CA2469941A1 - Novel nucleic acids and polypeptides - Google Patents

Abstract

The present invention provides novel nucleic acids, novel polypeptide sequences encoded by these nucleic acids and uses thereof.

Description

DEMANDE OU BREVET VOLUMINEUX
LA PRESENTE PARTIE DE CETTE DEMANDE OU CE BREVET COMPREND
PLUS D'UN TOME.

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NOVEL NUCLEIC ACIDS AND POLYPEPTIDES
1. CROSS REFERENCE TO RELATED APPLICATIONS
This application is a continuation-in-part application of U.S. Provisional Application S Serial No. 60/339,739 filed December 10, 2001 entitled "Novel Nucleic Acids and Secreted Polypeptides", Attorney Docket No. 811; U.S. Application Serial No. 10/128,558 filed April 22, 2002 entitled "Novel Nucleic Acids and Polypeptides", Attorney Docket No.
812A, which in turn claims the benefit of U.S. Provisional Application Serial No.
60/339,453 filed December 11, 2001 entitled "Novel Nucleic Acids and Polypeptides", Attorney Docket No.
812; U.S. Provisional Application Serial No. 60/365,384 filed March 14, 2002 entitled "Novel Nucleic Acids and Secreted Polypeptides", Attorney Doclcet No. 814;
U.S.
Provisional Application Serial No. 60/365,091 filed March 14, 2002 entitled "Novel Nucleic Acids and Polypeptides", Attorney Docket No. 815; U.S. Provisional Application Serial No.
60/372,615 filed April 12, 2002 entitled "Novel Nucleic Acids and Secreted Polypeptides", Attorney Docket No. 817; U.S. Provisional Application Serial No. 60/376,045 filed April 24, 2002 entitled "Novel Nucleic Acids and Secreted Polypeptides", Attorney Doclcet No.
817CIP; U.S. Provisional Application Serial No. 60/372,381 filed April 12, 2002 entitled "Novel Nucleic Acids and Polypeptides", Attorney Docket No. 818; PCT
Application Serial No. PCT/US00/35017 filed December 22, 2000 entitled "Novel Contigs Obtained from Various T~ibraries", Attorney Docket No. 784CIP3A/PCT, which in turn is a continuation-in-part application of U.S. Application Serial No. 09/552,317 filed April 25, 2000 entitled "Novel Contigs Obtained from Various Libraries", Attorney Docket No. 784CIP, which in turn is a continuation-in-part application of U.S. Application Serial No.
09/488,725 filed January 21, 2000 entitled "Novel Contigs Obtained from Various Libraries", Attorney Docket No. 784; PCT Application Serial No. PCT/LTSO1/02623 filed January 25, entitled "Novel Contigs Obtained from Various Libraries", Attorney Docket No.
785CIP3/PCT, which in turn is a continuation-in-part application of U.S.
Application Serial No. 09/491,404 filed January 25, 2000 entitled "Novel Contigs Obtained from Various.
Libraries", Attorney Docket No. 785; PCT Application Serial No.
PCT/LTSO1/03800 filed February 5, 2001 entitled "Novel Contigs Obtained from Various Libraries", Attorney Docket No. 787CIP3lPCT, which in turn is a continuation-in-part application of U.S.
Application Serial No. 09/560,875 filed April 27, 2000 entitled "Novel Contigs Obtained from Various Libraries", Attorney Docket No. 787CIP, which in turn is a continuation-in-part application of U.S. Application Serial No. 09/496,914 filed February 03, 2000 entitled "Novel Contigs Obtained from Various Libraries", Attorney Docket No. 787; PCT
Application Serial No. PCT/LTSOl/04927 filed February 26, 2001 entitled "Novel Contigs Obtained from Various Libraries", Attorney Docket No. 788CIP3/PCT, which in turn is a continuation-in-part application of U.S. Application Serial No. 09/577,409 filed May 18, 2000 entitled "Novel Contigs Obtained from Various Libraries", Attorney Docket No.
788CIP, which in turn is a continuation-in-part application of U.S.
Application Serial No.
09/515,126 filed February 28, 2000 entitled "Novel Contigs Obtained from Various Libraries", Attorney Docket No. 788; PCT Application Serial No.
PCT/LTSO1/04941 filed March 5, 2001 entitled "Novel Contigs Obtained from Various Libraries", Attorney Doclcet No. 789CIP3/PCT, which in turn is a continuation-in-part application of U.S.
Application Serial No. 09/574,454 filed May 19, 2000 entitled "Novel Contigs Obtained from Various Libraries", Attorney Docket No. 789CIP, which in turn is a continuation-in-part application of U.S. Application Serial No. 09/519,705 filed March 07, 2000 entitled "Novel Contigs Obtained from Various Libraries", Attorney Docket No. 789; PCT Application Serial No.
PCT/LJSO1/08631 filed March 30, 2001 entitled "Novel Contigs Obtained from Various Libraries", Attorney Docket No. 790CIP3/PCT, which in turn is a continuation-in-part application of U.S. Application Serial No. 09/649,167 filed August 23, 2000 entitled "Novel Contigs Obtained from Various Libraries", Attorney Docket No. 790CIP, which in turn is a continuation-in-part application of U.S. Application Serial No. 09/540,217 filed March 31, 2000 entitled "Novel Contigs Obtained from Various Libraries", Attorney Docket No. 790;
PCT Application Serial No. PCT/LJSO1/08656 filed April 18, 2001 entitled "Novel Contigs Obtained from Various Libraries", Attorney Docket No. 791 CIP3/PCT, which in turn is a continuation-in-part application of U. S. Application Serial No. 09/770,160 filed January 26, 2001 entitled "Novel Contigs Obtained from Various Libraries", Attorney Docket No.
791 CIP, which is in turn a continuation-in-part application of U.S.
Application Serial No.
09/552,929 filed April 18, 2000 entitled "Novel Contigs Obtained from Various Libraries", Attorney Docket No. 791; and PCT Application Serial No. PCT/IJSO1/14827 filed May 16, 2001 entitled "Novel Contigs Obtained from Various Libraries", Attorney Docket No.
792CIP3/PCT, which in turn is a continuation-in-part application of U.S.
Application Serial No. 09/577,408 filed May 18, 2000 entitled "Novel Contigs Obtained from Various Libraries", Attorney Docket No. 792; all of which are incorporated herein by reference in their entirety, specifically including, but not limited to , incorporation by reference of the tables in each application displaying sequence information, ematrix signatures, pfam signatures, signal peptide information, transmembrane domain information, chromosomal localization and tissue distribution information, and/or 3-dimensional structural information.
2. BACKGROUND OF THE INVENTION
2.1 TECHNICAL FIELD
The present invention provides novel polynucleotides and proteins encoded by such polynucleotides, along with uses for these polynucleotides and proteins, for example in therapeutic, diagnostic and research methods.
2.2 BACKGROUND
Technology aimed at the discovery of protein factors (including e.g., cytokines, such as lymphokines, interferons, circulating soluble factors, chernokines, and interleukins) has matured rapidly over the past decade. The now routine hybridization cloning and expression cloning techniques clone novel polynucleotides "directly" in the sense that they rely on information directly related to the discovered protein (i.e., partial DNA/amino acid sequence of the protein in the case of hybridization cloning; activity of the protein in the case of expression cloning). More recent "indirect" cloning techniques such as signal sequence cloning, which isolates DNA sequences based on the presence of a now well-recognized secretory leader sequence motif, as well as various PCR-based or low stringency hybridization-based cloning techniques, have advanced the state of the art by making available large numbers of DNA/amino acid sequences for proteins that are known to have biological activity, for example, by virtue of their secreted nature in the case of leader sequence cloning, by virtue of their cell or tissue source in the case of PCR-based techniques, or by virtue of structural similarity to other genes of known biological activity.
Identified polynucleotide and polypeptide sequences have numerous applications in, for example, diagnostics, forensics, gene mapping; identification of mutations responsible for genetic disorders or other traits, to assess biodiversity, and to produce many other types of data and products dependent on DNA and amino acid sequences.

3. SUMMARY OF THE INVENTION
The compositions of the present invention include novel isolated polypeptides, novel isolated polynucleotides encoding such polypeptides, including recombinant DNA
molecules, cloned genes or degenerate variants thereof, especially naturally occurnng variants such as allelic variants, antisense polynucleotide molecules, and antibodies that specifically recognize one or more epitopes present on such polypeptides, as well as hybridomas producing such antibodies.
The compositions of the present invention additionally include vectors, including expression vectors, containing the polynucleotides of the invention, cells genetically engineered to contain such polynucleotides and cells genetically engineered to express such polynucleotides.
The present invention relates to a collection or library of at least one novel nucleic acid sequence assembled from expressed sequence tags (ESTs) isolated mainly by sequencing by hybridization (SBIT), and in some cases, sequences obtained from one or more public databases. The invention relates also to the proteins encoded by such polynucleotides, along with therapeutic, diagnostic and research utilities for these polynucleotides and proteins. These nucleic acid sequences are designated as SEQ ID NO: 1-911, or 1823-2478 and are provided in the Sequence Listing. In the nucleic acids provided in the Sequence Listing, A
is adenine; C is cytosine; G is guanine; T is thymine; and N is any of the four bases or unknown. In the amino acids provided in the Sequence Listing, * corresponds to the, stop codon.
The nucleic acid sequences of the present invention also include, nucleic acid sequences that hybridize to the complement of SEQ ID NO: 1-911, or 1823-2478 under stringent hybridization conditions; nucleic acid sequences which are allelic variants or species homologues of any of the nucleic acid sequences recited above, or nucleic acid sequences that encode a peptide comprising a specific domain or truncation of the peptides encoded by SEQ
ID NO: 1-91 l, or 1823-2478. A polynucleotide comprising a nucleotide sequence having at least 90% identity to an identifying sequence of SEQ ID NO: 1-911, or 1823-2478 or a degenerate variant or fragment thereof. The identifying sequence can be 100 base pairs in length.
The nucleic acid sequences of the present invention also include the sequence information from the nucleic acid sequences of SEQ ID NO: 1-911, or 1823-2478.
The sequence information can be a segment of any one of SEQ ID NO: 1-911, or 1823-2478 that uniquely identifies or represents the sequence information of SEQ ID NO: 1-91 l, or 1823-2478.
A collection as used in this application can be a collection of only one polynucleotide.
The collection of sequence information or identifying information of each sequence can be provided on a nucleic acid array. In one embodiment, segments of sequence information are provided on a nucleic acid array to detect the polynucleotide that contains the segment. The array can be designed to detect full-match or mismatch to the polynucleotide that contains the segment. The collection can also be provided in a computer-readable format.
This invention also includes the reverse or direct complement of any of the nucleic acid 5 sequences recited above; cloning or expression vectors containing the nucleic acid sequences;
and host cells or organisms transformed with these expression vectors. Nucleic acid sequences (or their reverse or direct complements) according to the invention have numerous applications in a variety of techniques known to those skilled in the art of molecular biology, such as use as hybridization probes, use as primers for PCR, use in an array, use in computer-readable media, use in sequencing full-length genes, use for chromosome and gene mapping, use in the recombinant production of protein, and use in the generation of anti-sense DNA
or RNA, their chemical analogs and the like.
In a preferred embodiment, the nucleic acid sequences of SEQ ID NO: 1-911, or 2478 or novel segments or parts of the nucleic acids of the invention are used as primers in expression assays that are well known in the art. In a particularly preferred embodiment, the nucleic acid sequences of SEQ ID NO: 1-911, or 1823-2478 or novel segments or parts of the nucleic acids provided herein are used in diagnostics for identifying expressed genes or, as well known in the art and exemplified by Vollrath et al., Science 258:52-59 (1992), as expressed sequence tags for physical mapping of the human genome.
The isolated polynucleotides of the invention include, but are not limited to, a polynucleotide comprising any one of the nucleotide sequences set forth in SEQ
ID NO: 1-911, or 1823-2478; a polynucleotide comprising any of the full length protein coding sequences of SEQ ID NO: 1-911, or 1823-2478; and a polynucleotide comprising any of the nucleotide sequences of the mature protein coding sequences of SEQ ID NO: 1-911, or 1823-2478. The polynucleotides of the present invention also include, but are not limited to, a polynucleotide that hybridizes under stringent hybridization conditions to (a) the complement of any one of the nucleotide sequences set forth in SEQ ID NO: 1-911, or 1823-2478; (b) a nucleotide sequence encoding any one of the amino acid sequences set forth in SEQ ID NO: 1-911, or 1823-2478;
(c) a polynucleotide which is an allelic variant of any polynucleotides recited above; (d) a polynucleotide which encodes a species homologue (e.g. orthologs) of any of the proteins recited above; or (e) a polynucleotide that encodes a polypeptide comprising a specific domain or truncation of any of the polypeptides comprising an amino acid sequence set forth in SEQ D7 NO: 912-1822, or 2479-3134, or Tables 3A, 3B, 5, or 6.

The isolated polypeptides of the invention include, but are not limited to, a polypeptide comprising any of the amino acid sequences set forth in the Sequence Listing;
or the corresponding full length or mature protein. Polypeptides of the invention (SEQ ID NO: 912-1822, or 2479-3134) also include polypeptides with biological activity that are encoded by (a) any of the polynucleotides having a nucleotide sequence set forth in SEQ ID
NO: 1-911, or 1823-2478; or (b) polynucleotides that hybridize to the complement of the polynucleotides of (a) under stringent hybridization conditions. Biologically active variants of any of the polypeptide sequences in the Sequence Listing, and "substantial equivalents"
thereof (e.g., with at least about 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% amino acid sequence identity) that preferably retain biological activity are also contemplated.
The polypeptides of the invention may be wholly or partially chemically synthesized but are preferably produced by recombinant means using the genetically engineered cells (e.g. host cells) of the invention.
The invention also provides compositions comprising a polypeptide of the invention.
Polypeptide compositions of the invention may further comprise an acceptable carrier, such as a hydrophilic, e.g., pharmaceutically acceptable, carrier.
The invention also provides host cells transformed or transfected with a polynucleotide of the invention.
The invention also relates to methods for producing a polypeptide of the invention comprising growing a culture of the host cells of the invention in a suitable culture medium under conditions permitting expression of the desired polypeptide, and purifying the polypeptide from the culture or from the host cells. Preferred embodiments include those in which the protein produced by such processes is a mature form of the protein.
Polynucleotides according to the invention have numerous applications in a variety of techniques known to those skilled in the art of molecular biology. These techniques include use as hybridization probes, use as oligomers, or primers, for PCR, use for chromosome and gene mapping, use in the recombinant production of protein, and use in generation of anti-sense DNA or RNA, their chemical analogs and the like. For example, when the expression of an mRNA is largely restricted to a particular cell or tissue type, polynucleotides of the invention can be used as hybridization probes to detect the presence of the particular cell or tissue mRNA in a sample using, e.g., in situ hybridization.
In other exemplary embodiments, the polynucleotides are used in diagnostics as expressed sequence tags for identifying expressed genes or, as well known in the art and exemplified by Vollrath et al., Science 258:52-59 (1992), as expressed sequence tags for physical mapping of the human genome.
The polypeptides according to the invention can be used in a variety of conventional procedures and methods that are currently applied to other proteins. For example, a polypeptide of the invention can be used to generate an antibody that specifically binds the polypeptide. Such antibodies, particularly monoclonal antibodies, are useful for detecting or quantitating the polypeptide in tissue. The polypeptides of the invention can also be used as molecular weight markers, and as a food supplement.
Methods are also provided for preventing, treating, or ameliorating a medical condition which comprises the step of administering to a mammalian subject a therapeutically effective amount of a composition comprising a polypeptide of the present invention and a pharmaceutically acceptable carrier.
In particular, the polypeptides and polynucleotides of the invention can be utilized, for example, in methods for the prevention and/or treatment of disorders involving aberrant protein expression or biological activity.
The present invention further relates to methods for detecting the presence of the polynucleotides or polypeptides of the invention in a sample. Such methods can, for example, be utilized as part of prognostic and diagnostic evaluation of disorders as recited herein and for the identification of subjects exhibiting a predisposition to such conditions.
The invention provides a method for detecting the polynucleotides of the invention in a sample, comprising contacting the sample with a compound that binds to and forms a complex with the polynucleotide of interest for a period sufficient to form the complex and under conditions sufficient to form a complex and detecting the complex such that if a complex is detected, the polynucleotide of interest is detected. The invention also provides a method for detecting the polypeptides of the invention in a sample comprising contacting the sample with a compound that binds to and forms a complex with the polypeptide under conditions and for a period sufficient to form the complex and detecting the formation of the complex such that if a complex is formed, the polypeptide is detected.
The invention also provides kits comprising polynucleotide probes and/or monoclonal antibodies, and optionally quantitative standards, for carrying out methods of the invention. Furthermore, the invention provides methods for evaluating the efficacy of drugs, and monitoring the progress of patients, involved in clinical trials for the treatment of disorders as recited above.

The invention also provides methods for the identification of compounds that modulate (i.e., increase or decrease) the expression or activity of the polynucleotides and/or polypeptides of the invention. Such methods can be utilized, for example, for the identification of compounds that can ameliorate symptoms of disorders as recited herein.
Such methods can include, but are not limited to, assays for identifying compounds and other substances that interact with (e.g., bind to) the polypeptides of the invention. The invention provides a method for identifying a compound that binds to the polypeptides of the invention comprising contacting the compound with a polypeptide of the invention in a cell for a time sufficient to form a polypeptide/compound complex, wherein the complex drives expression of a reporter gene sequence in the cell; and detecting the complex by detecting the reporter gene sequence expression such that if expression of the reporter gene is detected the compound that binds to a polypeptide of the invention is identified.
The methods of the invention also provide methods for treatment which involve the administration of the polynucleotides or polypeptides of the invention to individuals exhibiting symptoms or tendencies. In addition, the invention encompasses.
methods for treating diseases or disorders as recited herein comprising administering compounds and other substances that modulate the overall activity of the target gene products. Compounds and other substances can affect such modulation either on the level of target gene/protein expression or target protein activity.
The polypeptides of the present invention (e.g. SEQ ID NO: 912-1822, or 2479-3134) and the polynucleotides encoding them (e.g. SEQ ID NO: 1-91 l, or 1823-2478) are also useful for the same functions known to one of skill in the art as the polypeptides and polynucleotides to which they have homology (set forth in Tables 2A and 2B);
for which they have a signature region (as set forth in Tables 3A and 3B); or for which they have homology to a gene family (as set forth in Tables 4A and 4B). If no homology is set forth for a sequence, then the polypeptides and polynucleotides of the present invention are useful for a variety of applications, as described herein, including use in arrays for detection.
4. DETAILED DESCRTPTION OF THE INVENTION
4.1 DEFINITIONS
It must be noted that as used herein and in the appended claims, the singular forms "a", "an" and "the" include plural references unless the context clearly dictates otherwise.

The term "active" refers to those forms of the polypeptide which retain the biologic and/or immunologic activities of any naturally occurring polypeptide.
According to the invention, the terms "biologically active" or "biological activity" refer to a protein or peptide having structural, regulatory or biochemical functions of a naturally occurring molecule.
Likewise "immunologically active" or "immunological activity" refers to the capability of the natural, recombinant or synthetic polypeptide to induce a specific immune response in appropriate animals or cells and to bind with specific antibodies.
The term "activated cells" as used in this application are those cells which are engaged in extracellular or intracellular membrane trafEcking, including the export of secretory or enzymatic molecules as part of a normal or disease process.
The terms "complementary" or "complementarity" refer to the natural binding of polynucleotides by base pairing. For example, the sequence 5'-AGT-3' binds to the complementary sequence 3'-TCA-5'. Complementarity between two single-stranded molecules may be "partial" such that only certain portions) of the nucleic acids bind or it may be "complete" such that total complementarity exists between the single stranded molecules. The degree of complementarity between the nucleic acid strands has significant effects on the efficiency and strength of the hybridization between the nucleic acid strands.
The term "embryonic stem cells (ES)" refers to a cell that can give rise to many differentiated cell types in an embryo or an adult, including the germ cells.
The term "germ line stem cells (GSCs)" refers to stem cells derived from primordial stem cells that provide a steady and continuous source of germ cells for the production of gametes. The term "primordial germ cells (PGCs)" refers to a small population of cells set aside from other cell lineages particularly from the yolk sac, mesenteries, or gonadal ridges during embryogenesis that have the potential to differentiate into germ cells and other cells. PGCs are the source from which GSCs and ES cells are derived. The PGCs, the GSCs and the ES cells are capable of self renewal. Thus these cells not only populate the germ line and give rise to a plurality of terminally differentiated cells that comprise the adult specialized organs, but are able to regenerate themselves.
The term "expression modulating fragment," EMF, means a series of nucleotides which modulates the expression of an operably linked ORF or another EMF.
As used herein, a sequence is said to "modulate the expression of an operably linked sequence" when the expression of the sequence is altered by the presence of the EMF.
EMFs include, but are not limited to, promoters, and promoter modulating sequences (inducible elements). One class of EMFs are nucleic acid fragments which induce the expression of an operably linked ORF in response to a specific regulatory factor or physiological event.
The terms "nucleotide sequence" or "nucleic acid" or "polynucleotide" or 5 "oligonucleotide" are used interchangeably and refer to a heteropolymer of nucleotides or the sequence of these nucleotides. 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. In the sequences herein A is adenine, C is cytosine, T is thyrnine, G is guanine and 10 N is A, C, G, or T (U) or unknown. It is contemplated that where the polynucleotide is RNA, the T (thymine) in the sequences provided herein is substituted with U
(uracil).
Generally, nucleic acid segments provided by this invention may be assembled from fragments of the genome and short oligonucleotide linkers, or from a series of oligonucleotides, or from individual nucleotides, to provide a synthetic nucleic acid which is capable of being expressed in a recombinant transcriptional unit comprising regulatory elements derived from a microbial or viral operon, or a eukaryotic gene.
The terms "oligonucleotide fragment" or a "polynucleotide fragment", "portion," or "segment" or "probe" or "primer" are used interchangeably and refer to a sequence of nucleotide residues which are at least about 5 nucleotides, more preferably at least about 7 nucleotides, more preferably at least about 9 nucleotides, more preferably at least about 11 nucleotides and most preferably at least about 17 nucleotides. The fragment is preferably less than about 500 nucleotides, preferably less than about 200 nucleotides, more preferably less than about 100 nucleotides, more preferably less than about 50 nucleotides and most preferably less than 30 nucleotides. Preferably the probe is from about 6 nucleotides to about 200 nucleotides, preferably from about 15 to about 50 nucleotides, more preferably from about 17 to 30 nucleotides and most preferably from about 20 to 25 nucleotides.
Preferably the fragments can be used in polymerase chain reaction (PCR), various hybridization procedures or microarray procedures to identify or amplify identical or related parts of mRNA or DNA molecules. A fragment or segment may uniquely identify each polynucleotide sequence of the present invention. Preferably the fragment comprises a sequence substantially similar to any one of SEQ ID NO: 1-911, or 1823-2478.
Probes may, for example, be used to determine whether specific mRNA molecules are present in a cell~or tissue or to isolate similar nucleic acid sequences from chromosomal DNA as described by Walsh et al. (Walsh, P.S. et al., 1992, PCR Methods Appl 1:241-250).
They may be labeled by nick translation, Klenow fill-in reaction, PCR, or other methods well known in the art. Probes of the present invention, their preparation and/or labeling are elaborated in Sambrook, J. et al., 1989, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, NY; or Ausubel, F.M. et al., 1989, Current Protocols in Molecular Biology, John Wiley & Sons, New York NY, both of which are incorporated herein by reference in their entirety.
The nucleic acid sequences of the present invention also include the sequence information from the nucleic acid sequences of SEQ ID NO: 1-911, or 1823-2478.
The sequence information can be a segment of any one of SEQ ID NO: 1-911, or 1823-2478 that uniquely identiftes or represents the sequence information of that sequence of SEQ ID NO:
1-91 l, or 1823-2478, or those segments identified in Tables 3A, 3B, 5, or 6.
One such segment can be a twenty-mer nucleic acid sequence because the probability that a twenty-mer is fully matched in the human genome is 1 in 300. In the human genome, there are three billion base pairs in one set of chromosomes. Because 42° possible twenty-mers exist, there are 300 times more twenty-mers than there are base pairs in a set of human chromosomes.
Using the same analysis, the probability for a seventeen-mer to be fully matched in the human genome is approximately 1 in 5. When these segments are used in arrays for expression studies, fifteen-mer segments can be used. The probability that the fifteen-mer is fully matched in the expressed sequences is also approximately one in ftve because expressed sequences comprise less than approximately 5% of the entire genome sequence.
Similarly, when using sequence information for detecting a single mismatch, a segment can be a twenty-five mer. The probability that the twenty-five mer would appear in a human genome with a single mismatch is calculated by multiplying the probability for a full match (1-4z5) times the increased probability for mismatch at each nucleotide position (3 x 25). The probability that an eighteen mer with a single mismatch can be detected in an array for expression studies is approximately one in five. The probability that a twenty-mer with a single mismatch can be detected in a human genome is approximately one in five.
The term "open reading frame," ORF, means a series of nucleotide triplets coding for amino acids without any termination codons and is a sequence translatable into protein.
The terms "operably linked" or "operably associated" refer to functionally related nucleic acid sequences. For example, a promoter is operably associated or operably linked with a coding sequence if the promoter controls the transcription of the coding sequence.

While operably linked nucleic acid sequences can be contiguous and in the same reading frame, certain genetic elements e.g. repressor genes are not contiguously linked to the coding sequence but still control transcription/translation of the coding sequence.
The term "pluripotent" refers to the capability of a cell to differentiate into a number of differentiated cell types that are present in an adult organism. A
pluripotent cell is restricted in its differentiation capability in comparison to a totipotent cell.
The terms "polypeptide" or "peptide" or "amino acid sequence" refer to an oligopeptide, peptide, polypeptide or protein sequence or fragment thereof and to naturally occurring or synthetic molecules. A polypeptide "fragment," "portion," or "segment" is a stretch of amino acid residues of at least about 5 amino acids, preferably at least about 7 amino acids, more preferably at least about 9 amino acids and most preferably at least about 17 or more amino acids. The peptide preferably is not greater than about 200 amino acids, more preferably less than 150 amino acids and most preferably less than 100 amino acids.
Preferably the peptide is from about 5 to about 200 amino acids. To be active, any polypeptide must have sufficient length to display biological and/or immunological activity.
The term "naturally occurring polypeptide" refers to polypeptides produced by cells that have not been genetically engineered and specifically contemplates various polypeptides arising from post-translational modifications of the polypeptide including, but not limited to, acetylation, carboxylation, glycosylation, phosphorylation, lipidation and acylation.
The term "translated protein coding portion" means a sequence which encodes for the full-length protein which may include any leader sequence or any processing sequence.
The term "mature protein coding sequence" means a sequence which encodes a peptide or protein without a signal or leader sequence. The "mature protein portion" means that portion of the protein which does not include a signal or leader sequence. The peptide may have been produced by processing in the cell which removes any leaderlsignal sequence. The mature protein portion may or may not include the initial methionine residue.
The methionine residue may be removed from the protein during processing in the cell. The peptide may be produced synthetically or the protein may have been produced using a polynucleotide only encoding for the mature protein coding sequence.
The term "derivative" refers to polypeptides chemically modified by such techniques as ubiquitination, labeling (e.g., with radionuclides or various enzymes), covalent polymer attachment such as pegylation (derivatization with polyethylene glycol) and insertion or substitution by chemical synthesis of amino acids such as ornithine, which do not normally occur in human proteins.
The term "variant"(or "analog") refers to any polypeptide differing from naturally occurring polypeptides by amino acid insertions, deletions, and substitutions, created using, a g., recombinant DNA techniques. Guidance in determining which amino acid residues may be replaced, added or deleted without abolishing activities of interest, may be found by comparing the sequence of the particular polypeptide with that of homologous peptides and minimizing the number of amino acid sequence changes made in regions of high homology (conserved regions) or by replacing amino acids with consensus sequence.
Alternatively, recombinant variants encoding these same or similar polypeptides may be synthesized or selected by making use of the "redundancy" in the genetic code. Various codon substitutions, such as the silent changes which produce various restriction sites, may be introduced to optimize cloning into a plasmid or viral vector or expression in a particular prokaryotic or eukaryotic system. Mutations in the polynucleotide sequence may be reflected in the polypeptide or domains of other peptides added to the polypeptide to modify the properties of any part of the polypeptide, to change characteristics such as ligand-binding affinities, interchain affinities, or degradation/turnover rate.
Preferably, amino acid "substitutions" are the result of replacing one amino acid with another amino acid having similar structural and/or chemical properties, i.e., conservative amino acid replacements. "Conservative" 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 involved. For example, nonpolar (hydrophobic) amino acids include alanine, leucine, isoleucine, valine, proline, phenylalanine, tryptophan, and methionine; polar neutral amino acids include glycine, serine, threonine, cysteine, tyrosine, asparagine, and glutamine; positively charged (basic) amino acids include arginine, lysine, and histidine; and negatively charged (acidic) amino acids include aspartic acid and glutamic acid. "Insertions" or "deletions" are preferably in the range of about 1 to 20 amino acids, more preferably 1 to 10 amino acids. The variation allowed may be experimentally determined by systematically making insertions, deletions, or substitutions of amino acids in a polypeptide molecule using recombinant DNA techniques and assaying the resulting recombinant variants for activity.
Alternatively, where alteration of function is desired, insertions, deletions or non-conservative alterations can be engineered to produce altered polypeptides. Such alterations can, for example, alter one or more of the biological functions or biochemical characteristics of the polypeptides of the invention. For example, such alterations may change polypeptide characteristics such as ligand-binding affinities, interchain affinities, or degradation/turnover rate. Further, such alterations can be selected so as to generate polypeptides that are better suited for expression, scale up and the like in the host cells chosen for expression. For example, cysteine residues can be deleted or substituted with another amino acid residue in order to eliminate disulfide bridges.
The terms "purified" or "substantially purified" as used herein denotes that the indicated nucleic acid or polypeptide is present in the substantial absence of other biological macromolecules, e.g., polynucleotides, proteins, and the like. In one embodiment, the polynucleotide or polypeptide is purified such that it constitutes at least 95% by weight, more preferably at least 99% by weight, of the indicated biological macromolecules present (but water, buffers, and other small molecules, especially molecules having a molecular weight of less than 1000 daltons, can be present).
°The term "isolated" as used herein refers to a nucleic acid or polypeptide separated from at least one other component (e.g., nucleic acid or polypeptide) present with the nucleic acid or polypeptide in its natural source. In one embodiment, the nucleic acid or polypeptide is found in the presence of (if anything) only a solvent, buffer, ion, or other component normally present in a solution of the same. The terms "isolated" and "purified" do not encompass nucleic acids or polypeptides present in their natural source.
The term "recombinant," when used herein to refer to a polypeptide or protein, means that a polypeptide or protein is derived from recombinant (e.g., microbial, insect, or mammalian) expression systems. "Microbial" refers to recombinant polypeptides or proteins made in bacterial or fungal (e.g., yeast) expression systems. As a product, "recombinant microbial" defines a polypeptide or protein essentially free of native endogenous substances and unaccompanied by associated native glycosylation. Polypeptides or proteins expressed in most bacterial cultures, e.g., E. coli, will be free of glycosylation modifications;
polypeptides or proteins expressed in yeast will have a glycosylation pattern in general different from those expressed in mammalian cells.
The term "recombinant expression vehicle or vector" refers to a plasmid or phage or virus or vector, for expressing a polypeptide from a DNA (RNA) sequence. An expression vehicle can comprise a transcriptional unit comprising an assembly of (1) a genetic element or elements having a regulatory role in gene expression, for example, promoters or enhancers, (2) a structural or coding sequence which is transcribed into mRNA
and translated into protein, and (3) appropriate transcription initiation and termination sequences.
Structural units intended for use in yeast or eukaryotic expression systems preferably include a leader sequence enabling extracellular secretion of translated protein by a host cell.
5 Alternatively, where recombinant protein is expressed without a leader or transport sequence, it may include an amino terminal methionine residue. This residue may or may not be subsequently cleaved from the expressed recombinant protein to provide a final product.
The term "recombinant expression system" means host cells which have stably 10 integrated a recombinant transcriptional unit into chromosomal DNA or carry the recombinant transcriptional unit extrachromosomally. Recombinant expression systems as defined herein will express heterologous polypeptides or proteins upon induction of the regulatory elements linked to the DNA segment or synthetic gene to be expressed. This term also means host cells which have stably integrated a recombinant genetic element or 15 elements having a regulatory role in gene expression, for example, promoters or enhancers.
Recombinant expression systems as defined herein will express polypeptides or proteins endogenous to the cell upon induction of the regulatory elements linked to the endogenous DNA segment or gene to be expressed. The cells can be prokaryotic or eukaryotic.
The term "secreted" includes a protein that is transported across or through a membrane, including transport as a result of signal sequences in its amino acid sequence when it is expressed in a suitable host cell. "Secreted" proteins include without limitation proteins secreted wholly (e.g., soluble proteins) or partially (e.g., receptors) from the cell in which they are expressed. "Secreted" proteins also include without limitation proteins that are transported across the membrane of the endoplasmic reticulum. "Secreted"
proteins are also intended to include proteins containing non-typical signal sequences (e.g. Interleukin-1 Beta, see Krasney, P.A. and Young, P.R. (1992) Cytokine 4(2): 134 -143) and factors released from damaged cells (e.g. Interleukin-1 Receptor Antagonist, see Arend, W.P. et. al.
(1998) Annu. Rev. Immunol. 16:27-55) Where desired, an expression vector may be designed to contain a "signal or leader sequence" which will direct the polypeptide through the membrane of a cell.
Such a sequence may be naturally present on the polypeptides of the present invention or provided from heterologous protein sources by recombinant DNA techniques.

The term "stringent" is used to refer to conditions that are commonly understood in the art as stringent. Stringent conditions can include highly stringent conditions (i.e., hybridization to filter-bound DNA in 0.5 M NaHP04, 7% sodium dodecyl sulfate (SDS), 1 mM EDTA at 65°C, and washing in O.1X SSC/0.1% SDS at 68°C), and moderately stringent conditions (i.e., washing in 0.2X SSC/0.1% SDS at 42°C). Other exemplary hybridization conditions are described herein in the examples.
In instances of hybridization of deoxyoligonucleotides, additional exemplary stringent hybridization conditions include washing in 6X SSC/0.05% sodium pyrophosphate at 37°C (for 14-base oligonucleotides), 48°C (for 17-base oligonucleotides), 55°C (for 20-base oligonucleotides), and 60°C (for 23-base oligonucleotides).
As used herein, "substantially equivalent" or "substantially similar" can refer both to nucleotide and amino acid sequences, for example a mutant sequence, that varies from a reference sequence by one or more substitutions, deletions, or additions, the net effect of which does not result in an adverse functional dissimilarity between the reference and subject sequences. Typically, such a substantially equivalent sequence varies from one of those listed herein by no more than about 35% (i.e., the number of individual residue substitutions, additions, and/or deletions in a substantially equivalent sequence, as compared to the corresponding reference sequence, divided by the total number of residues in the substantially equivalent sequence is about 0.35 or less). Such a sequence is said to have 65% sequence identity to the listed sequence. In one embodiment, a substantially equivalent, e.g., mutant, sequence of the invention varies from a listed sequence by no more than 30% (70% sequence identity); in a variation of this embodiment, by no more than 25%
(75% sequence identity); and in a further variation of this embodiment, by no more than 20% (80% sequence identity) and in a further variation of this embodiment, by no more than 10% (90% sequence identity) and in a further variation of this embodiment, by no more that 5% (95% sequence identity). Substantially equivalent, e.g., mutant, amino acid sequences according to the invention preferably have at least 80% sequence identity with a listed amino acid sequence, more preferably at least 85% sequence identity, more preferably at least 90%
sequence identity, more preferably at least 95% sequence identity, more preferably at least 98% sequence identity, and most preferably at least 99% sequence identity.
Substantially equivalent nucleotide sequence of the invention can have lower percent sequence identities, taking into account, for example, the redundancy or degeneracy of the genetic code.
Preferably, the nucleotide sequence has at least about 65% identity, more preferably at least about 75% identity, more preferably at least about 80% sequence identity, more preferably at least 85% sequence identity, more preferably at least 90% sequence identity, more preferably at least about 95% sequence identity, more preferably at least 98% sequence identity, and most preferably at least 99% sequence identity. For the purposes of the present invention, sequences having substantially equivalent biological activity and substantially equivalent expression characteristics are considered substantially equivalent. For the purposes of determining equivalence, truncation of the mature sequence (e.g., via a mutation which creates a new stop codon) should be disregarded. Sequence identity may be determined, e.g., using the Jotun Hein method (Hero, J. (1990) Methods Enzymol. 183:626-645).
Identity between sequences can also be determined by other methods known in the art, e.g.
by varying hybridization conditions.
The term "totipotent" refers to the capability of a cell to differentiate into all of the cell types of an adult organism.
The term "transformation" means introducing DNA into a suitable host cell so that the DNA is replicable, either as an extrachromosomal element, or by chromosomal integration. The term "transfection" refers to the taking up of an expression vector by a suitable host cell, whether or not any coding sequences are in fact expressed.
The term "infection" refers to the introduction of nucleic acids into a suitable host cell by use of a virus or viral vector.
As used herein, an "uptake modulating fragment," UMF, means a series of nucleotides which mediate the uptake of a linked DNA fragment into a cell.
UMFs can be readily identified using known UMFs as a target sequence or target motif with the computer-based systems described below. The presence and activity of a UMF can be confirmed by attaching the suspected UMF to a marker sequence. The resulting nucleic acid molecule is then incubated with an appropriate host under appropriate conditions and the uptake of the marker sequence is determined. As described above, a UMF will increase the frequency of uptake of a linked marker sequence.
Each of the above terms is meant to encompass all that is described for each, unless the context dictates otherwise.
4.2 NUCLEIC ACIDS OF THE INVENTION
Nucleotide sequences of the invention are set forth in the Sequence Listing.

The isolated polynucleotides of the invention include a polynucleotide comprising the nucleotide sequences of SEQ ID NO: 1-911, or 1823-2478; a polynucleotide encoding any one of the peptide sequences of SEQ ID NO: 1-911, or 1823-2478; and a polynucleotide .comprising the nucleotide sequence encoding the mature protein coding sequence of the polynucleotides of any one of SEQ ID NO: 1-911, or 1823-2478. The polynucleotides of the present invention also include, but are not limited to, a polynucleotide that hybridizes under stringent conditions to (a) the complement of any of the nucleotides sequences of SEQ ID
NO: 1-911, or 1823-2478; (b) nucleotide sequences encoding any one of the amino acid sequences set forth in the Sequence Listing, ; (c) a polynucleotide which is an allelic variant of any polynucleotide recited above; (d) a polynucleotide which encodes a species homologue of any of the proteins recited above; or (e) a polynucleotide that encodes a polypeptide comprising a specific domain or truncation of the polypeptides of SEQ ID NO:
912-1822, or 2479-3134 (for example, as set forth in Tables 3A, 3B, 5, or 6).
Domains of interest may depend on the nature of the encoded polypeptide; e.g., domains in receptor-like polypeptides include ligand-binding, extracellular, transmembrane, or cytoplasmic domains, or combinations thereof; domains in immunoglobulin-like proteins include the variable immunoglobulin-like domains; domains in enzyme-like polypeptides include catalytic and substrate binding domains; and domains in ligand polypeptides include receptor-binding domains.
The polynucleotides of the invention include naturally occurring or wholly or partially synthetic DNA, e.g., cDNA and genomic DNA, and RNA, e.g., mRNA. The polynucleotides may include entire coding region of the cDNA or may represent a portion of the coding region of the cDNA.
The present invention also provides genes corresponding to the cDNA sequences disclosed herein. The corresponding genes can be isolated in accordance with known methods using the sequence information disclosed herein. Such methods include the preparation of probes or primers from the disclosed sequence information for identification and/or amplification of genes in appropriate genomic libraries or other sources of genomic materials.
Further 5' and 3' sequence can be obtained using methods known in the art. For example, full length cDNA ~or genornic DNA that corresponds to any of the polynucleotides of SEQ ID NO:
1-911, or 1823-2478 can be obtained by screening appropriate cDNA or genomic DNA
libraries under suitable hybridization conditions using any of the polynucleotides of SEQ ID
NO: 1-911, or 1823-2478 or a portion thereof as a probe. Alternatively, the polynucleotides of SEQ m NO: 1-911, or 1823-2478 may be used as the basis for suitable primers) that allow identification and/or amplification of genes in appropriate genomic DNA or cDNA libraries.
The nucleic acid sequences of the invention can be assembled from ESTs and sequences (including cDNA and genomic sequences) obtained from one or more public databases, such as dbEST, gbpri, and UniGene. The EST sequences can provide identifying sequence information, representative fragment or segment information, or novel segment information for the full-length gene.
The polynucleotides of the invention also provide polynucleotides including nucleotide sequences that are substantially equivalent to the polynucleotides recited above.
Polynucleotides according to the invention can have, e.g., at least about 65%, at least about 70%, at least about 75%, at least about 80%, 81%, 82%, 83%, 84%, more typically at least about 85%, 86%, 87%, 88%, 89%, more typically at least about 90%, 91%, 92%, 93%, 94%, and even more typically at least about 95%, 96%, 97%, 98%, 99% sequence identity to a polynucleotide recited above.
Included within the scope of the nucleic acid sequences of the invention are nucleic acid sequence fragments that hybridize under stringent conditions to any of the nucleotide sequences of SEQ ID NO: 1-911, or 1823-2478, or complements thereof, which fragment is greater than about 5 nucleotides, preferably 7 nucleotides, more preferably greater than 9 nucleotides and most preferably greater than 17 nucleotides. Fragments of, e.g. 15, 17, or 20 nucleotides or more that are selective for (i.e. specifically hybridize to) any one of the polynucleotides of the invention are contemplated. Probes capable of specifically hybridizing to a polynucleotide can differentiate polynucleotide sequences of the invention from other polynucleotide sequences in the same family of genes or can differentiate human genes from genes of other species, and are preferably based on unique nucleotide sequences.
The sequences falling within the scope of the present invention are not limited to these specific sequences, but also include allelic and species variations thereof.
Allelic and species variations can be routinely determined by comparing the sequence provided in SEQ ID NO: 1-911, or 1823-2478, a representative fragment thereof, or a nucleotide sequence at least 90%
identical, preferably 95% identical, to SEQ ID NO: 1-911, or 1823-2478 with a sequence from another isolate of the same species. Furthermore, to accommodate codon variability, the invention includes nucleic acid molecules coding for the same amino acid sequences as do the specific ORFs disclosed herein. In other words, in the coding region of an ORF, substitution of one codon fox another codon that encodes the same amino acid is expressly contemplated.

The nearest neighbor or homology results for the nucleic acids of the present invention, including SEQ ID NO: 1-91 l, or 1823-2478 can be obtained by searching a database using an algorithm or a program. Preferably, a BLAST (Basic Local Alignment Search Tool) program is used to search for local sequence alignments (Altshul, S.F. J Mol. Evol. 36 290-300 (1993) and Altschul S.F. et al. J. Mol. Biol. 21:403-410 (1990)). Alternatively a FASTA
version 3 search against Genpept, using FASTXY algorithm may be performed.
Species homologs (or orthologs) of the disclosed polynucleotides and proteins are also provided by the present invention. Species homologs may be isolated and identified by making suitable probes or primers from the sequences provided herein and screening a 10 suitable nucleic acid source from the desired species.
The invention also encompasses allelic variants of the disclosed polynucleotides or proteins; that is, naturally-occurring alternative forms of the isolated polynucleotide which also encode proteins which are identical, homologous or related to that encoded by the polynucleotides.
15 The nucleic acid sequences of the invention are further directed to sequences which encode variants of the described nucleic acids. These amino acid sequence variants may be prepared by methods known in the art by introducing appropriate nucleotide changes into a native or variant polynucleotide. There are two variables in the construction of amino acid sequence variants: the location of the mutation and the nature of the mutation. Nucleic 20 acids encoding the amino acid sequence variants are preferably constructed by mutating the polynucleotide to encode an amino acid sequence that does not occur in nature.
These nucleic acid alterations can be made at sites that differ in the nucleic acids from different species (variable positions) or in highly conserved regions (constant regions). Sites at such locations will typically be modified in series, e.g., by substituting first with conservative choices (e.g., hydrophobic amino acid to a different hydrophobic amino acid) and then with more distant choices (e.g., hydrophobic amino acid to a charged amino acid), and then deletions or insertions may be made at the target site. Amino acid sequence deletions generally range from about 1 to 30 residues, preferably about 1 to 10 residues, and are typically contiguous. Amino acid insertions include amino- and/or carboxyl-terminal fusions ranging in length from one to one hundred or more residues, as well as intrasequence insertions of single or multiple amino acid residues. Intrasequence insertions may range generally from about 1 to 10 amino residues, preferably from 1 to 5 residues.
Examples of terminal insertions include the heterologous signal sequences necessary for secretion or for intracellular targeting in different host cells and sequences such as FLAG or poly-histidine sequences useful for purifying the expressed protein.
In a preferred method, polynucleotides encoding the novel amino acid sequences are changed via site-directed mutagenesis. This method uses oligonucleotide sequences to alter a polynucleotide to encode the desired amino acid variant, as well as sufficient adjacent nucleotides on both sides of the changed amino acid to form a stable duplex on either side of the site of being changed. In general, the techniques of site-directed mutagenesis are well known to those of skill in the art and this technique is exemplified by publications such as, Edelman et al., DNA 2:183 (1983). A versatile and efficient method for producing site-specific changes in a polynucleotide sequence was published by Zoller and Smith, Nucleic Acids Res. 10:6487-6500 (1982). PCR may also be used to create amino acid sequence variants of the novel nucleic acids. When small amounts of template DNA are used as starting material, primers) that differs slightly in sequence from the corresponding region in the template DNA can generate the desired amino acid variant. PCR
amplification results in a population of product DNA fragments that differ from the polynucleotide template encoding the polypeptide at the position specified by the primer. The product DNA
fragments replace the corresponding region in the plasmid and this gives a polynucleotide encoding the desired amino acid variant.
A further technique for generating amino acid variants is the cassette mutagenesis technique described in Wells et al., Gefze 34:315 (1985); and other mutagenesis techniques well known in the art, such as, for example, the techniques in Sambrook et al., supra, and Currezzt Protocols izz Molecular Biology, Ausubel et al. 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 used in the practice of the invention for the cloning and expression of these novel nucleic acids. Such DNA sequences include those which are capable of hybridizing to the appropriate novel nucleic acid sequence under stringent conditions.
Polynucleotides encoding preferred polypeptide truncations of the invention could be used to generate polynucleotides encoding chimeric or fusion proteins comprising one or more domains of the invention and heterologous protein sequences.
The polynucleotides of the invention additionally include the complement of any of the polynucleotides recited above. T'he polynucleotide can be DNA (genomic, cDNA, amplified, or synthetic) or RNA. Methods and algorithms for obtaining such polynucleotides are well known to those of skill in the art and can include, for example, methods for determining hybridization conditions that can routinely isolate polynucleotides of the desired sequence identities.
In accordance with the invention, polynucleotide sequences comprising the mature protein coding sequences corresponding to any one of SEQ ID NO: 1-911, or 1823-2478, or functional equivalents thereof, may be used to generate recombinant DNA
molecules that direct the expression of that nucleic acid, or a functional equivalent thereof, in appropriate host cells. Also included are the cDNA inserts of any of the clones identified herein.
A polynucleotide according to the invention can be joined to any of a variety of other nucleotide sequences by well-established recombinant DNA techniques (see Sambrook J et al. (1989) Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, NY).
Useful nucleotide sequences for joining to polynucleotides include an assortment of vectors, e.g., plasmids, cosmids, lambda phage derivatives, phagemids, and the like, that are well known in the art. Accordingly, the invention also provides a vector including a polynucleotide of the invention and a host cell containing the polynucleotide.
In general, the vector contains an origin of replication functional in at least one organism, convenient restriction endonuclease sites, and a selectable marker for the host cell.
Vectors according to the invention include expression vectors, replication vectors, probe generation vectors, and sequencing vectors. A host cell according to the invention can be a prokaryotic or eukaryotic cell and can be a unicellular organism or part of a multicellular organism.
The present invention further provides recombinant constructs comprising a nucleic acid having any of the nucleotide sequences of SEQ ID NO: 1-911, or 1823-2478 or a fragment thereof or any other polynucleotides of the invention. In one embodiment, the recombinant constructs of the present invention comprise a vector, such as a plasmid or viral vector, into which a nucleic acid having any of the nucleotide sequences of SEQ ID NO: 1-911, or 1823-2478 or a fragment thereof is inserted, in a forward or reverse orientation. In the case of a vector comprising one of the ORFs of the present invention, the vector may further comprise regulatory sequences, including for example, a promoter, operably linked to the ORF. Large numbers of suitable vectors and promoters are known to those of skill in the art and are commercially available for generating the recombinant constructs of the present invention. The following vectors are provided by way of example: Bacterial:
pBs, phagescript, PsiX174, pBluescript SK, pBs KS, pNHBa, pNHl6a, pNHl8a, pNH46a (Stratagene), pTrc99A, pKK223-3, pKK233-3, pDR540, pRITS (Pharmacia);
Eukaryotic:

pWLneo, pSV2cat, pOG44, PXTI, pSG (Stratagene) pSVK3, pBPV, pMSG, pSVL
(Pharmacia).
The isolated polynucleotide of the invention may be operably linked to an expression control sequence such as the pMT2 or pED expression vectors disclosed in Kaufman et al., Nucleic Acids Res. 19, 4485-4490 (1991), in order to produce the protein recombinantly.
Many suitable expression control sequences are known in the art. General methods of expressing recombinant proteins are also known and are exemplified in R.
Kaufman, Metlaods ih Eyazynaology 185, 537-566 (1990). As defined herein "operably linked" means that the isolated polynucleotide of the invention and an expression control sequence are situated within a vector or cell in such a way that the protein is expressed by a host cell which has been transformed (transfected) with the ligated polynucleotide/expression control sequence.
Promoter regions can be selected from any desired gene using CAT
(chloramphenicol transferase) vectors or other vectors with selectable markers. Two appropriate vectors are pKK232-8 and pCM7. Particular named bacterial promoters include lacI, lacZ, T3, T7, gpt, lambda PR, and trc. Eukaryotic promoters include CMV
immediate early, HSV thyrnidine kinase, early and late SV40, LTRs from retrovirus, and mouse metallothionein-I. Selection of the appropriate vector and promoter is well within the level of ordinary skill in the art. Generally, recombinant expression vectors will include origins of replication and selectable markers permitting transformation of the host cell, e.g., the ampicillin resistance gene of E. coli and S. cerevisiae TRP 1 gene, and a promoter derived from a highly expressed gene to direct transcription of a downstream structural sequence.
Such promoters can be derived from operons encoding glycolytic enzymes such as phosphoglycerate kinase (PGK), a-factor, acid phosphatase, or heat shock proteins, among others. The heterologous structural sequence is assembled in appropriate phase with translation initiation and termination sequences, and preferably, a leader sequence capable of directing secretion of translated protein into the periplasmic space or extracellular medium.
Optionally, the heterologous sequence can encode a fusion protein including an amino terminal identification peptide imparting desired characteristics, e.g., stabilization or simplified purification of expressed recombinant product. Useful expression vectors for bacterial use are constructed by inserting a structural DNA sequence encoding a desired protein together with suitable translation initiation and termination signals in operable reading phase with a functional promoter. The vector will comprise one or more phenotypic selectable markers and an origin of replication to ensure maintenance of the vector and to, if desirable, provide amplification within the host. Suitable prokaryotic hosts for transformation include E. coli, Bacillus subtilis, Salmonella typlairnurium and various species within the genera Pseudontonas, Streptornyces, and Staphylococcus, although others may also be employed as a matter of choice.
As a representative but non-limiting example, useful expression vectors for bacterial use can comprise a selectable marker and bacterial origin of replication derived from commercially available plasmids comprising genetic elements of the well known cloning vector pBR322 (ATCC 37017). Such commercial vectors include, for example, pI~I~223-3 (Pharmacia Fine Chemicals, Uppsala, Sweden) and GEM 1 (Promega Biotech, Madison, WI, USA). These pBR322 "backbone" sections are combined with an appropriate promoter and the structural sequence to be expressed. Following transformation of a suitable host strain and growth of the host strain to an appropriate cell density, the selected promoter is induced or derepressed by appropriate means (e.g., temperature shift or chemical induction) and cells are cultured for an additional period. Cells are typically harvested by centrifugation, disrupted by physical or chemical means, and the resulting crude extract retained for further purification.
Polynucleotides of the invention can also be used to induce immune responses.
For example, as described in Fan et al., Nat. Biotech 17, 870-872 (1999), incorporated herein by reference, nucleic acid sequences encoding a polypeptide may be used to generate antibodies against the encoded polypeptide following topical administration of naked plasmid DNA or following injection, and preferably infra-muscular injection of the DNA. The nucleic acid sequences are preferably inserted in a recombinant expression vector and may be in the form of naked DNA.
4.3 ANTISENSE
Another aspect of the invention pertains to isolated antisense nucleic acid molecules that are hybridizable to or complementary to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO: 1-91 l, or 1823-2478, or fragments, analogs or derivatives thereof. An "antisense" nucleic acid comprises a nucleotide sequence that is complementary to a "sense" nucleic acid encoding a protein, e.g., complementary to the coding strand of a double-stranded cDNA molecule or complementary to an mRNA
sequence. In specific aspects, antisense nucleic acid molecules are provided that comprise a sequence complementary to at least about 10, 25, 50, 100, 250 or 500 nucleotides or an entire coding strand, or to only a portion thereof. Nucleic acid molecules encoding fragments, homologs, derivatives and analogs of a protein of any of SEQ ID NO:
1-911, or 1823-2478 or antisense nucleic acids complementary to a nucleic acid sequence of SEQ ID
5 NO: 1-911, or 1823-2478 are additionally provided.
In one embodiment, an antisense nucleic acid molecule is antisense to a "coding region" of the coding strand of a nucleotide sequence of the invention. The term "coding region" refers to the region of the nucleotide sequence comprising codons which are translated into amino acid residues. In another embodiment, the antisense nucleic acid 10 molecule is antisense to a "noncoding region" of the coding strand of a nucleotide sequence of the invention. The term "noncoding region" refers to 5' and 3' sequences that flank the coding region that are not translated into amino acids (i.e., also referred to as 5' and 3' untranslated regions).
Given the coding strand sequences encoding a nucleic acid disclosed herein (e.g., 15 SEQ ID NO: 1-911, or 1823-2478, antisense nucleic acids of the invention can be designed according to the rules of Watson and Crick or Hoogsteen base pairing. The antisense nucleic acid molecule can be complementary to the entire coding region of an mRNA, but more preferably is an oligonucleotide that is antisense to only a portion of the coding or noncoding region of an mRNA. For example, the antisense oligonucleotide can be complementary to 20 the region surrounding the translation start site of an mRNA. An antisense oligonucleotide can be, for example, about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50 nucleotides in length. An antisense nucleic acid of the invention can be constructed using chemical synthesis or enzymatic ligation reactions using procedures known in the art. For example, an antisense nucleic acid (e.g., an antisense oligonucleotide) can be chemically synthesized using 25 naturally occurring nucleotides or variously modified nucleotides designed to increase the biological stability of the molecules or to increase the physical stability of the duplex formed betyveen the antisense and sense nucleic acids, e.g., phosphorothioate derivatives and acridine substituted nucleotides can be used.
Examples of modified nucleotides that can be used to generate the antisense nucleic acid include: 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xanthine, 4-acetylcytosine, 5-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyl-2-thiouridine, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, beta-D-rnannosylqueosine, 5'-rnethoxycarboxymethyluracil, 5-methoxyuracil, 2-methylthio-N6-isopentenyladenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5-methyl-2-thiouracil, 2-thiouracil, 4-thiouracil, 5-methyluracil, uracil-5-oxyacetic acid methylester, uracil-5-oxyacetic acid (v), 5-methyl-2-thiouracil, 3-(3-amino-3-N-2-carboxypropyl) uracil, (acp3)w, and 2,6-diaminopurine. Alternatively, the antisense nucleic acid can be produced biologically using an expression vector into which a nucleic acid has been subcloned in an antisense orientation (i.e., RNA transcribed from the inserted nucleic acid will be of an antisense orientation to a target nucleic acid of interest, described further in the following subsection).
The antisense nucleic acid molecules of the invention are typically administered to a subject or generated in situ such that they hybridize with or bind to cellular mRNA and/or genomic DNA encoding a protein according to the invention to thereby inhibit expression of the protein, e.g., by inhibiting transcription and/or translation. The hybridization can be by conventional nucleotide complementarity to form a stable duplex, or, for example, in the case of an antisense nucleic acid molecule that binds to DNA duplexes, through specific interactions in the major groove of the double helix. An example of a route of administration of antisense nucleic acid molecules of the invention includes direct injection at a tissue site. Alternatively, antisense nucleic acid molecules can be modified to target selected cells and then administered systemically. For example, for systemic administration, antisense molecules can be modified such that they specifically bind to receptors or antigens expressed on a selected cell surface, e.g., by linking the antisense nucleic acid molecules to peptides or antibodies that bind to cell surface receptors or antigens. The antisense nucleic acid molecules can also be delivered to cells using the vectors described herein. To achieve sufficient intracellular concentrations of antisense molecules, vector constructs in which the antisense nucleic acid molecule is placed under the control of a strong pol II
or pol III
promoter are preferred.
In yet another embodiment, the antisense nucleic acid molecule of the invention is an oc-anomeric nucleic acid molecule. An oc-anomeric nucleic acid molecule forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual cc-units, the strands run parallel to each other (Gaultier et al. (1987) Nucleic Acids Res 15:

6625-6641). The antisense nucleic acid molecule can also comprise a 2'-o-methylribonucleotide (moue et al. (1987) Nucleic Acids Res 15: 6131-6148) or a chimeric RNA -DNA analogue (moue et al. (1987) FEBSLett 215: 327-330).
4.4 RIBOZYMES AND PNA MOIETIES
In still another embodiment, an antisense nucleic acid of the invention is a ribozyme.
Ribozyrnes are catalytic RNA molecules with ribonuclease activity that are capable of cleaving a single-stranded nucleic acid, such as an mRNA, to which they have a complementary region. Thus, ribozymes (e.g., hammerhead ribozymes (described in Haselhoff and Gerlach (1988) Natuf°e 334:585-591)) can be used to catalytically cleave rnRNA transcripts to thereby inhibit translation of an mRNA. , A ribozyme having specificity for a nucleic acid of the invention can be designed based upon the nucleotide sequence of a DNA disclosed herein (i.e., SEQ ID NO: 1-911, or 1823-2478). For example, a derivative of Tetrahymena L-19 IVS RNA can be constructed in which the nucleotide sequence of the active site is complementary to the nucleotide sequence to be cleaved in a mRNA. See, e.g., Cech et al. U.S. Pat. No. 4,987,071; and Cech et al. U.S. Pat. No. 5,116,742.
Alternatively, mRNA of the invention can be used to select a catalytic RNA having a specific ribonuclease activity from a pool of RNA molecules. See, e.g., Bartel et al., (1993) Science 261:1411-1418.
Alternatively, gene expression can be inhibited by targeting nucleotide sequences complementary to the regulatory region (e.g., promoter and/or enhancers) to form triple helical structures that prevent transcription of the gene in target cells. See generally, Helene.
(1991) Anticancer Drug Des. 6: 569-84; Helene. et al. (1992) Ann. N. Y. Acad.
Sci.
660:27-36; and Maher (1992) Bioassays 14: 807-15.
In various embodiments, the nucleic acids of the invention can be modified at the base moiety, sugar moiety or phosphate backbone to improve, e.g., the stability, hybridization, or solubility of the molecule. For example, the deoxyribose phosphate backbone of the nucleic acids can be modified to generate peptide nucleic acids (see Hyrup et al. (1996) Bioo~g Med Cl2ern 4: 5-23). As used herein, the terms "peptide nucleic acids"
or "PNAs" refer to nucleic acid mimics, e.g., DNA mimics, in which the deoxyribose phosphate backbone is replaced by a pseudopeptide backbone and only the four natural nucleobases are retained. The neutral backbone of PNAs has been shown to allow for specific hybridization to DNA and RNA under conditions of low ionic strength.
The synthesis of PNA oligomers can be performed using standard solid phase peptide synthesis protocols as described in Hyrup et al. (1996) above; Perry-O'Keefe et al.
(1996) PNAS 93:
14670-675.
PNAs of the invention can be used in therapeutic and diagnostic applications.
For example, PNAs can be used as antisense or antigene agents for sequence-specific modulation of gene expression by, e.g., inducing transcription or translation arrest or inhibiting replication. PNAs of the invention can also be used, e.g., in the analysis of single base pair mutations in a gene by, e.g., PNA directed PCR clamping; as artificial restriction enzymes when used in combination with other enzymes, e.g., S1 nucleases (Hyrup B.
(1996) above);
or as probes or primers for DNA sequence and hybridization (Hyrup et al.
(1996), above;
Perry-O'Keefe (1996), above).
In another embodiment, PNAs of the invention can be modified, e.g., to enhance their stability or cellular uptake, by attaching lipophilic or other helper groups to PNA, by the formation of PNA-DNA chimeras, or by the use of liposomes or other techniques of drug delivery known in the art. For example, PNA-DNA chimeras can be generated that may combine the advantageous properties of PNA and DNA. Such chimeras allow DNA
recognition enzymes, e.g., RNase H and DNA polymerases, to interact with the DNA
portion while the PNA portion would provide high binding affinity and specificity.
PNA-DNA chimeras can be linked using linkers of appropriate lengths selected in terms of base stacking, number of bonds between the nucleobases, and orientation (Hyrup (1996) above). The synthesis of PNA-DNA chimeras can be performed as described in Hyrup (1996) above and Finn et al. (1996) Nucl Acids Res 24: 3357-63. For example, a DNA chain can be synthesized on a solid support using standard phosphoramidite coupling chemistry, and modified nucleoside analogs, e.g., 5'-(4-methoxytrityl)amino-5'-deoxy-thymidine phosphoramidite, can be used between the PNA and the 5' end of DNA (Mag et al.
(1989) Nucl Acid Res 17: 5973-88). PNA monomers are then coupled in a stepwise manner to produce a chimeric molecule with a 5' PNA segment and a 3' DNA segment (Finn et al.
(1996) above). Alternatively, chimeric molecules can be synthesized with a 5' DNA
segment and a 3' PNA segment. See, Petersen et al. ( 1975) Bioo~g Med Claena Lett 5:
1119-11124.
In other embodiments, the oligonucleotide may include other appended groups such as peptides (e.g., for targeting host cell receptors i~a vivo), or agents facilitating transport across the cell membrane (see, e.g., Letsinger et al., 1989, Proc. Natl. Acad.
Sci. U.S.A.

