phe Gly Asp Arg Phe Tyr Thr Phe Ile Cys Ser Val Cys Ser Ser Gly Pro Glu Tyr Leu Lys Arg Leu Pro Leu Gln Trp Val Asp Ile Ala His Leu Cys Leu Tyr Asn Leu Ser Val Ile His Lys Lys Lys Tyr Phe Asp Ser Glu Leu Glu Leu Met Thr Tyr Ile Asn Glu Asn Trp Asp Arg Leu His Pro Gly Glu Leu Ala Asp Thr Pro Lys Ser Glu Arg Tyr Glu His Val Leu Glu Ala Leu Asn Asp Tyr Lys Thr Met Phe Met Ser Gly Lys Glu Ile Lys Lys Lys Lys His Leu Phe Gly Leu Arg Ile Arg Val Pro Pro Val Pro Pro Asn Val Ala Phe Lys Ala Glu Lys Glu Pro Glu Gly Thr Ser His Glu Phe Lys Ile Lys Gly Arg Lys Ala Ser Lys Pro Ile Ser Asp Ser Arg Glu Val Ser Asn Gly Ile Glu Lys Lys Lys Lys Lys Lys Ser Val Gly Arg Pro Pro Gly Pro Tyr Thr Arg Lys Met Ile Gln Lys Thr Ala Glu Pro Leu Leu Asp Lys Glu Ser Ile Ser Glu Asn Pro Thr Leu Asp Leu Pro Cys Ser Ile Gly Arg Thr Glu Gly Thr Ala His Ser Ser Asn Thr Ser Asp Val Asp Phe Thr Gly Ala Ser Ser Ala Lys Glu Thr Thr Ser Ser Ser Ile Ser Arg His Tyr Gly Leu Ser Asp Ser Arg Lys Arg Thr Arg Thr Gly Arg Ser Trp Pro Ala Ala Ile Pro His Leu Arg Arg Arg Arg Gly Arg Leu Pro Arg Arg Ala Leu Gln Thr Gln Asn Ser Glu Ile Val Lys Asp Asp Glu Gly Lys Glu Asp Tyr Gln Phe Asp Glu Leu Asn Thr Glu Ile Leu Asn Asn Leu Ala Asp Gln Glu Leu Gln Leu Asn His Leu Lys Asn Ser Ile Thr Ser Tyr Phe Gly Ala Ala Gly Arg Ile Ala Cys Gly Glu Lys Tyr Arg Val Leu Ala Arg Arg Val Thr Leu Asp Gly Lys Val Gln Tyr Leu Val Glu Trp Glu Gly Ala Thr Ala Ser <210> 3 <211> 534 <212> PRT
<213> Homo Sapiens <220>

SUBSTITUTE SHEET (RULE 26) <221> misc-feature <223> Incyte ID No.: 116208CD1 <400> 3 Met Arg Ala Leu His Leu Leu Lys Ser Gly Cys Ser Pro Ala Val Gln Ile Lys Ile Arg Glu Leu Tyr Arg Arg Arg Tyr Pro Arg Thr Leu Glu Gly Leu Ser Asp Leu Ser Thr Ile Lys Ser Ser Val Phe Ser Leu Asp Gly Gly Ser Ser Pro Val Glu Pro Asp Leu Ala Val Ala Gly Ile His Ser Leu Pro Ser Thr Ser Val Thr Pro His Ser Pro Ser Ser Pro Val Gly Ser Val Leu Leu Gln Asp Thr Lys Pro Thr Phe Glu Met Gln Gln Pro Ser Pro Pro Ile Pro Pro Val His Pro Asp Val Gln Leu Lys Asn Leu Pro Phe Tyr Asp Val Leu Asp Val Leu Ile Lys Pro Thr Ser Leu Val Gln Ser Ser Ile Gln Arg Phe Gln Glu Lys Phe Phe Ile Phe Ala Leu Thr Pro Gln Gln Val Arg Glu Ile Cys Ile Ser Arg Asp Phe Leu Pro Gly Gly Arg Arg Asp Tyr Thr Val Gln Val Gln Leu Arg Leu Cys Leu Ala Glu Thr Ser Cys Pro Gln Glu Asp Asn Tyr Pro Asn Ser Leu Cys Ile Lys Val Asn Gly Lys Leu Phe Pro Leu Pro Gly Tyr Ala Pro Pro Pro Lys Asn Gly Ile Glu Gln Lys Arg Pro Gly Arg Pro Leu Asn Ile Thr Ser Leu Val Arg Leu Ser Ser Ala Val Pro Asn Gln Ile Ser Ile Ser Trp Ala Ser Glu I1e Gly Lys Asn Tyr Ser Met Ser Val Tyr Leu Val Arg Gln Leu Thr Ser Ala Met Leu Leu Gln Arg Leu Lys Met Lys Gly Ile Arg Asn Pro Asp His Ser Arg Ala Leu Ser Lys Glu Lys Leu Thr Ala Asp Pro Asp Ser Glu Ile Ala Thr Thr Ser Leu Arg Val Ser Leu Met Cys Pro Leu Gly Lys Met Arg Leu Thr Ile Pro Cys Arg Ala Val Thr Cys Thr His Leu Gln Cys Phe Asp Ala Ala Leu Tyr Leu Gln Met Asn Glu Lys Lys Pro Thr Trp Ile Cys Pro Val Cys Asp Lys Lys Ala Ala Tyr Glu Ser Leu Ile Leu Asp Gly Leu Phe Met Glu Ile Leu Asn Asp Cys Ser Asp Val Asp Glu Ile Lys Phe Gln Glu Asp Gly Ser Trp Cys Pro Met Arg Pro Lys Lys Glu Ala Met Lys Val Ser Ser Gln Pro Cys Thr Lys Ile Glu Ser Ser Ser Val Leu Ser Lys Pro Cys Ser Val Thr Val Ala Ser Glu Ala Ser Lys Lys Lys Val Asp Val Ile Asp Leu Thr SUBSTITUTE SHEET (RULE 26) Ile Glu Ser Ser Ser Asp Glu Glu Glu Asp Pro Pro Ala Lys Arg Lys Cys Ile Phe Met Ser Glu Thr Gln Ser Ser Pro Thr Lys Gly Val Leu Met Tyr Gln Pro Ser Ser Val Arg Val Pro Ser Val Thr Ser Val Asp Pro Ala Ala Ile Pro Pro Ser Leu Thr Asp Tyr Ser Val Pro Phe His His Thr Pro Ile Ser Ser Met Ser Ser Asp Leu Pro Gly Glu Gln Arg Arg Asn Asp Ile Asn Asn Glu Leu Lys Leu Gly Thr Ser Ser Asp Thr Val Gln Gln <210> 4 <211> 255 <212> PRT
<213> Homo Sapiens <220>
<221> misc feature <223> Incyte ID No.: 179261CD1 <400> 4 Met Lys Ile Ile Ser Glu Asn Val Pro Ser Tyr Lys Thr His Glu Ser Leu Thr Leu Pro Arg Arg 1'hr His Asp Ser Glu Lys Pro Tyr Glu Tyr Lys Glu Tyr Glu Lys Val Phe Ser Cys Asp Leu Glu Phe Asp Glu Tyr Gln Lys Ile His Thr Gly Gly Lys Asn Tyr Glu Cys Asn Gln Cys Trp Lys Thr Phe Gly Ile Asp Asn Ser Ser Met Leu Gln Leu Asn Ile His Thr Gly Val Lys Pro Cys Lys Tyr Met Glu Tyr Gly Asn Thr Cys Ser Phe Tyr Lys Asp Phe Asn Val Tyr Gln Lys Ile His Asn Glu Lys Phe Tyr Lys Cys Lys Glu Tyr Arg Arg Thr Phe Glu Arg Val Gly Lys Val Thr Pro Leu Gln Arg Val His Asp Gly Glu Lys His Phe Glu Cys Ser Phe Cys Gly Lys Ser Phe Arg Val His Ala Gln Leu Thr Arg His Gln Lys Ile His Thr Asp Glu Lys Thr Tyr Lys Cys Met Glu Cys Gly Lys Asp Phe Arg Phe His Ser Gln Leu Thr Glu His Gln Arg Ile His Thr Gly Glu Lys Pro Tyr Lys Cys Met His Cys Glu Lys Val Phe Arg Ile Ser Ser Gln Leu Ile Glu His Gln Arg Ile His Thr Gly Glu Lys Pro Tyr Ala Cys Lys Glu Cys Gly Lys Ala Phe Gly Val Cys Arg Glu Leu Ala Arg His Gln Arg Ile His Thr Gly Lys Tyr Cys Gly Trp Ile SUBSTITUTE SHEET (RULE 26) <210> 5 <211> 562 <212> PRT
<213> Homo sapiens <220>
<221> misc feature <223> Incyte ID No.: 259161CD1 <400> 5 Met Ala Ser Val Ser Ala Leu Thr Glu Glu Leu Asp Ser Ile Thr Ser Glu Leu His Ala Val Glu Ile Gln Ile Gln Glu Leu Thr Glu Arg Gln Gln Glu Leu Ile Gln Lys Lys Lys Val Leu Thr Lys Lys Ile Lys Gln Cys Leu Glu Asp Ser Asp Ala Gly Ala Ser Asn Glu Tyr Asp Ser Ser Pro Ala Ala Trp Asn Lys Glu Asp Phe Pro Trp Ser Gly Lys Val Lys Asp Ile Leu Gln Asn Val Phe Lys Leu Glu Lys Phe Arg Pro Leu Gln Leu Glu Thr Ile Asn Val Thr Met Ala Gly Lys Glu Val Phe Leu Val Met Pro Thr Gly Gly Gly Lys Ser Leu Cys Tyr Gln Leu Pro Ala Leu Cys Ser Asp Gly Phe Thr Leu Val Ile Cys Pro Leu Ile Ser Leu Met Glu Asp Gln Leu Met Val Leu Lys Gln Leu Gly Ile Ser Ala Thr Met Leu Asn Ala Ser Ser Ser Lys Glu His Val Lys Trp Val His Ala Glu Met Val Asn Lys Asn Ser Glu Leu Lys Leu Ile Tyr Val Thr Pro Glu Lys Ile Ala Lys Ser Lys Met Phe Met Ser Arg Leu Glu Lys Ala Tyr Glu Ala Arg Arg Phe Thr Arg Ile Ala Val Asp Glu Val His Cys Cys Ser Gln Trp Gly His Asp Phe Arg Pro Asp Tyr Lys Ala Leu Gly Ile Leu Lys Arg Gln Phe Pro Asn Ala Ser Leu Ile Gly Leu Thr Ala Thr Ala Thr Asn His Val Leu Thr Asp Ala Gln Lys Ile Leu Cys Ile Glu Lys Cys Phe Thr Phe Thr Ala Ser Phe Asn Lys Pro Asp Val Arg Phe Val Ile His His Ser Met Ser Lys Ser Met Glu Asn Tyr Tyr Gln Glu Ser Gly Arg Ala Gly Arg Asp Asp Met Lys Ala Asp Cys Ile Leu Tyr Tyr Gly Phe Gly Asp Ile Phe Arg Ile Ser Ser Met Val Val Met Glu Asn Val Gly Gln Gln Lys Leu Tyr Glu Met Val Ser Tyr Cys Gln Asn Ile Ser Lys Cys Arg Arg Val Leu Met Ala Gln His Phe Asp Glu Val Trp Asn Ser Glu Ala Cys Asn SUBSTITUTE SHEET (RULE 26) Lys Met Cys Asp Asn Cys Cys Lys Asp Ser Ala Phe Glu Arg Lys Asn Ile Thr Glu Tyr Cys Arg Asp Leu Ile Lys Ile Leu Lys Gln Ala Glu Glu Leu Asn Glu Lys Leu Thr Pro Leu Lys Leu Ile Asp Ser Trp Met Gly Lys Gly Ala Ala Lys Leu Arg Val Ala Gly Val Val Ala Pro Thr Leu Pro Arg Glu Asp Leu Glu Lys Ile Ile Ala His Phe Leu Ile Gln Gln Tyr Leu Lys Glu Asp Tyr Ser Phe Thr Ala Tyr Ala Thr Ile Ser Tyr Leu Lys Ile Gly Pro Lys Ala Asn Leu Leu Asn Asn Glu Ala His Ala Ile Thr Met Gln Val Thr Lys Ser Thr Gln Asn Ser Phe Arg Ala Glu Ser Ser Gln Thr Cys His Ser Glu Gln Gly Asp Lys Lys Ile Gly Gly Lys Lys Phe Gln Ala Thr Ser Arg Arg Arg Leu Gln Thr Cys Phe Ser Asn Leu Val Leu Arg Ile Gln Glu Leu Arg Lys Glu Lys Ser Met Met Pro Asp Met Thr Val Thr Lys Phe Ser Asn <210> 6 <211> 432 <212> PRT
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 320087CD1 <400> 6 Met Ser Glu Leu Lys Asp Cys Pro Leu Gln Phe His Asp Phe Lys Ser Val Asp His Leu Lys Val Cys Pro Arg Tyr Thr Ala Val Leu Ala Arg Ser Glu Asp Asp Gly Ile Gly Ile Glu Glu Leu Asp Thr Leu Gln Leu Glu Leu Glu Thr Leu Leu Ser Ser Ala Ser Arg Arg Leu Arg Val Leu Glu Ala Glu Thr Gln Ile Leu Thr Asp Trp Gln Asp Lys Lys Gly Asp Arg Arg Phe Leu Lys Leu Gly Arg Asp His Glu Leu Gly Ala Pro Pro Lys His Gly Lys Pro Lys Lys Gln Lys Leu Glu Gly Lys Ala Gly His Gly Pro Gly Pro Gly Pro Gly Arg Pro Lys Ser Lys Asn Leu Gln Pro Lys Ile Gln G1u Tyr Glu Phe Thr Asp Asp Pro Ile Asp Val Pro Arg Ile Pro Lys Asn Asp Ala SUBSTITUTE SHEET (RULE 26) Pro Asn Arg Phe Trp Ala Ser Val Glu Pro Tyr Cys Ala Asp Ile Thr Ser Glu Glu Val Arg Thr Leu Glu Glu Leu Leu Lys Pro Pro Glu Asp Glu Ala Glu His 'I'~~r Lys Ile Pro Pro Leu Gly Lys His Tyr Ser Gln Arg Trp Ala Gln Glu Asp Leu Leu Glu Glu Gln Lys Asp Gly Ala Arg Ala Ala Ala Val Ala Asp Lys Lys Lys Gly Leu Met Gly Pro Leu Thr Glu Leu Asp Thr Lys Asp Val Asp Ala Leu Leu Lys Lys Ser Glu Ala Gln His Glu Gln Pro Glu Asp Gly Cys Pro Phe Gly Ala Leu Thr Gln Arg Leu Leu Gln Ala Leu Val Glu Glu Asn Ile Ile Ser Pro Met Glu Asp Ser Pro Ile Pro Asp Met Ser Gly Lys Glu Ser Gly Ala Asp Gly Ala Ser Thr Ser Pro Arg Asn Gln Asn Lys Pro Phe Ser Val Pro His Thr Lys Ser Leu Glu Ser Arg Ile Lys Glu Glu Leu Ile Ala Gln Gly Leu Leu Glu Ser Glu Asp Arg Pro Ala Glu Asp Ser Glu Asp Glu Val Leu Ala Glu Leu Arg Lys Arg Gln Ala Glu Leu Lys Ala Leu Ser Ala His Asn Arg Thr Lys Lys His Asp Leu Leu Arg Leu Ala Lys Glu Glu Val Ser Arg Gln Glu Leu Arg Gln Arg Val Arg Met Ala Asp Asn Glu Val Met Asp Ala Phe Arg Lys Ile Met Ala Ala Arg Gln Lys Lys Arg Thr Pro Thr Lys Lys Glu Lys Asp Gln Ala Trp Lys Thr Leu Lys Glu Arg Glu Ser Ile Leu Lys Leu Leu Asp Gly <210> 7 <211> 799 <212> PRT
<213> Homo sapiens <220>
<221> misc-feature <223> 491271CD1 <400> 7 Met Pro Ser Gln Asn Tyr Asp Leu Pro Gln Lys Lys Gln Glu Lys Met Thr Lys Phe Gln Glu Ala Val Thr Phe Lys Asp Val Ala Val Val Phe Ser Arg Glu Glu Leu Arg Leu Leu Asp Leu Thr Gln Arg Lys Leu Tyr Arg Asp Val Met Val Glu Asn Phe Lys Asn Leu Val Ala Val Gly His Leu Pro Phe Gln Pro Asp biet Val Ser Gln Leu SUBSTITUTE SHEET (RULE 26) Glu Ala Glu Glu Lys Leu Trp Met Met Glu Thr Glu Thr Gln Arg Ser Ser Lys His Gln Asn Lys Met Glu Thr Leu Gln Lys Phe Ala Leu Lys 'I"yr Leu Ser Asn Gln Glu Leu Ser Cys Trp Gln Ile Trp Lys Gln Val Ala Ser Glu Leu Thr Arg Cys Leu Gln Gly Lys Ser Ser Gln Leu Leu Gln Gly Asp Ser Ile Gln Val Ser Glu Asn Glu Asn Asn Ile Met Asn Pro Lys Gly Asp Ser Pro Ile Tyr Ile Glu Asn Gln Glu Phe Pro Phe Trp Arg Thr Gln His Ser Cys Gly Asn Thr Tyr Leu ser Glu Ser Gln Ile Gln Ser Arg Gly Lys Gln Ile Asp Val Lys Asn Asn Leu Gln Ile Arg Glu Asp Phe Val Lys Lys Ser Pro Phe His Glu His Ile Lys Thr Asp Thr Glu Pro Lys Pro Cys Lys Gly Asn Glu Tyr Gly Lys Ile Ile Ser Asp Gly Ser Asn Gln Lys Leu Pro Leu Gly Glu Lys Pro His Pro Cys Gly Glu Cys Gly Arg Gly Phe Ser Tyr Ser Pro Arg Leu Pro Leu His Pro Asn Val His Thr Gly Glu Lys Cys Phe Ser Gln Ser Ser His Leu Arg Thr His Gln Arg Ile His Pro Gly Glu Lys Leu Asn Arg Cys His Glu Ser Gly Asp Cys Phe Asn Lys Ser Ser Phe His Ser Tyr Gln Ser Asn His Thr Gly Glu Lys Ser Tyr Arg Cys Asp Ser Cys Gly Lys Gly Phe Ser Ser Ser Thr Gly Leu Ile Ile His Tyr Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Glu Glu Cys Gly Lys Cys Phe Ser Gln Ser Ser Asn Phe Gln Cys His Gln Arg Val His Thr Glu Glu Lys Pro Tyr Lys Cys Glu Glu Cys Gly Lys Gly Phe Gly Trp Ser Val Asn Leu Arg Val His Gln Arg Val His Arg Gly Glu Lys Pro Tyr Lys Cys Glu Glu Cys Gly Lys Gly Phe Thr Gln Ala Ala His Phe His Ile His G1n Arg Val His Thr Gly Glu Lys Pro Tyr Lys Cys Asp Val Cys Gly Lys Gly Phe Ser His Asn Ser Pro Leu Ile Cys His Arg Arg Val His Thr Gly Glu Lys Pro Tyr Lys Cys Glu Ala Cys Gly Lys Gly Phe Thr Arg Asn Thr Asp Leu His Ile His Phe Arg Val His Thr Gly Glu Lys Pro Tyr Lys Cys Lys Glu Cys Gly Lys Gly Phe Ser Gln Ala Ser Asn Leu Gln Val His Gln Asn Val His Thr Gly Glu Lys Arg Phe Lys Cys Glu Thr Cys Gly Lys Gly Phe Ser Gln Ser Ser Lys Leu Gln Thr His Gln Arg SUBSTITUTE SHEET (RULE 26) Val His Thr Gly Glu Lys Pro Tyr Arg Cys Asp Val Cys Gly Lys Asp Phe Ser Tyr Ser Ser Asn Leu Lys Leu His Gln Val Ile His Thr Gly Glu Lys Pro Tyr Lys Cys Glu Glu Cys Gly Lys Gly Phe Ser Trp Arg Ser Asn Leu His Ala His Gln Arg Val His Ser Gly Glu Lys Pro Tyr Lys Cys Glu Gln Cys Asp Lys Ser Phe Ser Gln Ala Ile Asp Phe Arg Val His Gln Arg Val His Thr G1y Glu Lys Pro Tyr Lys Cys Gly Val Cys Gly Lys Gly Phe Ser Gln Ser Ser Gly Leu Gln Ser His Gln Arg Val His Thr Gly Glu Lys Pro Tyr Lys Cys Asp Val Cys Gly Lys Gly Phe Arg Tyr Ser Ser Gln Phe Ile Tyr His Gln Arg Gly His Thr Gly Glu Lys Pro Tyr Lys Cys Glu Glu Cys Gly Lys Gly Phe Gly Arg Ser Leu Asn Leu Arg His His Gln Arg Val His Thr Gly Glu Lys Pro His Ile Cys Glu Glu Cys Gly Lys Ala Phe Ser Leu Pro Ser Asn Leu Arg Val His Leu Gly Val His Thr Arg Glu Lys Leu Phe Lys Cys Glu Glu Cys Gly Lys Gly Phe Ser Gln Ser Ala Arg Leu Glu Ala His Gln Arg Val 755 760 '765 His Thr Gly Glu Lys Pro Tyr Lys Cys Asp Ile Cys Asp Lys Asp Phe Arg His Arg Ser Arg Leu Thr Tyr His Gln Lys Val His Thr Gly Lys Lys Leu <210> 8 <211> 137 <212> PRT
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 585172CD1 <400> 8 Met Leu Ser Gly Arg Leu Val Leu Gly Leu Val Ser Met Ala Gly Arg Val Cys Leu Cys Gln Gly Ser Ala Gly Ser Gly Ala Ile Gly Pro Val Glu Ala Ala Ile Arg Thr Lys Leu Glu Glu Ala Leu Ser Pro Glu Val Leu Glu Leu Arg Asn Glu Ser Gly Gly His Ala Val Pro Pro Gly Ser Glu Thr His Phe Arg Va1 Ala Val Val Ser Ser Arg Phe Glu Gly Leu Ser Pro Leu Gln Arg His Arg Leu Val His SUBSTITUTE SHEET (RULE 26) Ala Ala Leu Ala Glu Glu Leu Gly Gly Pro Val His Ala Leu Ala Ile Gln Ala Arg Thr Pro Ala Gln Trp Arg Glu Asn Ser Gln Leu Asp Thr Ser Pro Pro Cys Leu Gly Gly Asn Lys Lys Thr Leu Gly Thr Pro <210> 9 <211> 230 <212> PRT
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 615200CD1 <400> 9 Met Val Gly Ala Gly Ile Ser Thr Pro Ser Gly Ile Pro Asp Phe Arg Ser Pro Gly Ser Gly Leu Tyr Ser Asn Leu Gln Gln Tyr Asp Leu Pro Tyr Pro Glu Ala Ile Phe Glu Leu Pro Phe Phe Phe His Asn Pro Lys Pro Phe Phe Thr Leu Ala Lys Glu Leu Tyr Pro Gly Asn Tyr Lys Pro Asn Ile Thr His Tyr Phe Leu Arg Leu Leu His Asp Lys Gly Leu Leu Leu Arg Leu Tyr Thr Gln Asn Ile Asp Gly Leu Glu Arg Val Ser Gly Ile Pro Ala Ser Lys Leu Val Glu Ala His Gly Thr Phe Ala Ser Ala Thr Cys Thr Val Cys Gln Arg Pro Phe Pro Gly Glu Asp Ile Arg Ala Asp Val Met Ala Asp Arg Val Pro Arg Cys Pro Val Cys Thr Gly Val Val Lys Pro Asp Ile Val Phe Phe Gly Glu Pro Leu Pro Gln Arg Phe Leu Leu His Val Val Asp Phe Pro Met Ala Asp Leu Leu Leu Ile Leu Gly Thr Ser Leu Glu Val Glu Pro Phe Ala Ser Leu Thr Glu Ala Val Arg Thr Gln Phe Pro Asp Cys Ser Ser Thr Gly Thr Trp Trp Gly Pro Trp Leu Gly Ile Leu Ala Ala Gly Thr Trp Pro Ser Trp Gly Thr Trp Phe Thr Ala Trp Lys Ala <210> 10 <211> 446 <212> PRT
<213> Homo sapiens SUBSTITUTE SHEET (RULE 26) <220>
<221> misc-feature <223> Incyte ID No.: 997067CD1 <400> 10 Met Glu Thr Gln Ala Asp Leu Val Ser Gln Glu Pro Gln Ala Leu Leu Asp Ser Ala Leu Pro Ser Lys Val Pro Ala Phe Ser Asp Lys Asp Ser Leu Gly Asp Glu Met Leu Ala Ala Ala Leu Leu Lys Ala Lys 5er Gln Glu Leu Val Thr Phe Glu Asp Val Ala Val Tyr Phe Ile Arg Lys Glu Trp Lys Arg Leu Glu Pro Ala Gln Arg Asp Leu Tyr Arg Asp Val Met Leu Glu Asn Tyr Gly Asn Val Phe Ser Leu Asp Arg Glu Thr Arg Thr Glu Asn Asp Gln Glu Ile Ser Glu Asp Thr Arg Ser His Gly Val Leu Leu Gly Arg Phe Gln Lys Asp Ile Ser Gln Gly Leu Lys Phe Lys Glu Ala Tyr Glu Arg Glu Val Ser Leu Lys Arg Pro Leu Gly Asn Ser Pro Gly Glu Arg Leu Asn Arg Lys Met Pro Asp Phe Gly Gln Val Thr Val Glu Glu Lys Leu Thr Pro Arg Gly Glu Arg Ser Glu Lys Tyr Asn Asp Phe Gly Asn Ser Phe Thr Val Asn Ser Asn Leu Ile Ser His Gln Arg Leu Pro Val Gly Asp Arg Pro His Lys Cys Asp Glu Cys Ser Lys Ser Phe Asn Arg Thr Ser Asp Leu Ile Gln His Gln Arg Ile His Thr Gly Glu Lys Pro Tyr Glu Cys Asn Glu Cys Gly Lys Ala Phe Ser Gln Ser Ser His Leu Ile Gln His Gln Arg Ile His Thr Gly Glu Lys Pro Tyr Glu Cys Ser Asp Cys Gly Lys Thr Phe Ser Cys Ser Ser Ala Leu Ile Leu His Arg Arg Ile His Thr Gly Glu Lys Pro Tyr Glu Cys Asn Glu Cys Gly Lys Thr Phe Ser Trp Ser Ser Thr Leu Thr His His Gln Arg Ile His Thr Gly Glu Lys Pro Tyr Ala Cys Asn Glu Cys Gly Lys Ala Phe Ser Arg Ser Ser Thr Leu Ile His His Gln Arg Ile His Thr Gly Glu Lys Pro Tyr Glu Cys Asn Glu Cys Gly Lys Ala Phe Ser Gln Ser Ser His Leu Tyr Gln His Gln Arg Ile His Thr Gly Glu Lys Pro Tyr Glu Cys Met Glu Cys Gly Gly Lys Phe Thr Tyr Ser Ser Gly Leu Ile Gln His Gln Arg Ile His Thr Gly Glu Asn Pro Tyr Glu Cys Ser Glu Cys Gly Lys Ala Phe Arg Tyr Ser Ser Ala Leu Val Arg His Gln Arg Ile His Thr Gly Glu Lys Pro Leu Asn Gly Ile Gly Met Ser Lys Ser Ser Leu Arg SUBSTITUTE SHEET (RULE 26) Val Thr Thr Glu Leu Asn Ile Arg Glu Ser Thr <210> 11 <211> 428 <212> PRT
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID NO.: 1443262CD1 <400> 11 Met Glu Pro Leu Lys Val Glu Lys Phe Ala Thr Ala Asn Arg Gly Asn Gly Leu Arg Ala Val Thr Pro Leu Arg Pro Gly Glu Leu Leu Phe Arg Ser Asp Pro Leu Ala Tyr Thr Val Cys Lys Gly Ser Arg Gly Val Val Cys Asp Arg Cys Leu Leu Gly Lys Glu Lys Leu Met Arg Cys Ser Gln Cys Arg Val Ala Lys Tyr Cys Ser Ala Lys Cys Gln Lys Lys Ala Trp Pro Asp His Lys Arg Glu Cys Lys Cys Leu Lys Ser Cys Lys Pro Arg Tyr Pro Pro Asp Ser Val Arg Leu Leu Gly Arg Val Val Phe Lys Leu Met Asp Gly Ala Pro Ser Glu Ser Glu Lys Leu Tyr Ser Phe Tyr Asp Leu Glu Ser Asn Ile Asn Lys Leu Thr Glu Asp Lys Lys Glu Gly Leu Arg Gln Leu Val Met Thr Phe Gln His Phe Met Arg Glu Glu Ile Gln Asp Ala Ser Gln Leu Pro Pro Ala Phe Asp Leu Phe Glu Ala Phe Ala Lys Val Ile Cys Asn Ser Phe Thr Ile Cys Asn Ala Glu Met Gln Glu Val Gly Val Gly Leu Tyr Pro Ser Ile Ser Leu Leu Asn His Ser Cys Asp Pro Asn Cys Ser Ile Val Phe Asn Gly Pro His Leu Leu Leu Arg Ala Val Arg Asp Ile Glu Val Gly Glu Glu Leu Thr Ile Cys Tyr Leu Asp Met Leu Met Thr Ser Glu Glu Arg Arg Lys Gln Leu Arg Asp Gln Tyr Cys Phe Glu Cys Asp Cys Phe Arg Cys Gln Thr Gln Asp Lys Asp Ala Asp Met Leu Thr Gly Asp Glu Gln Val Trp Lys Glu Val Gln Glu Ser Leu Lys Lys Ile Glu Glu Leu Lys Ala His Trp Lys Trp Glu Gln Val Leu Ala Met Cys Gln Ala Ile Ile Ser Ser Asn Ser Glu Arg Leu Pro Asp Ile Asn Ile Tyr Gln Leu Lys Val SUBSTITUTE SHEET (RULE 26) Leu Asp Cys Ala Met Asp Ala Cys Ile Asn Leu Gly Leu Leu Glu Glu Ala Leu Phe Tyr Gly Thr Arg Thr Met Glu Pro Tyr Arg Ile Phe Phe Pro Gly Ser His Pro Val Arg Gly Val Gln Val Met Lys Val Gly Lys Leu Gln Leu His Gln Gly Met Phe Pro Gln Ala Met Lys Asn Leu Arg Leu Ala Phe Asp Ile Met Arg Val Thr His Gly Arg Glu His Ser Leu Ile Glu Asp Leu Ile Leu Leu Leu Glu Glu Cys Asp Ala Asn Ile Arg Ala Ser <210> 12 <211> 590 <212> PRT
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 1521648CD1 <400> 12 Met Ala Glu Asp Trp Leu Asp Cys Pro Ala Leu Gly Pro Gly Trp Lys Arg Arg Glu Val Phe Arg Lys Ser Gly Ala Thr Cys Gly Arg Ser Asp Thr Tyr Tyr Gln Ser Pro Thr Gly Asp Arg Ile Arg Ser Lys Val Glu Leu Thr Arg Tyr Leu Gly Pro Ala Cys Asp Leu Thr Leu Phe Asp Phe Lys Gln Gly Ile Leu Cys Tyr Pro Ala Pro Lys Ala His Pro Val Ala Val Ala Ser Lys Lys Arg Lys Lys Pro Ser Arg Pro Ala Lys Thr Arg Lys Arg Gln Val Gly Pro Gln Ser Gly Glu Val Arg Lys Glu Ala Pro Arg Asp Glu Thr Lys Ala Asp Thr Asp Thr Ala Pro Ala Ser Phe Pro Ala Pro Gly Cys Cys Glu Asn Cys Gly Ile Ser Phe Ser Gly Asp Gly Thr Gln Arg Gln Arg Leu Lys Thr Leu Cys Lys Asp Cys Arg Ala Gln Arg Ile Ala Phe Asn Arg Glu Gln Arg Met Phe Lys Arg Val Gly Cys Gly Glu Cys Ala Ala Cys Gln Val Thr Glu Asp Cys Gly Ala Cys Ser Thr Cys Leu Leu Gln Leu Pro His Asp Val Ala Ser Gly Leu Phe Cys Lys Cys Glu Arg Arg Arg Cys Leu Arg Ile Val Glu Arg Ser Arg Gly Cys Gly Val Cys Arg Gly Cys Gln Thr Gln Glu Asp Cys Gly His Cys Pro Ile Cys Leu Arg Pro Pro Arg Pro Gly Leu Arg Arg Gln Trp SUBSTITUTE SHEET (RULE 26) Lys Cys Val Gln Arg Arg Cys Leu Arg Gly Lys His Ala Arg Arg Lys Gly Gly Cys Asp Ser Lys Met Ala Ala Arg Arg Arg Pro Gly Ala Gln Pro Leu Pro Pro Pro Pro Pro Ser Gln Ser Pro Glu Pro Thr Glu Pro His Pro Arg Ala Leu Ala Pro Ser Pro Pro Ala Glu Phe Ile Tyr Tyr Cys Val Asp Glu Asp Glu Leu Gln Pro Tyr Thr Asn Arg Arg Gln Asn Arg Lys Cys Gly Ala Cys Ala Ala Cys Leu Arg Arg Met Asp Cys Gly Arg Cys Asp Phe Cys Cys Asp Lys Pro Lys Phe Gly Gly Ser Asn Gln Lys Arg Gln Lys Cys Arg Trp Arg Gln Cys Leu Gln Phe Ala Met Lys Arg Leu Leu Pro Ser Val Trp Ser Glu Ser Glu Asp Gly Ala Gly Ser Pro Pro Pro Tyr Arg Arg Arg Lys Arg Pro Ser Ser Ala Arg Arg His His Leu Gly Pro Thr Leu Lys Pro Thr Leu Ala Thr Arg Thr Ala Gln Pro Asp His Thr Gln Ala Pro Thr Lys Gln Glu Ala Gly Gly Gly Phe Val Leu Pro Pro Pro Gly Thr Asp Leu Val Phe Leu Arg Glu Gly Ala Ser Ser Pro Val Gln Val Pro Gly Pro Val Ala Ala Ser Thr Glu Ala Leu Leu Gln Val Lys Gln Glu Lys Ala Asp Thr Gln Asp Glu Trp Thr Pro Gly Thr Ala Val Leu Thr Ser Pro Val Leu Val Pro Gly Cys Pro Ser Lys Ala Val Asp Pro Gly Leu Pro Ser Val Lys Gln Glu Pro Pro Asp Pro Glu Glu Asp Lys Glu Glu Asn Lys Asp Asp Ser Ala Ser Lys Leu Ala Pro Glu Glu Glu Ala Gly Gly Ala Gly Thr Pro Val Ile Thr Glu Ile Phe Ser Leu Gly Gly Thr Arg Phe Arg Asp Thr Ala Val Trp Leu Pro Arg Ser Lys Asp Leu Lys Lys Pro Gly Ala Arg Lys Gln <210> 13 <211> 479 <212> PRT
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 1685494CD1 <400> 13 Met Ala Thr Ala Leu Val Ser Ala His Ser Leu Ala Pro Leu Ser SUBSTITUTE SHEET (RULE 26) Leu Lys Lys Glu Gly Leu Arg Val Val Arg Glu Asp His Tyr Ser Thr Trp Glu Gln Gly Phe Lys Leu Gln Gly Asn Ser Lys Gly Leu Gly Gln Glu Pro Leu Cys Lys Gln Phe Arg Gln Leu Arg Tyr Glu Glu Thr Thr Gly Pro Arg Glu Ala Leu Ser Arg Leu Arg Glu Leu Cys Gln Gln Trp Leu Gln Pro Glu Thr His Thr Lys Glu Gln Ile Leu Glu Leu Leu Val Leu Glu Gln Phe Leu Ile Ile Leu Pro Lys Glu Leu Gln Ala Arg Val Gln Glu His His Pro Glu Ser Arg Glu Asp Val Val Val Val Leu Glu Asp Leu Gln Leu Asp Leu Gly Glu Thr Gly Gln Gln Val Asp Pro Asp Gln Pro Lys Lys Gln Lys Ile Leu Val Glu Glu Met Ala Pro Leu Lys Gly Val Gln Glu Gln Gln Val Arg His Glu Cys Glu Val Thr Lys Pro Glu Lys Glu Lys Gly Glu Glu Thr Arg Ile Glu Asn Gly Lys Leu Ile Val Val Thr Asp Ser Cys Gly Arg Val Glu Ser Ser Gly Lys Ile Ser Glu Pro Met Glu Ala His Asn Glu Gly Ser Asn Leu Glu Arg His Gln Ala Lys Pro Lys Glu Lys Ile Glu Tyr Lys Cys Ser Glu Arg Glu Gln Arg Phe Ile Gln His Leu Asp Leu Ile Glu His Ala Ser Thr His Thr Gly Lys Lys Leu Cys Glu Ser Asp Val Cys Gln Ser Ser Ser Leu Thr Gly His Lys Lys Val Leu Ser Arg Glu Lys Gly His Gln Cys His Glu Cys Gly Lys Ala Phe Gln Arg Ser Ser His Leu Val Arg His Gln Lys Ile His Leu Gly Glu Lys Pro Tyr Gln Cys Asn Glu Cys Gly Lys Val Phe Ser Gln Asn Ala Gly Leu Leu Glu His Leu Arg Ile His Thr Gly Glu Lys Pro Tyr Leu Cys Ile His Cys Gly Lys Asn Phe Arg Arg Ser Ser His Leu Asn Arg His Gln Arg Ile His Ser Gln Glu Glu Pro Cys Glu Cys Lys Glu Cys Gly Lys Thr Phe Ser Gln Ala Leu Leu Leu Thr His His Gln Arg Ile His Ser His Ser Lys Ser His Gln Cys Asn Glu Cys Gly Lys Ala Phe Ser Leu Thr Ser Asp Leu Ile Arg His His Arg Ile His Thr Gly Glu Lys Pro Phe Lys Cys Asn Ile Cys Gln Lys Ala Phe Arg Leu Asn Ser His Leu Ala Gln His Val Arg Ile His Asn Glu Glu Lys Pro Tyr Gln Cys Ser Glu Cys Gly Glu Ala Phe Arg Gln Arg Ser Gly Leu Phe Gln His Gln Arg Tyr His His Lys Asp Lys Leu Ala SUBSTITUTE SHEET (RULE 26) <210> 14 <211> 433 <212> PRT
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 1730829CD1 <400> 14 Met Glu Ala Val Tyr Leu Val Val Asn Gly Leu Gly Leu Val Leu Asp Val Leu Thr Leu Val Leu Asp Leu Asn Phe Leu Leu Val Ser Ser Leu Leu Ala Ser Leu Ala Trp Leu Leu Ala Phe Val Tyr Asn Leu Pro His Thr Val Leu Thr Ser Leu Leu His Leu Gly Arg Gly Val Leu Leu Ser Leu Leu Ala Leu Ile Glu Ala Val Val Arg Phe Thr Cys Gly Gly Leu Gln Ala Leu Cys Thr Leu Leu Tyr Ser Cys Cys Ser Gly Leu Glu Ser Leu Lys Leu Leu Gly His Leu Ala Ser His Gly Ala Leu Arg Ser Arg Glu Ile Leu His Arg Gly Val Leu Asn Val Val Ser Ser Gly His Ala Leu Leu Arg Gln Ala Cys Asp Ile Cys Ala Ile Ala Met Ser Leu Val Ala Tyr Val Ile Asn 5er Leu Val Asn Ile Cys Leu Ile Gly Thr Gln Asn Leu Phe Ser Leu Val Leu Ala Leu Trp Asp Ala Val Thr Gly Pro Leu Trp Arg Met Thr Asp Val Val Ala Ala Phe Leu Ala His Ile Ser Ser Ser Ala Val Ala Met Ala Ile Leu Leu Trp Thr Pro Cys Gln Leu Ala Leu Glu Leu Leu Ala Ser Ala Ala Arg Leu Leu Ala Ser Phe Val Leu Val Asn Leu Thr Gly Leu Val Leu Leu Ala Cys Val Leu Ala Val Thr Val Thr Val Leu His Pro Asp Phe Thr Leu Arg Leu Ala Thr Gln Ala Leu Ser Gln Leu His Ala Arg Pro Ser Tyr His Arg Leu Arg Glu Asp Val Met Arg Leu Ser Arg Leu Ala Leu Gly Ser Glu Ala Trp Arg Arg Val Trp Ser Arg Ser Leu Gln Leu Ala Ser Trp Pro Asn Arg Gly Gly Ala Pro Gly Ala Pro Gln Gly Asp Pro Met Arg Val Phe Ser Val Arg Thr Arg Arg Gln Asp Thr Leu Pro Glu Ala Gly Arg Arg Ser Glu Ala Glu Glu Glu Glu Ala Arg Thr Ile Arg Val Thr Pro Val Arg Gly Arg Glu Arg Leu Asn Glu Glu Glu SUBSTITUTE SHEET (RULE 26) Pro Pro Gly Gly Gln Asp Pro Trp Lys Leu Leu Lys Glu Gln Glu Glu Arg Lys Lys Cys Val Ile Cys Gln Asp Gln Ser Lys Thr Val Leu Leu Leu Pro Cys Arg His Leu Cys Leu Cys Gln Ala Cys Thr Glu Ile Leu Met Arg His Pro Val Tyr His Arg Asn Cys Pro Leu Cys Arg Arg Gly Ile Leu Gln Thr Leu Asn Val Tyr Leu <210> 15 <211> 320 <212> PRT
<213> Homo sapiens <220>
<221> misc feature <223> Incyte ID No.: 1864641CD1 <400> 15 Met Pro Lys Lys Lys Thr Gly Ala Arg Lys Lys Ala Glu Asn Arg Arg Glu Arg Glu Lys Gln Leu Arg Ala Ser Arg Ser Thr Ile Asp Leu Ala Lys His Pro Cys Asn Ala Ser Met Glu Cys Asp Lys Cys Gln Arg Arg Gln Lys Asn Arg Ala Phe Cys Tyr Phe Cys Asn Ser Val Gln Lys Leu Pro Ile Cys Ala Gln Cys Gly Lys Thr Lys Cys Met Met Lys Ser Ser Asp Cys Val Ile Lys His Ala Gly Val Tyr Ser Thr Gly Leu Ala Met Val Gly Ala Ile Cys Asp Phe Cys Glu Ala Trp Val Cys His Gly Arg Lys Cys Leu Ser Thr His Ala Cys Ala Cys Pro Leu Thr Asp Ala Glu Cys Val Glu Cys Glu Arg Gly Val Trp Asp His Gly Gly Arg Ile Phe Ser Cys Ser Phe Cys His Asn Phe Leu Cys Glu Asp Asp Gln Phe Glu His Gln Ala Ser Cys Gln Val Leu Glu Ala Glu Thr Phe Lys Cys Val Ser Cys Asn Arg Leu Gly Gln His Ser Cys Leu Arg Cys Lys Ala Cys Phe Cys Asp Asp His Thr Arg Ser Lys Val Phe Lys Gln Glu Lys Gly Lys Gln Pro Pro Cys Pro Lys Cys Gly His Glu Thr Gln Glu Thr Lys Asp Leu Ser Met Ser Thr Arg Ser Leu Lys Phe Gly Arg Gln Thr Gly Gly Glu Glu Gly Asp Gly Ala Ser Gly Tyr Asp Ala Tyr Trp Lys Asn Leu Ser Ser Asp Lys Tyr Gly Asp Thr Ser Tyr His Asp Glu Glu Glu Asp Glu Tyr Glu Ala Glu Asp Asp Glu Glu Glu Glu Asp SUBSTITUTE SHEET (RULE 26) Glu Gly Arg Lys Asp Ser Asp Thr Glu Ser Ser Asp Leu Phe Thr Asn Leu Asn Leu Gly Arg Thr T~,rr Ala Ser Gly Tyr Ala His Tyr Glu Glu Gln Glu Asn <210> 16 <211> 179 <212> PRT
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2444604CD1 <400> 16 Met Ala Ala Gly Phe Phe Gln Pro Phe Met Ser Pro Arg Phe Pro Gly Gly Pro Arg Pro Thr Leu Arg Met Pro Ser Gln Pro Pro Ala Cys Leu Pro Gly Ser Gln Pro Leu Leu Pro Gly Ala Met Glu Pro Ser Pro Arg Ala Gln Gly His Pro Ser Met Gly Gly Pro Met Gln Arg Va.l Thr Pro Pro Arg Gly Met Ala Ser Val Gly Pro Gln Ser Tyr Gly Gly Gly Met Arg Pro Pro Pro Asn Ser Leu Ala Gly Pro Gly Leu Pro Ala Met Asn Met Gly Pro Gly Val Arg Gly Pro Trp Ala Ser Pro Ser Gly Asn Ser Ile Pro Tyr Ser Ser Ser Ser Pro Gly Ser Tyr Thr Gly Pro Pro Gly Gly Gly Gly Pro Pro Gly Thr Pro Ile Met Pro Ser Pro Gly Asp Ser Thr Asn Ser Ser Glu Asn Met Tyr Thr Ile Met Asn Pro Ile Gly Gln Gly Ala Gly Arg Ala Asn Phe Pro Leu Gly Pro Gly Pro Glu Gly Pro Trp Pro Pro <210> 17 <211> 494 <212> PRT
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2445008CD1 <400> 17 Met Gly Arg Lys Lys Lys Lys Gln Leu Lys Pro Trp Cys Trp Tyr Cys Asn Arg Asp Phe Asp Asp Glu Lys Ile Leu Ile Gln His Gln SUBSTITUTE SHEET (RULE 26) Lys Ala Lys His Phe Lys Cys His Ile Cys His Lys Lys Leu Tyr Thr Gly Pro Gly Leu Ala Ile His Cys Met Gln Val His Lys Glu Thr Ile Asp Ala Val Pro Asn Ala Ile Pro Gly Arg Thr Asp Ile Glu Leu Glu Ile Tyr Gly Met Glu Gly Ile Pro Glu Lys Asp Met Asp Glu Arg Arg Arg Leu Leu Glu Gln Lys Thr Gln Glu Ser Gln Lys Lys Lys Gln Gln Asp Asp Ser Asp Glu Tyr Asp Asp Asp Asp Ser Ala Ala Ser Thr Ser Phe Gln Pro Gln Pro Val Gln Pro Gln Gln Gly Tyr Ile Pro Pro Met Ala Gln Pro Gly Leu Pro Pro Val Pro Gly Ala Pro Gly Met Pro Pro Gly Ile Pro Pro Leu Met Pro Gly Val Pro Pro Leu Met Pro Gly Met Pro Pro Val Met Pro Gly Met Pro Pro Gly Leu His His Gln Arg Lys Tyr Thr Gln Ser Phe Cys Gly Glu Asn Ile Met Met Pro Met Gly Gly Met Met Pro Pro Gly Pro Gly Ile Pro Pro Leu Met Pro Gly Met Pro Pro Gly Met Pro Pro Pro Val Pro Arg Pro Gly Ile Pro Pro Met Thr Gln Ala Gln Ala Val Ser Ala Pro Gly Ile Leu Asn Arg Pro Pro Ala Pro Thr Ala Thr Val Pro Ala Pro Gln Pro Pro Val Thr Lys Pro Leu Phe Pro Ser Ala Gly Gln Met Gly Thr Pro Val Thr Ser Ser Ser Thr Ala Ser Ser Asn Ser Glu Ser Leu Ser Ala Ser Ser Lys Ala Leu Phe Pro Ser Thr Ala Gln Ala Gln Ala Ala Val Gln Gly Pro Val Gly Thr Asp Phe Lys Pro Leu Asn Ser Thr Pro Ala Thr Thr Thr Glu Pro Pro Lys Pro Thr Phe Pro Ala Tyr Thr Gln Ser Thr Ala Ser Thr Thr Ser Thr Thr Asn Ser Thr Ala Ala Lys Pro Ala Ala Ser Ile Thr Ser Lys Pro Ala Thr Leu Thr Thr Thr Ser Ala Thr Ser Lys Leu Ile His Pro Asp Glu Asp Ile Ser Leu Glu Glu Arg Arg Ala Gln Leu Pro Lys Tyr Gln Arg Asn Leu Pro Arg Pro Gly Gln Ala Pro Ile Gly Asn Pro Pro Val Gly Pro Ile Gly Gly Met Met Pro Pro Gln Pro Gly Ile Pro Gln Gln Gln Gly Met Arg Pro Pro Met Pro Pro His Gly Gln Tyr Gly Gly His His Gln Gly Met Pro Gly Tyr Leu Pro Gly Ala Met Pro Pro Tyr Gly Gln Gly Pro Pro Met Val Pro Pro ~'~r Gln Gly Gly Pro Pro Arg Pro Pro SUBSTITUTE SHEET (RULE 26) Met Gly Met Arg Pro Pro Val Met Ser Gln Gly Gly Arg Tyr <210> 18 <211> 401 <212> PRT