86:6553-6556; Lemaitre et al., 1987, Proc. Natl. Acad. Sci. 84:648-652; PCT
Publication No. W088/09810) or the blood-brain barner (see, e.g., PCT Publication No.
W089/10134).
In addition, oligonucleotides can be modified with hybridization triggered cleavage agents (See, e.g., Krol et al., 1988, BioTechraiques 6:958-976) or intercalating agents. (See, e.g., Zon, 1988, Plaarfra. Res. 5: 539-549). To this end, the oligonucleotide may be conjugated to another molecule, e.g., a peptide, a hybridization triggered cross-linking agent, a transport agent, a hybridization-triggered cleavage agent, etc.
4.5 HOSTS
The present invention further provides host cells genetically engineered to contain the polynucleotides of the invention. For example, such host cells may contain nucleic acids of the invention introduced into the host cell using known transformation, transfection or infection methods. The present invention still further provides host cells genetically engineered to express the polynucleotides of the invention, wherein such polynucleotides are in operative association with a regulatory sequence heterologous to the host cell which drives expression of the polynucleotides in the cell.
Knowledge of nucleic acid sequences allows for modification of cells to permit, or increase, expression of endogenous polypeptide. Cells can be modified (e.g., by homologous recombination) to provide increased polypeptide expression by replacing, in whole or in part, the naturally occurring promoter with all or part of a heterologous promoter so that the cells express the polypeptide at higher levels. The heterologous promoter is inserted in such a manner that it is operatively linked to the encoding sequences. See, for example, PCT International Publication No. W094/12650, PCT International Publication No. W092/20808, and PCT International Publication No. W091/09955. It is also contemplated that, in addition to heterologous promoter DNA, amplifiable marker DNA
(e.g., ada, dhfr, and the multifunctional CAD gene which encodes carbamyl phosphate synthase, aspartate transcarbamylase, and dihydroorotase) and/or intron DNA
may be inserted along with the heterologous promoter DNA. If linked to the coding sequence, amplification of the marker DNA by standard selection methods results in co-amplification of the desired protein coding sequences in the cells.
The host cell can be a higher eukaryotic host cell, such as a mammalian cell, a lower eukaryotic host cell, such as a yeast cell, or the host cell can be a prokaryotic cell, such as a bacterial cell. Introduction of the recombinant construct into the host cell can be effected by calcium phosphate transfection, DEAE, dextran mediated transfection, or electroporation (Davis, L. et al., Basic Methods isZ Molecular Biology (1986)). The host cells containing one of the polynucleotides of the invention, can be used in conventional manners to produce the gene product encoded by the isolated fragment (in the case of an ORF) or can be used to 5 produce a heterologous protein under the control of the EMF.
Any host/vector system can be used to express one or more of the ORFs of the present invention. These include, but are not limited to, eukaryotic hosts such as HeLa cells, Cv-1 cell, COS cells, 293 cells, and Sf9 cells, as well as prokaryotic host such as E. coli and B. subtilis. The most preferred cells are those which do not normally express the particular 10 polypeptide or protein or which expresses the polypeptide or protein at low natural level.
Mature proteins can be expressed in mammalian cells, yeast, bacteria, or other cells under the control of appropriate promoters. Cell-free translation systems can also be employed to produce such proteins using RNAs derived from the DNA constructs of the present invention. Appropriate cloning and expression vectors for use with prokaryotic and 15 eukaryotic hosts are described by Sambrook, et al., in Molecular Cloning: A
Laboratory Manual, Second Edition, Cold Spring Harbor, New York (1989), the disclosure of which is hereby incorporated by reference.
Various mammalian cell culture systems can also be employed to express recombinant protein. Examples of mammalian expression systems include the COS-7 lines 20 of monkey kidney fibroblasts, described by Gluzman, Cell 23:175 (1981).
Other cell lines capable of expressing a compatible vector are, for example, the 0127, monkey COS cells, Chinese Hamster Ovary (CHO) cells, human kidney 293 cells, human epidermal A431 cells, human Co1o205 cells, 3T3 cells, CV-1 cells, other transformed primate cell lines, normal diploid cells, cell strains derived from in vitro culture of primary tissue, primary explants, 25 HeLa cells, mouse L cells, BHK, HL-60, LT937, HaK or Jurkat cells.
Mammalian expression vectors will comprise an origin of replication, a suitable promoter and also any necessary ribosome binding sites, polyadenylation site, splice donor and acceptor sites, transcriptional termination sequences, and 5' flanking nontranscribed sequences. DNA sequences derived from the SV40 viral genome, for example, SV40 origin, early promoter, enhancer, splice, 30 and polyadenylation sites may be used to provide the required nontranscribed genetic elements. lZecombinant polypeptides and proteins produced in bacterial culture are usually isolated by initial extraction from cell pellets, followed by one or more salting-out, aqueous ion exchange or size exclusion chromatography steps. Protein refolding steps can be used, as necessary, in completing configuration of the mature protein. Finally, high performance liquid chromatography (HPLC) can be employed for final purification steps.
Microbial cells employed in expression of proteins can be disrupted by any convenient method, including freeze-thaw cycling, sonication, mechanical disruption, or use of cell lysing agents.
Alternatively, it may be possible to produce the protein in lower eukaryotes such as yeast or insects or in prokaryotes such as bacteria. Potentially suitable yeast strains include Saccharotnyces ce>"evisiae, Scltizosaccharomyces potnbe, Kluyverotnyces strains, Candida, or any yeast strain capable of expressing heterologous proteins. Potentially suitable bacterial strains include Eschez~ichia coli, Bacillus subtilis, Salntottella typhinturium, or any bacterial strain capable of expressing heterologous proteins. If the protein is made in yeast or bacteria, it may be necessary to modify the protein produced therein, for example by phosphorylation or glycosylation of the appropriate sites, in order to obtain the functional protein. Such covalent attachments may be accomplished using known chemical or enzymatic methods.
In another embodiment of the present invention, cells and tissues may be engineered to express an endogenous gene comprising the polynucleotides of the invention under the control of inducible regulatory elements, in which case the regulatory sequences of the endogenous gene may be replaced by homologous recombination. As described herein, gene targeting can be used to replace a gene's existing regulatory region with a regulatory sequence isolated from a different gene or a novel regulatory sequence synthesized by genetic engineering methods. Such regulatory sequences may be comprised of promoters, enhancers, scaffold-attachment regions, negative regulatory elements, transcriptional initiation sites, and regulatory protein binding sites or combinations of said sequences.
Alternatively, sequences which affect the structure or stability of the RNA or protein produced may be replaced, removed, added, or otherwise modified by targeting.
These sequence include polyadenylation signals, mRNA stability elements, splice sites, leader sequences for enhancing or modifying transport or secretion properties of the protein, or other sequences which alter or improve the function or stability of protein or RNA
molecules.
The targeting event may be a simple insertion of the regulatory sequence, placing the gene under the control of the new regulatory sequence, e.g., inserting a new promoter or enhancer or both upstream of a gene. Alternatively, the targeting event may be a simple deletion of a regulatory element, such as the deletion of a tissue-specific negative regulatory element. Alternatively, the targeting event may replace an existing element;
for example, a tissue-specific enhancer can be replaced by an enhancer that has broader or different cell-type specificity than the naturally occurring elements. Here, the naturally occurring sequences are deleted and new sequences are added. In all cases, the identification of the targeting event may be facilitated by the use of one or more selectable marker genes that are contiguous with the targeting DNA, allowing for the selection of cells in which the exogenous DNA has integrated into the host cell genome. The identification of the targeting event may also be facilitated by the use of one or more marker genes exhibiting the property of negative selection, such that the negatively selectable marker is linked to the exogenous DNA, but configured such that the negatively selectable marker flanks the targeting sequence, and such that a correct homologous recombination event with sequences in the host cell genome does not result in the stable integration of the negatively selectable marker.
Markers useful for this purpose include the Herpes Simplex Virus thymidine kinase (TIC) gene or the bacterial xanthine-guanine phosphoribosyl-transferase (gpt) gene.
The gene targeting or gene activation techniques which can be used in accordance with this aspect of the invention are more particularly described in U.S.
Patent No. 5,272,071 to Chappel; U.S. Patent No. 5,578,461 to Sherwin et al.; International Application No.
PCT/US92/09627 (W093/09222) by Selden et al.; and International Application No.
PCT/LTS90/06436 (W091/06667) by Skoultchi et al., each of which is incorporated by reference herein in its entirety.
4.6 POLYPEPTIDES OF THE INVENTION
The isolated polypeptides of the invention include, but are not limited to, a polypeptide comprising: the amino acid sequences set forth as any one of SEQ
ID NO: 912-1822, or 2479-3134 or an amino acid sequence encoded by any one of the nucleotide sequences SEQ ID NO: 1-911, or 1823-2478 or the corresponding full length or mature protein. Polypeptides of the invention also include polypeptides preferably with biological or immunological activity that are encoded by: (a) a polynucleotide having any one of the nucleotide sequences set forth in SEQ ID NO: 1-911, or 1823-2478 or (b) polynucleotides encoding any one of the amino acid sequences set forth as SEQ ID NO: 912-1822, or 2479-3134 or (c) polynucleotides that hybridize to the complement of the polynucleotides of either (a) or (b) under stringent hybridization conditions. The invention also provides biologically active or immunologically active variants of any of the amino acid sequences set forth as SEQ ID NO: 912-1822, or 2479-3134 or the corresponding full length or mature protein; and "substantial equivalents" thereof (e.g., with at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, 86%, 87%, 88%, 89%, at least about 90%, 91%, 92%, 93%, 94%, typically at least about 95%, 96%, 97%, more typically at least about 98%, or most typically at least about 99% amino acid identity) that retain biological activity. Polypeptides encoded by allelic variants may have a similar, increased, or decreased activity compared to polypeptides comprising SEQ ID NO: 912-1822, or 3134.
Fragments of the proteins of the present invention which are capable of exhibiting biological activity are also encompassed by the present invention. Fragments of the protein may be in linear form or they may be cyclized using known methods, for example, as described in H. U. Saragovi, et al., Bio/Technology 10, 773-778 (1992) and in R. S.
McDowell, et al., J. Amer. Chern. Soc. 114, 9245-9253 (1992), both of which are incorporated herein by reference. Such fragments rnay be fused to carrier molecules such as immunoglobulins for many purposes, including increasing the valency of protein binding sites. Fragments are also identified in Tables 3A, 3B, 5, or 6.
The present invention also provides both full-length and mature forms (for example, without a signal sequence or precursor sequence) of the disclosed proteins.
The protein coding sequence is identified in the sequence listing by translation of the disclosed nucleotide sequences. The predicted signal sequence is set forth in Table 6.
The mature form of such protein may be obtained and confirmed by expression of a full-length polynucleotide in a suitable mammalian cell or other host cell and sequencing of the cleaved product. One of skill in the art will recognize that the actual cleavage site may be different than that predicted in Table 6. The sequence of the mature form of the protein is also determinable from the amino acid sequence of the full-length form. Where proteins of the present invention are membrane bound, soluble forms of the proteins are also provided. In such forms, part or all of the regions causing the proteins to be membrane bound are deleted so that the proteins are fully secreted from the cell in which they are expressed (See, e.g., Sakal et al., Prep. Biochem. Biotechnol. (2000), 30(2), pp. 107-23, incorporated herein by reference).
Protein compositions of the present invention rnay further comprise an acceptable Garner, such as a hydrophilic, e.g~., pharmaceutically acceptable, carrier.

The present invention further provides isolated polypeptides encoded by the nucleic acid fragments of the present invention or by degenerate variants of the nucleic acid fragments of the present invention. By "degenerate variant" is intended nucleotide fragments which differ from a nucleic acid fragment of the present invention (e.g., an ORF) by nucleotide sequence but, due to the degeneracy of the genetic code, encode an identical polypeptide sequence. Preferred nucleic acid fragments of the present invention are the ORFs that encode proteins.
A variety of methodologies known in the art can be utilized to obtain any one of the isolated polypeptides or proteins of the present invention. At the simplest level, the amino acid sequence can be synthesized using commercially available peptide synthesizers. The synthetically-constructed protein sequences, by virtue of sharing primary, secondary or tertiary structural and/or conformational characteristics with proteins may possess biological properties in common therewith, including protein activity. This technique is particularly useful in producing small peptides and fragments of larger polypeptides.
Fragments are useful, for example, in generating antibodies against the native polypeptide.
Thus, they may be employed as biologically active or immunological substitutes for natural, purified proteins in screening of therapeutic compounds and in immunological processes for the development of antibodies.
The polypeptides and proteins of the present invention can alternatively be purified from cells which have been altered to express the desired polypeptide or protein. As used herein, a cell is said to be altered to express a desired polypeptide or protein when the cell, through genetic manipulation, is made to produce a polypeptide or protein which it normally does not produce or which the cell normally produces at a lower level. One skilled in the art can readily adapt procedures for introducing and expressing either recombinant or synthetic sequences into eukaryotic or prokaryotic cells in order to generate a cell which produces one of the polypeptides or proteins of the present invention.
The invention also relates to methods for producing a polypeptide comprising growing a culture of host cells of the invention in a suitable culture medium, and purifying the protein from the cells or the culture in which the cells are grown. For example, the methods of the invention include a process for producing a polypeptide in which a host cell containing a suitable expression vector that includes a polynucleotide of the invention is cultured under conditions that allow expression of the encoded polypeptide.
The polypeptide can be recovered from the culture, conveniently from the culture medium, or from a lysate prepared from the host cells and further purified. Preferred embodiments include those in which the protein produced by such process is a full length or mature form of the protein.
In an alternative method, the polypeptide or protein is purified from bacterial cells 5 which naturally produce the polypeptide or protein. One skilled in the art can readily follow known methods for isolating polypeptides and proteins in order to obtain one of the isolated polypeptides or proteins of the present invention. These include, but are not limited to, immunochromatography, HPLC, size-exclusion chromatography, ion-exchange chromatography, and immuno-affinity chromatography. See, e.g., Scopes, P~oteih 10 Purification: Priizciples ahd Practice, Springer-Verlag (1994); Sambrook, et al., in Molecular Cloning: A LaboYatory Mah.ual; Ausubel et al., Cur~ef~t Protocols ira Moleculaf°
Biology. Polypeptide fragments that retain biological/immunological activity include fragments comprising greater than about 100 amino acids, or greater than about 200 amino acids, and fragments that encode specific protein domains.
15 The purified polypeptides can be used in ifa vitro binding assays which are well known in the art to identify molecules which bind to the polypeptides. These molecules include but are not limited to, for e.g., small molecules, molecules from combinatorial libraries, antibodies or other proteins. The molecules identified in the binding assay are then tested for antagonist or agonist activity in ifi. vivo tissue culture or animal models that are 20 well known in the art. In brief, the molecules are titrated into a plurality of cell cultures or animals and then tested for either cell/animal death or prolonged survival of the animal/cells.
In addition, the peptides of the invention or molecules capable of binding to the peptides may be complexed with toxins, e.g., ricin or cholera, or with other compounds that are toxic to cells. The toxin-binding molecule complex is then targeted to a tumor or other 25 cell by the specificity of the binding molecule for SEQ ID NO: 912-1822, or 2479-3134.
The protein of the invention may also be expressed as a product of transgenic animals, e.g., as a component of the milk of transgenic cows, goats, pigs, or sheep which are characterized by somatic or germ cells containing a nucleotide sequence encoding the protein.
30 The proteins provided herein also include proteins characterized by amino acid sequences similar to those of purified proteins but into which modification are naturally provided or deliberately engineered. For example, modifications, in the peptide or DNA
sequence, can be made by those skilled in the art using known techniques.
Modifications of interest in the protein sequences may include the alteration, substitution, replacement, insertion or deletion of a selected amino acid residue in the coding sequence.
For example, one or more of the cysteine residues may be deleted or replaced with another amino acid to alter the conformation of the molecule. Techniques for such alteration, substitution, replacement, insertion or deletion are well known to those skilled in the art (see, e.g., U.S.
Pat. No. 4,518,584). Preferably, such alteration, substitution, replacement, insertion or deletion retains the desired activity of the protein. Regions of the protein that are important for the protein function can be determined by various methods known in the art including the alanine-scanning method which involved systematic substitution of single or strings of amino acids with alanine, followed by testing the resulting alanine-containing variant for biological activity. This type of analysis determines the importance of the substituted amino acids) in biological activity. Regions of the protein that are important for protein function may be determined by the eMATRIX program.
Other fragments and derivatives of the sequences of proteins which would be expected to retain protein activity in whole or in part and are useful for screening or other immunological methodologies may also be easily made by those skilled in the art given the disclosures herein. Such modifications are encompassed by the present invention.
The protein may also be produced by operably linking the isolated polynucleotide of the invention to suitable control sequences in one or more insect expression vectors, and employing an insect expression system. Materials and methods for baculoviruslinsect cell expression systems are commercially available in kit form from, e.g., Invitrogen, San Diego, Cali~, U.S.A. (the MaxBatTM kit), and such methods are well known in the art, as described in Summers and Smith, Texas Agricultural Experiment Station Bulletin No. 1555 (1987), incorporated herein by reference. As used herein, an insect cell capable of expressing a polynucleotide of the present invention is "transformed."
The protein of the invention may be prepared by culturing transformed host cells under culture conditions suitable to express the recombinant protein. The resulting expressed protein may then be purified from such culture (i.e., from culture medium or cell extracts) using known purification processes, such as gel filtration and ion exchange chromatography. The purification of the protein may also include an affinity column containing agents which will bind to the protein; one or more column steps over such affinity resins as concanavalin A-agarose, heparin-toyopearlTM or Cibacrom blue 3GA
SepharoseTM;

one or more steps involving hydrophobic interaction chromatography using such resins as phenyl ether, butyl ether, or propyl ether; or immunoaffinity chromatography.
Alternatively, the protein of the invention may also be expressed in a form which will facilitate purification. For example, it rnay be expressed as a fusion protein, such as those of maltose binding protein (MBP), glutathione-S-transferase (GST) or thioredoxin (TRX), or as a His tag. Kits for expression and purification of such fusion proteins are commercially available from New England BioLab (Beverly, Mass.), Pharmacia (Piscataway, N.J.) and Invitrogen, respectively. The protein can also be tagged with an epitope and subsequently purified by using a specific antibody directed to such epitope. One such epitope ("FLAG~") is commercially available from Kodak (New Haven, Conn.).
Finally, one or more reverse-phase high performance liquid chromatography (RP-HPLC) steps employing hydrophobic RP-HPLC media, e.g., silica gel having pendant methyl or other aliphatic groups, can be employed to further purify the protein. Some or all of the foregoing purification steps, in various combinations, can also be employed to provide a substantially homogeneous isolated recombinant protein. The protein thus purified is substantially free of other mammalian proteins and is defined in accordance with the present invention as an "isolated protein."
The polypeptides of the invention include analogs (variants). This embraces fragments, as well as peptides in which one ormore amino acids has been deleted, inserted, or substituted. Also, analogs of the polypeptides of the invention embrace fusions of the polypeptides or modifications of the polypeptides of the invention, wherein the polypeptide or analog is fused to another moiety or moieties, e.g., targeting moiety or another therapeutic agent. Such analogs may exhibit improved properties such as activity and/or stability.
Examples of moieties which may be fused to the polypeptide or an analog include, for example, targeting moieties which provide for the delivery of polypeptide to pancreatic cells, e.g., antibodies to pancreatic cells, antibodies to immune cells such as T-cells, monocytes, dendritic cells, granulocytes, etc., as well as receptor and ligands expressed on pancreatic or immune cells. Other moieties which may be fused to the polypeptide include therapeutic agents which are used for treatment, for example, immunosuppressive drugs such as cyclosporin, SK506, azathioprine, CD3 antibodies and steroids. Also, polypeptides may be fused to immune modulators, and other cytokines such as alpha or beta interferon.

4.6.1 DETERMINING POLYPEPTIDE AND POLYNUCLEOTIDE
IDENTITY AND SIMILARITY
Preferred identity and/or similarity are designed to give the largest match between the sequences tested. Methods to determine identity and similarity are codified in computer programs including, but are not limited to, the GCG program package, including GAP
(Devereux, J., et al., Nucleic Acids Research 12(1):387 (1984); Genetics Computer Group, University of Wisconsin, Madison, WI), BLASTP, BLASTN, BLASTX, FASTA
(Altschul, S.F. et al., J. Molec. Biol. 215:403-410 (1990), PSI-BLAST (Altschul S.F. et al., Nucleic Acids Res. vol. 25, pp. 3389-3402, herein incorporated by reference), eMatrix software (Wu et al., J. Comp. Biol., Vol. 6, pp. 219-235 (1999), herein incorporated by reference), eMotif software (Nevill-Manning et al, ISMB-97, Vol. 4, pp. 202-209, herein incorporated by reference), Pfam software (Sonnhammer et al., Nucleic Acids Res., Vol. 26(1), pp. 320-322 (1998), herein incorporated by reference) and the Kyte-Doolittle hydrophobocity prediction algorithm (J. Mol Biol, 157, pp. 105-31 (1982), the GeneAtlas software (Molecular Simulations Inc. (MSI), San Diego, CA) (Sanchez and Sali (1998) Proc. Natl.
Acad. Sci., 95, 13597-13602; Kitson DH et al, (2000) "Remote homology detection using structural modeling - an evaluation" Submitted; Fischer and Eisenberg (1996) Protein Sci.
5, 947-955), Neural Network SignalP V1.1 program (from Center for Biological Sequence Analysis, The Technical University of Denmark) incorporated herein by reference).
Polypeptide sequences were examined by a proprietary algorithm, SeqLoc that separates the proteins into three sets of locales: intracellular, membrane, or secreted.
This prediction is based upon three characteristics of each polypeptide, including percentage of cysteine residues, Kyte-Doolittle scores for the first 20 amino acids of each protein, and Kyte-Doolittle scores to calculate the longest hydrophobic stretch of the said protein. Values of predicted proteins are compared against the values from a set of 592 proteins of known cellular localization from the Swissprot database (http://www.expas .~prot).
Predictions are based upon the maximum likelihood estimation.
Pesence of transmembrane regions) was detected using the TMpred program (htt~//www ch embnet or~/software/TMPRED form.html).
The BLAST programs are publicly available from the National Center for Biotechnology Information (NCBI) and other sources (BLAST Manual, Altschul, S., et al.
NCBI NLM NIH Bethesda, MD 20894; Altschul, S., et al., J. Mol. Biol. 215:403-(1990).

4.7 CHIMERIC AND FUSION PROTEINS
The invention also provides chimeric or fusion proteins. As used herein, a "chimeric protein" or "fusion protein" comprises a polypeptide of the invention operatively linked to another polypeptide. Within a fusion protein the polypeptide according to the invention can correspond to all or a portion of a protein according to the invention. In one embodiment, a fusion protein comprises at least one biologically active portion of a protein according to the invention. In another embodiment, a fusion protein comprises at least two biologically active portions of a protein according to the invention. Within the fusion protein, the term "operatively linked" is intended to indicate that the polypeptide according to the invention and the other polypeptide are fused in-frame to each other. The polypeptide can be fused to the N-terminus or C-terminus, or to the middle.
For example, in one embodiment a fusion protein comprises a polypeptide according to the invention operably linked to the extracellular domain of a second protein.
In another embodiment, the fusion protein is a GST-fusion protein in which the polypeptide sequences of the invention are fused to the C-terminus of the GST
(i.e., glutathione S-transferase) sequences.
In another embodiment, the fusion protein is an immunoglobulin fusion protein in which the polypeptide sequences according to the invention comprise one or more domains fused to sequences derived from a member of the immunoglobulin protein family.
The immunoglobulin fiision proteins of the invention can be incorporated into pharmaceutical compositions and administered to a subject to inhibit an interaction between a ligand and a protein of the invention on the surface of a cell, to thereby suppress signal transduction in vivo. The immunoglobulin fusion proteins can be used to affect the bioavailability of a cognate ligand. Inhibition of the ligand/protein interaction may be useful therapeutically for both the treatment of proliferative and differentiative disorders, e.g., cancer as well as modulating (e.g., promoting or inhibiting) cell survival. Moreover, the immunoglobulin fusion proteins of the invention can be used as immunogens to produce antibodies in a subject, to purify ligands, and in screening assays to identify molecules that inhibit the interaction of a polypeptide of the invention with a ligand.
A chimeric or fusion protein of the invention can be produced by standard recombinant DNA techniques. For example, DNA fragments coding for the different polypeptide sequences are ligated together in-frame in accordance with conventional techniques, e.g., by employing blunt-ended or stagger-ended termini for ligation, restriction enzyme digestion to provide for appropriate termini, filling-in of cohesive ends as appropriate, alkaline phosphatase treatment to avoid undesirable joining, and enzymatic ligation. In another embodiment, the fusion gene can be synthesized by conventional techniques including automated DNA synthesizers. Alternatively, PCR
amplification of gene fragments can be carried out using anchor primers that give rise to complementary 5 overhangs between two consecutive gene fragments that can subsequently be annealed and reamplified to generate a chimeric gene sequence (see, for example, Ausubel et al. (eds.) CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, 1992). Moreover, many expression vectors are commercially available that already encode a fusion moiety (e.g., a GST polypeptide). A nucleic acid encoding a polypeptide of the invention can be 10 cloned into such an expression vector such that the fusion moiety is linked in-frame to the protein of the invention.
4.8 GENE THERAPY
Mutations in the polynucleotides of the invention gene may result in loss of normal 15 function of the encoded protein. The invention thus provides gene therapy to restore normal activity of the polypeptides of the invention; or to treat disease states involving polypeptides of the invention. Delivery of a functional gene encoding polypeptides of the invention to appropriate cells is effected ex vivo, ifz situ, or irz vivo by use of vectors, and more particularly viral vectors (e.g., adenovirus, adeno-associated virus, or a retrovirus), or ex vivo 20 by use of physical DNA transfer methods (e.g., liposomes or chemical treatments). See, for example, Anderson, Nature, supplement to vol. 392, no. 6679, pp.25-20 (1998).
For additional reviews of gene therapy technology see Friedmann, Science, 244:

(1989); Verma, Scientific American: 68-84 (1990); and Miller, Nature, 357: 455-460 (1992).
Introduction of any one of the nucleotides of the present invention or a gene encoding the 25 polypeptides of the present invention can also be accomplished with extrachromosomal substrates (transient expression) or artificial chromosomes (stable expression). Cells may also be cultured ex vivo in the presence of proteins of the present invention in order to proliferate or to produce a desired effect on or activity in such cells.
Treated cells can then be introduced izz vivo for therapeutic purposes. Alternatively, it is contemplated that in other 30 human disease states, preventing the expression of or inhibiting the activity of polypeptides of the invention will be useful in treating the disease states. It is contemplated that antisense therapy or gene therapy could be applied to negatively regulate the expression of polypeptides of the invention.

Other methods inhibiting expression of a protein include the introduction of antisense molecules to the nucleic acids of the present invention, their complements, or their translated RNA sequences, by methods known in the art. Further, the polypeptides of the present invention can be inhibited by using targeted deletion methods, or the insertion of a negative regulatory element such as a silencer, which is tissue specific.
The present invention still further provides cells genetically engineered ih vivo to express the polynucleotides of the invention, wherein such polynucleotides are in operative association with a regulatory sequence heterologous to the host cell which drives expression of the polynucleotides in the cell. These methods can be used to increase or decrease the expression of the polynucleotides of the present invention.
Knowledge of DNA sequences provided by the invention allows for modification of cells to permit, increase, or decrease, expression of endogenous polypeptide.
Cells can be modified (e.g., by homologous recombination) to provide increased polypeptide expression by replacing, in whole or in part, the naturally occurring promoter with all or part of a heterologous promoter so that the cells express the protein at higher levels. The heterologous promoter is inserted in such a manner that it is operatively linked to the desired protein encoding sequences.
See, for example, PCT International Publication No. WO 94/12650, PCT
International Publication No. WO 92/20808, and PCT International Publication No. WO
91/09955. It is also contemplated that, in addition to heterologous promoter DNA, amplifiable marker DNA (e.g., ada, dhfr, and the multifunctional CAD gene which encodes carbamyl phosphate synthase, aspartate transcarbamylase, and dihydroorotase) and/or intron DNA may be inserted along with the heterologous promoter DNA. If linked to the desired protein coding sequence, amplification of the marker DNA by standard selection methods results in co-amplification of the desired protein coding sequences in the cells. ' In another embodiment of the present invention, cells and tissues may be engineered to express an endogenous gene comprising the polynucleotides of the invention under the control of inducible regulatory elements, in which case the regulatory sequences of the endogenous gene may be replaced by homologous recombination. As described herein, gene targeting can be used to replace a gene's existing regulatory region with a regulatory sequence isolated from a different gene or a novel regulatory sequence synthesized by genetic engineering methods.
Such regulatory sequences may be comprised of promoters, enhancers, scaffold-attachment regions, negative regulatory elements, transcriptional initiation sites, regulatory protein binding sites or combinations of said sequences. Alternatively, sequences which affect the structure or stability of the RNA or protein produced may be replaced, removed, added, or otherwise modified by targeting. These sequences include polyadenylation signals, mRNA
stability elements, splice sites, leader sequences for enhancing or modifying transport or secretion properties of the protein, or other sequences which alter or improve the fiznction or stability of protein or RNA molecules.
The targeting event may be a simple insertion of the regulatory sequence, placing the gene under the control of the new regulatory sequence, e.g., inserting a new promoter or enhancer or both upstream of a gene. Alternatively, the targeting event may be a simple deletion of a regulatory element, such as the deletion of a tissue-specific negative regulatory element. Alternatively, the targeting event may replace an existing element;
for example, a tissue-specific enhancer can be replaced by an enhancer that has broader or different cell-type specificity than the naturally occurring elements. Here, the naturally occurnng sequences are deleted and new sequences are added. In all cases, the identification of the targeting event may be facilitated by the use of one or more selectable marker genes that are contiguous with the targeting DNA, allowing for the selection of cells in which the exogenous DNA
has integrated into the cell genome. The identification of the targeting event may also be facilitated by the use of one or more marker genes exhibiting the property of negative selection, such that the negatively selectable marker is linked to the exogenous DNA, but configured such that the negatively selectable marker flanks the targeting sequence, and such that a correct homologous recombination event with'sequences in the host cell genome does not result in the stable integration of the negatively selectable marker. Markers useful for this purpose include the Herpes Simplex Virus thymidine kinase (TK) gene or the bacterial xanthine-guanine phosphoribosyl-transferase (gpt) gene.
The gene targeting or gene activation techniques which can be used in accordance with this aspect of the invention are more particularly described in U.S. Patent No. 5,272,071 to Chappel; U.S. Patent No. 5,578,461 to Sherwin et al.; International Application No.
PCT/US92/09627 (W093/09222) by Selden et al.; and International Application No.
PCT/LTS90/06436 (W091/06667) by Skoultchi et al., each of which is incorporated by reference herein in its entirety.
4.9 TIZANSGENIC ANIII~dALS
In preferred methods to determine biological functions of the polypeptides of the invention in vivo, one or more genes provided by the invention are either over expressed or inactivated in the germ line of animals using homologous recombination [Capecchi, Science 244:1288-1292 (1989)]. Animals in which the gene is over expressed, under the regulatory control of exogenous or endogenous promoter elements, are known as transgenic animals.
Animals in which an endogenous gene has been inactivated by homologous recombination are referred to as "knockout" animals. Knockout animals, preferably non-human mammals, can be prepared as described in U.S. Patent No. 5,557,032, incorporated herein by reference.
Transgenic animals are useful to determine the roles polypeptides of the invention play in biological processes, and preferably in disease states. Transgenic animals are useful as model systems to identify compounds that modulate lipid metabolism. Transgenic animals, preferably non-human mammals, are produced using methods as described in U.S.
Patent No 5,489,743 and PCT Publication No. W094/28122, incorporated herein by reference.
Transgenic animals can be prepared wherein all or part of a promoter of the polynucleotides of the invention is either activated or inactivated to alter the level of expression of the polypeptides of the invention. Inactivation can be carried out using homologous recombination methods described above. Activation can be achieved by supplementing or even replacing the homologous promoter to provide for increased protein expression. The homologous promoter can be supplemented by insertion of one or more heterologous enhancer elements known to confer promoter activation in a particular tissue.
The polynucleotides of the present invention also make possible the development, through, e.g., homologous recombination or knock out strategies, of animals that fail to express polypeptides of the invention or that express a variant polypeptide.
Such animals are useful as models for studying the ifa vivo activities of polypeptide as well as for studying modulators of the polypeptides of the invention.
In preferred methods to determine biological functions of the polypeptides of the invention iii vivo, one or more genes provided by the invention are either over expressed or inactivated in the germ line of animals using homologous recombination [Capecchi, Science 244:1288-1292 (1989)]. Animals in which the gene is over expressed, under the regulatory control of exogenous or endogenous promoter elements, are known as transgenic animals.
Animals in which an endogenous gene has been inactivated by homologous recombination are referred to as "knockout" animals. Knockout animals, preferably non-human mammals, can be prepared as described in U.S. Patent No. 5,557,032, incorporated herein by reference.
Transgenic animals are useful to determine the roles polypeptides of the invention play in biological processes, and preferably in disease states. Transgenic animals are useful as model systems to identify compounds that modulate lipid metabolism. Transgenic animals, preferably non-human mammals, are produced using methods as described in U.S.
Patent No 5,489,743 and PCT Publication No. W094/28122, incorporated herein by reference.
Transgenic animals can be prepared wherein all or part of the polynucleotides of the invention promoter is either activated or inactivated to alter the level of expression of the polypeptides of the invention. Inactivation can be carned out using homologous recombination methods described above. Activation can be achieved by supplementing or even replacing the homologous promoter to provide for increased protein expression. The homologous promoter can be supplemented by insertion of one or more heterologous enhancer elements known to confer promoter activation in a particular tissue.
4.10 USES AND BIOLOGICAL ACTIVITY
The polynucleotides and proteins of the present invention are expected to exhibit one or more of the uses or biological activities (including those associated with assays cited herein) identified herein. Uses or activities described for proteins of the present invention may be provided by administration or use of such proteins or of polynucleotides encoding such proteins (such as, for example, in gene therapies or vectors suitable for introduction of DNA). The mechanism underlying the particular condition or pathology will dictate whether the polypeptides of the invention, the polynucleotides of the invention or modulators (activators or inhibitors) thereof would be beneficial to the subject in need of treatment.
Thus, "therapeutic compositions of the invention" include compositions comprising isolated polynucleotides (including recombinant DNA molecules, cloned genes and degenerate variants thereof) or polypeptides of the invention (including full length protein, mature protein and truncations or domains thereof), or compounds and other substances that modulate the overall activity of the target gene products, either at the level of target gene/protein expression or target protein activity. Such modulators include polypeptides, analogs, (variants), including fragments and fusion proteins, antibodies and other binding proteins; chemical compounds that directly or indirectly activate or inhibit the polypeptides of the invention (identified, e.g., via drug screening assays as described herein); antisense polynucleotides and polynucleotides suitable for triple helix formation; and in particular antibodies or other binding partners that specifically recognize one or more epitopes of the polypeptides of the invention.

The polypeptides of the present invention may likewise be involved in cellular activation or in one of the other physiological pathways described herein.
4.10.1 RESEARCH USES AND UTILITIES
5 The polynucleotides provided by the present invention can be used by the research community for various purposes. The polynucleotides can be used to express recombinant protein for analysis, characterization or therapeutic use; as markers for tissues in which the corresponding protein is preferentially expressed (either constitutively or at a particular stage of tissue differentiation or development or in disease states); as molecular weight markers on 10 gels; as chromosome markers or tags (when labeled) to identify chromosomes or to map related gene positions; to compare with endogenous DNA sequences in patients to identify potential genetic disorders; as probes to hybridize and thus discover novel, related DNA
sequences; as a source of information to derive PCR primers for genetic fingerprinting; as a probe to "subtract-out" known sequences in the process of discovering other novel 15 polynucleotides; for selecting and making oligomers for attachment to a "gene chip" or other support, including for examination of expression patterns; to raise anti-protein antibodies using DNA immunization techniques; and as an antigen to raise anti-DNA
antibodies or elicit another immune response. Where the polynucleotide encodes a protein which binds or potentially binds to another protein (such as, for example, in a receptor-ligand interaction), 20 the polynucleotide can also be used in interaction trap assays (such as, for example, that described in Gyuris et al., Cell 75:791-803 (1993)) to identify polynucleotides encoding the other protein with which binding occurs or to identify inhibitors of the binding interaction.
The polypeptides provided by the present invention can similarly be used in assays to determine biological activity, including in a panel of multiple proteins for high-throughput 25 screening; to raise antibodies or to elicit another immune response; as a reagent (including the labeled reagent) in assays designed to quantitatively determine levels of the protein (or its receptor) in biological fluids; as markers for tissues in which the corresponding polypeptide is preferentially expressed (either constitutively or at a particular stage of tissue differentiation or development or in a disease state); and, of course, to isolate correlative 30 receptors or ligands. Proteins involved in these binding interactions can also be used to screen for peptide or small molecule inhibitors or agonists of the binding interaction.
Any or all of these research utilities are capable of being developed into reagent grade or kit format for commercialization as research products.

Methods for performing the uses listed above are well known to those skilled in the art. References disclosing such methods include without limitation "Molecular Cloning: A
Laboratory Manual", 2d ed., Cold Spring Harbor Laboratory Press, Sambrook, J., E. F.
Fritsch and T. Maniatis eds., 1989, and "Methods in Enzymology: Guide to Molecular Cloning Techniques", Academic Press, Bergen S. L. and A. R. Kimmel eds., 1987.
4.10.2 NUTRITIONAL USES
Polynucleotides and polypeptides of the present invention can also be used as nutritional sources or supplements. Such uses include without limitation use as a protein or amino acid supplement, use as a carbon source, use as a nitrogen source and use as a source of carbohydrate. In such cases the polypeptide or polynucleotide of the invention can be added to the feed of a particular organism or can be administered as a separate solid or liquid preparation, such as in the form of powder, pills, solutions, suspensions or capsules. In the case of microorganisms, the polypeptide or polynucleotide of the invention can be added to the medium in or on which the microorganism is cultured.
4.10.3 CYTOKINE AND CELL PROLIFERATION/DIFFERENTIATION
ACTIVITY
A polypeptide of the present invention may exhibit activity relating to cytokine, cell proliferation (either inducing or inhibiting) or cell differentiation (either inducing or inhibiting) activity or may induce production of other cytokines in certain cell populations.
A polynucleotide of the invention can encode a polypeptide exhibiting such attributes.
Many protein factors discovered to date, including all known cytokines, have exhibited activity in one or more factor-dependent cell proliferation assays, and hence the assays serve as a convenient confirmation of cytokine activity. The activity of therapeutic compositions of the present invention is evidenced by any one of a number of routine factor dependent cell proliferation assays for cell lines including, without limitation, 32,D, DA2, DA1G, T10, B9, , B9/11, BaF3, MC9/G, M+(preB M+), 2E8, RBS, DA1, 123, T1165, HT2, CTLL2, TF-1, Mo7e, CMK, HUVEC, and Caco. Therapeutic compositions of the invention can be used in the following:
Assays for T-cell or thyrnocyte proliferation include without limitation those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A. M.
Kruisbeek, D. H.
Margulies, E. M. Shevach, W. Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, Ira Vitro assays for Mouse Lymphocyte Function 3.1-3.19;
Chapter 7, Immunologic studies in Humans); Takai et al., J. Immunol. 137:3494-3500, 1986;
Bertagnolli et al., J. Immunol. 145:1706-1712, 1990; Bertagnolli et al., Cellular Immunology 133:327-341, 1991; Bertagnolli, et al., I. Immunol. 149:3778-3783, 1992;
Bowman et al., I.
Immunol. 152:1756-1761, 1994.
Assays for cytokine production and/or proliferation of spleen cells, lymph node cells or thymocytes include, without limitation, those described in: Polyclonal T
cell stimulation, Kruisbeek, A. M. and Shevach, E. M. In Current Protocols in Immunology. J. E.
e.a. Coligan eds. Vol 1 pp. 3.12.1-3.12.14, John Wiley and Sons, Toronto. 1994; and Measurement of mouse and human interleukin-'y, Schreiber, R. D. In Current Protocols in Immunology. J. E.
e.a. Coligan eds. Vol 1 pp. 6.8.1-6.8.8, John Wiley and Sons, Toronto. 1994.
Assays for proliferation and differentiation of hematopoietic and lymphopoietic cells include, without limitation, those described in: Measurement of Human and Murine Interleukin 2 and Interleukin 4, Bottornly, K., Davis, L. S. and Lipsky, P. E.
In Current Protocols in Immunology. J. E. e.a. Coligan eds. Vol 1 pp. 6.3.1-6.3.12, John Wiley and Sons, Toronto. 1991; deVries et al., J. Exp. Med. 173:1205-1211, 1991; Moreau et al., Nature 336:690-692, 1988; Greenberger et al., Proc. Natl. Acad. Sci. U.S.A.
80:2931-2938, 1983; Measurement of mouse and human interleukin 6--Nordan, R. In Current Protocols in Immunology. J. E. Coligan eds. Vol 1 pp. 6.6.1-6.6.5, John Wiley and Sons, Toronto. 1991;
Smith et al., Proc. Natl. Aced. Sci. U.S.A. 83:1857-1861, 1986; Measurement of human Interleukin 11--Bennett, F., Giannotti, J., Clark, S. C. and Turner, K. J. In Current Protocols in Immunology. J. E. Coligan eds. Vol 1 pp. 6.15.1 John Wiley and Sons, Toronto. 1991;
Measurement of mouse and human Interleukin 9--Ciarletta, A., Giannotti, J., Clark, S. C.
and Turner, K. J. In Current Protocols in Immunology. J. E. Coligan eds. Vol 1 pp. 6.13.1, John Wiley and Sons, Toronto. 1991.
Assays for T-cell clone responses to antigens (which will identify, among others, proteins that affect APC-T cell interactions as well as direct T-cell effects by measuring proliferation and cytokine production) include, without limitation, those described in:
Current Protocols in Immunology, Ed by J. E. Coligan, A. M. Kruisbeek, D. H.
Margulies, E. M. Shevach, W Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function; Chapter 6, Cytokines and their cellular receptors; Chapter 7, Immunologic studies in Humans); Weinberger et al., Proc.
Natl. Acad. Sci. USA 77:6091-6095, 1980; Weinberger et al., Eur. J. Immun.
11:405-411, 1981; Takai et al., J. Immunol. 137:3494-3500, 1986; Takai et al., J. Immunol.
140:508-512, 1988.
4.10.4 STEM CELL GROWTH FACTOR ACTIVITY
A polypeptide of the present invention may exhibit stem cell growth factor activity and be involved in the proliferation, differentiation and survival of pluripotent and totipotent stem cells including primordial germ cells, embryonic stem cells, hematopoietic stem cells and/or germ line stem cells. Administration of the polypeptide of the invention to stem cells iya vivo or ex vivo is expected to maintain and expand cell populations in a totipotential or pluripotential state which would be useful for re-engineering damaged or diseased tissues, transplantation, manufacture of bio-pharmaceuticals and the development of bio-sensors.
The ability to produce large quantities of human cells has important working applications for the production of human proteins which currently must be obtained from non-human sources or donors, implantation of cells to treat diseases such as Parkinson's, Alzheimer's and other neurodegenerative diseases; tissues for grafting such as bone marrow, skin, cartilage, tendons, bone, muscle (including cardiac muscle), blood vessels, cornea, neural cells, gastrointestinal cells and others; and organs for transplantation such as kidney, liver, pancreas (including islet cells), heart and lung.
It is contemplated that multiple different exogenous growth factors and/or cytokines may be administered in combination with the polypeptide of the invention to achieve the desired effect, including any of the growth factors listed herein, other stem cell maintenance factors, and specifically including stem cell factor (SCF), leukemia inhibitory factor (LIF), Flt-3 ligand (Flt-3L), any of the interleukins, recombinant soluble IL-6 receptor fused to IL-6, macrophage inflammatory protein 1-alpha (MIP-1-alpha), G-CSF, GM-CSF, thrombopoietin (TPQ), platelet factor 4 (PF-4), platelet-derived growth factor (PDGF), neural growth factors and basic fibroblast growth factor (bFGF).
Since totipotent stem cells can give rise to virtually any mature cell type, expansion of these cells in culture will facilitate the production of large quantities of mature cells.
Techniques for culturing stem cells are known in the art and administration of polypeptides of the invention, optionally with other growth factors and/or cytokines, is expected to enhance the survival and proliferation of the stem cell populations. This can be accomplished by direct administration of the polypeptide of the invention to the culture medium. Alternatively, stroma cells transfected with a polynucleotide that encodes for the polypeptide of the invention can be used as a feeder layer for the stem cell populations in culture or in vivo. Stromal support cells for feeder layers may include embryonic bone marrow fibroblasts, bone marrow stromal cells, fetal liver cells, or cultured embryonic fibroblasts (see U.S. Patent No. 5,690,926).
Stem cells themselves can be transfected with a polynucleotide of the invention to induce autocrine expression of the polypeptide of the invention. This will allow for generation of undifferentiated totipotential/pluripotential stem cell lines that are useful as is or that can then be differentiated into the desired mature cell types. These stable cell lines can also serve as a source of undifferentiated totipotential/pluripotential mRNA to create cDNA libraries and templates for polymerase chain reaction experiments. These studies would allow for the isolation and identification of differentially expressed genes in stem cell populations that regulate stem cell proliferation and/or maintenance.
Expansion and maintenance of totipotent stem cell populations will be useful in the treatment of many pathological conditions. For example, polypeptides of the present invention may be used to manipulate stem cells in culture to give rise to neuroepithelial cells that can be used to augment or replace cells damaged by illness, autoimmune disease, accidental damage or genetic disorders. The polypeptide of the invention may be useful for inducing the proliferation of neural cells and for the regeneration of nerve and brain tissue, i.e. for the treatment of central and peripheral nervous system diseases and neuropathies, as well as mechanical and traumatic disorders which involve degeneration, death or trauma to neural cells or nerve tissue. In addition, the expanded stem cell populations can also be genetically altered for gene therapy purposes and to decrease host rejection of replacement tissues after grafting or implantation.
Expression of the polypeptide of the invention and its effect on stem cells can also be manipulated to achieve controlled differentiation of the stem cells into more differentiated cell types. A broadly applicable method of obtaining pure populations of a specific differentiated cell type from undifferentiated stem cell populations involves the use of a cell-type specific promoter driving a selectable marker. The selectable marker allows only cells of the desired type to survive. For example, stem cells can be induced to differentiate into cardiomyocytes (Wobus et al., Differentiation, 48: 173-182, (1991); Klug et al., J. Clin.
Invest., 98(1): 216-224, (1998)) or skeletal muscle cells (Browder, L. W. In:
Principles of Tissue Engiraee~ihg eds. Lanza et al., Academic Press (1997)). Alternatively, directed differentiation of stem cells can be accomplished by culturing the stem cells in the presence of a differentiation factor such as retinoic acid and an antagonist of the polypeptide of the invention which would inhibit the effects of endogenous stem cell factor activity and allow differentiation to proceed.
Ira vitro cultures of stem cells can be used to determine if the polypeptide of the 5 invention exhibits stem cell growth factor activity. Stem cells are isolated from any one of various cell sources (including hematopoietic stem cells and embryonic stem cells) and cultured on a feeder layer, as described by Thompson et al. Proc. Natl. Acad.
Sci, U.S.A., 92: 7844-7848 (1995), in the presence of the polypeptide of the invention alone or in combination with other growth factors or cytokines. The ability of the polypeptide of the 10 invention to induce stem cells proliferation is determined by colony formation on semi-solid support e.g. as described by Bernstein et al., Blood, 77: 2316-2321 (1991).
4.10.5 HEMATOPOIESIS REGULATING ACTIVITY
A polypeptide of the present invention may be involved in regulation of 15 hematopoiesis and, consequently, in the treatment of myeloid or lymphoid cell disorders.
Even marginal biological activity in support of colony forming cells or of factor-dependent cell lines indicates involvement in regulating hematopoiesis, e.g. in supporting the growth and proliferation of erythroid progenitor cells alone or in combination with other cytokines, thereby indicating utility, for example, in treating various anemias or for use in conjunction 20 with irradiation/chemotherapy to stimulate the production of erythroid precursors and/or erythroid cells; in supporting the growth and proliferation of myeloid cells such as granulocytes and monocytes/macrophages (i.e., traditional CSF activity) useful, for example, in conjunction with chemotherapy to prevent or treat consequent myelo-suppression; in supporting the growth and proliferation of megakaryocytes and consequently of platelets 25 thereby allowing prevention or treatment of various platelet disorders such as thrombocytopenia, and generally for use in place of or complimentary to platelet transfusions; and/or in supporting the growth and proliferation of hematopoietic stem cells which are capable of maturing to any and all of the above-mentioned hematopoietic cells and therefore find therapeutic utility in various stem cell disorders (such as those usually treated 30 with transplantation, including, without limitation, aplastic anemia and paroxysmal nocturnal hemoglobinuria), as well as in repopulating the stem cell compartment post irradiation/chemotherapy, either ira-vivo or ex-vivo (i.e., in conjunction with bone marrow transplantation or with peripheral progenitor cell transplantation (homologous or heterologous)) as normal cells or genetically manipulated for gene therapy.
Therapeutic compositions of the invention can be used in the following:
Suitable assays for proliferation and differentiation of various hematopoietic lines are cited above.
Assays for embryonic stem cell differentiation (which will identify, among others, proteins that influence embryonic differentiation hematopoiesis) include, without limitation, those described in: Johansson et al. Cellular Biology 15:141-151, 1995; Keller et al., Molecular and Cellular Biology 13:473-486, 1993; McClanahan et al., Blood 81:2903-2915, 1993.
Assays for stem cell survival and differentiation (which will identify, among others, proteins that regulate lympho-hematopoiesis) include, without limitation, those described in:
Methylcellulose colony forming assays, Freshney, M. G. In Culture of Hematopoietic Cells.
R. I. Freshney, et al. eds. Vol pp. 265-268, Wiley-Liss, Inc., New York, N.Y.
1994;
Hirayama et al., Proc. Natl. Acad. Sci. USA 89:5907-5911, 1992; Primitive hematopoietic colony fornling cells with high proliferative potential, McNiece, I. K. and Briddell, R. A. In Culture of Hematopoietic Cells. R. I. Freshney, et al. eds. Vol pp. 23-39, Wiley-Liss, Inc., New York, N.Y. 1994; Neben et al., Experimental Hematology 22:353-359, 1994;
Cobblestone area forming cell assay, Ploemacher, R. E. In Culture of Hematopoietic Cells.
R. I. Freshney, et al. eds. Vol pp. 1-21, Wiley-Liss, Inc., New York, N.Y.
1994; Long term bone marrow cultures in the presence of stromal cells, Spooncer, E., Dexter, M. and Allen, T. In Culture of Hematopoietic Cells. R. I. Freshney, et al. eds. Vol pp. 163-179, Wiley-Liss, Inc., New York, N.Y. 1994; Long term culture initiating cell assay, Sutherland, H. J. In Culture of Hematopoietic Cells. R. I. Freshney, et al. eds. Vol pp. 139-162, Wiley-Liss, Inc., New York, N.Y. 1994.
4.10.6 TISSUE GROWTH ACTIVITY
A polypeptide of the present invention also may be involved in bone, cartilage, tendon, ligament and/or nerve tissue growth or regeneration, as well as in wound healing and tissue repair and replacement, and in healing of burns, incisions and ulcers.
A polypeptide of the present invention which induces cartilage and/or bone growth in circumstances where bone is not normally formed, has application in the healing ofbone fractures and cartilage damage or defects in humans and other animals.
Compositions of a polypeptide, antibody, binding partner, or other modulator of the invention may have prophylactic use in closed as well as open fracture reduction and also in the improved fixation of artificial joints. De novo bone formation induced by an osteogenic agent contributes to the repair of congenital, trauma induced, or oncologic resection induced craniofacial defects, and also is useful in cosmetic plastic surgery.
A polypeptide of this invention may also be involved in attracting bone-forming cells, stimulating growth of bone-forming cells, or inducing differentiation of progenitors of bone-forming cells. Treatment of osteoporosis, osteoarthritis, bone degenerative disorders, or periodontal disease, such as through stimulation of bone and/or cartilage repair or by blocking inflammation or processes of tissue destruction (collagenase activity, osteoclast activity, etc.) mediated by inflammatory processes may also be possible using the composition of the invention.
Another category of tissue regeneration activity that may involve the polypeptide of the present invention is tendon/ligament formation. Induction of tendon/ligarnent-like tissue or other tissue formation in circumstances where such tissue is not normally formed, has application in the healing of tendon or ligament tears, deformities and other tendon or ligament defects in humans and other animals. Such a preparation employing a tendon/ligament-like tissue inducing protein may have prophylactic use in preventing damage to tendon or ligament tissue, as well as use in the improved fixation of tendon or ligament to bone or other tissues, and in repairing defects to tendon or ligament tissue. De novo tendon/ligament-like tissue formation induced by a composition of the present invention contributes to the repair of congenital, trauma induced, or other tendon or ligament defects of other origin, and is also useful in cosmetic plastic surgery for attachment or repair of tendons or ligaments. The compositions of the present invention may provide environment to attract tendon- or ligament-forming cells, stimulate growth of tendon- or ligament-forming cells, induce differentiation of progenitors of tendon- or ligament-forming cells, or induce growth of tendon/ligament cells or progenitors ex vzvo for return ifa vivo to effect tissue repair. The compositions of the invention may also be useful in the treatment of tendinitis, carpal tunnel syndrome and other tendon or ligament defects. The compositions may also include an appropriate matrix and/or sequestering agent as a carrier as is well known in the art.
The compositions of the present invention may also be useful for proliferation of neural cells and for regeneration of nerve and brain tissue, i.e. for the treatment of central and peripheral nervous system diseases and neuropathies, as well as mechanical and traumatic disorders, which involve degeneration, death or trauma to neural cells or nerve tissue. More specifically, a composition may be used in the treatment of diseases of the peripheral nervous system, such as peripheral nerve injuries, peripheral neuropathy and localized neuropathies, and central nervous system diseases, such as Alzheimer's, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and Shy-Drager syndrome. Further conditions which may be treated in accordance with the present invention include mechanical and traumatic disorders, such as spinal cord disorders, head trauma and cerebrovascular diseases such as stroke. Peripheral neuropathies resulting from chemotherapy or other medical therapies may also be treatable using a composition of the invention.
Compositions of the invention may also be useful to promote better or. faster closure of non-healing wounds, including without limitation pressure ulcers, ulcers associated with vascular insufficiency, surgical and traumatic wounds, and the like.
Compositions of the present invention may also be involved in the generation or regeneration of other tissues, such as organs (including, for example, pancreas, liver, intestine, kidney, skin, endothelium), muscle (smooth, skeletal or cardiac) and vascular (including vascular endothelium) tissue, or for promoting the growth of cells comprising such tissues. Part of the desired effects may be by inhibition or modulation of fibrotic scarring may allow normal tissue to regenerate. A polypeptide of the present invention may also exhibit angiogenic activity.
A composition of the present invention may also be useful for gut protection or regeneration and treatment of lung or liver fibrosis, reperfusion injury in various tissues, and conditions resulting from systemic cytokine damage.
A composition of the present invention may also be useful for promoting or inhibiting differentiation of tissues described above from precursor tissues or cells; or for inhibiting the growth of tissues described above.
Therapeutic compositions of the invention can be used in the following:
Assays for tissue generation activity include, without limitation, those described in:
International Patent Publication No. WO95116035 (bone, cartilage, tendon);
International Patent Publication No. W095/05846 (nerve, neuronal); International Patent Publication No.
W091/07491 (skin, endothelium).

Assays for wound healing activity include, without limitation, those described in:
Winter, Epidermal Wound Healing, pps. 71-112 (Maibach, H. I. and Rovee, D. T., eds.), Year Book Medical Publishers, Inc., Chicago, as modified by Eaglstein and Mertz, J. Invest.
Dermatol 71:32-~4 (1970.
4.10.7 IMMUNE STIMULATING OR SUPPRESSING ACTIVITY
A polypeptide of the present invention may also exhibit immune stimulating or immune suppressing activity, including without limitation the activities for which assays are described herein. A polynucleotide of the invention can encode a polypeptide exhibiting such activities. A protein may be useful in the treatment of various immune deficiencies and disorders (including severe combined immunode~ciency (SCID)), e.g., in regulating (up or down) growth and proliferation of T and/or B lymphocytes, as well as effecting the cytolytic activity of NK cells and other cell populations. These immune deficiencies may be genetic or be caused by viral (e.g., HIV) as well as bacterial or fungal infections, or may result from autoimmune disorders. More specifically, infectious diseases causes by viral, bacterial, fungal or other infection may be treatable using a protein of the present invention, including infections by HIV, hepatitis viruses, herpes viruses, mycobacteria, Leishmania spp., malaria spp. and various fungal infections such as candidiasis. Of course, in this regard, proteins of the present invention may also be useful where a boost to the immune system generally may be desirable, i.e., in the treatment of cancer.
Autoimmune disorders which may be treated using a protein of the present invention include, for example, connective tissue disease, multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, autoimmune pulmonary inflammation, Guillain-Barre syndrome, autoimmune thyroiditis, insulin dependent diabetes mellitis, myasthenia gravis, graft-versus-host disease and autoimrnune inflammatory eye disease. Such a protein (or antagonists thereof, including antibodies) of the present invention may also to be useful in the treatment of allergic reactions and conditions (e.g., anaphylaxis, serum sickness, drug reactions, food allergies, insect venom allergies, mastocytosis, allergic rhinitis, hypersensitivity pneumonitis, urticaria, angioedema, eczema, atopic dermatitis, allergic contact dermatitis, erythema multiforme, Stevens-Johnson syndrome, allergic conjunctivitis, atopic keratoconjunctivitis, venereal keratoconjunctivitis, giant papillary conjunctivitis and contact allergies), such as asthma (particularly allergic asthma) or other respiratory problems. Other conditions, in which immune suppression is desired (including, for , example, organ transplantation), may also be treatable using a protein (or antagonists thereof) of the present invention. The therapeutic effects of the polypeptides or antagonists thereof on allergic reactions can be evaluated by in vivo animals models such as the cumulative contact enhancement test (Lastbom et al., Toxicology 125: 59-66, 1998), skin 5 prick test (Hoffinann et al., Allergy 54: 446-54, 1999), guinea pig skin sensitization test (Vohr et al., Arch. ~'oxocol. 73: 501-9), and murine local lymph node assay (Limber et al., J. Toxicol. Environ. Health 53: 563-79).
Using the proteins of the invention it may also be possible to modulate immune responses, in a number of ways. Down regulation may be in the form of inhibiting or 10 blocking an immune response already in progress or may involve preventing the induction of an immune response. The functions of activated T cells may be inhibited by suppressing T
cell responses or by inducing specific tolerance in T cells, or both.
Immunosuppression of T
cell responses is generally an active, non-antigen-specific, process which requires continuous exposure of~the T cells to the suppressive agent. Tolerance, which involves inducing 15 non-responsiveness or anergy in T cells, is distinguishable from immunosuppression in that it is generally antigen-specific and persists after exposure to the tolerizing agent has ceased.
Operationally, tolerance can be demonstrated by the lack of a T cell response upon reexposure to specific antigen in the absence of the tolerizing agent.
Down regulating or preventing one or more antigen functions (including without 20 limitation B lymphocyte antigen functions (such as, for example, B7)), e.g., preventing high level lymphokine synthesis by activated T cells, will be useful in situations of tissue, skin and organ transplantation and in graft-versus-host disease (GVHD). For example, blockage of T cell function should result in reduced tissue destruction in tissue transplantation.
Typically, in tissue transplants, rejection of the transplant is initiated through its recognition 25 as foreign by T cells, followed by an immune reaction that destroys the transplant. The administration of a therapeutic composition of the invention may prevent cytokine synthesis by immune cells, such as T cells, and thus acts as an immunosuppressant.
Moreover, a lack of costimulation may also be sufficient to anergize the T cells, thereby inducing tolerance in a subject. Induction of long-term tolerance by B lymphocyte antigen-blocking reagents may 30 avoid the necessity of repeated administration of these blocking reagents.
To achieve sufficient immunosuppression or tolerance in a subject, it may also be necessary to block the function of a combination of B lymphocyte antigens.

The efficacy of particular therapeutic compositions in preventing organ transplant rejection or GVHD can be assessed using animal models that are predictive of efficacy in humans. Examples of appropriate systems which can be used include allogeneic cardiac grafts in rats and xenogeneic pancreatic islet cell grafts in mice, both of which have been used to examine the immunosuppressive effects of CTLA4Ig fusion proteins in vivo as described in Lenschow et al., Science 257:789-792 (1992) and Turka et al., Proc. Natl. Acad.
Sci USA, 89:11102-11105 (1992). In addition, marine models of GVHD (see Paul ed., Fundamental Immunology, Raven Press, New York, 1989, pp. 846-847) can be used to determine the effect of therapeutic compositions of the invention on the development of that disease.
Blocking antigen function may also be therapeutically useful for treating autoimmune diseases. Many autoimmune disorders are the result of inappropriate activation of T cells that are reactive against self tissue and which promote the production of cytokines and autoantibodies involved in the pathology of the diseases. Preventing the activation of autoreactive T cells may reduce or eliminate disease symptoms. Administration of reagents which block stimulation of T cells can be used to inhibit T cell activation and prevent production of autoantibodies or T cell-derived cytokines which may be involved in the disease process. Additionally, blocking reagents may induce antigen-specific tolerance of autoreactive T cells which could lead to long-term relief from the disease.
The efftcacy of blocking reagents in preventing or alleviating autoimmune disorders can be determined using a number of well-characterized animal models of human autoimmune diseases.
Examples include marine experimental autoimmune encephalitis, systemic lupus erythmatosis in MRL/lpr/lpr mice or NZB hybrid mice, marine autoimmune collagen arthritis, diabetes mellitus in NOD mice and BB rats, and marine experimental myasthenia gravis (see Paul ed., Fundamental Immunology, Raven Press, New York, 1989, pp.
840-856).
Upregulation of an antigen function (e.g., a B lymphocyte antigen function), as a means of up regulating immune responses, may also be useful in therapy.
Upregulation of immune responses may be in the form of enhancing an existing immune response or eliciting an initial immune response. For example, enhancing an immune response may be useful in cases of viral infection, including systemic viral diseases such as influenza, the common cold, and encephalitis.

Alternatively, anti-viral immune responses may be enhanced in an infected patient by removing T cells from the patient, costimulating the T cells in vitro with viral antigen-pulsed APCs either expressing a peptide of the present invention or together with a stimulatory form of a soluble peptide of the present invention and reintroducing the in vitro activated T
cells into the patient. Another method of enhancing anti-viral immune responses would be to isolate infected cells from a patient, transfect them with a nucleic acid encoding a protein of the present invention as described herein such that the cells express all or a portion of the protein on their surface, and reintroduce the transfected cells into the patient. The infected cells would now be capable of delivering a costimulatory signal to, and thereby activate, T
cells in vivo.
A polypeptide of the present invention may provide the necessary stimulation signal to T cells to induce a T cell mediated immune response against the transfected tumor cells.
In addition, tumor cells which lack MHC class I or MHC class II molecules, or which fail to reexpress sufficient mounts of MHC class I or MHC class II molecules, can be transfected with nucleic acid encoding all or a portion of (e.g., a cytoplasmic-domain truncated portion) of an MHC class I alpha chain protein and [32 microglobulin protein or an MHC
class II
alpha chain protein and an MHC class II beta chain protein to thereby express MHC class I
or MHC class II proteins on the cell surface. Expression of the appropriate class I or class II
MHC in conjunction with a peptide having the activity of a B lymphocyte antigen (e.g., B7-1, B7-2, B7-3) induces a T cell mediated immune response against the transfected tumor cell. Optionally, a gene encoding an antisense construct which blocks expression of an MHC
class II associated protein, such as the invariant chain, can also be cotransfected with a DNA
encoding a peptide having the activity of a B lymphocyte antigen to promote presentation of tumor associated antigens and induce tumor specific immunity. Thus, the induction of a T
cell mediated immune response in a human subject may be sufEcient to overcome tumor-specific tolerance in the subject.
The activity of a protein of the invention may, among other means, be measured by the following methods:
Suitable assays for thymocyte or splenocyte cytotoxicity include, without limitation, those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A.
M. Kruisbeek, D. H. Margulies, E. M. Shevach, W. Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19;
Chapter 7, Immunologic studies in Humans); Hemnann et al., Proc. Natl. Acad.
Sci. USA

78:2488-2492, 1981; Herrmann et al., J. Immunol. 128:1968-1974, 1982; Handa et al., J.
Immunol. 135:1564-1572, 1985; Takai et al., I. Immunol. 137:3494-3500, 1986;
Takai et al., J. Immunol. 140:508-512, 1988; Bowman et al., J. Virology 61:1992-1998;
Bertagnolli et al., Cellular Immunology 133:327-341, 1991; Brown et al., J. Immunol. 153:3079-3092, 1994.
Assays for T-cell-dependent immunoglobulin responses and isotype switching (which will identify, among others, proteins that modulate T-cell dependent antibody responses and that affect Thl/Th2 profiles) include, without limitation, those described in:
Maliszewski, J. Immunol. 144:3028-3033, 1990; and Assays for B cell function:
In vitro antibody production, Mond, J. J. and Brunswick, M. In Current Protocols in Immunology. J.
E. e.a. Coligan eds. Vol 1 pp. 3.8.1-3.8.16, John Wiley and Sons, Toronto.
1994.
Mixed lymphocyte reaction (MLR) assays (which will identify, among others, proteins that generate predominantly Thl and CTL responses) include, without limitation, those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A.
M. Kruisbeek, D. H. Margulies, E. M. Shevach, W. Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19;
Chapter 7, Immunologic studies in Humans); Takai et al., J. Immunol. 137:3494-3500, 1986;
Takai et al., J. Immunol. 140:508-512, 1988; Bertagnolli et al., J. Immunol.
149:3778-3783, 1992.
Dendritic cell-dependent assays (which will identify, among others, proteins expressed by dendritic cells that activate naive T-cells) include, without limitation, those described in: Guery et al., J. Immunol. 134:536-544, 1995; Inaba et al., Journal of Experimental Medicine 173:549-559, 1991; Macatonia et al., Journal of Immunology 154:5071-5079, 1995; Porgador et al., Journal of Experimental Medicine 182:255-260, 1995; Nair et al., Journal of Virology 67:4062-4069, 1993; Huang et al., Science 264:961-965, 1994; Macatonia et al., Journal of Experimental Medicine 169:1255-1264, 1989; Bhardwaj et al., Journal of Clinical Investigation 94:797-807, 1994; and Inaba et al., Journal of Experimental Medicine 172:631-640, 1990.
Assays for lymphocyte survival/apoptosis (which will identify, among others, proteins that prevent apoptosis after superantigen induction and proteins that regulate lymphocyte homeostasis) include, without limitation, those described in:
Darzynkiewicz et al., Cytometry 13:795-808, 1992; Gorczyca et al., Leukemia 7:659-670, 1993;
Gorczyca et al., Cancer Research 53:1945-1951, 1993; Itoh et al., Cell 66:233-243, 1991;
Zacharchuk, Journal of Immunology 145:4037-4045, 1990; Zamai et al., Cytometry 14:891-897, 1993;
Gorczyca et al., International Journal of Oncology 1:639-648, 1992.
Assays for proteins that influence early steps of T-cell commitment and development include, without limitation, those described in: Antica et al., Blood 84:111-117, 1994; Fine et al., Cellular Immunology 155:111-122, 1994; Galy et al., Blood 85:2770-2778, 1995;
Toki et al., Proc. Nat. Acad Sci. USA 88:7548-7551, 1991.
4.10.8 ACTIVIN/INHIBIN ACTIVITY
A polypeptide of the present invention may also exhibit activin- or inhibin-related activities. A polynucleotide of the invention may encode a polypeptide exhibiting such characteristics. Inhibins are characterized by their ability to inhibit the release of follicle stimulating hormone (FSH), while activins and are characterized by their ability to stimulate the release of follicle stimulating hormone (FSH). Thus, a polypeptide of the present invention, alone or in heterodimers with a member of the inhibin family, may be useful as a contraceptive based on the ability of inhibins to decrease fertility in female mammals and decrease spermatogenesis in male mammals. Administration of sufficient amounts of other inhibins can induce infertility in these mammals. Alternatively, the polypeptide of the invention, as a homodimer or as a heterodimer with other protein subunits of the inhibin group, may be useful as a fertility inducing therapeutic, based upon the ability of activin molecules in stimulating FSH release from cells of the anterior pituitary.
See, for example, U.S. Pat. No. 4,798,885. A polypeptide of the invention may also be useful for advancement of the onset of fertility in sexually immature mammals, so as to increase the lifetime reproductive performance of domestic animals such as, but not limited to, cows, sheep and pigs.
'The activity of a polypeptide of the invention may, among other means, be measured by the following methods.
Assays for activin/inhibin activity include, without limitation, those described in:
Vale et al., Endocrinology 91:562-572, 1972; Ling et al., Nature 321:779-782, 1986; Vale et al., Nature 321:776-779, 1986; Mason et al., Nature 318:659-663, 1985; Forage et al., Proc.
Natl. Acad. Sci. USA 83:3091-3095, 1986.
4.10.9 CHEMOTACTIC/CHEMOKINETIC ACTIVITY

A polypeptide of the present invention may be involved in chemotactic or chemokinetic activity for mammalian cells, including, for example, monocytes, fibroblasts, neutrophils, T-cells, mast cells, eosinophils, epithelial and/or endothelial cells. A
polynucleotide of the invention can encode a polypeptide exhibiting such attributes.
5 Chemotactic and chemokinetic receptor activation can be used to mobilize or attract a desired cell population to a desired site of action. Chemotactic or chemokinetic compositions (e.g. proteins, antibodies, binding partners, or modulators of the invention) provide particular advantages in treatment of wounds and other trauma to tissues, as well as in treatment of localized infections. For example, attraction of lymphocytes, monocytes or neutrophils to 10 tumors or sites of infection may result in improved immune responses against the tumor or infecting agent.
A protein or peptide has chemotactic activity for a particular cell population if it can stimulate, directly or indirectly, the directed orientation or movement of such cell population. Preferably, the protein or peptide has the ability to directly stimulate directed 15 movement of cells. Whether a particular protein has chemotactic activity for a population of cells can be readily determined by employing such protein or peptide in any known assay for cell chemotaxis.
Therapeutic compositions of the invention can be used in the following:
Assays for chemotactic activity (which will identify proteins that induce or prevent 20 chemotaxis) consist of assays that measure the ability of a protein to induce the migration of cells across a membrane as well as the ability of a protein to induce the adhesion of one cell population to another cell population. Suitable assays for movement and adhesion include, without limitation, those described in: Current Protocols in Immunology, Ed by J. E.
Coligan, A. M. I~ruisbeek, D. H. Marguiles, E. M. Shevach, W. Strober, Pub.
Greene 25 Publishing Associates and Wiley-Interscience (Chapter 6.12, Measurement of alpha and beta Chemokines 6.12.1-6.12.28; Taub et al. J. Clin. Invest. 95:1370-1376, 1995;
Lind et al.
APMIS 103:140-146, 1995; Muller et al Eur. J. Immunol. 25:1744-1748; Gruber et al. J. of Immunol. 152:5860-5867, 1994; Johnston et al. J. of Immunol. 153:1762-1768, 1994.
30 4.10.10 IiEMOSTATIC AND THROMBOLYTIC ACTIVITY
A polypeptide of the invention may also be involved in hemostatis or thrombolysis or thrombosis. A polynucleotide of the invention can encode a polypeptide exhibiting such attributes. Compositions may be useful in treatment of various coagulation disorders (including hereditary disorders, such as hemophilias) or to enhance coagulation and other hemostatic events in treating wounds resulting from trauma, surgery or other causes. A
composition of the invention may also be useful for dissolving or inhibiting formation of thromboses and for treatment and prevention of conditions resulting therefrom (such as, for example, infarction of cardiac and central nervous system vessels (e.g., stroke).
Therapeutic compositions of the invention can be used in the following:
Assay for hemostatic and thrornbolytic activity include, without limitation, those described in: Linet et al., J. Clin. Pharmacol. 26:131-140, 1986; Burdick et al., Thrombosis Res. 45:413-419, 1987; Humphrey et al., Fibrinolysis 5:71-79 (1991); Schaub, Prostaglandins 35:467-474, 1988.
4.10.11 CANCER DIAGNOSIS AND THERAPY
Polypeptides of the invention may be involved in cancer cell generation, proliferation or metastasis. Detection of the presence or amount of polynucleotides or polypeptides of the invention may be useful for the diagnosis and/or prognosis of one or more types of cancer.
For example, the presence or increased expression of a polynucleotide/polypeptide of the invention may indicate a hereditary risk of cancer, a precancerous condition, or an ongoing malignancy. Conversely, a defect in the gene or absence of the polypeptide may be associated with a cancer condition. Identification of single nucleotide polymorphisms associated with cancer or a predisposition to cancer may also be useful for diagnosis or prognosis.
Cancer treatments promote tumor regression by inhibiting tumor cell proliferation, inhibiting angiogenesis (growth of new blood vessels that is necessary to support tumor growth) and/or prohibiting metastasis by reducing tumor cell motility or invasiveness.
Therapeutic compositions of the invention may be effective in adult and pediatric oncology including in solid phase tumors/malignancies, locally advanced tumors, human soft tissue sarcomas, metastatic cancer, including lymphatic metastases, blood cell malignancies including multiple myeloma, acute and chronic leukemias, and lymphomas, head and neck cancers including mouth cancer, larynx cancer and thyroid cancer, lung cancers including small cell carcinoma and non-small cell cancers, breast cancers including small cell carcinoma and ductal carcinoma, gastrointestinal cancers including esophageal cancer, stomach cancer, colon cancer, colorectal cancer and polyps associated with colorectal neoplasia, pancreatic cancers, liver cancer, urologic cancers including bladder cancer and prostate cancer, malignancies of the female genital tract including ovarian carcinoma, uterine (including endometrial) cancers, and solid tumor in the ovarian follicle, kidney cancers including renal cell carcinoma, brain cancers including intrinsic brain tumors, neuroblastoma, astrocytic brain tumors, gliomas, metastatic tumor cell invasion in the central nervous system, bone cancers including osteomas, skin cancers including malignant melanoma, tumor progression of human skin keratinocytes, squamous cell carcinoma, basal cell carcinoma, hemangiopericytoma and I~arposi's sarcoma.
Polypeptides, polynucleotides, or modulators of polypeptides of the invention (including inhibitors and stimulators of the biological activity of the polypeptide of the invention) may be administered to treat cancer. Therapeutic compositions can be administered in therapeutically effective dosages alone or in combination with adjuvant cancer therapy such as surgery, chemotherapy, radiotherapy, thermotherapy, and laser therapy, and may provide a beneficial effect, e.g. reducing tumor size, slowing rate of tumor growth, inhibiting metastasis, or otherwise improving overall clinical condition, without necessarily eradicating the cancer.
The composition can also be administered in therapeutically effective amounts as a portion of an anti-cancer cocktail. An anti-cancer cocktail is a mixture of the polypeptide or modulator of the invention with one or more anti-cancer drugs in addition to a pharmaceutically acceptable carrier for delivery. The use of anti-cancer cocktails as a cancer treatment is routine. Anti-cancer drugs that are well known in the art and can be used as a treatment in combination with the polypeptide or modulator of the invention include:
Actinomycin D, Aminoglutethimide, Asparaginase, Bleomycin, Busulfan, Carboplatin, Carmustine, Chlorambucil, Cisplatin (cis-DDP), Cyclophosphamide, Cytarabine HCl (Cytosine arabinoside), Dacarbazine, Dactinomycin, Daunorubicin HCI, Doxorubicin HCI, Estramustine phosphate sodium, Etoposide (V16-213), Floxuridine, 5-Fluorouracil (5-Fu), Flutamide, Hydroxyurea (hydroxycarbamide), Ifosfamide, Interferon Alpha-Za, Interferon Alpha-Zb, Leuprolide acetate (LHRH-releasing factor analog), Lomustine, Mechlorethamine HCl (nitrogen mustard), Melphalan, Mercaptopurine, Mesna, Methotrexate (MTX), Mitomycin, Mitoxantrone HCl, Octreotide, Plicamycin, Procarbazine HCI, Streptozocin, Tamoxifen citrate, Thioguanine, Thiotepa, Vinblastine sulfate, Vincristine sulfate, Amsacrine, Azacitidine, Hexamethylmelamine, Interleukin-2, Mitoguazone, Pentostatin, Semustine, Teniposide, and Vindesine sulfate.
In addition, therapeutic compositions of the invention may be used for prophylactic treatment of cancer. There are hereditary conditions and/or environmental situations (e.g.
exposure to carcinogens) known in the art that predispose an individual to developing cancers. Under these circumstances, it may be beneficial to treat these individuals with therapeutically effective doses of the polypeptide of the invention to reduce the risk of developing cancers.
ha vitro models can be used to determine the effective doses of the polypeptide of the invention as a potential cancer treatment. These iya vitro models include proliferation assays of cultured tumor cells, growth of cultured tumor cells in soft agar (see Freshney, (1987) Culture of Animal Cells: A Manual of Basic Technique, Wily-Liss, New York, NY
Ch 18 and Ch 21), tumor systems in nude mice as described in Giovanella et al., J.
Natl. Can. Inst., 52: 921-30 (1974), mobility and invasive potential of tumor cells in Boyden Chamber assays as described in Pilkington et al., Anticancer Res., 17: 4107-9. (? 997), and angiogenesis assays such as induction of vascularization of the chick chorioallantoic membrane or induction of vascular endothelial cell migration as described in Ribatta et al., Intl. J. Dev.
Biol., 40: 1189-97 (1999) and Li et al., Clin. Exp. Metastasis, 17:423-9 (1999), respectively.
Suitable tumor cells lines are available, e.g. from American Type Tissue Culture Collection catalogs.
4.10.12 RECEPTOR/LIGAND ACTIVITY
A polypeptide of the present invention may also demonstrate activity as receptor, receptor ligand or inhibitor or agonist of receptor/ligand interactions. A
polynucleotide of the invention can encode a polypeptide exhibiting such characteristics.
Examples of such receptors and ligands include, without limitation, cytokine receptors and their ligands, receptor kinases and their ligands, receptor phosphatases and their ligands, receptors involved in cell-cell interactions and their ligands (including without limitation, cellular adhesion molecules (such as selectins, integrins and their ligands) and receptor/ligand pairs involved in antigen presentation, antigen recognition and development of cellular and humoral immune responses. Receptors and ligands are also useful for screening of potential peptide or small molecule inhibitors of the relevant receptor/ligand interaction. A protein of the present invention (including, without limitation, fragments of receptors and ligands) may themselves be useful as inhibitors of receptor/ligand interactions.
The activity of a polypeptide of the invention may, among other means, be measured by the following methods:

Suitable assays for receptor-ligand activity include without limitation those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A. M. Kruisbeek, D.
H.
Margulies, E. M. Shevach, W. Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 7.28, Measurement of Cellular Adhesion under static conditions 7.28.1- 7.28.22), Takai et al., Proc. Natl. Acad. Sci. USA 84:6864-6868, 1987;
Bierer et al., J. Exp. Med. 168:1145-1156, 1988; Rosenstein et al., J. Exp. Med. 169:149-160 1989;
Stoltenborg et al., J. Immunol. Methods 175:59-68, 1994; Stitt et al., Cell 80:661-670, 1995.
By way of example, the polypeptides of the invention may be used as a receptor for a ligand(s) thereby transmitting the biological activity of that ligand(s).
Ligands may be identified through binding assays, affinity chromatography, dihybrid screening assays, BIAcore assays, gel overlay assays, or other methods known in the art.
Studies characterizing drugs or proteins as agonist or antagonist or partial agonists or a partial antagonist require the use of other proteins as competing ligands.
The polypeptides of the present invention or ligand(s) thereof may be labeled by being coupled to radioisotopes, colorimetric molecules or a toxin molecules by conventional methods.
("Guide to Protein Purification" Murray P. Deutscher (ed) Methods in Enzymology Vol. 182 (1990) Academic Press, Inc. San Diego). Examples of radioisotopes include, but are not limited to, tritium and carbon-14 . Examples of colorimetric molecules include, but are not limited to, fluorescent molecules such as fluorescamine, or rhodamine or other colorimetric molecules. Examples of toxins include, but are not limited, to ricin.
4.10.13 DRUG SCREENING
This invention is particularly useful for screening chemical compounds by using the novel polypeptides or binding fragments thereof in any of a variety of drug screening techniques. The polypeptides or fragments employed in such a test may either be free in solution, affixed to a solid support, borne on a cell surface or located intracellularly. One method of drug screening utilizes eukaryotic or prokaryotic host cells which are stably transformed with recombinant nucleic acids expressing the polypeptide or a fragment thereof. Drugs are screened against such transformed cells in competitive binding assays.
Such cells, either in viable or fixed form, can be used for standard binding assays. One may measure, for example, the formation of complexes between polypeptides of the invention or fragments and the agent being tested or examine the diminution in complex formation between the novel polypeptides and an appropriate cell line, which are well known in the art.

Sources for test compounds that may be screened for ability to bind to or modulate (i.e., increase or decrease) the activity ofpolypeptides of the invention include (1) inorganic and organic chemical libraries, (2) natural product libraries, and (3) combinatorial libraries comprised of either random or mimetic peptides, oligonucleotides or organic molecules.
5 Chemical libraries may be readily synthesized or purchased from a number of commercial sources, and may include structural analogs of known compounds or compounds that are identified as "hits" or "leads" via natural product screening.
The sources of natural product libraries are microorganisms (including bacteria and fungi), animals, plants or other vegetation, or marine organisms, and libraries of mixtures for 10 screening may be created by: (1) fermentation and extraction of broths from soil, plant or marine microorganisms or (2) extraction of the organisms themselves. Natural product libraries include polyketides, non-ribosomal peptides, and (non-naturally occurring) variants thereof. For a review, see Science 282:63-68 (1998).
Combinatorial libraries are composed of large numbers of peptides, oligonucleotides 15 or organic compounds and can be readily prepared by traditional automated synthesis methods, PCR, cloning or proprietary synthetic methods. Of particular interest are peptide and oligonucleotide combinatorial libraries. Still other libraries of interest include peptide, protein, peptidomimetic, multiparallel synthetic collection, recombinatorial, and polypeptide libraries. For a review of combinatorial chemistry and libraries created therefrom, see 20 Myers, Curr. Opiia. Biotechnol. 8:701-707 (1997). For reviews and examples of peptidomimetic libraries, see Al-Obeidi et al., Mol. Bioteclanol, 9(3):205-23 (1998); Hruby et al., Curf° Opin Chefn Biol, 1(1):114-19 (1997); Dorner et al., Bioorg Med Claena, 4(5):709-15 (1996) (alkylated dipeptides).
Identification of modulators through use of the various libraries described herein 25 permits modification of the candidate "hit" (or "lead") to optimize the capacity of the "hit"
to bind a polypeptide of the invention. The molecules identified in the binding assay are then tested for antagonist or agonist activity in in vivo tissue culture or animal models that are well known in the art. In brief, the molecules are titrated into a plurality of cell cultures or animals and then tested for either cell/animal death or prolonged survival of the animal/cells.
30 The binding molecules thus identified may be complexed with toxins, e.g., ricin or cholera, or with other compounds that are toxic to cells such as radioisotopes. The toxin-binding molecule complex is then targeted to a tumor or other cell by the specificity of the binding molecule for a polypeptide of the invention. Alternatively, the binding molecules may be complexed with imaging agents for targeting and imaging purposes.
4.10.14 ASSAY FOR RECEPTOR ACTIVITY
The invention also provides methods to detect specific binding of a polypeptide e.g. a ligand or a receptor. The art provides numerous assays particularly useful for identifying previously unknown binding partners for receptor polypeptides of the invention. For example, expression cloning using mammalian or bacterial cells, or dihybrid screening assays can be used to identify polynucleotides encoding binding partners. As another example, affinity chromatography with the appropriate immobilized polypeptide of the invention can be used to isolate polypeptides that recognize and bind polypeptides of the invention. There are a number of different libraries used for the identification of compounds, and in particular small molecules, that modulate (i.e., increase or decrease) biological activity of a polypeptide of the invention. Ligands for receptor polypeptides of the invention can also be identified by adding exogenous ligands, or cocktails of ligands to two cells populations that are genetically identical except for the expression of the receptor of the invention: one cell population expresses the receptor of the invention whereas the other does not. The responses of the two cell populations to the addition of ligands(s) are then compared. Alternatively, an expression library can be co-expressed with the polypeptide of the invention in cells and assayed for an autocrine response to identify potential ligand(s). As still another example, BIAcore assays, gel overlay assays, or other methods known in the art can be used to identify binding partner polypeptides, including, (1) organic and inorganic chemical libraries, (2) natural product libraries, and (3) combinatorial libraries comprised of random peptides, oligonucleotides or organic molecules.
The role of downstream intracellular signaling molecules in the signaling cascade of the polypeptide of the invention can be determined. For example, a chimeric protein in which the cytoplasmic domain of the polypeptide of the invention is fused to the extracellular portion of a protein, whose ligand has been identified, is produced in a host cell. The cell is then incubated with the ligand specific for the extracellular portion of the chimeric protein, thereby activating the chimeric receptor. Known downstream proteins involved in intracellular signaling can then be assayed for expected modifications i.e.
phosphorylation. Other methods known to those in the art can also be used to identify signaling molecules involved in receptor activity.

4.10.15 ANTI-INFLAMMATORY ACTIVITY
Compositions of the present invention may also exhibit anti-inflammatory activity.
The anti-inflammatory activity may be achieved by providing a stimulus to cells involved in the inflammatory response, by inhibiting or promoting cell-cell interactions (such as, for example, cell adhesion), by inhibiting or promoting chemotaxis of cells involved in the inflammatory process, inhibiting or promoting cell extravasation, or by stimulating or suppressing production of other factors which more directly inhibit or promote an inflammatory response. Compositions with such activities can be used to treat inflammatory conditions including chronic or acute conditions), including without limitation intimation associated with infection (such as septic shock, sepsis or systemic inflammatory response syndrome (SIRS)), ischemia-reperfusion injury, endotoxin lethality, arthritis, complement-mediated hyperacute rejection, nephritis, cytokine or chemokine-induced lung injury, inflammatory bowel disease, Crohn's disease or resulting from over production of cytokines such as TNF or IL-1. Compositions of the invention may also be useful to treat anaphylaxis and hypersensitivity to an antigenic substance or material.
Compositions of this invention may be utilized to prevent or treat conditions such as, but not limited to, sepsis, acute pancreatitis, endotoxin shock, cytokine induced shock, rheumatoid arthritis, chronic inflammatory arthritis, pancreatic cell damage from diabetes mellitus type 1, graft versus host disease, inflammatory bowel disease, inflamation associated with pulmonary disease, other autoimmune disease or inflammatory disease, an antiproliferative agent such as for acute or chronic mylegenous leukemia or in the prevention of premature labor secondary to intrauterine infections.
4.10.16 LEUKEMIAS
Leukemias and related disorders may be treated or prevented by administration of a therapeutic that promotes or inhibits function of the polynucleotides and/or polypeptides of the invention. Such leukemias and related disorders include but are not limited to acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia, rnyeloblastic, promyelocytic, myelomonocytic, monocytic, erythroleukemia, chronic leukemia, chronic myelocytic (granulocytic) leukemia and chronic lymphocytic leukemia (for a review of such disorders, see Fishman et al., 1985, Medicine, 2d Ed., J.B. Lippincott Co., Philadelphia).

4.10.17 NERVOUS SYSTEM DISORDERS
Nervous system disorders, involving cell types which can be tested for efficacy of intervention with compounds that modulate the activity of the polynucleotides and/or polypeptides of the invention, and which can be treated upon thus observing an indication of therapeutic utility, include but are not limited to nervous system injuries, and diseases or disorders which result in either a disconnection of axons, a diminution or degeneration of neurons, or demyelination. Nervous system lesions which may be treated in a patient (including human and non-human mammalian patients) according to the invention include but are not limited to the following lesions of either the central (including spinal cord, brain) or peripheral nervous systems:
(i) traumatic lesions, including lesions caused by physical injury or associated with surgery, for example, lesions which sever a portion of the nervous system, or compression injuries;
(ii) ischemic lesions, in which a lack of oxygen in a portion of the nervous system results in neuronal injury or death, including cerebral infarction or ischemia, or spinal cord infarction or ischemia;
(iii) infectious lesions, in which a portion of the nervous system is destroyed or injured as a result of infection, for example, by an abscess or associated with infection by human immunodeficiency virus, herpes zoster, or herpes simplex virus or with Lyme disease, tuberculosis, syphilis;
(iv) degenerative lesions, in which a portion of the nervous system is destroyed or injured as a result of a degenerative process including but not limited to degeneration associated with Parkinson's disease, Alzheimer's disease, Huntington's chorea;
or amyotrophic lateral sclerosis;
(v) lesions associated with nutritional diseases or disorders, in which a portion of the nervous system is destroyed or injured by a nutritional disorder or disorder of metabolism including but not limited to, vitamin B 12 deficiency, folic acid deficiency, Wernicke disease, tobacco-alcohol amblyopia, Marchiafava-Bignami disease (primary degeneration of the corpus callosum), and alcoholic cerebellar degeneration;
(vi) neurological lesions associated with systemic diseases including but not limited to diabetes (diabetic neuropathy, Bell's palsy), systemic lupus erythematosus, carcinoma, or sarcoidosis;

(vii) lesions caused by toxic substances including alcohol, lead, or particular neurotoxins; and (viii) demyelinated lesions in which a portion of the nervous system is destroyed or injured by a demyelinating disease including but not limited to multiple sclerosis, human immunodeficiency virus-associated myelopathy, transverse myelopathy or various etiologies, progressive multifocal leukoencephalopathy, and central pontine myelinolysis.
Therapeutics which are useful according to the invention for treatment of a nervous system disorder may be selected by testing for biological activity in promoting the survival or differentiation of neurons. For example, and not by way of limitation, therapeutics which elicit any of the following effects may be useful according to the invention:
(i) increased survival time of neurons in culture;
(ii) increased sprouting of neurons in culture or in vivo;
(iii) increased production of a neuron-associated molecule in culture or ira vivo, e.g., choline acetyltransferase or acetylcholinesterase with respect to motor neurons; or (iv) decreased symptoms of neuron dysfunction in vivo.
Such effects may be measured by any method known in the art. In preferred, non-limiting embodiments, increased survival of neurons may be measured by the method set forth in Arakawa et al. (1990, J. Neurosci. 10:3507-3515); increased sprouting of neurons may be detected by methods set forth in Pestronk et al. (1980, Exp. Neurol.
70:65-82) or Brown et al. (1981, Ann. Rev. Neurosci. 4:17-42); increased production of neuron-associated molecules may be measured by bioassay, enzymatic assay, antibody binding, Northern blot assay, ete., depending on the molecule to be measured;
and motor neuron dysfunction may be measured by assessing the physical manifestation of motor neuron disorder, e.g., weakness, motor neuron conduction velocity, or functional disability.
In specific embodiments, motor neuron disorders that may be treated according to the invention include but are not limited to disorders such as infarction, infection, exposure to toxin, trauma, surgical damage, degenerative disease or malignancy that may affect motor neurons as well as other components of the nervous system, as well as disorders that selectively affect neurons such as amyotrophic lateral sclerosis, and including but not limited to progressive spinal muscular atrophy, progressive bulbar palsy, primary lateral sclerosis, infantile and juvenile muscular atrophy, progressive bulbar paralysis of childhood (Fazio-Londe syndrome), poliomyelitis and the post polio syndrome, and Hereditary Motorsensory Neuropathy (Charcot-Marie-Tooth Disease).

4.10.18 OTHER ACTIVITIES
A polypeptide of the invention may also exhibit one or more of the following additional activities or effects: inhibiting the growth, infection or function of, or killing, 5 infectious agents, including, without limitation, bacteria, viruses, fungi and other parasites;
effecting (suppressing or enhancing) bodily characteristics, including, without limitation, height, weight, hair color, eye color, skin, fat to lean ratio or other tissue pigmentation, or organ or body part size or shape (such as, for example, breast augmentation or diminution, change in bone form or shape); effecting biorhythms or circadian cycles or rhythms;
10 effecting the fertility of male or female subjects; effecting the metabolism, catabolism, anabolism, processing, utilization, storage or elimination of dietary fat, lipid, protein, carbohydrate, vitamins, minerals, co-factors or other nutritional factors or component(s);
effecting behavioral characteristics, including, without limitation, appetite, libido, stress, cognition (including cognitive disorders), depression (including depressive disorders) and 15 violent behaviors; providing analgesic effects or other pain reducing effects; promoting differentiation and growth of embryonic stem cells in lineages other than hematopoietic lineages; hormonal or endocrine activity; in the case of enzymes, correcting deficiencies of the enzyme and treating deficiency-related diseases; treatment of hyperproliferative disorders (such as, for example, psoriasis); immunoglobulin-like activity (such as, for 20 example, the ability to bind antigens or complement); and the ability to act as an antigen in a vaccine composition to raise an immune response against such protein or another material or entity which is cross-reactive with such protein.
4.10.19 IDENTIFICATION OF POLYMORPHISMS
25 The demonstration of polymorphisms makes possible the identification of such polymorphisms in human subjects and the pharmacogenetic use of this information for diagnosis and treatment. Such polymorphisms may be associated with, e.g., differential predisposition or susceptibility to various disease states (such as disorders involving inflammation or immune response) or a differential response to drug administration, and this 30 genetic information can be used to tailor preventive or therapeutic treatment appropriately.
For example, the existence of a polymorphism associated with a predisposition to inflammation or autoimmune disease makes possible the diagnosis of this condition in humans by identifying the presence of the polymorphism.

Polymorphisms can be identified in a variety of ways known in the art which all generally involve obtaining a sample from a patient, analyzing DNA from the sample, optionally involving isolation or amplification of the DNA, and identifying the presence of the polymorphism in the DNA. For example, PCR may be used to amplify an appropriate fragment of genomic DNA which may then be sequenced. Alternatively, the DNA
may be subjected to allele-specific oligonucleotide hybridization (in which appropriate oligonucleotides are hybridized to the DNA under conditions permitting detection of a single base mismatch) or to a single nucleotide extension assay (in which an oligonucleotide that hybridizes immediately adjacent to the position of the polymorphism is extended with one or more labeled nucleotides). In addition, traditional restriction fragment length polymorphism analysis (using restriction enzymes that provide differential digestion of the genomic DNA
depending on the presence or absence of the polymorphism) may be performed.
Arrays with nucleotide sequences of the present invention can be used to detect polymorphisms. The array can comprise modified nucleotide sequences of the present invention in order to detect the nucleotide sequences of the present invention. In the alternative, any one of the nucleotide sequences of the present invention can be placed on the array to detect changes from those sequences.
Alternatively a polymorphism resulting in a change in the amino acid sequence could also be detected by detecting a corresponding change in amino acid sequence of the protein, e.g., by an antibody specific to the variant sequence.
4.10.20 ARTHRITIS AND INFLAMMATION
The immunosuppressive effects of the compositions of the invention against rheumatoid arthritis is determined in an experimental animal model system. The experimental model system is adjuvant induced arthritis in rats, and the protocol is described by J. Holoshitz, et at., 1983, Science, 219:56, or by B. Waksman et al., 1963, Int. Arch.
Allergy Appl. Immunol., 23:129. Induction of the disease can be caused by a single injection, generally intradermally, of a suspension of killed Mycobacterium tuberculosis in complete Freund's adjuvant (CFA). The route of injection can vary, but rats may be injected at the base of the tail with an adjuvant mixture. The polypeptide is administered in phosphate buffered solution (PBS) at a dose of about 1-5 mg/kg. The control consists of administering PBS only.

The procedure for testing the effects of the test compound would consist of intradermally injecting killed Mycobacterium tuberculosis in CFA followed by immediately administering the test compound and subsequent treatment every other day until day 24. At 14, 15, 18, 20, 22, and 24 days after injection of Mycobacterium CFA, an overall arthritis score may be obtained as described by J. Holoskitz above. An analysis of the data would reveal that the test compound would have a dramatic affect on the swelling of the joints as measured by a decrease of the arthritis score.
4.11 THERAPEUTIC METHODS
The compositions (including polypeptide fragments, analogs, variants and antibodies or other binding partners or modulators including antisense polynucleotides) of the invention have numerous applications in a variety of therapeutic methods. Examples of therapeutic applications include, but are not limited to, those exemplified herein.
4.11.1 EXAMPLE
One embodiment of the invention is the administration of an effective amount of the polypeptides or other composition of the invention to individuals affected by a disease or disorder that can be modulated by regulating the peptides of the invention.
While the mode of administration is not particularly important, parenteral administration is preferred. An exemplary mode of administration is to deliver an intravenous bolus. The dosage of the polypeptides or other composition of the invention will normally be determined by the prescribing physician. It is to be expected that the dosage will vary according to the age, weight, condition and response of the individual patient. Typically, the amount of polypeptide administered per dose will be in the range of about 0.01 ~,g/kg to 100 mg/kg of body weight, with the preferred dose being about 0.1 ~g/kg to 10 mg/kg of patient body weight. For parenteral administration, polypeptides of the invention will be formulated in an injectable form combined with a pharmaceutically acceptable parenteral vehicle. Such vehicles are well known in the art and examples include water, saline, Ringer's solution, dextrose solution, and solutions consisting of small amounts of the human serum albumin.
The vehicle may contain minor amounts of additives that maintain the isotonicity and stability of the polypeptide or other active ingredient. The preparation of such solutions is within the skill of the art.

4.12 PHARMACEUTICAL FORMULATIONS AND ROUTES OF
ADMINISTRATION
A protein or other composition of the present invention (from whatever source derived, including without limitation from recombinant and non-recombinant sources and including antibodies and other binding partners of the polypeptides of the invention) may be administered to a patient in need, by itself, or in pharmaceutical compositions where it is mixed with suitable carriers or excipient(s) at doses to treat or ameliorate a variety of disorders. Such a composition may optionally contain (in addition to protein or other active ingredient and a carrier) diluents, fillers, salts, buffers, stabilizers, solubilizers, and other materials well known in the art. The term "pharmaceutically acceptable" means a non-toxic material that does not interfere with the effectiveness of the biological activity of the active ingredient(s). The characteristics of the carrier will depend on the route of administration.
The pharmaceutical composition of the invention may also contain cytokines, lymphokines, or other hematopoietic factors such as M-CSF, GM-CSF, TNF, IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-S, IL-9, IL-10, IL-11, IL-12, IL-13, IL-14, IL-15, IFN, TNFO, TNF1, TNF2, G-CSF, Meg-CSF, thrombopoietin, stem cell factor, and erythropoietin. In further compositions, proteins of the invention may be combined with other agents beneficial to the treatment of the disease or disorder in question. These agents include various growth factors such as epidermal growth factor (EGF), platelet-derived growth factor (PDGF), transforming growth factors (TGF-a, and TGF-(3), insulin-like growth factor (IGF), as well as cytokines described herein.
The pharmaceutical composition may further contain other agents which either enhance the activity of the protein or other active ingredient or complement its activity or use in treatment. Such additional factors and/or agents may be included in the pharmaceutical composition to produce a synergistic effect with protein or other active ingredient of the invention, or to minimize side effects. Conversely, protein or other active ingredient of the present invention may be included in formulations of the particular clotting factor, cytokine, lymphokine, other hematopoietic factor, thrombolytic or anti-thrombotic factor, or anti- inflammatory agent to minimize side effects of the clotting factor, cytokine, lyrnphokine, other hematopoietic factor, thrombolytic or anti-thrombotic factor, or anti-inflammatory agent (such as IL-lRa, IL-1 Hyl, IL-1 Hy2, anti-TNF, corticosteroids, immunosuppressive agents). A protein of the present invention may be active in multimers (e.g., heterodimers or homodimers) or complexes with itself or other proteins.
As a result, pharmaceutical compositions of the invention may comprise a protein of the invention in such multirneric or complexed form.
As an alternative to being included in a pharmaceutical composition of the invention including a first protein, a second protein or a therapeutic agent may be concurrently administered with the first protein (e.g., at the same time, or at differing times provided that therapeutic concentrations of the combination of agents is achieved at the treatment site).
Techniques for formulation and administration of the compounds of the instant application may be found in "Remington's Pharmaceutical Sciences," Mack Publishing Co., Easton, PA, latest edition. A therapeutically effective dose further refers to that amount of the compound sufficient to result in amelioration of symptoms, e.g., treatment, healing, prevention or amelioration of the relevant medical condition, or an increase in rate of treatment, healing, prevention or amelioration of such conditions. When applied to an individual active ' ingredient, administered alone, a therapeutically effective dose refers to that ingredient alone. When applied to a combination, a therapeutically effective dose refers to combined amounts of the active ingredients that result in the therapeutic effect, whether administered in combination, serially or simultaneously.
In practicing the method of treatment or use of the present invention, a therapeutically effective amount of protein or other active ingredient of the present invention is administered to a mammal having a condition to be treated. Protein or other active ingredient of the present invention may be administered in accordance with the method of the invention either alone or in combination with other therapies such as treatments employing cytokines, lymphokines or other hematopoietic factors. When co-administered with one or more cytokines, lymphokines or other hematopoietic factors, protein or other active ingredient of the present invention may be administered either simultaneously with the cytokine(s), lymphokine(s), other hematopoietic factor(s), thrombolytic or anti-thrombotic factors, or sequentially. If administered sequentially, the attending physician will decide on the appropriate sequence of administering protein or other active ingredient of the present invention in combination with cytokine(s), lymphokine(s), other hematopoietic factor(s), thrornbolytic or anti-thrombotic factors.
4.12.1 ROUTES OF ADMINISTRATION
Suitable routes of administration may, for example, include oral, rectal, transmucosal, or intestinal administration; parenteral delivery, including intramuscular, subcutaneous, intramedullary injections, as well as intrathecal, direct intraventricular, intravenous, intraperitoneal, intranasal, or intraocular injections.
Administration of protein or other active ingredient of the present invention used in the pharmaceutical composition or to practice the method of the present invention can be carried out in a variety of conventional ways, such as oral ingestion, inhalation, topical application or cutaneous, subcutaneous, intraperitoneal, parenteral or intravenous injection. Intravenous administration to the patient is preferred.
Alternately, one may administer the compound in a local rather than systemic manner, for example, via injection of the compound directly into a arthritic joints or in 10 fibrotic tissue, often in a depot or sustained release formulation. In order to prevent the scarnng process frequently occurnng as complication of glaucoma surgery, the compounds may be administered topically, for example, as eye drops. Furthermore, one may administer the drug in a targeted drug delivery system, for example, in a liposome coated with a specific antibody, targeting, for example, arthritic or fibrotic tissue. The liposomes will be targeted 15 to and taken up selectively by the afflicted tissue.
The polypeptides of the invention are administered by any route that delivers an effective dosage to the desired site of action. The determination of a suitable route of administration and an effective dosage for a particular indication is within the level of skill in the art. Preferably for wound treatment, one administers the therapeutic compound 20 directly to the site. Suitable dosage ranges for the polypeptides of the invention can be extrapolated from these dosages or from similar studies in appropriate animal models.
Dosages can then be adjusted as necessary by the clinician to provide maximal therapeutic benefit.
25 4.12.2 COMPOSITIONS/FORMULATIONS
Pharmaceutical compositions for use in accordance with the present invention thus may be formulated in a conventional manner using one or more physiologically acceptable carriers comprising excipients and auxiliaries which facilitate processing of the active compounds into preparations which can be used pharmaceutically. These pharmaceutical 30 compositions may be manufactured in a manner that is itself known, e.g., by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping or lyophilizing processes. Proper formulation is dependent upon the route of administration chosen. When a therapeutically effective amount of protein or other active ingredient of the present invention is administered orally, protein or other active ingredient of the present invention will be in the form of a tablet, capsule, powder, solution or elixir. When administered in tablet form, the pharmaceutical composition of the invention may additionally contain a solid carrier such as a gelatin or an adjuvant. The tablet, capsule, and powder contain from about 5 to 95% protein or other active ingredient of the present invention, and preferably from about 25 to 90% protein or other active ingredient of the present invention. When administered in liquid form, a liquid carrier such as water, petroleum, oils of animal or plant origin such as peanut oil, mineral oil, soybean oil, or sesame oil, or synthetic oils may be added. The liquid form of the pharmaceutical composition may further contain physiological saline solution, dextrose or other saccharide solution, or glycols such as ethylene glycol, propylene glycol or polyethylene glycol. When administered in liquid form, the pharmaceutical composition contains from about 0.5 to 90%
by weight of protein or other active ingredient of the present invention, and preferably from about 1 to 50% protein or other active ingredient of the present invention.
When a therapeutically effective amount of protein or other active ingredient of the present invention is administered by intravenous, cutaneous or subcutaneous injection, protein or other active ingredient of the present invention will be in the form of a pyrogen-free, parenterally acceptable aqueous solution. The preparation of such parenterally acceptable protein or other active ingredient solutions, having due regard to pH, isotonicity, stability, and the like, is within the skill in the art. A preferred pharmaceutical composition for intravenous, cutaneous, or subcutaneous injection should contain, in addition to protein or other active ingredient of the present invention, an isotonic vehicle such as Sodium Chloride Injection, Ringer's Injection, Dextrose Injection, Dextrose and Sodium Chloride Injection, Lactated Ringer's Injection, or other vehicle as known in the art.
The pharmaceutical composition of the present invention may also contain stabilizers, preservatives, buffers, antioxidants, or other additives known to those of skill in the art. For injection, the agents of the invention may be formulated in aqueous solutions, preferably in physiologically compatible buffers such as Hanks's solution, Ringer's solution, or physiological saline buffer. For transmucosal administration, penetrants appropriate to the barrier to be pernleated are used in the formulation. Such penetrants are generally known in the art.
For oral administration, the compounds can be formulated readily by combining the active compounds with pharmaceutically acceptable carriers well known in the art. Such carriers enable the compounds of the invention to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions and the like, for oral ingestion by a patient to be treated. Pharmaceutical preparations for oral use can be obtained from a solid excipient, optionally grinding a resulting mixture, and processing the mixture of granules, after adding suitable auxiliaries, if desired, to obtain tablets or dragee cores. Suitable excipients are, in particular, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as, for example, maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethyl-cellulose, sodium carboxymethylcellulose, and/or polyvinylpyrrolidone (PVP). If desired, disintegrating agents may be added, such as the cross-linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof such as sodium alginate. Dragee cores are provided with suitable coatings. For this purpose, concentrated sugar solutions may be used, which may optionally contain gum arabic, talc, polyvinyl pyrrolidone, 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 identification or to characterize different combinations of active compound doses.
Pharmaceutical preparations which can be used orally include push-~t capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. The push-fit capsules can contain the active ingredients in admixture with filler such as lactose, binders such as starches, and/or 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 paraffin, or liquid polyethylene glycols. In addition, stabilizers may be added. All formulations for oral administration should be in dosages suitable for such administration. For buccal administration, the compositions may take the form of tablets or lozenges formulated in conventional manner.
For administration by inhalation, the compounds for use according to the present invention are conveniently delivered in the form of an aerosol spray presentation from pressurized packs or a nebuliser, with the use of a suitable propellant, e.g., dichlorodifluoromethane, trichlorofluorornethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol the dosage unit may be determined by providing a valve to deliver a metered amount. Capsules and cartridges of, e.g., gelatin for use in an inhaler or insufflator may be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch. The compounds may be formulated for parenteral administration by injection, e.g., by bolus injection or continuous infusion. Formulations for injection may be presented in unit dosage form, e.g., in ampules or in multi-dose containers, with an added preservative. The compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents.
Pharmaceutical formulations for parenteral administration include aqueous solutions of the active compounds in water-soluble form. 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 or triglycerides, or liposomes. Aqueous injection suspensions may contain substances which increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Optionally, the suspension may also contain suitable stabilizers or agents which increase the solubility of the compounds to allow for the preparation of highly concentrated solutions. Alternatively, the active ingredient may be in powder form for constitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use.
The compounds may also be formulated in rectal compositions such as suppositories or retention enemas, e.g., containing conventional suppository bases such as cocoa butter or other glycerides. In addition to the formulations described previously, the compounds may also be formulated as a depot preparation. Such long acting formulations may be administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection. Thus, for example, the compounds may be formulated with suitable polymeric or hydrophobic materials (for example as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt.
A pharmaceutical carrier for the hydrophobic compounds of the invention is a co-solvent system comprising benzyl alcohol, a nonpolar surfactant, a water-miscible organic polymer, and an aqueous phase. The co-solvent system may be the VPD co-solvent system.
VPD is a solution of 3% w/v benzyl alcohol, 8% w/v of the nonpolar surfactant polysorbate 80, and 65% w/v polyethylene glycol 300, made up to volume in absolute ethanol. The VPD
co-solvent system (VPD:SW) consists of VPD diluted 1:1 with a 5% dextrose in water solution. This co-solvent system dissolves hydrophobic compounds well, and itself produces low toxicity upon systemic administration. Naturally, the proportions of a co-solvent system may be varied considerably without destroying its solubility and toxicity characteristics.