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2572462CD1 <400> 18 Met Ala Ser Ser Pro Arg Pro Lys Met Asp Ala Ile Leu Thr Glu Ala Ile Lys Ala Cys Phe Gln Lys Ser Gly Ala Ser Val Val Ala Ile Arg Lys Tyr Ile Ile His Lys Tyr Pro Ser Leu Glu Leu Glu Arg Arg Gly Tyr Leu Leu Lys Gln Ala Leu Lys Arg Glu Leu Asn Arg Gly Val Ile Lys Gln Val Lys Gly Lys Gly Ala Ser Gly Ser Phe Val Val Val Gln Lys Ser Arg Lys Thr Pro Gln Lys Ser Arg Asn Arg Lys Asn Arg Ser Ser Ala Val Asp Pro Glu Pro Gln Val Lys Leu Glu Asp Val Leu Pro Leu Ala Phe Thr Arg Leu Cys Glu Pro Lys Glu Ala Ser Tyr Ser Leu Ile Arg Lys Tyr Val Ser Gln Tyr Tyr Pro Lys Leu Arg Val Asp Ile Arg Pro Gln Leu Leu Lys Asn Ala Leu Gln Arg Ala Val Glu Arg Gly Gln Leu Glu Gln Ile Thr Gly Lys Gly Ala Ser Gly Thr Phe Gln Leu Lys Lys Ser Gly Glu Lys Pro Leu Leu Gly Gly Ser Leu Met Glu Tyr Ala Ile Leu Ser Ala Ile Ala Ala Met Asn Glu Pro Lys Thr Cys Ser Thr Thr Ala Leu Lys Lys Tyr Val Leu Glu Asn His Pro Gly Thr Asn Ser Asn Tyr Gln Met His Leu Leu Lys Lys Thr Leu Gln Lys Cys Glu Lys Asn Gly Trp Met Glu Gln Ile Ser Gly Lys Gly Phe Ser Gly Thr Phe Gln Leu Cys Phe Pro Tyr Tyr Pro Ser Pro Gly Val Leu Phe Pro Lys Lys Glu Pro Asp Asp Ser Arg Asp Glu Asp Glu Asp Glu Asp Glu Ser Ser Glu Glu Asp Ser Glu Asp Glu Glu Pro Pro Pro Lys Arg Arg Leu Gln Lys Lys Thr Pro Ala Lys Ser Pro Gly Lys Ala Ala Ser Val Lys G1n Arg Gly Ser Lys Pro Ala Pro Lys Val Ser Ala Ala Gln Arg Gly Lys Ala Arg Pro Leu Pro Lys Lys SUBSTITUTE SHEET (RULE 26) Ala Pro Pro Lys Ala Lys Thr Pro Ala Lys Lys Thr Arg Pro Ser Ser Thr Val Ile Lys Lys Pro Ser Gly Gly Ser Ser Lys Lys Pro Ala Thr Ser Ala Arg Lys Glu Va1 Lys Leu Pro Gly Lys Gly Lys Ser Thr Met Lys Lys Ser Phe Arg Val Lys Lys <210> 19 <211> 264 <212> PRT
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2572892CD1 <400> 19 Met Pro Arg Ser Phe Leu Val Arg Lys Pro Ser Asp Pro Asn Arg Lys Pro Asn Tyr Ser Glu Leu Gln Asp Ser Asn Pro Glu Phe Thr Phe Gln Gln Pro Tyr Asp Gln Ala His Leu Leu Ala Ala Ile Pro Pro Pro Glu Ile Leu Asn Pro Thr Ala Ser Leu Pro Met Leu Ile Trp Asp Ser Val Leu Ala Pro Gln Ala Gln Pro Ile Ala Trp Ala Ser Leu Arg Leu Gln Glu Ser Pro Arg Val Ala Glu Leu Thr Ser Leu Ser Asp Glu Asp Ser Gly Lys Gly Ser Gln Pro Pro Ser Pro Pro Ser Pro Ala Pro Ser Ser Phe Ser Ser Thr Ser Ala Ser Ser Leu Glu Ala Glu Ala Tyr Ala Ala Phe Pro Gly Leu Gly Gln Val Pro Lys Gln Leu Ala Gln Leu Ser Glu Ala Lys Asp Leu Gln Ala Arg Lys Ala Phe Asn Cys Lys Tyr Cys Asn Lys Glu Tyr Leu Ser Leu Gly Ala Leu Lys Met His Ile Arg Ser His Thr Leu Pro Cys Val Cys Gly Thr Cys Gly Lys Ala Phe Ser Arg Pro Trp Leu Leu Gln Gly His Val Arg Thr His Thr Gly Glu Lys Pro Phe Ser Cys Pro His Cys Ser Arg Ala Phe Ala Asp Arg Ser Asn Leu Arg Ala His Leu Gln Thr His Ser Asp Val Lys Lys Tyr Gln Cys Gln Ala Cys Ala Arg Thr Phe Ser Arg Met Ser Leu Leu His Lys His Gln Glu Ser Gly Cys Ser Gly Cys Pro Arg SUBSTITUTE SHEET (RULE 26) <210> 20 <211> 153 <212> PRT
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2785674CD1 <400> 20 Met Thr Lys Ile Lys Ala Asp Pro Asp Gly Pro Glu Ala Gln Ala Glu Ala Cys Ser Gly Glu Arg Thr Tyr Gln Glu Leu Leu Val Asn Gln Asn Pro Ile Ala Gln Pro Leu Ala Ser Arg Arg Leu Thr Arg Lys Leu Tyr Lys Cys Ile Lys Lys Ala Val Lys Gln Lys Gln Ile Arg Arg Gly Val Lys Glu Val Gln Lys Phe Val Asn Lys Gly Glu Lys Gly Ile Met Val Leu Ala Gly Asp Thr Leu Pro Ile Glu Val Tyr Cys His Leu Pro Val Met Cys Glu Asp Arg Asn Leu Pro Tyr Val Tyr Ile Pro Ser Lys Thr Asp Leu Gly Ala Ala Ala Gly Ser Lys Arg Pro Thr Cys Val Ile Met Val Lys Pro His Glu Glu Tyr Gln Glu Ala Tyr Asp Glu Cys Leu Glu Glu Val Gln Ser Leu Pro Leu Pro Leu <210> 21 <211> 243 <212> PRT
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2797479CD1 <400> 21 Met Gly Asp Asp Ile Ser Thr His Ile Ala Pro Lys Glu Leu Arg His Lys His Pro Ser Ser Val Asp Glu Val Ala Gln Val Val Lys Gln Leu Arg Ile Ile Leu Gln Gln Gln Val Arg Pro Gly Glu Ser Thr Val Leu Ala Leu Arg Pro Asn Val Gln Gln Ile Glu Ala Pro Asp Val Ser Arg Asp Pro Arg Val Leu Gly Phe Asp Phe Pro Gly 65 ?0 75 Ser Ala Arg I1e His Glu Gly Thr His Thr Leu Glu Lys Pro Tyr Glu Cys Lys Gln Cys Gly Lys Leu Leu Ser His Arg Ser Ser Phe Arg Arg His Met Met Ala His Thr Gly Asp G1y Pro His Lys Cys Thr Val Cys Gly Lys Ala Phe Asp Ser Pro Ser Val Phe Gln Arg SUBSTITUTE SHEET (RULE 26) His Glu Arg Thr His Thr Gly Glu Lys Pro Tyr Glu Cys Lys Gln Cys Gly Lys Ala Phe Arg Thr Ser Ser Ser Leu Arg Lys His Glu Thr Thr His Thr Gly Glu Gln Pro Tyr Lys Cys Lys Cys Gly Lys Ala Phe Ser Asp Leu Phe Ser Phe Gln Ser His Glu Thr Thr His Ser Glu Glu Glu Pro Tyr Glu Cys Lys Glu Cys Gly Lys Ala Phe Ser Ser Phe Lys Tyr Phe Cys Arg His Glu Arg Thr His Ser Glu Glu Lys Ser Tyr Glu Cys Gln Ile Cys Gly Lys Leu Ser Val Val Ser Val Thr <210> 22 <211> 485 <212> PRT
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2960640CD1 <400> 22 Met Arg Asp Asn Arg Ala Val Ser Leu Cys Gln Gln Glu Trp Met Cys Pro Gly Pro Ala Gln Arg Ala Leu Tyr Arg Gly Ala Thr Gln Arg Lys Asp Ser His Val Ser Leu Ala Thr Gly Val Pro Trp Gly Tyr Glu Glu Thr Lys Thr Leu Leu Ala Ile Leu Ser Ser Ser Gln Phe Tyr Gly Lys Leu Gln Thr Cys Gln Gln Asn Ser Gln Ile Tyr Arg Ala Met Ala Glu Gly Leu Trp Glu Gln Gly Phe Leu Arg Thr Pro Glu Gln Cys Arg Thr Lys Phe Lys Ser Leu Gln Leu Ser Tyr Arg Lys Val Arg Arg Gly Arg Val Pro Glu Pro Cys Ile Phe Tyr Glu Glu Met Asn Ala Leu Ser Gly Ser Trp Ala Ser Ala Pro Pro Met Ala Ser Asp Ala Val Pro Gly Gln Glu Gly Ser Asp Ile Glu Ala Gly Glu Leu Asn His Gln Asn Gly Glu Pro Thr Glu Val Glu Asp Gly Thr Val Asp Gly Ala Asp Arg Asp Glu Lys Asp Phe Arg Asn Pro Gly Gln Glu Val Arg Lys Leu Asp Leu Pro Val Leu Phe Pro Asn Arg Leu Gly Phe Glu Phe Lys Asn Glu Ile Lys Lys Glu Asn Leu Lys Trp Asp Asp Ser Glu Glu Val Glu Ile Asn Lys Ala Leu Gln Arg Lys Ser Arg Gly Val Tyr Trp His Ser Glu Leu Gln SUBSTITUTE SHEET (RULE 26) Lys Gly Leu Glu Ser Glu Pro Thr Ser Arg Arg Gln Cys Arg Asn Ser Pro Gly Glu Ser Glu Glu Lys Thr Pro Ser Gln Glu Lys Met Ser His Gln Ser Phe Cys Ala Arg Asp Lys Ala Cys Thr His Ile Leu Cys Gly Lys Asn Cys Ser Gln Ser Val His Ser Pro His Lys Pro Ala Leu Lys Leu Glu Lys Val Ser Gln Cys Pro Glu Cys Gly Lys Thr Phe Ser Arg Ser Ser Tyr Leu Val Arg His Gln Arg Ile His Thr Gly Glu Lys Pro His Lys Cys Ser Glu Cys Gly Lys Gly Phe Ser Glu Arg Ser Asn Leu Thr Ala His Leu Arg Thr His Thr Gly Glu Arg Pro Tyr Gln Cys Gly Gln Cys Gly Lys Ser Phe Asn Gln Ser Ser Ser Leu Ile Val His Gln Arg Thr His Thr G1y Glu Lys Pro Tyr Gln Cys Ile Val Cys Gly Lys Arg Phe Asn Asn Ser Ser Gln Phe Ser Ala His Arg Arg Ile His Thr Gly Glu Ser Pro Tyr Lys Cys Ala Val Cys Gly Lys Ile Phe Asn Asn Ser Ser His Phe Ser Ala His Arg Lys Thr His Thr Gly Glu Lys Pro Tyr Arg Cys Ser His Cys Glu Arg Gly Phe Thr Lys Asn Ser Ala Leu Thr Arg His Gln Thr Val His Met Lys Ala Val Leu Ser Ser Gln Glu Gly Arg Asp Ala Leu <210> 23 <211> 160 <212> PRT
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 3454051CD1 <400> 23 Met Ser Trp Thr Cys Pro Arg Cys Gln Gln Pro Val Phe Phe Ala Glu Lys Val Ser Ser Leu Gly Lys Asn Trp His Arg Phe Cys Leu Lys Cys Glu Arg Cys His Ser I1e Leu Ser Pro Gly Gly His Ala Glu His Asn Gly Arg Pro Tyr Cys His Lys Pro Cys Tyr Gly Ala Leu Phe Gly Pro Arg Gly Pro Pro His Met Lys Thr Phe Thr Gly Glu Thr Ser Leu Cys Pro Gly Cys Gly Glu Pro Val 'I'~~rr Phe A1a SUBSTITUTE SHEET (RULE 26) Glu Lys Val Met Ser Leu Gly Arg Asn Trp His Arg Pro Cys Leu Arg Cys Gln Arg Cys His Lys Thr Leu Thr Ala Gly Ser His Ala Glu His Asp Gly Val Pro Tyr Cys His -,lal Pro Cys Tyr Gly Tyr Leu Phe Gly Pro Lys Gly Val Asn Ile Gly Asp Val Gly Cys Tyr Ile Tyr Asp Pro Val Lys Ile Lys Phe Lys <210> 24 <211> 511 <212> PRT
<213> Homo sapiens <220>
<221>
<223> Incyte ID No.: 3510640CD1 <400> 24 Met Gln Glu Leu Tyr Ser Thr Pro Ala Ser Arg Leu Asp Ser Phe Val Ala Gln Trp Leu Gln Pro His Arg Glu Trp Lys Glu Glu Val Leu Asp Ala Val Arg Thr Val Glu Glu Phe Leu Arg Gln Glu His Phe Gln Gly Lys Arg Gly Leu Asp Gln Asp Val Arg Val Leu Lys Val Val Lys Val Gly Ser Phe Gly Asn Gly Thr Val Leu Arg Ser Thr Arg Glu Val Glu Leu Val Ala Phe Leu Ser Cys Phe His Ser Phe Gln Glu Ala Ala Lys His His Lys Asp Val Leu Arg Leu Ile Trp Lys Thr Met Trp Gln Ser Gln Asp Leu Leu Asp Leu Gly Leu Glu Asp Leu Arg Met Glu Gln Arg Val Pro Asp Ala Leu Val Phe Thr Ile Gln Thr Arg Gly Thr Ala Glu Pro Ile Thr Val Thr Ile Val Pro Ala Tyr Arg Ala Leu Gly Pro Ser Leu Pro Asn Ser Gln Pro Pro Pro Glu Val Tyr Val Ser Leu Ile Lys Ala Cys Gly Gly Pro Gly Asn Phe Cys Pro Phe Phe Ser Glu Leu Gln Arg Asn Phe Val Lys His Arg Pro Thr Lys Leu Lys Ser Leu Leu Arg Leu Val Lys His Trp Tyr Gln Gln Tyr Val Lys Ala Arg Ser Pro Arg Ala Asn Leu Pro Pro Leu Tyr Ala Leu Glu Leu Leu Thr Ile Tyr Ala Trp Glu Met Gly Thr Glu Glu Asp Glu Asn Phe Met Leu Asp Glu Gly Phe Thr Thr Val Met Asp Leu Leu Leu Glu Tyr Glu Val Ile Cys Ile Tyr Trp Thr Lys Tyr Tyr Thr Leu His Asn Ala Ile Ile SUBSTITUTE SHEET (RULE 26) Glu Asp Cys Val Arg Lys Gln Leu Lys Lys Glu Arg Pro Ile Ile Leu Asp Pro Ala Asp Pro Thr Leu Asn Val Ala Glu Gly Tyr Arg Trp Asp Ile Val Ala Gln Arg Ala Ser Gln Cys Leu Lys Gln Asp Cys Cys Tyr Asp Asn Arg Glu Asn Pro Ile Ser Ser Trp Asn Val Lys Arg Ala Arg Asp Ile His Leu Thr Val Glu Gln Arg Gly Tyr Pro Asp Phe Asn Leu Ile Val Asn Pro Tyr Glu Pro Ile Arg Lys Val Lys Glu Lys Ile Arg Arg Thr Arg Gly Tyr Ser Gly Leu Gln Arg Leu Ser Phe Gln Val Pro Gly Ser Glu Arg Gln Leu Leu Ser Ser Arg Cys Ser Leu Ala Lys Tyr Gly Ile Phe Ser His Thr His Ile Tyr Leu Leu Glu Thr Ile Pro Ser Glu Ile Gln Val Phe Val Lys Asn Pro Asp Gly Gly Ser Tyr Ala Tyr Ala Ile Asn Pro Asn Ser Phe Ile Leu Gly Leu Lys Gln Gln Ile Glu Asp Gln Gln Gly Leu Pro Lys Lys Gln Gln Gln Leu Glu Phe Gln Gly Gln Val Leu Gln Asp Trp Leu Gly Leu Gly Ile Tyr Gly Ile Gln Asp Ser Asp Thr Leu Ile Leu Ser Lys Lys Lys Gly Glu Ala Leu Phe Pro Ala Ser <210> 25 <211> 310 <212> PRT
<213> Homo sapiens <220> -<223> Incyte ID No.: 3815083CD1 <400> 25 Met Arg Pro Leu Gln Ile Val Pro Ser Arg Leu Ile Ser Gln Leu Tyr Cys Gly Leu Lys Pro Pro Ala Ser Thr Arg Asn Gln Ile Cys Leu Lys Met Ala Arg Pro Ser Ser Ser Met Ala Asp Phe Arg Lys Phe Phe Ala Lys Ala Lys His Ile Val Ile Ile Ser Gly Ala Gly Val Ser Ala Glu Ser Gly Val Pro Thr Phe Arg Gly Ala Gly Gly Tyr Trp Arg Lys Trp Gln A1a Gln Asp Leu Ala Thr Pro Leu Ala Phe Ala His Asn Pro Ser Arg Val Trp Glu Phe Tyr His Tyr Arg Arg Glu Val Met Gly Ser Lys Glu Pro Asn Ala Gly His Arg Ala SUBSTITUTE SHEET (RULE 26) Ile Ala Glu Cys Glu Thr Arg Leu Gly Lys Gln Gly Arg Arg Val Val Val Ile Thr Gln Asn Ile Asp Glu Leu His Arg Lys Ala Gly Thr Lys Asn Leu Leu Glu Ile His Gly Ser Leu Phe Lys Thr Arg Cys Thr Ser Cys Gly Val Val Ala Glu Asn Tyr Lys Ser Pro Ile Cys Pro Ala Leu Ser Gly Lys Gly Ala Pro Glu Pro Gly Thr Gln Asp Ala Ser Ile Pro Val Glu Lys Leu Pro Arg Cys Glu Glu Ala Gly Cys Gly Gly Leu Leu Arg Pro His Val Val Trp Phe Gly Glu Asn Leu Asp Pro Ala Ile Leu Glu Glu Val Asp Arg Glu Leu Ala His Cys Asp Leu Cys Leu Val Val Gly Thr Ser Ser Val Val Tyr Pro Ala Ala Met Phe Ala Pro Gln Val Ala Ala Arg Gly Val Pro Val Ala Glu Phe Asn Thr Glu Thr Thr Pro Ala Thr Asn Arg Phe Arg Phe His Phe Gln Gly Pro Cys Gly Thr Thr Leu Pro Glu Ala Leu Ala Cys His Glu Asn Glu Thr Val Ser <210> 26 <211> 331 <212> PRT
<213> Homo sapiens <220> -<221> misc-feature <223> Incyte ID No.: 3988457CD1 <400> 26 Met Ala Ile Asn Arg Phe Arg Leu Glu Asn Asp Leu Glu Glu Leu Ala Leu Tyr Gln Ile Gln Leu Leu Lys Asp Leu Arg His Thr Glu Asn Glu Glu Asp Lys Val Ser Ser Ser Ser Phe Arg Gln Arg Met Leu Gly Asn Leu Leu Arg Pro Pro Tyr Glu Arg Pro Glu Leu Pro Thr Cys Leu Tyr Val Ile Gly Leu Thr Gly Ile Ser Gly Ser Gly Lys Ser Ser Ile Ala Gln Arg Leu Lys Gly Leu Gly Ala Phe Val Ile Asp Ser Asp His Leu Gly His Arg Ala Tyr Ala Pro Gly Gly Pro Ala Tyr Gln Pro Val Val Glu Ala Phe Gly Thr Asp Ile Leu His Lys Asp Gly Ile Ile Asn Arg Lys Val Leu Gly Ser Arg Val Phe Gly Asn Lys Lys Gln Leu Lys Ile Leu Thr Asp Ile Met Trp Pro Ile Ile Ala Lys Leu Ala Arg Glu Glu Met Asp Arg Ala Val Ala Glu Gly Lys Arg Val Cys Val Ile Asp Ala Ala Val Leu Leu SUBSTITUTE SHEET (RULE 26) Glu Ala Gly Trp Gln Asn Leu Val His Glu Val Trp Thr Ala Val Ile Pro Glu Thr Glu Ala Val Arg Arg Ile Val Glu Arg Asp Gly Leu Ser Glu Ala Ala Ala Gln Ser Arg Leu Gln Ser Gln Met Ser Gly Gln Gln Leu Val Glu Gln Ser His Val Val Leu Ser Ser Pro Cys Gly Ser Arg Ile Ser Pro Asn Ala Arg Trp Arg Lys Pro Gly Pro Ser Cys Arg Ser Ala Phe Pro Arg Leu Ile Arg Pro Ser Thr Glu Lys Phe Ser Val Gly Pro Asp Trp Leu Leu Glu Leu Thr Ser Asp Pro Val Val Arg Arg Asn Gly Gly Leu Asp Ala His Pro Gly Ser Gly Pro Glu Val Gln Ala Ile Leu Cys Arg Thr Trp Pro Gly Leu Val Asp Thr Gly Ser Leu Pro Asn Thr Leu Val Phe Gly Gln His <210> 27 <211> 200 <212> PRT
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 131890CD1 <400> 27 Met Met Thr Ala Glu Ser Arg Glu Ala Thr Gly Leu Ser Pro Gln Ala Ala Gln Glu Lys Asp Gly Ile Val Ile Val Lys Val Glu Glu Glu Asp Glu Glu Asp His Met Trp Gly Gln Asp Ser Thr Leu G1n Asp Thr Pro Pro Pro Asp Pro Glu Ile Phe Arg Gln Arg Phe Arg Arg Phe Cys Tyr Gln Asn Thr Phe Gly Pro Arg Glu Ala Leu Ser Arg Leu Lys Glu Leu Cys His Gln Trp Leu Arg Pro Glu Ile Asn Thr Lys Glu Gln Ile Leu Glu Leu Leu Val Leu Glu Gln Phe Leu Ser Ile Leu Pro Lys Glu Leu Gln Val Trp Leu Gln Glu Tyr Arg Pro Asp Ser Gly Glu Glu Ala Val Thr Leu Leu Glu Asp Leu Glu Leu Asp Leu Ser Gly Gln Gln Val Pro Gly Gln Val His Gly Pro Glu Met Leu Ala Arg Gly Met Val Pro Leu Asp Pro Val Gln Glu Ser Ser Ser Phe Asp Leu His His Glu Ala Thr Gln Ser His Phe Lys His Ser Ser Arg Lys Pro Arg Leu Leu Gln Ser Arg Gly Lys Lys Gln Gly Phe Ile SUBSTITUTE SHEET (RULE 26) <210> 28 <211> 100 <212> PRT
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 238642CD1 <400> 28 Met Gln Lys Pro Cys Lys Glu Asn Glu Gly Lys Pro Lys Cys Ser Val Pro Lys Arg Glu Glu Lys Arg Pro Tyr Gly Glu Phe Glu Arg Gln Gln Thr Glu Gly Asn Phe Arg Gln Arg Leu Leu Gln Ser Leu Glu Glu Phe Lys Glu Asp Ile Asp Tyr Arg His Phe Lys Asp Glu Glu Met Thr Arg Glu Gly Asp Glu Met Glu Arg Cys Leu Glu Glu Ile Arg Gly Leu Arg Lys Lys Phe Arg Ala Leu His Ser Asn His Arg His Ser Arg Asp Arg Pro Tyr Pro Ile <210> 29 <211> 528 <212> PRT
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 669862CD1 <400> 29 Met Ser Ser Pro Tyr Pro Leu Leu Leu Glu Asn Ser Ile Cys Leu Phe Phe His Phe Leu Pro Asp Phe Asn Phe Thr Thr Glu Ser Asn Lys Leu Ser Ser Glu Lys Arg Asn Tyr Glu Val Asn Ala Tyr His Gln Glu Thr Trp Lys Arg Asn Lys Thr Phe Asn Leu Met Arg Phe Ile Phe Arg Thr Asp Pro Gln Tyr Thr Ile Glu Phe Gly Arg Gln Gln Arg Pro Lys Val Gly Cys Phe Ser Gln Met Ile Phe Lys Lys His Lys Ser Leu Pro Leu His Lys Arg Asn Asn Thr Arg Glu Lys Ser Tyr Glu Cys Lys Glu Tyr Lys Lys Gly Phe Arg Lys Tyr Leu His Leu Thr Glu His Leu Arg Asp His Thr Gly Val Ile Pro Tyr Glu Cys Asn Glu Cys Gly Lys Ala Phe Val Val Phe Gln His Phe SUBSTITUTE SHEET (RULE 26) Ile Arg His Arg Lys Ile His Thr Asp Leu Lys Pro Tyr Glu Cys Asn Gly Cys Glu Lys Ala Phe Arg Phe Tyr Ser G1n Leu Ile Gln His Gln Ile Ile His Thr Gly Met Lys Pro Tyr Glu Cys Lys Gln Cys Gly Lys Ala Phe Arg Arg His Ser His Leu Thr Glu His Gln Lys Ile His Val Gly Leu Lys Pro Phe Glu Cys Lys Glu Cys Gly Glu Thr Phe Arg Leu Tyr Arg His Met Cys Leu His Gln Lys Ile His His Gly Val Lys Pro Tyr Lys Cys Lys Glu Cys Gly Lys Ala Phe Gly His Arg Ser Ser Leu Tyr Gln His Lys Lys Ile His Ser Gly Glu Lys Pro Tyr Lys Cys Glu Gln Cys Glu Lys Ala Phe Val Arg Ser Tyr Leu Leu Val Glu His Gln Arg Ser His Thr Gly Glu Lys Pro His Glu Cys Met Glu Cys Gly Lys Ala Phe Ser Lys Gly Ser Ser Leu Leu Lys His Lys Arg Ile His Ser Ser Glu Lys Leu Tyr Asp Cys Lys Asp Cys Gly Lys Ala Phe Cys Arg Gly Ser Gln Leu Thr Gln His Gln Arg Ile His Thr Gly Glu Lys Pro His Glu Cys Lys Glu Cys Gly Lys Thr Phe Lys Leu His Ser Tyr Leu Ile Gln His ~ln ile Ile His Thr Asp Leu Lys Pro Tyr Glu Cys Lys Gln Cys Gly Lys Ala Phe Ser Arg Val Gly Asp Leu Lys Thr His Gln Ser Ile His Ala Gly Glu Lys Pro Tyr Glu Cys Lys Glu Cys Gly Lys Thr Phe Arg Leu Asn Ser Gln Leu Ile Tyr His Gln Thr Ile His Thr Gly Leu Lys Pro Tyr Val Cys Lys Glu Cys Lys Lys Ala Phe Arg Ser Ile Ser Gly Leu Ser Gln His Lys Arg Ile His Thr Gly Glu Lys Pro Tyr Glu Cys Lys Glu Cys Asp Lys Ala Phe Asn Arg Ser Asp Arg Leu Thr Gln His Glu Thr Ile His Thr Gly Val Lys Pro Gln Lys Cys Lys Glu Cys Gly Lys Ala Phe Ser His Cys Tyr Gln Leu Ser Gln His Gln Arg Phe His His Gly Glu Arg Leu Leu Met <210> 30 <211> 350 <212> PRT
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 1003663CD1 SUBSTITUTE SHEET (RULE 26) <400> 30 Met His Pro Ala Ala Phe Pro Leu Pro Val Val Val Ala Ala Val Leu Trp Gly Ala Ala Pro Thr Arg Gly Leu Ile Arg Ala Thr Ser Asp His Asn Ala Ser Met Asp Phe Ala Asp Leu Pro Ala Leu Phe Gly Ala Thr Leu Ser Gln Glu Gly Leu Gln Gly Phe Leu Val Glu Ala His Pro Asp Asn Ala Cys Ser Pro Ile Ala Pro Pro Pro Pro Ala Pro Val Asn Gly Ser Val Phe Ile Ala Leu Leu Arg Arg Phe Asp Cys Asn Phe Asp Leu Lys Val Leu Asn Ala Gln Lys Ala Gly Tyr Gly Ala Ala Val Val His Asn Val Asn Ser Asn Glu Leu Leu Asn Met Val Trp Asn Ser Glu Glu Ile Gln Gln Gln Ile Trp Ile Pro Ser Val Phe Ile Gly Glu Arg Ser Ser Glu Tyr Leu Arg Ala Leu Phe Val Tyr Glu Lys Gly Ala Arg Val Leu Leu Val Pro Asp Asn Thr Phe Pro Leu Gly Tyr Tyr Leu Ile Pro Phe Thr Gly Ile Val Gly Leu Leu Val Leu Ala Met Gly Ala Val Met Ile Ala Arg Cys Ile Gln His Arg Lys Arg Leu Gln Arg Asn Arg Leu Thr Lys Glu Gln :~eu Lys Gln Ile Pro Thr His Asp Tyr Gln Lys Gly Asp Gln Tyr Asp Val Cys Ala Ile Cys Leu Asp Glu Tyr Glu Asp Gly Asp Lys Leu Arg Val Leu Pro Cys Ala His Ala Tyr His Ser Arg Cys Val Asp Pro Trp Leu Thr Gln Thr Arg Lys Thr Cys Pro Ile Cys Lys Gln Pro Val His Arg Gly Pro Gly Asp Glu Asp Gln Glu Glu Glu Thr Gln Gly Gln Glu Glu Gly Asp Glu Gly Glu Pro Arg Asp His Pro Ala Ser G1u Arg Thr Pro Leu Leu Gly Ser Ser Pro Thr Leu Pro Thr Ser Phe Gly Ser Leu Ala Pro Ala Pro Leu Val Phe Pro Gly Pro Ser Thr Asp Pro Pro Leu Ser Pro Pro Ser Ser Pro Val Ile Leu Val <210> 31 <211> 315 <212> PRT
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 1432557CD1 SUBSTITUTE SHEET (RULE 26) <400> 31 Met Ala Ala Leu Gly Val Leu Glu Ser Asp Leu Pro Ser Ala Val Thr Leu Leu Lys Asn Leu Gln Glu G1n Val Met Ala Val Thr Ala Gln Val Lys Ser Leu Thr Gln Lys Val Gln Ala Gly Ala Tyr Pro Thr Glu Lys Gly Leu Ser Phe Leu Glu Val Lys Asp Gln Leu Leu Leu Met Tyr Leu Met Asp Leu Thr His Leu Ile Leu Asp Lys Ala Ser Gly Gly Ser Leu Gln Gly His Asp Ala Val Leu Arg Leu Va1 Glu Ile Arg Thr Val Leu Glu Lys Leu Arg Pro Leu Asp Gln Lys Leu Lys Tyr Gln Ile Asp Lys Leu Ile Lys Thr Ala Val Thr Gly Ser Leu Ser Glu Asn Asp Pro Leu Arg Phe Lys Pro His Pro Ser Asn Met Met Ser Lys Leu Ser Ser Glu Asp Glu Glu Glu Asp Glu Ala Glu Asp Asp Gln Ser Glu Ala Ser Gly Lys Lys Ser Val Lys Gly Val Ser Lys Lys Tyr Val Pro Pro Arg Leu Val Pro Val His Tyr Asp Glu Thr Glu Ala Glu Arg Glu Lys Lys Arg Leu Glu Arg Ala Lys Arg Arg Ala Leu Ser Ser Ser Val Ile Arg Glu Leu Lys Glu Gln Tyr Ser Asp Ala Pro Glu Glu Ile Arg Asp Ala Arg His Pro His Val Thr Arg Gln Ser Gln Glu Asp Gln His Arg Ile Asn Tyr Glu Glu Ser Met Met Val Arg Leu Ser Val Ser Lys Arg Glu Lys Gly Arg Arg Lys Arg Ala Asn Val Met Ser Ser Gln Leu His Ser Leu Thr His Phe Ser Asp Ile Ser Ala Leu Thr Gly Gly Thr Val His Leu Asp Glu Asp Gln Asn Pro Ile Lys Lys Arg Lys Lys Ile Pro Gln Lys Gly Arg Lys Lys Lys Gly Phe Arg Arg Arg Arg <210> 32 <211> 120 <212> PRT
<213> Homo Sapiens <220>
<221> misc-feature <223> 1441770CD1 <400> 32 Met Asp Asp Ser Lys Val Val Gly Gly Lys Val Lys Lys Pro Gly Lys Arg Gly Arg Lys Pro Ala Lys Ile Asp Leu Lys Ala Lys Leu Glu Arg Ser Arg Gln Ser Ala Arg Glu Cys Arg Ala Arg Lys Lys SUBSTITUTE SHEET (RULE 26) Leu Arg Tyr Gln Tyr Leu Glu Glu Leu Val Ser Ser Arg Glu Arg Ala Ile Cys Ala Leu Arg Glu Glu Leu Glu Met Tyr Lys Gln Trp Cys Met Ala Met Asp Gln Gly Lys Ile Prc Ser Glu Ile Lys Ala Leu Leu Thr Gly Glu Glu Gln Asn Lys Ser Gln Gln Asn Ser Ser Arg His Thr Lys Ala Gly Lys Thr Asp Ala Asn Ser Asn Ser Trp <210> 33 <211> 326 <212> PRT
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 1456684CD1 <400> 33 Met Gln Glu Glu Pro Leu Pro Gln Gly Asn Asp Pro Glu Pro Ser Gly Asp Ser Pro Leu Gly Leu Cys Gln Ser Glu Cys Met Glu Met Ser Glu Val Phe Asp Asp Ala Ser Asp Gln Asp Ser Thr Asp Lys 35 40 4.~
Pro ~rrp Arg Pro Tyr Tyr Asn Tyr Lys Pro Lys Lys Lys Ser Arg Gln Leu Lys Lys Met Arg Lys Val Asn Trp Arg Lys Glu His Gly Asn Arg Ser Pro Ser His Lys Cys Lys Tyr Pro Ala Glu Leu Asp Cys Ala Val G1y Lys Ala Pro Gln Asp Lys Pro Phe Glu Glu Glu Glu Thr Lys Glu Met Pro Lys Leu Gln Cys Glu Leu Cys Asp Gly Asp Lys Ala Val Gly Ala Gly Asn Gln Gly Arg Pro His Arg His Leu Thr Ser Arg Pro Tyr Ala Cys Glu Leu Cys Ala Lys Gln Phe Gln Ser Pro Ser Thr Leu Lys Met His Met Arg Cys His Thr Gly Glu Lys Pro Tyr Gln Cys Lys Thr Cys Gly Arg Cys Phe Ser Val Gln Gly Asn Leu Gln Lys His Glu Arg Ile His Leu Gly Leu Lys Glu Phe Val Cys Gln Tyr Cys Asn Lys Ala Phe Thr Leu Asn Glu Thr Leu Lys Ile His Glu Arg Ile His Thr Gly Glu Lys Arg Tyr His Cys Gln Phe Cys Phe Gln Arg Phe Leu Tyr Leu Ser Thr Lys Arg Asn His Glu Gln Arg His Ile Arg Glu His Asn Gly Lys Gly Tyr Ala Cys Phe Gln Cys Pro Lys Ile Cys Lys Thr Ala Ala Ala Leu Gly Met His Gln Lys Lys His Leu P:~ Lys Ser Pro Ser Gln SUBSTITUTE SHEET (RULE 26) Gln Glu Lys Ile Gly Asp Val Cys His Glu Asn Ser Asn Pro Leu Glu Asn Gln His Phe Ile Gly Ser Glu Asp Asn Asp Gln Lys Asp Asn Ile Gln Thr Gly Val Glu Asn Val Val Leu <210> 34 <211> 106 <212> PRT
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 1602916CD1 <400> 34 Met Phe Pro Trp Met Arg Pro Gln Ala Ala Pro Gly Arg Arg Arg Gly Arg Gln Thr Tyr Ser Arg Phe Gln Thr Leu Glu Leu Glu Lys Glu Phe Leu Phe Asn Pro Tyr Leu Thr Arg Lys Arg Arg Ile Glu Val Ser His Ala Leu Ala Leu Thr Glu Arg Gln Val Lys Ile Trp Phe Gln Asn Arg Arg Met Lys Trp Lys Lys Glu Asn Asn Lys Asp Lys Phe Pro Val Ser Arg Gln Glu Val Lys Asp Gly Glu Thr Lys Lys Glu Ala Gln Glu Leu Glu Glu Asp Arg Ala Glu Arg Leu Thr Asn <210> 35 <211> 209 <212> PRT
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 1692816CD1 <400> 35 Met Asn Pro Ser Met Lys Gln Lys Gln Glu Glu Ile Lys Glu Asn Ile Lys Asn Ser Ser Val Pro Arg Arg Thr Leu Lys Met Ile Gln Pro Ser Ala Ser Gly Ser Leu Val Gly Arg Glu Asn Glu Leu Ser Ala Gly Leu Ser Lys Arg Lys His Arg Asn Asp His Leu Thr Ser Thr Thr Ser Ser Pro Gly Val Ile Val Pro Glu Ser Ser Glu Asn Lys Asn Leu Gly Gly Val Thr Gln Glu Ser Phe Asp Leu Met Ile Lys Glu Asn Pro Ser Ser Gln Tyr Trp Lys Glu Val Ala Glu Lys SUBSTITUTE SHEET (RULE 26) Arg Arg Lys Ala Leu Tyr Glu Ala Leu Lys Glu Asn Glu Lys Leu His Lys Glu Ile Glu Gln Lys Asp Asn Glu Ile Ala Arg Leu Lys Lys Glu Asn Lys Glu Leu Ala Glu Val Ala Glu His Val Gln Tyr Met Ala Glu Leu Ile Glu Arg Leu Asn Gly Glu Pro Leu Asp Asn Phe Glu Ser Leu Asp Asn Gln Glu Phe Asp Ser Glu Glu Glu Thr Val Glu Asp Ser Leu Val Glu Asp Ser Glu Ile Gly Thr Cys Ala Glu Gly Thr Val Ser Ser Ser Thr Asp Ala Lys Pro Cys Ile <210> 36 <211> 212 <212> PRT
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 1968191CD1 <400> 36 Met Leu Gly Asn Glu Trp Ser Lys Leu Pro Pro Glu Glu Lys Gln Arg Tyr Leu Asp Glu Ala Asp Arg Asp Lys Glu Arg Tyr Met Lys Glu Leu Glu Gln Tyr Gln Lys Thr Glu Ala Tyr Lys Val Phe Ser Arg Lys Thr Gln Asp Arg Gln Lys Gly Lys Ser His Arg Gln Asp Ala Ala Arg Gln Ala Thr His Asp His Glu Lys Glu Thr Glu Val Lys Glu Arg Ser Val Phe Asp Ile Pro Ile Phe Thr Glu Glu Phe Leu Asn His Ser Lys Ala Arg Glu Ala Glu Leu Arg Gln Leu Arg Lys Ser Asn Met Glu Phe Glu Glu Arg Asn Ala Ala Leu Gln Lys His Val Glu Ser Met Arg Thr Ala Val Glu Lys Leu Glu Val Asp Val Ile Gln Glu Arg Ser Arg Asn Thr Val Leu Gln Gln His Leu Glu Thr Leu Arg Gln Val Leu Thr Ser Ser Phe Ala Ser Met Pro Leu Pro Gly Ser Gly Glu Thr Pro Thr Val Asp Thr Ile Asp Ser Tyr Met Asn Arg Leu His Ser Ile Ile Leu Ala Asn Pro Gln Asp Asn Glu Asn Phe Ile Ala Thr Val Arg Glu Val Val Asn Arg Leu Asp Arg SUBSTITUTE SHEET (RULE 26) <210> 37 <211> 359 <212> PRT
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2052061CD1 <400> 37 Met Val Asp Met Asp Lys Leu Ile Asn Asn Leu Glu Val Gln Leu Asn Ser Glu Gly Gly Ser Met Gln Val Phe Lys Gln Val Thr Ala Ser Val Arg Asn Arg Asp Pro Pro Glu Ile Glu Tyr Thr Ser Asn Met Thr Ser Pro Thr Leu Leu Asp Ala Asn Pro Met Glu Asn Pro Ala Leu Phe Asn Asp Ile Lys Ile Glu Pro Pro Glu Glu Leu Leu Ala Ser Asp Phe Ser Leu Pro Gln Val Glu Pro Val Asp Leu Ser Phe His Lys Pro Lys Ala Pro Leu Gln Pro Ala Ser Met Leu Gln Ala Pro Ile Arg Pro Pro Lys Pro Gln Ser Ser Pro Gln Thr Leu Val Val Ser Thr Ser Thr Ser Asp Met Ser Thr Ser Ala Asn Ile Pro Thr Val Leu Thr Pro Gly Ser Val Leu Thr Ser Ser Gln Ser Thr Gly Ser Gln Gln Ile Leu His Val Ile His Thr Ile Pro Ser Val Ser Leu Pro Asn Lys Met Gly Gly Leu Lys Thr Ile Pro Val Val Val Gln Ser Leu Pro Met Val Tyr Thr Thr Leu Pro Ala Asp Gly Gly Pro Ala Ala Ile Thr Val Pro Leu Ile Gly Gly Asp Gly Lys Asn Ala Gly Ser Val Lys Val Asp Pro Thr Ser Met Ser Pro Leu Glu Ile Pro Ser Asp Ser Glu Glu Ser Thr Ile Glu Ser Gly Ser Ser Ala Leu Gln Ser Leu Gln Gly Leu Gln Gln Glu Pro Ala Ala Met Ala Gln Met Gln Gly Glu Glu Ser Leu Asp Leu Lys Arg Arg Arg Ile His Gln Cys Asp Phe Ala Gly Cys Ser Lys Val Tyr Thr Lys Ser Ser His Leu Lys Ala His Arg Arg Ile His Thr Gly Glu Lys Pro Tyr Lys Cys Thr Trp Asp Gly Cys Ser Trp Lys Phe Ala Arg Ser Asp Glu Leu Thr Arg His Phe Arg Lys His Thr Gly Ile Lys Pro Phe Arg Cys Thr Asp Cys Asn Arg Ser Phe Ser Arg Ser Asp His Leu Ser Leu His Arg Arg Arg His Asp Thr Met SUBSTITUTE SHEET (RULE 26) <210> 38 <211> 445 <212> PRT
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2056207CD1 <400> 38 Met Val Glu Cys Ile Arg Glu Val Asn Glu Val Ile Gln Asn Pro Ala Thr Ile Thr Arg Ile Leu Leu Ser His Phe Asn Trp Asp Lys Glu Lys Leu Met Glu Arg Tyr Phe Asp Gly Asn Leu Glu Lys Leu Phe Ala Glu Cys His Val Ile Asn Pro Ser Lys Lys Ser Arg Thr Arg Gln Met Asn Thr Arg Ser Ser Ala Gln Asp Met Pro Cys Gln Ile Cys Tyr Leu Asn Tyr Pro Asn Ser Tyr Phe Thr Gly Leu Glu Cys Gly His Lys Phe Cys Met Gln Cys Trp Ser Glu Tyr Leu Thr Thr Lys Ile Met Glu Glu Gly Met Gly Gln Thr Ile Ser Cys Pro Ala His Gly Cys Asp Ile Leu Val Asp Asp Asn Thr Val Met Arg Leu Ile Thr Asp Ser Lys Val Lys Leu Lys Tyr Gln His Leu Ile Thr Asn Ser Phe Val Glu Cys Asn Arg Leu Leu Lys Trp Cys Pro Ala Pro Asp Cys His His Val Val Lys Val Gln Tyr Pro Asp Ala Lys Pro Val Arg Cys Lys Cys Gly Arg Gln Phe Cys Phe Asn Cys Gly Glu Asn Trp His Asp Pro Val Lys Cys Lys Trp Leu Lys Lys Trp Ile Lys Lys Cys Asp Asp Asp Ser Glu Thr Ser Asn Trp Ile Ala Ala Asn Thr Lys Glu Cys Pro Lys Cys His Val Thr Ile Glu Lys Asp Gly Gly Cys Asn His Met Val Cys Arg Asn Gln Asn Cys Lys Ala Glu Phe Cys Trp Val Cys Leu Gly Pro Trp Glu Pro His Gly Ser Ala Trp Tyr Asn Cys Asn Arg Tyr Asn Glu Asp Asp Ala Lys Ala Ala Arg Asp Ala Gln Glu Arg Ser Arg Ala Ala Leu Gln Arg Tyr Leu Phe Tyr Cys Asn Arg Tyr Met Asn His Met Gln Ser Leu Arg Phe Glu His Lys Leu Tyr Ala Gln Val Lys Gln Lys Met Glu Glu Met Gln Gln His Asn Met Ser Trp Ile Glu Val Gln Phe Leu Lys Lys Ala Val Asp Val Leu Cys Gln Cys Arg Ala Thr Leu Met Tyr Thr Tyr Val Phe Ala Phe Tyr Leu Lys Lys Asn Asn Gln Ser Ile Ile Phe Glu Asn Asn Gln Ala Asp Leu Glu Asn Ala Thr SUBSTITUTE SHEET (RULE 26) Glu Val Leu Ser Gly Tyr Leu Glu Arg Asp Ile Ser Gln Asp Ser Leu Gln Asp Ile Lys Gln Lys Val Gln Asp Lys Tyr Arg Tyr Cys Glu Ser Arg Arg Arg Val Leu Leu Gln His Val His Glu Gly Tyr Glu Lys Asp Leu Trp Glu Tyr Ile Glu Asp <210> 39 <211> 433 <212> PRT