Furthermore, the identity of the co-solvent components may be varied: for example, other low-toxicity nonpolar surfactants may be used instead of polysorbate 80; the fraction size of polyethylene glycol may be varied; other biocompatible polymers may replace polyethylene glycol, e.g. polyvinyl pyrrolidone; and other sugars or polysaccharides may substitute for dextrose. Alternatively, other delivery systems for hydrophobic pharmaceutical compounds may be employed. Liposomes and emulsions are well known examples of delivery vehicles or carriers for hydrophobic drugs. Certain organic solvents such as dimethylsulfoxide also may be employed, although usually at the cost of greater toxicity.
Additionally, the compounds may be delivered using a sustained-release system, such as semipermeable matrices of solid hydrophobic polymers containing the therapeutic agent.
Various types of sustained-release materials have been established and are well known by those skilled in the art. Sustained-release capsules may, depending on their chemical nature, release the compounds for a few weeks up to over 100 days. Depending on the chemical nature and the biological stability of the therapeutic reagent, additional strategies for protein or other active ingredient stabilization may be employed.
The pharmaceutical compositions also may comprise suitable solid or gel phase Garners or excipients. Examples of such Garners or excipients include but are not limited to calcium carbonate, calcium phosphate, various sugars, starches, cellulose derivatives, gelatin, and polymers such as polyethylene glycols. Many of the active ingredients of the invention may be provided as salts with pharmaceutically compatible counter ions. Such pharmaceutically acceptable base addition salts are those salts which retain the biological effectiveness and properties of the free acids and which are obtained by reaction with inorganic or organic bases such as sodium hydroxide, magnesium hydroxide, ammonia, trialkylamine, dialkylamine, monoalkylamine, dibasic amino acids, sodium acetate, potassium benzoate, triethanol amine and the like.
The pharmaceutical composition of the invention may be in the forni of a complex of the proteins) or other active ingredients) of present invention along with protein or peptide antigens. 'The protein and/or peptide antigen will deliver a stimulatory signal to both B and T
lymphocytes. B lymphocytes will respond to antigen through their surface immunoglobulin receptor. T lymphocytes will respond to antigen through the T cell receptor (TCR) following presentation of the antigen by MHC proteins. MHC and structurally related proteins including those encoded by class I and class II MHC genes on host cells will serve to present the peptide antigens) to T lymphocytes. The antigen components could also be supplied as purified MHC-peptide complexes alone or with co-stimulatory molecules that can directly signal T cells. Alternatively antibodies able to bind surface immunoglobulin and other molecules on B cells as well as antibodies able to bind the TCR and other molecules on T cells can be combined with the pharmaceutical composition of the invention.
The pharmaceutical composition of the invention may be in the form of a liposome in which protein of the present invention is combined, in addition to other pharmaceutically acceptable carriers, with amphipathic agents such as lipids which exist in aggregated form as micelles, insoluble monolayers, liquid crystals, or lamellar layers in aqueous solution.
Suitable lipids for liposomal formulation include, without limitation, monoglycerides, 10 diglycerides, sulfatides, lysolecithins, phospholipids, saponin, bile acids, and the like.
Preparation of such liposomal formulations is within the level of skill in the art, as disclosed, for example, in U.S. Patent Nos. 4,235,871; 4,501,728; 4,837,028; and 4,737,323, all of which are incorporated herein by reference.
The amount of protein or other active ingredient of the present invention in the 15 pharmaceutical composition of the present invention will depend upon the nature and severity of the condition being treated, and on the nature of prior treatments which the patient has undergone. Ultimately, the attending physician will decide the amount of protein or other active ingredient of the present invention with which to treat each individual patient.
Initially, the attending physician will administer low doses of protein or other active 20 ingredient of the present invention and observe the patient's response.
Larger doses of protein or other active ingredient of the present invention may be administered until the optimal therapeutic effect is obtained for the patient, and at that point the dosage is not increased further. It is contemplated that the various pharmaceutical compositions used to practice the method of the present invention should contain about 0.01 pg to about 100 mg 25 (preferably about 0.1 pg to about 10 mg, more preferably about 0.1 ~,g to about 1 mg) of protein or other active ingredient of the present invention per kg body weight. For compositions of the present invention which are useful for bone, cartilage, tendon or ligament regeneration, the therapeutic method includes administering the composition topically, systematically, or locally as an implant or device. When administered, the 30 therapeutic composition for use in this invention is, of course, in a pyrogen-free, physiologically acceptable form. Further, the composition may desirably be encapsulated or injected in a viscous form for delivery to the site of bone, cartilage or tissue damage.
Topical administration may be suitable for wound healing and tissue repair.
Therapeutically useful agents other than a protein or other active ingredient of the invention which may also optionally be included in the composition as described above, may alternatively or additionally, be administered simultaneously or sequentially with the composition in the methods of the invention. Preferably for bone and/or cartilage formation, the composition would include a matrix capable of delivering the protein-containing or other active ingredient-containing composition to the site of bone and/or cartilage damage, providing a structure for the developing bone and cartilage and optimally capable of being resorbed into the body. Such matrices may be formed of materials presently in use for other implanted medical applications.
The choice of matrix material is based on biocompatibility, biodegradability, mechanical properties, cosmetic appearance and interface properties. The particular application of the compositions will define the appropriate formulation.
Potential matrices for the compositions may be biodegradable and chemically defined calcium sulfate, tricalcium phosphate, hydroxyapatite, polylactic acid, polyglycolic acid and polyarhydrides.
Other potential materials are biodegradable and biologically well-defined, such as bone or dermal collagen. Further matrices are comprised of pure proteins or extracellular matrix components. Other potential matrices are nonbiodegradable and chemically defined, such as sintered hydroxyapatite, bioglass, aluminates, or other ceramics. Matrices may be comprised of combinations of any of the above-mentioned types of material, such as polylactic acid and hydroxyapatite or collagen and tricalcium phosphate. The bioceramics may be altered in composition, such as in calcium-aluminate-phosphate and processing to alter pore size, particle size, particle shape, and biodegradability. Presently preferred is a 50:50 (mole weight) copolymer of lactic acid and glycolic acid in the form of porous particles having diameters ranging from 150 to 800 microns. In some applications, it will be useful to utilize a sequestering agent, such as carboxymethyl cellulose or autologous blood clot, to prevent the protein compositions from disassociating from the matrix.
A preferred family of sequestering agents is cellulosic materials such as alkylcelluloses (including hydroxyalkylcelluloses), including methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropyl-methylcellulose, and carboxymethylcellulose, the most preferred being cationic salts of carboxymethylcellulose (CMC). Other preferred sequestering agents include hyaluronic acid, sodium alginate, polyethylene glycol), polyoxyethylene oxide, carboxyvinyl polymer and polyvinyl alcohol). The amount of sequestering agent useful herein is 0.5-20 wt %, preferably 1-10 wt % based on total formulation weight, which represents the amount necessary to prevent desorption of the protein from the polymer matrix and to provide appropriate handling of the composition, yet not so much that the progenitor cells are prevented from infiltrating the matrix, thereby providing the protein the opportunity to assist the osteogenic activity of the progenitor cells. In further compositions, proteins or other active ingredients of the invention may be combined with other agents beneficial to the treatment of the bone and/or cartilage defect, wound, or tissue in question.
These agents include various growth factors such as epidermal growth factor (EGF), platelet derived growth factor (PDGF), transforming growth factors (TGF-a and TGF-(3), and insulin-like growth factor (IGF).
The therapeutic compositions are also presently valuable for veterinary applications.
Particularly domestic animals and thoroughbred horses, in addition to humans, are desired patients for such treatment with proteins or other active ingredients of the present invention.
The dosage regimen of a protein-containing pharmaceutical composition to be used in tissue regeneration will be determined by the attending physician considering various factors which modify the action of the proteins, e.g., amount of tissue weight desired to be formed, tile site of damage, the condition of the damaged tissue, the size of a wound, type of damaged tissue (e.g., bone), the patient's age, sex, and diet, the severity of any infection, time of administration and other clinical factors. The dosage may vary with the type of matrix used in the reconstitution and with inclusion of other proteins in the pharmaceutical composition.
For example, the addition of other known growth factors, such as IGF I
(insulin like growth factor I), to the final composition, may also effect the dosage. Progress can be monitored by periodic assessment of tissue/bone growth and/or repair, for example, X-rays, histomorphometric determinations and tetracycline labeling.
Polynucleotides of the present invention can also be used for gene therapy.
Such polynucleotides can be introduced either in vivo or ex vivo into cells for expression in a mammalian subject. Polynucleotides of the invention may also be administered by other known methods for introduction of nucleic acid into a cell or organism (including, without limitation, in the form of viral vectors or naked DNA). Cells may also be cultured ex vivo in the presence of proteins of the present invention in order to proliferate or to produce a desired effect on or activity in such cells. Treated cells can then be introduced in vivo for therapeutic purposes.

4.12.3 EFFECTIVE DOSAGE
Pharmaceutical compositions suitable for use in the present invention include compositions wherein the active ingredients are contained in an effective amount to achieve its intended purpose. More specifically, a therapeutically effective amount means an amount effective to prevent development of or to alleviate the existing symptoms of the subject being treated. Determination of the effective amount is well within the capability of those skilled in the art, especially in light of the detailed disclosure provided herein. For any compound used in the method of the invention, the therapeutically effective dose can be estimated initially from appropriate in vitro assays. For example, a dose can be formulated in animal models to achieve a circulating concentration range that can be used to more accurately determine useful doses in humans. For example, a dose can be formulated in animal models to achieve a circulating concentration range that includes the ICso as determined in cell culture (i.e., the concentration of the test compound which achieves a half maximal inhibition of the protein's biological activity). Such information can be 2zsed to more accurately determine useful doses in humans.
A therapeutically effective dose refers to that amount of the compound that results in amelioration of symptoms or a prolongation of survival in a patient. Toxicity and therapeutic efficacy of such compounds can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., for determining the LDso (the dose lethal to 50%
of the population) and the EDso (the dose therapeutically effective in 50% of the population).
The dose ratio between toxic and therapeutic effects is the therapeutic index and it can be expressed as the ratio between LDso and EDSO. Compounds which exhibit high therapeutic indices are preferred. The data obtained from these cell culture assays and animal studies can be used in formulating a range of dosage for use in human. The dosage of such compounds lies preferably within a range of circulating concentrations that include the EDSo with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized. The exact formulation, route of administration and dosage can be chosen by the individual physician in view of the patient's condition. See, e.g., Fingl et al., 1975, in "The Pharmacological Basis of Therapeutics", Ch.
1 p.l. Dosage amount and interval may be adjusted individually to provide plasma levels of the active moiety which are sufficient to maintain the desired effects, or minimal effective concentration (MEC). The MEC will vary for each compound but can be estimated from ira vitf°o data. Dosages necessary to achieve the MEC will depend on individual characteristics and route of administration. However, HPLC assays or bioassays can be used to determine plasma concentrations.
Dosage intervals can also be determined using MEC value. Compounds should be administered using a regimen which maintains plasma levels above the MEC for 10-90% of the time, preferably between 30-90% and most preferably between 50-90%. In cases of local administration or selective uptake, the effective local concentration of the drug may not be related to plasma concentration.
An exemplary dosage regimen for polypeptides or other compositions of the invention will be in the range of about 0.01 ~,g/kg to 100 mg/kg of body weight daily, with the preferred dose being about 0.1 ~glkg to 25 mg/kg of patient body weight daily, varying in adults and children. Dosing may be once daily, or equivalent doses may be delivered at longer or shorter intervals.
The amount of composition administered will, of course, be dependent on the subject being treated, on the subject's age and weight, the severity of the affliction, the manner of administration and the judgment of the prescribing physician.
4.12.4 PACKAGING
The compositions may, if desired, be presented in a pack or dispenser device which may contain one or more unit dosage forms containing the active ingredient.
The pack may, for example, comprise metal or plastic foil, such as a blister pack. The pack or dispenser device may be accompanied by instructions for administration. Compositions comprising a compound of the invention formulated in a compatible pharmaceutical carrier may also b.e prepared, placed in an appropriate container, and labeled for treatment of an indicated condition.
4.13 ANTIBODIES
Also included in the invention are antibodies to proteins, or fragments of proteins of the invention. The term "antibody" as used herein refers to imrnunoglobulin molecules and immunologically active portions of immunoglobulin (Ig) molecules, i.e., molecules that contain an antigen-binding site that specifically binds (immunoreacts with) an antigen. Such antibodies include, but are not limited to, polyclonal, monoclonal, chimeric, single chain, Fab, Fab° and Ftab~>z fragments, and an Fab expression library. In general, an antibody molecule obtained from humans relates to any of the classes IgG, IgM, IgA, IgE and IgD, which differ from one another by the nature of the heavy chain present in the molecule.
Certain classes have subclasses as well, such as IgGI, IgG2, and others. Furthermore, in humans, the light chain may be a kappa chain or a lambda chain. Reference herein to antibodies includes a reference to all such classes, subclasses and types of human antibody species.
5 An isolated related protein of the invention may be intended to serve as an antigen, or a portion or fragment thereof, and additionally can be used as an immunogen to generate antibodies that imrnunospecifically bind the antigen, using standard techniques for polyclonal and monoclonal antibody preparation. The full-length protein can be used or, alternatively, the invention provides antigenic peptide fragments of the antigen for use as 10 immunogens. An antigenic peptide fragment comprises at least 6 amino acid residues of the amino acid sequence of the full length protein, such as an amino acid sequence shown in SEQ ID NO: 912-1 X22, or 2479-3134, or Tables 3A, 3B, 5, or 6, and encompasses an epitope thereof such that an antibody raised against the peptide forms a specific immune complex with the full length protein or with any fragment that contains the epitope.
15 Preferably, the antigenic peptide comprises at least 10 amino acid residues, or at least 15 amino acid residues, or at least 20 amino acid residues, or at least 30 amino acid residues.
Preferred epitopes encompassed by the antigenic peptide are regions of the protein that are located on its surface; commonly these are hydrophilic regions. r In certain embodiments of the invention, at least one epitope encompassed by the 20 antigenic peptide is a surface region of the protein, e.g., a hydrophilic region. A
hydrophobicity analysis of the human related protein sequence will indicate which regions of a related protein are particularly hydrophilic and, therefore, are likely to encode surface residues useful for targeting antibody production. As a means for targeting antibody production, hydropathy plots showing regions of hydrophilicity and hydrophobicity may be 25 generated by any method well known in the art, including, for example, the I~yte Doolittle or the Hopp Woods methods, either with or without Fourier transformation. See, e.g., Hopp and Woods, 1981, Proc. Nat. Acad. Sci. USA 78: 3824-3828; Kyte and Doolittle 1982, J. Mol.
Biol. 157: 105-142, each of which is incorporated herein by reference in its entirety.
Antibodies that are specific for one or more domains within an antigenic protein, or 30 derivatives, fragments, analogs or homologs thereof, are also provided herein.
A protein of the invention, or a derivative, fragment, analog, homolog or ortholog thereof, may be utilized as an immunogen in the generation of antibodies that immunospecifically bind these protein components.

The term "specific for" indicates that the variable regions of the antibodies of the invention recognize and bind polypeptides of the invention exclusively (i.e., able to distinguish the polypeptide of the invention from other similar polypeptides despite sequence identity, homology, or similarity found in the family of polypeptides), but may also interact with other proteins (for example, S. aureus protein A or other antibodies in ELISA
techniques) through interactions with sequences outside the variable region of the antibodies, and in particular, in the constant region of the molecule. Screening assays to determine binding specificity of an antibody of the invention are well known and routinely practiced in the art. For a comprehensive discussion of such assays, see Harlow et al.
(Eds), Antibodies A Laboratory Manual; Cold Spring Harbor Laboratory; Cold Spring Harbor, NY
(1988), Chapter 6. Antibodies that recognize and bind fragments of the polypeptides of the invention are also contemplated, provided that the antibodies are first and foremost specific for, as defined above, full-length polypeptides of the invention. As with antibodies that are specific for full length polypeptides of the invention, antibodies of the invention that recognize fragments are those which can distinguish polypeptides from the same family of polypeptides despite inherent sequence identity, homology, or similarity found in the family of proteins.
Antibodies of the invention are useful for, for example, therapeutic purposes (by modulating activity of a polypeptide of the invention), diagnostic purposes to detect or quantitate a polypeptide of the invention, as well as purification of a polypeptide of the invention. Kits comprising an antibody of the invention for any of the purposes described herein are also comprehended. In general, a kit of the invention also includes a control antigen for which the antibody is immunospecific. The invention further provides a hybridoma that produces an antibody according to the invention. Antibodies of the invention are useful for detection and/or purification of the polypeptides of the invention.
Monoclonal antibodies binding to the protein of the invention may be useful diagnostic agents for the immunodetection of the protein. Neutralizing monoclonal antibodies binding to the protein may also be useful therapeutics for both conditions associated with the protein and also in the treatment of some forms of cancer where abnormal expression of the protein is involved. In the case of cancerous cells or leukemic cells, neutralizing monoclonal antibodies against the protein may be useful in detecting and preventing the metastatic spread of the cancerous cells, which may be mediated by the protein.

The labeled antibodies of the present invention can be used for ih vitro, iT~
vivo, and in situ assays to identify cells or tissues in which a fragment of the polypeptide of interest is expressed. The antibodies may also be used directly in therapies or other diagnostics. The present invention further provides the above-described antibodies immobilized on a solid support. Examples of such solid supports include plastics such as polycarbonate, complex carbohydrates such as agarose and Sepharose~, acrylic resins and such as polyacrylamide and latex beads. Techniques for coupling antibodies to such solid supports are well known in the art (Weir, D.M. et al., "Handbook of Experimental Immunology" 4th Ed., Blaclcwell Scientific Publications, Oxford, England, Chapter 10 (1986); Jacoby, W.D. et al., Meth.
Enzym. 34 Academic Press, N.Y. (1974)). The immobilized antibodies of the present invention can be used for iya vitro, iyt vivo, and iya situ assays as well as for immuno-affinity purification of the proteins of the present invention.
Various procedures known within the art may be used for the production of polyclonal or monoclonal antibodies directed against a protein of the invention, or against derivatives, fragments, analogs homologs or orthologs thereof (see, for example, Antibodies:
A Laboratory Manual, Harlow E, and Lane D, 1988, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, incorporated herein by reference). Some of these antibodies are discussed below.
4.13.1 POLYCLONAL ANTIBODIES
For the production of polyclonal antibodies, various suitable host animals (e.g., rabbit, goat, mouse or other mammal) may be immunized by one or more injections with the native protein, a synthetic variant thereof, or a derivative of the foregoing.
An appropriate immunogenic preparation can contain, for example, the naturally occurring immunogenic protein, a chemically synthesized polypeptide representing the immunogenic protein, or a recombinantly expressed immunogenic protein. Furthermore, the protein may be conjugated to a second protein known to be immunogenic in the mammal being immunized.
Examples of such immunogenic proteins include but are not limited to keyhole limpet hemocyanin, serum albumin, bovine thyroglobulin, and soybean trypsin inhibitor. The preparation can further include an adjuvant. Various adjuvants used to increase the immunological response include, but are not limited to, Freund's (complete and incomplete), mineral gels (e.g., aluminum hydroxide), surface-active substances (e.g., lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, dinitrophenol, etc.), adjuvants usable in humans such as Bacille Calmette-Guerin and Corynebacterium parvum, or similar immunostimulatory agents. Additional examples of adjuvants that can be employed include MPL-TDM
adjuvant (monophosphoryl Lipid A, synthetic trehalose dicorynomycolate).
The polyclonal antibody molecules directed against the immunogenic protein can be isolated from the mammal (e.g., from the blood) and further purified by well known techniques, such as amity chromatography using protein A or protein G, which provide primarily the IgG fraction of immune serum. Subsequently, or alternatively, the specific antigen which is the target of the immunoglobulin sought, or an epitope thereof, may be immobilized on a column to purify the immune specific antibody by immunoaffmity chromatography. Purification of immunoglobulins is discussed, for example, by D.
Wilkinson (The Scientist, published by The Scientist, Inc., Philadelphia PA, Vol. 14, No. 8 (April 17, 2000), pp. 25-28).
4.13.2 MONOCLONAL ANTIBODIES
The term "monoclonal antibody" (MAb) or "monoclonal antibody composition", as used herein, refers to a population of antibody molecules that contain only one molecular species of antibody molecule consisting of a unique light chain gene product and a unique heavy chain gene product. In particular, the complementarity determining regions (CDRs) of the monoclonal antibody are identical in all the molecules of the population. MAbs thus contain an antigen-binding site capable of immunoreacting with a particular epitope of the antigen characterized by a unique binding affinity for it.
Monoclonal antibodies can be prepared using hybridoma methods, such as those described by Kohler and Milstein, Nature, 256, 495 (1975). In a hybridoma method, a mouse, hamster, or other appropriate host animal, is typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent. Alternatively, the lymphocytes can be immunized in vitro.
The immunizing agent will typically include the protein antigen, a fragment thereof or a fusion protein thereof. Generally, either peripheral blood lymphocytes are used if cells of human origin are desired, or spleen cells or lymph node cells are used if non-human mammalian sources are desired. The lymphocytes are then fused with an immortalized cell line using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell (Goding, Monoclonal Antibodies: Principles and Practice, Academic Press, (1986) pp. 59-103). Immortalized cell lines are usually transformed mammalian cells, particularly myeloma cells of rodent, bovine and human origin. Usually, rat or mouse myeloma cell lines are employed. The hybridoma cells can be cultured in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, immortalized cells. For example, if the parental cells lack the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT or HPRT), the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine ("HAT
medium"), which substances prevent the growth of HGPRT-deficient cells.
Preferred immortalized cell lines are those that fuse efficiently, support stable high level expression of antibody by the selected antibody-producing cells, and are sensitive to a medium such as HAT medium. More preferred immortalized cell lines are murine myeloma lines, which can be obtained, for instance, from the Salk Institute Cell Distribution Center, San Diego, California and the American Type Culture Collection, Manassas, Virginia.
Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies (I~ozbor, J. Immunol., 133:3001 (1984);
Brodeur et al., Monoclonal Antibody Production Techniques and Applications, Marcel Dekker, Inc., New York, (1987) pp. 51-63).
The culture medium in which the hybridoma cells are cultured can then be assayed for the presence of monoclonal antibodies directed against the antigen.
Preferably, the binding specificity of monoclonal antibodies produced by the hybridoma cells is determined by immunoprecipitation or by an in vitro binding assay, such as radioimmunoassay (RIA) or enzyme-linked immunoabsorbent assay (ELISA). Such techniques and assays are known in the art. The binding affinity of the monoclonal antibody can, for example, be determined by the Scatchard analysis of Munson and Pollard, Anal. Biochem., 107, 220 (1980).
Preferably, antibodies having a high degree of specificity and a high binding affinity for the target antigen are isolated.
After the desired hybridoma cells are identified, the clones can be subcloned by limiting dilution procedures and grown by standard methods. Suitable culture media for this purpose include, for example, Dulbecco's Modified Eagle's Medium and RPMI-1640 medium. Alternatively, the hybridoma cells can be grown in vivo as ascites in a mammal.
The monoclonal antibodies secreted by the subclones can be isolated or purified from the culture medium or ascites fluid by conventional immunoglobulin purification procedures such as, for example, protein A-Sepharose, hydroxylapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography.
The monoclonal antibodies can also be made by recombinant DNA methods, such as those described in U.S. Patent No. 4,816,567. DNA encoding the monoclonal antibodies of 5 the invention can be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of murine antibodies). The hybridoma cells of the invention serve as a preferred source of such DNA. Once isolated, the DNA can be placed into expression vectors, which are then transfected into host cells such as simian COS cells, Chinese hamster 10 ovary (CHO) cells, or myeloma cells that do not otherwise produce immunoglobulin protein, to obtain the synthesis of monoclonal antibodies in the recombinant host cells. The DNA
also can be modified, for example, by substituting the coding sequence for human heavy and light chain constant domains in place of the homologous murine sequences (U.S.
Patent No.
4,816,567; Morrison, Nature 368, 812-13 (1994)) or by covalently joining to the 15 immunoglobulin coding sequence all or part of the coding sequence for a non-immunoglobulin polypeptide. Such a non-immunoglobulin polypeptide can be substituted for the constant domains of an antibody of the invention, or can be substituted for the variable domains of one antigen-combining site of an antibody of the invention to create a chimeric bivalent antibody.
4.13.3 HUMANIZED ANTIBQDIES
The antibodies directed against the protein antigens of the invention can further comprise humanized antibodies or human antibodies. These antibodies are suitable for administration to humans without engendering an immune response by the human against the administered immunoglobulin. Humanized forms of antibodies are chimeric immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab', F(ab')2 or other antigen-binding subsequences of antibodies) that are principally comprised of the sequence of a human immunoglobulin, and contain minimal sequence derived from a non-human immunoglobulin. Humanization can be performed following the method of Winter and co-workers (Jones et al., Nature, 321, 522-525 (1986); Riechmann et al., Nature, 332, 323-327 (1988); Verhoeyen et al., Science, 239, 1534-1536 (1988)), by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. (See also U.S. Patent No. 5,225,539). In some instances, Fv framework residues of the human 91, immunoglobulin are replaced by corresponding non-human residues. Humanized antibodies can also comprise residues that are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the framework regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin (Jones et al., 1986; Riechmann et al., 1988; and Presta, Curr. Op. Struct.
Biol., 2, 593-596 (1992)).
4.13.4 HUMAN ANTIBODIES
Fully human antibodies relate to antibody molecules in which essentially the entire sequences of both the light chain and the heavy chain, including the CDRs, arise from human genes. Such antibodies are termed "human antibodies", or "fully human a ntibodies"
herein. Human monoclonal antibodies can be prepared by the trioma technique;
the human B-cell hybridoma technique (see I~ozbor, et al., 1983 Immunol Today 4: 72) anti the EBV
hybridoma technique to produce human monoclonal antibodies (see Cole, et al., 1985 In:
Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc., pp. 77-96).
Human monoclonal antibodies may be utilized in the practice of the present invention and may be produced by using human hybridomas (see Cote, et al., 1983. Proc Natl Acad Sci USA 80, 2026-2030) or by transforming human B-cells with Epstein Barr Virus in vitro (see Cole, et al., 1985 In: Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc., pp. 77-96).
In addition, human antibodies can also be produced using additional techniques, including phage display libraries (Hoogenboom and Winter, J. Mol. Biol., 227, 381 (1991);
Marks et al., J. Mol. Biol., 222:581 (1991)). Similarly, human antibodies can be made by introducing human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated.
Upon challenge, human antibody production is observed, which closely resembles that seen in humans in all respects, including gene rearrangement, assembly, and antibody repertoire.
This approach is described, for example, in U.S. Patent Nos. 5,545,807;
5,545,806;
5,569,825; 5,625,126; 5,633,425; 5,661,016, and in Marks et al.
(Bio/Technology 10, 779-783 (1992)); Lonberg et al. (Nature 368, 856-859 (1994)); Morrison (Nature 368, 812-13 (1994)); Fishwild et al, (Nature Biotechnology 14, 845-51 (1996)); Neuberger (Nature Biotechnology 14, 826 (1996)); and Lonberg and Huszar (Intern. Rev. Immunol.
13, 65-93 (1995)).
Human antibodies may additionally be produced using transgenic nonhuman animals that are modified so as to produce fully human antibodies rather than the animal's endogenous antibodies in response to challenge by an antigen. (See PCT
publication W094/02602). The endogenous genes encoding the heavy and light immunoglobulin chains in the nonhuman host have been incapacitated, and active loci encoding human heavy and light chain immunoglobulins are inserted into the host's genome. The human genes are incorporated, for example, using yeast artificial chromosomes containing the requisite human DNA segments. An animal which provides all the desired modifications is then obtained as progeny by crossbreeding intermediate transgenic animals containing fewer than the full complement of the modifications. The preferred embodiment of such a nonhuman animal is a mouse, and is termed the Xenomouse~ as disclosed in PCT
publications WO
96/33735 and WO 96/34096. This animal produces B cells that secrete fully human immunoglobulins. The antibodies can be obtained directly from the animal after immunization with an immunogen of interest, as, for example, a preparation of a polyclonal antibody, or alternatively from immortalized B cells derived from the animal, such as hybridomas producing monoclonal antibodies. Additionally, the genes encoding the immunoglobulins with human variable regions can be recovered and expressed to obtain the antibodies directly, or can be further modified to obtain analogs of antibodies such as, for example, single chain Fv molecules.
An example of a method of producing a nonhuman host, exemplified as a mouse, lacking expression of an endogenous immunoglobulin heavy chain is disclosed in U.S.
Patent No. 5,939,598. It can be obtained by a method including deleting the J
segment genes from at least one endogenous heavy chain locus in an embryonic stem cell to prevent rearrangement of the locus and to prevent formation of a transcript of a rearranged immunoglobulin heavy chain locus, the deletion being effected by a targeting vector containing a gene encoding a selectable marker; and producing from the embryonic stem cell a transgenic mouse whose somatic and germ cells contain the gene encoding the selectable marker.
A method for producing an antibody of interest, such as a human antibody, is disclosed in U.S. Patent No. 5,916,771. It includes introducing an expression vector that contains a nucleotide sequence encoding a heavy chain into one mammalian host cell in culture, introducing an expression vector containing a nucleotide sequence encoding a light chain into another mammalian host cell, and fusing the two cells to form a hybrid cell. The hybrid cell expresses an antibody containing the heavy chain and the light chain.
In a further improvement on this procedure, a method for identifying a clinically relevant epitope on an immunogen, and a correlative method for selecting an antibody that binds immunospecifically to the relevant epitope with high affinity, are disclosed in PCT
publication WO 99/53049.
4.13.5 FAE FRAGMENTS AND SINGLE CHAIN ANTIBODIES
According to the invention, techniques can be adapted for the production of single-chain antibodies specific to an antigenic protein of the invention (see e.g., U.S. Patent No. 4,946,778). In addition, methods can be adapted for the construction of Fab expression libraries (see e.g., Huse, et al., 1989 Science 246, 1275-1281) to allow rapid and effective identification of monoclonal Fab fragments with the desired specificity for a protein or derivatives, fragments, analogs or homologs thereof. Antibody fragments that contain the idiotypes to a protein antigen may be produced by techniques known in the art including, but not limited to: (i) an F~ab')2 fragment produced by pepsin digestion of an antibody molecule;
(ii) an Fab fragment generated by reducing the disulfide bridges of an F~ab')2 fragment; (iii) an Fab fragment generated by the treatment of the antibody molecule with papain and a reducing agent and (iv) F~ fragments.
4.13.6 BISPECIFIC ANTIBODIES
Bispecific antibodies are monoclonal, preferably human or humanized, antibodies that have binding specificities for at least two different antigens. In the present case, one of the binding specificities is for an antigenic protein of the invention. The second binding target is any other antigen, and advantageously is a cell-surface protein or receptor or receptor subunit.
Methods for making bispecific antibodies are known in the art. Traditionally, the recombinant production of bispecific antibodies is based on the co-expression of two irnmunoglobulin heavy-chain/light-chain pairs, where the two heavy chains have different specificities (Milstein and Cuello, Nature, 305, 537-539 (1983)). Because of the random assortment of immunoglobulin heavy and light chains, these hybridomas (quadromas) produce a potential mixture of ten different antibody molecules, of which only one has the correct bispecific structure. The purification of the correct molecule is usually accomplished by affinity chromatography steps. Similar procedures are disclosed in WO
93/08829, published 13 May 1993, and in Traunecker et al., 1991 EMBO J., 10, 3655-3659.
Antibody variable domains with the desired binding specificities (antibody-antigen combining sites) can be fused to immunoglobulin constant domain sequences. The fusion preferably is with an immunoglobulin heavy-chain constant domain, comprising at least part of the hinge, CH2, and CH3 regions. It is preferred to have the first heavy-chain constant region (CH1) containing the site necessary for light-chain binding present in at least one of the fusions. DNAs encoding the immunoglobulin heavy-chain fusions and, if desired, the immunoglobulin light chain, are inserted into separate expression vectors, and are co-transfected into a suitable host organism. For further details of generating bispecific antibodies see, for example, Suresh et al., Methods in Enzymology, 121, 210 (1986).
According to another approach described in WO 96/27011, the interface between a pair of antibody molecules can be engineered to maximize the percentage of heterodimers that are recovered from recombinant cell culture. The preferred interface comprises at least a part of the CH3 region of an antibody constant domain. In this method, one or more small amino acid side chains from the interface of the first antibody molecule are replaced with larger side chains (e.g. tyrosine or tryptophan). Compensatory "cavities" of identical or similar size to the large side chains) are created on the interface of the second antibody molecule by replacing large amino acid side chains with smaller ones (e.g.
alanine or threonine). This provides a mechanism for increasing the yield of the heterodimer over other unwanted end-products such as homodimers.
Bispecific antibodies can be prepared as full-length antibodies or antibody fragments (e.g. F(ab')Z bispecific antibodies). Techniques for generating bispecific antibodies from antibody fragments have been described in the literature. For example, bispecific antibodies can be prepared using chemical linkage. Brennan et al., Science 229, 81 (1985) describe a procedure wherein intact antibodies are proteolytically cleaved to generate F(ab')Z
fragments. These fragments are reduced in the presence of the dithiol complexing agent sodium arsenite to stabilize vicinal dithiols and prevent intermolecular disulfide formation.
The Fab' fragments generated are then converted to thionitrobenzoate (TNB) derivatives.
One of the Fab'-TNB derivatives is then reconverted to the Fab'-thiol by reduction with mercaptoethylamine and is mixed with an equimolar amount of the other Fab'-TNB

derivative to form the bispecific antibody. The bispecific antibodies produced can be used as agents for the selective immobilization of enzymes.
Additionally, Fab' fragments can be directly recovered from E. coli and chemically coupled to form bispecific antibodies. Shalaby et al., J. Exp. Med, 175, 217-225 (1992) 5 describe the production of a fully humanized bispecific antibody F(ab')2 molecule. Each Fab' fragment was separately secreted from E. coli and subjected to directed chemical coupling in vitro to form the bispecific antibody. The bispecific antibody thus formed was able to bind to cells overexpressing the ErbB2 receptor and normal human T
cells, as well as trigger the lytic activity of human cytotoxic lymphocytes against human breast tumor targets.
10 Various techniques for making and isolating bispecific antibody fragments directly from recombinant cell culture have also been described. For example, bispecihc antibodies have been produced using leucine zippers. Kostelny et al., J. Immunol. 148(5), (1992). The leucine zipper peptides from the Fos and Jun proteins were linked to the Fab' portions of two different antibodies by gene fusion. The antibody homodimers were reduced 15 at the hinge region to form monomers and then re-oxidized to form the antibody heterodimers. This method can also be utilized for the production of antibody homodimers.
The "diabody" technology described by Hollinger et al., Proc. Natl. Acad. Sci.
USA 90, 6444-6448 (1993) has provided an alternative mechanism for making bispecihc antibody fragments. The fragments comprise a heavy-chain variable domain (VH) connected to a 20 light-chain variable domain (VL) by a linker which is too short to allow pairing between the two domains on the same chain. Accordingly, the VH and VL domains of one fragment are forced to pair with the complementary VL and VH domains of another fragment, thereby forming two antigen-binding sites. Another strategy for making bispecific antibody fragments by the use of single-chain Fv (sFv) dimers has also been reported.
See, Gruber et 25 al., J. Immunol. 152, 5368 (1994).
Antibodies with more than two valencies are contemplated. For example, trispecific antibodies can be prepared. Tutt et al., J. Immunol. 147, 60 (1991).
Exemplary bispecific antibodies can bind to two different epitopes, at least one of which originates in the protein antigen of the invention. Alternatively, an anti-antigenic ann 30 of an immunoglobulin molecule can be combined with an arm which binds to a triggering molecule on a leukocyte such as a T-cell receptor molecule (e.g. CD2, CD3, CD28, or B7), or Fc receptors for IgG (Fc~yR), such as Fc~yRI (CD64), Fc~yRII (CD32) and Fc~yRIII (CD 16) so as to focus cellular defense mechanisms to the cell expressing the particular antigen.

Bispecific antibodies can also be used to direct cytotoxic agents to cells which express a particular antigen. These antibodies possess an antigen-binding arm and an arm which binds a cytotoxic agent or a radionuclide chelator, such as EOTUBE, DPTA, DOTA, or TETA.
Another bispeci~c antibody of interest binds the protein antigen described herein and further binds tissue factor (TF).
4.13.7 HETEROCONJUGATE ANTIBODIES
Heteroconjugate antibodies are also within the scope of the present invention.
Heteroconjugate antibodies are composed of two covalently joined antibodies.
Such antibodies have, for example, been proposed to target immune system cells to unwanted cells (U.S. Patent No. 4,676,980), and for treatment of HIV infection (WO 91/00360;
WO
92/200373; EP 03089). It is contemplated that the antibodies can be prepared in vitro using known methods in synthetic protein chemistry, including those involving crosslinking agents. For example, immunotoxins can be constructed using a disulfide exchange reaction or by forming a thioether bond. Examples of suitable reagents for this purpose include iminothiolate and methyl-4-mercaptobutyrimidate and those disclosed, for example, in U.S.
Patent No. 4,676,980.
4.13.8 EFFECTOR FUNCTION ENGINEERING
It can be desirable to modify the antibody of the invention with respect to effector function, so as to enhance, e.g., the effectiveness of the antibody in treating cancer. For example, cysteine residues) can be introduced into the Fc region, thereby allowing interchain disulfide bond formation in this region. The homodimeric antibody thus generated can have improved internalization capability and/or increased complement-mediated cell killing and antibody-dependent cellular cytotoxicity (ADCC). See Caron et al., J. Exp Med., 176, 1191-1195 (1992) and Shopes, J. Immunol., 148, 2918-2922 (1992).
Homodimeric antibodies with enhanced anti-tumor activity can also be prepared using heterobifunctional cross-linkers as described in Wolff et al. Cancer Research, 53, 2560-2565 (1993). Alternatively, an antibody can be engineered that has dual Fc regions and can thereby have enhanced complement lysis and ADCC capabilities. See Stevenson et al., Anti-Cancer Drug Design, 3, 219-230 (1989).
4.13.9 IMMUNOCONJUGATES

The invention also pertains to immunoconjugates comprising an antibody conjugated to a cytotoxic agent such as a chemotherapeutic agent, toxin (e.g., an enzymatically active toxin of bacterial, fungal, plant, or animal origin, or fragments thereof), or a radioactive isotope (i.e., a radioconjugate).
Chemotherapeutic agents useful in the generation of such imrnunoconjugates have been described above. Enzymatically active toxins and fragments thereof that can be used include diphtheria A chain, nonbinding active fragments of diphtheria toxin, exotoxin A
chain (from Pseudomonas aeruginosa), ricin A chain, abrin A chain, modeccin A
chain, alpha-sarcin, Aleurites fordii proteins, dianthin proteins, Phytolaca americana proteins (PAPI, PAPII, and PAP-S), momordica charantia inhibitor, curcin, crotin, sapaonaria officinalis inhibitor, gelonin, mitogellin, restrictocin, phenomycin, enomycin, and the tricothecenes. A variety of radionuclides are available for the production of radioconjugated antibodies. Examples include ZlzBi, 1311, 131In, 9oY, and 186Re.
Conjugates of the antibody and cytotoxic agent are made using a variety of bifunctional protein-coupling agents such as N-succinimidyl-3-(2-pyridyldithiol) propionate (SPDP), iminothiolane (IT), bifunctional derivatives of imidoesters (such as dimethyl adipimidate HCL), active esters (such as disuccinimidyl suberate), aldehydes (such as glutareldehyde), bis-azido compounds (such as bis (p-azidobenzoyl) hexanediamine), bis-diazonium derivatives (such as bis-(p-diazoniumbenzoyl)-ethylenediamine), diisocyanates (such as tolyene 2,6-diisocyanate), and bis-active fluorine compounds (such as 1,5-difluoro-2,4-dinitrobenzene). For example, a ricin immunotoxin can be prepared as described in Vitetta et al., Science, 238: 1098 (1987). Carbon-14-labeled 1-isothiocyanatobenzyl-3-methyldiethylene triaminepentaacetic acid (1VIX-DTPA) is an exemplary chelating agent for conjugation of radionucleotide to the antibody. See W094/11026.
In another embodiment, the antibody can be conjugated to a "receptor" (such streptavidin) for utilization in tumor pretargeting wherein the antibody-receptor conjugate is administered to the patient, followed by removal of unbound conjugate from the circulation using a clearing agent and then administration of a "ligand" (e.g., avidin) that is in turn conjugated to a cytotoxic agent.
4.14 COMPUTER READABLE SEQUENCES

In one application of this embodiment, a nucleotide sequence of the present invention can be recorded on computer readable media. As used herein, "computer readable media"
refers to any medium which can be read and accessed directly by a computer.
Such media include, but are not limited to: magnetic storage media, such as floppy discs, hard disc storage medium, and magnetic tape; optical storage media such as CD-ROM;
electrical storage media such as RAM and ROM; and hybrids of these categories such as magnetic/optical storage media. A skilled artisan can readily appreciate how any of the presently known computer readable mediums can be used to create a manufacture comprising computer readable medium having recorded thereon a nucleotide sequence of the present invention. As used herein, "recorded" refers to a process for storing information on computer readable medium. A skilled artisan can readily adopt any of the presently known methods for recording information on computer readable medium to generate manufactures comprising the nucleotide sequence information of the present invention.
A variety of data storage structures are available to a skilled artisan for creating a computer readable medium having recorded thereon a nucleotide sequence of the present invention. The choice of the data storage structure will generally be based on the means chosen to access the stored information. In addition, a variety of data processor programs and formats can be used to store the nucleotide sequence information of the present invention on computer readable medium. The sequence information can be represented in a word processing text file, formatted in commercially-available software such as WordPerfect and Microsoft Word, or represented in the form of an ASCII file, stored in a database application, such as DB2, Sybase, Oracle, or the like. A skilled artisan can readily adapt any number of data processor structuring formats (e.g. text file or database) in order to obtain computer readable medium having recorded thereon the nucleotide sequence information of the present invention.
By providing any of the nucleotide sequences SEQ ID NO: 1-911, or 1823-2478 or a representative fragment thereof; or a nucleotide sequence at least 95%
identical to any of the nucleotide sequences of SEQ ID NO: 1-911, or 1823-2478 in computer readable form, a skilled artisan can routinely access the sequence information for a variety of purposes.
Computer software is publicly available which allows a skilled artisan to access sequence information provided in a computer readable medium. The examples which follow demonstrate how software which implements the BLAST (Altschul et al., J. Mol.
Biol.
215:403-410 (1990)) and BLAZE (Brutlag et al., Comp. Chem. 17:203-207 (1993)) search algorithms on a Sybase system is used to identify open reading frames (ORFs) within a nucleic acid sequence. Such ORFs may be protein-encoding fragments and may be useful in producing commercially important proteins such as enzymes used in fermentation reactions and in the production of commercially useful metabolites.
As used herein, "a computer-based system" refers to the hardware means, software means, and data storage means used to analyze the nucleotide sequence information of the present invention. The minimum hardware means of the computer-based systems of the present invention comprises a central processing unit (CPU), input means, output means, and data storage means. A skilled artisan can readily appreciate that any one of the currently available computer-based systems are suitable for use in the present invention. As stated above, the computer-based systems of the present invention comprise a data storage means having stored therein a nucleotide sequence of the present invention and the necessary hardware means and software means for supporting and implementing a search means. As used herein, "data storage means" refers to memory which can store nucleotide sequence information of the present invention, or a memory access means which can access manufactures having recorded thereon the nucleotide sequence information of the present invention.
As used herein, "search means" refers to one or more programs which are implemented on the computer-based system to compare a target sequence or target structural motif with the sequence information stored within the data storage means.
Search means are used to identify fragments or regions of a known sequence which match a particular target sequence or target motif. A variety of known algorithms are disclosed publicly and a variety of commercially available software for conducting search means are and can be used in the computer-based systems of the present invention. Examples of such software includes, but is not limited to, Smith-Waterman, MacPattern (EMBL), BLAS'TN and BLASTA
(NPOLYPEPTIDEIA). A skilled artisan can readily recognize that any one of the available algorithms or implementing software packages for conducting homology searches can be adapted for use in the present computer-based systems. As used herein, a "target sequence"
can be any nucleic acid or amino acid sequence of six or more nucleotides or two or more amino acids. A skilled artisan can readily recognize that the longer a target sequence is, the less likely a target sequence will be present as a random occurrence in the database. The most preferred sequence length of a target sequence is from about 10 to 300 amino acids, more preferably from about 30 to 100 nucleotide residues. However, it is well recognized that searches for commercially important fragments, such as sequence fragments involved in gene expression and protein processing, may be of shorter length.
As used herein, "a target structural motif," or "target motif," refers to any rationally selected sequence or combination of sequences in which the sequences) are chosen based on a three-dimensional configuration which is formed upon the folding of the target motif.
There are a variety of target motifs known in the art. Protein target motifs include, but are not limited to, enzyme active sites and signal sequences. Nucleic acid target motifs include, but are not limited to, promoter sequences, hairpin structures and inducible expression elements (protein binding sequences).
4.15 TRIPLE HELIX FORMATION
In addition, the fragments of the present invention, as broadly described, can be used to control gene expression through triple helix formation or antisense DNA or RNA, both of which methods are based on the binding of a polynucleotide sequence to DNA or RNA.
Polynucleotides suitable for use in these methods are preferably 20 to 40 bases in length and are designed to be complementary to a region of the gene involved in transcription (triple helix-see Lee et al., Nucl. Acids Res. 6, 3073 (1979); Cooney et al., Science 15241, 456 (1988); and Dervan et al., Science 251, 1360 (1991)) or to the mRNA itself (antisense Olmno, J. Neurochem. 56:560 (1991); Oligodeoxynucleotides as Antisense Inhibitors of Gene Expression, CRC Press, Boca Raton, FL (1988)). Triple helix-formation optimally results in a shut-off of RNA transcription from DNA, while antisense RNA
hybridization blocks translation of an mRNA molecule into polypeptide. Both techniques have been demonstrated to be effective in model systems. Information contained in the sequences of the present invention is necessary for the design of an antisense or triple helix oligonucleotide.
4.16 DIAGNOSTIC ASSAYS AND KITS
The present invention further provides methods to identify the presence or expression of one of the ORFs of the present invention, or homolog thereof, in a test sample, using a nucleic acid probe or antibodies of the present invention, optionally conjugated or otherwise associated with a suitable label.
In general, methods for detecting a polynucleotide of the invention can comprise contacting a sample with a compound that binds to and forms a complex with the polynucleotide for a period sufficient to form the complex, and detecting the complex, so that if a complex is detected, a polynucleotide of the invention is detected in the sample.
Such methods can also comprise contacting a sample under stringent hybridization conditions with nucleic acid primers that anneal to a polynucleotide of the invention under such conditions, and amplifying annealed polynucleotides, so that if a polynucleotide is amplified, a polynucleotide of the invention is detected in the sample.
In general, methods for detecting a polypeptide of the invention can comprise contacting a sample with a compound that binds to and forms a complex with the polypeptide for a period sufficient to form the complex, and detecting the complex, so that if a complex is detected, a polypeptide of the invention is detected in the sample.
In detail, such methods comprise incubating a test sample with one or more of the antibodies or one or more of the nucleic acid probes of the present invention and assaying for binding of the nucleic acid probes or antibodies to components within the test sample.
Conditions for incubating a nucleic acid probe or antibody with a test sample vary.
Incubation conditions depend on the format employed in the assay, the detection methods employed, and the type and nature of the nucleic acid probe or antibody used in the assay.
One skilled in the art will recognize that any one of the commonly available hybridization, amplification or immunological assay formats can readily be adapted to employ the nucleic acid probes or antibodies of the present invention. Examples of such assays can be found in Chard, T., An Introduction to Radioimmunoassay and Related Techniques, Elsevier Science Publishers, Amsterdam, The Netherlands (1986); Bullock, G.R. et al., Techniques in Immunocytochemistry, Academic Press, Orlando, FL Vol. 1 (1982), Vol. 2 (1983), Vol. 3 (1985); Tijssen, P., Practice and Theory of immunoassays: Laboratory Techniques in Biochemistry and Molecular Biology, Elsevier Science Publishers, Amsterdam, The Netherlands (1985). The test samples of the present invention include cells, protein or membrane extracts of cells, or biological fluids such as sputum, blood, serum, plasma, or urine. The test sample used in the above-described method will vary based on the assay format, nature of the detection method and the tissues, cells or extracts used as the sample to be assayed. Methods for preparing protein extracts or membrane extracts of cells are well known in the art and can be readily be adapted in order to obtain a sample which is compatible with the system utilized.
In another embodiment of the present invention, kits are provided which contain the necessary reagents to carry out the assays of the present invention.
SpeciEcally, the invention provides a compartment kit to receive, in close confinement, one or more containers which comprises: (a) a first container comprising one of the probes or antibodies of the present invention; and (b) one or more other containers comprising one or more of the following: wash reagents, reagents capable of detecting presence of a bound probe or antibody.
In detail, a compartment kit includes any kit in which reagents are contained in separate containers. Such containers include small glass containers, plastic containers or strips of plastic or paper. Such containers allows one to efficiently transfer reagents from one compartment to another compartment such that the samples and reagents are not cross-contaminated, and the agents or solutions of each container can be added in a quantitative fashion from one compartment to another. Such containers will include a container which will accept the test sample, a container which contains the antibodies used in the assay, containers which contain wash reagents (such as phosphate buffered saline, Tris-buffers, etc.), and containers which contain the reagents used to detect the bound antibody or probe. Types of detection reagents include labeled nucleic acid probes, labeled secondary antibodies, or in the alternative, if the primary antibody is labeled, the enzymatic, or antibody binding reagents which are capable of reacting with the labeled antibody. One skilled in the art will readily recognize that the disclosed probes and antibodies of the present invention can be readily incorporated into one of the established kit formats which are well known in the art.
4.17 MEDICAL IMAGING
The novel polypeptides and binding partners of the invention are useful in medical imaging of sites expressing the molecules of the invention (e.g., where the polypeptide of the invention is involved in the immune response, for imaging sites of inflammation or infection). See, e.g., Kunkel et al., U.S. Pat. NO. 5,413,778. Such methods involve chemical attachment of a labeling or imaging agent, administration of the labeled polypeptide to a subject in a pharmaceutically acceptable carrier, and imaging the labeled polypeptide in vivo at the target site.
4.18 SCREENING ASSAY'S
Using the isolated proteins and polynucleotides of the invention, the present invention further provides methods of obtaining and identifying agents which bind to a polypeptide encoded by an ORF corresponding to any of the nucleotide sequences set forth in SEQ ID NO: 1-911, or 1823-2478, or bind to a specific domain of the polypeptide encoded by the nucleic acid. In detail, said method comprises the steps of:
(a) contacting an agent with an isolated protein encoded by an ORF of the present invention, or nucleic acid of the invention; and (b) determining whether the agent binds to said protein or said nucleic acid.
In general, therefore, such methods for identifying compounds that bind to a polynucleotide of the invention can comprise contacting a compound with a polynucleotide of the invention for a time sufficient to form a polynucleotide/compound complex, and detecting the complex, so that if a polynucleotide/compound complex is detected, a compound that binds to a polynucleotide of the invention is identified.
Likewise, in general, therefore, such methods for identifying compounds that bind to a polypeptide of the invention can comprise contacting a compound with a polypeptide of the invention for a time sufficient to form a polypeptide/compound complex, and detecting the complex, so that if a polypeptide/compound complex is detected, a compound that binds to a polynucleotide of the invention is identified.
Methods for identifying compounds that bind to a polypeptide of the invention can also comprise contacting a compound with a polypeptide of the invention in a cell for a time sufficient to form a polypeptide/compound complex, wherein the complex drives expression of a receptor gene sequence in the cell, and detecting the complex by detecting reporter gene sequence expression, so that if a polypeptide/compound complex is detected, a compound that binds a polypeptide of the invention is identified.
Compounds identified via such methods can include compounds which modulate the activity of a polypeptide of the invention (that is, increase or decrease its activity, relative to activity observed in the absence of the compound). Alternatively, compounds identified via such methods can include compounds which modulate the expression of a polynucleotide of the invention (that is, increase or decrease expression relative to expression levels observed in the absence of the compound). Compounds, such as compounds identified via the methods of the invention, can be tested using standard assays well known to those of skill in the art for their ability to modulate activitylexpression.
The agents screened in the above assay can be, but are not limited to, peptides, carbohydrates, vitamin derivatives, or other pharmaceutical agents. The agents can be selected and screened at random or rationally selected or designed using protein modeling techniques.
For random screening, agents such as peptides, carbohydrates, pharmaceutical agents and the like are selected at random and are assayed for their ability to bind to the protein encoded by the ORF of the present invention. Alternatively, agents may be rationally selected or designed. As used herein, an agent is said to be "rationally selected or designed"
when the agent is chosen based on the configuration of the particular protein.
For example, one skilled in the art can readily adapt currently available procedures to generate peptides, pharmaceutical agents and the like, capable of binding to a specific peptide sequence, in order to generate rationally designed antipeptide peptides, for example see Hurby et al., Application of Synthetic Peptides: Antisense Peptides," In Synthetic Peptides, A User's Guide, W.H. Freeman, NY (1992), pp. 289-307, and I~aspczak et al., Biochemistry 28:9230-8 (1989), or pharmaceutical agents, or the like.
In addition to the foregoing, one class of agents of the present invention, as broadly described, can be used to control gene expression through binding to one of the ORFs or EMFs of the present invention. As described above, such agents can be randomly screened or rationally designed/selected. Targeting the ORF or EMF allows a skilled artisan to design sequence specific or element specific agents, modulating the expression of either a single ORF or multiple ORFs which rely on the same EMF for expression control. One class of DNA binding agents are agents which contain base residues which hybridize or form a triple helix formation by binding to DNA or RNA. Such agents can be based on the classic phosphodiester, ribonucleic acid backbone, or can be a variety of sulflrydryl or polymeric derivatives which have base attachment capacity.
Agents suitable for use in these methods preferably contain 20 to 40 bases and are designed to be complementary to a region of the gene involved in transcription (triple helix -see Lee et al., Nucl. Acids Res. 6, 3073 (1979); Cooney et al., Science 241, 456 (1988); and Dervan et al., Science 251, 1360 (1991)) or to the mRNA itself (antisense-Okano, J.
Neurochem. 56, 560 (1991); Oligodeoxynucleotides as Antisense Inhibitors of Gene Expression, CRC Press, Boca Raton, FL (1988)). Triple helix-formation optimally results in a shut-off of RNA transcription from DNA, while antisense RNA hybridization blocks translation of an mRNA molecule into polypeptide. Both techniques have been demonstrated to be effective in model systems. Information contained in the sequences of the present invention is necessary for the design of an antisense or triple helix oligonucleotide and other DNA binding agents.
Agents which bind to a protein encoded by one of the ORFs of the present invention can be used as a diagnostic agent. Agents which bind to a protein encoded by one of the ORFs of the present invention can be formulated using known techniques to generate a pharmaceutical composition.
4.19 USE OF NUCLEIC ACIDS AS PROBES
Another aspect of the subject invention is to provide for polypeptide-specific nucleic acid hybridization probes capable of hybridizing with naturally occurring nucleotide sequences. The hybridization probes of the subject invention may be derived from any of the nucleotide sequences SEQ ID NO: 1-911, or 1823-2478. Because the corresponding gene is only expressed in a limited number of tissues, a hybridization probe derived from any of the nucleotide sequences SEQ ID NO: 1-911, or 1823-2478 can be used as an indicator of the presence of RNA of cell type of such a tissue in a sample.
Any suitable hybridization technique can be employed, such as, for example, in situ hybridization. PCR as described in US Patents Nos. 4,683,195 and 4,965,188 provides additional uses for oligonucleotides based upon the nucleotide sequences. Such probes used in PCR may be of recombinant origin, may be chemically synthesized, or a mixture of both.
The probe will comprise a discrete nucleotide sequence for the detection of identical sequences or a degenerate pool of possible sequences for identification of closely related genomic sequences.
Other means for producing specific hybridization probes for nucleic acids include the cloning of nucleic acid sequences into vectors for the production of mRNA
probes. Such vectors are known in the art and are commercially available and may be used to synthesize RNA probes ih vitro by means of the addition of the appropriate RNA polymerise as T7 or SP6 RNA polymerise and the appropriate radioactively labeled nucleotides. The nucleotide sequences may be used to construct hybridization probes for mapping their respective genomic sequences. The nucleotide sequence provided herein may be mapped to a chromosome or specific regions of a chromosome using well-known genetic and/or chromosomal mapping techniques. These techniques include in situ hybridization, linkage analysis against known chromosomal markers, hybridization screening with libraries or flow-sorted chromosomal preparations specific to known chromosomes, and the like. The technique of fluorescent in situ hybridization of chromosome spreads has been described, among other places, in Verma et al (1988) Human Chromosomes: A Manual of Basic Techniques, Pergamon Press, New York NY.
Fluorescent i~a situ hybridization of chromosomal preparations and other physical chromosome mapping techniques may be correlated with additional genetic map data.
Examples of genetic map data can be found in the 1994 Genome Issue of Science (265:1981f). Correlation between the location of a nucleic acid on a physical chromosomal map and a specific disease (or predisposition to a specific disease) may help delimit the region of DNA associated with that genetic disease. The nucleotide sequences of the subject invention may be used to detect differences in gene sequences between normal, Garner or affected individuals.
4.20 PREPARATION OF SUPPORT BOUND OLIGONUCLEOTIDES
Oligonucleotides, i.e., small nucleic acid segments, may be readily prepared by, for example, directly synthesizing the oligonucleotide by chemical means, as is commonly practiced using an automated oligonucleotide synthesizer.
Support bound oligonucleotides may be prepared by any of the methods known to those of skill in the art using any suitable support such as glass, polystyrene or Teflon. One strategy is to precisely spot oligonucleotides synthesized by standard synthesizers.
Immobilization can be achieved using passive adsorption (Inouye & Hondo, (1990) J. Clin.
Microbiol. 28(6), 1469-72); using UV light (Nagata et al., 1985; Dahlen et al., 1987; Morrissey &
Collins, (1989) Mol.
Cell Probes 3(2) 189-207) or by covalent binding of base modified DNA (I~eller et al., 1988;
1989); all references being specifically incorporated herein.
Another strategy that may be employed is the use of the strong biotin-streptavidin interaction as a linker. For example, Broude et al. (1994) Proc. Natl. Acad.
Sci. USA 91 (8), 3072-6, describe the use of biotinylated probes, although these are duplex probes, that are immobilized on streptavidin-coated magnetic beads. Streptavidin-coated beads may be purchased from Dynal, Oslo. Of course, this same linking chemistry is applicable to coating any surface with streptavidin. Biotinylated probes may be purchased from various sources, such as, e.g., Operon Technologies (Alameda, CA).
Nunc Laboratories (Naperville, IL) is also selling suitable material that could be used.
Nunc Laboratories have developed a method by which DNA can be covalently bound to the microwell surface termed Covalink NH. CovaLink NH is a polystyrene surface grafted with secondary amino groups (>NH) that serve as bridgeheads for further covalent coupling.

CovaLink Modules may be purchased from Nunc Laboratories. DNA molecules may be bound to CovaLink exclusively at the 5'-end by a phosphoramidate bond, allowing immobilization of more than 1 pmol of DNA (Rasmussen et al., (1991) Anal. Biochem. 198(1) 138-42).
The use of CovaLink NH strips for covalent binding of DNA molecules at the 5'-end has been described (Rasmussen et al., (1991). In this technology, a phosphoramidate bond is employed (Chu et al., (1983) Nucleic Acids Res. 11(8) 6513-29). This is beneficial as immobilization using only a single covalent bond is preferred. The phosphoramidate bond joins the DNA to the CovaLink NH secondary amino groups that are positioned at the end of spacer arms covalently grafted onto the polystyrene surface through a 2 nm long spacer arm. To link an oligonucleotide to CovaLink NH via an phosphoramidate bond, the oligonucleotide terniinus must have a 5'-end phosphate group. It is, perhaps, even possible for biotin to be covalently bound to CovaLink and then streptavidin used to bind the probes.
More specifically, the linkage method includes dissolving DNA in water (7.5 ng/~,l) and denaturing for 10 min. at 95°C and cooling on ice for 10 min. Ice-cold 0.1 M 1-methylimidazole, pH 7.0 (1-MeIm~), is then added to a final concentration of 10 mM 1-Melm~.
A ss DNA solution is then dispensed into CovaLink NH strips (75 ~,1/well) standing on ice.
Carbodiimide 0.2 M 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC), dissolved in 10 mM 1-MeIm~, is made fresh and 25 p,l added per well. The strips are incubated for 5 hours at 50°C. After incubation the strips are washed using, e.g., Nunc-Immuno Wash;
first the wells are washed 3 times, then they are soaked with washing solution for 5 min., and finally they are washed 3 times (where in the washing solution is 0.4 N NaOH, 0.25% SDS
heated to 50°C).
It is contemplated that a further suitable method for use with the present invention is that described in PCT Patent Application WO 90/03382 (Southern & Maskos), incorporated herein by reference. This method of preparing an oligonucleotide bound to a support involves attaching a nucleoside 3'-reagent through the phosphate group by a covalent phosphodiester link to aliphatic hydroxyl groups carried by the support. The oligonucleotide is then synthesized on the supported nucleoside and protecting groups removed from the synthetic oligonucleotide chain under standard conditions that do not cleave the oligonucleotide from the support.
Suitable reagents include nucleoside phosphoramidite and nucleoside hydrogen phosphorate.
An on-chip strategy for the preparation of DNA probe for the preparation of DNA probe arrays may be employed. For example, addressable laser-activated photodeprotection may be employed in the chemical synthesis of oligonucleotides directly on a glass surface, as described by Fodor et al. (1991) Science 251 (4995), 767-73, incorporated herein by reference. Probes may also be immobilized on nylon supports as described by Van Ness et al.
(1991) Nucleic Acids Res., 19(12) 3345-50; or linked to Teflon using the method of Duncan &
Cavalier (1988) Anal. Biochem. 169(1), 104-8; all references being specifically incorporated herein.
To link an oligonucleotide to a nylon support, as described by Van Ness et al.
(1991), requires activation of the nylon surface via alkylation and selective activation of the 5'-amine of oligonucleotides with cyanuric chloride.
One particular way to prepare support bound oligonucleotides is to utilize the light-generated synthesis described by Pease et al., (1994) Proc. Nafl. Acad.
Sci., USA 91(11), 5022-6, incorporated herein by reference). These authors used current photolithographic techniques to generate arrays of immobilized oligonucleotide probes (DNA
chips). These methods, in which light is used to direct the synthesis of oligonucleotide probes in high-density, miniaturized arrays, utilize photolabile 5'-protected N aryl-deoxynucleoside phosphoramidites, surface linker chemistry and versatile combinatorial synthesis strategies. A
matrix of 256 spatially defined oligonucleotide probes may be generated in this manner.
4.21 PREPARATION OF NUCLEIC ACID FRAGMENTS
The nucleic acids may be obtained from any appropriate source, such as cDNAs, genomic DNA, chromosomal DNA, microdissected chromosome bands, cosmid or YAC
inserts, and RNA, including mRNA without any amplification steps. For example, Sambrook et al. (1989) describes three protocols for the isolation of high molecular weight DNA from mammalian cells (p. 9.14-9.23).
DNA fragments may be prepared as clones in M13, plasmid or lambda vectors and/or prepared directly from genomic DNA or cDNA by PCR or other amplification methods.
Samples may be prepared or dispensed in multiwell plates. About 100-1000 ng of DNA
samples may be prepared in 2-500 ml of final volume.
The nucleic acids would then be fragmented by any of the methods known to those of skill in the art including, for example, using restriction enzymes as described at 9.24-9.28 of Sarnbrook et al. (1989), shearing by ultrasound and NaOH treatment.
Low pressure shearing is also appropriate, as described by Schriefer et al.
(1990) Nucleic Acids Res. 18(24), 7455-6, incorporated herein by reference). In this method, DNA
samples are passed through a small French pressure cell at a variety of low to intermediate pressures. A lever device allows controlled application of low to intermediate pressures to the cell. The results of these studies indicate that low-pressure shearing is a useful alternative to sonic and enzymatic DNA fragmentation methods.
One particularly suitable way for fragmenting DNA is contemplated to be that using the two base recognition endonuclease, CviJI, described by Fitzgerald et al.
(1992) Nucleic Acids Res. 20(14) 3753-62. These authors described an approach for the rapid fragmentation and fractionation of DNA into particular sizes that they contemplated to be suitable for shotgun cloning and sequencing.
The restriction endonuclease CviJI normally cleaves the recognition sequence PuGCPy between the G and C to leave blunt ends. Atypical reaction conditions, which alter the specificity of this enzyme (CviJI**), yield a quasi-random distribution of DNA
fragments form the small molecule pUCl9 (2688 base pairs). Fitzgerald et al. (1992) quantitatively evaluated the randomness of this fragmentation strategy, using a CviJI** digest of pUCl9 that was size fractionated by a rapid gel filtration method and directly ligated, without end repair, to a lac Z
minus M13 cloning vector. Sequence analysis of 76 clones showed that CviJI**
restricts pyGCPy and PuGCPu, in addition to PuGCPy sites, and that new sequence data is accumulated at a rate consistent with random fragmentation.
As reported in the literature, advantages of this approach compared to sonication and agarose gel fractionation include: smaller amounts of DNA are required (0.2-0.5 ~,g instead of 2-5 ~;g); and fewer steps are involved (no preligation, end repair, chemical extraction, or agarose gel electrophoresis and elution are needed).
Irrespective of the manner in which the nucleic acid fragments are obtained or prepared, it is important to denature the DNA to give single stranded pieces available for hybridization.
This is achieved by incubating the DNA solution for 2-5 minutes at 80-90°C. The solution is then cooled quickly to 2°C to prevent renaturation of the DNA fragments before they are contacted with the chip. Phosphate groups must also be removed from genomic DNA by methods known in the art.
4.22 PREPARATION OF DNA ARRAYS
Arrays may be prepared by spotting DNA samples on a support such as a nylon membrane. Spotting may be performed by using arrays of metal pins (the positions of which correspond to an array of wells in a microtiter plate) to repeated by transfer of about 20 nl of a DNA solution to a nylon membrane. By offset printing, a density of dots higher than the density of the wells is achieved. One to 25 dots may be accommodated in 1 mm2, depending on the type of label used. By avoiding spotting in some preselected number of rows and columns, separate subsets (subarrays) may be formed. Samples in one subarray may be the same genomic segment of DNA (or the same gene) from different individuals, or may be different, overlapped genomic clones. Each of the subarrays may represent replica spotting of the same samples. In one example, a selected gene segment may be amplified from 64 patients. For each patient, the amplified gene segment may be in one 96-well plate (all 96 wells containing the same sample).
A plate for each of the 64 patients is prepared. By using a 96-pin device, all samples may be spotted on one 8 x 12 cm membrane. Subarrays may contain 64 samples, one from each patient.
Where the 96 subarrays are identical, the dot span may be 1 mm2 and there may be a 1 mm space between subarrays.
Another approach is to use membranes or plates (available from NUNC, Naperville, Illinois) which may be partitioned by physical spacers e.g. a plastic grid molded over the membrane, the grid being similar to the sort of membrane applied to the bottom of multiwell plates, or hydrophobic strips. A fixed physical spacer is not preferred for imaging by exposure to flat phosphor-storage screens or x-ray films.
The present invention is illustrated in the following examples. Upon consideration of the present disclosure, one of skill in the art will appreciate that many other embodiments and variations may be made in the scope of the present invention. Accordingly, it is intended that the broader aspects of the present invention not be limited to the disclosure of the following examples. The present invention is not to be limited in scope by the exemplified embodiments which are intended as illustrations of single aspects of the invention, and compositions and methods which are functionally equivalent are within the scope of the invention. Indeed, numerous modifications and variations in the practice of the invention are expected to occur to those skilled in the art upon consideration of the present preferred embodiments. Consequently, the only limitations which should be placed upon the scope of the invention are those which appear in the appended claims.
All references cited within the body of the instant specification are hereby incorporated by reference in their entirety.
5.0 E~~AMPLES
5.1 E~~AMPLE 1 Novel Nucleic Acid Seauences Obtained From Various Libraries A plurality of novel nucleic acids were obtained from cDNA libraries prepared from various human tissues and in some cases isolated from a genomic library derived from human chromosome using standard PCR, SBH sequence signature analysis and Sanger sequencing techniques. The inserts of the library were amplified with PCR using primers specific for the vector sequences which flank the inserts. Clones from cDNA libraries were spotted on nylon membrane filters and screened with oligonucleotide probes (e.g., 7-mers) to obtain signature sequences. The clones were clustered into groups of similar or identical sequences.
Representative clones were selected for sequencing.
In some cases, the 5' sequence of the amplified inserts was then deduced using a typical Sanger sequencing protocol. PCR products were purified and subjected to fluorescent dye terminator cycle sequencing. Single pass gel sequencing was done using a 377 Applied Biosystems (ABI) sequencer to obtain the novel nucleic acid sequences.
5.2 EXAMPLE 2 Assemblage of Novel Nucleic Acids The contigs or nucleic acids of the present invention, designated as SEQ ID
NO: 1823-2478 were assembled using an EST sequence as a seed. Then a recursive algorithm was used to extend the seed EST into an extended assemblage, by pulling additional sequences from different databases (i.e., Hyseq's database containing EST sequences, dbEST, gb pri, and UniGene, and exons from public domain genomic sequences predicated by GenScan) that belong to this assemblage. The algorithm terminated when there were no additional sequences from the above databases that would extend the assemblage. Further, inclusion of component sequences into the assemblage was based on a BLASTN hit to the extending assemblage with BLAST score greater than 300 and percent identity greater than 95%.
5.3 EXAMPLE 3 Novel Nucleic Acids The novel nucleic acids of the present invention were assembled from sequences that were obtained from a cDNA library by methods described in Example 1 above, and in some cases sequences obtained from one or more public databases. The nucleic acids were assembled using an EST sequence as a seed. Then a recursive algorithm was used to extend the seed EST into an extended assemblage, by pulling additional sequences from different databases (Hyseq's database containing EST sequences, dbEST, gb pri, and UniGene) that belong to this assemblage. The algorithm terminated when there was no additional sequences from the above databases that would extend the assemblage. Inclusion of component sequences into the assemblage was based on a BLASTN hit to the extending assemblage with BLAST
score greater than 300 and percent identity greater than 95%.
Using PHRAP (CTniv. of Washington) or CAP4 (Paracel), a full-length gene cDNA
sequence and its corresponding protein sequence were generated from the assemblage. Any frame shifts and incorrect stop codons were corrected by hand editing. During editing, the sequences were checked using FASTY and/or BLAST against Genebank (i.e., dbEST, gb pri, UniGene, and Genpept) and the Geneseq (Derwent). Other computer programs which may have been used in the editing process were phredPhrap and Consed (CTniversity of Washington) and ed-ready, ed-ext and cg-zip-2 (Hyseq, Inc.). The full-length nucleotide and amino acid sequences, including splice variants resulting from these procedures are shown in the Sequence Listing as SEQ ID NO: 1-1822.
Table 1 shows the various tissue sources of SEQ ID NO: 1-911.
The homologs for polypeptides SEQ ID NO: 912-1822, that correspond to nucleotide sequences SEQ ID NO: 1-911 were obtained by a BLASTP version 2.Oa1 19MP-WashU
searches against Genpept and Geneseq (Derwent) using BLAST algorithm. The results showing homologues for SEQ ID NO: 912-1822 from Genpept 127-129 are shown in Table 2A. The results showing homologues for SEQ ID NO: 912-1822 from Genpept 131 are shown in Table 2B.
Using eMatrix software package (Stanford University, Stanford, CA) (Wu et al., J.
Comp. Biol., Vol. 6, 219-235 (1999), http://motif.stanford.edu/ematrix-search/
herein incorporated by reference), all the polypeptide sequences were examined to determine whether they had identifiable signature regions. Scoring matrices of the eMatrix software package are derived from the BLOCKS, PRINTS, PFAM, PRODOM, and DOMO
databases. Table 3 shows the accession number of the homologous eMatrix signature found in the indicated polypeptide sequence, its description, and the results obtained which include accession number subtype; raw score; p-value; and the position of signature in amino acid sequence. The results showing homologous signatures for SEQ ID NO: 912-1822 from eMatrix version 1.0 are shown in Table 3A. The results showing homologous signatures for SEQ ID NO: 912-1822 from eMatrix version 2.0 are shown in Table 3B.
Using the Pfam software program (Sonnhammer et al., Nucleic Acids Res., Vol.
26(1) pp. 320-322 (1998) herein incorporated by reference) all the polypeptide sequences were examined for domains with homology to certain peptide domains. Table 4A
shows the name of the Pfam model found, the description, the e-value and the Pfam score for the identified model within the sequence using Pfam versions 7.0 and 7.2. Table 4B
shows the name of the Pfam model found, the description, the e-value and the Pfam score for the identified model within the sequence using Pfam version 7.5. Further description of the Pfam models can be found at http:/lpfam.wustl.edu/.
The GeneAtlas'~ software package (Molecular Simulations Inc. (MSI), San Diego, CA) was used to predict the three-dimensional structure models for the polypeptides encoded by SEQ ID NO: 1-911 (i.e. SEQ ID NO: 912-1822). Models were generated by (1) PSI-BLAST which is a multiple alignment sequence profile-based searching developed by Altschul et al, (Nucl. Acids. Res. 25, 3389-3408 (1997)), (2) High Throughput Modeling (HTM) (Molecular Simulations Inc. (MSI) San Diego, CA,) which is an automated sequence and structure searching procedure (http://www.msi.com~, and (3) SeqFold''"~
which is a fold recognition method described by Fischer and Eisenberg (J. Mol. Biol. 209, 779-791 (1998)).
This analysis was carried out, in part, by comparing the polypeptides of the invention with the known NMR (nuclear magnetic resonance) and x-ray crystal three-dimensional structures as templates. Table 5 shows: "PDB ID", the Protein DataBase (PDB) identifier given to template structure; "Chain ID", identifier of the subcomponent of the PDB
template structure; "Compound Information", information of the PDB template structure and/or its subcomponents; "PDB Function Annotation" gives function of the PDB template as annotated by the PDB files (http~/www.rcsb.or~JPDB~; start and end amino acid position of the protein sequence aligned; PSI-BLAST score, the verify score, the SeqFold score, and the Potentials) of Mean Force (PMF). The verify score is produced by GeneAtlas~M
software (MSI), is based on Dr. Eisenberg's Profile-3D threading program developed in Dr. David Eisenberg's laboratory (US patent no. 5,436,850 and Luthy, Bowie, and Eisenberg, Nature, 356:83-85 (1992)) and a publication by R. Sanchez and A. Sali, Proc. Natl.
Acad. Sci. USA, 95:13597-12502. The verify score produced by GeneAtlas normalizes the verify score for proteins with different lengths so that a unified cutoff can be used to select good models as follows: Verify score (normalized) _ (raw score -1/2 high score)/(1/2 high score) The PFM score, produced by GeneAtlas'~ software (MSI), is a composite scoring function that depends in part on the compactness of the model, sequence identity in the alignment used to build the model, pairwise and surface mean force potentials (MFP). As given in table 5, a verify score between 0 to 1.0, with 1 being the best, represents a good model. Similarly, a PMF score between 0 to 1.0, with 1 being the best, represents a good model. A SeqFold~' score of more than 50 is considered significant. A good model may also be determined by one of skill in the art based all the information in Table 5 taken in totality.
Table 6 shows the position of the signal peptide in each of the polypeptides and the maximum score and mean score associated with that signal peptide using Neural Network SignalP V1.1 program (from Center for Biological Sequence Analysis, The Technical University of Denmark). The process for identifying prokaryotic and eukaryotic signal peptides and their cleavage sites are also disclosed by Henrik Nielson, Jacob Engelbrecht, Soren Brunak, and Gunnar von Heijne in the publication " Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites" Protein Engineering, Vol.
10, no. 1, pp. 1-6 (1997), incorporated herein by reference. A maximum S score and a mean S score, as described in the Nielson et al reference, was obtained for the polypeptide sequences.
Table 7 correlates nucleotide sequences of the invention to a specific chromosomal location when assignable.
Table 8 shows the number of transmembrane regions, their location(s), and TMPred score obtained, for each of the SEQ ID NO: 912-1822 that had a TMPred score of 500 or greater, using the TMpred program (http://www.ch.embnet.orgJsoftware/TMPRED form.html).
Table 9 is a correlation table of the novel polynucleotide sequences SEQ ID
NO: 1-911, their corresponding polypeptide sequences SEQ ID NO: 912-1822, their corresponding priority contig nucleotide sequences SEQ ID NO: 1823-2478, their corresponding priority contig polypeptide sequences SEQ ID NO: 2479-3134, and the US serial number of the priority application (all of which are herein incorporated in their entirety), in which the contig sequence was filed.
Table 10 is a correlation table of the novel polynucleotide sequences SEQ ID
NO: 1-911, the novel polypeptide sequences SEQ ID NO: 912-1822, and the US
application serial number and corresponding SEQ ID NO in which the sequence was previously filed.

Table 1 Tissue Library/13NA IiYSEQ SEQ ID NOS:
Origin Source Library Name *Mixture Various VendorsCGd011 58 74 147 267 277 432 of 16 489 496 618 tissues - mRNA

*Mixture Various VendorsCGd012 3-4 6 9 19-20 41 56-58 of 16 62 71-72 74 78 tissues 81 91-92 114 118-119 - mRNA 128 133 141 *Mixture Various VendorsCGd013 55 71 78 92 165 228 of 16 271 276 279-280 tissues 310 353 355 422 424 - mRNA 496 526 531 606 *Mixture Various VendorsCGd015 10 97 100 194-195 246 of 16 258-260 266 tissues 270 282 311 355-357 - mRNA 398 408 423 428-*Mixture Various VendorsCGd016 10 14 20 51 71 75 83 of 16 116 139 149 168 tissues 174-175 194-195 209 - mRNA 230 233 238-239 *Mixture Various VendorsCGd010 176 185 352 380 386 of 16 403 422 425-426 tissues 517 537 606 - mRNA

adrenal Clontech ADR002 7 21 36 40 43 64 69 gland 88 101 120 130 adult bladderInvitrogen BLD001 19 33 54 128 195 220 adult brainBioChain ABR012 184 246 355 364 adult brainBioChain ABR013 102 226 355 423 432 adult brainGIBCO AB3001 3 87 97 100 236 269 adult brainGIBCO ABD003 16 20-21 27 40 59 62 adult brainInvitrogen ABR014 120 199 226 246 248 adult brainInvitrogen ABR015 20 27 42 49 100 135 adult brainInvitrogen ABR016 16 100 120 195 226 267 adult brainClontech ABR001 21 27 40 59 87 101 112 Table 1 Tissue Library/ItNA HYSEQ SEQ ID NOS:
Origin Source Library Name adult brainClontech ABR006 17 23 30 33 41 43 59 adult brainClontech ABR008 3 17 23 26 29 31 36 adult brainClontech ABRO11 26 285-286 431 adult brainInvitrogen ABT004 19-21 30 35 44 57 59 adult cervixBioChain CVX001 10 22-23 36 41 43 62-63 adult colonInvitrogen CLN001 19 21 57 109 128 130 adult heartGIBCO AHR001 3 19-20 22 26 41 45 adult kidneyGIBCO AKD001 3 17 19-20 25 32 35-37 Table 1 Tissue Library/RNA IiYSEQ SEQ ID NOS:
Origin Source Library Name adult kidneyInvitrogen AKT002 1 17 20 26 59 62 73 adult liverInvitrogen ALV002 1 3-4 14-16 19-20 32-33 adult liverClontech ALV003 14 24 34 40 94 160 195 adult lungGIBCO ALG001 20 36 40 100 105 120 adult ovaryInvitrogen AOV001 1 13 15 17 19-22 36 adult placentaClontech APL001 16 195 256 285 399 421 adult spleenClontech SPLc01 17 22 36 46 88 91 93 adult spleenGIBCO ASP001 3 10 46 77 81 94 97 Table 1 Tissue Library/RNA HYSEQ SEQ ID NOS:
Origin Source Library Name adult testisGIBCO ATS001 20-21 100-101 105-106 bone marrowGF BMD002 10 17 20 25 36 41 43 bone marrowClontech BMD001 10 16 20 22 25 36 41 ' 99-100 120 128 130 134 bone marrowClontech BMD004 259 398 bone marrowClontech BMD007 36 259 398 bone marrowBMD008 259 398 bone marrownull STM001 91 136 166 195 256 362 cultured Stratagene ADP001 9 17 76 100 120 134 preadipocytes 246 248 263-264 267 . 275 281 295 323 endothelialStratagene EDT001 3-4 10 20 22-23 35-36 cells 41 47 51 57 59 esophagus BioChain ES0002 532 607 fetal brainInvitro en FBT002 3 20 42 57 64 100 130 Table 1 Tissue Library/RNA I3YSEQ SEQ ID NOS:
Origin Source Library Name fetal brainGIBCO HFB001 4 20 22 26-31 36 42 fetal brainClontech FBRs03 49 fetal brainClontech FBR001 30 87 100 182 199 268 fetal brainClontech FBR004 36 214 224 229 376 fetal brainClontech FBR006 3 12 15 20-21 23 25 fetal heartInvitrogen FHR001 3 7 12 16 19-20 26 fetal kidneyInvitrogen FKD007 26 111 162-163 fetal kidneyClontech FKD001 46 186-187 195 267 fetal kidneyClontech FI~1D00212 44 49 71 93 97 100 fetal liverClontech FLV002 20 34 40 68 78 85 93 fetal liverClontech FLV004 5 12 14 20 24 32-33 Table 1 Tissue Library/RNA I3YSEQ SEQ ID NOS:
Origin Source Library Name fetal liverInvitrogen FLV001 20 32-33 36 85 94 128 fetal liver-Columbia UniversityFLS001 2-3 10 12 14-17 19-24 spleen 41 43 49 51 57 59 62 fetal liver-Columbia UniversityFLS002 2-3 6 10 14-15 17-20 spleen 41 48-49 56-57 62 69 fetal liver-Columbia UniversityFLS003 14 17 20 26 34 63 86 spleen 187 195 211 220 227 fetal lungClontecb FLG001 22 49 160 176 195 237 fetal lungClontecb FLG004 12 41 506 fetal lungInvitrogen FLG003 15 64 115 128 135 142 fetal muscleInvitrogen FMS001 20 94 100 128 138 171 fetal muscleInvitrogen FMS002 12 21 38 57 71 86 100-101 Table 1 Tissue Library/RNA I3YSEQ SEQ ID NOS:
Origin Source Library Name fetal sltinInvitrogen FSIC0012 6 12 30-31 56 59 62-63 fetal skinInvitrogen FSK002 9 12 17 20 33 46 58 fetal spleenBioChain FSP001 46 256 induced Stratagene NTD001 15 20 49 87 109 119-120 neuron- 157 179 195 cells 208 226 234 238-239 infant Columbia UniversityIB2003 21-22 26 3148 77 82 brain 98-99 103 128 infant Columbia UniversityIBS001 21 59 77 98 131 154 brain 224 244 371 513 infant Columbia UniversityIBM002 19 26 77 248 516 brain infant Columbia UniversityIB2002 19 21-22 26-27 31 36 brain 57 62 77 93 97-leukocyte GIBCO LUC001 3 20 23 35-36 39 59 Table 1 Tissue Library/RNA I3YSEQ SEQ ID NOS:
Origin Source Library Name leukocyte Clontech LUC003 41 47 59 71 100 144 lung tumorInvitrogen LGT002 20 35-37 4143-44 47-49 lung, fibroblastStratagene LFB001 3-4 16 22 35-36 41 94 lymph nodeClontech ALN001 10 53 57 81 136 182 lymphocytenull DGD001 267 311 373-374 412 lymphocytesATCC LPC001 35-36 41 57 77 99-100 macrophageInvitrogen HMP001 87 128 177 187 196-197 mammary Invitrogen MMG001 8 16 20 36 44 56-57 gland 59-60 64 74 77 90 melanoma MEL004 3 20 from-cell-line- 59 100 ATCC-#CltL 120 Clontech 160 Table 1 Tissue Library/RNA IiYSEQ SEQ ID NOS:
Origin Source Library Name neuronal Stratagene NTU001 21 49 51 57 59 83 96 cells 120 134 179 195 pituitary Clontech PIT004 16 19 68 87 100 112 gland 128 192 195 246 placenta Invitrogen APL002 16 36 57 77 141 187 placenta Clontech PLA003 20 33 70 88 90 109 115 prostate Clontech PRT001 10 20 36 49 85 94 100 rectum Invitrogen REC001 35 77 120 128 136 153 retinoic Stratagene NTR001 120 130 179 183 193 acid- 256 355 460 478 induced- 503 890 neuronal-cells saliva Clontech SALs03 475 gland salivary Clontech SAL001 19 38 66 134-136 139 gland 191 195 206 240 skeletal Clontech SI~M00117 41 100 195 197-198 muscle 211215 236 skin fibroblastATCC SFB001 49 464 skin fibroblastATCC SFB002 49 246 267 477 skin fibroblastATCC SFB003 49 small intestineClontech SIN001 3 6 10 46 57 59 62 77 spinal Clontech SPC001 3 17 27 34 41 57 64 cord 87 100-101 128 stomach Clontech STO001 36 57 104 115 120 134-135 thalamus Clontech THA002 19 87 113 121 160 182 Table 1 Tissue Library/RNA I3YSEQ SEQ ID NOS:
Origin Source Library Name thymus Clontech THMc02 3 12 20 36 58-60 70-72 thymus Clontech THM001 20 53 59 71 100-101 thyroid Clontech THR001 3 16 19-20 23 33 35 gland 41 43-44 48-49 57 trachea Clontech TRC001 100-101 120 130 184 umbilical BioChain FUC001 7 26 36 40 43 46 50-51 cord 57 68 71 77-78 uterus Clontech UTR001 16 22 64 77 87 100 128 young liverGIBCO ALV001 5 14 20 26 32-33 57 *The 16 tissue/mRNAs and their vendor sources are as follows: 1) Normal adult brain mRNA (Invitrogen), 2) Normal adult kidney mRNA (Invitrogen), 3) Normal fetal brain mRNA
(Invitrogen), 4) Normal adult liver mRNA (Invitrogen), 5) Normal fetal kidney mRNA (Invitrogen), 6) Normal fetal liver mRNA (Invitrogen), 7) normal fetal skin mRNA (Invitrogen), 8) human adrenal gland mRNA (Clontech), 9) Human bone marrow mRNA (Clontech), 10) Human leukemia lymphoblastic mRNA (Clontech), 11) Human thymus mRNA
(Clontech), 12) human lymph node mRNA (Clontech), 13) human so~spinal cord mRNA (Clontech), 14) Table 1 human thyroid mRNA (Clontech), 15) human esophagus mRNA (BioChain), 16) human conceptional umbilical cord mRNA (BioChain).

Table 2A

SEQ Hit H) Species Descri tion S score% Identi ID

912 gi12803215Homo Sapiensglutathione S-transferase1263 100 theta 2, clone MGC:744 IMAGE:3164017, mRNA, complete cds.

912 gi601918Homo Sapiensglutathione S-transferase1263 100 theta 2 (GSTT2) mRNA, complete cds.

912 gi9937244Homo Sapiensglutathione S-transferase1259 99 theta 2 (GSTT2) and glutathione S-transferase theta 1 (GSTT1) genes, complete cds.

913 gi13872813Homo Sapienspartial mRNA for 4548 93 fibulin-6 (FIBL-6 gene).

913 gi14575679Homo Sapienshemicentin mRNA, 4542 93 complete cds.

913 gi14041957Homo sapienscDNA FLJ14438 fis, 2795 85 clone HEMBB 1000317, wealdy similar to FIBULIN-1, ISOFORM
D

PRECURSOR.

914 gi13543645Homo SapiensD-dopachrome tautomerase,450 94 clone MGC:14637 IMAGE:4082777, mRNA, com fete cds.

914 gi15930140Homo SapiensSimilar to D-dopachrome450 94 tautomerase, clone MGC:9158 IMAGE:3902943, mRNA, complete cds.

914 gi2352915Homo SapiensD-dopachrome tautomerase450 94 (DDT) gene, exon 3 and complete cds.

915 gi13543645Homo SapiensD-dopachrome tautomerase,537 86 clone MGC:14637 IMAGE:4082777, mRNA, complete cds.

915 gi15930140Homo SapiensSimilar to D-dopachrome537 86 tautomerase, clone MGC:9158 IMAGE:3902943, mRNA, complete cds.

915 gi2352915Homo SapiensD-dopachrome tautomerase537 86 (DDT) gene, exon 3 and complete cds.

916 gi4190954Homo Sapiensgene for hepatocyte 2089 100 growth factor activator, complete cds.

916 gi219681Homo SapiensHuman mRNA for hepatocyte2089 100 growth factor (HGF) activator precursor, complete cds.

916 AAR89197Homo sapiensHuman hepatocellular2089 100 growth factor single chain precursor protein.

917 gi5441937Homo SapiensBAC clone CTB-15P3 8964 100 from 7q22-q31.2, complete sequence.

917 AAY15457Homo SapiensHuman laminin beta 6164 96 4 protein.

917 AAY15459Homo SapiensSEQ ID 5 of W09919347.6046 97 918 gi10998440Mus musculusEGF-related protein 2116 52 918 gi8052320Mus musculusCegpl protein 1124 79 918 AAY07735Homo SapiensHuman breast-specific1125 79 protein.

919 gi13543621Homo Sapiensparathyroid hormone-like905 100 hormone, clone MGC:14611 IMAGE:4050706, mRNA, complete cds.

919 gi190712Homo sapiensHuman parathyroid 905 100 hormone-like protein (PLP) gene, exon 4, clones lambda-PLPg(1,3,7-2).

Table 2A

SE ID Ilit ID S ecies Descri otion S score% Identi 919 gi190713 Homo SapiensHuman parathyroid 905 100 hormone-like protein (PLP) gene, exon 5, clones lambda-PLPg(1,3,7-2).

920 gi3449294Rattus MEGF6 2229 78 norve icus 920 AAY72715 Homo SapiensHFICU08 clone human 554 43 attractin-like protein.

920 AAG75479 Homo SapiensHuman colon cancer 518 43 antigen protein SEQ ID N0:6243.

921 gi1296610Homo SapiensH.sapiens mRNA for 346 100 chemoldne CC-2 and CC-1.

921 gi1004267Homo SapiensH.sapiens gene for 346 100 chemokine HCC-1.

921 gi1004269Homo SapiensH.sapiens mRNA for 346 100 chemoltine HCC-1.

922 gi35330 Homo SapiensH.sapiens mRNA for 1126 61 procarboxypeptidase A1.

922 AAR97618 Homo sa Human carboxypeptidase1126 61 iens A1.

922 AAY28915 Homo SapiensHuman regulatory 1126 61 protein HRGP-1.

923 gi790817 Homo SapiensHuman microfibril-associated1198 99 glycoprotein 4 (MFAP4) mRNA, 3' end of cds.

923 AAY42563 Homo SapiensHuman microfibril-associated1197 100 glycoprotein 4 splice variant (MAG4u).

923 AAY85177 Homo SapiensMicrofibril associated1197 100 glycoprotein 4 splice variant protein sequence.

924 AAY06940 Homo SapiensHuman secretory protein1648 100 ZSIG-11.

924 AAY66650 Homo SapiensMembrane-bound protein1648 100 PRO536.

924 AAY50944 Homo SapiensHuman adult heart 1648 100 cDNA clone vfl 1 derived protein.

925 gi13528981Homo Sapiensapolipoprotein A-II,438 90 clone MGC:12334 IMAGE:3934476, mRNA, complete cds.

925 gi28748 Homo sapiensHuman mRNA for apolipoprotein438 90 All precursor.

925 gi296633 Homo sapiensHuman DNA for apolipoprotein438 90 A-II.

926 AAY76156 Homo SapiensHuman secreted protein419 90 encoded by gene 33.

926 AAE04850 Homo SapiensHuman SGP014 phosphatase63 33 polypeptide related exon 4.

926 gi599904 Albinaria ATPase subunit 8 40 39 turrita 927 gi13097252Homo SapiensSimilar to FI~506 640 91 binding protein 2 (13 kDa), clone MGC:5177 IMAGE:3445148, mRNA, complete cds.

927 gi337370 Homo SapiensHuman rapamycin- 640 91 and FK506-binding protein, complete cds.

927 AAQ31004 Homo sapienshRFKBP cDNA. 636 90 aal 928 AAB53360 Homo sapiensHuman colon cancer 230 95 antigen protein sequence SEQ ID N0:900.

928 AAG73789 Homo sapiensHuman colon cancer 230 95 antigen protein SEQ ID NO:4553.

Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

928 AAY86330 Homo SapiensHuman secreted protein60 66 HI~GC027, SEQ ID
N0:24S.

929 gi191613 Mus musculusacetylcholine receptorSS 43 929 AAY07766 Homo SapiensHuman secreted proteinSS 40 fragment encoded from ene 23.

930 gi1S1S7181AgrobacteriumAGR C 3718p 1148 SO

tumefaciens 930 gi14022240Mesorhizobiumprobable D-lactate 1106 47 dehydrogenase loti 930 gi1S07S160SinorhizobiumPUTATIVE D-LACTATE 1097 48 meliloti DEHYDROGENASE

(CYTOCHROME) PROTEIN

931 AAW64S48 Homo SapiensHuman epidermoid 231 100 carcinoma cell line KB clone HP
10179 protein.

931 AAW78146 Homo SapiensHuman secreted protein231 100 encoded by gene 21 clone HWTAZ7S.

931 gi7106778Homo SapiensHSPC194 1S1 7S

932 AAY24793 Homo SapiensHuman secreted protein1107 99 yc2_l.

932 gi38S8883Acanthamoebamyosin I heavy chain143 30 kinase castellanii 932 gi137S LeishmaniaC2 domain protein 126 32 major 933 gi1S028816Homo SapiensmRNA for beta-1,3- 172 28 galactosyltransferase b3Ga1-T8.

933 gi8927164Mus musculuscorel UDP-galactose:N-173 28 acetylgalactosamine-alpha-R
beta 1,3-galactosyltransferase 933 gi8927166Rattus corel UDP-galactose:N-173 26 norvegicusacetylgalactosamine-alpha-R
beta 1,3-galactosyltransferase 934 AAY73383 Homo SapiensHTRM clone 2280456 1571 100 protein sequence.

934 gi1S929192Homo Sapiensclone MGC:9S22 1487 99 IMAGE:3909690, mRNA, complete cds.

934 AAG7S282 Homo SapiensHuman colon cancer 619 99 antigen protein SEQ ID N0:6046.

93S gi1S70S411Homo Sapienspeptidoglycan recognition3041 99 protein L precursor (PGLYRP) mRNA, complete cds.

93S AAY72664 Homo SapiensMurine peptidoglycan1484 76 recognition protein-related liver protein.

93S gi66S1239MusmusculusTAGL-alpha 1471 76 936 AAB244S0 Homo SapiensHuman secreted protein361 97 sequence encoded by gene 14 SEQ ID

NO:7S.

936 AAB49409 Homo SapienshCRFl-TM8 construct 39 69 peptide.

936 gi12619689Conus conotoxin scaffold SS 21 VI/VII

ventricosusprecursor 937 gi12804373Homo Sapienstyrosine 3- 1094 94 monooxygenaseltryptophan S-monooxygenase activation protein, eta polypeptide, clone MGC:67S

IMAGE:3S43S71, mRNA, complete cds.

937 gi1711232Homo SapiensHuman DNA for 14-3-31094 94 protein eta chain, exon2 and complete cds.

Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

937 1531590 Homo SapiensH. Sapiens ene for 1094 94 14-3-3 protein.

938 gi12804681Homo Sapiens5100 calcium-binding479 100 protein, beta (neural), clone MGC:1323 IMAGE:3543825, mRNA, complete Gds.

938 gi337730 Homo SapiensHuman 5100 protein 479 100 beta-subunit ene, exon 3.

938 gi16118441OryctolagusS-100 calcium-binding479 100 protein beta cuniculus subunit 939 AAW75082 Homo SapiensHuman secreted protein392 92 encoded by gene 26 clone HTLEV 12.

939 AAG00461 Homo SapiensHuman secreted protein,72 50 SEQ ID

NO: 4542.

939 AAY86322 Homo SapiensHuman secreted protein72 50 HTLFGOS, SEQ ID NO:237.

941 gi9280025Macaca Nogo receptor 804 49 fascicularis 941 gi15080005Homo Sapiensnogo receptor, clone792 49 MGC:19831 IMAGE:4040540, mRNA, complete Gds.

941 gi12407653Homo SapiensNogo receptor mRNA, 792 49 complete Gds.

942 AAB25674 Homo SapiensHuman secreted protein768 98 sequence encoded by gene 10 SEQ ID

N0:63.

942 gi14603247Homo SapiensSimilar to RIKEN 238 90 cDNA

5730409615 gene, clone MGC:19636 IMAGE:2822323, mRNA, complete Gds.

942 AAB36613 Homo SapiensHuman FLEXHT-35 protein238 90 sequence SEQ ID N0:35.

943 AAY85678 Homo SapiensHuman kidney disease751 98 associated protein SEQ ID 10.

943 gi3127193Rattus kidney-specific protein686 75 norvegicus 943 gi5019275Bos taurusxenobiotic/medium-chain474 54 fatty acid:CoA li ase form XL-III

944 gi1197499Homo SapiensH.sapiens gene for 2527 100 C1 inhibitor exon 2 (and joined CDS).

944 gi29535 Homo SapiensHuman gene for C1-inhibitor.2527 100 944 gi15029894Homo Sapiensserine (or cysteine)2524 99 proteinase inhibitor, Glade G (C1 inhibitor), member 1, clone MGC:17091 t IMAGE:4150091, mRNA, complete Gds.

945 gi15157854AgrobacteriumAGR C_4799p 218 38 tumefaciens 945 gi15076099SinorhizobiumHYPOTHETICAL PROTEIN233 36 meliloti 945 gi9951121Pseudomonasribosomal protein 116 38 Ll l aeruginosamethyltransferase 946 AAB03948 Homo SapiensHuman mesenchymal 462 98 stem cell polypeptide.

946 AAB64909 Homo sapiensHuman secreted protein166 63 sequence encoded by gene 28 SEQ ID

NO:87.

946 '1531983 Homo sapiensH.sapiens mRNA for 77 31 CC-Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

chemolcine, eotaxin variant (clone 53).

947 gi13958036Homo SapiensFYVE-finger protein 2917 97 EIP1 mRNA, complete cds.

947 AAY29861 Homo SapiensHuman secreted protein2910 96 clone cb98 4.

947 gi11558044Mus musculusFYVE-finger containing2752 91 protein 948 AAW75000 Homo SapiensHuman secreted protein49 29 encoded by gene 146 clone HSNAK17.

948 gi10176829Arabidopsisgene id:MBB18.16~ 79 32 thaliana 949 gi13279266Homo Sapiensclone MGC:10946 466 100 IMAGE:3631700, mRNA, complete cds.

949 AAG81435 Homo SapiensHuman AFP protein 466 100 sequence SEQ

ID NO:388.

949 AAE03208 Homo SapiensHuman gene 7 encoded466 100 secreted protein HNTDL21, SEQ ID

N0:58.

950 AAY16787 Homo SapiensHuman secreted protein557 100 (clone dy41 2).

950 gi6682818Sus scrofalectin-like oxidized235 29 LDL receptor-950 AAW52837 Homo SapiensHuman C-type lectin 206 34 MCTL.

951 AAY41720 Homo SapiensHuman PR0792 protein1140 87 sequence.

951 AAB44276 Homo SapiensHuman PRO792 (UNQ431)1140 87 protein sequence SEQ ID N0:231.

951 AAB24055 Homo SapiensHuman PR0792 protein1140 87 sequence SE ID N0:31.

952 gi7670746Homo sapiensUDP-glucose:glycoprotein7968 98 glucosyltransferase 1 precursor, mRNA, complete cds.

952 gi13275621synthetic Rat RUGT 7313 91 construct 952 gi7677176Rattus UDP-glucose 7313 91 norvegicusglycoprotein:glucosyltransferase precursor 953 AAB64390 Homo SapiensAmino acid sequence 409 51 of human intracellular signalling molecule INTRA22.

953 AAG00975 Homo SapiensHuman secreted protein,212 46 SEQ ID

NO: 5056.

953 gi2623224Mus musculusFK-506 binding protein118 30 homolog 954 gi1778061Saccharomycestranscription/repair83 31 factor TFIIH

cerevisiaesubunit Tfb3 954 gi927727 SaccharomycesTfb3p: TFIIH subunit83 31 Tfb3;

cerevisiaeYDR460W

954 gi3372804Rattus focal adhesion kinase-related65 25 norvegicusprotein 955 AAG81399 Homo SapiensHuman AFP protein 1910 100 sequence SEQ

ID N0:316.

955 AAB61421 Homo SapiensHuman TANGO 300 protein.1904 99 955 AAB23618 Homo SapiensHuman secreted protein1902 99 SEQ ID

NO: 36.

956 gi296532 Homo SapiensH.sapiens mRNA for 1043 66 I beta 1-6 N-acetyl lucosaminyltransferase.

Table 2A

SEQ Hit ID S ecies Descri tion ~S score% Identi ID

956 gi1315909Homo SapiensHuman beta-1,6-N- 1043 66 acetylglucosaminyltransferase (IGnT) gene, exon 3, complete cds.

956 gi307298Homo SapiensHuman I beta 1-6 1043 66 N-acetylglucosaminyltransferase mRNA, complete cds.

957 gi2065165Homo SapiensH.sapiens mRNA for 776 93 extracellular matrix protein collagen type XIV, N-terminus.

957 AAG00322Homo SapiensHuman secreted protein,482 98 SEQ ID

NO: 4403.

957 gi288875Gallus collagen XIV 467 68 gallus 958 gi15530201Homo SapiensSimilar to matrix 2381 93 metalloproteinase 1 (interstitial collagenase), clone MGC:10479 IMAGE:3834572, mRNA, complete cds.

958 gi30126 Homo SapiensH.sapiens mRNA for 2381 93 type I

interstitial collagenase.

958 gi1688258Homo SapiensHuman collagenase 2381 93 and stromelysin genes, complete cds, and metalloelastase gene, partial cds.

959 AAY25868Homo sapiensHuman secreted protein993 99 fragment encoded from gene 57.

959 gi4008584Rattus huntingtin 61 66 norvegicus 959 gi6006615Saimiri Alanine Glyoxylate 71 31 sciureus Aminotransferase 960 AAB58288Homo SapiensLung cancer associated474 85 polypeptide sequence SEQ ID 626.

960 gi13378304Homo Sapiensdynein-associated 473 98 protein HKM23 (1an23) mRNA, com fete cds.

960 gi12803327Homo SapiensHSPC162 protein, 473 98 clone MGC:773 IMAGE:3347555, mRNA, complete cds.

961 gi930078Homo SapiensHuman Koxl6 mRNA 56 34 for zinc finger protein, partial.

961 AAE01364Homo SapiensHuman gene 13 encoded54 43 secreted protein HDPIW06, SEQ ID

NO:86.

961 AAE01398Homo SapiensHuman gene 13 encoded54 43 secreted protein HDPIW06, SEQ ID

N0:120.

962 gi9956936Mus musculusSu(var)3-9 homolog 1313 84 Suv39h2 962 gi10440094Homo SapienscDNA: FLJ23414 fis, 1236 100 clone HEP20704.

962 gi13623277Homo Sapienssuppressor of variegation821 55 (Drosophila) homolog 1, clone MGC:10376 IMAGE:3945632, mRNA, complete cds.

963 gi12654023Homo SapiensNADH dehydrogenase 432 90 (ubiquinone) 1 alpha subcomplex, 5 (l3kD, B13), clone MGC:5042 IMAGE:3453236, mRNA, complete cds.

963 gi1373173Homo SapiensNADH:ubiquinone oxidoreductase432 90 Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

subunit B13 (B13) mRNA, complete cds.

963 gi1698653Homo SapiensHuman NADH:ubiquinone432 90 oxidoreductase subunit mRNA, complete cds.

964 gi37347 Homo sapiensHuman mRNA for T-cell1645 94 rearranging gamma gene (TRG) V(g)8-J(g)2-C(g)2.

964 gi339407Homo SapiensHuman T-cell receptor1617 93 Ti rearranged gamma-chain mRNA

V-J-C region, complete cds.

964 gi37018 Homo sapiensHuman mRNA for T-cell1439 87 receptor gamma-chain.

965 AAE06606Homo SapiensHuman protein having566 96 hydrophobic domain, HP10794.

965 gi6996628Triticum phenylalanine ammonia72 46 lyase aestivum 965 gi12667442Rattus synaptotagmin VIITl 75 34 norvegicus 966 gi13654639Bos taurus D-glucuronyl CS epimerase3165 97 966 gi13442978Mus musculusD- lucuronyl CS-epimerase3142 95 966 gi11935177Mus musculusheparin/heparan sulfate:glucuronic3137 95 acid CS epimerase 967 AAG71875Homo sapiensHuman olfactory receptor709 86 polypeptide, SEQ
ID NO: 1556.

967 AAG71443Homo SapiensHuman olfactory receptor692 79 polypeptide, SEQ
ID NO: 1124.

967 AAG71816Homo sapiensHuman olfactory receptor684 82 polypeptide, SEQ
ID NO: 1497.

968 gi12655133Homo SapiensSimilar to CGI-63 1918 100 protein, clone MGC:708 IMAGE:3139846, mRNA, complete cds.

968 AAB73679Homo SapiensHuman oxidoreductase1918 100 protein ORP-12.

968 gi4929595Homo SapiensCGI-63 protein mRNA,1874 98 complete cds.

969 gi6062874Homo Sapienscandidate tumor suppressor1313 81 protein DICEl mRNA, complete cds.

969 AAY15344Homo SapiensTumour suppressor 1313 81 protein del-27.

969 AAY28995Homo SapiensTumour suppressor 1313 81 Del-27 protein sequence.

970 gi387011Homo SapiensHuman pyruvate dehydrogenase2187 99 E1-alpha subunit mRNA, cds.

970 gi12803199Homo Sapienspyruvate dehydrogenase2049 100 (lipoamide) alpha 1, clone MGC:8609 IMAGE:2961286, mRNA, complete cds.

970 gi35379 Homo SapiensHuman mRNA for brain2049 100 pyruvate dehydrogenase (EC
1.2.4.1).

971 gi2275569Homo SapiensT cell receptor beta660 99 locus, TCRBV6S4A1 to TCRBV8S1 region.

971 gi2104755Homo SapiensT cell receptor V-beta660 99 (TCRBV) gene, partial cds.

971 gi495404Pan troglodytesT cell receptor beta657 88 chain 972 AAG89141Homo SapiensHuman secreted protein,1272 100 SEQ ID

Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

NO: 261.

972 gi12053273Homo SapiensmRNA; cDNA DKFZp434K11721271 99 (from clone DKFZp434K1172);

complete cds.

972 gi292836 Homo SapiensHuman trichohyalin 146 29 (TRHY) gene, complete cds.

973 gi126S4633Homo Sapiensprotein inhibitor 2708 96 of activated STAT3, clone MGC:1417 IMAGE:3528679, mRNA, complete cds.

973 gi4996563Homo SapiensPIAS3 mRNA for protein2708 96 inhibitor of activatied STAT3, complete cds.

973 AAE02937 Homo SapiensHuman TFRP protein. 2708 96 974 gi1S099957Homo Sapiensdiacylglycerol acyltransferase856 79 like protein mRNA, complete cds.

974 gi15099955Mus musculusdiacylglycerol acyltransferase676 S9 like protein 974 AAY94889 Homo sapiensHuman protein clone S78 S6 HP02485.

975 gi7022243Homo SapienscDNA FLJ10300 fis, 1432 100 clone NT2RM2000030.

975 AAB92669 Homo SapiensHuman protein sequence1432 100 SEQ ID

N0:11033.

975 gi3834427Drosophilacytoplasmic dynein 134 24 intermediate melanogasterchain isoform DIClc 976 gi12803965Homo Sapiensclone MGC:4294 519 100 IMAGE:3636069, mRNA, complete cds.

976 gi15919713Homo Sapiensisolate NSB11-3-K3-A1062 32 immunoglobulin kappa chain variable region gene, partial cds.

976 gi15919629Homo Sapiensisolate NSB11-4-I~3-B660 33 immunoglobulin kappa chain variable region gene, partial cds.

977 gi1209685Homo SapiensHuman salivaryperoxidase3408 99 mRNA, complete cds.

977 gi163307 Bostaurus lactoperoxidase 2906 77 _ gi11990122Camelus peroxidase 2882 84 dromedarius 978 AAY01603 Homo SapiensAmino acid sequence 501 97 of the human defensin (Def X) protein.

978 gi29735 Homo SapiensH.sapiens mRNA for 214 46 corticostatin HP-4 precursor.

978 gi665927 Homo SapiensHuman corticostatin/defensin214 46 precursor gene, complete cds.

979 AAG81415 Homo SapiensHuman AFP protein 848 100 sequence SEQ

ID N0:348.

979 gi11559416OryctolagusNADPH-dependent retinol75 31 cuniculus dehydrogenase/reductase 980 AAR94422 Homo SapiensBactericidal/permeability63 56 increasing peptide (BPL245).

980 AAR76424 Homo SapiensBacterial permeability-increasing63 56 peptide BPL24S.

980 AAW63485 Homo SapiensHuman BPI protein 63 56 derived peptide XMP.245.

981 gi4309953Homo SapiensBAC clone RP11-121A8951 95 from 7p14-p13, complete sequence.

Table 2A

SEQ Hit ID S ecies Descri tion S score % Identi ID

981 gi296680Homo SapiensHuman germline TCR-gamma570 85 gene variable region V-gamma 5.

981 gi4309952Homo SapiensBAC clone RP11-121A8544 68 from 7p14-p13, complete sequence.

982 gi1223888synthetic T cell receptor alpha1070 79 chain construct 982 gi338766Homo sapiensHuman T-cell receptor994 73 rearranged alpha-chain V-region (V-D-J) mRNA, complete cds.

982 gi3089419Homo SapiensSSC11 rearranged 976 71 T cell receptor alpha chain (TCRAV
17) gene, complete cds.

983 gi14249942Homo SapiensSimilar to RIKEN 309 46 cDNA

0610008P16 gene, clone MGC:15937 IMAGE:3537224, mRNA, complete cds.

983 AAB73512Homo SapiensHuman transferase 309 46 HTFS-19, SEQ

ID N0:19.

983 gi2828262Bos taurusaralkyl acyl-CoA:amino285 42 acid N-acyltransferase 984 AAG71251Homo SapiensHuman gene 9-encoded311 90 secreted protein HMSDL37, SEQ ID

N0:99.

984 AAG71286Homo SapiensHuman gene 9-encoded311 90 secreted protein HMSDL37, SEQ ID

N0:135.

984 gi13096922Mus musculusSimilar to nadrin 76 44 985 gi4519541Mus musculusthrombospondin type 1299 88 1 domain 985 gi13625176Homo Sapiensclone 1 thrombospondin646 46 mRNA, complete cds.

985 AAW85607Homo SapiensSecreted protein 646 46 clone da228_6.

986 AAG81417Homo SapiensHuman AFP protein 287 100 sequence SEQ

ID N0:352.

986 gi176558Aotus trivirgatusinvolucrin (lar a 53 40 allele) 986 AAG77243Homo SapiensHuman colon cancer 36 70 antigen protein SEQ ID N0:8009.

987 gi2104856Rattus platelet glycoprotein551 36 V

norvegicus 987 gi6449037Mus musculusplatelet glycoproteinS50 36 V

987 gi312502Homo SapiensH.sapiens GPV gene 486 34 encoding platelet glycoprotein V precursor.

988 gi12803851Homo Sapiensnucleotide binding 1385 100 protein 2 (E.coli MinD like), clone MGC:3473 IMAGE:3633393, mRNA, complete cds.

988 gi14124958Homo Sapiensnucleotide binding 1385 100 protein 2 (E.coli MinD like), clone MGC:15834 IMAGE:3507768, mRNA, complete cds.

988 AAB59022Homo SapiensBreast and ovarian 1385 100 cancer associated antigen protein sequence SEQ ID 730.

989 gi9864185DrosophilaCrossveinless 2 1031 35 melano aster 989 gi7768636Xenopus Kielin 911 31 laevis 989 gi9887910Oryctolaguszonadhesin precursor540 31 cuniculus Table 2A

SE Hit ID S ecies Descri tion S score% Identi ID

990 113161011Homo sapienssclerostin gene, 417 92 complete cds.

990 113161020Homo Sapienssclerostin mRNA, 417 92 com fete cds.

990 gi13236418Homo SapiensSOST (SOST) mRNA, 417 92 complete cds.

991 1335148 Tacaribe P-11 protein 69 39 virus 991 gi5596437Petunia Stigl 58 30 x hybrida 992 gi4490538Homo SapiensHuman U266 rearranged933 81 DNA for lambda-immunoglobulin light chain.

992 gi33746 Homo SapiensHuman rearranged 920 80 immunoglobulin lambda light chain mRNA.

992 AAB36212 Homo sapiensHuman immune system 913 81 associated protein HISAP-10.

993 AAG03466 Homo SapiensHuman secreted protein,104 31 SEQ ID

NO: 7547.

993 gi259589 Cercopithecineglycoprotein J; gJ 88 42 herpesvirus 993 gi3514059Cercopithecineglycoprotein gJ 87 42 herpesvirus 994 gi203246 Rattus cell adhesion-like 1739 97 molecule norve icus 994 gi514374 Homo SapiensHuman (clone pHOM) 1666 94 opioid-binding cell adhesion molecule mRNA, complete cds.

994 gi586 Bos taurusput. pre-OPCAM (AA 1643 93 1 - 345) 995 AAB88408 Homo SapiensHuman membrane or 1358 92 secretory protein clone PSEC0164.

995 AAY13392 Homo SapiensAmino acid sequence 1355 100 ofprotein PR0328.

995 AAB01373 Homo SapiensNeuron-associated 1355 100 protein.

996 AAB85144 Homo SapiensHuman NKCR polypeptide982 89 (clone ID HMSOM53).

996 gi31332 Homo SapiensHuman mRNA for high 364 42 affinity Fc race for (FcRI .

996 AAY96226 Homo SapiensHuman high affinity 364 42 Fc receptor, FcgammaRI.

997 gi14165486Homo Sapiensclone MGC:15041 70 37 IMAGE:3831657, mRNA, complete cds.

997 gi9909361Homo Sapienssphingosine kinase 70 37 (SPHIC) mRNA, complete cds.

997 gi8132868Homo Sapienssphingosine kinase-170 37 mRNA, complete cds.

998 AAB56802 Homo SapiensHuman prostate cancer417 100 antigen protein sequence SEQ ID

N0:1380.

998 gi2983321Aquifex cytochrome c-type 61 36 aeolicus biogenesis protein 998 gi6941880Escherichiaflagellin 63 35 coli 999 AAB08732 Homo SapiensAmino acid sequence 1375 87 of a human OLD-35 polypeptide.

999 gi14042110Homo SapienscDNA FLJ14531 fis, 1265 88 clone NT2RM2000371, weakly similar to POLYRIBONUCLEOTIDE

Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

NUCLEOTIDYLTRANSFERASE

(EC 2.7.7.8).

999 AAB92684Homo SapiensHuman protein sequence1265 88 SEQ ID

N0:11065.

1000 gi199582Mus musculusB(2)-micro lobulin 616 95 1000 gi50105 Mus musculusbeta2-microglobulin 614 95 precursor (aa -20 to 99) 1000 1199576 Mus musculusB(2)-microglobulin 609 94 1001 gi7023273Homo SapienscDNA FLJ10922 fis, 672 99 clone OVARC1000420.

1001 AAB93335Homo SapiensHuman protein sequence672 99 SEQ ID

N0:12441.

1001 AAM06337Homo SapiensHuman foetal protein,328 75 SEQ ID NO:

68.

1002 gi15559608Homo SapiensSimilar to zinc finger2079 100 protein 16 (KOX 9), clone MGC:20886 IMAGE:4549240, mRNA, complete cds.

1002 gi55471 Mus musculusZfp-29 725 59 1002 gi6409345Homo Sapienszinc finger protein 730 54 (ZNF180) mRNA, complete cds.

1003 gi488555Homo SapiensHuman zinc finger 1664 60 protein ZNF135 mRNA, complete cds.

1003 gi1769491Homo SapiensHuman kruppel-related1633 49 zinc finger protein (ZNF184) mRNA, partial cds.

1003 gi10436789Homo SapienscDNA FLJ14345 fis, 1619 57 clone THYR01001189, weakly similar to ZINC FINGER PROTEIN
91.

1005 AAB23641Homo SapiensHuman secreted protein609 100 SEQ ID

NO: 97.

1005 AAE01594Homo SapiensHuman gene 12 encoded93 35 secreted protein HHSGW69, SEQ ID

N0:144.

1005 gi5668598Homo SapiensWiskott-Aldrich syndrome92 35 protein interacting protein (WASPIP) mRNA, partial cds.

1006 gi11493473Homo SapiensPR02225 163 67 ~

1006 gi9654986Vibrio autoinducer-2 production64 33 cholerae protein 1006 AAG02328Homo SapiensHuman secreted protein,58 45 SEQ ID

NO: 6409.

1008 AAM00955Homo SapiensHuman bone marrow 704 100 protein, SEQ

ID NO: 431.

1008 gi4902661Homo SapiensNovel human gene 635 100 mapping to chomosome 22.

1008 gi12052896Homo SapiensmRNA; cDNA DKFZp564F1978635 100 (from clone DKFZp564F1978);

complete cds.

1009 AAE01420Homo SapiensHuman secreted protein612 100 fragment, SEQ ID NO:144.

1009 gi4028545Homo SapiensLIM domain only 7 65 44 (LM07) gene, exon T and alternative splice products, partial cds.

1009 gi1620061Parameciuma389R 66 46 bursaria Chlorella virus Table 2A

SE Hit ID S ecies Description S score% Identi ID

1010 19408382 Raja eglanteriaeos 79 26 1010 gi2062744Xenopus Ikaros homolog 63 27 laevis/gilli 1010 gi1199604Homo SapiensHuman zinc finger 97 27 protein C2H2-25 mRNA, complete cds.

1011 gi1309?207Homo sapiensribosomal protein, 332 100 large, P1, clone MGC:5215 IMAGE:2900846, mRNA, complete cds.

1011 gi14043204Homo Sapiensribosomal protein, 332 100 large, P1, clone MGC:15616 IMAGE:3343021, mRNA, complete cds.

1011 gi190234 Homo SapiensHuman acidic ribosomal332 100 phosphoprotein P
1 mRNA, com lete cds.

1012 AAW88457 Homo SapiensHuman lysophospholipase1113 93 IHLP.

1012 AAY64648 Homo SapiensHuman lysophospholipase825 100 homology protein.

1012 gi10303289Neurosporarelatedtolysophospholipase201 34 crassa 1013 gi14043417Homo Sapiensclone IMAGE:3953868,919 98 mRNA, partial cds.

1013 gi15080096Homo Sapiensclone MGC:20451 919 98 IMAGE:3830864, mRNA, complete cds.

1013 AAG81374 Homo SapiensHuman AFP protein 919 98 sequence SEQ

ID N0:266.

1014 gi13543427Homo SapiensSimilar to RIKEN 191 36 cDNA

5730469M10 gene, clone MGC:4248 IMAGE:3010078, mRNA, complete cds.

1014 AAW67858 Homo SapiensHuman secreted protein191 36 encoded by gene 52 clone HAUCC47.

1014 AAY66746 Homo SapiensMembrane-bound protein191 36 PRO1198.

1015 AAB56791 Homo sapiensHuman prostate cancer496 98 antigen protein sequence SEQ ID

N0:1369.

1015 gi2984030Aquifex phosphofructokinase 70 25 aeolicus 1015 gi1388150Haemophilusribosomal protein 51 45 ducreyi 1016 129509 Homo SapiensHuman BTG1 mRNA. 655 100 1016 150188 Mus musculusbtgl 655 100 1016 gi293306 Mus musculusB-cell translocation655 100 gene-1 protein 1017 gi13623633Homo Sapiensclone MGC:13105 2984 100 IMAGE:3957973, mRNA, complete cds.

1017 AAB81188 Homo SapiensHuman zinc anger 2389 98 protein 52 (ZFP-52).

1017 AAB95368 Homo SapiensHuman protein sequence1712 100 SEQ ID

N0:17684.

1018 gi12002127Homo SapiensCCKl protein (CCKl) 55 45 mRNA, complete cds.

1018 gi9392591Homo SapiensCC chemokine CCL28 55 45 (SCYA28) mRNA, complete cds.