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2101803CD1 <400> 39 Met Arg Ala Glu Gly Leu Gly Gly Leu Glu Arg Phe Cys Ser Pro Gly Lys Gly Arg Gly Leu Arg Ala Leu Gln Pro Phe Gln Val Gly Asp Leu Leu Phe Ser Cys Pro Ala Tyr Ala Tyr Val Leu Thr Val Asn Glu Arg Gly Asn His Cys Glu Tyr Cys Phe Thr Arg Lys Glu Gly Leu Ser Lys Cys Gly Arg Cys Lys Gln Ala Phe Tyr Cys Asn Val Glu Cys Gln Lys Glu Asp Trp Pro Met His Lys Leu Glu Cys Ser Pro Met Val Val Phe Gly Glu Asn Trp Asn Pro Ser Glu Thr Val Arg Leu Thr Ala Arg Ile Leu Ala Lys Gln Lys Ile His Pro Glu Arg Thr Pro Ser Glu Lys Leu Leu Ala Val Lys Glu Phe Glu Ser His Leu Asp Lys Leu Asp Asn Glu Lys Lys Asp Leu Ile Gln Ser Asp Ile Ala Ala Leu His His Phe Tyr Ser Lys His Leu Glu Phe Pro Asp Asn Asp Ser Leu Val Val Leu Phe Ala Gln Val Asn Cys Asn Gly Phe Thr Ile Glu Asp Glu Glu Leu Ser His Leu Gly Ser Ala Ile Phe Pro Asp Val Ala Leu Met Asn His Ser Cys Cys Pro Asn Val Ile Val Thr Tyr Lys Gly Thr Leu Ala Glu Val Arg Ala Val Gln Glu Ile Lys Pro Gly Glu Glu Val Phe Thr Ser Tyr Ile Asp Leu Leu Tyr Pro Thr Glu Asp Arg Asn Asp Arg Leu Arg Asp Ser Tyr Phe Phe Thr Cys Glu Cys Gln Glu Cys Thr Thr Lys Asp Lys Asp Lys Ala Lys Val Glu Ile Arg Lys Leu Ser Asp Pro Pro Lys Ala Glu Ala Ile Arg Asp Met Val Arg Tyr Ala Arg Asn SUBSTITUTE SHEET (RULE 26) Val Ile Glu Glu Phe Arg Arg Ala Lys His Tyr Lys Ser Pro Ser Glu Leu Leu Glu Ile Cys Glu Leu Ser Gln Glu Lys Met Ser Ser Val Phe Glu Asp Ser Asn Val Tyr Met Leu His Met Met Tyr Gln Ala Met Gly Val Cys Leu Tyr Met Gln Asp Trp Glu Gly Ala Leu Gln Tyr Gly Gln Lys Ile Ile Lys Pro Tyr Ser Lys His Tyr Pro Leu Tyr Ser Leu Asn Val Ala Ser Met Trp Leu Lys Leu Gly Arg Leu Tyr Met Gly Leu Glu His Lys Ala Ala Gly Glu Lys Ala Leu Lys Lys Ala Ile Ala Ile Met Glu Val Ala His Gly Lys Asp His Pro Tyr Ile Ser Glu Ile Lys Gln Glu Ile Glu Ser His <210> 40 <211> 355 <212> PRT
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2112362CD1 <400> 40 Met Ser Val Asn Tyr Ala Ala Gly Leu Ser Pro Tyr Ala Asp Lys Gly Lys Cys Gly Leu Pro Glu Ile Phe Asp Pro Pro Glu Glu Leu Glu Arg Lys Val Trp Glu Leu Ala Arg Leu Val Trp Gln Ser Ser Asn Val Val Phe His Thr Gly Ala Gly Ile Ser Thr Ala Ser Gly Ile Pro Asp Phe Arg Gly Pro His Gly Val Trp Thr Met Glu Glu Arg Gly Leu Ala Pro Lys Phe Asp Thr Thr Phe Glu Ser Ala Arg Pro Thr Gln Thr His Met Ala Leu Val Gln Leu Glu Arg Val Gly Leu Leu Arg Phe Leu Val Ser Gln Asn Val Asp Gly Leu His Val Arg Ser Gly Phe Pro Arg Asp Lys Leu Ala Glu Leu His Gly Asn Met Phe Val Glu Glu Cys Ala Lys Cys Lys Thr Gln Tyr Val Arg Asp Thr Val Val Gly Thr Met Gly Leu Lys Ala Thr Gly Arg Leu Cys Thr Val Ala Lys Ala Arg Gly Leu Arg Ala Cys Arg Gly Glu Leu Arg Asp Thr Ile Leu Asp Trp Glu Asp Ser Leu Pro Asp Arg Asp Leu Ala Leu Ala Asp Glu Ala Ser Arg Asn Ala Asp Leu Ser Ile Thr Leu Gly Thr Ser Leu Gln Ile Arg Pro Ser Gly Asn Leu SUBSTITUTE SHEET (RULE 26) Pro Leu Ala Thr Lys Arg Arg Gly Gly Arg Leu Val Ile Val Asn Leu Gln Pro Thr Lys His Asp Arg His Ala Asp Leu Arg Ile His Gly Tyr Val Asp Glu Val Met Thr Arg Leu Met Lys His Leu Gly Leu Glu Ile Pro Ala Trp Asp Gly Pro Arg Val Leu Glu Arg Ala Leu Pro Pro Leu Pro Arg Pro Pro Thr Pro Lys Leu Glu Pro Lys Glu Glu Ser Pro Thr Arg Ile Asn Gly Ser Ile Pro Ala Gly Pro Lys Gln Glu Pro Cys Ala Gln His Asn Gly Ser Glu Pro Ala Ser Pro Lys Arg Glu Arg Pro Thr Ser Pro Ala Pro His Arg Pro Pro Lys Arg Val Lys Ala Lys Ala Val Pro Ser <210> 41 <211> 443 <212> PRT
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2117346CD1 <400> 41 Met Asp Arg Leu Gly Ser Phe Ser Asn Asp Pro Ser Asp Lys Pro Pro Cys Arg Gly Cys Ser Ser Tyr Leu Met Glu Pro Tyr Ile Lys Cys Ala Glu Cys Gly Pro Pro Pro Phe Phe Leu Cys Leu Gln Cys Phe Thr Arg Gly Phe Glu Tyr Lys Lys His Gln Ser Asp His Thr Tyr Glu Ile Met Thr Ser Asp Phe Pro Val Leu Asp Pro Ser Trp Thr Ala Gln Glu Glu Met Ala Leu Leu Glu Ala Val Met Asp Cys Gly Phe Gly Asn Trp Gln Asp Val Ala Asn Gln Met Cys Thr Lys Thr Lys Glu Glu Cys Glu Lys His Tyr Met Lys His Phe Ile Asn Asn Pro Leu Phe Ala Ser Thr Leu Leu Asn Leu Lys Gln Ala Glu Glu Ala Lys Thr Ala Asp Thr Ala Ile Pro Phe His Ser Thr Asp Asp Pro Pro Arg Pro Thr Phe Asp Ser Leu Leu Ser Arg Asp Met Ala Gly Tyr Met Pro Ala Arg Ala Asp Phe Ile Glu Glu Phe Asp Asn Tyr Ala Glu Trp Asp Leu Arg Asp Ile Asp Phe Val Glu Asp Asp Ser Asp Ile Leu His A1a Leu Lys Met Ala Val Val Asp Ile Tyr His Ser Arg Leu Lys Glu Arg Gln Arg Arg Lys Lys Ile Ile SUBSTITUTE SHEET (RULE 26) Arg Asp His Gly Leu Ile Asn Leu Arg Lys Phe Gln Leu Met Glu Arg Arg Tyr Pro Lys Glu Val Gln Asp Leu Tyr Glu Thr Met Arg Arg Phe Ala Arg Ile Val Gly Pro Val Glu His Asp Lys Phe Ile Glu Ser His Ala Leu Glu Phe Glu Leu Arg Arg Glu Ile Lys Arg Leu Gln Glu Tyr Arg Thr Ala Gly Ile Thr Asn Phe Cys Ser Ala Arg Thr Tyr Asp His Leu Lys Lys Thr Arg Glu Glu Glu Arg Leu Lys Arg Thr Met Leu Ser Glu Val Leu Gln Tyr Ile Gln Asp Ser Ser Ala Cys Gln Gln Trp Leu Arg Arg Gln Ala Asp Ile Asp Ser Gly Leu Ser Pro Ser Ile Pro Met Ala Ser Asn Ser Gly Arg Arg Ser Ala Pro Pro Leu Asn Leu Thr Gly Leu Pro Gly Thr Glu Lys Leu Asn Glu Lys Glu Lys Glu Leu Cys Gln Met Val Arg Leu Val Pro Gly Ala Tyr Leu Glu Tyr Lys Ser Ala Leu Leu Asn Glu Cys Asn Lys Gln Gly Gly Leu Arg Leu Ala Gln Ala Arg Ala Leu Ile Lys Ile Asp Val Asn Lys Thr Arg Lys Ile Tyr Asp Phe Leu Ile Arg Glu Gly Tyr Ile Thr Lys Gly <210> 42 <211> 164 <212> PRT
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2119917CD1 <400> 42 Met Thr Ala Ser Ala Gln Pro Arg Gly Arg Arg Pro G1y Val Gly Val Gly Val Val Val Thr Ser Cys Lys His Pro Arg Cys Val Leu Leu Gly Lys Arg Lys Gly Ser Val Gly Ala Gly Ser Phe Gln Leu Pro Gly Gly His Leu Glu Phe Gly Glu Thr Trp Glu Glu Cys Ala Gln Arg Glu Thr Trp Glu Glu Ala Ala Leu His Leu Lys Asn Val His Phe Ala Ser Val Val Asn Ser Phe Ile Glu Lys Glu Asn Tyr His Tyr Val Thr Ile Leu Met Lys Gly Glu Val Asp Val Thr His Asp Ser Glu Pro Lys Asn Val Glu Pro Glu Lys Asn Glu Ser Trp Glu Trp '.'al Pro Trp Glu Glu Leu Pro Pro Leu Asp Gln Leu Phe SUBSTITUTE SHEET (RULE 26) Trp Gly Leu Arg Cys Leu Lys Glu Gln Gly Tyr Asp Pro Phe Lys Glu Asp Leu Asn His Leu Val Gly Tyr Lys Gly Asn His Leu <210> 43 <211> 215 <212> PRT
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2123456CD1 <400> 43 Met Leu Gly Ala Glu Trp Ser Lys Leu Gln Pro Thr Glu Lys Gln Arg Tyr Leu Asp Glu Ala Glu Arg Glu Lys Gln Gln Tyr Met Lys Glu Leu Arg Ala Tyr Gln Gln Ser Glu Ala Tyr Lys Met Cys Thr Glu Lys Ile Gln Glu Lys Lys Ile Lys Lys Glu Asp Ser Ser Ser Gly Leu Met Asn Thr Leu Leu Asn Gly His Lys Gly Gly Asp Cys Asp Gly Phe Ser Thr Phe Asp Val Pro Ile Phe Thr Glu Glu Phe Leu Asp Gln Asn Lys Aia Arg Glu Ala Glu Leu Arg Arg Leu Arg Lys Met Asn Val Ala Phe Glu Glu Gln Asn Ala Val Leu Gln Arg His Thr Gln Ser Met Ser Ser Ala Arg Glu Arg Leu Glu Gln Glu Leu Ala Leu Glu Glu Arg Arg Thr Leu Ala Leu Gln Gln Gln Leu Gln Ala Val Arg Gln Ala Leu Thr Ala Ser Phe Ala Ser Leu Pro Val Pro Gly Thr Gly Glu Thr Pro Thr Leu Gly Thr Leu Asp Phe Tyr Met Ala Arg Leu His Gly Ala Ile Glu Arg Asp Pro Ala Gln His Glu Lys Leu Ile Val Arg Ile Lys Glu Ile Leu Ala Gln Val Ala Ser Glu His Leu <210> 44 <211> 539 <212> PRT
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2148792CD1 <400> 44 SUBSTITUTE SHEET (RULE 26) Met Ala Ala Leu Phe Leu Ser Ala Pro Pro Gln Ala Glu Val Thr Phe Glu Asp Val Ala Val Tyr Leu Ser Arg Glu Glu Trp Gly Arg Leu Gly Pro Ala Gln Arg Gly Leu Tyr Arg Asp Val Met Leu Glu Thr Tyr Gly Asn Leu Val Ser Leu Gly Val Gly Pro Ala Gly Pro Lys Pro Gly Val Ile Ser Gln Leu Glu Arg Gly Asp Glu Pro Trp Val Leu Asp Val Gln Gly Thr Ser Gly Lys Glu His Leu Arg Val Asn Ser Pro Ala Leu Gly Thr Arg Thr Glu Tyr Lys Glu Leu Thr Ser Gln Glu Thr Phe Gly Glu Glu Asp Pro Gln Gly Ser Glu Pro Val Glu Ala Cys Asp His Ile Ser Lys Ser Glu Gly Ser Leu Glu Lys Leu Val Glu Gln Arg Gly Pro Arg Ala Val Thr Leu Thr Asn Gly Glu Ser Ser Arg Glu Ser Gly Gly Asn Leu Arg Leu Leu Ser Arg Pro Val Pro Asp Gln Arg Pro His Lys Cys Asp Ile Cys Glu Gln Ser Phe Glu Gln Arg Ser Tyr Leu Asn Asn His Lys Arg Val His Arg Ser Lys Lys Thr Asn Thr Val Arg Asn Ser Gly Glu Ile Phe Ser Ala Asn Leu Val Val Lys Glu Asp Gln Lys Ile Pro Thr 21.5 220 225 Gly Lys Lys Leu His Tyr Cys Ser Tyr Cys Gly Lys Thr Phe Arg Tyr Ser Ala Asn Leu Val Lys His Gln Arg Leu His Thr Glu Glu Lys Pro Tyr Lys Cys Asp Glu Cys Gly Lys Ala Phe Ser Gln Ser Cys Glu Phe Ile Asn His Arg Arg Met His Ser Gly Glu Ile Pro Tyr Arg Cys Asp Glu Cys Gly Lys Thr Phe Thr Arg Arg Pro Asn Leu Met Lys His Gln Arg Ile His Thr Gly Glu Lys Pro Tyr Lys Cys Gly Glu Cys Gly Lys His Phe Ser Ala Tyr Ser Ser Leu Ile Tyr His Gln Arg Ile His Thr Gly Glu Lys Pro Tyr Lys Cys Asn Asp Cys Gly Lys Ala Phe Ser Asp Gly Ser Ile Leu Ile Arg His Arg Arg Thr His Thr Gly Glu Lys Pro Phe Glu Cys Lys Glu Cys Gly Lys Gly Phe Thr Gln Ser Ser Asn Leu Ile Gln His Gln Arg Ile His Thr Gly Glu Lys Pro Tyr Lys Cys Asn Glu Cys Glu Lys Ala Phe Ile Gln Lys Thr Lys Leu Val Glu His Gln Arg Ser His Thr Gly Glu Lys Pro Tyr Glu Cys Asn Asp Cys Gly Lys Val Phe Ser Gln Ser Thr His Leu Ile Gln His G1n Arg Ile His Thr Gly Glu Lys Pro Tyr Lys Cys Ser Glu Cys Gly Lys Ala Phe His Asn SUBSTITUTE SHEET (RULE 26) Ser Ser Arg Leu Ile His His Gln Arg Leu His His Gly Glu Lys Pro Tyr Arg Cys Ser Asp Cys Lys Lys Ala Phe Ser Gln Ser Thr Tyr Leu Ile Gln His Arg Arg Ile His ~hr Gly Glu Lys Pro Tyr Lys Cys Ser Glu Cys Gly Lys Ala Phe Arg His Ser Ser Asn Met Cys Gln His Gln Arg Ile His Leu Arg Glu Asp Phe Ser Met <210> 45 <211> 182 <212> PRT
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2751943CD1 <400> 45 Met Ala Arg Leu Leu Trp Leu Leu Arg Gly Leu Thr Leu Gly Thr Ala Pro Arg Arg Ala Val Arg Gly Gln Ala Gly Gly Gly Gly Pro' Gly Thr Gly Pro Gly Leu Gly Glu Ala Gly Ser Leu Ala Thr Cys Glu Leu Pro Leu Ala Lys Ser Glu Trp Gln Lys Lys Leu Thr Pro Glu Gln Phe Tyr Val Thr Arg Glu Lys Gly Thr Glu Pro Pro Phe Ser Gly Ile Tyr Leu Asn Asn Lys Glu Ala Gly Met Tyr His Cys Val Cys Cys Asp Ser Pro Leu Phe Ser Ser Glu Lys Lys Tyr Cys Ser Gly Thr Gly Trp Pro Ser Phe Ser Glu Ala His Gly Thr Ser Gly Ser Asp Glu Ser His Thr Gly I1~ Leu Arg Arg Leu Asp Thr Ser Leu Gly Ser Ala Arg Thr Glu Val Val Cys Lys Gln Cys Glu Ala His Leu Gly His Val Phe Pro Asp Gly Pro Gly Pro Asn Gly Gln Arg Phe Cys Ile Asn Ser Val Ala Leu Lys Phe Lys Pro Arg Lys His <210> 46 <211> 534 <212> PRT
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 3128913CD1 SUBSTITUTE SHEET (RULE 26) <400> 46 Met Ala Val Glu Ser Gly Val Ile Ser Thr Leu Ile Pro Gln Asp Pro Pro Glu Gln Glu Leu Ile Leu Val Lys Val Glu Asp Asn Phe Ser Trp Asp Glu Lys Phe Lys Gln Asn Gly Ser Thr Gln Ser Cys Gln Glu Leu Phe Arg Gln Gln Phe Arg Lys Phe Cys Tyr Gln Glu Thr Pro Gly Pro Arg Glu Ala Leu Ser Arg Leu Gln Glu Leu Cys Tyr Gln Trp Leu Met Pro Glu Leu His Thr Lys Glu Gln Ile Leu Glu Leu Leu Val Leu Glu Gln Phe Leu Ser Ile Leu Pro Glu Glu Leu Gln Ile Trp Val Gln Gln His Asn Pro Glu Ser Gly Glu Glu Ala Val Thr Leu Leu Glu Asp Leu Glu Arg Glu Phe Asp Asp Pro Gly Gln Gln Val Pro Ala Ser Pro Gln Gly Pro Ala Val Pro Trp Lys Asp Leu Thr Cys Leu Arg Ala Ser Gln Glu Ser Thr Asp Ile His Leu Gln Pro Leu Lys Thr Gln Leu Lys Ser Trp Lys Pro Cys Leu Ser Pro Lys Ser Asp Cys Glu Asn Ser Glu Thr Ala Thr Lys Glu Gly Ile Ser Glu Glu Lys Ser Gln Gly Leu Pro Gln Glu Pro _ 200 205 210 Ser Phe Arg Gly Ile Ser Glu His Glu Ser Asn Leu Val Trp Lys Gln Gly Ser Ala Thr Gly Glu Lys Leu Arg Ser Pro Ser Gln Gly Gly Ser Phe Ser Gln Val Ile Phe Thr Asn Lys Ser Leu Gly Lys Arg Asp Leu Tyr Asp Glu Ala Glu Arg Cys Leu Ile Leu Thr Thr Asp Ser Ile Met Cys Gln Lys Val Pro Pro Glu Glu Arg Pro Tyr Arg Cys Asp Val Cys Gly His Ser Phe Lys Gln His Ser Ser Leu Thr Gln His Gln Arg Ile His Thr Gly Glu Lys Pro Tyr Lys Cys Asn Gln Cys Gly Lys Ala Phe Ser Leu Arg Ser Tyr Leu Ile Ile His Gln Arg Ile His Ser Gly Glu Lys Ala Tyr Glu Cys Ser Glu Cys Gly Lys Ala Phe Asn Gln Ser Ser Ala Leu Ile Arg His Arg Lys Ile His Thr Gly Glu Lys Ala Cys Lys Cys Asn Glu Cys Gly Lys Ala Phe Ser Gln Ser Ser Tyr Leu Ile Ile His Gln Arg Ile His Thr Gly Glu Lys Pro Tyr Glu Cys Asn Glu Cys Gly Lys Thr Phe Ser Gln Ser Ser Lys Leu Ile Arg His Gln Arg Ile His Thr Gly Glu Arg Pro Tyr Glu Cys Asn Glu Cys Gly Lys Ala Phe Arg Gln Ser Ser Glu Leu Ile Thr His Gln Arg Ile His Ser Gly Glu Lys Pro Tyr Glu Cys Ser Glu Cys Gly Lys Ala Phe Ser Leu Ser SUBSTITUTE SHEET (RULE 26) Ser Asn Leu Ile Arg His Glri Arg Ile His Ser Gly Glu Glu Pro Tyr Gln Cys Asn Glu Cys Gly Lys Thr Phe Lys Arg Ser Ser Ala Leu Val Gln His Gln Arg Ile His Ser Gly Asp Glu Ala Tyr Ile Cys Asn Glu Cys Gly Lys Ala Phe Arg His Arg Ser Val Leu Met Arg His Gln Arg Val His Thr Ile Lys <210> 47 <211> 206 <212> PRT
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 3282941CD1 <400> 47 Met Ser Thr Gly Ser Val Ser Asp Pro Glu Glu Met Glu Leu Arg Gly Leu Gln Arg Glu Tyr Pro Val Pro Ala Ser Lys Arg Pro Pro Leu Arg Gly Val Glu Arg Ser Tyr Ala Ser Pro Ser Asp Asn Ser Ser Ala Glu Glu Glu Asp Pro Asp Gly Glu Glu Glu Arg Cys Ala Leu Gly Thr Ala Gly Ser Ala Glu Gly Cys Lys Arg Lys Arg Pro Arg Val Ala Gly Gly Gly Gly Ala Gly Gly Ser Ala Gly Gly Gly Gly Lys Lys Pro Leu Pro Ala Lys Gly Ser Ala Ala Glu Cys Lys Gln Ser Gln Arg Asn Ala Ala Asn Ala Arg Glu Arg Ala Arg Met Arg Val Leu Ser Lys Ala Phe Ser Arg Leu Lys Thr Ser Leu Pro Trp Val Pro Pro Asp Thr Lys Leu Ser Lys Leu Asp Thr Leu Arg Leu Ala Ser Ser Tyr Ile Ala His Leu Arg Gln Leu Leu Gln Glu Asp Arg Tyr Glu Asn Gly Tyr Val His Pro Val Asn Leu Thr Trp Pro Phe Val Val Ser Gly Arg Pro Asp Ser Asp Thr Lys Glu Val Ser Ala Ala Asn Arg Leu Cys Gly Thr Thr Ala <210> 48 <211> 172 <212> PRT
<213> Homo Sapiens SUBSTITUTE SHEET (RULE 26) <220>
<221> misc-feature <223> Incyte ID No.: 3286656CD1 <400> 48 Met Glu Ser Val Thr Phe Glu Asp Val Ala Val Glu Phe Ile Gln Glu Trp Ala Leu Leu Asp Ser Ala Arg Arg Ser Leu Cys Lys Tyr Arg Met Leu Asp Gln Cys Arg Thr Leu Ala Ser Arg Gly Thr Pro Pro Cys Lys Pro Ser Cys Val Ser Gln Leu Gly Gln Arg Ala Glu Pro Lys Ala Thr_Glu Arg Gly Ile Leu Arg Ala Thr Gly Val Ala Trp Glu Ser Gln Leu Lys Pro Glu Glu Leu Pro Ser Met Gln Asp Leu Leu Glu Glu Ala Ser Ser Arg Asp Met Gln Met Gly Pro Gly Leu Phe Leu Arg Met Gln Leu Val Pro Ser Ile Glu Glu Arg Glu Thr Pro Leu Thr Arg Glu Asp Arg Pro Ala Leu Gln Glu Pro Pro Trp Ser Leu Gly Cys Thr Gly Leu Lys Ala Ala Met Gln Ile Gln Arg Val Val Ile Pro Val Pro Thr Leu Gly His Arg Asn Pro Trp Val Ala Arg Asp Ser Ala Met <210> 49 <211> 275 <212> PRT
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 3490802CD1 <400> 49 Met Gly Pro Leu Gln Phe Arg Asp Val Ala Ile Glu Phe Ser Leu Glu Glu Trp His Cys Leu Asp Thr Ala Gln Arg Asn Leu Tyr Arg Asp Val Met Leu Glu Asn Tyr Arg Asn Leu Val Phe Leu Gly Ile Val Val Ser Lys Pro Asp Leu Val Thr Cys Leu Glu Gln Gly Lys Lys Pro Leu Thr Met Glu Arg His Glu Met Ile Ala Lys Pro Pro Val Met Ser Ser His Phe Ala Gln Asp Leu Trp Pro Glu Asn Ile Gln Asn Ser Phe Gln Ile Gly Met Leu Arg Arg Tyr Glu Glu Cys Arg His Asp Asn Leu Gln Leu Lys Lys Gly Cys Lys Ser Val Gly Glu His Lys Val His Lys Gly Gly Tyr Asn Gly Leu Asn Gln Cys Leu Thr Thr Thr Gln Lys Glu Ile Phe Gln Cys Asp Lys Tyr Gly SUBSTITUTE SHEET (RULE 26) Lys Val Phe His Lys Phe Ser Asn Ser Asn Thr Tyr Lys Thr Arg His Thr Gly Ile Asn Leu Phe Lys Cys Ile Ile Cys Gly Lys Ala Phe Lys Arg Ser Ser Thr Leu Thr Thr His Lys Lys Ile His Thr Gly Glu Lys Pro Tyr Lys Cys Glu Glu Cys Gly Lys Ala Phe Asn Gl.n Ser Ser Asn Leu Thr Thr His Lys Arg Ile His Thr Gly Glu Lys Pro Tyr Lys Cys Glu Glu Cys Gly Lys Ala Phe Asn Trp Ser Ser Asp Leu Asn Lys His Lys Lys Ile His Ile Glu Arg Lys Pro Tyr Ile Val Lys Asn Val Thr Asp Leu Leu Asn Val Pro Pro Leu Leu Ile Ser Ile Arg <210> 50 <211> 236 <212> PRT
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 3507366CD1 <400> 50 Met Asp Lys Arg Tyr Leu Gln Phe Asp Ile Lys Ala Phe Val Glu Asn Asn Pro Ala Ile Lys Trp Cys Pro Thr Pro Gly Cys Asp Arg Ala Val Arg Leu Thr Lys Gln Gly Ser Asn Thr Ser Gly Ser Asp Thr Leu Ser Phe Pro Leu Leu Arg Ala Pro Ala Val Asp Cys Gly Lys Gly His Leu Phe Cys Trp Glu Cys Leu Gly Glu Ala His Glu Pro Cys Asp Cys Gln Thr Trp Lys Asn Trp Leu Gln Lys Ile Thr Glu Met Lys Pro Glu Glu Leu Val Gly Val Ser Glu Ala Tyr Glu Asp Ala Ala Asn Cys Leu Trp Leu Leu Thr Asn Ser Lys Pro Cys Ala Asn Cys Lys Ser Pro Ile Gln Lys Asn Glu Gly Cys Asn His Met Gln Cys Ala Lys Cys Lys Tyr Asp Phe Cys Trp Ile Cys Leu Glu Glu Trp Lys Lys His Ser Ser Ser Thr Gly Gly Tyr Tyr Arg Cys Thr Arg Tyr Glu Val Ile Gln His Val Glu Glu Gln Ser Lys Glu Met Thr Val Glu Ala Glu Lys Lys His Lys Arg Phe Gln Glu Leu Asp Arg Phe Met His Tyr Tyr Thr Arg Phe Lys Asn His Glu His Ser Tyr Gln Leu Glu Gln Arg Leu Leu Lys Thr Ala Lys Glu SUBSTITUTE SHEET (RULE 26) Lys Met Glu Gln Met Ser Arg Val Ser Lys Asn <210> 51 <211> 214 <212> PRT
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 3573060CD1 <400> 51 Met Asn Leu Ser Ser Ala Ser Ser Thr Glu Glu Lys Ala Val Thr Thr Val Leu Trp Gly Cys Glu Leu Ser Gln Glu Arg Arg Thr Trp Thr Phe Arg Pro Gln Leu Glu Gly Lys Gln Ser Cys Arg Leu Leu Leu His Thr Ile Cys Leu Gly Glu Lys Ala Lys Glu Glu Met His Arg Val Glu Ile Leu Pro Pro Ala Asn Gln Glu Asp Lys Lys Met Gln Pro Val Thr Ile Ala Ser Leu Gln Ala Ser Val Leu Pro Met Val Ser Met Val Gly Val Gln Leu Ser Pro Pro Val Thr Phe Gln Leu Arg Ala Gly Ser Gly Pro Val Phe Leu Ser Gly Gln Glu Arg Tyr Glu Ala Ser Asp Leu Thr Trp Glu Glu Glu Glu Glu Glu Glu Gly Glu Glu Glu Glu Glu Glu Glu Glu Asp Asp Glu Asp Glu Asp Ala Asp Ile Ser Leu Glu Glu Gln Ser Pro Val Lys Gln Val Lys Arg Leu Val Pro Gln Lys Gln Ala Ser Val Ala Lys Lys Lys Lys Leu Glu Lys Glu Glu Glu Glu Ile Arg Ala Ser Val Arg Asp Lys Ser Pro Val Lys Lys Ala Lys Ala Thr Ala Arg Ala Lys Lys Pro Gly Phe Lys Lys <210> 52 <211> 396 <212> PRT
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 3573661CD1 <400> 52 Met Asn Phe Thr Val Gly Phe Lys Pro Leu Leu Gly Asp Ala His SUBSTITUTE SHEET (RULE 26) Ser Met Asp Asn Leu Glu Lys Gln Leu Ile Cys Pro Ile Cys Leu Glu Met Phe Ser Lys Pro Val Val Ile Leu Pro Cys Gln His Asn Leu Cys Arg Lys Cys Ala Asn Asp Val Phe Gln Ala Ser Asn Pro Leu Trp Gln Ser Arg Gly Ser Thr Thr Val Ser Ser Gly Gly Arg Phe Arg Cys Pro Ser Cys Arg His Glu Val Val Leu Asp Arg His Gly Val Tyr Gly Leu Gln Arg Asn Val Leu Val Glu Asn Ile Ile Asp Ile Tyr Lys Gln Glu Ser Ser Lys Pro Leu His Ser Lys Aia Glu Gln His Leu Met Cys Glu Glu His Glu Glu Glu Lys Ile Asn Ile Tyr Cys Leu Ser Cys Glu Val Pro Thr Cys Ser Leu Cys Lys Val Phe Gly Ala His Lys Asp Cys Glu Val Ala Pro Leu Pro Thr Ile Tyr Lys Arg Gln Lys Ser Glu Leu Ser Asp Gly Ile Ala Met Leu Val Ala Gly Asn Asp Arg Val Gln Ala Val I1e Thr Gln Met Glu Glu Val Cys Gln Thr Ile Glu Asp Asn Ser Arg Arg Gln Lys Gln Leu Leu Asn Gln Arg Phe Glu Ser Leu Cys Ala Val Leu Glu Glu Arg Lys Gly Glu Leu Leu Gln Ala Leu Ala Arg Glu Gln Glu Glu Lys Leu Gln Arg Val Arg Gly Leu Ile Arg Gln Tyr Gly Asp His Leu Glu Ala Ser Ser Lys Leu Val Glu Ser Ala Ile Gln Ser Met Glu Glu Pro Gln Met Ala Leu Tyr Leu Gln Gln Ala Lys.Glu Leu Ile Asn Lys Val Gly Ala Met Ser Lys Val Glu Leu Ala Gly Arg Pro Glu Pro Gly Tyr Glu Ser Met Glu Gln Phe Thr Val Arg Val Glu His Val Ala Glu Met Leu Arg Thr Ile Asp Phe Gln Pro Gly Ala Ser Gly Gly Gly Arg Gly Gly Gly Pro Arg Arg Lys Lys Arg Ala Thr Arg Gly Pro Glu Glu Lys Thr Ala Arg Met Gly Pro Tyr Arg Pro Leu Arg Pro Asn Pro Asp Pro Leu Leu Arg Lys Ser Pro Arg Arg Leu Arg Ile Ser Gly Gly Arg Asn Ser Cys Arg Lys Lys Thr Pro Ala Ser Phe <210> 53 <211> 486 <212> PRT
<213> Homo Sapiens SUBSTITUTE SHEET (RULE 26) <220>
<221> misc-feature <223> Incyte ID No.: 3633422CD1 <400> 53 Met Arg Arg Leu Val His Asp Leu Leu Pro Pro Glu Val Cys Ser Leu Leu Asn Pro Ala Ala Ile Tyr Ala Asn Asn Glu Ile Ser Leu Arg Asp Val Glu Val Tyr Gly Phe Asp Tyr Asp Tyr Thr Leu Ala Gln Tyr Ala Asp Ala Leu His Pro Glu Ile Phe Ser Thr Ala Arg Asp Ile Leu Ile Glu His Tyr Lys Tyr Pro Glu Gly Ile Arg Lys Tyr Asp Tyr Asn Pro Ser Phe Ala Ile Arg Gly Leu His Tyr Asp Ile Gln Lys Ser Leu Leu Met Lys Ile Asp Ala Phe His Tyr Val Gln Leu Gly Thr Ala Tyr Arg Gly Leu Gln Pro Val Pro Asp Glu Glu Val Ile Glu Leu Tyr Gly Gly Thr Gln His Ile Pro Leu Tyr Gln Met Ser Gly Phe Tyr Gly Lys Gly Pro Ser Ile Lys Gln Phe Met Asp Ile Phe Ser Leu Pro Glu Met Ala Leu Leu Ser Cys Val Val Asp Tyr Phe Leu Gly His Ser Leu Glu Phe Asp Gln Ala His Leu Tyr Lys Asp Val Thr Asp Ala Ile Arg Asp Val His Val Lys Gly Leu Met Tyr Gln Trp Ile Glu ~ln Asp Met Glu Lys Tyr Ile 200 ~ 205 210 Leu Arg Gly Asp Glu Thr Phe Ala Val Leu Ser Arg Leu Val Ala His Gly Lys Gln Leu Phe Leu Ile Thr Asn Ser Pro Phe Ser Phe Val Asp Lys Gly Met Arg His Met Val Gly Pro Asp Trp Arg Gln Leu Phe Asp Val Val Ile Val Gln Ala Asp Lys Pro Ser Phe Phe Thr Asp Arg Arg Lys Pro Phe Arg Lys Leu Asp Glu Lys Gly Ser Leu Gln Trp Asp Arg Ile Thr Arg Leu Glu Lys Gly Lys Ile Tyr Arg Gln Gly Asn Leu Phe Asp Phe Leu Arg Leu Thr Glu Trp Arg Gly Pro Arg Val Leu Tyr Phe Gly Asp His Leu Tyr Ser Asp Leu Ala Asp Leu Met Leu Arg His Gly Trp Arg Thr Gly Ala Ile Ile Pro Glu Leu Glu Arg Glu Ile Arg Ile Ile Asn Thr Glu Gln Tyr Met His Ser Leu Thr Trp Gln Gln Ala Leu Thr Gly Leu Leu Glu Arg Met Gln Thr Tyr Gln Asp Ala Glu Ser Arg Gln Val Leu Ala Ala Trp Met Lys Glu Arg Gln Glu Leu Arg Cys Ile Thr Lys Ala Leu Phe Asn Ala Gln Phe Gly Ser Ile Phe Arg Thr Phe His Asn Pro Thr Tyr Phe Ser Arg Arg Leu Val Arg Phe Ser Asp Leu Tyr SUBSTITUTE SHEET (RULE 26) Met Ala Ser Leu Ser Cys Leu Leu Asn Tyr Arg Val Asp Phe Thr Phe Tyr Pro Arg Arg Thr Pro Leu Gln His Glu Ala Pro Leu Trp Met Asp Gln Leu Cys Thr Gly Cys Met Lys Thr Pro Phe Leu Gly Asp Met Ala His Ile Arg 485 ' <210> 54 <211> 555 <212> PRT
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 3993377CD1 <400> 54 Met Gly Ala Glu Asp Lys Leu Pro Leu Glu Asp Ser Pro Val Ile Ala Ala Leu Asp Cys Pro Ser Leu Asn Asn Ala Thr Ala Phe Ser Leu Leu Ala Asp Asp Ser Gln Thr Ser Thr Ser Ile Phe Ala Ser Pro Thr Ser Pro Pro Val Leu Gly Glu Ser Val Leu Gln Asp Asn Ser Phe Asp Leu Asn Asn Gly Ser Asp Ala Glu Gln Glu Glu Met Glu Thr Gln Ser Ser Asp Phe Pro Pro Ser Leu Thr Gln Pro Ala Pro Asp Gln Ser Ser Thr Ile Gln Leu His Pro Ala Thr Ser Pro Ala Val Ser Pro Thr Thr Ser Pro Ala Val Ser Leu Val Val Ser Pro Ala Ala Ser Pro Glu Ile Ser Pro Glu Val Cys Pro Ala Ala Ser Thr Val Val Ser Pro Ala Val Phe Ser Val Val Ser Pro Ala Ser Ser Ala Val Leu Pro Ala Val Ser Leu Glu Val Pro Leu Thr Ala Ser Val Thr Ser Pro Lys Ala Ser Pro Val Thr Ser Pro Ala Ala Ala Phe Pro Thr Ala Ser Pro Ala Asn Lys Asp Val Ser Ser Phe Leu Glu Thr Thr Ala Asp Val Glu Glu Ile Thr Gly Glu Gly Leu Thr Ala Ser Gly Ser Gly Asp Val Met Arg Arg Arg Ile Ala Thr Pro Glu Glu Val Arg Leu Pro Leu Gln His Gly Trp Arg Arg Glu Val Arg Ile Lys Asn Ser Ser His Arg Trp Gln Gly Glu Thr Trp Tyr Tyr Gly Pro Cys Gly Lys Arg Met Lys Gln Phe Pro Glu Val Ile Lys Tyr Leu Ser Arg Asn Val Val His Ser Val Arg Arg Glu His Phe Ser Phe Ser Pro Arg Met Pro Val Gly Asp Phe Phe SUBSTITUTE SHEET (RULE 26) Glu Glu Arg Asp Thr Pro Glu Gly Leu Gln Trp Val Gln Leu Ser Ala Glu Glu Ile Pro Ser Arg Ile Gln Ala Ile Thr Gly Lys Arg Gly Arg Pro Arg Asn Thr Glu Lys Ala Lys Thr Lys Glu Val Pro Lys Val Lys Arg Gly Arg Gly Arg Pro Pro Lys Val Lys Ile Thr Glu Leu Leu Asn Lys Thr Asp Asn Arg Pro Leu Lys Lys Leu Glu Ala Gln Glu Thr Leu Asn Glu Glu Asp Lys Ala Lys Ile Ala Lys Ser Lys Lys Lys Met Arg Gln Lys Val Gln Arg Gly Glu Cys Gln Thr Thr Ile Gln Gly Gln Ala Arg Asn Lys Arg Lys Gln Glu Thr Lys Ser Leu Lys Gln Lys Glu Ala Lys Lys Lys Ser Lys Ala Glu Lys Glu Lys Gly Lys Thr Lys Gln Glu Lys Leu Lys Glu Lys Val Lys Arg Glu Lys Lys Glu Lys Val Lys Met Lys Glu Lys Glu Glu Val Thr Lys Ala Lys Pro Ala Cys Lys Ala Asp Lys Thr Leu Ala Thr Gln Arg Arg Leu Glu Glu Arg Gln Arg Gln Gln Met Ile Leu Glu Asp Met Lys Lys Pro Thr Glu Asp Met Cys Leu Thr Asp His Gln Pro Leu Pry Asp Phe Ser Arg Val Pro Gly Leu Thr Leu Pro Ser Gly Ala Phe Ser Asp Cys Leu Thr Ile Val Glu Phe Leu His Ser Phe Gly Lys Val Leu Gly Leu Asp Pro Ala Gln Gly Cys Ala <210> 55 <211> 61 <212> PRT
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 4717936CD1 <400> 55 Met Gln Pro Arg Thr Gln Pro Leu Ala Gln Thr Leu Pro Phe Phe Leu Gly Gly Ala Pro Arg Asp Thr Gly Leu Arg Val Pro Val Ile Lys Met Gly Thr Gly Trp Glu Gly Phe Gln Arg Thr Leu Lys Glu Val Ala Tyr Ile Leu Leu Cys Cys Trp Cys Ile Lys Glu Leu Leu Asp SUBSTITUTE SHEET (RULE 26) <210> 56 <211> 2781 <212> DNA
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 025733CB1 <400> 56 gaagtggggt gcacgcttcg ggttggtgtc atggcagctg cggggagccg caagaggcgc 60 ctggcggagc tgacggtgga cgagttccta gcttcgggct ttgactccga gtccgaatcc 120 gagtccgaaa attctccaca agcggagaca cgggaagcac gcgaggctgc ccggagtccg 180 gataagccgg gcgggagccc ctcggccagc cggcgtaaag gccgtgcctc tgagcacaaa 240 gaccagctct ctcggctgaa ggacagagac cccgagttct acaagttcct gcaggagaat 300 gaccagagcc tgctaaactt cagcgactcg gacagctctg aggaggaaga ggggccgttc 360 cactccctgc cagatgtgct ggaggaagcc agtgaggagg aggatggagc ggaggaagga 420 gaagatgggg acagagtccc cagagggctg aaggggaaga agaattctgt tcctgtgacc 480 gtcgccatgg ttgagagatg gaagcaggca gcaaagcaac gcctcactcc aaagctgttc 540 catgaagtgg tacaggcgtt ccgagcagct gtggccacca cccgagggga ccaggaaagt 600 gctgaggcca acaaattcca ggtcacggac agtgctgcat tcaatgctct ggttaccttc 660 tgcatcagag acctcattgg ctgtctccag aagctgctgt ttggaaaggt ggcaaaggat 720 agcagcagga tgctgcagcc gtccagcagc ccgctctggg ggaagcttcg tgtggacatc 780 aaggcttacc tgggctcggc catacagctg gtgtcctgtc tgtcggagac gacggtgttg 840 gcggccgtgc tgcggcacat cagcgtgctg gtgccctgct tcctgacctt ccccaagcag 900 tgccgcatgc tgctcaagag aatggtggtc gtatggagca ctggggagga gtctctgcgg 960 gtgctggctt tcctggtcct cagcagagtc tgccggcaca agaaggacac tttccttggc 1020 cccgtcctca agcaaatgta catcacgtat gtgaggaact gcaagttcac ctcgcctggt 1080 gccctcccct tcatcagttt catgcagtgg accttgacgg agctgctggc cctggagccg 1140 ggtgtggcct accagcacgc cttcctctac atccgccagc tcgccataca cctgcgcaac 1200 gccatgacca cccgcaagaa ggaaacatac cagtctgtgt acaactggca gtatgtgcac 126 tgcctcttcc tgtggtgccg ggtcctgagc actgcgggcc ccagcgaagc cctccagccc 1320 ttggtctacc cccttgccca agtcatcatt ggctgtatca agctcatccc cactgcccgc 1380 ttctacccgc tgcgaatgca ctgcatccgt gccctgacgc tgctctcggg gagctcgggg 1440 gccttcatcc cggtgctgcc tttcatcctg gagatgttcc agcaggtcga cttcaacagg 1500 aagccagggc gcatgagctc caagcccatc aacttctccg tgatcctgaa gctgtccaat 1560 gtcaacctgc aggagaaggc gtaccgggac ggcctggtgg agcagctgta cgacctcacc 1620 ctggagtacc tgcacagcca ggcacactgc atcggcttcc cggagctggt gctgcctgtg 1680 gtcctgcagc tgaagtcgtt cctccgggag tgcaaggtgg ccaactactg ccggcaggtg 1740 cagcagctgc ttgggaaggt tcaggagaac tcggcataca tctgcagccg ccgccagagg 1800 gtttccttcg gcgtctctga gcagcaggca gtggaagcct gggagaagct gacccgggaa 1860 gaggggacac ccttgacctt gtactacagc cactggcgca agctgcgtga ccgggagatc 1920 cagctggaga tcagtggcaa agagcggctg gaagacctga acttccctga gatcaaacga 1980 aggaagatgg ctgacaggaa ggatgaggac aggaagcaat ttaaagacct ctttgacctg 2040 aacagctctg aagaggacga caccgaggga ttctcggaga gagggatact gaggcccctg 2100 agcactcggc atggggtgga agacgatgaa gaggacgagg aggagggcga ggaggacagc 2160 agcaactcgg agggtgaatg gtcttgggat ggagacccag acgcagaggc ggggctggcc 2220 cctggggagc tgcagcagct ggcccagggg ccggaggacg agctggagga tctgcagctc 2280 tcagaggacg actgaggcag cccatctggg gggcctgtag gggctgccgg gctggtggcc 2340 agtgtttcca cctccctggc agtcaggcct agaggctggc gtctgtgcag ttgggggagg 2400 cagtagacac gggacaggct ttattattta tttttcagca tgaaagacca aacgtatcga 2460 gagctgggct gggctgggct ggtgtggctg ctgaagcccc acagctgtgg gctgctgaag 2520 tcagctccgc gggggagctg accctgacgt cagcagaccg agaccagtcc cagttccagg 2580 gggaggcctg caggcccctg gccccttcca ccacctctgc cctccgtctg cagacctcgt 2640 ccatctgcac caggctctgc cttcactccc ccaagtcttt gaaaatttgt tcctttcctt 2700 tgaagtcaca ttttctttta aaattttttg ttttgcatcc gaaaccgaaa gaaataaagc 2760 ggtgggaggc aaaaaaaaaa a 2781 <210> 57 <211> 2544 <212> DNA