1018 gi10312152Homo Sapiensmucosae-associated 55 45 epithelial chemokine mRNA, complete cds.

Table 2A
13~
SEQ Hit ID S ecies Descri tion S score% Identi ID

1019 AAB90816 Homo SapiensHuman shear stress-response365 100 protein SEQ ID NO:
140.

1019 gi10039341Dugesia Vasa-related protein67 45 dorotocephala 1019 gi15158371AgrobacteriumAGR L_42GMp 64 30 tumefaciens 1020 gi1377897Homo Sapiensheart protein (FHL-2)1631 100 mRNA, com lete cds.

1020 gi1160932Homo Sapiens(clone 35.3) DR.AL 1625 99 mRNA, complete cds.

1020 gi7209525Homo Sapiensgene for DRAL/Slim3/FHL2,1625 99 exon 5 and complete cds.

1021 gi7770259Homo SapiensPR02975 794 100 1021 gi1142588TrypanosomaCR3 55 40 brucei 1021 gi1237130EscherichiaO anti en olymerase 89 28 coli 1022 AAG81348 Homo SapiensHuman AFP protein 530 63 sequence SEQ

ID N0:214.

1022 gi4206763Arabidopsiscell wall-plasma 119 30 membrane linleer thaliana protein homolog 1022 gi2623666Canis familiarisdentatorubro-pallidoluysian101 30 atrophy protein 1023 AAG01390 Homo SapiensHuman secreted protein,297 100 SEQ ID

NO: 5471.

1023 AAB57280 Homo SapiensHuman prostate cancer66 34 antigen protein sequence SEQ ID

N0:1858.

1023 gi456681 Pseudorabieshelicase 80 26 virus 1024 gi1017722Homo SapiensHuman repressor transcriptional1344 58 factor (ZNF85) mRNA, complete cds.

1024 gi14348591Homo SapiensKRAB zinc finger 1342 58 protein (KR19) mRNA, complete cds.

1024 14454678 Homo Sapienszinc finger protein 1321 59 1025 gi165680 Oryctolagusrecombination activating2666 91 protein cuniculus 1025 gi2576246Mus musculusRAG-2 protein 2594 88 1025 gi15809414Mormoops recombination activator2387 91 protein 2 blainvillii 1026 AAG75278 Homo SapiensHuman colon cancer 1061 95 antigen protein SEQ ID NO:6042.

1026 gi211896 Gallus h-caldesmon 153 29 allus 1026 gi600255 Gallus caldesmon 153 29 gallus 1027 AAY87341 Homo SapiensHuman signal peptide699 99 containing protein HSPP-118 SEQ ID

N0:118.

1027 AAY12929 Homo SapiensAmino acid sequence 66 51 of a human secreted peptide.

1027 gi930084 Homo SapiensHuman I~ox21 mRNA 41 31 for zinc iin er protein, artial.

1028 1173324 Candida metallothionein II 37 71 glabrata 1028 gi173326 Candida metallothionein (MTII)37 71 glabrata 1028 1173328 Candida metallothionein II 37 71 glabrata 1029 AAE02058 Homo SapiensHuman four disulfide598 44 core domain (FDCD)-containing protein.

Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

1029 gi12655452Homo sapiensmRNA for keratin 557 46 associated rotein 4.7 (KRTAP4.7 gene).

1029 gi12655456Homo Sapienspartial mRNA for 540 42 keratin associated protein 4.9 (KRTAP4.9 gene).

1030 gi10639287Thermoplasmaamino acid transporter66 29 related acidophilumprotein 1030 gi14325303Thermoplasmaamino acid transporter64 28 volcanium 1030 gi15341701Homo Sapiensclone MGC:19805 60 34 IMAGE:3939974, mRNA, complete cds.

1031 gi12653801Homo sapienspeptidylprolyl isomerase820 93 A

(cyclophilin A), clone MGC:2351 IMAGE:3349335, mRNA, complete cds.

1031 gi12804335Homo Sapiensclone IMAGE:2823490,820 93 mRNA, partial cds.

1031 gi13529080Homo Sapienspeptidylprolyl isomerase820 93 A

(cyclophilin A), clone MGC:12404 IMAGE:3935025, mRNA, complete cds.

1032 gi207621Rattus uromodulin 98 36 norve icus 1032 gi912817Rattus sp. Tamm-Horsfall protein;98 36 THP

1032 gi602768Mytilus adhesive plaque matrix86 29 protein galloprovincialisprecursor 1033 AAG03055Homo SapiensHuman secreted protein,269 100 SEQ ID

NO: 7136.

1033 AAY73471Homo SapiensHuman secreted protein62 33 , clone yd153_1 protein sequence SEQ ID

N0:164.

1034 AAB38043Homo SapiensFragment of human 124 38 secreted protein encoded by gene 10 clone HWHGP71.

1034 gi5305335Mycobacteriumproline-rich mucin 114 36 homolog tuberculosis 1034 gi22599 ArabidopsisAPG 112 37 thaliana 1035 gi6467206Homo SapiensGIOT-4 mRNA for gonadotropin2004 60 inducible transcription repressor-4, complete cds.

1035 AAY58627Homo SapiensProtein regulating 1732 56 gene expression PRGE-20.

1035 gi3953593Mus musculusZinc finger protein 1720 54 sl l-6 1036 AAB95007Homo SapiensHuman protein sequence518 86 SEQ ID

N0:16685.

1036 gi45906 Proteus hlyC protein (AA 72 45 vulgaris 1-54) 1036 AAB56607Homo SapiensHuman prostate cancer74 56 antigen protein sequence SEQ ID

N0:1185.

1037 AAY27616Homo SapiensHuman secreted protein562 99 encoded by ene No. 50.

1037 gi12957417Casuarius ATPase subunit 8 62 35 bennetti 1037 gi332009Murine leukemiap15-gag protein 57 27 virus Table 2A

SEQID Hit H) S ecies Descri tion S score% Identi _ gi15822827Homo SapiensmRNA for pendrin-like1154 39 1038 protein 1, complete cds.

1038 gi13344999Homo Sapienssolute carrier family1300 37 26 member 6 (SLC26A6) mRNA, complete cds.

1038 AAY71067Homo SapiensHuman membrane transport1297 37 protein, MTRP-12.

1039 AAY57945Homo SapiensHuman transmembrane 780 100 protein HTMPN-69.

1039 AAY76141Homo SapiensHuman secreted protein780 100 encoded by gene 18.

1039 AAB24037Homo SapiensHuman PR01555 protein356 47 sequence SEQ ID N0:49.

1040 AAY59672Homo SapiensSecreted protein 553 83 FL.

1040 gi10435214Homo sapienscDNA FLJ13263 Bs, 549 82 clone OVARC 1000924.

1040 AAB94543Homo SapiensHuman protein sequence549 82 SEQ ID

N0:15290.

1041 AAY92710Homo SapiensHuman membrane-associated704 97 protein Zsig24.

1041 AAY87250Homo SapiensHuman signal peptide566 99 containing rotein HSPP-27 SEQ
ID NO:27.

1041 AAG00627Homo SapiensHuman secreted protein,260 100 SEQ ID

NO: 4708.

1042 gi14572521Homo SapiensNEPHl (NEPHl) mRNA, 1512 51 complete cds.

1042 AAB37996Homo SapiensHuman secreted protein1164 92 encoded by gene 13 clone HIBEU15.

1042 gi10434261Homo SapienscDNA FLJ12646 fis, 1035 41 clone NT2RM4001987, weakly similar to NEURAL CELL ADHESION

MOLECULE 1, LARGE

ISOFORM PRECURSOR.

1043 gi29806 Homo SapiensHuman mRNA for CD59,710 100 an LY-6-like protein regulating complement membrane attack.

1043 gi825637Homo SapiensH.sapiens gene for 710 100 CD59 protein, exon 2.

1043 gi29815 Homo SapiensHuman mRNA for CD59 710 100 anti en.

1044 gi6841140Homo SapiensHSPC100 mRNA, partial498 100 cds.

1044 gi2828808Bacillus glucose transporter 111 25 subtilis _ gi9106658~ylella glucoselgalactose 140 23 1044 transporter fastidiosa 9a5c 1045 AAB56632Homo SapiensHuman prostate cancer3377 99 antigen protein sequence SEQ ID

N0:1210.

1045 gi13097708Homo sapiensribophorin IT, clone3152 100 MGC:1817 IMAGE:3546673, mRNA, complete cds.

1045 gi5834424Homo SapiensRIBIIR gene (partial),3152 100 exon 1 and joined CDS.

1046 gi13182757Homo SapiensHTPAP mRNA, complete598 100 cds.

1046 AAG89279Homo sapiensHuman secreted protein,598 100 SEQ TD

NO: 399.

1046 AAB70690Homo SapiensHuman hDPP protein 598 100 sequence SEQ ID N0:7.

Table 2A

SEQ Hit ID S ecies Description S score% Identi ID

1047 gi2276448Homo SapiensHuman MHC class I 1794 93 HLA-A

(HLA-A-0302-new allele) mRNA, complete cds.

1047 gi6815812Homo SapiensMHC class I antigen 1794 93 heavy chain (HLA-A) mRNA, HLA-A*0302 allele, complete cds.

1047 gi1245460Homo SapiensHuman MHC class I 1786 92 HLA-A allele (HLA-A) mRNA, complete cds.

1048 AAB95392 Homo SapiensHuman protein sequence567 78 SEQ ID

N0:17743.

1048 AAB29645 Homo SapiensHuman membrane-associated548 70 protein HUMAP-2.

1048 AAB95049 Homo SapiensHuman protein sequence396 78 SEQ ID

N0:16845.

1049 gi14017773Mus musculusCg10671-like 1517 96 1049 gi14017764Mus musculusCG10671-like 1517 96 1049 gi16198091DrosophilaLD30661p 184 30 melanogaster 1050 AAG81431 Homo SapiensHuman AFP protein 503 97 sequence SEQ

ID N0:380.

1050 gi6707026Monodelphisimmunoglobulin light108 26 chain kappa domestics 1050 gi6653413Oryctolagusimmunoglobulin light102 27 chain VJ

cuniculus kappa region 1051 '12836893Gallus IPR328-like protein 158 29 gallus 1051 gi3093433Homo sapiensChromosome 16 BAC 151 29 clone CIT987SIC-625P11, complete sequence.

1051 gi4558766Homo Sapiensneuronal voltage 151 29 gated calcium channel gamma-3 subunit mRNA, complete cds.

1052 gi4337100Homo SapiensMSH55 gene, partial 400 100 cds; and CLIC1, DDAH, G6b, G6c, GSb, G6d, G6e, G6f, BATS, GSb, CSK2B, BAT4, G4, Apo M, BAT3, BAT2, AIF-1, 1C7, LST-1, LTB, TNF, and LTA
genes, complete cds.

1052 gi5304878Homo Sapiensgenes encoding RNCC 400 100 protein, DDAH protein, Ly6-C
protein, Ly6-D protein and immunoglobulin receptor.

1052 AAY27597 Homo SapiensHuman secreted protein400 100 encoded by gene No. 31.

1053 AAB88325 Homo sapiensHuman membrane or 912 99 secretory protein clone PSEC0020.

1053 AAB53257 Homo SapiensHuman colon cancer 859 99 antigen protein sequence SEQ ID NO:797.

1053 gi13325409Homo Sapiensclone IMAGE:3845253,774 100 mRNA, partial cds.

1054 gi1234787Xenopus up-regulated by thyroid917 61 laevis hormone in tadpoles; expressed specifically in the tail and only at metamorphosis; membrane bound or extracellular protein; C-terminal basic region 1054 gi10435980Homo SapienscDNA FLJ13840 fis, 812 62 clone Table 2A

SE ID Hit ID S ecies Descri tion S score% Identi THYR01000783, moderately similar to Xenopus laevis tail-speciflc thyroid hormone up-regulated ( ene 5) mRNA.

1054 AAB94773Homo SapiensHuman protein sequence812 62 SEQ ID

N0:15860.

1055 gi4099139Homo SapiensHuman P2X4 purinoreceptor2014 100 gene, exons 9, 10, 11 and 12 and complete cds.

1055 gi4099121Homo SapiensHuman P2X4 purinoreceptor2014 100 mltNA, complete cds.

1055 AAW47066Homo SapiensHuman brain P2X-1 2014 100 receptor polype tide.

1056 AAE03560Homo SapiensHuman differentially1020 99 expressed kidney cDNA 22360 encoded protein.

1056 115637151Beta vulgarisglycine decarboxylase62 36 subunit P

1056 gi5824822CaenorhabditisY53F4A.2 62 25 elegans 1057 gi972946Mus musculusZP1 precursor 2217 67 1057 gi1113794Mus musculuszona pellucida 2210 67 1057 gi2804566Rattus zona pellucida 1 2200 67 glycoprotein norvegicus 1058 gi15779156Homo SapiensSimilar to RIKEN 1858 100 cDNA

1810073N04 gene, clone MGC:15523 IMAGE:3028844, mRNA, complete cds.

1058 gi13097045Mus musculusSimilar to RIKEN 1719 91 cDNA

1810073N04 gene 1058 gi603254SaccharomycesYe1064cp 319 27 , cerevisiae 1059 AAW03516Homo SapiensProstaglandin DP 1467 100 receptor.

1059 gi940379Homo SapiensHuman DP prostanoid 1467 100 receptor (PTGDR) gene, 5' region and partial cds.

1059 gi4567038Rattus prostaglandin D2 1127 77 receptor norvegicus 1060 gi2811122Xenopus NaDC-2 1274 56 laevis 1060 gi1098557Homo SapiensHuman renal sodium/dicarboxylate1618 55 cotransporter (NADC1) mRNA, complete cds.

1060 gi3168585Rattus sodium-dependent 1614 54 dicarboxylate norvegicustransporter 1061 gi3036840Homo SapiensmltNA for cystinosin.1686 88 1061 gi3036851Homo SapiensCTNS gene, exon 3, 1686 88 flanking intronic regions and joined CDS.

1061 gi7239176Homo sapiensvanilloid receptor 1686 88 gene, partial sequence; CARI~L
and CTNS

genes, complete cds;
TIP1 gene, partial cds; P2X5b and P2X5a genes, complete cds;
and HUMINAE gene, partial cds.

1062 gi41077 Escherichiacal protein precursor63 42 coli (aa 1-51) 1062 gi6474978SchizosaccharomAmino acid permease 62 27 yces pombe 1062 AAB40157Homo SapiensHuman secreted protein60 27 sequence encoded by gene 7 SEQ ID N0:67.

Table 2A

SEQ Hit ID S ecies Description S score% Identi ID

1063 AAY36071 Homo SapiensExtended human secreted1252 92 protein sequence, SEQ ID
NO. 456.

1063 gi15990604Homo SapiensRAE-1-like transcript1022 97 4 mRNA, complete cds.

1063 AAG00501 Homo sapiensHuman secreted protein,533 95 SEQ ID

NO: 4582.

1064 gi14290560Homo SapiensSimilar to transmembrane1548 98 superfamily member 2, clone MGC:9286 IMAGE:3874367, mltNA, complete cds.

1064 gi15277509Homo SapiensSimilar to transmembrane1548 97 superfamily member 2, clone MGC:17157 IMAGE:4214662, mRNA, complete cds.

1064 gi3211722Homo Sapienslamin B receptor 1132 77 homolog TM7SF2 (TM7SF2) mRNA, complete cds.

1066 AAE06611 Homo SapiensHuman protein having1552 99 hydrophobic domain, HP03696.

1066 gi13676372Homo Sapiensclone MGC:4595 469 50 IMAGE:3345729, mRNA, complete cds.

1066 AAY41690 Homo sapiensHuman PRO329 protein469 50 sequence.

1067 AAG72119 Homo SapiensHuman olfactory receptor1036 81 polypeptide, SEQ
ID NO: 1800.

1067 gi3769616Rattus olfactory receptor 887 81 norve icus 1067 gi12054453Homo Sapiens6M1-18*O1 gene for 547 42 olfactory receptor, cell line BM28.7.

1068 17106778 Homo sa HSPC194 530 95 iens 1068 AAW64547 Homo SapiensHuman stomach cancer530 95 cell clone HP 10175 protein.

1068 AAY35949 Homo SapiensExtended human secreted530 95 protein sequence, SEQ ID
NO. 198.

1069 gi402185 Homo SapiensH.sapiens ALK-2 mRNA.1572 100 1069 gi338219 Homo SapiensHuman novel serine 1572 100 kinase receptor mRNA, complete cds.

1069 AAR85206 Homo SapiensHuman ALK-2. 1572 100 1070 gi4128041Homo Sapiensclaudin-9 (CLDN9) 227 35 ene.

1070 AAB64401 Homo SapiensAmino acid sequence 227 35 of human intracellular signalling molecule INTRA33.

1070 gi4325296Mus musculusclaudin-9 214 34 1071 gi1405893Homo sapiensH.sapiens MICA gene.1896 93 1071 AAW60043 Homo SapiensHuman MHC class I 1896 93 chain-related ene A (MICA) polypetide.

1071 gi508492 Homo SapiensHuman MHC class I-related1838 90 protein mRNA, complete cds.

1072 gi15292437DrosophilaLP10272p 444 39 melanogaster 1072 gi4877582Homo Sapienslipoma HMGIC fusion 221 28 partner (LHFP) mRNA, complete cds.

1072 AAY87336 Homo SapiensHuman signal peptide221 28 containing protein HSPP-113 SEQ ID

N0:113.

1073 AAB58289 Homo SapiensLung cancer associated1338 100 Table 2A

SEQ Hit ID S ecies Description S score% Identi ID

polypeptide sequence SEQ ID 627.

1073 AAY29332Homo SapiensHuman secreted protein1338 100 clone pe584 2 protein sequence.

1073 AAB75295Homo SapiensHuman secreted protein1247 100 sequence encoded by gene 7 SEQ ID

N0:114.

1074 AAB58289Homo SapiensLung cancer associated1338 100 polypeptide sequence SEQ ID 627.

1074 AAY29332Homo SapiensHuman secreted protein1338 100 clone pe584 2 protein sequence.

1074 AAB75295Homo SapiensHuman secreted protein1247 100 sequence encoded by gene 7 SEQ ID

N0:114.

1075 AAE04780Homo SapiensHuman vesicle trafficking864 100 protein-23 (VETRP-23) protein.

1075 AAB28629Homo SapiensHuman B11Ag1 antigen546 39 splice isoform B11C-8.

1075 AAB28630Homo SapiensHuman B11Ag1 antigen546 39 splice isoform B 11 C-9-16.

1076 gi15811373Mus musculusG protein coupled 1269 83 receptor affectin testicular descent 1076 gi10441730Homo sapiensleucine-rich repeat-containing1004 62 G

protein-coupled receptor 7 (LGR7) mRNA, complete cds.

1076 AAY42170Homo SapiensHuman LGR7 long form1004 62 protein sequence.

1077 gi13544043Homo Sapiensclone IMAGE:3627317,1257 52 mRNA, partial cds.

1077 gi14249892Homo Sapiensspinster-like protein,1257 52 clone MGC:15767 IMAGE:3501826, mRNA, complete cds.

1077 gi12003980Homo sapiensspinster-like protein1257 52 mRNA, complete cds.

1078 AAB85029Homo SapiensProtein encoded by 1618 68 BAP28 cDNA

consisting of exons 1 to 45.

1078 AAW54099Homo SapiensHomo Sapiens BAP28 1617 67 sequence.

1078 gi7022341Homo SapienscDNA FLJ10359 fis, 1588 92 clone NT2RM2001243.

1079 gi13491841Rattus gamma-glutamyltranspeptidase-209 34 norvegicus like protein 1079 AAG75266Homo SapiensHuman colon cancer 217 100 antigen protein SEQ ID N0:6030.

1079 gi57806 Rattus sp. gamma-glutamyltranspeptidase186 33 (AA 1-568) 1080 gi5262646Homo SapiensmRNA; cDNA DI~FZp434I0912917 100 (from clone DI~FZp434I091);

partial cds.

1080 gi6807820Homo SapiensmRNA; cDNA DKFZp434A2372629 100 (from clone DI~FZp434A2372);

partial cds.

1080 gi1408182Homo SapiensHuman LGN protein 282 31 mRNA, complete cds.

1081 gi4878022Homo Sapiensacyl-coenzyme A: 930 98 cholesterol acyltransferase mRNA, complete cds.

1081 AAR53079Homo SapiensAcetyl coenzyme A: 925 98 cholesterol acetyltransferase (ACAT).

Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

1081 AAW38416Homo SapiensHuman acyl-coenzyme 925 98 A:cholesterol acyltransferase I.

1082 gi458938SaccharomycesYhr186cp 1004 58 cerevisiae 1082 gi5921144Schizosaccharommipl 2049 52 yces pombe 1082 gi9366720Trypanosomapossible t16o11.22 277 45 protein.

brucei 1083 gi402187Homo SapiensH.sapiens ALK-3 mRNA.1664 99 1083 AAR55368Homo SapiensHuman Activin receptor-like1664 99 kinase 3 (hALK-3).

1083 AAR85207Homo SapiensHuman ALK-3. 1664 99 1084 1609354 Xenopus BMP receptor 1485 90 laevis 1084 gi2446992Xenopus 'BMP receptor' 1483 89 laevis 1084 gi3551073Danio reriotype I serin/threonine1451 87 kinase receptor 1085 AAW90873Homo SapiensHuman brain-specific1340 53 dysferlin protein.

1085 gi3600028Homo Sapiensdysferlin mRNA, complete1340 53 cds.

1085 AAY82643Homo SapiensHuman dysferlin protein1340 53 sequence SEQ ID NO:2.

1086 gi3600028Homo Sapiensdysferlin mRNA, complete1866 49 cds.

1086 AAY82643Homo SapiensHuman dysferlin protein1866 49 sequence SEQ ID N0:2.

1086 AAW90868Homo SapiensHuman dysferlin protein.1866 49 1087 AAY92321Homo SapiensHuman alpha-2-delta-D5881 99 calcium channel subunit.

1087 AAB62262Homo SapiensHuman calcium channel5745 99 alpha2delta subunit.

1087 AAY92323Homo SapiensHuman alpha-2-delta-D4976 99 polypeptide from splice variant 1.

1088 gi2104689Mus musculusalpha lucosidase 1796 55 II, alpha subunit 1088 gi1890664Sus scrofaglucosidase II 1792 55 1088 gi7672977Homo Sapiensglucosidase II alpha1783 55 subunit mRNA, complete cds.

1089 AAY01143Homo SapiensSecreted protein 238 100 encoded by gene 9 clone HSIDY06.

1089 gi6692409Otus longicorniscytochrome b 64 38 1089 gi10312185Otus watsoniicytochrome b 61 43 1090 gi13477285Homo Sapiensstructure specific 3683 100 recognition protein 1, clone MGC:1608 IMAGE:3536048, mRNA, complete cds.

1090 gi184242Homo SapiensHuman high mobility 3683 100 group box (SSRP1) mRNA, complete cds.

1090 AAR38744Homo SapiensHuman SSRP. 3683 100 1091 gi177814Homo SapiensHuman alpha-1-antitrypsin-related1925 90 protein gene, exons 3, 4 and 5.

1091 AAP50132Homo SapiensSequence of the predominant828 59 form of human alpha-1-antitrypsin(AT).

1091 gi15990507Homo SapiensSimilar to serine 1409 66 (or cysteine) proteinase inhibitor, Glade A

(alpha-1 antiproteinase, antitrypsin), member 1, clone MGC:23330 IMAGE:4644658, mRNA, complete Gds.

Table 2A

SE ID Hit ID S ecies . Descri ~tion S score% Identi 1092 AAB56819Homo SapiensHuman prostate cancer1054 100 antigen protein sequence SEQ ID

N0:1397.

1092 115981490Yersinia protease 137 28 pestis 1092 gi9654995Vibrio protease DegS 135 29 cholerae 1093 gi13543976Homo sapiensclone IMAGE:3603998,1523 100 mRNA, partial cds.

1093 gi15930240Homo SapiensSimilar to CAP-binding1523 100 protein complex interacting protein 2, clone MGC:9962 IMAGE:3878011, mRNA, complete cds.

1093 AAY57946Homo SapiensHuman transmembrane 1128 100 protein HTMPN-70.

1094 AAY53031Homo SapiensHuman secreted protein590 93 clone dd426_1 protein sequence SEQ ID

N0:68.

1094 AAY71062Homo sapiensHuman membrane transport158 26 protein, MTRP-7.

1094 gi15529155ArabidopsisAT3g30390/T6J22_16 135 22 thaliana 1095 gi4959568Homo Sapiensnuclear pore complex1650 94 interacting protein NPIP (NPIP) mRNA, complete cds.

1095 gi2342743Homo SapiensHuman Chromosome 1627 93 clone CIT987SK-A-589H1, complete sequence.

1095 AAY10915Homo SapiensAmino acid sequence 760 88 of a human secreted peptide.

1096 gi7022118Homo sapienScDNA FLJ10213 fis, 1074 99 clone HEMBA1006474, weakly similar to 40 KD PROTEIN.

1096 AAB92609Homo SapiensHuman protein sequence1074 99 SEQ ID

N0:10874.

1096 gi456886Borna diseasep40 396 41 virus 1097 gi38432 Homo SapiensH.sapiens gene for 612 90 mitochondria) ATP synthase c subunit (P2 form).

1097 gi285910Homo SapiensP2 mRNA for ATP synthase612 90 subunit c, complete cds.

1097 AAB43694Homo SapiensHuman cancer associated612 90 protein sequence SEQ ID N0:1139.

1098 gi897827Homo SapiensHuman iron-responsive4968 99 element-binding protein/iron regulatory protein 2 (IRE-BP2/IRP2) mRNA, partial cds.

1098 gi897581Homo sapiensHuman iron-regulatory4909 99 protein 2 (IRP2) mRNA, partial cds.

1098 gi897583Rattus iron-regulatory protein4700 93 norvegicus 1099 gi5732908Homo sapiensBPAGln3 (BPAG1) mRNA,75 32 partial cds.

1099 AAY87302Homo SapiensHuman signal peptide61 35 containing protein HSPP-79 SEQ
ID N0:79.

1099 AAY76213Homo SapiensHuman secreted protein61 35 encoded by gene 90.

1100 gi5732908Homo sapiensBPAGln3 (BPAGl) mRNA,75 32 Table 2A

SE ID Hit ID S ~ecies Description S score% Identi partial cds.

1100 AAY87302Homo sapiensHuman signal peptide61 35 containing protein HSPP-79 SEQ
ID N0:79.

1100 AAY76213Homo SapiensHuman secreted protein61 35 encoded by gene 90.

1101. gi5732908Homo sapiensBPAGln3 (BPAGl) mRNA,75 32 partial cds.

1101 AAY87302Homo SapiensHuman signal peptide61 35 containing protein HSPP-79 SEQ
ID N0:79.

1101 AAY76213Homo SapiensHuman secreted protein61 35 encoded by gene 90.

1102 AAY86234Homo SapiensHuman secreted protein88 31 HNTNC20, SEQ ID N0:149.

1102 gi5430769ArabidopsisSimilar to somatic 88 32 embryogenesis thaliana rece tor-like kinase 1102 AAB24074Homo SapiensHuman PR01153 protein79 22 sequence SEQ ID N0:49.

1103 gi13447199Homo Sapienssphingosine-1-phosphate1931 98 phosphatase mRNA, complete cds.

1103 gi9623190Mus musculussphingosine-1-phosphate1692 83 phosphohydrolase 1103 gi15778670Mus musculussphingosine-1-phosphate1692 83 phosphatase 1104 gi12052824Homo SapiensmRNA; cDNA DKFZp564H15621544 100 (from clone DKFZp564H1562);

complete cds.

1104 gi5326797Homo Sapiensfunctional adhesion 1544 100 molecule (JAMl) mRNA, complete cds.

1104 gi5731339Homo Sapiensfunctional adhesion 1544 100 molecule-1 mRNA, complete cds.

1105 gi296636Homo SapiensHuman apoC-II gene 506 100 for preproapolipoprotein C-II.

1105 gi757915Homo SapiensHuman mRNA for lipoprotein506 100 apoCII.

1105 gi178836Homo SapiensAPOC2 gene, complete506 100 sequence;

and apolipoprotein C-II (APOC2) gene, complete cds.

1106 gi13097159Homo Sapienstumor protein, translationally-794 97 controlled 1, clone MGC:5308 IMAGE:2899964, mRNA, complete cds.

1106 gi7573519Homo SapiensTPT1 gene for translationally794 97 controlled tumor protein (TCTP), exons 1-6.

1106 gi37496 Homo SapiensHuman mRNA for translationally794 97 controlled tumor protein.

1107 gi12082725Mus musculusB cell phosphoinositide3523 84 3-kinase adaptor 1107 gi12082723Gallus gallusB cell phosphoinositide2821 69 ~ 3-kinase adaptor 1107 AAB43816Homo SapiensHuman cancer associated1257 98 protein sequence SEQ ID N0:1261.

1108 gi10177622Arabidopsisgene id:K6M13.11~ 201 39 thaliana 1108 gi10437414Homo SapienscDNA: FLJ21330 fis, 165 34 clone COL02466.

Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

1108 gi499199Schizosaccharomuvi22 155 33 yces ombe 1109 gi 13436446Homo Sapiensmyosin regulatory 881 99 light chain, clone MGC:4405 IMAGE:2906108, mRNA, complete cds.

1109 gi829623Homo SapiensHuman myosin regulatory881 99 light chain mRNA, complete cds.

1109 gi15076511Homo SapiensMLC-2 mRNA for nonmuscle881 99 myosin light chain 2, complete cds.

1110 gi5305502Mus musculusphospholemman precursor153 45 1110 gi1916012Rattus phospholemman chloride142 53 channel norvegicus 1110 gi1916010Homo SapiensHuman phospholemman 133 47 chloride channel mRNA, complete cds.

1111 gi13272522Homo Sapienstranscription factor1344 90 NYD-spl0 mRNA, complete cds.

1111 gi14278918Homo SapiensmRNA for transcription1166 82 factor RFX4, complete cds.

1111 gi583352synthetic does not include 162 29 the start of stop construct codon 1112 AAB47296Homo SapiensPR04401 polypeptide.1062 58 1112 AAY22496Homo SapiensHuman secreted protein1062 58 sequence clone cn621_8.

1112 gi14042441Homo SapienscDNA FLJ14724 fis, 400 43 clone NT2RP3001716.

1113 gi15341863Homo SapiensSimilar to RIKEN 758 98 cDNA

2900052H21 gene, clone MGC:21625 IMAGE:4214683, mRNA, complete cds.

1113 AAY33297Homo SapiensHuman membrane spanning758 98 protein MSP-4.

1113 AAB61149Homo SapiensHuman NOV18 protein.758 98 1114 gi11125139Homo SapiensNovel human gene 476 89 mapping to chomosome 22.

1114 AAY94914Homo SapiensHuman secreted protein476 89 clone pw337_6 protein sequence SEQ ID

N0:34.

1114 gi602584Methanosarcinacytochrome b 75 33 mazei 1115 AAG72267Homo SapiensHuman olfactory receptor1281 100 polypeptide, SEQ
ID NO: 1948.

1115 AAG72407Homo SapiensHuman OR-like polypeptide1281 100 query sequence, SEQ ID
NO: 2088.

1115 AAG72270Homo SapiensHuman olfactory receptor997 73 polypeptide, SEQ
ID NO: 1951.

1116 gi12002782Homo Sapiensolfactory receptor-like1538 100 protein JCG2 (JCG2) mRNA, partial cds.

1116 gi12002784Homo sapiensolfactory receptor-like1538 100 protein JCG2 (JCG2) gene, complete cds.

1116 AAE04555Homo SapiensHuman G-protein coupled1538 100 receptor-11 (GCREC-11) protein.

1117 gi5802817Homo Sapiensendogenous retrovirus479 77 HERV-K104 long terminal repeat, complete sequence;
and Gag protein (gag) and envelope protein (env) genes, complete cds.

Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

1117 gi1469243Human pol/env 466 77 endogenous retrovirus K

1117 gi3150438Human pol-env 466 77 endogenous retrovirus K

1118 AAG89341Homo SapiensHuman secreted protein,501 99 SEQ ID

NO: 461.

1118 gi6651037Mus musculussimilar to RNA binding411 96 protein domesticus 1118 AAG02095Homo SapiensHuman secreted protein,167 55 SEQ ID

NO: 6176.

1119 AAB20155Homo SapiensSecreted protein 3983 51 SECP1.

1119 gi3080663Homo SapiensPAC clone RPS-1168D111408 47 from 7p21-p22, complete sequence.

1119 gi2897863Homo SapiensBAC clone GS1-164B5 1340 50 from 7p21-p22, complete sequence.

1120 gi32329 Homo SapiensHuman HMG-17 gene 429 94 for non-histone chromosomal protein HMG-17.

1120 gi306864Homo SapiensHuman non-histone 429 94 chromosomal protein HMG-17 mRNA, complete cds.

1120 AAB28199Homo sapiensHuman HMG-17 non 429 94 histone chromosomal protein.

1121 gi 13905022Homo SapiensSimilar to interferon444 69 induced transmembrane protein 3 (1-8U), clone MGC:5225 IMAGE:2986145, mRNA, complete cds.

1121 gi14250038Homo SapiensSimilar to interferon436 68 induced transmembrane protein 3 (1-8U), clone MGC:14565 IMAGE:4075453, mRNA, complete cds.

1121 gi23398 Homo sapiensHuman 1-8U gene from435 67 interferon-inducible gene family.

1122 gi7019933Homo SapienscDNA FLJ20071 fis, 2163 100 clone COL01887.

1122 AAB36618Homo SapiensHuman FLEXHT-40 protein1051 100 sequence SEQ ID N0:40.

1122 AAW88957Homo SapiensPolypeptide fragment902 100 encoded by gene 128.

1123 AAB60112Homo SapiensHuman transport protein775 100 TPPT-32.

1123 gi11558029Homo Sapiensboct gene for organic382 48 canon transporter.

1123 gi9663117Homo sapiensmRNA for organic 382 48 cation transporter.

1124 AAR28120Homo SapiensNKG2 transmembrane 727 95 protein-D.

1124 gi2980865Homo SapiensNKG2D gene, exons 724 94 2-5 and joined mRNA and CDS.

1124 gi35063 Homo SapiensHuman mRNA for NKG2-D724 94 gene.

1125 gi7767239Homo sapiensnectin-like protein 612 39 2 (NECL2) mRNA, complete cds.

1125 gi4519602Homo SapiensIGSF4 gene, exon 609 38 10 and complete cds.

1125 AA1'45092Homo SapiensHuman lymphoid derived609 38 dendritic Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

cell adhesion molecule.

1126 gi7020365Homo SapienscDNA FLJ20336 fls, 4316 99 clone HEP 11722.

1126 gi10435830Homo SapienscDNA FLJ13727 fls, 3079 99 clone PLACE3000103.

1126 AAB94738Homo SapiensHuman protein sequence3079 99 SEQ ID

N0:15776.

1127 AAB75594Homo SapiensHuman secreted protein678 99 sequence encoded by gene 37 SEQ ID

N0:148.

1127 AAB75542Homo SapiensHuman secreted protein294 100 sequence encoded by gene 37 SEQ ID

N0:96.

1127 gi1864011Homo SapiensmRNA for SHPS-1, 261 43 complete cds.

1128 gi7020372Homo SapienscDNA FLJ20340 fis, 1692 99 clone HEP 12374.

1128 gi4098525ProchlorothrixCytM 80 31 hollandica 1128 gi324932Influenza PA polymerise 67 38 A virus 1129 gi7023403Homo SapienscDNA FLJ11006 fis, 499 59 clone PLACE 1003045.

1129 AAB93412Homo SapiensHuman protein sequence499 59 SEQ ID

N0:12616.

1129 gi13542919Mus musculusSimilar to mucolipin432 61 1130 gi15488920Homo SapiensSimilar to RIKEN 107 42 cDNA

2010107623 gene, clone MGC:9596 IMAGE:3896656, mRNA, complete cds.

1130 AAW74777Homo SapiensHuman secreted protein74 40 encoded by gene 48 clone HFCAI74.

1130 gi1304441PseudorabiesRsp40 69 32 virus 1131 gi10119918Homo Sapiensbrain otoferlin short1315 49 isoform (OTOF) mRNA, complete cds.

1131 gi10119916Homo Sapiensbrain otoferlin long1315 49 isoform (OTOF) mRNA, complete cds.

1131 gi4588470Homo Sapiensotoferlin (OTOF) 2214 43 mRNA, complete cds.

1132 gi1006665Homo SapiensH.sapiens mRNA for 442 98 transcript associated with monocyte to macrophage differentiation.

1132 gi15155898AgrobacteriumAGR_C_1653p 167 31 tumefaciens 1132 gi15023850ClostridiumPredicted membrane 117 44 protein, acetobutylicumhemolysin III homolog 1133 AAG71803Homo SapiensHuman olfactory receptor1494 92 polypeptide, SEQ
ID NO: 1484.

1133 AAG71805Homo SapiensHuman olfactory receptor1205 92 polypeptide, SEQ
ID NO: 1486.

1133 AAG71807Homo SapiensHuman olfactory receptor1178 70 polypeptide, SEQ
ID NO: 1488.

1134 AAY70455Homo SapiensHuman membrane channel609 91 protein-5 (MECHP-5).

1134 AAV83992_Homo SapiensNucleic acid encoding608 92 a protein ail with water channel activity.

1134 gi2317274Homo sa mRNA for a uaporin 608 92 iens adipose, Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

complete cds.

1135 gi3319326Homo Sapiensprotein associated 111 33 with Myc mRNA, complete cds.

1136 gi2463632Homo Sapiensmonocarboxylate transporter2574 97 homologue MCT6 mRNA, complete cds.

1136 gi10880482Mus musculusmonocarboxylate transporter393 39 1136 gi2463634Homo Sapiensmonocarboxylate transporter394 40 (MCT3) mRNA, complete cds.

1137 gi13528675Homo SapiensATPase, H+transporting,705 94 lysosomal (vacuolar proton pump) l6kD, clone MGC:3723 IMAGE:3618755, mRNA, complete cds.

1137 gi13938484Homo sapiensATPase, H+transporting,705 94 lysosomal (vacuolar proton pump) l6kD, clone MGC:16271 IMAGE:3831016, mRNA, complete cds.

1137 gi14043553Homo SapiensATPase, H+transporting,705 94 lysosomal (vacuolar proton pump) l6kD, clone MGC:12873 IMAGE:4127653, mRNA, complete cds.

1138 gi15080314Homo SapiensSimilar to RII~EN 514 100 cDNA

0610010D20 gene, clone MGC:20590 IMAGE:4310241, mRNA, complete cds.

1138 gi10580053Halobacteriumdihydrodipicolinate 379 33 synthase;

sp. NRC-1 DapA

1138 gi1590977Methanococcusdihydrodipicolinate 336 29 synthase jannaschii (dapA) 1139 AAE06614Homo SapiensHuman protein having1394 100 hydrophobic domain, HP03974.

1139 gi520469Oryctolagus597 as protein related1231 85 to cuniculus Na/glucose cotransporters 1139 gi338055Homo SapiensHuman Na+/glucose 705 57 cotransporter 1 mRNA, complete cds.

1140 gi6708478Mus musculusformin-like protein 1571 66 1140 gi4101720Mus musculuslymphocyte specific 1543 65 formin related protein 1140 gi1914849Mus musculusWW domain binding 299 54 protein 3;

1142 gi12052738Homo sapiensmRNA; cDNA DKFZp564H13221755 96 (from clone DKFZp564H1322);

complete cds.

1142 gi10434632Homo sapienscDNA FLJ12886 fis, 1755 96 clone NT2RP2004041, weakly similar to SYNAPSINS IA AND
IB.

1142 AAB94358Homo SapiensHuman protein sequence1755 96 SEQ ID

N0:14883.

1143 AAW54370Homo SapiensG-protein coupled 1815 100 receptor HLTEX11.

1143 AAB64854Homo SapiensHuman secreted protein1792 100 sequence encoded by gene 36 SEQ ID

N0:140.

1143 AAW70504Homo SapiensLeukocyte seven times821 46 membrane-Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

penetrating type receptor protein JEG18.

1144 gi15278128Mus musculuschemokine-like factor412 49 2 variant 2 1144 AAB51648 Homo SapiensHuman secreted protein410 100 sequence encoded by gene 29 SEQ ID

N0:88.

1144 AAE03929 Homo SapiensHuman gene 32 encoded410 100 secreted protein HTLIF12, SEQ ID N0:92.

1146 gi13477335Homo Sapiensvitamin A responsive;777 95 cytoskeleton related, clone MGC:1917 IMAGE:3510436, mRNA, complete cds.

1146 gi3746652Homo SapiensJWA protein mRNA, 777 95 complete cds.

1146 gi6563260Homo Sapiensjmx protein mRNA, 777 95 complete cds.

1147 gi2970431FlorometraNADH dehydrogenase 94 31 subunit 4 serratissima 1147 gi15042530Chilo iridescent450L 70 24 virus 1147 AAY87197 Homo SapiensHuman secreted protein90 27 sequence SEQ ID N0:236.

1148 AAB93562 Homo SapiensHuman protein sequence2402 100 SEQ ID

N0:12957.

1148 gi7023538Homo SapienscDNA FLJ11091 fis, 860 100 clone PLACE1005313.

1148 AAB93489 Homo SapiensHuman protein sequence860 100 SEQ ID

N0:12790.

1150 gi10438431Homo SapienscDNA: FLJ22155 fis, 1995 100 clone HRC00205.

1150 gi10437336Homo SapienscDNA: FLJ21267 fis, 1776 99 clone COL01717.

1150 gi7020065Homo SapienscDNA FLJ20152 ~s, 705 100 clone COL08515.

1151 gi12654159Homo Sapiensinterferon induced 569 93 transmembrane protein 1 (9-27), clone MGC:5195 IMAGE:3464598, mRNA, complete cds.

1151 gi1177476Homo SapiensH.sapiens mRNA for 569 93 interferon-induced l7kDa membrane protein.

1151 gi177802 Homo SapiensHuman interferon-inducible563 92 protein 9-27 mRNA, complete cds.

1152 AAG72230 Homo SapiensHuman olfactory receptor1615 100 polypeptide, SEQ
ID NO: 1911.

1152 AAG72382 Homo SapiensHuman OR-like polypeptide1615 100 query sequence, SEQ ID
NO: 2063.

1152 gi15293613Homo Sapiensclone OR5C1 olfactory1097 100 receptor gene, partial cds.

1153 gi784997 Homo sapiensH.sapiens mRNA for 5025 95 tumour suppressor protein, HUGL.

1153 gi1944491Homo SapiensHuman LLGL mRNA, 4797 91 complete cds.

1153 gi854124 Homo SapiensH.sapiens mRNA for 2837 58 human giant larvae homolog.

1154 AAB95830 Homo SapiensHuman protein sequence219 72 SEQ ID

N0:18850.

1154 gi7959889Homo SapiensPR02221 137 49 Table 2A

SEQ Hit ID S ecies Descri tion S score % Identi ID

1154 gi2072969Homo SapiensHuman Ll element 133 48 L1.24 p40 gene, complete cds.

1155 gi15277644Homo Sapiensamino acid transporter2487 100 (SLC7A10) ene, exon 11 and complete cds.

1155 gi9309293Homo Sapienshasc-1 mRNA for asc-type2487 100 amino acid transporter 1, complete cds.

1155 gi7415938Mus musculusascl 2329 91 1156 gi6760373Homo SapiensODZ3 (ODZ3) mRNA, 2323 100 partial cds.

1156 gi4760780Mus musculusTen-m3 2248 96 1156 16010049Gallus teneurin-2 protein 878 62 gallus 1157 gi14286298Homo sapiensclone MGC:3593 630 99 IMAGE:2963628, mRNA, complete cds.

1157 gi4877285Homo SapiensmRNA for prenylated 630 99 Rab acceptor 1.

1157 gi6563192Homo Sapiensprenylated rab acceptor630 99 1 mRNA, complete cds.

1158 gi1780976Human protease 915 58 endogenous retrovirus K

1158 gi5802824Homo Sapiensendogenous retrovirus909 59 HERV-K109, complete sequence.

1158 gi9558703Homo Sapienstandemly repeated 905 59 human endogenous retrovirus HERV-K

(HML-2.HOM), complete sequence.

1159 gi13111941Homo Sapiensvesicle-associated 804 91 soluble NSF

attachment protein receptor (v-SNARE; homolog of S. cerevisiae VTI1), clone MGC:3767 IMAGE:2958320, mRNA, complete cds.

1159 gi3861488Homo Sapiensvesicle soluble NSF 804 91 attachment protein receptor VTI2 mRNA, complete cds.

1159 AAY73339Homo SapiensHTRM clone 2056042 804 91 protein sequence.

1160 11922891Mus musculusalpha 3B chain of 10355 75 laminin-5 1160 gi5777581Homo SapiensH.sapiens mRNA for 9398 99 laminin-5, alpha3b chain.

1160 gi551597Homo Sapienslaminin-related protein8690 100 (LamA3) mRNA, complete cds.

1161 AAD05056_Homo SapiensHUMA- Human secreted1524 83 protein-aal encoding gene 4 cDNA
clone HKAAV61, SEQ ID N0:14.

1161 AAE01167Homo SapiensHUMA- Human gene 1523 82 4 encoded secreted protein HKAAV61, SEQ

ID N0:68.

1161 AAG67516Homo SapiensSMIK Amino acid sequence1523 82 of a human secreted polypeptide.

1162 AAM42034Homo SapiensHYSE- Human polypeptide900 99 SEQ

ID NO 6965.

1162 AAM40248Homo SapiensHYSE- Human polypeptide821 100 SEQ

ID NO 3393.

1162 gi491284synthetic IFN-pseudo-omega 800 98 construct 1163 AAI70234Homo SapiensAMGE- Human interleulcin-1819 100 Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

aal receptor antagonist related protein cDNA.

1163 AAD11148 Homo SapiensIMMV Human FIL-1 819 100 theta full-aal len h DNA.

1163 AAA89175_Homo SapiensHYSE- Human interleulcin-1819 100 Hy2 aal cDNA.

1164 gi340215 Homo SapiensHuman vascular endothelial1056 97 owth factor gene, axon 8.

1164 gi340301 Homo SapiensHuman vascular permeability1056 97 factor mRNA, complete cds.

1164 AAR91077 Homo SapiensPRIZ- Human vascular1056 97 endothelial growth factor-189, VEGF-189.

1166 gi1321816Gorilla interleukin-8 receptor602 90 gorilla type B

1166 gi1109691Homo SapiensHuman interleukin-8 599 88 receptor type B (IL8RB) mRNA, complete cds.

1166 gi186378 Homo SapiensHuman interleuken 599 88 8 receptor B

mRNA, complete cds.

1167 gi1160967Homo Sapienspalmitoyl-protein 1285 100 thioesterase gene, complete cds.

1167 gi1314355Homo SapiensHuman palmitoyl protein1285 100 thioesterase mRNA, complete cds.

1167 gi14250054Homo Sapienspalmitoyl-protein 1285 100 thioesterase 1 (ceroid-lipofuscinosis, neuronal 1, infantile), clone MGC:14590 IMAGE:4249991, mRNA, complete cds.

1168 gi177814 Homo SapiensHuman alpha-1-antitrypsin-related1956 90 protein ene, axons 3, 4 and 5.

1168 AAP50132 Homo SapiensZYMO- Sequence of 1009 72 the predominant form of human alpha-1-antitrypsin(AT).

1168 gi15990507Homo SapiensSimilar to serine 1450 69 (or cysteine) proteinase inhibitor, Glade A

(alpha-1 antiproteinase, antitrypsin), member 1, clone MGC:23330 IMAGE:4644658, mRNA, complete Gds.

1169 AA012931 Homo SapiensHYSE- Human polypeptide346 100 SEQ

ID NO 26823.

1169 AAO02697 Homo SapiensHYSE- Human polypeptide143 66 SEQ

ID NO 16589.

1169 AA008307 Homo SapiensHYSE- Human polypeptide137 80 SEQ

ID NO 22199.

1170 AAR15222 Homo SapiensTEXA Chronic myelogenous635 100 leukaemia-derived myeloid-related protein.

1170 gi181527 Homo SapiensHuman neutrophil 493 100 peptide (defensin) 1 mRNA, complete Gds.

1170 gi181529 Homo SapiensHuman defensin 1 493 100 protein mRNA, complete Gds.

1171 gi1001697Synechocystissensory transduction67 37 histidine sp. PCC leinase 1171 gi2353225Acromyrmexcytochrome oxidase 54 40 I

octospinosus 1171 AAG02950 Homo SapiensGEST Human secreted 54 32 protein, SEQ ID NO: 7031.

~ 1172 gi4884282Homo SapiensmRNA; cDNA DKFZp566K05241998 99 ~ ~ ~ ~ ~

Table 2A

SEQ Hit ID S ~ecies Descri tion S score% Identi ID

(from clone DKFZp566K0524);

partial cds.

1172 gi2665458Mus musculusprotein-tyrosine-phosphatase1363 63 1172 gi452194Homo SapiensHuman mRNA for protein618 48 tyrosine phosphatase (PTP-BAS, type 3), complete cds.

1173 AAY48226Homo SapiensMETA- Human prostate956 96 cancer-associated protein 12.

1173 AAM25683Homo SapiensHYSE- Human protein 956 96 sequence SEQ ID N0:1198.

1173 AAY99342Homo SapiensGETH Human PR01018 950 94 (UNQ501) amino acid sequence SEQ ID N0:8.

1174 gi178018Homo SapiensHuman activation 125 84 (Act-2) mRNA, complete cds.

1174 gi34218 Homo SapiensHuman LAG-1 mRNA. 125 84 1174 gi533213Homo Sapienssecreted T cell protein125 84 (H400; SIS-gamma) mRNA, complete cds.

1175 gi178018Homo SapiensHuman activation 123 92 (Act-2) mRNA, complete cds.

1175 gi34218 Homo SapiensHuman LAG-1 mRNA. 123 92 1175 gi533213Homo Sapienssecreted T cell protein123 92 (H400; SIS-amma) mRNA, complete cds.

1176 AAG03315Homo SapiensLEST Human secreted 314 100 protein, SE ID NO: 7396.

1176 gi965069Serratia phage-holin analog 71 40 protein marcescens 1176 gi16415877Octopus cytochrome oxidase 74 28 salutii subunit III

1177 gi178836Homo SapiensAPOC2 gene, complete453 89 sequence;

and apolipoprotein C-II (APOC2) gene, complete cds.

1177 gi296636Homo SapiensHuman apoC-II gene 453 89 for preproapolipoprotein C-II.

1177 gi757915Homo SapiensHuman mRNA for lipoprotein453 89 apoCII.

1178 AA007986Homo SapiensHYSE- Human polypeptide77 34 SEQ

ID NO 21878.

1179 AAB60502Homo SapiensINCY- Human cell 1205 100 cycle and proliferation protein CCYPR-50, SEQ ID N0:50.

1179 AAB12144Homo SapiensPROT- Hydrophobic 1205 100 domain protein isolated from WERI-RB

cells.

1179 AAG81333Homo SapiensZYMO Human AFP protein687 99 sequence SEQ ID N0:184.

1180 AAW67880Homo SapiensHiTMA- Human secreted378 97 protein encoded by gene 74 clone HNTAC73.

1180 gi9949887Pseudomonasprobable transcriptional65 41 regulator aeruginosa 1180 gi3130050Schizosaccharomhaloacid dehalogenase-like62 32 yces pombe hydrolase 1181 AAG01183Homo SapiensGEST Human secreted 278 94 protein, SEQ ID NO: 5264.

1181 AAO00621Homo SapiensHYSE- Human polypeptide84 47 SEQ

ID NO 14513.

Table 2A

SEQ Hit ID S ecies Descri tion S score% Identit ID

1181 AA002188Homo SapiensHYSE- Human polypeptide78 40 SEQ

ID NO 16080, 1182 ABB 12063Homo SapiensHYSE- Human secreted326 100 protein homologue, SEQ ID
N0:2433.

1182 AAE06730Homo sa SMIK Human CASB765 200 100 iens protein.

1182 AAW75098Homo SapiensHUMA- Human secreted143 81 protein encoded by gene 42 clone HSXBI25.

1183 gi13278924Homo Sapiensneural proliferation,748 98 differentiation and control, 1, clone MGC:4597 IMAGE:3347743, mRNA, complete cds.

1183 gi8515886Homo SapiensNPDC1-like protein 748 98 (NPDC1) mRNA, complete cds.

1183 AAB43904Homo SapiensHUMA- Human cancer 748 98 associated protein sequence SEQ ID

N0:1349.

1184 gi13128925Homo SapiensULBP2 protein mRNA, 1025 90 complete cds.

I 184 gi14530663Homo SapiensmRNA for ALLAN-alpha,1025 90 complete cds.

1184 AAY15238Homo SapiensIMMV ULBP-2 amino 1025 90 acid sequence.

1185 gi4164134Homo Sapienscosmid clone U169D2 76 36 from Xp22.1-22.2, complete sequence.

1185 AAU22866Homo SapiensHUMA- Human prostate60 35 cancer anti en, Seq ID No 385.

1185 AAM96178Homo SapiensHUMA- Human reproductive60 35 system related antigen SEQ ID

NO: 4836.

1186 gi7770223Homo SapiensPRO2714 282 84 1186 ABB 15615Homo SapiensHUMA- Human nervous 63 48 system related polypeptide SEQ ID NO

4272.

1186 AA007531Homo SapiensHYSE- Human polypeptide67 46 SEQ

ID NO 21423.

1187 AAE05962Homo SapiensHYSE- Human phospholipase-2521 99 ~

related protein.

1187 gi3811347Homo Sapienscytosolic phospholipase1209 44 A2 beta (cPLA2 beta) mRNA, complete cds.

1187 gi4886978Homo Sapienscytosolic phospholipase1209 44 A2 beta mRNA, complete cds.

1188 AA001938Homo SapiensHYSE- Human polypeptide93 36 SEQ

ID NO 15830.

1188 gi2992470Mus sp. mitochondrial capsule95 31 selenoprotein; MCS

1188 gi14717800Mus musculusseleno-protein 95 31 1189 gi186600Homo SapiensHuman inter-alpha-trypsin1461 93 inhibitor light chain (ITI) gene, exons 7-10.

1189 gi24479 Homo SapiensHuman mRNA for alpha-1-1461 93 microglobulin and HI-30.

1189 gi32047 Homo SapiensHuman mRNA for protein1461 93 HC

(alpha-1-micro lobulin).

1190 gi673422Homo SapiensH.sapiens mRNA fragment1322 93 for T-cell receptor alpha chain.

Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

1190 AAU69943Homo SapiensLORI- Human T cell 1097 77 receptor Va chain of clone 4E5 for prostate protein P501S, 1190 AAM01298Homo SapiensCORI- P501S-specific1097 77 T cell clone 4E5 Va chain T cell receptor amino acid.

1191 gi673422Homo SapiensH.sapiens mRNA fragment859 95 for T-cell receptor alpha chain.

1191 gi623119Macaca T-cell receptor alpha605 86 mulatta 1191 AAU69943Homo SapiensLORI- Human T cell 594 65 receptor Va chain of clone 4E5 for prostate protein P501S.

1192 gi13097588Homo Sapiensclone MGC:10745 201 100 IMAGE:2820343, mRNA, complete cds.

1192 gi53861 Mus musculusQ300 protein (AA 72 38 1-77) 1192 AA002105Homo SapiensHYSE- Human polypeptide50 56 SEQ

ID NO 15997.

1193 AAB08894Homo SapiensHUMA- Human secreted208 57 protein sequence encoded by gene 4 SEQ

ID NO:51.

1193 gi15088679Homo Sapienscysteine and tyrosine-rich59 28 protein 1 (CYYRl) mRNA, complete cds.

1193 AAY87233Homo SapiensINCY- Human signal 59 28 peptide containing protein ID NO:10.

1194 AAG03963Homo SapiensGEST Human secreted 417 80 protein, SEQ ID NO: 8044.

1194 ABB 10168Homo SapiensHUMA- Human cDNA 289 100 SEQ ID

NO: 476.

1194 ABB10412Homo SapiensHUMA- Human cDNA 289 100 SEQ ID

NO: 720.

1195 gi9758052Arabidopsis 64 46 thaliana 1195 gi6815537Human gag protein 47 62 immunodeficienc y virus type 1 1195 114269033Sus scrofainterferon beta-1 42 47 1196 gi7582276Homo SapiensBM-002 328 100 1196 AAM78626Homo SapiensHYSE- Human protein 328 100 SEQ ID

NO 1288.

1196 AAM79610Homo SapiensHYSE- Human protein 328 100 SEQ ID

NO 3256.

1197 gi1181885Mus musculuspatched 209 62 1197 AAV21590Homo SapiensSTRD Human patched 215 63 (ptc) aal protein encoding cDNA.

1197 gi1335864Homo SapiensHuman patched homolog214 63 (PTC) mRNA, complete cds.

1198 AAB25674Homo SapiensHUMA- Human secreted646 84 protein sequence encoded by gene 10 SEQ

ID N0:63.

1198 gi14603247Homo SapiensSimilar to RII~EN 420 94 cDNA

5730409615 gene, clone MGC:19636 IMAGE:2822323, mRNA, complete cds.

1198 AAB36613Homo SapiensINCY- Human FLEXHT-35420 94 protein sequence SEQ ID N0:35.

Table 2A

SEQ Hit ID S ecies ~~ Description S score% Identi ID

1200 AAU12292Homo SapiensGETH Human PR06027 990 98 polypeptide sequence.

1200 AAU27673Homo SapiensZYMO Human protein 987 99 AFP235412.

1200 gi13477121Homo Sapiensclone IMAGE:3636082,291 95 mRNA, partial cds.

1201 AAB43928Homo SapiensHUMA- Human cancer 216 58 associated protein sequence SEQ ID

N0:1373.

1201 gi13325337Homo Sapiensclone MGC:10520 219 48 IMAGE:3938462, mRNA, complete cds.

1201 AAB21040Homo Sapiens1NCY- Human nucleic 219 48 acid-binding protein, NuABP-44.

1202 AAB43928Homo SapiensHUMA- Human cancer 223 55 associated protein sequence SEQ ID

N0:1373.

1202 gi16550327Homo SapienscDNA FLJ31005 fis, 215 67 clone HLUNG2000068, wealdy similar to ZINC FINGER PROTEIN
157.

1202 gi16552980Homo SapienscDNA FLJ32768 fis, 215 67 clone TESTI2001879, weakly similar to ZINC FINGER PROTEIN
157.

1203 gi4322936Homo sapiensHPI~/GCK-like kinase120 85 HGK

mRNA, complete cds.