SUBSTITUTE SHEET (RULE 26) <213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 079702CB1 <400> 57 cgggaaacca aaatggcgag gggctgtatt gaagtgggct gtgtttgagg ccggtgtaag 60 aacgctcatt ctacccccaa cccttgtctc caaggacctc ggtttgtgcg tgcatatgtg 120 ccgggtaccc ggtggggcgg gtgcccagta agtgctcgga ctcgcagggg aagcgcccac 180 ggggacggat tggttgtttt ttcctgtatg aagcggttgg caccactgaa gtgaccgaat 240 gagagactct acaggggcag gtaattcact ggtccacaag cggtctcctt tacgtcgaaa 300 ccaaaagacc ccaacatcct tgaccaagct gtctttacag gatggacata aagccaaaaa 360 gccagcatgt aaatttgaag agggtcagga tgtcctagct agatggtcag atggcttgtt 420 ttatcttggc actatcaaaa agataaacat attgaaacag agctgcttca tcatatttga 480 agacagttct aaatcctggg ttctctggaa ggacattcaa acaggagcca ctggaagtgg 540 ggaaatggtc tgtacaatat gtcaagaaga gtattcagaa gctcccaatg aaatggttat 600 atgtgacaag tgtggccaag gatatcatca gttgtgtcac acacctcata ttgattccag 660 tgtgattgat tcagatgaaa aatggctctg tcggcagtgt gtttttgcaa caacaacaaa 720 gaggggtggt gcacttaaga aaggaccaaa tgccaaagca ttgcaagtca tgaagcagac 780 attaccctat agtgtggcag accttgaatg ggatgcaggt cataaaacca atgtccagca 840 gtgttactgc tattgtggag gccctggaga ctggtatttg aagatgctac agtgctgcaa 900 atgtaagcag tggtttcatg aggcttgtgt gcaatgcctt caaaagccaa tgctatttgg 960 agacagattt tatacgttta tatgctctgt ctgcagttct ggaccagaat acctcaaacg 1020 tctaccatta cagtgggtag atatagcaca cctatgcctt tacaacctaa gtgttattca 1080 taagaagaaa tactttgatt ctgaacttga gcttatgaca tacattaatg aaaactggga 1140 tagattgcac cctggagagc tggcagacac accaaaatct gaaagatatg agcatgttct 1200 ggaggcatta aatgattaca agaccatgtt tatgtctggg aaagaaataa agaagaagaa 1260 gcatttgttt gggttgcgaa ttcgtgttcc tcctgtgcca ccaaatgtgg ctttcaaagc 1320 agagaaagaa cctgaaggaa catctcatga atttaaaatt aaaggcagaa aggcatccaa 138t~
acc'Latatct gattcaaggg aagtaagcaa tggcatagaa aaaaaaaaaa aaaaaaaatc 1440 tgtaggtcgt ccacctggcc catatacaag aaaaatgatt caaaaaactg ctgagccact 1500 tttggataag gaatcaattt cagagaatcc tactttggat ttaccttgtt ctatagggag 1560 aactgaggga actgcacatt catccaatac ctcagatgtg gatttcacgg gtgcttccag 1620 tgcaaaagaa actacctcgt ctagcatttc caggcattat ggattatctg actccagaaa 1680 aagaacgcgt acaggaagat cttggcctgc tgcaatacca catttgcgga gaagaagagg 1740 tcgtcttcca agaagagcac tccagactca gaactcagaa attgtaaaag atgatgaagg 1800 caaagaagat tatcagtttg atgaactcaa cacagagatt ctgaataact tagcagatca 1860 ggagttacaa ctcaatcatc taaagaactc cattaccagt tattttggtg ctgcaggtag 1920 aatagcatgt ggcgaaaaat accgagtttt ggcacgtcgg gtgacacttg atggaaaggt 1980 gcagtatctt gtggaatggg aaggagcaac tgcatcctga ctgtaggact gaacattatg 2040 ttcactgcac tctgattttc tgtaggtaca gttcaaagcc ctaaaggagt ctggctttta 2100 ctatctttct taaaaaaaaa aaaaagtcaa aaaaattcaa aaaaggggat gatactagcc 2160 ttaacatgta cctgtcaatg ttatggatat tgtcataaaa aggtatcttt taaaaatcag 2220 aacagagact taatttttta aatcttaaga tttgtagaat gtttctagga taggatatta 2280 aaaatgattg aaacccatgc atggtgttag acaatttttc taattattcc attgagtcag 2340 ttttttgtga ttagtgatta tcagagcaaa catcatgtag atagcacaag tatttggaga 2400 aacgttgttt gttttgttac caaaatgttg gaaaaattta tttcaatacc ttttagattt 2460 cataaagtgc agtgtatata atgcctactg aaagactgta aaatattgaa attttctttc 2520 aagcaaagtg taaataaata tatc 2544 <210> 58 <211> 1627 <212> DNA
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 116208CB1 <400> 58 SUBSTITUTE SHEET (RULE 26) ctgatgaggg cgctgcattt attgaagagc ggctgcagcc ctgcggttca gattaaaatc 60 cgagaattgt atagacgccg atatccacga ac~cttgaag gactttctga tttatccaca 120 atcaaatcat cggttttcag tttggatggt ggctcatcac ctgtagaacc tgacttggcc 180 gtggctggaa tccactcgtt gccttccact tcagttacac ctcactcacc atcctctcct 240 gttggttctg tgctgcttca agatactaag cccacatttg agatgcagca gccatctccc 300 ccaattcctc ctgtccatcc tgatgtgcag ttaaaaaatc tgccctttta tgatgtcctt 360 gatgttctca tcaagcccac gagtttagtt caaagcagta ttcagcgatt tcaagagaag 420 ttttttattt ttgctttgac acctcaacaa gttagagaga tatgcatatc cagggatttt 480 ttgccaggtg gtaggagaga ttatacagtc caagttcagt tgagactttg cctggcagag 540 acaagttgcc ctcaagaaga taactatcca aatagtctat gtataaaagt aaatgggaag 600 ctatttcctt tgcctggcta tgcaccaccg cctaaaaatg ggattgaaca gaagcgccct 660 ggacgcccct tgaatattac atctttagtt aggttatctt cagctgtgcc aaaccaaatt 720 tccatttctt gggcatcaga aattgggaag aattactcta tgtctgtata tcttgtacgg 780 cagcttacat cagccatgtt attacagaga ttaaaaatga aaggtattag aaaccctgat 840 cattccagag cactaagtaa agaaaaactt actgcagatc ctgatagtga aattgctaca 900 actagccttc gggtatcctt gatgtgccct ttaggaaaaa tgaggctgac aatcccatgc 960 cgtgcagtga cttgtacaca tctgcagtgt tttgatgctg ccctctatct acaaatgaat 1020 gagaaaaagc ccacctggat ttgtcctgtg tgtgacaaaa aagctgccta tgaaagtcta 1080 atattagatg ggctttttat ggaaattctc aatgactgtt ctgatgtaga tgagatcaaa 1140 ttccaagaag atggttcttg gtgtccaatg agaccgaaga aagaagctat gaaagtatcc 1200 agccaaccgt gtacaaaaat agaaagttca agcgtcctca gtaagccttg ttcagtgact 1260 gtagccagtg aggcaagcaa gaagaaagta gatgttattg atcttacaat agaaagctct 1320 tctgacgaag aggaagaccc tcctgccaaa aggaaatgca tctttatgtc agaaacacaa 1380 agcagcccaa ccaaaggggt tctcatgtat cagccatctt ctgtaagggt gcccagtgtg 1440 acttcggttg atcctgctgc tattccgcct tcattaacag actactcagt accattccac 1500 catacgccaa tatcaagcat gtcatcagat ttgccaggag aacaaagaag aaatgatatt 1560 aataatgaac tgaagcttgg aacatcttct gatactgtgc aacagtgaat acaaaataaa 1620 accgata 1627 <210> 59 <211> 1043 <212> DNA
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 179261CB1 <400> 59 gtgggatatt tcagtcaaat gaaaatcatc tctgaaaatg tgcccagtta caaaactcat 60 gaatctctta ctttacctcg gagaactcat gacagtgaga agccctatga atacaaggaa 120 tatgagaagg tcttcagttg tgacttagag tttgatgaat atcagaaaat acatactggt 180 ggaaaaaact atgaatgtaa tcaatgttgg'aaaacctttg ggatagataa ctccagtatg 240 ttacaactga atattcatac tggtgtgaaa ccttgtaaat atatggaata tgggaataca 300 tgtagttttt ataaagactt taatgtatac cagaaaattc ataatgagaa gttctataaa 360 tgtaaggaat acagaaggac ctttgaaaga gttggaaaag ttactccact tcaaagagtt 420 catgatggtg agaaacactt tgaatgctca ttctgtggga aatcctttag agtgcatgca 480 caacttactc gacatcagaa aatccatact gatgagaaaa cttacaaatg tatggaatgt 540 ggcaaggact tcagatttca ttcacagctt accgaacatc agagaattca tactggtgag 600 aaaccctaca aatgtatgca ctgtgagaag gtttttagaa ttagttcaca gctcattgaa 660 catcagagaa ttcacactgg tgagaaacct tatgcatgta aggaatgtgg gaaggctttt 720 ggagtatgta gagaacttgc tcgtcatcag agaattcata ctggaaaata ctgtggatgg 780 atttaatagg taatcaaggc aattcagtat ctccctctct taaagtctgt ttttagactt 840 catggtcatt ctgtatgtag acgtagaatt gcttagtcat agctgatata tacttatagc 900 tttgttagat gttgccaaat atttctcctt tttatgttaa aaagtttttt tcatgagttt 960 ctcatcctgg catgttttgt ttacaatagc ttttgatgtt tgtattattg ctcttttgac 1020 taatcagttt tttaattctg gat 1043 <210> 50 <211> 2448 ~ 8/91 SUBSTITUTE SHEET (RULE 26) <212> DNA
<213> Homo Sapiens <220>
<221> misc-Leature <223> Incyte ID No.: 259161CB1 <400> 60 ctggcgggaa gattttactc ccgagtagcg gaaagatctg ctcgaggcct gggtgctttg 60 gtgtcggaga tccgagagtc ggagatcgga gagtcggaca caggacagtc ggacaccgga 120 cagtcaaaca ccggagagtt agactgggct tctcggtggg gagaggctct gggataacta 180 ctgttacagc tttgaagggt caagggagga ttggccacca aagcctgttt attagcagct 240 gccatttgtt gaaagaaatt tggattattt tagaaacaaa tttggaaaga aaaagaatgg 300 cgtccgtttc agctctaact gaggaactgg attctataac cagtgagcta catgcagtag 360 aaattcaaat tcaagaactt acggaaaggc aacaagagct tattcagaaa aaaaaagtcc 420 tgacaaagaa aataaagcag tgtttagagg attctgatgc cggggcaagc aatgaatatg 480 attcttcacc tgccgcttgg aataaagaag attttccatg gtctggtaaa gttaaagata 540 ttctgcaaaa tgtctttaaa ctggaaaagt tcagaccact tcagcttgaa actattaacg 600 taacaatggc tggaaaggag gtatttcttg ttatgcctac aggaggtgga aagagcttat '060 gttaccagtt accagcatta tgttcagatg gttttacact cgtcatttgc ccattgatct 720 ctcttatgga agaccaatta atggttttaa aacaattagg aatttcagca accatgttaa 780 atgcttctag ttctaaggag catgttaaat gggttcatgc tgaaatggta aataaaaact 840 ccgagttaaa gctgatttat gtgactccag agaaaattgc aaaaagcaaa atgtttatgt 900 caagactaga gaaagcctat gaagcaagga gatttactcg aattgctgtg gatgaagttc 960 actgctgtag tcagtgggga catgatttca gacctgatta taaggcactt ggtatcttaa 1020 agcggcagtt ccctaacgca tcactaattg ggctgactgc aactgcaaca aatcacgttt 1080 tgacggatgc tcagaaaatt ttgtgcattg aaaagtgttt tacttttaca gcttctttta 1140 ataagccaga tgtgaggttt gttatccatc attcaatgag taaatccatg gaaaattatt 1200 accaagagag tggacgtgca ggtcgagatg acatgaaagc agactgtatt ttgtactacg 1260 gctttggaga tatattcaga ataagttcaa tggtggtgat ggaaaatgtg ggacagcaga 1320 agctttatga gatggtatca tactgtcaaa acataagcaa atgtcgtcgt gtgttgatgg 1380 ctcaacattt tgatgaagta tggaactcag aagcatgtaa caaaatgtgc gataactgct 1440 gtaaagacag tgcatttgaa agaaagaaca taacagagta ctgcagagat ctaatcaaga 1500 tcctgaagca ggcagaggaa ctgaatgaaa aactcactcc attgaaactg attgattctt 1560 ggatgggaaa gggtgcagca aaactgagag tagcaggtgt tgtggctccc acacttcctc 1620 gtgaagatct ggagaagatt attgcacact ttctaataca gcagtatctt aaagaagact 1680 acagttttac agcttatgct accatttcgt atttgaaaat aggacctaaa gctaatcttc 1740 tgaacaatga ggcacatgct attactatgc aagtgacaaa gtccacgcag aactctttca 1800 gggctgaatc gtctcaaact tgtcattctg aacaaggtga taaaaagatt ggaggaaaaa 1860 aattccaggc aacttccaga agaaggctgc aaacatgctt cagcaatctg gttctaagaa 1920 tacaggagct aagaaaagaa aaatcgatga tgcctgatat gactgttact aaattttcta 1980 attaaagatg gtttatgcat gtatatgcca ttatttttgt agttagacaa tagtttttaa 2040 aagaatttca tagatatttt atatgtatgg atctatattt tcagagctta tctctgaaga 2100 tctaaacttt tgagaatgtt tgaaaattag agatcatgaa ttatataatt ttccagtata 2160 aaacaaggga aaaattttta tgtaaaaccc tttaaatgta aaatatttga gaataagttc 2220 atacaatcgt cttaagtttt ttatgccttt atatacttag ctatattttt tcttttgaca 2280 taactatctt tttgaaagca atattatact gacagaggct cactgagtga tactttaagt 2340 taaatatgta gatcaaggat gtccaatctt ttggcttccc tgagccacac tggaagaaga 2400 attgtcttgg gccgcacata aaatatgcta acactgatga tagctgat 2448 <210> 61 <211> 2255 <212> DNA
<213> Homo Sapiens <220>
<221> misc-Laature <223> Incyte ID No.: 320087CB1 SUBSTITUTE SHEET (RULE 26) <400> 61 ttccggttct gtacccccat cctttctctc gcccctccta cccgcagctc ctggcgctcg 60 gcggggctaa ctgcagcggg gagatctcgg ccgccaagct ccgcctcccg ccccgggctg 120 tgccccgggg ctcgcctgag gccgaccacc cgcaacccac ctctagcggc tttgctcgag 180 gcccaccttc ttcccacccc cggcaaactc cagtaggctc gccc~cgctg actccccgc~ 240 cccgcgtcaa ctgcaagggg cccgcccata gccagttccg gggcggttgc tcacatcgac 300 cggaactccc cgccccctcc cgcggcccct ggggccgtag gaggccgcag cgaggaggta 360 gagggggcgg gggtcgcact agggtgtccc tagagaacga ggactctgaa ggcgggacat 420 ttgggcgacc cccgggcggg gccagccatt aaacagtccc acttctgtgc cagacactga 480 actgggctct tgacgggcat catctcttaa tcctcagaac atcccaggga gctccacagg 540 atccccatat cctgggccat gagtgagttg aaagactgcc ccttgcagtt ccacgacttc 600 aagtctgtgg atcacctgaa ggtctgtccc cgctacacgg cagtgctggc acgctctgag 660 gatgatggca tcggcatcga ggagctggac accctgcagc tggagctgga gaccctgctg 720 tcttctgcca gccggcgcct gcgtgtgctt gaggccgaaa cccagatcct caccgactgg 780 caggataaga aaggtgacag acgattcctg aagctgggtc gagaccatga acttggagct 840 ccccccaaac atgggaagcc caagaagcag aaactggaag ggaaggcagg acatgggccg 900 ggccctggcc caggacggcc caaatccaaa aaccttcagc ccaagatcca ggaatatgaa 960 ttcactgatg accctatcga cgtgccacgg atccccaaaa atgatgcccc caacaggttc 1020 tgggcttcag tggagcccta ctgtgctgac atcaccagcg aggaggtccg cacacttgag 1080 gagttactga agcccccaga agatgaggct gagcattaca agatcccacc cctggggaag 1140 cactactccc agcgctgggc ccaggaggac ctgctggagg agcagaagga tggggcccgg 1200 gcagcggctg tggctgacaa gaagaaaggc ctcatggggc cactgaccga actggacact 1260 aaagatgtgg atgccctgct gaagaagtct gaggcccagc atgaacagcc ggaagatgga 1320 tgcccctttg gtgccctgac gcagcgcctc ctgcaggccc tggtggagga aaatattatt 1380 tcccctatgg aggattctcc tattcctgac atgtctggga aagaatcagg ggctgacggg 1440 gcaagcacct cccctcgcaa tcagaacaag cccttcagtg tgccgcatac taagtccctg 1500 gagagccgca tcaaggagga gctaattgcc cagggccttt tggagtctga ggaccgcccc 1560 gcagaggact ccgaggatga ggtccttgct gagcttcgca aacggcaggc tgagctgaag 1620 gcacttagtg cccacaaccg caccaagaag cacgacctgc tgaggctggc aaaggaggag 1680 gtgagccggc aggagctgag gcagcgggtg cgcatggctg acaacgaggt catggacgcc 1740 tttcgcaaga tcatggctgc ccggcagaag aagcggactc ccaccaagaa agaaaaggac 1800 caggcctgga agactctgaa ggagcgtgag agcatcctga agctgctgga tgggtagccc 1860 tcacccctgc ctcaggctga ttatctggcc taggggaggg gaagggaggc ccacttcctt 1920 ctttgggcac aggaaacatt ggcctgtggc tgtccctcaa atggcggcag tctctagagg 1980 gccgtggccc ttcccctgag gtcttttggc ctagctctgt acaaccagga cacaggaagc 2040 cctgctgggc tagcctgagg cctagtctct gcttggtccc cgagatgggg ttggagggga 2100 cttcgtttct gggtcttcct cttcccctct ttaccatccc ccactcccta atcccctacc 2160 cctgtctccc cttcaaggac ttctcccttg tggttttgta aagtgcaaac ttaagaataa 2220 agtgactgct gtggtttttc aaaaaaaaaa aaaaa 2255 <210> 62 <211> 2982 <212> DNA
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 491271CB1 <400> 62 gcgtggggat gtttaccgcc gtttatccgg gatagagact ccatcgtgct gacagcatcc 60 ttttattcac cgcctccgaa tttgcaaaga ggaggaagga gggacttctt ggcttctccc 120 agcatagccc cagttatgcc atctcagaac tatgaccttc cccagaagaa gcaggagaaa 180 atgaccaagt ttcaggaggc tgtgacattc aaggatgtgg ctgtggtctt ctccagggag 240 gaactgcgac tgctcgatct tacccagagg aagctgtacc gagatgtcat ggtggagaac 300 ttcaagaacc tggttgcagt ggggcatctt cccttccaac cagatatggt atcccaattg 360 gaagcagaag aaaagctttg gatgatggaa acagaaaccc aaagaagcag caagcatcaa 420 aataagatgg aaacactcca aaaatttgca ttaaaatacc tttcaaatca agagctgtcc 480 tgctggcaaa tctggaaaca ggttgcaagt gaattaacca ggtgtct_ca ggggaagagt 540 tcccagttat tacaaggtga ctctattcag gtttctgaaa atgagaacaa tataatgaac 500 cctaaaggag atagccctat ttatattgaa aatcaagagt ttccat~rtg gagaacccag 660 SUBSTITUTE SHEET (RULE 26) cattcttgcg ggaatacata tctgagtgag tcacagattc agagtagagg taagcaaatt 720 gatgtgaaaa ataacctgca aatacgtgaa gacttcgtga agaaatcacc atttcatgag 780 catattaaaa ctgacacaga accaaaaccc tgcaaaggta atgaatatgg caaaatcatt 840 agtgatggct ccaaccagaa attaccctta ggagagaaac cccatccatg tggtgagtgt 900 ggaaggggct tcagtcatag cccaaggctt ccccttcatc cgaatgttca cacaggagaa 960 aaatgcttca gtcaaagctc acatctgcga actcatcaga gaattcaccc aggagagaaa 1020 ctcaatagat gtcatgaatc tggtgattgc ttcaataaga gctcttttca ttcttatcaa 1080 tctaatcata caggagagaa gtcttataga tgcgacagtt gcggcaaggg attcagtagc 1140 agcacgggtc ttatcattca ttacagaact catactggag agaaacccta taaatgcgag 1200 gaatgtggta aatgctttag tcaaagttca aattttcagt gccatcagag agtccacact 1260 gaagaaaaac catacaaatg cgaagagtgt ggtaagggct tcggttggag tgttaatctc 1320 cgtgttcacc agagggtcca caggggtgag aagccctata aatgtgagga atgtggtaag 1380 ggcttcactc aggctgcaca ttttcacatc catcagagag tccacactgg agagaaaccc 1440 tacaagtgtg atgtgtgtgg taagggcttc agccacaatt caccattaat atgccatcgg 1500 agagtccaca caggagagaa gccatacaag tgtgaggcgt gtgggaaagg ctttacccgt 1560 aatacagatc tgcatattca tttcagagtt cacacgggag agaaacccta taaatgtaag 1620 gagtgtggta agggcttcag tcaggcttca aatcttcaag tccatcagaa tgtccacact 1680 ggggagaaac gattcaagtg tgaaacgtgt gggaagggct tcagtcagtc ctcaaagctt 1740 caaacccatc agcgagtcca cactggagag aaaccatata gatgtgatgt gtgtggtaag 1800 gacttcagtt atagttcaaa tcttaaacta caccaagtaa ttcacactgg agaaaaacca 1860 tataaatgtg aggaatgtgg gaagggcttc agttggagat caaatcttca tgcacatcaa 1920 agagttcact caggagaaaa accctataaa tgtgagcagt gtgataagag cttcagtcag 1980 gccatagatt ttcgggtaca tcagagagtc catactggag agaagccata caaatgtggt 2040 gtctgtggta agggcttcag tcagtcctct ggtcttcaat cccatcagag agtccacacg 2100 ggggaaaagc catacaaatg tgatgtgtgt ggaaagggct ttagatacag ttcgcagttt 2160 atataccatc agagaggcca cactggagaa aaaccttaca aatgtgaaga gtgtgggaaa 2220 ggctttggta ggagcttgaa tcttcgccat catcagaggg tccacacggg agagaaaccc 2280 catatatgtg aggagtgtgg taaggccttc agtctcccct caaatcttcg agtccacctg 2340 ggtgttcaca ccagggaaaa actctttaaa tgtgaagagt gtggtaaagg cttcagtcag 2400 agtgcacgtc ttgaagccca tcagagagtc .cacactggag aaaaaccata caaatgtgac 2460 atatgtgata aggacttccg tcaccgttca cgtcttacat atcatcagaa agtccatact 2520 ggtaaaaagc tttagaaatg agaaatgtgt taccaacttt tgtctgaatg cacatcttca 2580 agtttttggc tagtccatgc tggtggtaaa ccctgtaaaa ctactgagag tggaaggggg 2640 tttgttcaca cttggaatct ttctaacaaa tccatcaaga tgataacaca gaaccatgaa 2700 caggaataga actcgtattt aggggagaaa tagggctggt ggctctcttg gtaagatcta 2760 gttaatataa atgatcacct ttcattgtga atatatgcct gaagataatg tgtggaagga 2820 tatttgccat atgctaactg gttttttggc cagggagagt tttgggttat tatccctttt 2880 ctttaatttt cattttatac ttacagtgat cattattttc ataaaagctg taaagctatg 2940 aaaaatgaat aaaattacta aaaattttct gtaaaaaaaa as 2982 <210> 63 <211> 1185 <212> DNA
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 585172CB1 <400> 63 ggagcgtcca gagtcctggc cctgagcggg aatcgcagtg gccgaggctg agcggcaggt 60 agaaggggcg tctccggggc ttcacaggga acacaggggc ttcggcccaa ccacaagtac 120 gcagttgcac atgccctact tttgcccatt ctttgcaaat cccctaagga acgaacgcgc 180 ctcgcgtgcg ggcctttcta atcttcgctt gtcccttcac ttccacagct ggaggtcgaa 240 ttcaccacgt cacgtagaga aaaggggcgg tgtctcgggt ctccccgtgt ggcatcaagg 300 cgggctccct ataggagctg gtgtggacgt ccgggcgtgg ggttagggcg gatgcgggga 360 tcgcggggcg ggtgttgaca ttgtgctctc accaggcgga tcgccccgac cctcactcct 420 ggcgtctgag tctctggcgt agccatgctg agtgggcggc tggtcctggg tctggtctcc 480 atggctggcc gcgtttgttt gtgccagggc agcgcgggat ccggggccat cggtccggtg 540 gaggccgcca ttcgcacgaa gttggaggag gccctgagcc ccgaggtgct agagcttcgc 600 aacgagagcg gtggccacgc ggtcccgcct ggcagtgaga ctcacttccg cgtggctgtg 660 SUBSTITUTE SHEET (RULE 26) gtgagctctc gtttcgaggg actgagcccc ctacaacgac accggctggt ccacgcagcg 720 ctggccgagg agctgggagg tccggtccat gcgctggcca tccaggcacg gacccccgcc 780 cagtggagag agaactctca gctggacact agccccccat gcctgggtgg gaacaagaaa 840 actctaggaa ccccctgaac cccaagagag ggaggaccag gatccgaatg ggctgggtga 900 gcacgaatta ccgaggcctt ccctttgata ca4tccagga tttgtaaggg atgaagaccc 960 ctgggcccca ttctgttggg gtccatacat actctccgaa gatagcaact tgcttcaggt 1020 caaagtgaac ccgagaaaag agaagaatca ctcactactg ctcttgccct ggactattca 1080 ggaagggcag cccggatgtt ccatgttaaa tcgtgacaga attgcaccag acctgatgag 1140 ttggaaacaa tcctatacat taaaagaaat tacactaaaa aaaaa 1185 <210> 64 <211> 1191 <212> DNA
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 615200CB1 <400> 64 tggacggacg cgtgggcttg atttctgatt tatgactgct ttttgttgta ccccaatagt 60 cgtctaagaa aggtgattat tttgagaggc ctggggagac acacatgctc attctcgagg 120 gtggcggtgg tgcagagggc agagccatgc tcgttcttgc tatcctgaga ttggttgcta 180 tctgtttcct ttgctgctgt gtttttttct gtcagtatta aaggtggaag aaggtccata 240 tctttttctg tgggtgcttc aagtgttgtt ggaagtggag gcagcagtga caaggggaag 300 ctttccctgc aggatgtagc tgagctgatt cgggccagag cctgccagag ggtggtggtc 360 atggtggggg ccggcatcag cacacccagt ggcattccag acttcagatc tccggggagt 420 ggcctgtaca gcaacctcca gcagtacgat ctcccgtacc ccgaggccat ttttgaactc 480 ccattcttct ttcacaaccc ca.agcc~ttt ttcactttgg ccaaggagct gtaccctgga 540 aactacaagc ccaacatcac tcactacttt ctc~ggctgc ttcatgacaa ggggctgctt 600 ctgcggctct acacgcagaa catcgatggg cttgagagag tgtcgggcat ccctgcctca 660 aagctggttg aagctcatgg aacctttgcc tctgccacct gcacagtctg ccaaagaccc 720 ttcccagggg aggacattcg ggctgacgtg atggcagaca gggttccccg ctgcccggtc 780 tgcaccggcg ttgtgaagcc cgacattgtg ttctttgggg agccgctgcc ccagaggttc 840 ttgctgcatg tggttgattt ccccatggca gatctgctgc tcatccttgg gacctccctg 900 gaggtggagc cttttgccag cttgaccgag gccgtgcgga ctcagttccc cgactgctca 960 tcaaccggga cttggtgggg cccttggctt ggcatcctcg cagcagggac gtggcccagc 1020 tgggggacgt ggttcacggc gtggaaagcc tagtggagct tctgggctgg acagaagaga 1080 tgcgggacct tgtgcagcgg gaaactggga agcttgatgg accagacaaa taggatgatg 1140 gctgccccca cacaataaat ggtaacatag gagacatcca catcccaatt c 1191 <210> 65 <211> 2596 <212> DNA
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 997067CB1 <400> 65 ccggtgtgtg ggtctgtgac agggtccaac agggcctggt ccgtgtccgg tcccccaaat 60 ctgtcgtccc tgcccccagg cattggcatc aacaaaagtc agaattcccg ggaacttgaa 120 cagaggctgc taaattccca gtaattgctc ctttggcctt ctagggactg acttcaaaga 180 aggaaggaaa gaatcaggca gtgcttcctc attctctttt aaaacccgct tcccgctgag 240 tctgcaccca ggagaccaga gagcaccttg cccttccatg gaaactcagg ctgatctcgt 300 atctcaggaa cctcaggccc tgcttgacag tgctcttcct tcaaaagttc ctgccttttc 360 cgacaaggac agcctggggg atgagatgtt ggcggctgcg ctcctaaagg ccaagtccca 420 ggagctggta acctttgagg atgtagctgt gtacttcatc cggaaggagt ggaagcgttt 480 ggaacctgct cagagggacc tctatagaga tgtgatgctg gagaattacg ggaatgtgtt 540 SUBSTITUTE SHEET (RULE 26) ctcactggat cgtgagacca ggactgaaaa tgatcaagaa atttctgaag acacaagatc 600 acatggggtc ctactgggaa gatttcaaaa ggatatttct cagggtctca agtttaaaga 660 agcctatgaa cgagaagtca gtctgaaaag gccgctgggg aactcccctg gagaaagact 720 gaacaggaaa atgccagatt ttggtcaagt gacagttgag gagaagctaa cccccagggg 780 agagagaagc gagaaatata atgattttgg gaacagcttc actgtgaatt ccaaccttat 840 ctcacatcag agactccccg tgggagacag accccataag tgtgatgaat gtagcaagag 900 ctttaatcga acttcagacc ttattcaaca tcagagaatc cacactgggg aaaagcccta 960 tgaatgtaat gagtgtggga aggccttcag ccagagctca caccttattc agcatcagag 1020 aatccacact ggggaaaaac cttatgaatg tagtgattgt gggaaaacct tcagctgtag 1080 ctctgccctc attctgcatc ggaggatcca cacgggggag aaaccctatg aatgtaatga 1140 gtgtgggaag accttcagct ggagctccac cctcacccac catcagagaa tccacactgg 1200 tgagaaaccc tacgcctgca atgaatgtgg gaaggccttc agcaggagct caacccttat 1260 tcaccatcag agaatccaca ctggagaaaa accctatgaa tgtaatgaat gtgggaaagc 1320 cttcagccag agctcacacc tctatcagca ccagagaatc cacactggag agaagcccta 1380 cgaatgtatg gaatgtggag gaaagtttac ctacagttca ggccttattc agcatcaaag 1440 aatccacacc ggggagaacc cctatgaatg tagtgagtgt gggaaagcct tcaggtacag 1500 ctcggctctt gttcgccatc agagaattca cactggagag aagcctttga atgggatcgg 1560 catgagcaaa agctccctca gagttacgac cgagttaaat atcagagagt ccacgtgaaa 1620 gagccacaca cccattttcc tcactttccc tgagtctcaa gagctcttgc cttaccctat 1680 aaatctcaac agcttaggat gtgtcccttt caactcagac ttttcatttt agagaatggg 1740 gcagatgggg caaatcgttg aattttccca gaaatcacac cagccttaga aagcgtcaag 1800 gcaagtggat ggcgtgctgg gaatagaaag cagctctggg accagttacc ccatttagga 1860 aaggagtttg cactaaactg tttttctcac agcagaggaa cctttccaag gtggggatgg 1920 aagcacagtc gggacagaat tcgatggatt cctttagttg gagtccgcgt agtcagcaca 1980 gacagcagtg gaaaggacgc tctgggtcct gttatttgct agggagggta aagggagact 2040 atttcaaagc tactgttcct agtccagctt taagtttcgg taagaaacat gctgttttgt 2100 ttcatgattt cgttaattat ggaaatttgg cattgaggga ttattttatt gagggtagaa 2160 gagattccag aatcatcatc tgtgatgatg gtgtccttta gggctcttgg agcagccaga 2220 ccatgtttcc aagagaaacc tggtgatatt gccagcagac cccctgccat cccccccagt 2280 tgtcctgggg ctgaatgggc aaarctgtcc aaacagctag taaccggctg tgagggagag 2340 ggtcagaagc acttagcgtt ggcctctgat tgctgtcctc tcttgtcctc ttcccactcc 2400 aatgatgaaa atgattttct ctauatgcct gggtaaggat gctttcaagg agctcacttg 2460 gcctgcttgc cctgccctct cacctctgac acccagcccc aggagccaga ccactcctgc 2520 ctccacctct gactcttcag cagctgaaga ttaatgcaga gaaagagcaa agcccaaaag 2580 ggagaaaaaa aaaaaa 2596 <210> 66 <211> 1574 <212> DNA
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 1443262CB1 <400> 66 cagcccgtga gacgcccgct gctggacgcg ggtagccgtc tgaggtgccg gagctgcggg 60 aggatggagc cgctgaaggt ggaaaagttc gcaaccgcca acaggggaaa cgggctgcgc 120 gccgtgaccc cgctgcgccc cggagagcta ctcttccgct cggatccctt ggcgtacacg 180 gtgtgcaagg ggagtcgtgg cgtcgtctgc gaccgctgcc ttctcgggaa ggaaaagctg 240 atgcgatgct ctcagtgccg cgtcgccaaa tactgtagtg ctaagtgtca gaaaaaagct 300 tggccagacc acaagcggga atgcaaatgc cttaaaagct gcaaacccag atatcctcca 360 gactccgttc gacttcttgg cagagttgtc ttcaaactta tggatggagc accttcagaa 420 tcagagaagc tttactcatt ttatgatctg gagtcaaata ttaacaaact gactgaagat 480 aagaaagagg gcctcaggca actcgtaatg acatttcaac atttcatgag agaagaaata 540 caggatgcct ctcagctgcc acctgccttt gacctttttg aagcctttgc aaaagtgatc 600 tgcaactctt tcaccatctg taatgcggag atgcaggaag ttggtgttgg cctatatccc 660 agtatctctt tgctcaatca cagctgtgac cccaactgtt cgattgtgtt caatgggccc 720 cacctcttac tgcgagcagt ccgagacatc gaggtgggag aggagctcac catctgctac 780 ctggatatgc tgatgaccag tgaggagcgc cggaagcagc tgagggacca gtactgcttt 840 gaatgtgact gtttccgttg ccaaacccag gacaaggatg ctgatatgct aactggtgat 900 SUBSTITUTE SHEET (RULE 26) gagcaagtat ggaaggaagt tcaagaatcc ctgaaaaaaa ttgaagaact gaaggcacac 960 tggaagtggg agcaggttct ggccatgtgc caggcgatca taagcagcaa ttctgaacgg 1020 cttcccgata tcaacatcta ccagctgaag gtgctcgact gcgccatgga tgcctgcatc 1080 aacctcggcc tgttggagga agccttgttc tatggtactc ggaccatgga gccatacagg 1140 atttttttcc caggaagcca tcccgtcaga ggggttcaag tgatgaaagt tggcaaactg 1200 cagctacatc aaggcatgtt tccccaagca atgaagaatc tgagactggc ttttgatatt 1260 atgagagtga cacatggcag agaacacagc ctgattgaag atttgattct acttttagaa 1320 gaatgcgacg ccaacatcag agcatcctaa gggaacgcag tcagagggaa atacggcgtg 1380 tgtctttgtt gaatgcctta ttgaggtcac acactctatg ctttgttagc tgtgtgaacc 1440 tctcctattg gaaattctgt tccgtgtttg tgtaggtaaa taaaggcaga catggtttgc 1500 aaaccacaag aatcat.tagt tgtagagaag cacgattata ataaattcaa aacatttggt 1560 tgaaaaaaaa aaaa 1574 <210> 67 <211> 2197 <212> DNA
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 1521648CB1 <400> 67 cccgacgaac gcgaggaggg cgaggcggga ggtgcaggag ggaccctcgc catgggtcca 60 cgggcctaga gtggcggaag ataccggcct ggtgccaaac tggctactgc tgcttcctgt 120 ggcctccatg gctgaggact ggctggactg cccggccctg ggccctggct ggaagcgccg 180 cgaagtcttt cgcaagtcag gggccacctg tggacgctca gacacctatt accagagccc 240 cacaggagac aggatccgaa gcaaagttga gctgactcga tacctgggcc ctgcgtgtga 300 tctcaccctc ttcgactt_ca aacaaggcat cttgtgctat ccagccccca aggcccatcc 360 cgtggcggtt gccagcaaga agcgaaagaa gccttcaagg ccagccaaga ctcggaaacg 42G
tcaggttgga ccccagagtg gtgaggtcag gaaggaggcc ccgagggatg agaccaaggc 480 tgacactgac acagccccag cttcattccc tgctcctggg tgctgtgaga actgtggaat 540 cagcttctca ggggatggca cccaaaggca gcggctcaaa acgttgtgca aagactgtcg 600 agcacagaga attgccttca accgggaaca gagaatgttt aagcgtgtgg gctgtgggga 660 gtgtgcagcc tgccaggtaa cagaagactg tggggcctgc tccacctgcc tcctgcagct 720 gccccatgat gtggcatcgg ggctgttctg caagtgtgaa cggagacgct gcctccggat 780 tgtggaaagg agccgagggt gtggagtatg ccggggctgt cagacccaag aggattgtgg 840 ccattgcccc atctgccttc gccctccccg ccctggtctc aggcgccagt ggaaatgtgt 900 ccagcgacgt tgcctacggg gtaaacatgc ccgccgcaag ggaggctgtg actccaagat 960 ggctgccagg cggcgccccg gagcccagcc actgcctcca ccacccccat cacagtcccc 1020 agagcccaca gagccgcacc ccagagccct ggccccctcg ccacctgccg agttcatcta 1080 ttactgtgta gacgaggacg agctacagcc ctacacgaac cgccggcaga accgcaagtg 1140 cggggcctgt gcagcctgcc tacggcggat ggactgtggc cgctgcgact tctgctgcga 1200 caagcccaaa ttcgggggca gcaaccagaa gcgccagaag tgtcgttggc gccaatgcct 1260 gcagtttgcc atgaagcggc tgctgcccag tgtctggtca gagtctgagg atggggcagg 1320 atcgccccca ccttaccgtc gtcgaaagag gcccagctct gcccgacggc accatcttgg 1380 ccctaccttg aagcccacct tggctacacg cacagcccaa ccagaccata cccaggctcc 1440 aacgaagcag gaagcaggtg gtggctttgt gctgcccccg cctggcactg accttgtgtt 1500 tttacgggaa ggcgcaagca gtcctgtgca ggtgccgggc cctgttgcag cttccacaga 1560 agccctgttg caggtgaagc aagagaaggc ggatacccag gacgagtgga caccaggcac 1620 agctgtcctg acttctcccg tattggtgcc tggctgccct agcaaggcag tagacccagg 1680 cctgccttct gtgaagcaag agccacctga cccagaggag gacaaggagg agaacaagga 1740 tgattctgcc tccaaattgg ccccagagga agaggcagga ggggctggca cacccgtgat 1800 cacggagatt ttcagcctgg gtggaacccg cttccgagat acagcagtct ggttgccaag 1860 gtccaaagac cttaaaaaac ctggagctag aaagcagtag actggaggct tctacagact 1920 gtaggattca agtctgcagg gcaggcactc gggaagggaa gatggatgta aagtgtggga 1980 gaccgaggac acagtggagc ccacgagcac gagctggaac ccacgaggat ggcctggaac 2040 ccatgtcagt ctctcaccac ctccagcttc gatgatgtgg gtgtcctgca gaagaagctg 2100 gtgcccttcc tcacagagtt aaatatgcat ctggcccagg aattagagaa gctgaaagga 2160 tgatcctggg gaaggcggaa cagctgcagg cctggct 2197 SUBSTITUTE SHEET (RULE 26) <210> 68 <211> 2081 <212> DNA
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 1685494CB1 <400> 68 gcatacgcag tccgtgccta agcggcacga ccatcgagcc aaggtcctcc agcgttccta 60 gagcggagaa gaaagcgctc cgaagagcta gagctgacac tcggcgatga gctaagacgc 120 tgtttcagag cgtttgggtc ctctgaggcc ccttgaccag gagtgtctct gaagatacag 180 tccaaagaag gttctccaaa acaaggagag cagtctgaag ctggggatgg caacagcatt 240 ggtgagtgcc cattccctgg ctcccctgag tctgaagaag gaggggcttc gggtagtgag 300 ggaggatcac tactctactt gggaacaggg attcaagctg caaggaaaca gtaaaggcct 360 tggacaggag ccattgtgca aacaattcag gcagttgcgt tatgaagaga ccacaggacc 420 tcgagaagca ctaagtcggc tccgggagct ctgtcaacag tggctacagc ccgagaccca 480 taccaaggag cagatcctgg agctgctggt gctggagcag tttctgatca tcctgcctaa 540 ggagctccag gcccgggtgc aggagcatca cccagagagc agggaggacg tggttgttgt 600 tctggaggat ttgcagctgg atcttggaga aacaggacaa caggtggacc cagaccagcc 660 aaagaaacaa aaaatacttg tggaggagat ggcccctctg aaaggagtac aggaacagca 720 ggttcggcat gagtgtgaag ttacaaagcc tgagaaagag aagggtgagg agacaaggat 780 tgagaatggg aagcttattg tagtaacaga ctcttgtgga agagtagagt catctgggaa 840 aatatctgaa cccatggagg ctcataatga gggctctaac ttggaaaggc atcaggccaa 900 gcccaaagag aagattgagt ataaatgctc agaacgtgag cagagattca tccagcactt 960 ggacctgatt gaacatgcga gtacacacac gggaaagaaa ctctgcgagt ctgatgtgtg 1020 tcagagttcc agtcttacag gacataagaa agtcctctct agagagaaag gtcatcagtg 1080 tcatgagtgt gggaaagcct ttcagaggag ttcacacctc gtcagacatc agaaaatcca 1140 tcttggtgag aagccttatc agtgcaatga gtgtggcaaa gtctttagcc agaatgcagg 1200 ccttttggaa catctcagaa ttcatactgg agagaaacct tatctatgta tccattgtgg 1260 aaaaaatttt aggcgcagct ctcaccttaa tcgacatcag agaattcaca gtcaggagga 1320 gccctgtgag tgcaaggagt gtggaaaaac ctttagtcag gccttactcc tcacccacca 1380 tcagagaatc catagtcact ccaaaagcca tcaatgtaac gagtgtggaa aagctttcag 1440 tttgacctca gaccttattc gacaccacag aattcatact ggagaaaaac ctttcaagtg 1500 taacatatgc cagaaagcct tccgactaaa ctcacacctt gctcagcatg taagaatcca 1560 caatgaagaa aaaccctatc agtgtagtga atgtggagaa gccttcaggc aaaggtcagg 1620 tctttttcaa catcagagat atcaccacaa agacaaactg gcttgatgag gtgttctctc 1680 cttgtagaac atcagagaag gcacattgac tagcaaacag cactttagga aaagtcaccg 1740 tagcccactg tggcatcaga aaattcttgg gggctgagtt ggaggctccc tgcctctatt 1800 ctctctcctt tgctttcctt gaagtcagct ttggaccaca ataatttcac tgtagatgat 1860 atgctaggat caaagttaaa cagcattctt cactgcagga catctcagag catgtaacat 1920 aactgcatga ttatatactc taagcaatag agagcttcat gactgagtaa gagttttgaa 1980 gtcagcagtg aatcaagtgc ccacagattt gcaggcttaa gcagaacaag ggaagattga 2040 tatttttgga tatgctatag cagctttctc ctatgaaata a 2081 <210> 69 <211> 2785 <212> DNA
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 1730829CB1 <400> 69 gaccgtgcgg cgcccagcgg agtaggggct gcgcttgggg tttgctgaag ctggctgcct 60 ctcccactcc ccttttgggt gcaaagcgcc gctagcggga agacgggggc cgggcgggga 120 caggggcacc tgcgtactgg actgagagcc tgcgcccagc ttacatcgac cccacccggc 180 cccggcccga cccgacgcga cccgatccga tccgaLccca ttccatccgt tcctcg fete 240 ctcccggtct gacccgttgc ccggccgtgg ttcgccacac caggcatcca aagctgaggt 300 SUBSTITUTE SHEET (RULE 26) cgctcctacg gcctgggctc gccttcgctt tagagatgtt tggcctcttc cctcccaaac 360 agctcatctt caaaacctgg actcttggac tggcacctgg ccacctttcc ctctaccaag 420 actccacttc cgtcttaccc acttcttcct cagattcttg gtaccccctg ggttggagac 480 tgctcatttt ccttccaaat taatcccaga ccccctaaaa tattgacaac cttgacaacc 540 ccccaaccga ggagccagac tttgttttgg actaacttcc atagccctat catggaggca 600 gtgtacctgg tagtgaatgg gttgggcctg gtgctggacg tgctgacctt ggtgttggac 660 ctcaacttcc tgctggtgtc ctccctcctg gcttccctgg cctggctcct ggccttcgtc 720 tacaacctgc cgcacacggt actgactagt cttctgcact tgggccgcgg agtcttgctt 780 tcattgctgg ccttgatcga agccgtggtc cggttcacat gtgggggctt gcaggccttg 840 tgtactctgc tgtatagctg ctgctctggc ctagagagcc taaagctcct ggggcacctg 900 gcctctcatg gggcactgcg gagcagggag atactgcacc ggggcgtcct caatgtggtc 960 tccagtggcc atgctttgct gcgccaggcc tgtgacatct gtgccattgc catgagcctg 1020 gtggcttatg tgatcaacag cctggtcaac atctgcctca tcggcactca gaacctcttt 1080 tccctggtgc tggccctgtg ggatgcagtg accgggcctc tgtggaggat gacagacgta 1140 gtggctgcct tcctagccca catttccagc agtgctgtgg ccatggccat cctcctttgg 1200 acaccctgcc aactagccct ggagctgctg gcctcagctg cccgcctcct ggccagcttt 1260 gtgcttgtca atctcactgg cttggtgttg ctagcttgtg tgctggcagt gacggtgact 1320 gtgttgcatc cggacttcac cctgaggctg gctacccagg cactcagcca gctccatgcc 1380 cggccatcct accaccgtct tcgagaggat gtcatgcggc tctctcgcct agcactgggc 1440 tcagaggcct ggcgccgagt ctggagccgc agtctgcagc tggcgagttg gccaaaccgg 1500 ggaggggcac ctggagctcc ccagggtgac cctatgaggg tattctcagt taggacccgg 1560 agacaggaca ctcttcctga agcggggcgc agatcagagg cagaagagga ggaggccagg 1620 accatcagag tgacacctgt caggggccga gagaggctca atgaggagga gcctccaggt 1680 gggcaagacc cttggaaatt gctgaaggag caagaggagc ggaagaagtg tgtcatctgc 1740 caggaccaga gcaagacagt gttgctcctg ccctgccggc atctgtgcct gtgccaggcc 1800 tgcactgaaa tcctgatgcg ccaccccgtc taccaccgca attgcccgct ctgccgccgg 1860 ggcatcctgc agaccctcaa tgtctacctc tgaagcctcc ttccctgcct gcccacccct 1920 ccatgctcca cgcaggcact cacgctagga cagcattaac acctcatctc cgggtcctgg 1980 tctgaatccc ctcctacccc tgtggccatc ctgccataca tccaggacat tgagttggaa 2040 gactatgatc tgggtggggg caggataaca tggcttctct ttacccagtg ggtcccttcg 2'._70 atgctgaggg tggtgagtat gtcactatgc aagggccctg agactatttg ctgtgggctc 2160 tcctccagcc tgcccagggc ccacccagat gcctctgggg ttacccctgt ctgc~tctgg 2220 tttttctgtt ggagatctat aggtcctttt cctgcctcct tcacatttcc tccccagctt 2280 ttgcggccac aacacatcag tgtcatttgg gtgttttggc aactcagggg ccttcggatg 2340 atcttaaacc tttgtgttca gccagagccc ctgtgccctg gtaggcgttg gggttagtat 2400 ctctcgggtg ccctcagagc cacctctgcc tgtgatcgtc tgatgaggct ccctcccaac 2460 ctgatccaaa agccagtctc aggagtttac ccctgggatg ggggatgcat ctgcacctga 2520 ctttggggcc acgtgccctg tggcacccca gctcactggg agtctcagga gggataaccg 2580 gatttctgct ctttcccctg tcactcccac atcacacaga aaaatggcat tcctctctgt 2640 ctctccctgg catggagagg gcagactgtg cacatttcac tagggttcaa atacagaagg 2700 cccagggccc aggggttgca gcttcgtgag gggtctctgg cccagtttcc aatgaataaa 2760 gttctcttga cagctaaaaa aaaaa 2785 <210> 70 <211> 1231 <212> DNA
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 1864641CB1 <400> 70 tcccgtccta tgacgtcagc cgtaaggcgc tgctgtcgta aaaggacgtc cggtccgtct 60 cctagtgtcc ggaatcggct gtcagcctcc ctggctgtta gtaccttctt tcccggagtc 120 ctggtccacg agttggattt actgctgtcg cgggtgggcc tcacgccatt ccctgtccct 180 cggccccctg agtgagtccg gtctcccggc gaaagtgagc gaggtttgcc cggagcgcgc 240 acgaggggaa aatgcctaaa aaaaagactg gtgcgaggaa gaaggctgag aaccgccgag 300 aacgtgaaaa acaactaaga gcatcaagaa gcactataga tttagctaaa catccatgta 360 atgcctcaat ggaatgtgac aagtgtcaga ggcggcagaa gaatagagca ttttgctact 420 SUBSTITUTE SHEET (RULE 26) tttgtaattc tgtacagaag ttaccaattt gtgcacagtg tgggaaaaca aagtgcatga 480 tgaagtcttc agactgtgtc ataaagcatg ctggtgtata cagtactggc cttgcaatgg 540 tgggtgcaat atgtgacttc tgtgaagctt gggtttgcca tggtaggaaa tgtctcagta 600 cacatgcttg tgcctgccct cttaccgatg ctgagtgtgt tgaatgtgaa cgaggcgtgt 660 gggaccatgg aggcagaata ttcagttgtt ctttttgcca taactttctc tgtgaagatg 720 atcaatttga gcatcaagcc agctgccagg ttttagaggc agaaacattt aaatgtgttt 780 catgcaatcg gcttggtcag cactcatgtc tccgttgtaa ggcttgtttc tgtgatgatc 840 atacaaggag caaagtgttt aagcaagaaa aaggaaaaca gcctccttgt cctaaatgtg 900 ggcatgaaac tcaggagact aaggacctta gcatgtcaac acgctccctg aaatttggca 960 ggcagactgg aggtgaagag ggagatggag cttctgggta tgatgcttat tggaagaacc 1020 tttcatctga taagtatggt gataccagct accacgatga ggaggaggat gagtatgaag 1080 cagaggatga tgaagaggaa gaagatgaag gcagaaagga ttcagatact gagtcatcag 1140 atttgtttac taatttgaat ttaggaagga cctatgctag tggctatgct cactatgagg 1200 aacaagagaa ctaggggagc tgctctggtg g 1231 <210> 71 <211> 700 <212> DNA
<213> Homo sapiens <220> -<221> misc-feature <223> Incyte ID No.: 2444604CB1 <400> 71 gccccaggtg acacaatggc cgcagtccat ggcggctggc ttcttccagc ccttcatgtc 60 accgcgcttc ccagggggcc cccggcccac cctgcggatg ccgagtcagc ctcccgcatg 120 cctccctggc tcccagcccc tcctccctgg cgccatggag ccctccccac gagcccaggg 180 gcatccgagc atgggcggcc caatgcagag ggtgacgcct cctcc~tggca tggccagcgt 240 ggggccccag agctatggag gtggcatgcg acccccaccc aactccctcg ccggcccagg 300 cctgcctgcc atgaacatgg gcccaggagt tcgtggcccg tgggecagcc ccagtggaaa 360 ctcgatcccc tactcctcct catcccccgg cagctacacc ggacccccag gaggaggtgg 420 gccccctgga acacccatca tgcctagccc tggagattcc accaactcca gcgaaaacat 480 gtacactatc atgaacccca tcgggcaggg cgccggcagg gctaatttcc cgctcggccc 540 tggcccggag ggcccatggc cgccatgagc gcgatggagc ctcaccacgt gaacggatcc 600 ctgggctcgg gcgacatgga cgggttgccg aagagttccc ccggcgccgt ggccggcctg 660 agcaacgccc cggggcaccc cgcgggacga cggcgagatg 700 <210> 72 <211> 2332 <212> DNA
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2445008CB1 <400> 72 aggcggacgg ggaacgaggc cgtcggccat tttgtgtctg cttcctgtgg gacgtggtgg 60 tagccgttgg gttgggaaag tgagggattt ttggcctcgt ttctcctgct tcttttctcc 120 tcccttttac tttgccggta gaacacagtt atgggtcgca agaagaagaa gcagctgaag 180 ccgtggtgct ggtattgtaa tagagatttt gatgatgaga agatccttat tcagcaccaa 240 aaagcaaagc attttaaatg ccatatatgt cacaagaaat tgtatacagg acctggctta 300 gctattcatt gcatgcaggt acataaagaa acaatagatg ccgtaccaaa tgcaatacct 360 ggaagaacag acatagagtt ggaaatatat ggtatggaag gtattccaga aaaagacatg 420 gatgaaagac gacgacttct tgaacagaaa acacaagaaa gtcaaaaaaa gaagcaacaa 480 gatgattctg atgaatatga tgatgacgac tctgcagcct caacttcatt tcagccacag 540 cctgttcaac ctcagcaagg ttatattcct ccaatggcac agccaggact gccaccagta 600 ccaggagcac caggaatgcc tccaggcata cctccattaa tgccaggtgt tcctcctctg 660 atgccaggaa tgccaccagt tatgccaggc atgccacctg gattgcatca tcagagaaaa 720 SUBSTITUTE SHEET (RULE 26) tacacccagt cattttgcgg tgaaaacata atgatgccaa tgggtggaat gatgccacct 780 ggaccaggaa taccacctct gatgcctgga atgccaccag gtatgccccc acctgttcca 840 cgtcctggaa ttcctccaat gactcaagca caggctgttt cagcgccagg tattcttaat 900 agaccacctg caccaacagc aactgtacct gccccacagc ctccagttac taagcctctt 960 ttccccagtg ctggacagat ggggacacct gtcacaagct caagtacagc ttcatccaat 1020 tcagaaagtc tgtctgcatc ttctaaagct ctgtttccta gcacagcaca agctcaggca 1080 gctgtccaag gacctgttgg tacagatttc aaacccttaa atagtacccc tgcaacaact 1140 acagaacccc caaagcctac attccctgct tatacacagt ctacagcttc aacaactagt 1200 acaacaaata gtactgcagc taaaccagcg gcttcaataa caagtaagcc tgctacactt 1260 acaacaacta gtgcaaccag taagttgatc catccagatg aggatatatc cctggaagag 1320 agaagggcac agttacctaa gtatcaacgt aatcttcctc ggccaggaca ggcccccatc 1380 ggtaatccac cagttggacc aattggaggt atgatgccac cacagccagg catcccacag 1440 caacaaggaa tgagaccccc aatgccacct catggtcagt atggtggtca tcatcaaggc 1500 atgccaggat accttcctgg tgctatgccc ccgtatgggc agggaccgcc aatggtgccc 1560 ccttaccagg gtgggcctcc tcgacctccg atgggaatga gacctcctgt aatgtcgcaa 1620 ggtggccgtt actgatctta cttcatccag tctaataggt ttggagatta aaccttttct 1680 caacttgtgc tgtttatata gccaagcttc cgtcaataag gcttcattgt gactttaaca 1740 aacattatct tcccacatac caggaactat tggacattta ttttacatgg gaaaaattat 1800 ttggaataat aaagcaggaa cttttcctga agttgcaatt tatactgtat ggcttctttt 1860 tcatgtttca tctaggtttt tagaagtgaa gtatagtaaa tttggttcgt taaattgtga 1920 aggcgctgga attacatgaa cataccaccc tagtaaaggc aagttctgta agcttacatt 1980 gctatttgta aagtttgcct tcacagcatt tcagatgctg ttggacttca tgtccccaac 2040 ctagcttggt gagggctgta actgtttcca agtacttgta cattggaagt ctgaatgtgt 2100 aacaatattt aatgtattta gagttcctca tgttgcaggg tttaagaaat ctgacccacc 2160 aaggtcatgt gacttttctg tactgttaaa cttcattgta ataaaatgag agaaaaattt 2220 atgccttttt attcataacc cagctgtgga ccactgcctg aaaggtttgt acagatgcat 2280 gccacagtag atgtccacat aataaaattc atagttacca aaaaaaaaaa as 2332 <210> 73 <211> 1936 <212> DNA
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2572462CB1 <400> 73 ttggttctat attactgttt tatagctgag gagaaagact cacatcattt actaagatca 60 tatagctagc tagtaaatgt ttgagtgaaa atacaaacaa aggttttctg actttaagag 120 cttgagtttt ttccactata ccatattgca tctgttgtaa ttgttaacta atgtgcattt 180 taaaattctc atttgtctta tgtactgagc ccttatacca gtgctaattt atgtgactcc 240 tttctcctgc agctaagaga aaaatacctt tttaattcat ttatagtacc cagtttttaa 300 agaagattta ttttgtaaaa ttttgcttat ggtacatgtc atcttagcct gtaaataaat 360 taaagcatta atttttatcc ctccctggtc ttttcctcct tctgacttta.tacgtctttc 420 tagagagctt atcttctata ataacaattc tttgttttaa agtgagaaag atcagtctaa 480 agaaaaggag aagaaagtga aaaaaacaat tccttcctgg gctacccttt ctgccagcca 540 gctagccagg gcccagaaac aaacaccgat ggcttcttcc ccacgtccca agatggatgc 600 aatcttaact gaggccatta aggcatgctt ccagaagagt ggtgcatcag tggttgctat 660 tcgaaaatac atcatccata agtatccttc tctggagctg gagagaaggg gttatctcct 720 taaacaagca ctgaaaagag aattaaatag aggagtcatc aaacaggtta aaggaaaagg 780 tgcttctgga agttttgttg tggttcagaa atcaagaaaa acacctcaga aatccagaaa 840 cagaaagaat aggagctctg cagtggatcc agaaccacaa gtaaaattgg aggatgtcct 900 cccactggcc tttactcgcc tttgtgaacc taaagaagct tcctacagtc tcatcaggaa 960 atatgtgtct cagtattatc ctaagcttag agtggacatc aggcctcagc tgttgaagaa 1020 cgctctgcag agagcagtag agaggggcca gttagaacag ataactggca aaggtgcttc 1080 ggggacattc cagctgaaga aatcagggga gaaacccctg cttggtggaa gcctgatgga 1140 atatgcaatc ttgtctgcca ttgctgccat gaatgagccg aagacctgct ctaccactgc 1200 tctgaagaag tatgtcctag agaatcaccc aggaaccaat tctaactatc aaatgcattt 1260 gctgaaaaaa accctgcaga aatgcgaaaa gaatgggtgg atggaacaga tctctgggaa 1320 agggttcagt ggcaccttcc agctctgttt tccctattat cccagcccag gagttctgtt 1380 SUBSTITUTE SHEET (RULE 26) tccgaagaaa gagccagatg attctagaga tgaggatgaa gatgaagatg agtcatcaga 1440 agaagactct gaggatgaag agccgccacc taagagaagg ttgcagaaga aaaccccagc 1500 caagtcccca gggaaggccg catctgtgaa gcagagaggg tccaaacctg cacctaaagt 1560 ctcagctgcc cagcggggga aagctaggcc cttgcctaag aaagcacctc ctaaggccaa 1620 aacgcctgcc aagaagacca gaccctcatc cacagtcatc aagaaaccta gtggtggctc 1680 ctcaaagaag cctgcaacca gtgcaagaaa ggaagtaaaa ttgccgggca agggcaaatc 1740 caccatgaag aagtctttca gagtgaaaaa gtaaatttta taggaaaaaa gggtatcatg 1800 atgaaattca aaatcttatt ttctaaggtc agtgtgcatt tgtttagttt tgatgctttt 1860 caaattacat tattttcctc ccctatgaac attgtgggga gggactctaa ataaaccagt 1920 ttaggcaaaa aaaaaa 1936 <210> 74 <211> 1667 <212> DNA
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2572892CB1 <400> 74 cgcgaatcgg cgaccccagt gcctcgacca ctatgccgcg ctctttcctc gtcaggaagc 60 cctccgaccc caatcggaag cctaactaca gcgagctgca ggactctaat ccagagttta 120 ccttccagca gccctacgac caggcccacc tgctggcagc catcccacct ccggagatcc 180 tcaaccccac cgcctcgctg ccaatgctca tctgggactc tgtcctggcg ccccaagccc 240 agccaattgc ctgggcctcc cttcggctcc aggagagtcc cagggtggca gagctgacct 300 ccctgtcaga cgaggacagt gggaaaggct cccagccccc cagcccaccc tcaccggctc 360 cttcgtcctt ctcctctact tcagcctctt ccttggaggc cgaggcctat gctgccttcc 420 caggcttggg ccaagtgccc aagcagctgg cccagctctc tgaggccaag gatctccagg 480 ctcgaaaggc cttcaactgc aaatactgca acaaggaata cctcagcctg ggtgccctca 540 agatgcacat ccgaagccac acgctgccct gcgtctgcgg aacctgcggg aaggccttct 600 ctaggccctg gctgctacaa ggccatgtcc ggacccacac tggcgagaag cccttctcct 660 gtccccactg cagccgtgcc ttcgctgacc gctccaacct gcgggcccac ctccagaccc 720 actcagatgt caagaagtac cagtgccagg cgtgtgctcg gaccttctcc cgaatgtccc 780 tgctccacaa gcaccaagag tccggctgct caggatgtcc ccgctgaccc tcgaggctcc 840 ctcttcctct ccatacctgc ccctgcctga cagccttccc cagctccagc aggaaggacc 900 ccacatcctt ctcactgcca tggaattccc tcctgagtgc cccacttctg gccacatcag 960 ccccacagga ctttgatgaa gaccattttc tggttctgtg tcctctgcct gggctctgga 1020 agaggccttc ccgtggccat ttctgtggag ggagggcagc tggcccccag ccctggggga 1080 ttcctgagct ggcctgtctg cgtgggtttt tgtatccaga gctgtttgga tacagctgct 1140 ttgagctaca ggacaaaggc tgacagactc actgggaagc tcccacccca ctcaggggac 1200 cccactcccc tcacacacac ccccccacaa ggaaccctca ggccaccctc cacgaggtgt 1260 gactaactat gcaataatcc acccccaggt gcagccccag ggcctgcgga ggcggtggca 1320 gactagagtc tgagatgccc cgagcccagg cagctatttc agcctcctgt ttggtggggt 1380 ggcacctgtt tcccgggcaa tttaacaatg tctgaaaagg gactgtgagt aatggctgtc 1440 acttgtcggg ggcccaagtg gggtgctctg gtctgaccga tgtgtctccc agaactattc 1500 tgggggcccg acaggtgggc ctgggaggaa gatgtttaca tttttaaagg tacactggta 1560 tttatatttc aaacattttg tatcaaggaa acgttttgta tagttatatg tacagtttat 1620 tgatattcaa taaagcagtt aatttatata ttaaaaaaaa aaaaaaa 1667 <210> 75 <211> 759 <212> DNA
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2785674CB1 <400> 75 SUBSTITUTE SHEET (RULE 26) tgggctcgcc tccctgggac taggtttcag cggccgctgc gatgaccaaa ataaaggcag 60 atcccgacgg gcccgaggct caggcggagg cgtgttccgg ggagcgcacc taccaggagc 120 tgctggtcaa ccagaacccc atcgcgcagc ccctggcttc tcgccgcctc acgcggaagc 180 tctacaaatg catcaagaaa gcggtgaagc agaagcagat tcggcgcggg gtgaaagagg 240 ttcagaaatt tgtcaacaaa ggagaaaaag ggatcatggt tttggcagga gacacactgc 300 ccattgaggt atactgccat ctcccagtca tgtgtgagga ccgaaatttg ccctatgtct 360 atatcccctc taagacggac ctgggtgcag ccgcaggctc caagcgcccc acctgtgtga 420 taatggtcaa gccccatgag gagtaccagg aggcttacga tgagtgcctg gaggaggtgc 480 agtccctgcc cctaccccta tgaggggctc cggtagcacc tgggcacctg ccgctggaag 540 ctattgggct ggcagcagga cgactggctg tcctcctgcc cacccacact gacggcatct 600 tcccagttcc ccaaggcacg ccttcttccc aggcagctct aacagccctt tcatgaaggt 660 aatgctagtc ttctgtccat cagtgccatt tcctgtagaa ctaaaggctg ttccaagaat 720 gtggggtggg gaaagtaaat gctaagacta aaaaaaaaa 759 <210> 76 <211> 1421 <212> DNA