1203 gi4262362Caenorhabditisalternatively spliced119 81 elegans serine/threonine protein kinase 1203 AAB50058Homo SapiensIMMV SS-4694. 117 81 1204 11754714Xenopus oviductin 378 40 laevis 1204 gi15277254Bufo japonicusoviductin 351 36 1204 gi2981641Xenopus polyprotein 339 46 laevis 1205 gi15214578Homo Sapiensclone MGC:9135 451 76 IMAGE:3865141, mRNA, complete cds.

1205 AAW67901Homo SapiensHUMA- Human secreted451 76 protein encoded by gene 36 clone HODCL36.

1205 gi1946205Homo SapiensH.sapiens mRNA for 445 75 CHDS

protein.

1206 AAG01971Homo SapiensGEST Human secreted 314 100 protein, SEQ ID NO: 6052.

1206 gi4200340LycopersiconP69D protein 83 43 esculentum 1206 gi3183989LycopersiconP69E protein 82 43 esculentum 1207 gi14043211Homo SapiensSimilar to RIKEN 878 83 cDNA

4931428F04 gene, clone IMAGE:3346497, mRNA, partial cds.

1207 gi9711595XanthomonasHpaA 71 24 oryzae pv.

oryzae 1207 AA010768Homo SapiensHYSE- Human polypeptide72 34 SEQ

ID NO 24660.

1208 AAY91512Homo SapiensHUMA- Human secreted606 100 protein sequence encoded by gene 62 SEQ

Table 2A

SEQ Hit ID Species Descri tion S score % Identi ID

ID N0:185.

1208 AAY91653_ HUMA- Human secreted606 100 Homo Sapiensprotein sequence encoded by gene 62 SEQ

ID N0:326.

1208 AAY71277Homo sa ZYMO Human Zlipo3 606 100 iens protein.

1209 AAY27648Homo SapiensHUMA- Human secreted322 98 protein encoded by gene No.
82.

1209 gi7959897Homo SapiensPR02379 72 39 1209 AA003791Homo SapiensHYSE- Human polypeptide61 68 SEQ

ID NO 17683.

1210 gi17431247Ralstonia HYPOTHETICAL PROTEIN70 38 solanacearum 1211 AAB08765Homo SapiensINCY- A human leukocyte339 62 and blood related protein (LBAP).

1211 AAB74718Homo SapiensINCY- Human membrane314 66 associated protein MEMAP-24.

1211 gi2587024Homo SapiensmRNA containing human259 67 endogenous retrovirus H and human endogenous retrovirus E

sequences.

1212 gi10440139Homo SapienscDNA: FLJ23447 fis, 1339 95 clone HSI03346.

1212 AAY13396Homo SapiensGETH Amino acid sequence872 48 of protein PR0332.

1212 AAB33425Homo SapiensGETH Human PR0332 872 48 protein UNQ293 SEQ ID N0:57.

1213 AAG66547Homo SapiensHYSE- Human secreted1551 99 metallocarboxypeptidase-like polypeptide.

1213 AAG66565Homo SapiensHYSE- Human secreted1548 98 metallocarboxypeptidase-like variant polypeptide.

1213 AAB74682Homo SapiensINCY- Human protease1482 98 and protease inhibitor PPIM-15.

1214 gi15528833Homo SapiensFc receptor-like 528 100 protein 2 (FCRH2) mRNA, complete cds.

1214 AAB85464Homo SapiensHYSE- Human immunoglobulin528 100 domain-containing polypeptide.

1214 AAB82317Homo SapiensUYCO Human immunoglobulin528 100 receptor IRTA4 protein.

1215 AAU27663Homo SapiensZYMO Human protein 555 100 AFP285042.

1215 AAE06599Homo SapiensSAGA Human protein 510 100 having hydrophobic domain, HP10782.

1215 gi15558917Magnaporthesimilarity to Lec35 169 30 protein grisea 1216 gi10439008Homo sapienscDNA: FLJ22573 fis, 682 99 clone HSI02387.

1216 AAM87876Homo SapiensHUMA- Human 169 70 immune/haematopoietic antigen SEQ ID NO:15469.

1216 gi1616747Tupaia GnRH preprohormone 68 33 glis second belangeri form 1217 gi10439008Homo SapienscDNA: FLJ22573 fis, 529 92 clone HSI02387.

1217 AAM87876Homo SapiensHUMA- Hurnan 109 71 Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

immune/haematopoietic antigen SEQ ID N0:15469.

1217 AAM87620Homo SapiensHUMA- Human 70 35 immune/haematopoietic antigen SEQ ID N0:15213.

1218 AAM60951Homo SapiensMOLE- Human brain 58 36 expressed single exon probe encoded protein SEQ ID NO: 33056.

1218 AAM73644Homo SapiensMOLE- Human bone 58 36 marrow expressed probe encoded protein SEQ ID NO: 33950.

1218 AA000109Homo SapiensHYSE- Human polypeptide58 45 SEQ

ID NO 14001.

1219 gi16950537Hop mosaiccysteine-rich nucleic41 47 acid binding virus protein 1219 AAY19474Homo sapiensHUMA- Amino acid 43 43 sequence of a human secreted protein.

1219 AA003071Homo SapiensHYSE- Human polypeptide45 31 SEQ

ID NO 16963.

1220 gi1171589Plasmodiumframeshift 76 37 falciparum 1220 gi4512010EscherichiaOrfY 66 50 coli 1220 gi1870470Mus musculusanti-DNA immunoglobulin46 37 light chain IgG

1221 gi13274524Homo Sapienscomplement-clq tumor1451 94 necrosis factor-related protein (CTRP7) mRNA, complete cds.

1221 AAB50371Homo SapiensZYMO Human ZACRP7. 1451 94 1221 gi13274518Homo Sapienscomplement-clq tumor831 61 necrosis factor-related protein (CTRP2) mRNA, complete cds.

1222 AAO03899Homo SapiensHYSE- Human polypeptide67 50 SEQ

ID NO 17791.

1222 AAG73465Homo SapiensHUMA- Human gene 75 31 12-encoded secreted protein fragment, SEQ ID

N0:240.

1222 AAM85406Homo SapiensHUMA- Human 60 40 immune/haematopoietic antigen SEQ ID NO:12999.

1223 gi8850245Homo Sapiensactivated p21cdc42Hs5605 100 kinase (ACKl) mRNA, complete cds.

1223 gi2921447Mus musculusnon-receptor protein4238 79 tyrosine kinase Ack 1223 gi2078388Bos taurusCdc42-associated 3493 90 tyrosine kinase 1224 AAB84696Homo SapiensZYMO Amino acid sequence358 35 of a human zkunl0 polypeptide.

1224 gi211622Gallus alpha-3 collagen 308 33 allus type VI

1224 AAM42089Homo SapiensHYSE- Human polypeptide276 32 SEQ

ID NO 7020.

1225 AAB66065Homo SapiensMILL- Human TANGO 2113 99 294.

1225 AAB66067Homo SapiensMILL- Human TANGO 2015 99 mature protein.

1225 gi434306Homo SapiensH.sapiens mRNA for 1290 60 lysosomal acid lipase.

1226 AAM06483Homo SapiensHYSE- Human foetal 282 98 protein, SEQ

Table 2A

SEQ Hit ID Species Descri tion S score% Identi ID

ID NO: 214.

1226 gi3694984_ metallothionein-1-like57 30 Pimpinellaprotein brachycarpa 1226 AAU22415Homo SapiensHUMA- Human cardiovascular56 27 system antigen polypeptide SEQ

ID No 1189.

1227 gi15029634Homo sapiensSimilar to tetranectin725 100 (plasminogen-binding protein), clone MGC:13592 IMAGE:4042921, mRNA, complete cds.

1227 gi37409 Homo SapiensH.sapiens mRNA for 725 100 tetranectin.

1227 gi825722Homo SapiensH.sapiens tetranectin725 100 gene, exon 1.

1228 gi5790207Taenia ATPase subunit 6 70 32 saginata 1228 gi3927873CyanidioschyzonNADH-ubiquinone oxidoreductase44 19 merolae chain 3 1228 gi4378776PedinomonasNADH dehydrogenase 47 30 subunit 3 minor 1229 AAE01790Homo SapiensHUMA- Human gene 142 59 21 encoded secreted protein HDPTW65, SEQ

ID NO:111.

1229 AAE01838Homo SapiensHUMA- Human gene 140 57 21 encoded secreted protein HDPTW65, SEQ

ID N0:159.

1229 ABB 11479Homo SapiensHYSE- Human reverse 92 55 transcriptase homologue, SEQ ID

N0:1849.

1230 AAE04775Homo SapiensINCY- Human vesicle 327 100 trafficking protein-18 (VETRP-18) protein.

1230 gi11120502Homo SapiensERGL mRNA, complete 327 100 cds.

1230 AAW88699Homo SapiensHUMA- Secreted protein333 100 encoded by gene 166 clone HCEQA68.

1231 AAG00381Homo SapiensGEST Human secreted 266 91 protein, SEQ ID NO: 4462.

1231 AAU19357Homo SapiensPHAA Human G protein-coupled125 50 receptor nGPCR-2290.

1231 AAO09238Homo SapiensHYSE- Human polypeptide109 75 SEQ

ID NO 23130.

1232 AAM06558Homo SapiensHYSE- Human foetal 301 98 protein, SEQ

ID NO: 289.

1232 gi2648055Xenopus corticotropin releasing48 29 laevis factor receptor, type 2 1232 AAU21458Homo SapiensHUMA- Human novel 45 36 foetal antigen, SEQ ID NO
1702.

1233 AAM06562Homo SapiensHYSE- Human foetal 383 100 protein, SEQ

ID NO: 293.

1233 AAG72602Homo SapiensYEDA Human OR-like 65 42 polypeptide query sequence, SEQ

ID NO: 2283.

1233 gi7547265Canis familiaris5-Hydroxytryptamine 67 39 1D receptor subtype beta; 5-HT1D
beta 1234 AAM92283Homo SapiensHUMA- Human digestive76 36 system antigen SEQ ID NO:
1632.

1234 AA009955Homo SapiensHYSE- Human polypeptide70 35 SEQ

ID NO 23847.

1234 gi8778849ArabidopsisT7N9.1 69 42 Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

thaliana 1235 AAM63797Homo SapiensMOLE- Human brain 48 34 expressed single exon probe encoded protein SEQ ID NO: 35902.

1235 AAM76610Homo SapiensMOLE- Human bone 48 34 marrow expressed probe encoded protein SEQ ID NO: 36916.

1235 ABB12222Homo SapiensHYSE- Human secreted52 42 protein homologue, SEQ ID
N0:2592.

1236 gi160822Sarcocystis31-leDa major surface55 37 antigen muris 1236 gi5305067Mus musculusimmunoglobulin light61 34 chain variable region 1236 AAM60441Homo SapiensMOLE- Human brain 61 40 expressed single exon probe encoded protein SEQ ID NO: 32546.

1237 gi4929790Homo Sapiensangiopoietin-related1489 98 protein 3 (ANGPTL3) mRNA, complete cds.

1237 AAY05395Homo SapiensGETH Human TIE ligand1489 98 protein sequence.

1237 AAB 12135Homo SapiensPROT- Hydrophobic 1489 98 domain protein from clone isolated from Liver cells.

1238 AAM06568Homo SapiensHYSE- Human foetal 142 57 protein, SEQ

ID NO: 299.

1238 gi1334599Magnaportheubiquinol:cytochrome48 42 c grisea oxireductase 1238 gi13487283Mycosphaerellacytochrome b 46 42 fijiensis 1239 gi15930235Homo Sapiensclone IMAGE:3846772,46 40 mRNA, partial cds.

1239 gi1334235Rattus MIP protein (261 65 45 ratios AA; AA 3 - 263) 1239 gi1185419Mus musculusmajor intrinsic protein65 45 1240 AAM60668Homo SapiensMOLE- Human brain 62 31 expressed ' single exon probe encoded protein SEQ ID NO: 32773.

1240 AAM73340Homo SapiensMOLE- Human bone 62 31 marrow expressed probe encoded protein SEQ ID NO: 33646.

1240 gi975678Albinaria start codon=CAT, 65 27 termination caerulea codon=TAA

1241 AAG03454Homo SapiensGEST Human secreted 40 26 protein, SEQ ID NO: 7535.

1241 gi1245208Danio rerioZgl3 57 47 1241 AAY19486Homo sapiensHUMA- Amino acid 33 41 sequence of a human secreted protein.

1242 gi3157920ArabidopsisF12F1.6 46 37 thaliana 1242 AAY48414Homo SapiensMETA- Human prostate36 46 cancer-associated protein 111.

1242 gi927722SaccharomycesErdlp; YDR414C; CAI:61 44 0.11 cerevisiae 1243 gi9657469Vibrio soxR protein 39 46 cholerae 1243 gi3493510Mus musculusYmp ' 47 43 1243 gi2358254Mus musculusHNMP-1 47 43 Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

1244 AA012129 Homo SapiensHYSE- Human polypeptide64 90 SEQ

ID NO 26021.

1244 gi3874749CaenorhabditisC34E7.3 50 56 ele ans 1244 AAO12895 Homo SapiensHYSE- Human polypeptide64 44 SEQ

ID NO 26787.

1245 AAY99386 Homo sapiensGETH Human PR01305 71 39 (UNQ671) amino acid sequence SEQ ID N0:153.

1245 AA002040 Homo SapiensHYSE- Human polypeptide63 33 SEQ

ID NO 15932.

1245 gi15073483SinorhizobiumPUTATIVE SENSORY 77 39 meliloti TRANSDUCTION HISTIDINE

KINASE TRANSMEMBItANE

PROTEIN

1246 AAG75420 Homo SapiensHUMA- Human colon 49 40 cancer antigen protein SEQ
ID N0:6184.

1246 gi4099021Helicobacteramino acid permease 47 39 pylori 1246 gi2314328Helicobacterglutamine ABC transporter,47 39 pylori permease protein 26695 (glnP) 1248 gi2959352Brugia cuticle collagen 68 37 pahangi 2(F) 1248 AA003627 Homo SapiensHYSE- Human polypeptide59 40 SEQ

ID NO 17519.

1248 gi13959819MyxococcusUSC6-lp 67 43 xanthus 1249 gi8249629Homo Sapienspartial IGHV gene 62 44 for immunoglobulin heavy chain variable region, clone B31.

1249 gi6646882ParagonimusNADH dehydrogenase 63 40 subunit 1 westermani 1249 AAR39641 Homo SapiensCIBA Transforming 44 37 Growth Factor-betal(44/45)beta2 hybrid.

1250 AAU04613 Homo SapiensUNIW Gonadotropin 40 58 analogue, beta subunit.

1250 gi3242155Drosophila153C9.b 60 43 melanogaster 1250 AAM63639 Homo SapiensMOLE- Human brain 59 42 expressed single exon probe encoded protein SEQ ID NO: 35744.

1251 AA011677 Homo SapiensHYSE- Human polypeptide74 54 SEQ

ID NO 25569.

1251 gi7716782Drosophilahelicase pitchoune 77 44 simulans 1251 gi3342758Drosophilahelicase pitchoune 77 44 melanogaster 1252 gi482846 Torgos cytochrome b 51 40 tracheliotus 1252 gi22737 Hordeum beta-hordothionin 42 38 vulgare 1252 AAM79945 Homo SapiensHYSE- Human protein 45 40 SEQ ID

NO 3591.

1253 gi424891 Human envelope glycoprotein37 33 immunodeficienc y virus type 1 1253 gi9654985Vibrio glutamate--cysteine 62 28 cholerae ligase Table 2A
1 f4 SEQ Hit ID S ecies Descri tion S score% Identi ID

1254 gi3805960Populus lactase 47 72 balsamifera subsp.

trichocarpa 1254 gi15074016SinorhizobiumPUTATIVE TRANSCRIPTION57 35 meliloti REGULATOR PROTEIN

1254 gi12652993Homo Sapiensclone IMAGE:3357862,56 47 mRNA, artial cds.

1255 gi1655739Peromyscus NADH dehydrogenase 44 _ 24 subunit 4 maniculatus 1255 gi16551105Crotalus NADH dehydrogenase 66 28 subunit 5 adamanteus 1255 gi16551107Crotalus NADH dehydrogenase 65 28 atrox subunit 5 1256 AA006799Homo SapiensHYSE- Human polypeptide43 37 SEQ

ID NO 20691.

1256 AA000659Homo SapiensHYSE- Human polypeptide41 52 SEQ

ID NO 14551.

1256 AAB51937Homo sapiensHUMA- Human secreted37 60 protein sequence encoded by gene 9 SEQ

ID N0:69.

1257 16449037Mus musculusplatelet glycoprotein738 38 V

1257 gi2104856Rattus platelet glycoprotein735 37 V

norvegicus 1257 gi2104845Mus musculusplatelet glycoprotein722 37 V

1258 AA011326Homo SapiensHYSE- Human polypeptide61 40 SEQ

ID NO 25218.

1258 gi7576909Danio rerioher7-protein 64 37 1258 AAG81428Homo SapiensZYMO Human AFP protein47 38 sequence SEQ ID N0:374.

1259 gi18349 Daucus carotaglycine rich protein65 45 (AA 1 - 96) 1259 gi336034Vesicular M-protein 70 26 stomatitis virus 1259 gi335876Vesicular matrix (M) protein 70 26 stomatitis virus 1260 AA009307Homo SapiensHYSE- Human polypeptide41 37 SEQ

ID NO 23199.

1260 .gi15042581EchinococcusNADH dehydrogenase 59 41 subunit2 granulosus 1261 gi10436454Homo SapienscDNA FLJ14082 fis, 983 99 clone HEMBB 1002300.

1261 AAB95686Homo SapiensHELI- Human protein 983 99 sequence SEQ ID N0:18490.

1261 AAY20668Homo SapiensUYRO- Human neurofilament-M44 50 wild type protein fragment 10.

1263 gi965014Mus musculusADAM 4 protein precursor1303 51 1263 gi1061159Macaca testicular Metalloprotease-like,1277 39 fascicularisDisintegrin-like, Cysteine-rich protein IVa 1263 gi1061161Macaca testicular Metalloprotease-like,1249 38 fascicularisDisintegrin-like, Cysteine-rich protein IVb 1264 AAM79049Homo SapiensHIfSE- Human protein1895 98 SEQ ID

NO 1711.

1264 AAM80033Homo SapiensHI'SE- Human protein1895 98 SEQ ID

NO 3679.

1264 AAM53458Homo SapiensMOLE- Human brain 1074 100 expressed Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

single exon probe encoded protein SEQ ID NO: 25563.

1265 AAB44605Homo SapiensHUMA- Human secreted 93 70 protein sequence encoded by gene 10 SEQ

ID N0:70.

1265 AAG71789Homo SapiensYEDA Human olfactory 42 63 receptor polypeptide, SEQ ID
NO: 1470.

1265 AAG72517Homo SapiensVEDA Human OR-like 42 63 polypeptide query sequence, SEQ

ID NO: 2198.

1266 gi14714741Homo Sapiensclusterin (complement1629 99 lysis inhibitor, SP-40,40, sulfated glycoprotein 2, testosterone-repressed prostate message 2, apolipoprotein J), clone MGC:18080 IMAGE:4150452, mRNA, complete cds.

1266 gi292843Homo SapiensHuman TRPM-2 protein 1629 99 gene, exons 7,8,9 and complete cds.

1266 gi30251 Homo sapiensHuman SP-40,40 mRNA 1629 99 for complement-associated protein SP-40,40 alpha-1 and beta-1 chain.

1267 gi11493504Homo SapiensPR00309 1192 98 1267 gi412723synthetic synthetic antithrombin1192 98 III

construct 1267 gi583741synthetic Antithrombin III 1192 98 construct 1268 gi11493504Homo sapiensPRO0309 1439 98 1268 gi412723synthetic synthetic antithrombin1439 98 III

construct 1268 gi583741synthetic Antithrombin III 1439 98 construct 1269 gi203710Rattus cytochrome c oxidase 250 65 subunit VIc norvegicus 1269 gi1200057Homo SapiensHuman mRNA for cytochrome229 61 c oxidase subunit VIc.

1269 gi12652867Homo Sapienscytochrome c oxidase 229 61 subunit VIc, clone MGC:1520 IMAGE:3350637, mRNA, complete cds.

1270 AAM96033Homo SapiensHUMA- Human reproductive465 98 system related antigen SEQ ID

NO: 4691.

1270 AAU18881Homo SapiensHUMA- Novel prostate 465 98 gland antigen, Seq ID No 180.

1270 gi9622236Homo Sapienscadherin-like protein272 100 mRNA, partial cds.

1271 gi552137Drosophilatropomyosin isoform 118 27 melano aster 1271 gi158693Drosophilatropomyosin isoform 118 27 melanogaster 1271 gi158696Drosophilatropomyosin isoform 118 27 melanogaster 1272 gi6689249StreptococcusM-like protein 122 24 dysgalactiae subsp.

dysgalactiae Table 2A

SEQ Hit ID S ecies Descri tion- S score% Identi ID

1272 gi6692690ArabidopsisF12K11.14 114 28 thaliana 1272 gi4778 SaccharomycesUsol protein 122 29 cerevisiae 1273 gi13097573Homo SapiensSimilar to thiosulfate1469 94 sulfurtransferase (rhodanese), clone MGC:10492 IMAGE:3611253, mRNA, complete cds.

1273 gi16876913Homo Sapiensmercaptopyruvate 1469 94 sulfurtransferase, clone MGC:24539 IMAGE:4105509, mRNA, complete cds.

1273 gi17511726Homo Sapiensmercaptopyruvate 1469 94 sulfurtransferase, clone MGC:31798 IMAGE:4131927, mRNA, complete cds.

1274 AAB85039Homo SapiensCURA- Human SERS 767 48 protein sequence.

1274 gi6137097Homo Sapiens,serine protease DESC1749 48 (DESC1) mRNA, complete cds.

1274 AAY99414Homo SapiensGETH Human PR01461 749 48 (UNQ742) amino acid sequence SEQ ID N0:269.

1275 gi12584839Homo SapiensHT036-ISO (HT036-ISO)997 94 mRNA, complete cds.

1275 gi12584841Homo SapiensHT036 (HT036) mRNA, 820 93 complete cds.

1275 gi17427028Ralstonia CONSERVED HYPOTHETICAL502 42 solanacearumPROTEIN

1276 gi310691Simian small T anti en 48 47 virus 1276 gi8886685Centris cytochrome b 53 40 inermis 1276 gi625084Oncorhynchusheat-shock protein 37 44 tshawytscha 1277 gi7106820Homo SapiensHSPC215 261 100 1277 AAU16225Homo SapiensHUMA- Human novel 261 100 secreted protein, Seq ID 1178.

1277 AAG81441Homo SapiensZYMO Human AFP protein261 100 sequence SEQ ID N0:400.

1278 AAM25840Homo SapiensHYSE- Human protein 208 88 sequence SEQ ID N0:1355.

1278 AAM74914Homo SapiensMOLE- Human bone 63 68 marrow expressed probe encoded protein SEQ ID NO: 35220.

1278 AAM06639Homo SapiensHYSE- Human foetal 36 70 protein, SEQ

ID NO: 370.

1279 17023943Homo SapiensGC36 mRNA, complete 360 35 cds.

1279 gi2502077Homo Sapiensdigestive tract-specific360 35 calpain (nCL-4) mRNA, complete cds.

1279 gi2358262Rattus calpain large subunit351 35 norve icus 1280 gi4153951Homo SapiensH.sapiens gene from 259 37 PACs 295C6 and 313L4.

1280 AAY32437Homo SapiensTEXA Absorptive hypercalciuria259 37 associated gene protein prodict.

1280 gi15383934Homo Sapienstesticular soluble 259 37 adenylyl cyclase mRNA, complete cds.

Table 2A

SEQ Hit ID Species Descri tion S score% Identi ID

1281 AAM89651 Homo SapiensHUMA- Human 66 31 immune/haematopoietic antigen SEQ ID N0:17244.

1281 gi408591 Influenza nonstructural protein62 28 A virus 1281 AAM82524 Homo SapiensHUMA- Human 62 55 immune/haematopoietic antigen SEQ ID N0:10117.

1282 14079820 Mus musculusHERC2 67 40 1282 gi459017 Allomyces subunit 6 of the 71 44 ATPase complex macrogynus 1282 gi1236414Allomyces H(+)-transporting 71 44 ATPase, FO

macrogynussubunit 6 1283 AAM63001 Homo SapiensMOLE- Human brain 153 67 expressed single exon probe encoded protein SEQ ID NO: 35106.

1283 AAM75812 Homo SapiensMOLE- Human bone 153 67 marrow expressed probe encoded protein SEQ ID NO: 36118.

1283 AAE10197 Homo SapiensHYSE- Human bone 60 36 marrow derived peptide, SEQ ID NO: 41.

1284 AAG81367 Homo SapiensZYMO Human AFP protein816 98 sequence SEQ ID N0:252.

1284 gi7582286Homo SapiensBM-007 530 98 1284 AAG02907 Homo SapiensGEST Human secreted 408 95 protein, SEQ ID NO: 6988.

1285 AAG81367 Homo SapiensZYMO Human AFP protein906 98 sequence SEQ ID N0:252.

1285 gi7582286Homo sapiensBM-007 538 99 1285 AAG02907 Homo sapiensGEST Human secreted ~ 416 96 protein, SEQ ID NO: 6988.

1286 AAW49716 Homo SapiensPROT- Protein polymer54 31 adhesive substrate PPAS1-C
monomer.

1286 AAW49721 Homo SapiensPROT- Protein polymer54 31 adhesive substrate PPAS1-D
monomer.

1286 gi683735 Macaca endothelin 3 50 62 fascicularis 1287 gi5689766Homo SapiensmRNA for zinc finger2092 99 2 (ZNF2 gene).

1287 gi14602980Homo Sapiensclone MGC:16594 1609 100 IMAGE:4110322, mRNA, complete cds.

1287 gi13477207Homo Sapiensclone MGC:12980 1604 99 IMAGE:3350363, mRNA, complete cds.

1288 AAB44228 Homo sapiensHUMA- Human cancer 284 86 associated protein sequence SEQ ID

N0:1673.

1288 AAM90208 Homo SapiensHUMA- Human 43 50 immune/haematopoietic antigen SEQ ID N0:17801.

1288 gi733438 Cepaea NADH dehydrogenase 62 31 subunit 4L

nemoralis 1289 gi10764264synthetic mutated NSSA 67 30 construct 1289 AA002625 Homo SapiensHYSE- Human polypeptide58 26 SEQ

ID NO 16517.

Table 2A

SE ID Hit ID S ecies Descri ~tion S score% Identi 1289 gi10644188Hepatitis polyprotein 67 30 C virus type la 1290 AAG03150Homo SapiensGEST Human secreted 307 98 protein, SEQ ID NO: 7231.

1290 AAW48931Homo SapiensCEDA- Schwannomin-binding286 100 protein C-terminal fragment.

1290 AA004324Homo SapiensHYSE- Human polypeptide63 33 SEQ

ID NO 18216.

1291 AAB60098Homo SapiensINCY- Human transport1822 92 protein TPPT-18.

1291 gi1537070Rattus nucleoporin p54 1767 92 norvegicus 1291 gi15214835Homo Sapiensclone MGC:13407 1822 92 IMAGE:3931652, mRNA, complete cds.

1292 AAY94621Homo SapiensMILL- Epidermal growth385 100 factor-like variant in skin-2 amino acid sequence.

1292 AAE06697Homo SapiensHYSE- Human TGF alpha-like385 100 protein.

1292 AAE06698Homo SapiensHYSE- Human TGF alpha-like385 100 splice variant protein.

1293 AAW78245Homo SapiensHUMA- Fragment of 1018 98 human secreted protein encoded by gene 19.

1293 ABB 11835Homo SapiensHYSE- Human secreted1018 98 protein homolo ue, SEQ ID
N0:2205.

1293 AAM79352Homo SapiensHYSE- Human protein 1018 98 SEQ ID

NO 2998.

1294 AAM99920Homo sapiensHUMA- Human polypeptide667 97 SEQ

ID NO 36.

1294 gi16552010Homo SapienscDNA FLJ32009 fis, 667 97 clone NT2RP7009498, weakly similar to FIBULIN-1, ISOFORM
A

PRECURSOR.

1294 AAM99933Homo SapiensHUMA- Human polypeptide627 93 SEQ

ID NO 49.

1295 gi2598167Homo sapienszinc finger protein 2772 99 (HZF6) mRNA, 5' UTR and partial cds.

1295 gi5640019Mus musculuszinc finger protein 1565 68 1295 gi1184371Mus musculuszinc finger protein;1278 55 Method:

conceptual translation supplied by author 1296 gi15679947Homo Sapiensendothelial zinc 2734 100 finger protein induced by tumor necrosis factor alpha, clone MGC:11153 IMAGE:3840512, mRNA, complete cds.

1296 gi9502202Homo Sapiensendothelial zinc 2734 100 finger protein induced by tumor necrosis factor alpha (EZFIT) mRNA, complete cds.

1296 gi10437767Homo SapienscDNA: FLJ21628 fis, 1713 77 clone COL08076.

1297 AAM56742Homo SapiensMOLE- Human brain 99 55 expressed single exon probe encoded protein SEQ ID NO: 28847.

Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

1297 AA009197Homo SapiensHYSE- Human polypeptide66 45 SEQ

ID NO 23089.

1297 gi12543402CorynebacteriumFRXA00675 79 26 glutamicum 1298 AAM79176Homo SapiensHYSE- Human protein 601 100 SEQ ID

NO 1838.

1298 ABB 11626Homo SapiensHYSE- Human Fas-associated559 94 phosphatase homologue, SEQ ID

N0:1996.

1298 AAM80160Homo SapiensHYSE- Human protein 559 94 SEQ ID

NO 3806.

1299 gi12698338Homo sapiensmatrix metalloproteinase-282424 96 precursor, mRNA, complete cds.

1299 gi12698852Homo Sapiensmatrix metalloprotease2424 96 mRNA, complete cds.

1299 AAU12243Homo SapiensGETH Human PR04339 2424 96 polypeptide sequence.

1300 gi14210477Homo Sapiensinterleulcin 18 precursor,138 92 mRNA, complete cds.

1300 AAW31757Homo SapiensINCY- Interferon 138 92 gamma inducing factor-2 (IGIF-2) R140I variant.

1300 110799833Ovis ariesinterleukin-18 (IGIF)122 78 1301 AAE05302Homo SapiensMILL- Human TANGO 623 97 protein.

1301 AAE05303Homo SapiensMILL- Human mature 611 100 TANGO

457 protein.

1301 AAE05305Homo SapiensMILL- Human TANGO 605 100 protein cytoplasmic domain.

1302 AAM55396Homo sapiensMOLE- Human brain 64 38 expressed single exon probe encoded protein SEQ ID NO: 27501.

1302 AAM57742Homo SapiensMOLE- Human brain 64 38 expressed single exon probe encoded protein SEQ ID NO: 29847.

1302 AAM67792Homo SapiensMOLE- Human bone 64 38 marrow expressed probe encoded protein SEQ ID NO: 28098.

1303 AAM88370Homo sapiensHUMA- Human 38 35 immune/haematopoietic antigen SEQ ID N0:15963.

1303 gi7330034Macaca helicase-primase 56 30 mulatta rhadinovirus 1303 gi4494949Macaca helicaselprimase 56 30 mulatta rhadinovirus 1304 gi190870Homo SapiensHuman retinoic acid 274 100 receptor gamma 2 mRNA, 5' end.

1304 gi297146Homo SapiensH.sapiens gene for 274 100 retinoic acid receptor amma-2.

1304 gi200660Mus musculusretinoic acid receptor252 92 gamma 2 1305 AAM39737Homo SapiensHYSE- Human polypeptide992 99 SEQ

ID NO 2882.

1305 AAM39736Homo SapiensHYSE- Human polypeptide875 100 SEQ

ID NO 2881.

1305 AAM41522Homo SapiensHYSE- Human polypeptide875 100 SEQ

ID NO 6453.

Table 2A

SEQ Hit ID S ecies Description S score% Identi ID

1306 ABB 17891Homo SapiensHUMA- Human nervous 54 38 system related polypeptide SEQ ID NO

6548.

1306 AAM88996 Homo SapiensHUMA- Human 57 40 immune/haematopoietic antigen SEQ ID N0:16589.

1306 AAM65093 Homo SapiensMOLE- Human brain 55 50 expressed single exon probe encoded protein SEQ ID NO: 37198.

1307 AAY19551 Homo SapiensHUMA- Amino acid 133 42 sequence of a human secreted protein.

1307 AAY75972 Homo SapiensGENE- Human skin 133 42 cell protein, SEQ ID 150.

1307 AAB55911 Homo sapiensGENE- Slcin cell 133 42 protein, SEQ ID

NO: 150.

1308 AAU27671 Homo SapiensZYMO Human protein 486 100 AFP355471.

1308 AA012566 Homo SapiensHYSE- Human polypeptide61 28 SEQ

ID NO 26458.

1308 gi167933 Dictyosteliumthioredoxin 67 34 discoideum 1309 AAR15222 Homo SapiensTEXA Chronic myelogenous620 100 leukaemia-derived myeloid-related protein.

1309 gi181527 Homo SapiensHuman neutrophil 493 100 peptide (defensin) 1 mRNA, complete cds.

1309 gi181529 Homo SapiensHuman defensin 1 493 100 protein mRNA, complete cds.

1310 gi2911559Human E6 protein 66 27 papillomavirus .

type 77 1310 gi9800324rat pr109 62 25 cytomegalovirus Maastricht 1310 gi397007 Human envelope protein 60 31 papillomavirus type 3 1311 AAU19632 Homo SapiensHUMA- Human novel 205 40 extracellular matrix protein, Seq ID No 282.

1311 gi3127926Homo SapiensH.sapiens RNA for 186 42 type VI

collagen alpha3 chain.

1311 gi57960 Mus musculuscollagen alpha 3 176 40 chain type VI

1312 gi16508176Homo Sapienssmall GTP-binding 1012 100 tumor suppressor 1 mRNA, complete cds.

1312 gi16555334Homo sapiensRig protein mRNA, 1012 100 complete cds.

1312 gi16508174Mus musculussmall GTP-binding 963 93 tumor suppressor 1 1313 AAG73984 Homo SapiensHUMA- Human colon 55 40 cancer anti en protein SEQ
ID N0:4748.

1313 13041771 Homo SapiensmRNA for perilipin, 83 32 complete cds.

1313 AAY22157 Homo SapiensABBO Human BS135 83 32 protein sequence.

1314 AAM71801 Homo SapiensMOLE- Human bone 1872 100 marrow expressed probe encoded protein SEQ ID NO: 32107.

1314 gi16549907Homo SapienscDNA FLJ30663 fis, 1203 58 clone Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

FCBBF1000598, moderately similar to ZINC FINGER

PROTEIN 84.

1314 AAM78565Homo SapiensHYSE- Human protein 1151 55 SEQ ID

NO 1227.

1315 gi32472 Homo SapiensH.sapiens mRNA for 785 76 high-sulphur keratin.

1315 gi3228239Homo SapiensUHS KerA gene. 774 76 1315 gi34079 Homo SapiensHuman gene for ultra774 76 high-sulphur keratin protein.

1316 gi12655446Homo SapiensmRNA for keratin 755 80 associated protein 4.4 (KRTAP4.4 gene).

1316 gi12655460Homo SapiensmRNA for keratin 726 75 associated protein 4.12 (KRTAP4.12 gene).

1316 gi13278825Homo SapiensSimilar to RIKEN 726 75 cDNA

1110054P19 gene, clone MGC:2782 IMAGE:2959821, mRIVA, complete cds.

1317 gi12655462Homo SapiensmIRNA for keratin 1102 88 associated protein 4.14 (KRTAP4.14 ene).

1317 gi12655452Homo SapiensmRNA for keratin 1081 84 associated protein 4.7 (KRTAP4.7 gene).

1317 gi12655460Homo sapiensmRNA for keratin 997 79 associated protein 4.12 (KRTAP4.12 gene).

1318 AAM79404Homo SapiensNYSE- Human protein 850 74 SEQ ID

NO 3050.

1318 AAM39466Homo SapiensHYSE- Human polypeptide844 77 SEQ

ID NO 2611.

1318 AAM41252Homo SapiensHYSE- Human polypeptide836 77 SEQ

ID NO 6183.

1319 gi16552172Homo SapienscDNA FLJ32133 fis, 800 65 clone PEBLM2000308, moderately similar to ZINC FINGER

PROTEIN 135.

1319 gi6467200Homo SapiensGIOT-1 mRNA for gonadotropin775 60 inducible transcription repressor-1, partial cds.

1319 gi498721Homo SapiensH.sapiens HZF10 mRNA770 63 for zinc finger protein.

1320 '3036963Ciona savignyiCsCDC42 163 60 1320 gi15072535Schizophyllumsmall GTPase CDC42 162 60 commune 1320 gi520533DrosophilaDcdc42 161 60 melanogaster 1321 AAE02058Homo SapiensHUMA- Human four 517 43 disulfide core domain (FDCD)-containing protein.

1321 gi12655452Homo SapiensmRNA for keratin 509 44 associated protein 4.7 (KRTAP4.7 gene).

1321 gi200964Mus musculusserine 2 ultra high 494 42 sulfur protein 1322 ABB 12490Homo SapiensHYSE- Human bone 169 72 marrow expressed protein SEQ ID NO:

329.

1322 gi14647047Puntius ATP synthase 8 56 37 titteya 1322 gi14646929Barbus ATP synthase 8 54 44 cyclolepis cyclolepis Table 2A

SEQ Hit ID S ecies Description S score% Identi ID

1323 gi5921470Homo SapiensmRNA for G8 protein 405 89 (G8 gene, located in the class III region of the major histocompatibility complex).

1323 gi5921473Homo SapiensmRNA for G8 protein 381 92 (G8 gene, located in the class III region of the major histocompatibility complex), alternative splice variant lacking exon 2.

1323 AAM39144 Homo SapiensHYSE- Human polypeptide381 92 SEQ

ID NO 2289.

1324 AAM87150 Homo SapiensHUMA- Human 74 38 immune/haematopoietic antigen SEQ ID N0:14743.

1324 AAB59115 Homo SapiensHUMA- Breast and 62 36 ovarian cancer associated antigen protein sequence SEQ ID 823.

1324 gi15158712AgrobacteriumAGR_L 725p 46 52 tumefaciens str.

058 (Cereon) 1325 AAY48404 Homo SapiensMETA- Human prostate55 50 cancer-associated protein 101.

1325 AAM59935 Homo SapiensMOLE- Human brain 55 38 expressed single exon probe encoded protein SEQ ID NO: 32040.

1325 AAM72530 Homo SapiensMOLE- Human bone 55 38 marrow expressed probe encoded protein SEQ ID NO: 32836.

1326 gi466912 Mycobacteriumtp2; B1549_02_206 60 45 leprae 1326 gi1220377Avian infectiousnucleocapsid protein64 56 bronchitis virus 1326 gi13177409EctocarpusEsV-1-135 65 34 siliculosus virus 1327 gi200964 Mus musculusserine 2 ultra high 207 32 sulfur protein 1327 gi200962 Mus musculusserine 1 ultra high 202 32 sulfur protein 1327 gi32472 Homo SapiensH.sapiens mRNA for 196 32 high-sulphur keratin.

1328 AAR23732 Homo SapiensMINU Gene 519 cDNA 316 68 derived peptide.

1328 gi35065 Homo SapiensHuman NKGS mRNA, 314 66 expressed in natural killer cells and T-cells.

1328 AAW59874 Homo SapiensHUMA- Amino acid 314 66 sequence of the cDNA clone CAT-1 (HTXET53).

1329 gi200964 Mus musculusserine 2 ultra high 359 49 sulfur protein 1329 AAM39466 Homo SapiensNYSE- Human polypeptide341 51 SEQ

ID NO 2611.

1329 AAM78420 Homo SapiensHYSE- Human protein 337 53 SEQ ID

NO 1082.

1330 gi13937769Homo SapiensSimilar to RIKEN 1256 100 cDNA

1200013F24 gene, clone MGC:12197 IMAGE:3997840, mRNA, complete cds.

1330 17582294 Homo SapiensBM-011 781 98 1330 AAM79664 Homo SapiensHYSE- Human protein 255 31 SEQ ID

NO 3310.

1331 114718451Homo Sapienssialic acid-binding 796 71 lectin 11 Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

(SIGLEC11) mRNA, complete cds.

1331 AAY41724Homo SapiensGETH Human PR0940 535 50 protein sequence.

1331 AAB44280Homo SapiensGETH Human PR0940 535 50 (UNQ477) protein sequence SEQ ID NO:259.

1332 AAT90731_Homo SapiensFARB Human placental849 98 bikunin aal cDNA.

1332 gi12804515Homo Sapiensserine protease inhibitor,848 98 Kunitz type, 2, clone MGC:2021 IMAGE:2959462, mRNA, complete cds.

1332 gi2065529Homo Sapiensplacental bikunin 848 98 mRNA, complete cds.

1333 gi14042550Homo SapienscDNA FLJ14779 Es, 2165 98 clone NT2RP4000398, moderately similar to ZINC FINGER

PROTEIN 140.

1333 AAB93164Homo SapiensHELI- Human protein 2165 98 sequence SEQ ID N0:12091.

1333 AAM93693Homo SapiensHELI- Human polypeptide,2159 100 SEQ

ID NO: 3604.

1334 gi12804907Homo SapiensSimilar to metaxin 1512 100 1, clone MGC:2518 IMAGE:3546178, mRNA, complete cds.

1334 gi1326108Homo SapiensHuman metaxin (MTV 1098 100 gene, complete cds.

1334 gi2564913Homo Sapiensclk2 kinase (CLIC2),1098 100 propinl, cotel, glucocerebrosidase (GBA), - and metaxin genes, complete cds;

metaxin pseudogene and glucocerebrosidase pseudogene;

and thrombospondin3 (THBS3) gene, partial cds.

1335 AAW85614Homo SapiensGEMY Secreted protein381 83 clone fr473 2.

1335 AAY94865Homo SapiensPROT- Human protein 381 83 clone HP 10540.

1335 AAY36022Homo SapiensGEST Extended human 365 80 secreted protein sequence, SEQ ID NO.

407.

1336 AAB 18447Homo SapiensMILL- Amino acid 2257 99 sequence of human TANGO 216 polypeptide.

1336 AAB 18455Homo SapiensMILL- A human TANGO 2257 99 olypeptide clone.

1336 AAU19662Homo sapiensHUMA- Human novel 1876 96 extracellular matrix protein, Seq ID No 312.

1337 AAB 18447Homo SapiensMILL- Amino acid 2257 99 sequence of human TANGO 216 polypeptide.

1337 AAB18455Homo SapiensMILL- A human TANGO 2257 99 polypeptide clone.

1337 AAU19662Homo sapiensHUMA- Human novel 1876 96 extracellular matrix protein, Seq ID No 312.

1338 AAY86303Homo SapiensHUMA- Human secreted2133 94 protein HOGCK20, SEQ ID N0:218.

Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

1338 gi14456615Homo SapiensPIG-T mRNA for phosphatidyl2120 96 inositol glycan class T, complete cds.

1338 gi15929132Homo Sapiensclone MGC:8909 2120 96 IMAGE:3921680, mRNA, complete cds.

1339 112836893Gallus IPR328-like protein 160 29 gallus 1339 gi3093433Homo SapiensChromosome 16 BAC 153 29 clone CIT987SK-625P11, complete sequence.

1339 gi4558766Homo Sapiensneuronal voltage 153 29 gated calcium channel gamma-3 subunit mRNA, complete cds.

1340 gi12836893Gallus IPR328-like protein 158 29 anus 1340 gi3093433Homo SapiensChromosome 16 BAC 151 29 clone CIT987SK-625P11, complete sequence.

1340 gi4558766Homo Sapiensneuronal voltage 151 29 gated calcium channel gamma-3 subunit mRNA, complete cds.

1341 AAW85737 Homo SapiensSAGA Polypeptide 692 100 with transmembrane domain.

1341 ABB 11882Homo SapiensHYSE- Human transmembrane692 100 protein homologue, SEQ ID

N0:2252.

1341 AAG89353 Homo SapiensGEST Human secreted 692 100 protein, SEQ ID NO: 473.

1342 ABB 12032Homo SapiensHYSE- Human SIGP 866 97 homologue, SEQ ID
N0:2402.

1342 AAY21851 Homo SapiensINCY- Human signal 866 97 peptide-contianing protein (SIGP) (clone ID 2328134).

1342 gi4101574Homo Sapiens54TMp (54tm) mRNA, 860 96 complete cds.

1343 gi3002925Homo SapiensT cell receptor beta1658 100 chain (TCRBV 13S 1-TCRBJ2S
1) mRNA, complete cds.

1343 gi2982508Homo SapiensmRNA for TCR beta 1527 94 chain, s ecific for Mage 3lHLA-A2.

1343 gi3002933Homo SapiensT cell receptor beta1251 76 chain (TCRBV3S1-TCRBJ2S3) mRNA, complete cds.

1344 gi14973269Streptococcuscell wall surface 481 19 anchor family pneumoniaeprotein 1344 gi15991793Streptococcusplatelet binding 303 17 protein GspB

gordonii 1344 gi8885520Streptococcusstreptococcal hemagglutinin293 16 gordonii 1345 AAY07751 Homo SapiensHUMA- Human secreted293 100 protein fragment encoded from gene 8.

1345 gi1142588TrypanosomaCR3 85 42 brucei 1345 gi3037018Bodo saltansNADH dehydrogenase 80 35 subunit 5 1346 AAG78000 Homo SapiensBIOW- Human actin 663 100 14.

1346 ABB 17913Homo sapiensHUMA- Human nervous 644 98 system related polypeptide SEQ ID NO

Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

6570.

1346 AAY94954 Homo sapiensGEMY Human secreted 596 68 protein clone iw66_1 protein sequence SEQ ID N0:114.

1347 gi9837433Homo Sapienssialic acid binding 2206 88 immunoglobulin-like lectin 8 long splice variant (Siglec8) gene, complete cds.

1347 gi6746556Homo Sapienssialic acid-binding 2031 93 immunoglobulin-like lectin-8 (SIGLECB) mRNA, complete cds.

1347 gi6980022Homo Sapienssiglec SAF2 (SAF2) 2031 93 mRNA, complete cds.

1348 gi15451469Homo Sapienssiglec-like protein 2689 99 (SLG2) gene and alternatively spliced variants, complete cds.

1348 gi15217166Homo Sapienssialic acid-binding 2682 99 Ig-like lectin 10 (SIGLEC10) mRNA, complete cds.

1348 gi14164613Homo sapienssialic acid binding 2356 98 immunoglobulin-like lectin 10 (SIGLEC10) mRNA, complete cds.

1349 AAB60112 Homo SapiensINCY- Human transport775 100 protein TPPT-32.

1349 gi9663117Homo SapiensmRNA for organic 382 48 canon transporter.

1349 AAB47000 Homo sapiensBOEN/ Human BOOT 382 48 protein.

1350 AAY76219 Homo SapiensHUMA- Human secreted336 94 protein encoded by gene 96.

1350 gi2906006Homo SapiensWASP interacting 134 30 protein (WIP) mRNA, partial cds.

1350 gi22269 Zea mays cell wall protein 105 34 (108 AA) 1351 AAB08767 Homo SapiensINCY- A human leukocyte92 37 and ' blood related protein (LBAP).

1351 gi576631 Torpedo 14 kDa transmembrane87 32 protein marmorata 1351 AAM78542 Homo SapiensHYSE- Human protein 72 31 SEQ ID

NO 1204.

1352 gi5817194Homo SapiensmRNA; cDNA DKFZp434F011221 95 (from clone DI~FZp434F011);

partial cds.

1352 gi7576452Homo SapienshBOIT mRNA for potent160 36 brain type organic ion transporter, complete cds.

1352 AAY06116 Homo SapiensMILL- Human organic 154 35 cation transporter OCT-3.

1353 gi16552104Homo sapienscDNA FLJ32082 Es, 2566 99 clone OCBBF2000231, weakly similar to PHOSPHOLIPASE

INHIBITOR SUBUNIT
B

PRECURSOR.

1353 AAY66713 Homo SapiensGETH Membrane-bound 2566 99 protein PR01309.

1353 AAU12396 Homo SapiensGETH Human PRO1309 2566 99 polypeptide sequence.

1354 gi15559274Homo Sapiensclone MGC:20205 502 40 Table 2A

SEQ Hit ID S ecies Descri tion ~~ S score% Identi ID

IMAGE:3627858, mRNA, complete cds.

1354 AAB15549Homo SapiensINCY- Human immune 502 40 system molecule from Incyte clone 2774913.

1354 AAB19729Homo SapiensCURA- Human SECX 502 40 Clone 4339264-2 encoded protein.

1355 AAY99399Homo SapiensGETH Human PR01268 603 100 (UNQ638) amino acid sequence SEQ ID N0:214.

1355 AAY78808Homo SapiensPROT- Hydrophobic 603 100 domain containing protein clone HP10537 protein sequence.

1355 AAB87570Homo SapiensGETH Human PR01268. 603 100 1356 AAM78418Homo SapiensHYSE- Human protein 1902 97 SEQ ID

NO 1080.

1356 ABB11897Homo SapiensHYSE- Human F22162_11827 93 homologue, SEQ ID
N0:2267.

1356 AAM79402Homo SapiensHYSE- Human protein 1820 93 SEQ ID

NO 3048.

1357 gi397607Homo SapiensH.sapiens encoding 2331 99 mRNA.

1357 AAY49573Homo SapiensWHED Human CLA-1 2331 99 protein sequence.

1357 AAW97900Homo SapiensMILL- Human SR-BI 2318 98 class B

scavenger.

1358 gi854065Human U88 348 31 herpesvirus 1358 gi10434098Homo SapienscDNA FLJ12547 fis, 273 32 clone NT2RM4000634.

1358 AAB95124Homo SapiensHELI- Human protein 273 32 sequence SEQ ID N0:17122.

1359 AAE05302Homo SapiensMILL- Human TANGO 1521 96 protein.

1359 AAE05303Homo SapiensMILL- Human mature 1397 96 TANGO

457 protein.

1359 AAE05305Homo SapiensMILL- Human TANGO 1260 100 protein cytoplasmic domain.

1360 gi10129690Homo sapiensmRNA for mucolipidin804 53 (ML4 gene).

1360 gi10438844Homo SapienscDNA: FLJ22449 fis, 804 53 clone HRC09609.

1360 gi13477347Homo Sapiensmucolipin 1, clone 804 53 MGC:3287 IMAGE:3507836, mRNA, complete cds.

1361 AAE04122Homo SapiensHUMA- Human gene 214 61 23 encoded secreted protein HE8OK73, SEQ

ID NO:108.

1361 AAE04169Homo SapiensHUMA- Human gene 207 60 23 encoded secreted protein HE80K73, SEQ

ID NO:158.

1361 AAG00392Homo SapiensGEST Human secreted 117 43 protein, SEQ ID NO: 4473.

1362 AAY27853Homo SapiensHUMA- Human secreted274 94 protein encoded by ene No.
101.

1362 gi904289Phaseolus fungine endopolygalacturonase66 41 vulgaris inhibitor Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

1362 AAB27594Homo SapiensHUMA- Human secreted60 58 protein SEQ ID NO: 95.

1363 gi17016967Homo SapiensNUANCE (NUA) mRNA, 3404 71 complete cds; alternatively spliced.

1363 gi17861384Homo Sapiensnesprin-2 gamma mRNA,3404 71 complete cds.

1363 gi5262574Homo SapiensmRNA; cDNA DKFZp434G1733404 71 (from clone DKFZp434G173);

complete cds.

1364 AAB95854Homo SapiensHELI- Human protein 72 37 sequence SEQ ID N0:18912.

1364 gi9621943PelargoniumNADH dehydrogenase 58 42 senecioides 1364 gi9621945PelargoniumNADH dehydrogenase 58 42 trifidum 1365 AAW29654Homo SapiensGEMY Human secreted 140 48 protein DM406_l.

1365 gi10187870RhodococcusohpA transport 75 26 sp.

1365 gi15559671Homo Sapiensclone MGC:20633 72 33 IMAGE:4761663, mRNA, complete cds.

1366 110566471Mus musculusGliacolin 850 (8 1366 gi14278927Mus musculusgliacolin 850 68 1366 gi3747099Mus musculusClq-related factor 724 66 1367 gi2745756Aotus trivirgatusribonuclease k6 precursor431 91 1367 gi5730384Eulemur ribonuclease k6 precursor305 86 fulvus collaris 1367 gi5730382Nycticebus ribonuclease k6 precursor279 80 coucang 1368 AAE09651Homo SapiensHUMA- Human gene 484 98 13 encoded lipid metabolism protein HT.>NI73, SEQ ID N0:45.

1368 AAG64355Homo SapiensUYFU- Human lambda 400 97 crystallin.

1368 AAY92506Homo SapiensINCY- Human OXRE-3 381 98 with identity to lambda crystallin.

1369 AAM25241Homo SapiensHYSE- Human protein 484 95 sequence SEQ ID NO:756.

1369 AAE09651Homo SapiensHUMA- Human gene 352 100 13 encoded lipid metabolism protein HTJNI73, SEQ ID N0:45.

1369 AAG64355Homo SapiensUYFU- Human lambda 268 98 crystallin.

1370 AAM79626Homo SapiensHYSE- Human protein 214 100 SEQ ID

NO 3272.

1370 AAM79368Homo SapiensHYSE- Human protein 70 44 SEQ ID

NO 3014.

1370 AA002702Homo sapiensNYSE- Human polypeptide65 36 SEQ

ID NO 16594.

1371 gi6653659Oryctolaguschloride channel 3919 96 cuniculus 1371 ABB11826Homo SapiensHYSE- Human Cl channel3865 96 homolo ue, SEQ ID
N0:2196.

1371 gi1770376Homo SapiensH.sapiens mRNA for 1620 100 chloride channel, C1C-6a.

1372 AAG71967Homo SapiensYEDA Human olfactory725 97 receptor polypeptide, SEQ
ID NO: 1648.

1372 AAG71962Homo SapiensYEDA Human olfactory714 95 receptor Table 2A

SEQ Hit S ep cies Descri tion S score% Identi ID ID

_ polypeptide, SEQ
ID NO: 1643.

1372 gi12007416_ m51 olfactory receptor553 72 Mus musculus 1373 AAM63071 Homo sapiensMOLE- Human brain 278 100 expressed single exon probe encoded protein SEQ ID NO: 35176.

1373 AAM75882 Homo SapiensMOLE- Human bone 278 100 marrow expressed probe encoded protein SEQ ID NO: 36188.

1373 AAM67333 Homo sapiensMOLE- Human bone 234 100 marrow expressed probe encoded protein SEQ ID NO: 27639.

1374 AAI~126531_Homo SapiensREGC Human 920 100 aal proton/oligonucleotide transporter hPHTl cDNA.

1374 AAB82821 Homo SapiensREGC Human 815 100 proton/oligonucleotide transporter hPHTI polypeptide.

1374 gi2208839Rattus peptide/histidine 721 82 transporter norvegicus 1375 gi190418 Homo SapiensHuman cathepsin L 1597 87 gene, complete cds.

1375 gi29715 Homo SapiensHuman mRNA for pro-cathepsin1597 87 L

(major excreted protein MEP).

1375 AAW47031 Homo SapiensUSSH Human procathepsin1597 87 L.

1376 gi16566341Homo SapiensG protein-coupled 2554 98 receptor (GPR101) gene, complete cds.

1376 AAB86428 Homo SapiensBOEN/ Human brain 2554 98 SERALPHA

protein.

1376 AAU04369 Homo SapiensAREN- Human G-protein2554 98 coupled receptor, hRUPlS.

1377 AAY53605 Homo SapiensMETR- Peptide of 79 35 human KChAP

that binds to KValpha and Kvbeta subunits.

1377 AAY53608 Homo SapiensMETR- KChAP domain 78 35 that binds to KValpha and Kvbeta subunits.

1377 gi6102853Homo SapiensmRNA; cDNA DKFZp727A05182 38 (from clone DKFZp727A051);

partial cds.

1378 AAB61616 Homo SapiensPROT- Human protein 2416 94 HP10678.

1378 AAG68126 Homo SapiensFARB Human 7TM-GPCR 966 40 protein sequence SEQ ID N0:6.

1378 AAE12023 Homo SapiensINCY- Human G-protein951 40 coupled receptor, GCREC-2.

1379 AAY30735 Homo sapiensHUMA- Amino acid 280 100 sequence of a human secreted protein.

1379 gi333947 Human membrane glycoprotein48 39 respiratory syncytial virus 1379 gi222567 Human SH protein 48 39 respiratory syncytial virus 1380 gi2459682Homo SapiensMAGE-B2 IMAGE-B2), 884 55 MACE-B3 IMAGE-B3), MACE-B4 (MADE-B4), and MAGE-B

IMAGE-B1) genes, complete cds.

1380 gi3687199Homo SapiensXp22 bins 169-171 884 55 BAC GSHB-383H3 (Genome Systems Human Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

BAC Library) complete sequence.

1380 gi4033512Homo SapiensDAM10 exon 3, partial867 54 sequence;

and DAM10=DSS-AHC
critical interval MAGE superfamily protein (DAM10) gene, complete cds.

1381 gi10198115Homo Sapiens2P domain potassium 2697 100 channel TREK2 (KCNK10) mRNA, complete cds.

1381 gi8452900Rattus potassium channel 2556 95 norvegicus 1381 gi4584799Mus musculusTREK-1 K+ channel 1244 65 subunit 1382 ABB 11297Homo SapiensHYSE- Human Coxsackie699 97 adenovirus receptor homologue, SEQ ID N0:1667.

1382 gi14279421Danio reriocoxsackievirus and 312 40 adenovirus receptor-like protein 1382 gi6013133Rattus coxsackie-adenovirus-receptor306 39 norvegicushomolog 1383 gi17016394Homo Sapienscervical cancer 1 753 100 proto-oncogene-binding protein KG19 (KG19) mRNA, complete cds.

1383 AAM58441 Homo SapiensMOLE- Human brain 99 28 expressed single exon probe encoded protein SEQ ID NO: 30546.

1383 AAB86126 Homo SapiensHUMA- Human MIT-like99 28 protein fragment encoded by cDNA clone HMSMI80.

1384 AAM06866 Homo SapiensHYSE- Human foetal 1133 95 protein, SEQ

ID NO: 1074.

1384 gi15099951Mus musculusdiacylglycerol acyltransferase959 51 1384 gi15099953Homo Sapiensdiacylglycerol acyltransferase951 50 mRNA, complete cds.

1386 gi338506 Homo SapiensHuman salivary statherin254 83 gene, exons 2-6.

1386 gi338508 Homo SapiensHuman statherin mRNA,254 83 complete cds.