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2797479CB1 <400> 76 ccccagtcac tgttcctgcc cgttgcctgt cagcctcact gcctttaatc cgcttccagg 60 gctcattcac ctgaatatat tggttgccat gtcgagatat ggtgaggata ctgcgcaagg 120 catcccggat ccgaaccttc tcaagtagct gttgatagtg ctggagctcc acggtgacat 180 gagctaacag gcgctgatca tcatgggtga tgacatatcg acgcacatag cccccaaaga 240 acttagacac aaacatccca gctctgttga ~gaagttgcc caggttgtta agcagctcag 300 aattattctt cagcagcagg tccgtccagg agaaagcact gtcctggccc tcaggccgaa 360 tgtacagcag atagaagcgc cagatgtcag cagggatccc cgtgtcctgg gctttgattt 420 tcctggttca gcacgaattc atgaaggaac tcacactcta gagaaaccct atgaatgtaa 480 gcaatgtggg aaattgttat ctcatcgctc aagctttcga agacacatga tggcacacac 540 tggagatggc cctcataaat gcacagtatg tgggaaagcc tttgactctc ctagtgtatt 600 tcaaagacat gaaaggactc acactggaga gaaaccctat gaatgcaagc aatgtgggaa 660 agccttccgt acttccagtt cccttcgaaa acatgaaaca acacacactg gagagcaacc 720 ctataaatgt aaatgtggaa aagcttttag tgatttattt tcctttcaaa gtcatgaaac 780 aacacacagt gaagaggagc cttatgaatg taaggagtgt gggaaagcat ttagttcttt 840 taaatacttt tgtcgccatg aacggactca cagtgaagaa aaatcttatg agtgtcaaat 900 ttgtggcaaa ctttcagtcg tttcagttac ttaaaaactc atgaaaggac tcacacggca 960 gagaagccat atgaatgtaa gcaatgcagg aaagcattct tttggccctc tttccttcta 1020 agacatgaaa ggactcacac tggagaaaga ccctatgaat gtaaacactg tggtaaagcc 1080 ttcagtcgtt ccagtttctg tcgagaacat gaaagaactc acgctggaga gaagccctat 1140 gaatgtaagg aatgtgggaa agccttcagt tctctcagtt cctttaatag acataaaagg 1200 acacactgga aggatattct ataagtgtat ggaatgtggg aaagcattca ttggttttat 1260 cacattcaga tacttgaaag aaataaatcc tgtgaatgta aacgtggtaa agccttaaga 1320 agtttccagg ctgggcgcag cggctcacac ctgtaatccc agcactttga gaggccgagg 1380 agggcatatc acgaggccag gagatcgaga ccagcctggg g 1421 <210> 77 <211> 2386 <212> DNA
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2960640CB1 <400> 77 gacttttaag ggatcacaga gctcacacca aagaccaggg gaacagtcag aagcctggct 60 SUBSTITUTE SHEET (RULE 26) tgctcctcag gctcccagga acctgcctca aaacacaggt ctccacgacc aggagacagg 120 tgctgtggtc tggacagctg ggtcccaggg accagccatg cgtgacaaca gagctgtatc 180 cctctgtcag caagaatgga tgtgcccagg ccctgcacaa agggccctct acaggggtgc 240 cacccagagg aaggacagtc acgtctcgct ggcaacaggt gtgccctggg gctatgaaga 300 gaccaagacg ctcctggcta ttcttagtag ttctcaattt tatggaaaac tccagacctg 360 tcagcagaac agccagatct acagggccat ggcggaagga ctctgggagc agggttttct 420 gcggacccca gaacagtgtc gcaccaagtt caaaagccta cagttgagtt accgcaaagt 480 gaggagaggc cgtgtgcctg agccttgtat cttttatgag gaaatgaatg ctctttcagg 540 ctcctgggcc tctgcacctc ctatggcaag cgatgctgtt cctggccaag aaggaagtga 600 tattgaggct ggagagctga atcaccagaa tggggaaccc acggaggtag aagatggcac 660 tgtggatggt gcagacaggg atgaaaagga cttcaggaat cctggccagg aagtcaggaa 720 actagacctg ccagtgctgt tcccaaacag acttggtttt gagttcaaga acgagattaa 780 aaaagaaaat ctaaaatggg atgattcaga ggaagtagaa ataaacaagg ctttacagag 840 aaagtccaga ggagtttatt ggcactctga gctacaaaaa ggcttggaga gtgagccaac 900 atcaagaagg caatgtagaa attctccagg ggagagtgag gagaaaaccc catcccagga 960 gaagatgagt caccagagtt tttgtgccag ggacaaagcc tgtacacata tcctctgtgg 1020 gaaaaactgc tctcagagtg tgcactctcc ccacaagcca gcgctcaaac tggaaaaagt 1080 atctcaatgt cctgaatgtg ggaaaacctt tagccgaagt tcttatcttg ttcggcatca 1140 aagaatccac acaggcgaga agcctcacaa gtgcagtgag tgcgggaagg gctttagtga 1200 gcgctccaac ctcactgccc acctacgaac tcacacaggg gagaggccct atcagtgtgg 1260 gcaatgtggg aaaagcttca accagagttc cagcctcatt gtccaccaga ggacccatac 1320 cggggaaaag ccttaccagt gcattgtctg tggaaagaga ttcaacaaca gttcccagtt 1380 cagtgctcac cggcgcatcc acactgggga gagcccatac aagtgtgcag tgtgtgggaa 1440 aatcttcaac aatagctccc acttcagtgc ccaccgaaaa acccacactg gtgaaaagcc 1500 ttacaggtgt tctcactgtg agagaggctt cactaagaac tctgccctca cccgtcatca 1560 gacagtacac atgaaagcag tactctcatc acaggaagga agagatgcgt tatgagtgtg 1620 tcggtaaact gtcagattaa gttcctcagg tcagcatgta tgagctttct tctgctgtgg 1680 agagatctag ccagtccctg actttgcaac agacctactg actactggat cttaagaccc 1740 atgtctagga ccaggagtca gcataaggac gctgacctct cctggctgtg cctgtgactc 1800 cagagtccta tcttactgtg acttaaagtt tga::ggagag aaagctgtag gatccataaa 1860 ttctaccagg aatccagggt cttcctgttc ctagcactga gaatgggcac ccagtggtcc 1920 aagaacactt tctgggctaa catagtcctc acacagggct gagaaagaaa gtgtctcctt 1980 tcctggaaag cacatgtaaa agttaagggc ctgaatctct tctaaaccaa taattgacct 2040 ctaggcaccc accgtaatac tgctaccttc agagcagaag acactgctct ttgtaaccca 2100 gccaccacca aaaagcaaac agaaagaagg aaggatggtt aagccattgg ataatactga 2160 atctgtttcc ctaagtgact taaccttaga gcaagcacaa catccaggtt aattaattgt 2220 aagatttctc ctctcattat tgccctcatc atagttcctg attgtctctt aaagtaagtg 2280 gtttatagac attactattt ctgataataa tttacaaact actataaaca aatttataaa 2340 cattactaat ttctgatgaa aataaagttg tttctccctc caccac 2386 <210> 78 <211> 1432 <212> DNA
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 3454051CB1 <400> 78 agtatgagct ggacctgtcc gcgttgccag caacctgttt tcttcgctga gaaggtgagc 60 tccctgggca agaactggca ccgcttctgc ctgaaatgtg agcgctgcca cagcatcctg 120 tcccctggcg ggcatgcaga gcacaatggg aggccatact gccacaagcc atgctatggg 180 gctctctttg gacccagggg ccctccccat atgaagacat tcactgggga gacctcgctg 240 tgccctggct gtggggagcc cgtctatttt gctgagaagg tgatgtcatt aggcagaaat 300 tggcaccgac cgtgtctgag gtgccagcgt tgccacaaga ccctgactgc tgggagtcat 360 gctgagcatg atggagtccc ctactgccac gtcccctgct acggctacct gtttggcccc 420 aaaggtgtga acattggcga tgtgggctgc tacatctatg acccagtgaa gataaaattc 480 aaatgagacg ctcacaaaaa aggtcaccct aactcaggcc tcccatcatg cccctcatgg 540 tccaatggaa gctacaaaaa tctccagtcc catgggggtt ggggaaggtg ggatcttggg 600 ggcctgggcc taggctccat ggtaggccag agagtctaga ctttctctgc caattttttc 660 SUBSTITUTE SHEET (RULE 26) cctttcccat ttctatctgg ttagggaaca gcccgttttg aagggtatcc tcctcctggc 720 catcacaacc cctttcccca gcacattctg gagcttcaag gtactcataa aacttgtgtt 780 tattgaattt cagcctctgt ggcttcttca ataaaatgtt ggctcccatg ccttcaactc 840 ttctttgggc atgagaccag tgggttggag gatggggagt gtgggggttg ggatgacatg 900 cattgccctg cagggtgcct cggaggtagc agggccagcc atgagaacaa aaagctctgt 960 tctttttgtc ccttgggcct ggcattggca gtcctagcac cacacagtgg acagcatgcc 1020 caccagcccc attggtacca gaagtctcat atgctagtcc tttctttagc accatctcta 1080 gaagaagcag aagcacctta ttcagtaact catttgagca tggcaacaga tcctatggta 1140 gggcctccca agaggcttca ttatccattt gggagatgaa cagactgagg cccagagagg 1200 gaaagccaca tgcccaaggt cacacagcaa gttaatggtg aaggttttat cagagcccag 1260 ggcagactca gtggcttcct atccagggct cttctcacag ctcgtcacca ctgccccaac 1320 ccaaggggca cctttattta cagaatctcc ccaaccgtga gacgggtgcc agcagaccac 1380 tgcattctgg gaagtcaact gttcctagaa gcaaataatc aaggatggat ga 1432 <210> 79 <211> 1816 <212> DNA
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 3510640CB1 <400> 79 cactgatgca ggaactgtat agcacaccag cctccaggct ggactccttc gtggctcagt 60 ggctgcagcc ccaccgggag tggaaggaag aggtgctaga cgctgtgcgg accgtggagg 120 agtttctgag gcaggagcat ttccagggga agcgtgggct ggaccaggat gtgcgggtgc 180 tgaaggtagt caaggtgggc tccttcggga atggcacggt tctcaggagc accagagagg 240 tggagctggt ggcgtttctg agctgtttcc acagcttcca ggaggcagcc aagcatcaca 300 aagatgttct gaggctgata tggaaaacca tgtggcaaag ccaggacctg ctggacctcg 360 ggctcgagga cctgaggatg gagcagagag tccccgatgc tctcgtcttc accatccaga 420 ccagggggac tgcggagccc atcacggtca ccattgtgcc tgcctacaga gccctggggc 480 cttctcttcc caactcccag ccaccccctg aggtctatgt gagcctgatc aaggcctgcg 540 gtggtcctgg aaatttctgc ccattcttca gcgagctgca gagaaatttc gtgaaacatc 600 ggccaactaa gctgaagagc ctcctgcgcc tggtgaaaca ctggtaccag cagtatgtga 660 aagccaggtc ccccagagcc aatctgcccc ctctctatgc tcttgaactt ctaaccatct 720 atgcctggga aatgggtact gaagaagacg agaatttcat gttggacgaa ggcttcacca 780 ctgtgatgga cctgctcctg gagtatgaag tcatctgtat ctactggacc aagtactaca 840 cactccacaa tgcaatcatt gaggattgtg tcagaaaaca gctcaaaaaa gagaggccca 900 tcatcctgga tccggccgac cccaccctca acgtggcaga agggtacaga tgggacatcg 960 ttgctcagag ggcctcccag tgcctgaaac aggactgttg ctatgacaac agggagaacc 1020 ccatctccag ctggaacgtg aagagggcac gagacatcca cttgacagtg gagcagaggg 1080 gttacccaga tttcaacctc atcgtgaacc cttatgagcc cataaggaag gttaaagaga 1140 aaatccggag gaccaggggc tactctggcc tgcagcgtct gtccttccag gttcctggca 1200 gtgagaggca gcttctcagc agcaggtgct ccttagccaa atatgggatc ttctcccaca 1260 ctcacatcta tctgctggag accatcccct ccgagatcca ggtcttcgtg aagaatcctg 1320 atggtgggag ctacgcctat gccatcaacc ccaacagctt catcctgggt ctgaagcagc 1380 agattgaaga ccagcagggg cttcctaaaa agcagcagca gctggaattc caaggccaag 1440 tcctgcagga ctggttgggt ctggggatct atggcatcca agacagtgac actctcatcc 1500 tctcgaagaa gaaaggagag gctctgtttc cagccagtta gttttctctg ggagacttct 1560 ctgtacattt ctgccatgta ctccagaact catcctgtca atcactctgt cccattgtct 1620 actgggaagg tcccaggtct tcaccagttt tacaatgagt tatcccaggc cagacgtggt 1680 agctcacacc tgtaatccca gaactttggg aggccgaggt gggaggagcg cttgagccga 1740 ggagttcaag accagcctgg gtatcatagg gagaccccgt ctctacaaaa taaaaaaata 1800 attcactggg aaaaaa <210> 80 <211> 1556 <212> DNA
<213> Homo sapiens SUBSTITUTE SHEET (RULE 26) <220>
<221> misc-feature <223> Incyte ID No.: 3815083CB1 <400> 80 ctcaggtccg gagcgcggtc gggacacagc gcctctagga gaaagcctgg aaggcgctcc 60 gggggtatcc agagctctta gcgggccggc agcatgtgcg gggccccagt aaatggaaat 120 gttttctaac atataaaaac ctacagaaga agaaaataat tttctggatc aaattagaag 180 tctgtattat attgatgtct ccagattcaa atatattaga aagcagccgt ggagacaacc 240 atcttcattt tgggagaaat aactaaagcc cgcctcaagc attagaacta cagacaaacc 300 ctgatgcgac ctctccagat tgtcccaagt cgattgattt cccagctata ttgtggcctg 360 aagcctccag cgtccacacg aaaccagatt tgcctgaaaa tggctcggcc aagttcaagt 420 atggcagatt ttcgaaagtt ttttgcaaaa gcaaagcaca tagtcatcat ctcaggagct 480 ggtgttagtg cagaaagtgg tgttccgacc ttcagaggag ctggaggtta ttggagaaaa 540 tggcaagccc aggacctggc gactcccctg gcctttgccc acaacccgtc ccgggtgtgg 600 gagttctacc actaccggcg ggaggtcatg gggagcaagg agcccaacgc cgggcaccgc 660 gccatagccg agtgtgagac ccggctgggc aagcagggcc ggcgagtcgt ggtcatcacc 720 cagaacatcg atgagctgca ccgcaaggct ggcaccaaga accttctgga gatccatggt 780 agcttattta aaactcgatg tacctcttgt ggagttgtgg ctgagaatta caagagtcca 840 atttgtccag ctttatcagg aaaaggtgct ccagaacctg gaactcaaga tgccagcatc 900 ccagttgaga aacttccccg gtgtgaagag gcaggctgcg ggggcttgct gcgacctcac 960 gtcgtgtggt ttggagaaaa cctggatcct gccattctgg aggaggttga cagagagctc 1020 gcccactgtg atttatgtct agtggtgggc acttcctctg tggtgtaccc agcagccatg 1080 tttgcccccc aggtggctgc caggggcgtg ccagtggctg aatttaacac ggagaccacc 1140 ccagctacga acagattcag gtttcatttc cagggaccct gtggaacgac tcttcctgaa 1200 gcccttgcct gtcatgaaaa tgaaactgtt tcttaagtgt cctggggaag aaagaaatta 1260 cagtatatct aagaactagg ccacacgcag aggagaaatg gtcttatggg tggtgagctg 1320 agtactgaac aatctaaaaa tagcctctga ttccctcgct ggaatccaac ctgttgataa 1380 gtgatggggg tttagaagta gcaaagagca cccacattca aaagtcacag aactggaaag 1440 ttaattcata ttatttggtt tgaactgaaa cgtgaggtat ctttgatgtg tatggttggt 1500 tattgggagg gaaaaatttt gtaaattaga ttgtctaaaa aaaataaaaa aaaaaa 1556 <210> 81 <211> 1951 <212> DNA
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 3988457CB1 <400> 81 ctccgattat gggataggag aagtgcccgt ggagcccctg gatgtcccct taccctccac 60 gatcaggcca gcttcccccg tggccgggtc tccaaagcag ccggtgcgtg gctactaccg 120 tggcgctgtc ggtggcacgt ttgaccgcct gcacaacgcc cacaaggtgt tgctcagtgt 180 cgcgtgcatc ctggcccagg agcagcttgt ggtgggagta gcagacaaag atctgttgaa 240 gagcaagttg ctccctgagc tgctccaacc ttatacagaa cgtgtggaac atctgagtga 300 attcctggtg gacatcaagc cctccttgac ttttgatgtc atccccctgc tggaccccta 360 tgggcccgct ggctctgacc cctccctgga gttcctggtg gtcagcgagg agacctatcg 420 tggggggatg gccatcaacc gcttccgcct tgagaatgac ctggaggaac ttgctttgta 480 ccagatccag ctgctgaagg acctcagaca tacagagaat gaagaggaca aagtcagctc 540 ctccagcttc cgccagcgaa tgttggggaa cctgcttcgg cctccatatg aaaggccaga 600 gctccccaca tgtctctatg taattgggct gactggcatc agtggctctg ggaagagctc 660 aatagctcag cgactgaagg gcctgggggc gtttgtcatt gacagtgacc acctgggtca 720 tcgggcctat gccccaggtg gccctgccta ccagcctgtg gtggaggcct ttggaacaga 780 tattctccat aaagatggca tcatcaacag gaaggtccta ggcagccggg tgtttgggaa 840 taagaagcag ctgaagatac tcacggacat tatgtggcca attatcgcaa agctggcccg 900 agaggagatg gatcgggctg tggctgaggg aaagcgtgtg tgtgtgattg atgccgctgt 960 gttgcttgaa gccggctggc agaacctggt ccatgaggtg tggactgctg tcatcccaga 1020 gactgaggct gtaagacgca ttgtggagag ggatggcctc agtgaagccg cggctcaaag 1080 ccggctgcag agccagatga gcgggcagca gcttgtggaa cagagccacg tggtgctcag 1140 SUBSTITUTE SHEET (RULE 26) cagcccttgt gggagccgca tatcacccaa cgccaggtgg agaaagcctg ggccctcttg 1200 cagaagcgca ttcccaagac tcatcaggcc ctcgactgaa aagttctcag tggggccaga 1260 ctggctcctg gagctgacaa gcgaccccgt ggtgaggaga aatgggggcc ttgatgctca 1320 ccctggttca ggcccagagg tccaagctat actgtgcagg acatggccag gcctggtgga 1380 cacaggaagc ctacccaaca cgctggtatt tggccaacac tgaggatgtg gttcatgggg 1440 gagcagtccc ctccccactc ttgcccatgg gtgactctta cccacagctg actagggcca 1500 gcgcaaatac tggaacctgt aacagaatta aaggtgaatg ttctgaaaaa aaaatagaat 1560 tttggacatc tacaactaac tcgatttaca cttacgaaca taatggactc ttaaaaaatg 1620 gaaagggata acagggaccc cccgggttct gcatccttcc tcccggggat ttttttccgg 1680 ccgggtcctt gcgggtgaac tgattttcct tacactgcgc ctatttaaac gttggggtaa 1740 ccagggtcgg accttttccc ttggaacttt ttttacccgt cacgatttcc actgcaactt 1800 agactcggga aacttagggt ggaatccctg gggggcctaa ggcgggaact ccctcccttt 1860 atctgctttg ggtcaaagag cccgtttctc catctggcaa ctctgtccat ccaaggggtt 1920 ttcgggttct cgggccaagg cccggggtgg g 1951 <210> 82 <211> 1313 <212> DNA
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 131890CB1 <400> 82 cgtcgggagg gcctaagtcc gtgtgcggtg cccttcggcc ggcctgagcc ccagagtcag 60 ctcccctttc tcgcccagcg cccccaggcc gctcccgggg ctcacggaat agtaaagaaa 120 cacatcataa aacctcccag gacataaagg tgagcacaga ccctgtttgg atcaagtcag 180 ttcctggagc ctgaatgatg actgctgaat cacgggaagc cacgggtctg tccccacagg 240 ctgcacagga gaaggatggt atcgttatag tgaaggtgga agaggaagat gaggaagacc. 300 acatgtgggg gcaggattcc accctacagg acacgcctcc tccagaccca gagatattcc 360 gccaacgctt caggcgcttc tgttaccaga acacttttgg gccccgagag gctctcagtc 420 ggctgaagga actttgtcat cagtggctgc ggccagaaat aaacaccaag gaacagatcc 480 tggagcttct ggtgctagag cagtttcttt ccatcctgcc caaggagctc caggtctggc 540 tgcaggaata ccgccccgat agtggagagg aggccgtgac ccttctagaa gacttggagc 600 ttgatttatc aggacaacag gtcccaggtc aagttcatgg acctgagatg ctcgcaaggg 660 ggatggtgcc tctggatcca gttcaggagt cctcgagctt tgaccttcat cacgaggcca 720 cccagtccca cttcaaacat tcgtctcgga aaccccgcct cttacagtca cgaggtaaga 780 agcaaggttt catttagggg aagggaaatg attcaggacg agagtctttg tgctgctgag 840 tgcctgtgat gaagaagcat gttagtcctg ggcaacgtag cgagacccca tctctacaaa 900 aaatagaaaa attagccagg tatagtggcg cacacctgtg attccagcta cgcaggaggc 960 tgaggtggga ggattgcttg agcccaggag gttgaggctg cagtgagctg taatcatgcc 1020 actactccaa cctgggcaac acagcaagga ccctgtctca aaagctactt acagaaaaga 1080 attaggctcg gcacggtagc tcacacctgt aatcccagca ctttgggagg ctgaggcggg 1140 cagatcactt gaggtcagga gtttgagacc agcctggcca acatggtgaa accttgtctc 1200 tactaaaaat atgaaaatta gccaggcatg gtggcacatt cctgtaatcc cagctactcg 1260 ggaggctgag gcaggagaat cacttgaacc caggaggtgg aggttgcagt aag 1313 <210> 83 <211> 1197 <212> DNA
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 238642CB1 <400> 83 cggctcgagc gtgaaccgaa gtccttatat tcccgggctt ctttctcctc tgggtaccag 60 ctccttactg ccctgcagac aagcgtgccg tgcgtgcttg tggccaaggg aaggaagagc 120 tggttgatcc acagatagct ccttcctccc cgccccttcc tttttgtttg gaggtcccag 180 SUBSTITUTE SHEET (RULE 26) gatctgtgtt cacagacatc tgggggaaga aaaggagcag gaaactaccc cgcacagagt 240 taagcaggaa acaacaacaa catcatgcaa aaaccctgca aagaaaacga aggaaagcca 300 aagtgcagcg tgccaaagag ggaggaaaaa cgcccgtatg gagaatttga acgccagcaa 360 acagaaggga attttagaca gaggctgctt cagtctctcg aagaatttaa agaggacata 420 gactataggc attttaaaga tgaagaaatg acaagggagg gagatgagat ggaaaggtgt 480 ttggaagaga taaggggtct gagaaagaaa tttagggctc tgcattctaa ccataggcat 540 tctcgggacc gtccttatcc catttaatta atttctctga caattcaatt attttctgtt 600 attaatgttg ccactgcttt ctgtttgtct gcactttctt gataaatatt tgctatcgtt 660 ttactccagt cattcgatgt tgctgagatt tacatatgac tcttgtcaac atctcatctt 720 ttgacccaat cttattcatt taataagagg tctcattcat ttgcatggaa aaatgctcat 780 tgtatattgc aaagtgaaaa taacgagttg caaaacagtg tatacatata tgtgtgtata 840 tatgtacact ttatttgtac atttctatgt gacataatgc aaaggaaagt gtctgatttt 900 attatacacc aaaggttaac agtgaatctc tgtgtgatct cttttttttt ctttttgcct 960 atctgcatct tctcacttgc caaaaaatga atatatgttt atgtgtgtat attacttgtg 1020 tcacaaaaaa ccctaaagta gacagtaaaa gaacttgtca atcgcctttg gaaggcaatg 1080 aaacacttaa taaactctca ataacagaag cgtaaaaatg aaatgtaaac ctccaattac 1140 ctctggatct cttagccaga gtaataaact ggtaattatt acagataaaa aaaaaaa 1197 <210> 84 <211> 2170 <212> DNA
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 669862CB1 <400> 84 agcgtgcgcg ataggacagg gccttaaatt catggttatg tgtttggttt tca~,:tctaag 60 ataaagccga accactgaca aaattatata gagagcaatg tgataatgtt aggaatagag 120 atattcagga catactcctg tgcattctga tccactcagt ctgagtggat atctaaaaga 180 tagtgtatgt aaaatgctcc tatggtaatt ctgatttgca actaaatatg agaactagtg 240 actttgtctt tgcctactca taaatcttac atcctcctgt gcactttcat aattttctgt 300 gcccttcttg ccttttatat attgcttggc agtactttag aattttctaa actctttgat 360 tactaacaga tacacttttt agttgatcac tatttttaat atagatgtcc tctccctacc 420 cgctattatt ggaaaatagc atttgtttgt tttttcattt tcttccagac tttaatttca 480 caactgaaag caacaagtta tcttcagaaa aaagaaatta tgaagtaaat gcgtaccatc 540 aggagacatg gaaaagaaat aaaaccttca accttatgag gtttattttc agaactgacc 600 cacagtacac aattgaattt gggagacaac agagacctaa agtgggatgt tttagtcaaa 660 tgatattcaa aaaacataaa tcccttcctc tacataagag aaataacaca agagagaaat 720 catatgagtg taaggaatat aagaagggct ttagaaaata tttgcacctt actgaacatc 780 tgagagacca tactggtgtg ataccctatg aatgtaatga atgtggaaaa gcatttgtag 840 ttttccagca ttttattaga catcgaaaaa tccacactga tttgaaaccc tatgaatgca 900 atggatgtga gaaggccttt aggttttatt cacagcttat tcagcatcag ataattcata 960 ctggtatgaa accctatgaa tgtaagcaat gcgggaaggc ttttagacgt cattctcacc 1020 ttacagaaca tcagaaaatt catgttggct tgaaaccctt tgaatgtaag gaatgtgggg 1080 aaacgtttag attatatcga catatgtgtc tgcatcagaa aattcatcat ggtgtgaaac 1140 cctacaaatg taaagaatgt ggaaaggctt ttggtcatcg ttcaagtctt taccaacata 1200 agaaaattca ttctggtgag aaaccatata aatgtgaaca atgtgaaaag gcctttgttc 1260 gcagctatct acttgttgaa catcaaagaa gtcatactgg tgagaaacct catgaatgca 1320 tggaatgtgg aaaggctttt agtaagggct caagccttct taaacataag agaattcata 1380 gtagtgagaa actctatgat tgtaaggatt gtggaaaggc cttttgtaga ggctctcaac 1440 ttacacagca tcagagaatt catactggtg agaagccaca tgaatgtaaa gaatgtggga 1500 agacttttaa gcttcattca tatcttattc aacatcagat aattcatact gatttgaagc 1560 catatgaatg taagcaatgt gggaaagcct tcagtcgtgt tggagacctt aagacacatc 1620 aatcaattca tgctggggag aaaccctatg aatgtaagga atgtggaaaa acctttagac 1680 ttaattctca actaatttat catcagacaa ttcatactgg tttgaaaccc tatgtatgta 1740 aagaatgtaa gaaggccttt cgttctatct caggtctttc tcaacataag agaattcata 1800 ctggtgaaaa accctatgaa tgtaaagaat gtgataaggc ctttaatcgc agtgatcgac 1860 ttactcaaca tgagacaatt catactggtg tgaaaccaca gaaatgcaaa gaatgtggta 1920 aggcctttag tcattgctat caacttagtc aacatcaaag atttcaccat ggtgagagac 1980 SUBSTITUTE SHEET (RULE 26) tcttaatgta atgagaggga aagcctttag ccatggcaca tttttactgt tgtcactatt 2040 atgatgctat agtgaagatt aaactagtta atatagaata taaatacttg gaaaggcatc 2100 tggcacatcg tatttgctta ctaaatacat tatttttatg ataattgtta gaattactaa 2160 gaataaatga 2170 <210> 85 <211> 1904 <212> DNA
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 1003663CB1 <400> 85 cagctctcag gtccgacacc cgctggaagc cggcgcgggc gcaggcgcgc acgcaaaggc 60 ggccgggagt aaggcggact gaaggaggag cttgatggaa gcgtgcgaga aggggcgtaa 120 ctgatttgga aaccagagga aaggcgctgt tttcaccgaa ttagaatcgc gggaaaatag 180 agaagagttt gtttgaaggt ctcgcgagat cgagaccgga agtccttcat ctcaagcatc 240 caatgctgaa agcggcctga ttttctctac cggaagccct tttccagagg ctgggaacac 300 ggcccaccta gcaggaagtc ccacctcctt gagctccgcc acccttcccg aagtttttct 360 gtcacctgtg ttaggctccg tcccctttcc gcgttttatc cccgtaccag aaaaggatac 420 atttagtgcc tcccacccag ctccactaaa cgggttggat atctcattct ttgagttggt 480 gttccttccc cggcgccccc atgtagctgg gaagtgggac ctgggggtgg ttggacccct 540 gggatcctaa aggaggggca gggagggcgc agaactccgc ttctgctcct tgctaccagg 600 acgcgcggcc tcctcagcct ctttcctccc gctgccatgc accctgcagc cttcccgctt 660 cctgtggttg tggccgctgt gctgtgggga gcggccccga cccgggggct cattcgagcg 720 acctcggacc acaatgccag catggacttt gcagaccttc cagctctgtt tggggctacc 780 ttgagccagg agggcctcca ggggttcctt gtggaggctc acccagacaa tgcctgcagc 840 cccattgccc caccaccccc agccccggtc aatgggtcag tctttattgc gctgcttcga 900 agattcgact gcaactttga cctcaaggtc ctaaatgccc agaaggctgg atatggtgcc 960 gctgtagtac acaatgtgaa ttccaatgaa cttctgaaca tggtgtggaa tagtgaggaa 1020 atccagcagc agatctggat cccgtctgta tttattgggg agagaagctc cgagtacctg 1080 cgtgccctct ttgtctacga gaagggggct cgggtgcttc tggttccaga caataccttc 1140 cccttgggct attacctcat ccctttcaca gggattgtgg gactgctggt tttggccatg 1200 ggagcagtaa tgatagctcg ttgtatccag caccggaaac ggctccagcg gaatcgactt 1260 accaaagagc aactgaaaca gattcctaca catgactatc agaagggaga ccagtatgat 1320 gtctgtgcca tttgcctgga tgaatatgag gatggggaca agctgcgggt actcccctgt 1380 gctcatgcct accacagccg ctgcgtggac ccctggctca ctcagacccg gaagacctgc 1440 cccatttgca agcagcctgt tcatcggggt cctggggacg aagaccaaga ggaagaaact 1500 caagggcaag aggagggtga tgaaggggag ccaagggacc accctgcctc agaaaggacc 1560 ccacttttgg gttctagccc cactcttccc acctcctttg gttccttagc cccagctccc 1620 cttgtttttc ctgggccttc aacagatccc ccactgtccc ctccctcttc ccctgttatc 1680 ctggtctaat aaccccccac acatacacct ctggtgacct atttgcacag accgtcgtct 1740 tccctccagt cttctgaggg ataggggaca ttccatccca agcttctccc ttacccacac 1800 ctatcctttt gaggggcttt ggggtggggc tggggcaagc agagggactg ggtcttcact 1860 tcttgggcta ataaaattgt ttctttgtgg actaaaaaaa aaaa 1904 <210> 86 <211> 1249 <212> DNA
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 1432557CB1 <400> 86 cgtttatcct gttgggggcg gaagtgagag agcccttatt cgtattggct tagatttgca 60 agcggcagtt gtctatcaaa tctatcaagt cgcccttagc gctcaggaag tacgacaccg 120 SUBSTITUTE SHEET (RULE 26) gaaggggtgg gctttgcgaa gatggcggcg ctgggggtgc tggagtccga cctgccaagt 180 gccgtgacac ttctgaaaaa tctccaggag caagtgatgg ctgtaactgc acaagtgaaa 240 tcactgacac aaaaagttca agctggtgcc tatcctacag aaaagggtct cagcttcttg 300 gaagtgaaag accagctgct gctcatgtac cttatggatt tgacccacct cattctggac 360 aaagcctcag gaggatctct tcagggacat gatgcagttt tgagactggt agagattcga 420 acggttttgg aaaagcttcg tcccttggac caaaagctga agtatcaaat tgacaagctg 480 atcaagactg cagtgacagg cagccttagt gagaatgacc cacttcgttt taagcctcat 540 cccagcaata tgatgagcaa gttgagctct gaggatgagg aggaagatga agcagaagat 600 gaccagtctg aggcttcagg gaagaaatct gtgaagggag tgtctaagaa atatgttcct 660 ccacgcttgg ttccagtaca ttatgatgaa acagaagctg agcgggagaa gaagcgtcta 720 gaacgagcca agagacgggc attgagcagc tctgtcattc gtgaacttaa ggagcagtac 780 tcagatgctc cagaggaaat ccgtgatgct cggcatcccc atgttacccg ccagagtcag 840 gaggaccaac acaggattaa ctatgaggag agcatgatgg tgcgtttgag cgtcagtaag 900 cgagagaaag gacggcgaaa acgagcaaat gtcatgagct cacaacttca ttcccttaca 960 cacttcagtg acatcagtgc tttgacaggg ggaactgttc atcttgatga ggatcagaat 1020 cctattaaga agcggaagaa gatacctcag aaaggtcgga agaaaaaagg ttttcggagg 1080 cggcggtgat tatgggtgta catatttgta tattttttgt catcctgaga tacttctaat 1140 ttcattgtat ataggtggtt ttccctggaa ttcattaatt gtttgctttg gacatgtgga 1200 aagagcctta ctaataaaat tgattttact tatgaaaaaa aaaaaaaaa 1249 <210> 87 <211> 1064 <212> DNA
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 1441770CB1 <400> 87 cggctctcca gagcgtctgt aaacacccag agactgtcat ggagggggag gaggaggcgg 60 cggcggcgaa gggaggcgtt tggggccgcc tccagggtcc gctctgccat tcctgaactg 120 gtccctcgtc cccgtgactc tggcatcagg gaagcgaact gttaggcgag aggaggaggc 180 agccagaacc atatcccctt cttcctcggg gcgggggccg ggccaggccg gctgagccgg 240 gggagggctc cgggagggag tgcctggcca ggccggcctg tctgccgcga tggatgacag 300 taaggtggtt ggaggcaaag taaagaagcc cggtaaacgt ggtcggaagc cagccaaaat 360 tgacttgaaa gcaaaacttg agaggagccg gcagagtgca agagaatgcc gagcccgaaa 420 aaagctgaga tatcagtatt tggaagagtt ggtatccagt cgagaaagag ctatatgtgc 480 cctcagagag gaactggaaa tgtacaagca gtggtgcatg gcaatggacc aaggaaaaat 540 cccttctgaa ataaaggccc tactcactgg agaagagcag aacaaatctc agcagaactc 600 aagcaggcat accaaggctg ggaagacaga tgctaatagc aattcctggt gaagattata 660 taaagatgag tcagtgattg aagccaatat tctgattccc atggaagatg gatgggcaag 720 agtgtacttc ttggctccat ttactaccta ctgctcagta gtcatctctg taaatctgca 780 atttctacca aaatgtgtga tcgtagatct caaaggatct tgctttaact ttcaacactt 840 agaaaatcta caaacattca gacctgtctg ggttggtatt gccacccatg acatttaaca 900 tgttgtgatg cttgaaaaca caggagtaga gaaaatcgat gaagattgta tttttgcacc 960 ttaactccac attgctttat tggttaattt atattctttc catgtaattc atgtaattgt 1020 atgtctgtgt gtgttttatg tgtcaccacc tttcatgttt ttga 1064 <210> 88 <211> 1398 <212> DNA
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 1456684CB1 <400> 88 agacccaaaa gcattaagga gaaaaagaaa actacatcac ataccagggg agaaataccg 60 SUBSTITUTE SHEET (RULE 26) gaggagtcaa actatgttgc tgatcctgga ggatcactga gcaaaaccac aaatattgct 120 gaagaaacca gcaaaattga aacctacatt gcaaaacctg ctctgccggg aacctccaca 180 aatagtaatg ttgcacccct ttgccaaata acagtgaaaa ttggaaacga agccattgtg 240 aaaaggcaca ttctaggatc taaattgttt tataaaagag ggagaagacc caagtatcag 300 atgcaggagg agcctttgcc acaggggaat gacccagaac ccagtggaga cagcccactc 360 gggctttgcc aatccgagtg catggagatg agtgaagtgt tcgatgacgc aagtgaccag 420 gattccactg acaaaccgtg gcgcccttac tacaactaca aacccaaaaa gaaatccaga 480 cagttgaaaa aaatgaggaa agtcaactgg aggaaggagc acggaaacag gagcccgagc 540 cataaatgta aatacccagc agaactggat tgcgccgtgg ggaaggctcc tcaggataaa 600 ccctttgagg aagaagaaac taaagagatg cccaagctgc agtgtgaact ctgtgatgga 660 gacaaagcag tgggggctgg aaaccaagga aggccccacc gacatcttac ttctcggcca 720 tatgcctgcg agctctgcgc caagcagttc cagagccctt ccacactcaa aatgcacatg 780 agatgtcaca ccggggagaa gccataccag tgcaagacct gcggacggtg cttttcggtg 840 caaggaaact tacagaaaca tgaacgcatc cacctgggct tgaaggagtt cgtctgtcag 900 tattgcaaca aggcattcac cttgaatgag accctcaaaa tccatgaaag aatccatact 960 ggagaaaagc gttaccactg tcagttctgc tttcagagat ttttgtatct ctccaccaaa 1020 aggaatcacg agcagaggca tattcgggag cataatggga agggctatgc ctgcttccag 1080 tgccccaaaa tttgcaaaac agctgctgcc cttggaatgc accaaaagaa acacttattc 1140 aaaagcc.caa gtcagcagga gaaaataggt gacgtgtgcc acgaaaactc aaatcccttg 1200 gagaatcaac atttcattgg ttcagaagac aatgaccaaa aggataacat acaaaccggt 1260 gtggaaaatg ttgtcctttg agtggcaaga attagaaaaa tcttcaaaaa tatagttggt 1320 ggttttttta gttatgattt aagtttagtt tcattttgtc catgtgacag tcatgaagga 1380 gtgaaaaaaa aaaaaaaa 1398 <210> 89 <211> 746 <212> DNA
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 1602916CB1 <400> 89 cggctcgagg cgtctttatg ggcccccttt aaggccggcg gaggcatctc gggccgggcg 60 cggcgctccg tccgtcggcc gtagcgactg aactgcgcgc ggatccctcc gcggggctcc 120 tcgtccccgt cacgctgact ttccgtgcag tgccgtggtg cgaaaatgcc tcgccggtgc 180 gcaccggaga cagccgattt ttacgaccca gcaagaggcc gagctggtac aatatcctga 240 ctgtaaatcg tccagtggta atattggcga ggacccagac cacttaaatc agagctcgtc 300 tccttctcaa atgtttccgt ggatgagacc acaagcagct cctggtagac gaagaggaag 360 acaaacctac agtcgcttcc aaactctaga gttggaaaag gaatttcttt ttaaccccta 420 tctgaccagg aaaagaagaa tcgaggtttc ccacgcccta gccctcaccg agagacaggt 480 aaaaatctgg ttccagaaca ggagaatgaa atggaaaaag gaaaacaaca aggacaaatt 540 tcccgtttcc cggcaggagg tgaaggacgg ggaaacgaaa aaggaagccc aagagctgga 600 ggaagacaga gccgaacgct tgacaaatta acttctacct ttaaaattta ccacagacta 660 ttaaaactaa taatcaccat atgctgtgga caccacctat tttctttgtt ggaaaagacc 720 ttactgtgtt tcaagctacc ttcatg 746 <210> 90 <211> 1270 <212> DNA
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 1692816CB1 <400> 90 gttggtcacg tggttgttcg gagcgggcga gcggagttag cagggcttta ctgcagagcg 60 cgccgggcac tccagcgacc gtggggatca gcgtaggtga gctgtggcct tttgcgaggt 120 SUBSTITUTE SHEET (RULE 26) gctgcagcca tagctacgtg cgttcgctac gaggattgag cgtctccacc cagtaagtgg 180 gcaagaggcg gcaggaagtg ggtacgcagg ggcgcaaggc gcacagcctc tagacgactc 240 gctttccctc cggccaacct ctgaagccgc gtcctacttt gacagctgca gggccgcggc 300 ctggtcttct gtgcttcacc atctacataa tgaatcccag tatgaagcag aaacaagaag 360 aaatcaaaga gaatataaag aatagttctg tcccaagaag aactctgaag atgattcagc 420 cttctgcatc tggatctctt gttggaagag aaaatgagct gtccgcaggc ttgtccaaaa 480 ggaaacatcg gaatgaccac ttaacatcta caacttccag ccctggggtt attgtcccag 540 aatctagtga aaataaaaat cttggaggag tcacccagga gtcatttgat cttatgatta 600 aagaaaatcc atcctctcag tattggaagg aagtggcaga aaaacggaga aaggcgctgt 660 atgaagcact taaggaaaat gagaaacttc ataaagaaat tgaacaaaag gacaatgaaa 720 ttgcccgcct gaaaaaggag aataaagaac tggcagaagt agcagaacat gtacagtata 780 tggcagagct aatagagaga ctgaatggtg aacctctgga taattttgaa tcactggata 840 atcaggaatt tgattctgaa gaagaaactg ttgaggattc tctagtggaa gactcagaaa 900 ttggcacgtg tgctgaagga actgtatctt cctctacgga tgcaaagcca tgtatatgaa 960 atgcattaat atttgactgt tgagaatttt actgccgaag tttacctcca ctagttcttt 1020 gtagcagagt acataactac ataatgccaa ctctggaatc aaatttcctt gtttgaatcc 1080 tgggacccta ttgcattaaa gtacaaatac tatgtatttt taatctatga tggtttatgt 1140 gaataggatt ttctcagttg tcagccatga cttatgttta ttactaaata aacttcaaac 1200 tcctgttgaa cattgtgtat aacttagaat aatgaaatat aaggagtatg tgtagaaaaa 1260 aaaaaaaaaa 1270 <210> 91 <211> 943 <212> DNA
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 1968191CB1 <400> 91 gtcccatttc cagaaatcac aaggatgtta ggcaatgaat ggagtaaact gcctcctgag 60 gaaaaacagc gctaccttga tgaagcagac agagataagg agcgttacat gaaggaactg 120 gaacagtatc agaaaacaga ggcctacaag gtcttcagta ggaaaaccca ggaccgtcag 180 aaaggcaaat ctcataggca agatgcagcc cggcaggcca ctcatgatca tgagaaagaa 240 acagaggtaa aggaacggtc tgtttttgac atccctatat ttacagagga attcttgaac 300 catagcaaag ctcgggaagc agagctccgc cagcttcgca aatccaacat ggagtttgag 360 gagaggaatg cagccctgca aaagcacgtg gagagcatgc gcacagcagt ggagaagctg 420 gaggtggatg tgatccagga gcggagccgc aacacagtct tacagcagca cctggagacc 480 ctgcggcagg tgctgaccag cagctttgcc agcatgccct tgcctggaag tggagagaca 540 cctacagtgg acaccattga ctcatatatg aacagactgc acagtattat tttagctaat 600 ccccaagaca atgaaaactt catagctaca gttcgagaag ttgtgaacag actcgatcgt 660 tagggaatgg tgagtgctca ctgataaata tttatatgcc agcacatcat caaaaataag 720 atgtcatcag actttatcaa tactactaaa accctgggat tacattggat gaacaagttg 780 gagacttggt taagattcct gttgcatggt tgttaaatgt agtaaataat attagaaaag 840 agaatcactg tagtcccagc tacttgggag gctgaggtgg gaggattgct tgagcccagc 900 agttcaagtc cagagagatc ctgtctctaa aaataaaaga aaa 943 <210> 92 <211> 1997 <212> DNA
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2052061CB1 <400> 92 cgaccacgcg tccgctcgcg tggggcgcga ggtaccccgt ggggcagcta ggtgcctcca o0 agaaaccccg ccccagagga cccgcacgag ttgttgccat ttttcgctga agcccctgcc 120 SUBSTITUTE SHEET (RULE 26) ctgggggtgg tgttcttctc tatgattcta ccaatcgtcg gaattttttt cctcccttct 180 ttctttttag gaaggcgctg gggtgtgcgg cggaaacggc ggcggtgaag ggatcctctt 240 gtggtatctc ctccccggag aaatagggga gtgggggccc.aagaacgaga agacgagaac 300 gcgtcgccct gcgctatgtc agaatggggc gggtgtgagg ggaacagctc tcttgcgatc 360 agatcaggag tatgagcctc ccggaggacg gcatgagttc tggacacttc aggagtcctc 420 agctagtgac atggtcgata tggataaact cataaacaac ttggaggtcc aacttaattc 480 agaaggtggc tcaatgcagg tattcaagca ggtcactgct tctgttcgga acagagatcc 540 ccctgagata gaatacacaa gtaatatgac ttctccaaca ctcctggatg ccaaccccat 600 ggagaaccca gcactgttta atgacatcaa gattgagccc ccagaagaac ttttggctag 660 tgatttcagc ctgccccaag tggaaccagt tgacctctcc tttcacaagc ccaaggctcc 720 tctccagcct gctagcatgc tacaagctcc aatacgtccc cccaagccac agtcttctcc 780 ccagaccctt gtggtgtcca cgtcaacatc tgacatgagc acttcagcaa acattcctac 840 tgttctgacc ccaggctctg tcctgacctc ctctcagagc actggtagcc agcagatctt 900 acatgtcatt cacactatcc cctcagtcag tctgccaaat aagatgggtg ggctgaagac 960 catcccagtg gtagtgcagt ctctgcccat ggtgtatact actttgcctg cagatggggg 1020 gcctgcagcc attacagtcc cactcattgg gggagatggt aaaaatgctg gatcagtgaa 1080 agttgacccc acctccatgt ctccactgga aattccaagt gacagtgagg agagtacaat 1140 tgagagtgga tcctcagcct tgcagagtct gcagggacta cagcaagaac cagcagcaat 1200 ggcccaaatg cagggagaag agtcgcttga cttgaagaga agacggattc accaatgtga 1260 ctttgcagga tgcagcaaag tgtacaccaa aagctctcac ctgaaagctc accgcagaat 1320 ccatacagga gagaagcctt ataaatgcac ctgggatggc tgctcctgga aatttgctcg 1380 ctcagatgag ctcactcgcc atttccgcaa gcacacaggc atcaagcctt ttcggtgcac 1440 agactgcaac cgcagctttt ctcgttctga ccacctgtcc ctgcatcgcc gtcgccatga 1500 caccatgtga gccgcacagg tcacactaga gaagctgcgc tggtatcttt cctggtcgtg 1560 tgctgaggtt gggacaattt tttcctcttt gacttcagct tgcatatggg gttgaagcag 1620 cccactgagc caagttgagg agactggagg aaaagagagc tggtctcccg tggggctctt 1680 catattctac ctccacttct ccactgtcca gacccgtttt tttcaacccc cacatgggtt 1740 gacttccagc gtggcaccca tgggtgcctt cccatccccc cctgttctga aatagggaat 1800 ttttccccca gcaacaccac aggaatcaaa ctcaaggctg gcaaccacat ccgctgtttc 1860 ttcctcccac ttccctcttg tctctagaac tcttatccaa tgtcttaaca tcctaccaaa 1920 agggctcgat gcgttccaca gatttttcac ttcttattgc agggatacat tcgtggtcgc 1980 cacataaggg ttgcttc <210> 93 <211> 4334 <212> DNA
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2056207CB1 <400> 93 cggtggtggt ggcgggccgg ggcatgagca ggaggaggat taccgctacg aggtgctcac 60 ggccgagcag attctacaac acatggtgga atgtatccgg gaggtcaacg aggtcatcca 120 gaatccagca actatcacaa gaatactcct tagccacttc aattgggata aagagaagct 180 aatggaaagg tactttgatg gaaacctgga gaagctcttt gctgagtgtc atgtaattaa 240 tccaagtaaa aagtctcgaa cacgccagat gaatacaagg tcatcagcac aggatatgcc 300 ttgtcagatc tgctacttga actaccctaa ctcgtatttc actggccttg aatgtggaca 360 taagttttgt atgcagtgct ggagtgaata tttaactacc aaaataatgg aagaaggcat 420 gggtcagact atttcgtgtc ctgctcatgg ttgtgatatc ttagtggatg acaacacagt 480 tatgcgcctg atcacagatt caaaagttaa attaaagtat cagcatttaa taacaaatag 540 ctttgtagag tgcaatcgac tgttaaagtg gtgtcctgcc ccagattgcc accatgttgt 600 taaagtccaa tatcctgatg ctaaacctgt tcgctgcaaa tgtgggcgcc aattttgctt 660 taactgtgga gaaaattggc atgatcctgt taaatgtaag tggttaaaga aatggattaa ?20 aaagtgtgat gatgacagtg aaacctccaa ttggattgca gccaacacaa aggaatgtcc 780 caaatgccat gtcacaattg agaaggatgg tggttgtaat cacatggtct gtcgtaacca 840 gaattgtaaa gcagagtttt gctgggtgtg tcttggccca tgggaaccac atggatctgc 900 ctggtacaac tgtaaccgct ataatgaaga tgatgcaaag gcagcaagag atgcacagga 960 gcgatctagg gcagccctgc agaggtacct gttctactgt aatcgctata tgaaccacat 1020 gcagagcctg cgctttgagc acaaactata tgctcaggtg aaacagaaaa tggaggagat 1080 gcagcagcac aacatgtcct ggattgaggt gcagttcctg aagaaggcag ttgatgtcct 1140 SUBSTITUTE SHEET (RULE 26) ctgccagtgt cgtgccacac tcatgtacac ttatgtcttc gctttctacc tcaaaaagaa 1200 taaccagtcc attatctttg agaataacca agcagatcta gagaatgcca cagaggtgct 1260 ctcgggctac cttgaacgag atatttccca agattctctg caggatataa agcagaaagt 1320 acaagacaag tacagatact gtgagagtcg acgaagggtt ttgttacagc atgtgcatga 1380 aggctatgaa aaagatctgt gggagtacat tgaggactga gaatggccct gcataaaatg 1440 aactctgaaa actttaccat ctagagtgct catgcaatta aaacaaaaca aacacaaaca 1500 aggaggcact aagcctattc tgacaccact ggtctgtagt accagaattg ttttgttaat 1560 ggaaagttta agtaaattat attgtaataa aaaggtagat aaaccattgt acaacagtat 1620 tctaggccgc caacaaaagt gtgacagaca cactaaaagc cctccaactt taacttgtaa 1680 cgtagcttca ttctcaaagc tgactccttt tttttctttt tccttttcct gagtgtagta 1740 cagttaaaat ttcaaacagc tccttgacac tgcttttcat gttcaaacca gccattttgt 1800 tgtactttgg taaaggacct cttccccttc ctcccctaca catacagata cacccacaca 1860 cagactgact ctctttctct cataccccaa ggtcatgagt gaatgatgct tagttccttg 1920 taaagaaaat cttgggatgg ggaaaggggt aggcagcaag aggattcaac aaacgaaaaa 1980 cataaaaact ttgtatatga cttttaaaac aagaggacaa cacagtattt ttcaaaattg 2040 tatatagcgc atatgcatgg acaaagcaag cgtggcacgt gtttgcataa tgtttaatta 2100 caaaaaaata tttattcttt aaaaatcttc aagattatgt ctatttgctg tgcattttct 2160 ttcagtttgc ttatctttcc cgggttgggg ttgggataaa ggtgtgtcgg tttagcacct 2220 ctggaagacc tatctagagc tctttcactt tcctgaggtt attttgccct ttctggtgtt 2280 ggtatgtctg ttgccggcca tgggcctcat gccttgaatt cctgctcttg atcagggaca 2340 agggaggtca agctctgact aatgccatga cctgattaag gggtacagca gggagttttg 2400 ttgctacagc tcatgaatta acctgtccca acctaatccc cctccatggc atcatgcctc 2460 tacccaagcc tttgtgtgcc catgttatgc acacagctgc aggcattctt aagtcccctg 2520 tcgcatccag tggaagcatt ttaaaatttc ttttactttt tggttttccc ttaattgctg 2580 cttttcagat tttagttatg gctcgtctgc tcaccccttc tctacattag ggtgtcaaag 2640 agaatgtttt gctttaaata taaatagcca ttcatttagt ctcagattgt gaatttaaaa 2700 tggtggatac cgaaattgct tgtgtgtgtt gctgtgggtt tggtttgaag gcaaacaccc 2760 ctagaacatg atattcccat ctagtgcatt taaatagaaa tcactgagtt tgctgctttt 2820 ttattgtcag cagataggag aattaataat gcattttagc tgtgatgtcc atttttatga 2880 aattcctact aagagctatg ttaaaagtaa aggatggtgg tggttgtatt aactatatac 2940 ctgtttaggc cattctggct gtggtatttt tcaataggtc agcatctgta aatctgtcag 3000 ttttat~.cag gagtgcagag tgaactaggc aactagatta agaggtctaa atatgaaata 3060 ccagttgagg ctgaggacct cttcgtcttc ctttagatgt cttttgccta gggagtgttt 3120 accatttgtg aggcagcttt gtctgctctt acactgtaca tcctattact ccattgggaa 3180 gtaggttcac tttcctctgg ccttttgcct aagttaggct ttgctgaatc aaccctactt 3240 ttccttttag aaaaggttgt tacaggagat ttactggcaa ctgttctttt cccatcaaaa 3300 atcagtgaat gtttgctgag tataaatgct gcttccttaa accacttgtc gctttaggat 3360 caactttacc tgtacctttt ctcctttcct cccttgccac ctcaggtgca aatctgaact 3420 cagtgtctgc ttcttccatt ttctcgtctc tctcccctct tcccccatta tccatatgac 3480 attattttac ttcaaatgac agcatcaatc ttaaaaagat atacattaaa actaaggagt 3540 ttttttaaag aaagcctgaa taagttcctt tccctggtaa ctttgaaaag cagtcagagt 3600 tgctatatag atatatgtgg ctcctttaaa atgctttgtg tatgtgtggt gtttaaaaaa 3660 aaaaatctta ccagttaact ttgcagtgtc taggtttgag tgtcataaat ccacgtgttc 3720 ctgttgcaac aaatacccaa aaattgtgtg tgcacttcct aataccagtc ttcacccatg 3780 gaggaacagt gctttttaga gatgctttct atttcaatgt tggcatactg cctgagggta 3840 ttgcagttgt gggtgcattc cctaatttgt atgatcaaga tgaactggcc cttttctact 3900 tccaagcttt taacagatac caccatattt gacagaattc ccagagtgaa ttgcttgtgt 3960 tattagtaga ttcagtgccc ccagctggga taggcaagcc atgacagctt ccctgtttca 4020 cctacagaag tcttatctga gggatctatt cacagtaagc accaaggtct ccatgtcttg 4080 aggtcagttt cattgtcttt tgaaaagtgc atgcttcatt tgaacaattc attcagcagc 4140 agatggactt tcagtgattt aaaataaaat tttgatccaa agctcaggac acaaaccaca 4200 gtggtaaaat tgagtagcat ataatatcag actaaattat ctgtaatttt ccacaaccca 4260 gattgtatgt gttttatgtg tgtttaaata aatatgttag atacacgtgt atacatacac 4320 ccatatacag caga 4334 <210> 94 <211> 1706 <212> DNA
<213> Homo sapiens <220>
<221> misc-feature SUBSTITUTE SHEET (RULE 26) <223> Incyte ID No.: 2101803CB1 <400> 94 ccgcgccccg ccgccaccat gagggccgag ggcctcggcg gcctggagcg cttctgcagc 60 ccgggcaaag gccgggggct gcgggctctg cagcccttcc aggtggggga cttgctgttc 120 tcctgcccgg cctatgccta cgtgctcacg gtcaacgagc ggggcaacca ctgcgagtac 180 tgcttcacca ggaaagaagg attgtccaaa tgtggaagat gcaagcaggc attttactgc 240 aatgtggagt gtcagaaaga agattggccc atgcacaagc tggaatgttc tcccatggtt 300 gtttttgggg aaaactggaa tccctcggag actgtaagac taacagcaag gattctggcc 360 aaacagaaaa tccacccaga gagaacacct tcggaaaaat tgttagctgt gaaggagttt 420 gaatcacatc tggataagtt agacaatgag aagaaggatt tgattcagag tgacatagct 480 gctctccatc acttttactc caagcatctc gaattccctg acaatgatag cctcgtagta 540 ctctttgcac aggttaactg taatggcttc acaattgaag atgaagaact ttctcatttg 600 ggatcagcga tatttcctga tgttgcattg atgaatcata gctgttgccc caatgtcatt 660 gtgacctaca aagggaccct ggcagaagtc agagctgtac aggaaatcaa gccgggagag 720 gaggttttta ccagctatat tgatctcctg tacccaacgg aagatagaaa tgaccggtta 780 agagattctt atttctttac ctgtgagtgc caggagtgta ccaccaagga caaggataag 840 gccaaggtgg aaatccggaa gctcagcgat cccccaaagg cagaagccat ccgagacatg 900 gtcagatatg cacgcaacgt cattgaagag ttccggaggg ccaagcacta taaatcccct 960 agtgagctgc tggagatctg cgagctcagc caggagaaga tgagctctgt gtttgaggac 1020 agtaacgtgt acatgttgca catgatgtac caggccatgg gtgtctgctt gtacatgcag 1080 gactgggaag gagccctgca atatggacag aaaatcatta agccctacag taagcactat 1140 cctttgtact ccctcaacgt ggcctccatg tggttgaagc tagggagact ctacatgggc 1200 ctggaacaca aagccgcagg ggagaaagcc ctgaagaagg ccattgcaat catggaagta 1260 gctcacggca aagatcatcc atatatttct gagatcaaac aggaaattga aagccactga 1320 aactatgcag catttcagtt ttcatttaaa cacttagttc agaaacctta aaggatttga 1380 atatttcaaa ttgcacacgt cactccagca tctctgtaaa ataattggaa tgaaaatact 1440 tcttgcactt aaacactgca catgccgtac tttgaggtta gtctgaatct tgaactttaa 1500 taccaaatta attttgaatg cttttgtttc ctaagagata atggcatggt ttcatatgtt 1560 atactttgga cagacagagt tttaaaaatg gaattatttt ttctttcatg cctcttgtaa 1620 tgttctgaac aaacttgaat gatgaaagta ttaaagagat atcagtaaaa agaacaaaaa 1680 ataaagatcc agaaagaaaa aaaggg 1706 <210> 95 <211> 1602 <212> DNA
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2112362CB1 <400> 95 ccgtggggca gtcgaggatg tcggtgaatt acgcggcggg gctgtcgccg tacgcggaca 60 agggcaagtg cggcctcccg gagatcttcg accccccgga ggagctggag cggaaggtgt 120 gggaactggc gaggctggtc tggcagtctt ccaatgtggt gttccacacg ggtgccggca 180 tcagcactgc ctctggcatc cccgacttca ggggtcccca cggagtctgg accatggagg 240 agcgaggtct ggcccccaag ttcgacacca cctttgagag cgcgcggccc acgcagaccc 300 acatggcgct ggtgcagctg gagcgcgtgg gcctcctccg cttcctggtc agccagaacg 360 tggacgggct ccatgtgcgc tcaggcttcc ccagggacaa actggcagag ctccacggga 420 acatgtttgt ggaagaatgt gccaagtgta agacgcagta cgtccgagac acagtcgtgg 480 gcaccatggg cctgaaggcc acgggccggc tctgcaccgt ggctaaggca agggggctgc 540 gagcctgcag gggagagctg agggacacca tcctagactg ggaggactcc ctgcccgacc 600 gggacctggc actcgccgat gaggccagca ggaacgccga cctgtccatc acgctgggta 660 catcgctgca gatccggccc agcgggaacc tgccgctggc taccaagcgc cggggaggcc 720 gcctggtcat cgtcaacctg cagcccacca agcacgaccg ccatgctgac ctccgcatcc 780 atggctacgt tgacgaggtc atgacccggc tcatgaagca cctggggctg gagatccccg 840 cctgggacgg cccccgtgtg ctggagaggg cgctgccacc cctgccccgc ccgcccaccc 900 ccaagctgga gcccaaggag gaatctccca cccggatcaa cggctctatc cccgccggcc 960 ccaagcagga gccctgcgcc cagcacaacg gctcagagcc cgccagcccc aaacgggagc 1020 ggcccaccag ccctgccccc cacagacccc ccaaaagggt gaaggccaag gcggtcccca 1080 gctgaccagg gtgcttgggg agggtggggc tttttgtaga aactgtggat tctttttctc 1140 SUBSTITUTE SHEET (RULE 26) tcgtggtctc actttgttac ttgtttctgt ccccgggagc ctcagggctc tgagagctgt 1200 gctccaggcc aggggttaca cctgccctcc gtggtccctc cctgggctcc aggggcctct 1260 ggtgcggttc cgggaagaag ccacacccca gaggtgacag ctgagcccct gccacacccc 1320 agcctctgac ttgctgtgtt gtccagaggt gaggctgggc cctccctggt ctccagctta 1380 aacaggagtg aactccctct gtccccaggg cctcccttct gggcccccta cagcccaccc 1440 tacccctcct ccatgggccc tgcaggaggg gagacccacc ttgaagtggg ggatcagtag 1500 aggcttgcac tgcctttggg gctggaggga gacgtgggtc caccaggctt ctggaaaagt 1560 cctcaatgca ataaaaacaa tttctttctt gcaaaaaaaa as 1602 <210> 96 <211> 1951 <212> DNA
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2117346CB1 <400> 96 gaggcgcgcg cgaccggcgg ctctttggcg cggattaggg ggtctcggcg agggagtcat 60 caagctttgg tgtatgtgtt ggccggttct gaagtcttga agaagctctg ctgaggaaga 120 ccaaagcagc actcgttgcc aattagggaa tggaccgttt gggttccttt agcaatgatc 180 cctctgataa gccaccttgc cgaggctgct cctcctacct catggagcct tatatcaagt 240 gtgctgaatg tgggccacct ccttttttcc tctgcttgca gtgtttcact cgaggctttg 300 agtacaagaa acatcaaagc gatcatactt atgaaataat gacttcagat tttcctgtcc 360 ttgatcccag ctggactgct caagaagaaa tggccctttt agaagctgtg atggactgtg 420 gctttggaaa ttggcaggat gtagccaatc aaatgtgcac caagaccaag gaggagtgtg 480 agaagcacta tatgaagcat ttcatcaata accctctgtt tgcatctacc ctgctgaacc 540 tgaaacaagc agaggaagca aaaactgctg acacagccat tccatttcac tctacagatg 600 accctccccg acctaccttt gactccttgc tttctcggga catggccggg tacatgccag 660 ctcgagcaga tttcattgag gaatttgaca attatgcaga atgggacttg agagacattg 720 attttgttga agatgactcg gacattttac atgctctgaa gatggctgtg gtagatatct 780 atcattccag gttaaaggag agacaaagac gaaaaaaaat tataagagac catggattaa 840 tcaaccttag aaagtttcaa ttaatggaac ggcggtatcc caaggaggtc caggacctgt 900 atgaaacaat gaggcgattt gcaagaattg tggggccagt ggaacatgac aaattcattg 960 aaagccatgc attggaattt gaactccgaa gggaaatcaa gaggctccaa gaatacagga 1020 cagcaggcat taccaatttt tgtagtgcca gaacctacga tcacctcaag aagacacggg 1080 aggaagagcg ccttaaacgc actatgctct cagaagttct ccagtatatc caggacagta 1140 gtgcttgcca gcagtggctc cgccggcaag ctgacattga ttccggcctg agtccttcca 1200 ttccaatggc ttcgaattca ggtagacgga gtgcaccacc cttgaacctc actggcctcc 1260 ctggcacaga gaagctgaat gaaaaagaaa aggagctctg tcagatggtg aggttggtcc 1320 ctggagccta tttagaatac aaatctgctc tattgaacga atgtaacaag caaggaggct 1380 taagactggc gcaggcaaga gcactcatca agatagatgt gaacaaaacc cggaaaatct 1440 atgatttcct catcagagaa ggatacatca ctaaaggcta aggctccaag agcttgggat 1500 cagaagtcag aagtttggaa tgtggtgggt caaaggacaa tatgggtggg cattctggag 1560 agttgttttt cagctgaatt ctcatggtga aaacagggga aaggacaaag gaaaccttaa 1620 gttgtattgt ctactttctt ctccatcctg ctttaaaaca ctcctgttgt tggtattatg 1680 ctgcagagtt gtgtgctaca taagctatta ttaaatgtga gtgggcattc attcctaaca 1740 cctcttgtaa ctaaaagacc catagtaccc tcacatcaca gtgcctggga gaaattggac 1800 ctaaacccac agtctgtaaa tcccaggagt tcaagcctag aatccttaat attgtccggg 1860 gaaaggtttt tctgaataaa acacggcttt ggcctttaaa aaaactttgg ggaaacgaat 1920 tttaaaaatt aaaagggaaa agggtttttt a 1951 <210> 97 <211> 854 <212> DNA
<213> Homo sapiens <220>

SUBSTITUTE SHEET (RULE 26) <221> misc-feature <223> Incyte ID No.: 2119917CB1 <400> 97 cccacgcgtc cgcggacggt gggcgcgcgc tatgacggcc agcgcacagc cgcgcgggcg 60 gcggccagga gtcggagtcg gagtcgtggt gaccagctgc aagcatccgc gttgcgtcct 120 cctggggaag aggaaaggct cggttggagc tggcagtttc caactccctg gaggtcatct 180 ggagttcggt gaaacctggg aagaatgtgc tcaaagggaa acctgggaag aagcagctct 240 tcacctgaaa aatgttcact ttgcctcagt tgtgaattct ttcattgaga aggagaatta 300 ccattatgtt actatattaa tgaaaggaga agtggatgtg actcatgatt cagaaccaaa 360 gaatgtagag cctgaaaaaa atgaaagttg ggagtgggtt ccttgggaag aactacctcc 420 cctggaccag cttttctggg gactgcgttg tttaaaagaa caaggctatg atccatttaa 480 agaagatctg aaccatctgg tgggatacaa aggaaatcat ctctaggtgg ccgagaagat 540 ttgattttct ttaaaaagac aagaataagg tctggttagg gaatgaaaaa tgtatacatt 600 tcggaacaac tccattttat ctaaaaaagt tcttgtgatt gccagtttat ttgcagtctc 660 ttaatgtatc ccccactctt tcagccagta cttgagaaaa tttttctgaa atatgtcatt 720 gaattgtatt ccagacacag aatacatgat aaatactgat attatgggta atctgctttc 780 catatttacc tatggatatg tacgtgcaat gtgccataac tagttgagag ggtgggtgag 840 gcagattttc cttt 854 <210> 98 <211> 1581 <212> DNA
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2123456CB1 <400> 98 tccgggaaag tttctttgga ggtccggccc ggagcggcca tgtcccacgg ccccaagcag 60 cccggcgcgg ccgccgtgcc ggcgggcggc aaggctccgg gccagcatgg gggcttcgtg 120 gtgactgtca agcaagagcg cggcgagggt ccacgcgcgg gcgagaaggg gtcccacgag 180 gaggagcccg gttctgcagc cggtgaagaa acgcggctgg cccaagggca agaagcggaa 240 gaagattctg ccgaatgggc ccaaggcacc ggtcacgggc tacgtgcgct tcctgaacga 300 gcggcgcgag cagatccgca cgcgccaccc ggatctgccc tttcccgaga tcaccaagat 360 gctgggcgcc gagtggagca agctgcagcc aacggaaaag cagcggtacc tggatgaggc 420 cgagagagag aagcagcagt acatgaagga gctgcgggcg taccagcagt ctgaagccta 480 taagatgtgc acggagaaga tccaggagaa gaagatcaag aaagaagact cgagctctgg 540 gctcatgaac actctcctga atggacacaa gggtggggac tgcgatggct tctccacctt 600 cgatgttccc atcttcactg aagagttctt ggaccaaaac aaagcgcgtg aggcggagct 660 tcggcgcttg cggaagatga atgtggcctt cgaggagcag aacgcggtac tgcagaggca 720 cacgcagagc atgagcagcg cgcgcgagcg tctggagcag gagctggcgc tggaggagcg 780 gaggacgctg gcgctgcagc agcagctcca ggccgtgcgc caggcgctca ccgccagctt 840 cgcctcactg ccggtgccgg gcacgggcga aacgcccacg ctgggcactc tggacttcta 900 catggcccgg cttcacggag ccatcgagcg cgaccccgcc cagcacgaga agctcatcgt 960 ccgcatcaag gaaatcctgg cccaggtcgc cagcgagcac ctgtgaggag tgggcgggcc 1020 cacgatgcag aggagaagct gtgggcgcgg ccctgccaca ccccaccccg tggacgagag 1080 gctgggggtc caccctttgg ggcctggtcc catcctgcac cttgggggct ccagcccccc 1140 taaaattaaa tttctgcagc atccctttag ctttcaatct ccccagcccc ctgaacccgg 1200 aaaaagcact cgctgcgcga tacacccaga agaacctcac agccgagggt gcccctcctc 1260 ggaggacagc cacgcgctac actggctctc cgggccaccc ccaggacaca gggcagacga 1320 aacccacccc cagcacacgg caggaccccc caaattactc actacggggg gctgtgccat 1380 aggccacaca ggaagctgcc ttgtggggac ttacctgggg tgtcccccgc atgcctgtac 1440 cccagatggg tgggggccgg ctttgcccat cctgctctcc tccagccgag ggaccctggt 1500 gggggtggct ccttctcact gctggatccg gactttttaa ataaaaacaa gtaaaatttg 1560 tgttttaaaa aaaaaaaaaa a 1581 <210> 99 <211> 2150 SUBSTITUTE SHEET (RULE 26) <212> DNA
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2148792CB1 <400> 99 gtctcgatct cctgacctcg ccatccaccc gcctcagcca cccgaagtgt tgggatttca 60 ggggccaaat agttgcatca catgtatcta atccgagagt ctcatgcttc tggtagctcc 120 tcagtgacca gctcctgctc actgccctca gaaagcccaa ccctcaggca atggcggcct 180 tgttcctgtc tgccccaccc caggccgagg tgaccttcga ggacgtggct gtgtacctct 240 cccgggagga atggggccgc ctgggccctg ctcagagggg cctctacagg gacgtgatgc 300 tggagaccta cgggaaccta gtctcactgg gagtaggacc tgcaggcccc aagcctggag 360 tgatctcgca gttggagcga ggggatgagc cctgggtcct ggatgttcag ggcacctctg 420 ggaaagagca cctgagagtc aacagcccag ctcttgggac cagaactgag tacaaggagt 480 tgacttcaca ggagacattt ggtgaggaag atccccaggg atctgagcca gtagaagcct 540 gtgaccacat cagtaagtca gaggggagcc tggaaaagct agtggagcag agaggcccca 600 gggcagtcac actgaccaac ggggagagca gcagggagtc tgggggaaac ctcaggttgc 660 tgtcaagacc tgttcctgat cagagacctc acaaatgtga tatatgtgag caaagttttg 720 aacagagatc atatctcaac aaccataagc gtgtacacag gtcaaaaaaa acaaatacag 780 ttcgtaactc tggggaaatc ttcagtgcaa acttagttgt taaagaagat cagaaaattc 840 ctactgggaa aaaattgcat tattgcagtt actgtgggaa aacattcagg tacagtgcca 900 accttgtcaa gcatcagcgg cttcacactg aagagaagcc ctacaaatgt gatgagtgtg 960 ggaaagcctt cagccagagc tgcgagttca tcaatcaccg aaggatgcac tcaggagaga 1020 ttccctaccg gtgtgacgag tgtgggaaga cattcacccg gaggcccaac ctcatgaagc 1080 accagaggat tcacactggg gagaaaccct acaagtgtgg ggagtgtggg aagcacttta 1140 gcgcctactc ttccctgatt tatcaccaga gaatccacac cggagagaaa ccctataaat 1200 gtaatgactg cgggaaagcc ttcagtgatg gctcaatcct tatccgacat cgtcggactc 1260 acaccggaga gaagccattt gagtgcaagg aatgtggcaa aggctttaca caaagttcta 1320 accttatcca acatcagaga attcacactg gagagaaacc ctataaatgt aatgaatgtg 1380 agaaagcttt cattcaaaaa accaaactcg tggaacatca gagaagccac actggagaga 1440 agccctatga atgcaatgac tgtggcaaag ttttcagcca aagcacacac ctcatccagc 1500 accagagaat ccacacagga gagaagccct acaagtgcag cgagtgtggg aaagccttcc 1560 acaacagttc cagactcatc caccaccaga ggctgcacca cggagagaaa ccctacagat 1620 gcagcgattg caagaaagcc ttcagccaga gcacgtactt gattcagcac cggaggatcc 1680 acaccgggga gaagccctac aagtgcagcg agtgtgggaa ggccttccgg cacagttcca 1740 acatgtgtca gcatcagcgg attcacctcc gggaggactt ctccatgtaa cagtggcgcg 1800 gtgtccgagg gcagagtcca gctgagcact tcctgcatgc gcccccggca cctgactctg 1860 ccctttatgt attatccaca cgatgttttc acagagtgaa aggacgtttc tcattaaaca 1920 aacctctttt cttaaatcaa aaaaaaaaaa agggggggcc gctttagggg tcccaggggt 1980 tcccaacccc taatcctaaa caatgtaata gctgttcccg gtgtaaaatt gttagcggcc 2040 caaaattccc tggcaaatta tcgaaccggg aatccttaaa tgtttaaaac ccccggggtg 2100 gcccccaaaa agggttgact cgaaacttcc acattaaaat tcgggggggg 2150 <210> 100 <211> 691 <212> DNA
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 2751943CB1 <400> 100 cggcgccgga gcgggcgtca tggcgcggct cctctggttg ctccggggcc tgaccctcgg 60 aactgcgcct cggcgggcgg tgcggggcca agcgggcggc ggcgggcccg gcaccgggcc 120 gggactgggg gaggcagggt ctcttgcaac gtgtgagctg cctcttgcca agagtgagtg 180 gcaaaagaaa ctaaccccgg agcagttcta cgtcacaaga gaaaagggaa cggaaccgcc 240 tttcagtggg atctacctga ataacaagga agcaggaatg tatcattgcg tgtgctgcga 300 cagtccactc ttcagttctg agaaaaagta ctgctctggc actgggtggc cttcgttttc 360 cgaggctcat ggtacgtctg gctctgatga aagccacaca gggatcctga gacgtctgga 420 SUBSTITUTE SHEET (RULE 26) tacctcgtta ggatcagctc gcacagaggt tgtctgcaag cagtgtgaag ctcatctagg 480 tcacgtgttt cctgatggac ctgggcccaa tggtcagagg ttttgcatca acagtgtggc 540 tttgaagttc aaaccaagga aacactgacc atcttcaaga gtcccgttcc cttgccaccc 600 cttcacgtgc accctcaatt tccacaattc acttgaatga cttgttttat ttgcaataaa 660 actgggctga atttgcaaaa aaaaaaaaaa a 691 <210> 101 <211> 2101 <212> DNA
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 3128913CB1 <400> 101 gtggcttgca gctcggggtg ggtggctcat ttcctggccg ctcctgggct tcgcggaaag 60 aagagattac tcacactcct tctcaagcac agaaccagtt gtactgagct ttttgctaag 120 ctgtttcagc caagaatggc tgtggaatct ggagtgattt caaccctgat acctcaggat 180 cctccggaac aagaactaat actagtgaaa gtagaagata acttttcctg ggatgagaaa 240 tttaagcaga atgggagtac tcaatcctgc caagaattgt ttcgtcagca attcagaaaa 300 ttttgctacc aggagacacc tgggccccgg gaggctctga gccgactcca ggaactttgc 360 tatcagtggc taatgccaga gttgcacaca aaggagcaga tcttagaact gctggtactg 420 gagcagttcc tgagcattct gcctgaggag ctgcagatct gggttcagca acataatcca 480 gaaagcggcg aggaagctgt gaccctgttg gaggatttag agagggagtt tgatgaccca 540 gggcagcagg tcccagctag tccacaggga ccagcagtgc catggaagga tttaacatgt 600 ctcagagcat cccaagagtc aacagacatc cacctccagc ccttaaagac acagctgaaa 660 tcctggaaac catgcctttc ccctaaaagt gattgtgaga acagtgaaac agcaacaaaa 720 gagggcatct cagaagaaaa atcacaggga ctccctcagg aaccttcatt tcgaggaatt 780 agtgagcatg aaagcaattt agtgtggaag caaggaagtg ctacagggga gaaactaaga 840 tctccttccc aagggggcag ttttagtcaa gtgatcttca caaacaaatc tctaggaaag 900 agagaccttt atgatgaggc tgaaagatgc ttgattctaa ctacagactc tataatgtgt 960 cagaaagttc ctccagaaga gagaccttat agatgtgatg tatgtgggca cagcttcaag 1020 cagcattcct ctctaacaca acatcagaga atccatactg gagaaaagcc ctataaatgt 1080 aaccagtgtg ggaaggcctt tagtttgagg tcctatctta ttattcatca gagaattcat 1140 agtggtgaga aagcatatga atgtagtgaa tgtgggaaag ctttcaatca gagctcagcc 1200 ctcattagac atcggaaaat ccatactggt gagaaagctt gtaaatgtaa tgagtgtggc 1260 aaagcattca gtcaaagttc atatctcatt atacatcaaa gaattcacac tggtgagaaa 1320 ccttatgagt gtaatgaatg tgggaaaacc tttagccaga gctcaaaact cattagacat 1380 cagcgaattc acacaggaga gagaccctat gaatgtaatg aatgtggaaa agctttcagg 1440 cagagctcag agctgattac tcatcagaga atacatagtg gagagaaacc ctatgaatgt 1500 agtgaatgtg gaaaagcttt cagtttgagc tcaaacctta tcagacatca gagaattcat 1560 agtggggagg aaccttatca gtgtaatgaa tgtggcaaaa ctttcaaaag gagctcagcc 1620 cttgttcagc atcagagaat tcattctggg gatgaagctt atatatgtaa tgaatgtggg 1680 aaggctttca ggcacagatc ggtccttatg cgccatcaaa gagtccacac tataaagtaa 1740 tttgtgaata ctgtgaatag tgtaaatact tcagtcagat ttttaagttt gttagtcaaa 1800 agagtttact ttggagcaaa actccataaa ggttataaaa tactaggtct tgagtctagc 1860 ttgctttgtg cagcatttcc cagtgctaat gtaaagtgtc ccttgaaagc ttttcctgtg 1920 actaatcaga acagaataca gaagaatcat tacttccagc tcttctctta ttaggaatac 1980 tcaggaaata cgaaaagtgg gaatgtaaca ttgaaacctc attttgtatg aaagtgtcat 2040 gaatatagca acccaggctc tgtcactgca tctgattgtt agtgtgccag gttatggggg 2100 g 2101 <210> 102 <211> 2196 <212> DNA
<213> Homo sapiens <220>
<221> misc-feature <223> Incyte ID No.: 3282941CB1 SUBSTITUTE SHEET (RULE 26) <400> 102 cctactttct ctagaccaga aaattcccaa aattgtgcac attagaatca cgtgggtagc 60 ccacaaaatt cccagtgcca aattataacc tgcctttcct gtggcccagt ggtttccaac 120 gacattgggc cctcggtctg agaagtgcct ataatactgg cttacatggc cctcaggctg 180 aaccttggac gtggcaggta ttgcaaatat tttccgcggt gcgcgcggat tctggacttg 240 ggcgccaact cgtagtccac gctccccggg gtcagcagag gggcgtcacg ctctcgccac 300 ccacctcgct ttctcacccc gcgcttcccg gcctgggttt ttagtcttcc ttggagcgct 360 ctctggcctc cgcctccgcc agggagcgga aggcggagac agcgagactg gccagggggg 420 aggaaagagg acgcgtgtgg gcaaggggga caacgggatg tccacgggct cggtgagtga 480 tccggaggag atggagcttc gggggctgca gcgggagtac ccggtccccg cctccaagag 540 gccgcccctc cgcggcgtag agcgcagcta cgcctcgccc agtgacaact cgtcggcaga 600 ggaggaggac cccgacggcg aggaggagcg ctgcgctctg ggcacagccg gcagcgcgga 660 aggctgcaag aggaagcggc cccgtgtggc tgggggcggc ggcgcaggtg gtagcgcggg 720 cggtggtggc aagaagcccc tcccggccaa gggctcagcc gcagagtgca agcagtcgca 780 gcggaacgcg gccaacgccc gtgagcgtgc ccggatgcgc gtgctgagca aagccttctc 840 caggctcaag accagcctgc cctgggtgcc ccccgacact aagctctcca agctggacac 900 gctccggctg gcttccagtt acatcgctca cctgcggcag ctgttgcagg aggaccgcta 960 tgagaacggc tacgtgcacc cagtgaacct gacatggcca ttcgtggtct cgggaagacc 1020 ggactctgac accaaagaag tttccgcagc caacagacta tgtggaacca ccgcttaaat 1080 cggactggaa ctcacttgat gggattattc gttaaatgcg agtgtttggg ggccacggag 1140 agaagggaga gctcgtgaga tgggaagaag tttccgctgg attctccttg acccttcccc 1200 tttccctgga actgtgatcg tgacaggtgg cgggtgtggc tgtcactgca cagcgcccac 1260 ggctacagct gcgccggatc tgggcgacca cgttttgcct ctccaaaaag agcttccttt 1320 cgtgacgaga cgcggacgca ggtccaccct cgggccctag ctctgtagac taactctcgg 1380 ctgctgcccc agcccgcgcc agacagccca cggatccgtt ctcagcggac gcagattcat 1440 cgcacacgtg cgggacggtt ccacacagcc ccggcctttc gcggtgacac aatggttagg 1500 gaacggttag aacgcgctct acatccgctt taaagacaga ggtctagacg tgagatccgc 1560 gtcgggacag ggttttaagt gacaaagaag ggcgagtggc ttctctgggc cgggttcgta 1620 ctccagcaca gcgcccttct aacgggcggg aggaaggccg ctgctcgcag ggctaggtgg 1680 agacacactt cccagatcac cgcaggcggg ttttacccgg agagctctgg gccgttcggc 1740 ctccctgccg ggtggcttct tcaatcccgt ctccttccca agctcccggc tttttctaat 1800 caggcaggcg tctgtcaacc ctctccactt ctgggctgaa gcctccccaa gccccgctgc 1860 gccaacctgt gtggggtctt cttcgggcct ccctctccgc cccgctcctg ctcctacctg 1920 cagcaccccc agctccgact ccagactctc tgcatcaggt ctccccactc cacgctccgg 1980 gcgccccaac tccaacacca cgtcctgccg cgcaggttct tccccgcgcg gaggagcgcg 2040 cagggtgggc ggcttaccat agcaagtgat cctgcgatag ggaacgcgcc cttgccccga 2100 ggctgcacta ccacaggaaa taacatatgt aaataaattt atttttttat gaataataaa 2160 acgcgctgta aaaaccgtga aaaaaaaaaa aaaagg 2196 <210> 103 <211> 749 <212> DNA
<213> Homo sapiens <220>
<221> unsure <222> 735, 736, 741 <223> a or g or c or t, unknown, or other <223> Incyte ID No.: 3286656CB1 <400> 103 gctgagctgt gctgcgcggc gcggcgcggc gcggtgcggc acggcacggt gggagtgtct 60 ccggctggct tgcagggaga acaccgactg agacctcaaa ccctggctcc agtgtcatgg 120 aatccgtcac ctttgaggat gtggccgtgg agttcatcca ggagtgggca ttgctggaca 180 gcgcacggag gagcctgtgc aaatacagga tgcttgacca gtgcaggacc ctggcctcca 240 ggggaactcc accatgcaaa cccagttgtg tctcccagct ggggcaaaga gcagagccaa 300 aggcaacaga acgagggatt ctccgtgcca caggtgttgc ctgggaatct caacttaaac 360 ccgaagagtt gccttctatg caggatcttt tggaagaagc atcctccagg gacatgcaaa 420 tggggccggg gctgttcctg aggatgcagc tggtgccctc catagaagag agggagacac 480 cattgactcg agaggaccgg ccagctctcc aggagccgcc ttggtctctg ggatgcacgg 540 gactgaaggc cgctatgcag attcagaggg tggtgatacc agtgcctact ctgggccacc 600 gcaacccatg ggtggccagg gattctgcca tgtagcacgt gcctgcttcc cctttgcctt 660 SUBSTITUTE SHEET (RULE Z6) ccgccatgat tgtaagtttc tcgagtcctc cccagccatg cgtcctgtac aacctgtgga 720 accaggcagc caaanncagt natagttgt 749 <210> 104 <211> 1311 <212> DNA
<213> Homo sapiens <220>
<221> unsure <222> 1294 <223> a or g or c or t, unknown, or other <223> Incyte ID No.: 3490802CB1 <400> 104 gggcctttgt ttctcgctgc agcgggagct ccaggtttat cctctgtgtt ctgtgtcctg 60 tgcttataga ggcccgtcct ctgtggccgt gtgacctgca agtattggga gagccacagc 120 taaaccccgg gacccctgga agcctagaaa tgggaccatt gcaatttaga gatgtggcca 180 tagaattctc tctggaggag tggcattgcc tggacactgc acagcggaat ttatataggg 240 atgtgatgtt agagaactac agaaacttgg tcttccttgg tattgttgtc tctaagccag 300 acctggttac ctgtctggag caaggaaaaa aacctttaac tatggaaaga catgagatga 360 ttgccaaacc cccagttatg agttctcatt ttgcccaaga cctttggcca gagaacatac 420 aaaattcttt ccaaataggg atgctgagaa gatatgaaga atgcagacat gacaatttac 480 agttaaaaaa aggctgtaaa agcgtgggtg agcataaggt gcacaaagga ggttataatg 540 gacttaacca atgtttgaca actacccaga aagaaatatt tcaatgtgat aaatatggaa 600 aagtctttca taagttttca aattcaaaca catataagac aagacatact ggaataaatc 660 ttttcaaatg tataatatgt ggcaaagctt ttaaacggtc ctcaaccctt actacacata 720 agaaaattca tactggagag aaaccttaca aatgtgaaga atgtggcaaa gcttttaacc 780 aatcctcaaa ccttactaca cataagagaa ttcatactgg agagaaacct tacaaatgtg 840 aagaatgtgg caaagctttt aactggtcct cagaccttaa taaacataag aaaattcata 900 ttgaacgaaa accctacata gtgaagaatg tgacagatct tttaaatgtt cctccacttt 960 taattagcat aagataattc atactggaga gaaaccctat gaatgtgatg aatgtgggaa 1020 agcctttaac cagccctcga ctcttagtaa atttgagagt ttatatggaa cacaaaccct 1080 acaaatataa agaatgtgac aaagcttttt aaggaagttc tcaaccctta ttacacataa 1140 ttcataccaa acagaagccc tacaagtgtg aagaatgtgg caaaacctat aaacctataa 1200 caagttctca attccttttt ttttgagatg gagtttcact cttgtcaccg aggcagaggt 1260 tgcagtgagc actccagtct aggcgacaga gtangccttg tcgcgatccc a 1311 <210> 105 <211> 990 <212> DNA
<213> Homo Sapiens <220>
<221>
<223> Incyte ID No.: 3507366CB1 <400> 105 caaaaaggaa agaataaggc aaattcttag aatgtatgca caacttaata tccttgctcg 60 tttgatgtgc attgatctca tttaataggt ttttgaatct gaaaattcaa gaaggtgaag 120 ctcacaacat tttttgccct gcatatgatt gcttccaact tgtacctgtg gatatcatag 180 aaagtgtagt ttcaaaggag atggacaaac gatacctaca gtttgatatt aaggcctttg 240 ttgaaaataa tcctgccatt aaatggtgtc ctactccagg ctgtgacaga gcagtaagac 300 taacgaaaca agggtcaaat acatctggat ctgatacact cagcttccca ttgctgagag 360 ctcctgctgt tgattgtgga aaaggacacc tcttctgctg ggagtgcctt ggtgaagcac 420 atgagccttg tgactgccaa acatggaaga attggctgca aaaaataacc gaaatgaaac 480 cagaagaact tgtgggagtt agtgaagcct acgaggatgc cgccaattgt ctctggttat 540 taactaactc caagccttgt gccaactgta agtctccaat acagaagaat gaaggctgca 600 atcacatgca gtgtgctaag tgcaagtatg acttttgctg gatttgcctt gaagagtgga 660 aaaaacatag ttcgtccact ggaggttatt acagatgtac tcgctatgaa gtcattcaac 720 acgtggagga gcaatccaag gaaatgactg tggaggctga gaaaaaacac aaacgatttc 780 SUBSTITUTE SHEET (RULE 26) aggaacttga cagatttatg cactattata caagatttaa aaaccatgag catagttatc 840 agctagaaca acgccttctt aaaacagcca aagaaaagat ggagcaaatg agcagagtct 900 caaagaactg aaggaggctg tccagatacc actttcattg gagatgagtt catgtgctct 960 aaaaatcggc gcatctcaag tgtcttatca 990 <210> 106 <211> 1048 <212> DNA
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 3573060CB1 <400> 106 ccgctgcagc tctccgcggg acatctcacc gttctggaga cagggctcgc tcgctctcac 60 ggcttcttag gccggggttg gacagccgcc ttccggccag aggggatgag gttgcgctgc 120 gctccgggag cgccgatggc gtgactggcc ccgcgcggag cagcgacact gcccggccag 180 cccgcttctc tgcccggagc catgaatctc agtagcgcca gtagcacgga ggaaaaggca 240 gtgacgaccg tgctctgggg ctgcgagctc agtcaggaga ggcggacttg gaccttcaga 300 ccccagctgg aggggaagca gagctgcagg ctgttgcttc atacgatttg cttgggggag 360 aaagccaaag aggagatgca tcgcgtggag atcctgcccc cagcaaacca ggaggacaag 420 aagatgcagc cggtcaccat tgcctcactc caggcctcag tcctccccat ggtctccatg 480 gtaggagtgc agctttctcc cccagttact ttccagctcc gggctggctc aggacccgtg 540 ttcctcagtg gccaggaacg ttatgaagca tcagacctaa cctgggagga ggaggaggaa 600 gaagaagggg aggaggagga agaggaagag gaagatgatg aggatgagga tgcagatata 660 tctctggagg agcaaagccc tgtcaaacaa gtcaaaaggc tggtgcccca gaagcaggcg 720 agcgtggcta agaaaaaaaa gctggaaaaa gaagaagagg aaataagagc cagcgttaga 780 gacaagagcc ctgtgaaaaa ggccaaagcc acagccagag ccaagaagcc aggattcaag 840 aaatgaggag ccacgccttg gggggcacgg tgcaaagtgg gccttccctg ggctgtgctg 900 caggcacagg gtgcccctgt ccagcccctc cacctgtgtc tgaatgcaac aggggtgttg 960 cgggggcaac atgagagccc ctcaccccca actctccact ttcaggaggc ccccagtgaa 1020 gagccccacc tcgggtcaca ataagtgt 1048 <210> 107 <211> 1349 <212> DNA
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 3573661CB1 <400> 107 gagaaagcag agctatttca agagtgagcc acagaaggga atccagaggc catctaagcg 60 aggaagggtc tacaggcagt gagtgaaggc caggagcagg gcccaggcca ggcacgacca 120 ccgaggggat gaacttcaca gtgggtttca agccgctgct aggggatgca cacagcatgg 180 acaacctgga gaagcagctc atctgcccca tctgcctgga gatgttctcc aaaccagtgg 240 tgatcctgcc ctgccaacac aacctgtgcc gcaaatgtgc caacgacgtc ttccaggcct 300 cgaatcctct atggcagtcc cggggctcca ccactgtgtc ttcaggaggc cgtttccgct 360 gcccatcgtg caggcatgag gttgtcctgg acagacacgg tgtctacggc ctgcagcgaa 420 acgtgctagt ggagaacatt atcgacattt acaagcagga gtcatccaag ccgctgcact 480 cgaaggctga gcagcacctc atgtgcgagg agcatgaaga agagaagatc aatatttact 540 gcctgagctg tgaggtgccc acctgctctc tctgcaaggt cttcggtgcc cacaaggact 600 gtgaggtggc cccactgccc accatttaca aacgccagaa gagtgagctc agcgatggca 660 tcgcgatgct ggtggcaggc aatgaccgcg tgcaagcagt gatcacacag atggaggagg 720 tgtgccagac tatcgaggac aatagccgga ggcagaagca gttgttaaac cagaggtttg 780 agagcctgtg cgcagtgctg gaggagcgca agggtgagct gctgcaggcg ctggcccggg 840 agcaagagga gaagctgcag cgcgtccgcg gcctcatccg tcagtatggc gaccacctgg 900 aggcctcctc taagctggtg gagtctgcca tccagtccat ggaagagcca caaatggcgc 960 SUBSTITUTE SHEET (RULE 26) tgtatctcca gcaggccaag gagctgatca ataaggtcgg ggccatgtcg aaggtggagc 1020 tggcagggcg gccggagcca ggctatgaga gcatggagca attcaccgta agggtggagc 1080 acgtggccga aatgctgcgg accatcgact tccagccagg cgcttccggg ggaggaagag 1140 gaggtggccc cagacggaag aagagggcaa cccgggggcc ggaagaaaaa acggcccgga 1200 tggggcctta taggcctttg cgcccgaacc ccgaccccct gcttcgaaaa agcccccggc 1260 gcttaagaat ttccggggga aggaattctt gccgcaaaaa aaccccggca agcttttaac 1320 cccccaaaat tccggggcgc ccggggccc 1349 <210> 108 <211> 1642 <212> DNA
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 3633422CB1 <400> 108 ctagttctag atcgcgagcg cccgcccagg cacccaccag cggcgccgac ctcagcgcgc 60 acctatgggc tcgctaccag gacatgcgga gactggtgca cgacctcctg ccccccgagg 120 tctgcagtct cctgaaccca gcagccatct acgccaacaa cgagatcagc ctgcgtgacg 180 ttgaggtcta cggctttgac tacgactaca ccctggccca gtatgcagac gcactgcacc 240 ccgagatctt cagtaccgcc cgtgacatcc tgatcgagca ctacaagtac ccagaaggga 300 ttcggaagta tgactacaac cccagctttg ccatccgtgg cctccactat gacattcaga 360 agagccttct gatgaagatt gacgccttcc actacgtgca gctggggaca gcctacaggg 420 gcctccagcc tgtgccagac gaggaggtga ttgagctgta tgggggtacc cagcacatcc 480 cactatacca gatgagtggc ttctatggca agggtccctc cattaagcag ttcatggaca 540 tcttctcgct accggagatg gctctgctgt cctgtgtggt ggactacttt ctgggccaca 600 gcctggagtt tgaccaagca catctctaca aggacgtgac ggacgccatc cgagacgtgc 660 atgtgaaggg cctcatgtac cagtggatcg agcaggacat ggagaagtac atcctgagag 720 gggatgagac gtttgctgtc ctgagccgcc tggtggccca tgggaaacag ctgttcctca 780 tcaccaacag tcctttcagc ttcgtagaca aggggatgcg gcacatggtg ggtcccgatt 840 ggcgccagct cttcgatgtg gtcattgtcc aggcagacaa gcccagcttc ttcactgacc 900 ggcgcaagcc tttcagaaaa ctcgatgaga agggctcact tcagtgggac cggatcaccc 960 gcttggaaaa gggcaagatc tatcggcagg gaaacctgtt tgacttctta cgcttgacgg 1020 aatggcgtgg cccccgcgtg ctctacttcg gggaccacct ctatagtgat ctggcggatc 1080 tcatgctgcg gcacggctgg cgcacaggcg ccatcatccc cgagctggag cgtgagatcc 1140 gcatcatcaa cacggagcag tacatgcact cgctgacgtg gcagcaggcg ctcacggggc 1200 tgctggagcg catgcagacc tatcaggacg cggagtcgag gcaggtgctg gctgcctgga 1260 tgaaagagcg gcaggagctg aggtgcatca ccaaggccct gttcaatgcg cagttcggca 1320 gcatcttccg caccttccac aaccccacct acttctcaag gcgcctcgtg cgcttctctg 1380 acctctacat ggcctccctc agctgcctgc tcaactaccg cgtggacttc accttctacc 1440 cacgccgtac gccgctgcag cacgaggcac ccctctggat ggaccagctc tgcaccggct 1500 gcatgaagac ccccttcctt ggtgacatgg cccacatccg ctgagggcac ctttattgtc 1560 tgggacaggc cctcagcccc tcctgcccca tccacccaga caagcaataa aagtggtctc 1620 ctccctgaaa aaaaaaaaaa as <210> 109 <211> 1818 <212> DNA
<213> Homo Sapiens <220>
<221> misc-feature <223> Incyte ID No.: 3993377CB1 <400> 109 gaagactctc tggagccctt caactctctg gcaccagagc cagtgagtgg aggactatat 60 ggtattgatg acacggagct gatgggtgca gaggacaagc tgcctcttga ggacagccct 120 gtgattgctg cccttgattg cccttccctc aataatgcta ctgccttcag tctcctggca 180 gatgatagtc aaacatcaac ctctatcttt gccagtccca cctctccacc tgtcctaggg 240 SUBSTITUTE SHEET (RULE 26) gagtctgtcc tgcaagataa cagctttgac ctgaataatg gtagtgacgc tgaacaggaa 300 gaaatggaaa ctcaatcttc agacttccca ccatccctga cccagccagc tcctgatcag 360 tcatccacta ttcagctaca tccagcaacc tcaccagcag tctcgccaac aacctcccca 420 gcagtctccc tagtggtttc tccagcagcc tccccagaaa tctctccaga agtttgtccc 480 gcagcttcta cagttgtctc tccagcagtc ttctcagtgg tctctccagc ttcctcagca 540 gtcctcccag cagtctcctt agaagtcccg ttgacggctt cagtgacatc cccaaaagcc 600 tctcccgtaa cttccccagc agctgccttt ccaacagcct ccccagcaaa taaggatgtc 660 agcagctttc tagaaaccac tgctgacgtg gaagagatca ctggagaagg actcactgct 720 tctggtagtg gtgatgtcat gaggagacgt attgctaccc cagaagaagt tcgtcttccc 780 ctccaacatg ggtggcggag agaggtgcgc atcaagaaca gcagccaccg atggcagggg 840 gagacctggt attatggccc ctgtgggaag aggatgaagc aatttccaga agtgatcaag 900 tacctgagcc gcaacgtggt acacagtgtc cgccgagagc acttcagctt cagtccccgt 960 atgcctgttg gagatttctt tgaagaaaga gacacgccag agggcttgca gtgggtgcag 1020 ctctcagcag aggagatccc gtcgaggatt caggcaatta ctggcaaacg gggtcgacct 1080 cgaaacactg agaaggctaa gactaaggaa gtccccaagg tgaaacgggg tcgaggtcgg 1140 ccacctaagg tcaaaatcac tgagctattg aacaagacag acaaccgccc cctaaagaaa 1200 ctggaggccc aagaaacatt gaatgaggag gataaagcaa agattgctaa aagcaagaag 1260 aagatgaggc agaaggttca acggggagag tgtcagacta ctatccaagg gcaggccaga 1320 aataagcgga aacaagagac caagagctta aagcagaagg aagctaagaa gaaatccaag 1380 gctgagaaag aaaaaggaaa gacaaagcag gaaaaactga aggaaaaagt caagagggaa 1440 aagaaggaga aggtaaaaat gaaggaaaag gaggaggtga ccaaagccaa gccagcctgt 1500 aaagcagata agaccctggc cacacagagg cgcttggagg aacggcagag gcagcagatg 1560 atcttggagg acatgaagaa gccgacagag gatatgtgtc tgactgacca ccagcccctg 1620 cctgacttct cacgagtccc tggtctgaca ttgcccagtg gagccttctc agactgcttg 1680 accattgtgg agttcctgca tagctttggc aaggtgctgg gccttgatcc tgcccaaggt 1740 tgtgcctagc ctggggggtc ctgcaggaag gggctcctgt gttcaaggtg accactctgg 1800 gtgaaggtgc aaaacccg <210> 110 <211> 785 <212> DNA
<213> Homo Sapiens <220>
<221> unsure <222> 738 <223> a or g or c or t, unknown, or other <223> Incyte ID No.: 4717936CB1 <400> 110 gtctctgtag tcatgaggct gaagggggtg gggacagtgt tgataaaagg cactagaggc 60 agctcccaca cccttcctcg gaactgttgc ccacatgcag ccccggacac agcccctagc 120 ccaaacccta cccttcttcc tcggaggggc ccctcgagac actgggctgc gggtgcctgt 180 cattaagatg ggcacagggt gggagggctt ccagcggacc ctgaaggaag tcgcctacat 240 cctcctctgc tgctggtgta tcaaggaact gctggattaa tggtagcagg gaactgcctc 300 ctctccccac cagcaccatg gctggcatcg ctcaggtggg cagggtagag taaacaggag 360 gcatagctgc agcttctgtg gcagagcttg ccttagcttc tcattctctt ctttagcccc 420 cagcccaatt gccatcaaga ctcctgaagc cagctgtgct tgaccaagga tgggccataa 480 acaatgagta aacagtaaag tgtggatcct gctttgagct gtgtcatcta gcagacctgc 540 ctcatctctg agcctccttc attcccaacc cctgcctctg gtggacctct ggtgggcagg 600 agcttggact gctctggcta ggaccccagt aagattgtgg caagacctgg cactcctcca 660 agcttggcac agtgagccca ccagctcaga tggttgatct taccataccc tcatagtacc 720 aagaatggac tgcccccnta agaaacctgt ttgagaatca ctgaattata aatataaacc 780 cagat SUBSTITUTE SHEET (RULE 26)

Claims (23)

What is claimed is:

1. An isolated polypeptide comprising:
a) an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID
NO:3-5, SEQ ID NO:7-14, SEQ ID NO:16-31, SEQ ID NO:33-34, SEQ ID NO:36-40,SEQ
ID
NO:42-48, SEQ ID NO:50-55.
b) a naturally occurring amino acid sequence having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID
NO:3-S, SEQ ID
NO:7-14, SEQ ID NO:16-31, SEQ ID NO:33-34, SEQ ID NO:36-40,SEQ ID NO:42-48, SEQ ID
NO:50-55, c) a biologically active fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3-5, SEQ ID NO:7-14, SEQ ID NO:16-31, SEQ
ID NO:33-34, SEQ ID NO:36-40,SEQ ID NO:42-48, SEQ ID NO:50-55, or d) an immunogenic fragment of an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3-5, SEQ ID NO:7-14, SEQ ID NO:16-31, SEQ ID NO:33-34, SEQ ID
NO:36-40,SEQ ID NO:42-48, SEQ ID NO:50-55.

2. An isolated polypeptide of claim 1, having an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3-5, SEQ ID NO:7-14, SEQ ID NO:16-31, SEQ ID
NO:33-34, SEQ ID NO:36-40,SEQ ID NO:42-48, SEQ ID NO:50-55.

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

4. An isolated polynucleotide of claim 3, having a sequence selected from the group consisting of SEQ ID NO:56-110.

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

6. A cell transformed with a recombinant polynucleotide of claim 5.

7. A transgenic organism comprising a polynucleotide of claim 5.

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

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

10. An isolated polynucleotide comprising:
a) a polynucleotide sequence selected from the group consisting of SEQ ID
NO:56-110, b) a naturally occurring polynucleotide sequence having at least 90% sequence identity to a polynucleotide sequence selected from the group consisting of SEQ ID NO:56-110, c) a polynucleotide sequence complementary to a), or d) a polynucleotide sequence complementary to b).

11. An isolated polynucleotide comprising at least 60 contiguous nucleotides of a polynucleotide of claim 10.

12. A method for detecting a target polynucleotide in a sample, said target polynucleotide having a sequence of a polynucleotide of claim 10, the method comprising:
a) hybridizing the sample with a probe comprising at least 16 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, and b) detecting the presence or absence of said hybridization complex, and, optionally, if present, the amount thereof.

13. A method of claim 12, wherein the probe comprises at least 30 contiguous nucleotides.

14. A method of claim 12, wherein the probe comprises at least 60 contiguous nucleotides.

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

16. A method of treating a disease or condition associated with decreased expression of functional NuABP, comprising administering to a patient in need of such treatment the pharmaceutical composition of claim 15.

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

18. A pharmaceutical composition comprising an agonist compound identified by a method of claim 17 and a pharmaceutically acceptable excipient.

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

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

21. A pharmaceutical composition comprising an antagonist compound identified by a method of claim 20 and a pharmaceutically acceptable excipient.

22. A method for treating a disease or condition associated with overexpression of functional NuABP, comprising administering to a patient in need of such treatment a pharmaceutical composition of claim 21.

23. A method for screening a compound for effectiveness in altering expression of a target polynucleotide, wherein said target polynucleotide comprises a sequence of claim 4, the method comprising:
a) exposing a sample comprising the target polynucleotide to a compound, and b) detecting altered expression of the target polynucleotide.