1386 AAY94527 Homo SapiensINCY- Human statherin254 83 protein.

1387 gi10435784Homo SapienscDNA FLJ13693 fis, 1011 100 clone PLACE2000111.

1387 AAB94721 Homo SapiensHELI- Human protein 1011 100 sequence SEQ ID N0:15739.

1387 gi13592427Caenorhabditissimilar to glycoproteins124 34 ele ans 1388 gi12654579Homo Sapienspeptidylprolyl isomerase918 98 B

(cyclophilin B), clone MGC:2224 IMAGE:2966791, mRNA, complete cds.

1388 gi14250758Homo Sapienspeptidylprolyl isomerase918 98 B

(cyclophilin B), clone MGC:14109 IMAGE:3502055, mRNA, complete cds.

1388 gi337999 Homo SapiensHuman secreted cyclophilin-like918 98 protein (SCYLP) mRNA, complete cds.

1389 AAE07112 Homo SapiensHUMA- Human gene 2473 99 6 encoded secreted protein fragment, SEQ ID

Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

N0:129.

1389 gi9368530Homo SapiensmRNA full length 2457 99 insert cDNA

clone EUROIMAGE 363668.

1389 gi12053163Homo SapiensmRNA; cDNA DKFZp434D07272378 99 (from clone DICFZp434D0727);

complete cds.

1390 gi16589056Homo Sapienstype II gonadotropin-releasing1021 99 hormone receptor gene, partial cds.

1390 gi17048804Homo SapiensThe CDS shown includes1008 98 some apparent amino acids (from Gly 10 onw ards) which would be deleted in a short intron 1390 gi14029600CercopithecusGnRH receptor II 944 92 aethiops 1391 gi16359249Mus musculusRIKEN cDNA 1300010M032226 91 gene 1391 AAM93450Homo SapiensHELI- Human polypeptide,575 37 SEQ

ID NO: 3100.

1391 gi10438431Homo SapienscDNA: FLJ22155 fis, 596 34 clone HRC00205.

1392 AAE04896Homo SapiensINCY- Human transporter825 100 and ion channel-9 (TRICH-9) protein.

1392 gi12003980Homo Sapiensspinster-like protein695 52 mRNA, complete cds.

1392 gi14249892Homo Sapiensspinster-like protein,695 52 clone MGC:15767 IMAGE:3501826, mRNA, complete cds.

1393 AAG71515Homo SapiensYEDA Human olfactory1051 94 receptor polypeptide, SEQ
ID NO: 1196.

1393 AAG72603Homo SapiensYEDA Human OR-like 1051 94 polypeptide query sequence, SEQ

ID NO: 2284.

1393 AAU24762Homo SapiensSENO- Human olfactory482 47 receptor AOLFR130B.

1394 AAB08894Homo SapiensHUMA- Human secreted165 59 protein sequence encoded by gene 4 SEQ

ID N0:51.

1394 gi15626257Buffalopoxp8 protein homologue69 40 virus 1394 AA006451Homo SapiensHYSE- Human polypeptide69 35 SEQ

ID NO 20343.

1395 gi2792525Equus caballusconnexin 43 64 35 1395 gi15148992Human vpu protein 64 30 immunodeficienc y virus type 1 1395 gi5738572Human VPU protein 60 33 immunodeficienc y virus type 1 1396 AAM83617Homo SapiensHUMA- Human 61 41 immune/haematopoietic antigen SEQ ID N0:11210.

1396 gi4467773Helicobactercytotoxin associated60 34 protein A

pylori 1396 gi7248699Helicobactercytotoxin associated60 34 protein CagA

pylori 1397 gi11862939Mus musculusDDM36 5233 88 1397 gi11862941Mus musculusDDM36E 5224 88 1397 gi7650186Mus musculusneighbor of Punc 5196 87 el l protein Table 2A

SE Hit ID S ~ecies Descri tion S score% Identi ID

1398 gi5596705Homo SapiensNovel human mRNA 1305 71 similar to C.

elegans gene WP:CE18674, TR: Q 19985.

1398 gi15292481Drosophila SD03655p 1174 59 melanogaster 1398 AAB88372Homo SapiensHELI- Human membrane886 71 or secretory protein clone PSEC0108.

1399 gi1335598Simian sarcomacoding sequence of 64 33 plSE

virus 1399 gi14039584Casuarius ATPase 8 55 50 casuarius 1399 gi17427567Ralstonia HYPOTHETICAL 72 42 solanacearumTRANSMEMBRANE PROTEIN

1400 AAM88491Homo SapiensHUMA- Human 38 41 immune/haematopoietic antigen SEQ ID N0:16084.

1400 AA009674Homo SapiensHYSE- Human polypeptide38 44 SEQ

ID NO 23566.

1400 gi3845106Plasmodium metal binding protein55 36 (DHHC

falciparum domain) 1401 gi10434098Homo SapienscDNA FLJ12547 fis, 149 34 clone NT2RM4000634.

1401 AAB95124Homo SapiensHELI- Human protein 149 34 sequence SEQ ID N0:17122.

1401 AA009309Homo SapiensHYSE- Human polypeptide139 26 SEQ

ID NO 23201.

1402 AAE01249Homo sapiensHUMA- Human gene 222 100 18 encoded secreted protein HFIIN69, SEQ ID

NO:111.

1402 AAE01299Homo SapiensHUMA- Human gene 222 100 18 encoded secreted protein HFIIN69, SEQ ID

N0:162.

1402 AAE01332Homo SapiensHUMA- Human gene 222 100 18 encoded secreted protein fragment, SEQ ID

N0:197.

1403 AAM06589Homo sapiensHYSE- Human foetal 237 100 protein, SEQ

ID NO: 320.

1403 gi10732779Mus musculusAPRIL 56 43 1403 AAM87662Homo SapiensHUMA- Human 38 58 ~

immune/haematopoietic antigen SEQ ID N0:15255.

1404 AAO09486Homo SapiensHYSE- Human polypeptide486 98 SEQ

ID NO 23378.

1404 gi9955912Homo SapiensGPVI mRNA for platelet288 37 lycoprotein VI-2, complete cds.

1404 AAB40232Homo SapiensHUMA- Human secreted326 40 protein sequence encoded by gene 46 SEQ

ID N0:142.

1405 AAM06606Homo SapiensHYSE- Human foetal 50 34 protein, SEQ

ID NO: 337.

1405 gi495989Homo SapiensHuman rearranged 58 27 IgH chain gene, VJ6 region, partial cds.

1405 AAM85487Homo SapiensHUMA- Human 56 32 immune/haematopoietic antigen SEQ ID N0:13080.

1406 gi13377867Gallus gallusclaudin-3 116 24 1406 gi15553371Danio rerioclaudin c 112 26 Table 2A

SEQ Hit ID S ecies Descri _tion S score% Identit ID

1406 115553375Danio rerioclaudin h _ 110 23 1407 AAY78801 Homo SapiensPROT- Hydrophobic 701 100 domain containing protein clone HP00631 amino acid sequence.

1407 AAY32204 Homo SapiensINCY- Human receptor701 100 molecule (REC) encoded by Incyte clone 2132179.

1407 gi5231135Homo Sapiensandrogen induced 695 99 protein (AIG-1) mRNA, complete cds.

1408 gi13543940Homo SapiensSimilar to RIKEN 2232 96 cDNA

2610017609 gene, clone MGC:12975 IMAGE:3347312, mRNA, complete cds.

1408 AAB 12138Homo SapiensPROT- Hydrophobic 2221 96 domain protein isolated from HT-1080 cells.

1408 AAG81335 Homo SapiensZYMO Human AFP protein2218 96 sequence SEQ ID N0:188.

1410 gi10719608Homo SapiensIL-22 receptor (IL22R)1699 100 mRNA, complete cds.

1410 AAW97861 Homo SapiensZYMO Human cytokine 1699 100 receptor 11 (Zcytorll).

1410 AAY97045 Homo SapiensMILL- Human TANGO 1699 100 241.

1411 gi14090278Rattus TAT1 668 84 norvegicus 1411 gi458247 Homo SapiensHuman X-linked PEST-containing414 51 transporter (XPCT) mRNA, partial cds.

1411 gi458255 Homo SapiensHuman X-linked PEST-containing414 51 transporter (XPCT) gene, exon 6.

1412 gi4378057Homo Sapiensorganic anion transporter317 51 (OAT)) mRNA, complete cds.

1412 gi4579725Homo SapiensmRNA for hOATl-2, 317 51 complete cds.

1412 gi5901645Homo Sapiensorganic anion transporter317 51 (SLC22A6) mRNA, complete cds.

1413 gi3881524CaenorhabditisZK1067.4 714 41 elegans 1413 gi19322 Lycopersiconglycine-rich protein63 50 esculentum 1413 gi2204081Pinctada insoluble protein 93 52 fucata 1414 AAB43682 Homo SapiensHLTMA- Human cancer 1522 100 associated protein sequence SEQ ID

N0:1127.

1414 gi12654351Homo Sapienssolute carrier family1522 100 (mitochondria) carrier;
phosphate carrier), member 3, clone MGC:5280 IMAGE:2984830, mRNA, complete cds.

1414 gi12654961Homo Sapienssolute carrier family1522 100 (mitochondria) carrier;
phosphate carrier), member 3, clone MGC:5556 IMAGE:3457151, mRNA, complete cds.

1415 gi1764015Ciona intestinalisCOS41.5 314 42 1415 AAM42167 Homo SapiensHYSE- Human polypeptide284 30 SEQ

ID NO 7098.

Table 2A

SE Hit ID S ecies Descri ~tion ~ S score % Identi ID

1415 AAE03438 Homo SapiensHUMA- Human gene 258 30 12 encoded secreted protein HETHW90, SEQ

ID NO: 121.

1416 gi13591714Homo Sapiensimmunoglobulin superfamily1128 88 receptortranslocation associated protein 2c (IRTA2) mRNA, complete cds, alternatively s liced.

1416 gi15277746Homo SapiensFc receptor-like 1128 88 protein 5 (FCRHS) mRNA, complete cds.

1416 AAB82315 Homo SapiensUYCO Human immunoglobulin1128 88 receptor isoform IRTA2c.

1417 AAV40386_Homo SapiensINCY- Human zinc 525 80 binding aal protein ZB-2 encoding cDNA.

1417 gi13278762Homo Sapiensring finger protein 525 80 5, clone MGC:2407 IMAGE:2822537, mRNA, complete cds.

1417 gi13366064Homo SapiensmRNA for Hsltmal, 525 80 complete cds.

1418 gi3077703Oryctolagusmitsugumin29 1336 93 cuniculus 1418 gi3461888Mus musculusmitsugumin29 1314 91 1418 AAU25436 Homo sapiensINCY- Human mddt 1050 96 protein from clone LG:171377.1:2000MAY19.

1419 gi13452508Mus musculusclaudin 14 371 40 1419 gi12597447Homo Sapiensclaudin 14 (CLDN14) 370 40 mRNA, complete cds.

1419 gi15082421Homo SapiensSimilar to claudin 370 40 14, clone MGC:20195 IMAGE:4684949, mRNA, complete cds.

1420 AAG00539 Homo SapiensGEST Human secreted 173 49 protein, SEQ ID NO: 4620.

1420 AAU20426 Homo SapiensHUMA- Human secreted163 47 protein, Seq ID No 418.

1420 AAG75413 Homo SapiensHUMA- Human colon 159 50 cancer antigen protein SEQ
ID N0:6177.

1421 gi14486155Bos taurusRh type B glycoprotein1703 86 1421 gi15718471Homo SapiensRh type B glycoprotein1448 80 (RHBG) gene, exons 9, and 10 and complete cds.

1421 gi9858562Homo SapiensRh type B glycoprotein1448 80 (RHBG) mRNA, complete cds.

1422 AAM00949 Homo SapiensHYSE- Human bone 215 46 marrow protein, SEQ ID NO:
425.

1422 AAE01852 Homo SapiensHUMA- Human gene 174 40 11 encoded secreted protein fragment, SEQ ID

N0:175.

1422 gi14209834Mus musculusATP-binding cassette178 38 transporter sub-family A member 1423 gi12053628Homo SapiensmRNA for ribonuclease718 99 7.

1423 AAY44192 Homo SapiensINNO- Human keratinocyte-718 99 derived RNase-like protein.

1423 AAB10601 Homo SapiensSCHD Human SAP-2 718 99 pre-protein.

1424 AAM83996 Homo SapiensHUMA- Human 1153 99 immune/haematopoietic antigen SEQ ID N0:11589.

1424 AAG02219 Homo SapiensGEST Human secreted 483 99 protein, SEQ ID NO: 6300.

Table 2A

SEQ Hit ID S ecies Description S score% Identi ID

1424 gi222902 Oncorhynchuspituitary-specific 98 32 transcription keta factor, Pit-lIGHF-1 1425 AAB82485 Homo SapiensZYMO Human secretin-like499 92 receptor Zgprl.

1425 AAB82487 Homo SapiensZYMO Human secretin-like499 92 receptor Zgprl splice variant.

1425 AAE03382 Homo SapiensHUMA- Human gene 499 92 5 encoded secreted protein HEOMX53, SEQ

ID N0:40.

1426 gi6808374Homo SapiensmRNA; cDNA DKFZp434G08123211 100 (from clone DKFZp434G0812);

partial cds.

1426 gi433383 Tripneustesdynein heavy chain 241 26 isotype 5A

gratilla 1426 gi6706264Leishmaniadynein heavy chain 271 26 major 1428 gi13540300Mus musculusnucleolar protein 427 34 1428 gi13561516Mus musculusnucleolar protein 426 34 1428 AAM25939 Homo SapiensHYSE- Human protein 156 90 sequence SEQ ID N0:1454.

1429 AAU27632 Homo SapiensZYMO Human protein 117 49 AFP674535.

1429 AAM40391 Homo SapiensHYSE- Human polypeptide117 49 SEQ

ID NO 3536.

1429 gi7022187Homo SapienscDNA FLJ10261 fis, 85 42 clone HEMBB 1000975.

1430 AAY07751 Homo SapiensHUMA- Human secreted293 100 protein fragment encoded from gene 8.

1430 gi1142588TrypanosomeCR3 84 43 brucei 1430 AAO05990 Homo SapiensHYSE- Human polypeptide72 33 SEQ

ID NO 19882.

1431 AAM93525 Homo SapiensHELI- Human polypeptide,246 36 SEQ

ID NO: 3259.

1431 AAY66693 Homo sapiensGETH Membrane-bound 191 38 protein PRO 1004.

1431 AAB65216 Homo SapiensGETH Human PR01004 191 38 (UNQ488) protein sequence SEQ

ID N0:227.

1432 AAB88388 Homo SapiensHELI- Human membrane316 44 or secretory protein clone PSEC0131.

1432 AAB25719 Homo SapiensHUMA- Human secreted84 73 protein sequence encoded by gene 6 SEQ

ID N0:108.

1432 AAM62047 Homo SapiensMOLE- Human brain 45 39 expressed single exon probe encoded protein SEQ ID NO: 34152.

1433 AAB88388 Homo SapiensHELI- Human membrane318 44 or secretory protein clone PSEC0131.

1433 AAB25719 Homo SapiensHUMA- Human secreted86 66 protein sequence encoded by gene 6 SEQ

ID N0:108.

1433 gi5629917Homo Sapienspartial FLN2 gene 77 34 for ABP-L, gamma filamin, exons 1 to 3.

1434 AAG75991 Homo SapiensHUMA- Human colon 235 77 cancer antigen protein SEQ
ID N0:6755.

Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

1434 AAM78941Homo SapiensHYSE- Human protein 220 86 SEQ ID

NO 1603.

1434 ABB 14802Homo SapiensHUMA- Human nervous 58 40 system related polypeptide SEQ ID NO

3459.

1435 gi9621664Homo SapiensRHBDL gene for rhomboid-related1129 56 protein.

1435 gi14336709Homo Sapiens16p13.3 sequence 1123 56 section 3 of 8.

1435 gi3287191Homo SapiensmRNA for rhomboid-related1123 56 protein, complete CDS.

1436 gi7106866Homo SapiensHSPC238 238 56 1436 AAU15887Homo SapiensHUMA- Human novel 238 56 secreted protein, Seq ID 840.

1436 AAU16342Homo SapiensHUMA- Human novel 238 56 secreted protein, Seq ID 1295.

1437 11418942Mus musculussamaphorin G 5660 93 1437 AAY94990Homo SapiensALPH- Human secreted5403 99 protein vb21_1, SEQ ID N0:20.

1437 gi2772584Homo Sapienssemaphorin F homolog3560 59 mRNA, complete cds.

1439 gi11055322Homo Sapiensvanilloid receptor-related3324 100 osmotically activated channel (VROAC) mRNA, complete cds.

1439 AAI66972_Homo SapiensMILL- Human ion channel3319 99 aal cDNA sequence.

1439 AAG65787Homo sapiensMILL- Human ion channel3318 99 protein sequence.

1440 gi4155033Helicobactercag island protein 72 25 pylori 1440 AAU69567Homo SapiensPHAA Human G protein-coupled77 23 receptor from cDNA
Seq-2643.

1440 gi13171062turkey M protein 56 41 coronavirus 1441 gi16554186Homo SapienscDNA FLJ25409 fis, 644 100 clone TST03074.

1441 gi4235228Mus musculusleucine zipper-EF-hand497 59 containing transmembrane protein 1441 gi6599194Homo sapiensmRNA; cDNA DI~FZp434C229493 63 (from clone DI~FZp434C229);

partial cds.

1442 gi16359165Homo Sapiensclone IMAGE:4645529,1270 100 mRNA, partial cds.

1442 ABB11242Homo SapiensHYSE- Human SLIT-2 653 99 homologue, SEQ ID
N0:1612.

1442 AAB07469Homo SapiensZYMO A human leucine-rich451 36 repeat protein designated Zlrr3.

1443 AAE03245Homo SapiensHUMA- Human gene 804 100 3 encoded secreted protein fragment, SEQ ID

N0:95.

1443 AAE03244Homo SapiensHUMA- Human gene 799 100 3 encoded secreted protein fragment, SEQ ID

N0:94.

1443 AAE03204Homo SapiensHUMA- Human gene 617 100 3 encoded secreted protein HNGNN78, SEQ

ID N0:54.

1444 '4062463EscherichiaABC transporter probable697 91 coli ATP-Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

bindin subunit homolog 1444 gi15487341Escherichiamacrolide-specific 697 91 coli ABC-type efflux carrier 1444 gi17743610AgrobacteriumABC transporter, 366 51 nucleotide tumefaciensbinding/ATPase protein str.

C58 (Dupont) 1446 gi3168602Homo Sapiensp160 mRNA, partial 3755 89 cds.

1446 AAW31185 Homo SapiensDAND Human p160 polypeptide3169 87 160.1.

1446 gi3168604Homo Sapiensproline and glutamic1641 99 acid rich nuclear protein isoform mRNA, partial cds.

1447 gi14042515Homo SapienscDNA FLJ14761 fis, 67 36 clone NT2RP3003302.

1447 AAG67254 Homo SapiensHELI- Amino acid 67 36 sequence of a human liver-associated gene.

1447 AAB94495 Homo SapiensHELI- Human protein 67 36 sequence SEQ ID N0:15188.

1448 AAB24058 Homo SapiensGETH Human PR0290 1972 100 protein sequence SEQ ID N0:7.

1448 AAY66639 Homo SapiensGETH Membrane-bound 1972 100 protein PR0290.

1448 AAB65162 Homo SapiensGETH Human PR0290 1972 100 (UNQ253) protein sequence SEQ ID N0:33.

1449 gi14043409Homo SapiensSimilar to procollagen,89 75 type IV, alpha 3, clone MGC:11337 IMAGE:3953131, mRNA, complete cds.

1449 gi5420387Leishmaniaproteophosphoglycan 86 24 major 1449 gi16117372MacropodidICP4 102 27 herpesvirus 1450 AAU27660 Homo SapiensZYMO Human protein 889 100 AFP671052.

1450 AAG74151 Homo SapiensHUMA- Human colon 748 100 cancer antigen protein SEQ
ID N0:4915.

1450 gi5670326Homo SapiensICERE-1 mRNA, complete110 31 cds.

1451 AAY86519 Homo SapiensHUMA- Human gene 46 60 71-encoded protein fra ent, SEQ ID N0:434.

1451 AAM59183 Homo SapiensMOLE- Human brain 61 39 expressed single exon probe encoded protein SEQ ID NO: 31288.

1451 AAM71718 Homo SapiensMOLE- Human bone 61 39 marrow expressed probe encoded protein SEQ ID NO: 32024.

1452 gi12053219Homo SapiensmRNA; cDNA DKFZp434N12351031 93 (from clone DKFZp434N1235);

complete cds.

1452 gi15559050EthmostigmusADP-ATP translocator738 68 rubripes 1452 gi339723 Homo SapiensHuman ADPIATP translocase693 68 mRNA, 3' end, clone pHATB.

1453 gi15025781ClostridiumPredicted membrane 136 32 protein acetobutylicum 1453 AAM95190 Homo SapiensHUMA- Human reproductive42 23 system related antigen SEQ ID

NO: 3848.

Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

1453 AAM55650 Homo SapiensMOLE- Human brain 61 31 expressed single exon probe encoded protein SEQ ID NO: 27755.

1454 gi4929597Homo SapiensCGI-64 protein mRNA,1879 96 complete cds.

1454 gi6995987Homo Sapiensmitochondria) carrier1818 99 homolog 1 isoform a mRNA, complete cds;

nuclear gene for mitochondria) product.

1454 gi6995989Homo Sapiensmitochondria) carrier1483 99 homolog 1 isoform b (MTCH1) mItNA, partial cds; nuclear gene for mitochondria) product.

1455 gi17131893Nostoc WD-repeat protein 248 26 sp. PCC

1455 gi886024 ThermomonospoPkwA 248 30 ra curvata 1455 gi17225210Podospora beta transducin-like250 25 protein HET-anserina D2Y

1456 AAB36840 Homo SapiensZYMO Human insulin 6733 98 receptor-related receptor protein with signal peptide.

1456 gi186555 Homo SapiensHuman insulin receptor-related6728 99 receptor (IRR) mRNA, 3 ' end.

1456 AAB36836 Homo sapiensZYMO Human insulin 6728 99 receptor-related receptor protein.

1457 gi6453436Homo SapiensmRNA; cDNA DKFZp586E04110115 100 (from clone DKFZp586E041);

partial cds.

1457 ABB11803 Homo SapiensHYSE- Human GPI-122 6423 99 homologue, SEQ ID
N0:2173.

1457 AAY50125 Homo SapiensGEMY Human 6323 100 glycophosphatidylinositol-anchored protein GPI-122.

1458 AAU00023 Homo SapiensBIOJ Human activated3623 99 T-lymphocyte associated sequence 2, ATLAS-2.

1458 AAE04546 Homo sapiensINCY- Human G-protein2570 79 coupled receptor-2 (GCREC-2) protein.

1458 ABB11735 Homo SapiensHYSE- Human vasopressin2546 100 receptor homologue, SEQ ID

NO:2105.

1459 gi7021924Homo SapienscDNA FLJ10081 fis, 2742 100 clone HEMBA1002018.

1459 AAB92508 Homo SapiensHELI- Human protein 2742 100 sequence SEQ ID N0:10631.

1459 gi10435862Homo SapienscDNA FLJ13751 Es, 2687 99 clone PLACE3000339, weakly similar to PRECURSOR (EC 3.2.1.3).

1460 AAM95163 Homo SapiensHUMA- Human reproductive75 33 system related antigen SEQ ID

NO: 3821.

1460 AAM06875 Homo SapiensHYSE- Human foetal 68 45 protein, SEQ

ID NO: 1083.

1460 AAG76978 Homo SapiensHUMA- Human colon 65 39 cancer antigen protein SEQ
ID NO:7742.

Table 2A

SEQ Hit ID S ecies Description S score% Identi ID

1461 gi1353365Macaca MHC-G 84 30 fascicularis 1461 gi2655072Pan troglodytesMHC class I antigen 72 28 HLA-H

ortholog 1461 gi2655078Pan paniscusMHC class I antigen 72 28 HLA-H

ortholog 1462 gi11066090Homo Sapiensmatrix metalloprotease1191 85 mRNA, complete cds. I

1462 AAE10410Homo SapiensSCHA/ Human full 1188 85 length matrix metalloproteinase-251 (MMP-251) rotein.

1462 AAY90293Homo SapiensINCY- Human peptidase,1188 85 HPEP-10 protein sequence.

1463 gi601948Drosophila Inscuteable 126 25 melanogaster 1463 gi1657962Drosophila Nem 115 26 melanogaster 1463 gi15281684Bacteriophagep4 66 40 Mx8 1464 AAB45378Homo SapiensHUMA- Human secreted434 87 protein sequence encoded by gene 38 SEQ

ID N0:130.

1464 gi406058Mus musculusprotein kinase 219 54 1464 gi13537204Homo SapiensmRNA for MAST205, 216 54 complete cds.

1466 AAY97293Homo SapiensINCY- Lipid associated1894 77 protein (LIPAP) 3335404CD1.

1466 AAB24231Homo SapiensINCY- Human vesicle 1116 48 associated protein 10 SEQ ID
NO:10.

1466 AAM39997Homo SapiensHYSE- Human polypeptide1116 48 SEQ

ID NO 3142. ' 1467 gi13278855Homo Sapienscalcium binding atopy-related919 96 autoantigen 1, clone MGC:2891 IMAGE:3009677, mRNA, complete cds.

1467 gi13278921Homo Sapienscalcium binding atopy-related919 96 autoantigen 1, clone MGC:4521 IMAGE:3009677, mRNA, complete cds.

1467 AAB58329Homo SapiensLung cancer associated919 96 polypeptide sequence SEQ ID 667.

1468 gi12654401Homo SapiensSimilar to RNA cyclase690 78 homolog, clone MGC:1390 IMAGE:3343468, mRNA, complete cds.

1468 gi10434565Homo SapienscDNA FLJ12842 fis, 690 78 clone NT2RP2003286, weakly similar to PROBABLE RNA 3'-TERMINAL

PHOSPHATE CYCLASE
(EC

6.5.1.4).

1468 AAB97250Homo SapiensHOMO RNA cyclase 690 78 41 protein.

1469 gi12053215Homo SapiensmRNA; cDNA DI~FZp434K2435273 98 (from clone DKFZp434K2435);

complete cds.

1469 gi2633333Bacillus yhaJ 57 25 subtilis 1469 gi15023682ClostridiumGlycosyltransferase 73 34 involved in acetobutylicumcell wall biogenesis Table 2A

SE ID Hit ID S ecies Descri tion S score% Identi 1470 gi14290599Homo Sapiensclone MGC:17624 347 100 IMAGE:3855543, mRNA, complete cds.

1470 gi65265 Xenopus a xenopus upstream 131 29 laevis binding factor 1470 gi65201 Xenopus RNA polymerase I 128 29 laevis transcription factor 1471 gi13182747Homo Sapiensmicrosomal signal 148 96 peptidase subunit mRNA, complete cds.

1471 AAW29660Homo SapiensHomo Sapiens CH27_1 148 96 clone secreted protein.

1471 gi164084Canis familiarissignal peptidase 141 90 21 kDa subunit 1472 AAG03600Homo SapiensHuman secreted protein,245 86 SEQ ID

NO: 7681.

1472 gi7770239Homo SapiensPR02831 139 71 1472 gi14026000Mesorhizobiumtransposase 64 46 loti 1473 gi3065951Homo SapiensNotch3 (NOTCH3) gene,99 58 exon 33 and complete cds.

1473 gi2668592Homo SapiensNotch3 (NOTCH3) mRNA,99 58 complete cds.

1473 AAW49698Homo SapiensHuman Notch3 protein.99 58 1474 gi458938SaccharomycesYhr186cp 156 58 cerevisiae 1474 gi5921144Schizosaccharommipl 151 83 yces pombe 1474 gi6459542Deinococcusserine/threonine 96 31 protein ldnase-radioduransrelated protein 1475 gi6562173Homo SapiensmRNA; cDNA DKFZp566H033295 91 (from clone DKFZp566H033);

partial cds.

1475 AAB38280Homo SapiensHuman secreted protein289 96 sequence encoded by gene 20 SEQ ID

N0:136.

1475 AAB94892Homo SapiensHuman protein sequence284 89 SEQ ID

N0:16234.

1476 17160973Homo SapiensmRNA for VNN3 protein.1954 93 1476 gi6102996Mus musculusVanin-3 1661 73 1476 gi6649540Canis familiarisTIFF66 1370 67 1477 gi7959741Homo SapiensPRO1051 134 76 1477 gi172903Saccharomycestranscription factor113 26 IIIA

cerevisiae 1477 gi786305SaccharomycesTranscription factor113 26 TFIIIA (PIR

cerevisiae accession number . 520050) 1478 gi12652825Homo Sapiensvoltage-dependent 483 74 anion channel 2, clone MGC:5237 IMAGE:2901130, mRNA, complete cds.

1478 gi15277577Homo Sapiensvoltage-dependent 483 74 anion channel 2, clone MGC:21498 IMAGE:3875077, mRNA, complete cds.

1478 gi5114261Homo Sapiensvoltage-dependent 483 74 anion channel isoform 2 (VDAC2) gene, exon 10 and complete cds.

1479 gi10435380Homo SapienscDNA FLJ13381 fis, 133 58 clone PLACE 1001010.

Table 2A

SE(~ Hit ID S ecies Descri tion S score% Identit ID ~

1479 AAB94622Homo SapiensHuman protein sequence133 58 SEQ ID

N0:15476.

1479 AAB85361Homo SapiensHuman phosphatase 118 50 (PP) (clone ID

7472032CD1).

1480 gi12803725Homo SapiensAPGS (autophagy 5, 204 100 S.

cerevisiae)-like, clone MGC:3622 IMAGE:3609927, mRNA, complete cds.

1480 gi2995198Homo SapiensH.sapiens mRNA for 204 100 apoptosis specific protein.

1480 gi12006864Homo Sapiensapoptosis-related 204 100 protein (APGSL) mRNA, complete cds, alternatively spliced.

1481 gi12619679Conus arenatusconotoxin scaffold 56 25 VI/VII

precursor 1481 gi2661493Drosophila56F3.e 72 34 melanogaster 1481 gi2648663ArchaeoglobusDNA-directed RNA polymerise,55 27 fulgidus subunit H (rpoH) 1482 gi12654623Homo SapiensRAB31, member RAS 194 58 oncogene family, clone MGC:1258 IMAGE:3534853, mRNA, complete cds.

1482 gi1457954Homo SapiensHuman small GTP-binding194 58 protein rab22b mRNA, complete cds.

1482 gi1388195Homo SapiensHuman low-Mr GTP-binding194 58 protein (RAB31) mRNA, complete cds.

1483 gi7959778Homo SapiensPR01546 163 65 1483 AAG02753Homo SapiensHuman secreted protein,154 68 SEQ ID

NO: 6834.

1483 AAB93922Homo SapiensHuman protein sequence137 59 SEQ ID

N0:13907.

1484 gi6979921DrosophilaRhoGTPase y 160 32 melanogaster 1484 gi7263024DrosophilaG protein RhoBTB 160 32 melano aster 1484 gi15291731DrosophilaLD24835p 160 32 melanogaster 1485 gi14150450Rattus UDP-GaINAc:polypeptide246 93 N-norvegicusacetyl alactosaminyltransferase 1485 gi3047203CaenorhabditisGLY7 128 54 elegans 1485 gi304259Bos taurusUDP-GaINAc:polypeptide,109 45 N-acetylgalactosaminyltransferase 1486 AAB95830Homo SapiensHuman protein sequence202 76 SEQ ID

N0:18850.

1486 AAG03710Homo SapiensHuman secreted protein,192 73 SEQ ID

NO: 7791.

1486 AAG02922Homo SapiensHuman secreted protein,182 69 SEQ ID

NO: 7003.

1487 AAB38012Homo SapiensHuman secreted protein1244 84 encoded by gene 3 clone HNHCT15.

1487 AAB64943Homo SapiensHuman secreted protein1249 85 sequence encoded by gene 7 SEQ ID

N0:121.

1487 gi339771Homo SapiensHuman transposon Ll.l1243 84 with a Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

base deletion relative to L1.2B

resulting in a premature stop codon in the coding region.

1488 gi13560707Homo Sapiensgroup XIII secreted 383 98 phospholipase A2 mRNA, complete cds.

1488 gi15824793Homo Sapiensgroup XIII secreted 383 98 phospholipase 1488 AAY27572Homo SapiensHuman secreted protein383 98 encoded by gene No. 6.

1489 gi2995442Homo SapiensmRNA for UDPGaI:GIcNAc996 98 b1,4 galactosyltransferase.

1489 gi4520136Homo SapiensmRNA for beta-1,4- 996 98 galactosyltransferase II, complete cds.

1489 gi3869131Mus musculusbeta-1,4-galactosyltransferase946 94 II

1490 AAM06551Homo SapiensHuman foetal protein,140 49 SEQ ID NO:

282.

1490 AAB51718Homo SapiensHuman secreted protein129 58 sequence encoded by gene 45 SEQ ID

N0:158.

1490 gi1196431Homo SapiensHuman factor VIII 124 52 gene Ll element insertion DNA.

1491 gi12052884Homo SapiensmRNA; cDNA DKFZp564C2478487 98 (from clone DKFZp564C2478);

complete cds.

1491 gi7023332Homo SapienscDNA FLJ10961 fis, 487 98 clone PLACE1000588, highly similar to INTERFERON-INDUCED

GUANYLATE-BINDING

PROTEIN 1.

1491 AAB93371Homo SapiensHuman protein sequence487 98 SEQ ID

N0:12521.

1492 AAG00392Homo SapiensHuman secreted protein,150 81 SEQ ID

NO: 4473.

1492 AAB54106Homo SapiensHuman pancreatic 136 71 cancer antigen protein sequence SEQ ID N0:558.

1492 gi914110StreptococcusEmmLlS 107 20 pyogenes 1493 gi6855513Gallus syndesmos 554 60 gallus 1493 gi13623247Homo SapiensSimilar to RII~EN 534 58 cDNA

1110001I~21 gene, clone MGC:11275 IMAGE:3944355, mRNA, complete cds.

1493 gi12544542CorynebacteriumRXA02115 99 28 glutamicum 1494 gi12082725Mus musculusB cell phosphoinositide335 62 3-kinase adaptor 1494 gi12082811Gallus B cell phosphoinositide211 48 gallus 3-ldnase adaptor 1494 gi330842Equine myristylated virion 61 33 protein herpesvirus 1495 AAB43811Homo SapiensHuman cancer associated273 100 protein sequence SEQ ID N0:1256.

1495 AAB64482Homo SapiensHuman secreted protein273 100 sequence encoded by gene 13 SEQ ID

N0:120.

1495 15106795Homo Sapienssec61 homolog mRNA, 273 100 complete Table 2A

SEQ Hit ID S ecies Description S score% Identi ID

cds.

1496 AAE01786Homo SapiensHuman gene 17 encoded4730 97 secreted protein HWBEM18, SEQ ID

N0:107.

1496 gi6650678Mus musculusnuclear pore membrane4025 76 glycoprotein POM210 1496 gi56463 Rattus gp210 (AA 1-1886) 4000 79 norve icus 1497 gi185996Homo SapiensHuman Ig germline 607 100 kappa L-chain V-region gene (HK166), V-kappa-1.

1497 AAR38651Homo SapiensHuman V-kappa fragment607 100 encoded by clone vk65.15.

1497 AAR62931Homo SapiensHuman V-kappa vk65.15607 100 region.

1498 gi431857Homo SapiensH.sapiens mRNA for 460 76 delta 4-3-oxosteroid 5 beta-reductase.

1498 gi11640835Homo Sapiens5-beta steroid reductase460 76 (SRD5B1) gene, exon 9 and complete cds.

1498 gi5689216Oryctolagusdelta4-3-oxosteroid 442 70 5beta-cuniculus reductase 1499 gi1752736Saccharomycesgene required for 210 47 phosphoylation cerevisiaeof oligosaccharides/
has high homology with YJR061w 1499 AAB53977Homo SapiensHuman colon cancer 178 71 antigen protein sequence SEQ ID

N0:1517.

1499 AAB27956Homo SapiensHuman secreted protein177 65 SEQ ID

NO: 110.

1500 AAB93159Homo SapiensHuman protein sequence2209 64 SEQ ID

N0:12081.

1500 AAB58796Homo SapiensBreast and ovarian 1455 65 cancer associated antigen protein sequence SEQ ID 504.

1500 gi13377567Vibrio accessory colonization105 26 cholerae factor AcfD

1501 AAB95655Homo SapiensHuman protein sequence186 78 SEQ ID

N0:18417.

1501 AAB95596Homo SapiensHuman protein sequence172 80 SEQ ID

NO:18279.

1501 gi1196433Homo SapiensHuman factor VIII 182 78 gene Ll element insertion DNA.

1502 AAB58202Homo SapiensLung cancer associated427 100 polypeptide sequence SEQ ID 540.

1502 gi4572328Homo Sapienscaveolin-1 gene, 345 100 exon 3 and complete cds.

1502 gi6599075Homo Sapienscaveolin-1/-2 locus,345 100 Contigl, D7S522, genes CAV2 (exons 1, 2a, and 2b), CAV
1 (exons 1 and 2).

1503 gi199584Mus musculusMHox 405 96 1503 gi51362 Mus musculusDNA-binding protein 405 96 1503 gi1836044Rattus rHox protein 405 96 sp.

1504 gi8163762Homo Sapiensmembrane cofactor 639 83 protein CD46 variant (MCP) mRNA, partial cds.

1504 AAB58394Homo sapiensLung cancer associated635 82 polypeptide sequence SEQ ID 732.

1504 AAG75528Homo SapiensHuman colon cancer 635 82 antigen Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

protein SEQ ID N0:6292.

1505 gi15990400Homo Sapiensclone IMAGE:3954884,872 83 mRNA, partial cds.

1505 gi3523113Homo Sapiensprostate-specific 92 46 transglutaminase (TGM4) gene, alternative spliced variant, exon 2 and partial cds.

1505 AAB54389Homo SapiensHuman pancreatic 84 56 cancer antigen rotein sequence SEQ
ID N0:841.

1506 AAB94891Homo sapiensHuman protein sequence214 65 SEQ ID

N0:16231.

1506 gi1196431Homo SapiensHuman factor VIII 197 66 gene L1 element insertion DNA.

1506 AAB38280Homo SapiensHuman secreted protein196 69 sequence encoded by gene 20 SEQ ID

N0:136.

1507 gi1184173Homo SapiensHuman nucleoporin 1058 100 98 (NUP98) mRNA, complete cds.

1507 gi11414896Homo SapiensNUP98 mRNA for nucleoporin,1058 100 complete cds.

1507 gi4545101Homo Sapienscell-line HeLa Nup98-Nup961060 88 precursor splice variant 1 mRNA, complete cds.

1508 gi5106521Homo SapiensK-Cl cotransporter 1062 96 KCC4 mRNA, complete cds.

1508 gi10440500Homo SapiensmRNA for FLJ00098 1062 96 protein, partial cds.

1508 gi10440514Homo SapiensmRNA for FLJ00105 1062 96 protein, partial cds.

1509 gi6691968Homo SapiensHuman DNA sequence 293 81 from clone RP1-148M19 on chromosome Xp11.22-11.3 Contains (zinc finger protein), a ribosomal protein L23a pseudogene, STSs and GSSs, complete sequence.

1509 gi4096339Homo SapiensHuman zinc finger 293 81 protein (ZNF741) mRNA, complete cds.

1509 AAB21033Homo SapiensHuman nucleic acid-binding293 81 protein, NuABP-37.

1510 AAB38012Homo SapiensHuman secreted protein426 57 encoded by gene 3 clone HNHCT15.

1510 gi5052951Homo SapiensLINEl element inserted425 57 in B-globin gene intron 2.

1510 AAB64943Homo SapiensHuman secreted protein426 57 sequence encoded by gene 7 SEQ ID

NO:121.

1511 gi16041769Homo Sapiensclone MGC:23189 313 55 IMAGE:4854518, mRNA, complete cds.

1511 gi4454678Homo Sapienszinc finger protein 308 55 1511 gi186774Homo SapiensHuman Kruppel related321 55 zinc finger protein (HTF10) mRNA, complete cds.

1512 gi14027838Mesorhizobiumtranscriptional regulator91 26 loti 1513 gi4886463Homo SapiensmRNA; cDNA DKFZp586G12191039 100 (from clone DKFZp586G1219);

partial cds.

Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

1513 gi4337460Homo Sapiensneuroblastoma-amplified1039 100 protein mRNA, complete cds.

1513 AAB38417 Homo sapiensFragment of human 1039 100 secreted protein encoded by gene 5 clone HCGMF 16.

1514 gi1621611Homo SapiensHuman TRAF family 1667 76 member-associated NF-kB
activator TANK

mRNA, complete cds.

1514 gi1518018Homo SapiensHuman TRAF-interacting1655 77 protein I-TRAF mRNA, complete cds.

1514 AAW27163 Homo SapiensHuman TRAF inhibitor1655 77 protein I-TRAF.

1515 gi12957169Mus musculussynaptotagmin-like 142 60 protein 3-b 1515 gi13647085Mus musculussynaptotagmin-like 142 60 protein 3-a delta 3S-II

1515 gi13647079Mus musculussynaptotagmin-like 142 60 protein 3-a+

1516 gi6688199Homo SapiensmRNA for AMP-activated1055 93 protein kinase gamma2 subunit (AMPK

gamma2 gene).

1516 gi5931569Homo SapiensmRNA for H91620p, 1055 93 complete cds.

1516 gi12642942Homo SapiensAMP-activated protein1055 93 kinase gamma subunit (PRKAG2) mRNA, complete cds.

1517 gi6807587Homo SapiensNovel human gene 2360 100 mapping to chomosome 1.

1517 gi1769491Homo SapiensHuman kruppel-related1135 49 zinc finger protein (ZNF184) mRNA, partial cds.

1517 gi186774 Homo SapiensHuman Kruppel related904 41 zinc finger protein (HTF10) mRNA, complete cds.

1518 gi9956065Homo Sapiensclone CDABP0092 mRNA602 100 sequence.

1518 gi4038733Homo SapiensmRNA for beta 2-microglobulin,602 100 complete cds.

1518 gi5725512Homo Sapiensbeta-2 microglobulin602 100 gene, complete cds.

1519 gi187177 Homo sapiensHuman lamin-like 216 57 protein in HindIII repetitive element derived DNA, 3' end.

1519 gi339771 Homo SapiensHuman transposon 223 57 L1.1 with a base deletion relative to L1.2B

resulting in a premature stop codon in the coding re 'on.

1519 gi5070622Homo Sapiensretrotransposon Ll 223 57 insertion in X-linked retinitis pigmentosa locus, complete sequence.

1520 AAE03963 Homo SapiensHuman gene 17 encoded110 47 secreted protein fragment, SEQ ID N0:142.

1520 gi4097459Elephantulusreverse transcriptase109 47 edwardii 1520 AAB94930 Homo SapiensHuman protein sequence109 46 SEQ ID

NO:16405.

1521 gi10934047Mus musculusScot-tl 1035 77 1521 110934052Mus musculusScot-t2 1035 77 Table 2A

SEQ Hit ID S ecies Description S score% Identi ID

1521 gi164423 Sus scrofasuccinyl-CoA:alpha-ketoacid1024 81 coenzyme A transferase 1522 gi12003128EremotheciumYer154p 108 31 goss ii 1522 gi5052482DrosophilaBcDNA.GH02220 102 29 melanogaster 1522 gi6227006ArabidopsisF16G16.8 94 50 thaliana 1523 gi3419880Homo SapiensmRNA for MDC/ADAM11,2989 100 complete cds.

1523 gi836683 Homo SapiensHuman 2989 100 metalloprotease/disintegrin-like (MDC) gene, partial cds.

1523 AAR75352 Homo SapiensHuman fetal brain 2984 99 MDC protein.

1524 gi1109782Homo SapiensHuman protein-tyrosine2518 97 phosphatase mRNA, complete cds.

1524 gi1781037Mus musculusneuronal tyrosine 1996 87 threonine phosphatase 1 1524 AAB66436 Homo SapiensHuman MAP-kinase 883 99 phosphatase hVHS.

1525 gi757911 Homo SapiensH.sapiens mRNA for 442 100 A2b adenosine receptor.

1525 gi178150 Homo SapiensHuman adenosine A2b 442 100 receptor (ADORA2) mRNA, complete cds.

1525 AAR41526 Homo SapiensHuman A2b adenosine 442 100 receptor.

1526 gi13540160Homo SapiensTCF12-TEC fusion 335 79 protein mRNA, partial cds.

1526 gi183930 Homo SapiensHuman HEB helix-loop-helix337 75 protein (HEB) mRNA, complete cds.

1526 gi184448 Homo Sapienstranscription factor337 75 (HTF4) mRNA, complete cds.

1527 AAB43940 Homo SapiensHuman cancer associated741 95 protein sequence SEQ ID N0:1385.

1527 gi14602778Homo Sapiensspermine synthase, 690 95 clone MGC:2071 IMAGE:3506022, mRNA, complete cds.

1527 gi2198557Homo Sapiensspermidine aminopropyltransferase690 95 mRNA, complete cds.

1528 gi13436152Homo Sapiensreticulocalbin 2, 674 81 EF-hand calcium binding domain, clone MGC:1650 IMAGE:3505241, mRNA, complete cds.

1528 gi469885 Homo SapiensH.sapiens ERC-55 674 81 mRNA.

1528 AAW21949 Homo SapiensE6-binding protein 674 81 E6-BPSD7.

1529 gi10440331Homo SapienscDNA: FLJ23591 fis, 606 100 clone , LNG14729.

1529 AAB84327 Homo SapiensAmino acid sequence 606 100 of a human lyase and associated protein HLYAP-2.

1529 gi15150358Mus musculusUDP-glucuronic acid 605 99 decarboxylase 1530 AAB38012 Homo SapiensHuman secreted protein3094 92 encoded by gene 3 clone HNHCT15.

1530 AAB64943 Homo SapiensHuman secreted protein3094 92 sequence encoded by gene 7 SEQ ID

Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

N0:121.

1530 gi5052951Homo SapiensLINEl element inserted3083 91 in B-globin gene intron 2, 1531 gi5596433Homo Sapienscandidate tumor suppressor330 87 protein NOC2 (NOC2) mRNA, complete cds.

1531 gi7020579Homo sapienscDNA FLJ20462 fis, 330 87 clone KAT06107.

1531 gi 13477353Homo SapiensSimilar to rabphilin329 87 3A-like (without C2 domains), clone MGC:3453 IMAGE:3529317, mRNA, complete cds.

1532 gi1531645Rattus C2-HC type zinc finger1914 67 protein r-norve icus MyT3 1532 gi2914751Rattus neural zinc finger 1909 66 factor 3; NZF-3 norvegicus 1532 gi1531653Xenopus C2-HC type zinc forger300 42 laevis protein X-MyTl 1533 gi12805043Homo Sapiensclone IMAGE:3461487,364 41 mRNA, partial cds, 1533 AAG81328Homo SapiensHuman AFP protein 356 41 sequence SEQ

ID NO:174.

1533 gi2226004Homo SapiensHuman Tiggerl transposable441 71 element, complete consensus sequence.

1534 gi10436783Homo SapienscDNA FLJ14341 fis, 3184 97 clone THYR01000343, wealdy similar to ATROPHIN-1.

1534 AAB95860Homo SapiensHuman protein sequence3184 97 SEQ ID

N0:18924.

1534 gi12802159Homo SapiensSH3-SAM adaptor protein515 46 (HACS1) mRNA, complete cds.

1535 gi15928572Mus musculusSimilar to leucine 103 66 rich repeat (in FLII) interacting protein 2 1535 gi14091821Oryza sativaPutative protein 98 38 with region similar to cyclin-dependent kinase like proteins 1535 gi7020214Homo SapienscDNA FLJ20248 fis, 97 63 clone COLF6543.

1536 AAG02639Homo SapiensHuman secreted protein,160 71 SEQ ID

NO: 6720.

1536 AAG02753Homo SapiensHuman secreted protein,141 60 SEQ ID

NO: 6834.

1536 gi7959778Homo SapiensPR01546 140 60 1537 gi7022610Homo SapienscDNA FLJ10521 fis, 184 39 clone NT2RP2000841.

1537 AAB92909Homo SapiensHuman protein sequence184 39 SEQ ID

N0:11539.

1537 gi11527193Drosophila Sunday driver 112 41 melanogaster 1538 gi12654055Homo Sapiensclone IMAGE:3455871,849 85 mRNA, partial cds.

1538 gi3133291Homo Sapiensmitogen activated 844 85 protein kinase activated protein kinase gene, complete cds.

1538 gi2911813Mus musculusmitogen-activated 841 84 protein kinase-activated protein kinase Table 2A

SEQ Hit ID S ecies Description S score% Identi ID

1539 gi11761810Arabidopsisglutathione dependent60 32 thaliana dehydroascorbate reductase precursor 1540 gi13162677Homo SapiensGLUT4 enhancer factor1399 99 rnRNA, complete cds.

1540 gi12655101Homo Sapiensclone IMAGE:3140406,1399 99 mItNA, partial cds.

1540 AAB58934 Homo SapiensBreast and ovarian 1395 99 cancer associated antigen protein sequence SEQ ID 642.

1541 gi30058 Homo SapiensHuman mRNA for pro-alpha-11606 98 type 3 collagen.

1541 gi16197601Homo Sapienstype III preprocollagen1606 98 alpha 1 chain (COL3A1) gene, exon 1 and complete cds.

1541 AAW12842 Homo sapiensTruncated pro-alphal(III)1606 98 chain.

1542 AAE01436 Homo SapiensHuman gene 1 encoded1622 99 secreted protein HWLFJ10, SEQ ID

N0:91.

1542 AAE01464 Homo SapiensHuman gene 1 encoded1618 98 secreted protein HWLFJ10, SEQ ID

N0:119.

1542 AAE01515 Homo SapiensHuman gene 1 encoded1618 98 secreted protein fragment, SEQ ID N0:172.

1543 gi186043 Homo Sapiensimmunoglobulin light547 86 chain variable region (IGL@) mRNA, partial cds.

1543 gi219886 Homo SapiensHuman Ig kappa light543 89 chain gene, V- and J-region.

1543 gi33248 Homo SapiensH.sapiens gene for 540 89 Ig kappa light chain variable region'012'.

1544 gi7673618Mus musculusubiquitin specific 1972 73 protease 1544 gi7328168Homo SapiensmRNA; cDNA DKFZp434K18221004 74 (from clone DKFZp434K1822);

partial cds.

1544 gi5823525Drosophilaubiquitin-specific 957 41 protease nonstop melanogaster 1545 gi6693836Rattus SNIP-b 3975 85 norvegicus 1545 gi6693834Rattus SNIP-a 3975 85 norvegicus 1545 gi3098418Mus musculusP140 3699 75 1546 gi179433 Homo SapiensHuman biglycan (BGN)2032 95 gene, exon 8.

1546 gi12803217Homo Sapiensbiglycan, clone MGC:22981512 96 IMAGE:3162633, mRNA, complete cds.

1546 gi13279002Homo Sapiensbiglycan, clone MGC:104611512 96 IMAGE:3503374, mRNA, complete cds.

1547 gi14718648Homo Sapiensallantoicase mRNA, 777 95 partial cds.

1547 gi9255889Mus musculusallantoicase 1039 58 1547 gi4929823Xenopus allantoicase 681 41 laevis 1548 gi12653161Homo Sapiensribosomal protein 203 78 L35, clone MGC:8582 IMAGE:2960987, mRNA, complete cds.

Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

1548 gi15012043Homo SapiensSimilar to ribosomal203 78 protein L35, clone MGC:13488 IMAGE:4251487, mRNA, complete cds.

1548 gi562074 Homo SapiensHuman ribosomal protein203 78 mRNA, complete cds.

1549 gi1903236Mus musculuscappin protein beta 156 100 3 subunit 1549 gi595257 Homo sapiensHuman F-actin capping156 100 protein beta subunit mRNA, complete cds.

1549 gi500749 Mus musculuscapping protein beta156 100 subunit, isoform 2 1550 gi15278186Homo SapiensMAGI-lA mRNA, complete526 91 cds, alternatively spliced.

1550 gi3370998Homo SapiensmRNA for BAI1-associated526 91 protein 1, complete cds.

1550 gi15278182Homo SapiensMAGI-1B alpha beta 526 91 mRNA, complete cds, alternatively spliced.

1551 gi12654299Homo Sapiensclone IMAGE:3447394,1945 99 mRNA, artial cds.

1551 gi11095188Homo Sapiensdipeptidyl peptidase1357 67 8 (DPP8) mRNA, com lete cds.

1551 AAB47187 Homo SapiensHuman DPP8. 1357 67 1552 gi191012 Cricetus ornithine decarboxylase153 38 cricetus 1552 gi49440 Cricetus ornithine decarboxylase153 38 cricetus (AA 1-455) 1552 gi9858179Danio rerioornithine decarboxylase149 44 1553 gi12053087Homo SapiensmRNA; cDNA DI~FZp434B0819168 100 (from clone DKFZp434B0819);

complete cds.

1553 gi16118555Homo SapiensELMOl mRNA, complete168 100 cds.

1553 gi16118551Mus musculusELMOl 168 100 1554 AAY91640 Homo SapiensHuman secreted protein238 81 sequence encoded by gene 34 SEQ ID

NO:313.

1554 AAB93352 Homo sapiensHuman protein sequence238 81 SEQ ID

N0:12476.

1554 AAY91484 Homo SapiensHuman secreted protein233 100 sequence encoded by gene 34 SEQ ID

N0:157.

1555 AAB38012 Homo SapiensHuman secreted protein726 87 encoded by gene 3 clone HNHCT15.

1555 AAB64943 Homo SapiensHuman secreted protein726 87 sequence encoded by gene 7 SEQ ID

N0:121.

1555 gi1196433Homo SapiensHuman factor VIII 727 87 gene Ll element insertion DNA.

1556 gi4530437Homo Sapiensthyroid hormone receptor-1125 90 associated protein complex component TRAP240 mRNA, complete cds.

1556 gi7109237DrosophilaTRAP240 213 44 melanogaster 1556 gi7230590DrosophilaPapIDTRAP240 213 44 melanogaster 1557 AAB64943 Homo SapiensHuman secreted protein2330 89 sequence encoded by gene 7 SEQ ID

Table 2A

SEQ Hit ID S ~ecl ies Descri tion S score % Identi ID

N0:121.

1557 AAB38012Homo SapiensHuman secreted protein2325 89 encoded by gene 3 clone HNHCT15.

1557 gi5052951Homo SapiensLINE1 element inserted2309 88 in B-globin gene intron 2.

1558 gi11066463Rattus RhoGEF glutamate 3450 72 transport norvegicus modulator GTRAP48 1558 gi7110160Homo Sapiensguanine nucleotide 1063 50 exchange factor (LARG) mRNA, complete cds.

1558 AAW64468Homo SapiensHuman secreted protein1063 50 from clone CW420_2.

1559 gi10440888Morone saxatilismyosin heavy chain 456 51 1559 gi15982970Danio reriomyosin IIIA 476 55 1559 gi7958618Homo sapiensclass III myosin 456 51 (MY03A) mRNA, complete cds, alternatively spliced.

1560 AAB93846Homo SapiensHuman protein sequence1112 66 SEQ ID

N0:13688.

1560 gi3834629Mus musculusdiaphanous-related 565 28 formin; p134 mDia2 1560 gi3171906Homo SapiensmRNA for dia-156 559 30 protein.

1561 AAB59019Homo SapiensBreast and ovarian 162 47 cancer associated antigen protein sequence SEQ ID
727.

1561 AAG74843Homo SapiensHuman colon cancer 88 52 antigen protein SEQ ID NO:5607.

1561 AAB95751Homo SapiensHuman protein sequence85 30 SEQ ID

N0:18660.

1562 gi13195147Mus musculusHCH 1228 87 1562 AAW03515Homo SapiensHuman DOCK180 protein.1308 56 1562 gi1339910Homo SapiensHuman DOCK180 protein1304 56 mRNA, complete cds.

1563 AAB52017Homo SapiensHuman secreted protein266 100 sequence encoded by ene 6 SEQ ID NO:66.

1563 gi6449393Callinectescopper-specific 57 37 metallothionein sapidus CuMT-II

1563 gi6010621Human RNA-dependent RNA 51 36 polymerise calicivirus strain BAVl2.1/98/DE

U

1564 gi540073Homo SapiensHuman agouti gene, 362 97 exon 3 and complete cds.

1564 gi608648Homo Sapiensagouti signalling 356 96 protein (ASP) gene, complete cds.

1564 AAW10102Homo SapiensHuman agouti signalling352 84 protein.

1565 gi2463646Homo SapiensHuman 3-hydroxy-3- 1277 100 methylglutaryl CoA
synthase gene, exon 9 and complete cds.

1565 gi619877Homo SapiensH.sapiens mRNA for 1277 100 3-hydroxy-3-methylglutaryl coenzyme A

synthase.

1565 gi15928472Mus musculus3-hydroxy-3-methylglutaryl-1155 88 Coenzyme A synthase 1566 gi5912057Homo SapiensmRNA; cDNA DKFZp434B172350 98 (from clone DKFZp434B
172);

partial cds.

Table 2A

SEQ Hit ID S ecies D_escri tion S score% Identi ID

1566 gi7578787Homo SapiensAD021 protein (AD021)157 41 mRNA, complete cds.

1566 AAB57036 Homo SapiensHuman prostate cancer69 33 antigen protein sequence SEQ ID

N0:1614.

1567 gi2226005Homo SapiensHuman Tiggerl transposable269 53 element, complete consensus sequence.

1567 gi7634783Homo SapiensHDCMB45P mRNA, partial210 43 cds.

1567 AAB39252 Homo SapiensHuman secreted protein126 61 sequence encoded by gene 12 SEQ ID

NO:132.

1568 gi12653985Homo Sapiensglycine cleavage 846 91 system protein H

(aminomethyl carrier), clone MGC:5190 IMAGE:3451361, mRNA, complete cds.

1568 gi184348 Homo SapiensHuman H-protein mRNA,846 91 complete cds.

1568 gi219671 Homo SapiensmRNA for hydrogen 846 91 carrier protein, a component of an enzyme complex, glycine synthase (EC

2.1.2.10).

1569 gi388109 Enterococcusregulatory protein 64 47 faecalis 1569 AAY25744 Homo SapiensHuman secreted protein56 50 encoded from gene 34.

1570 gi532505 Homo sapiensHuman bile acid CoA:2049 99 Amino acid N-acyltransferase mRNA, complete cds.

1570 gi15215152Mus musculusSimilar to bile acid-Coenzyme1412 68 A

dehydrogenase: amino acid n-acyltransferase 1570 gi604902 Rattus Iran-1 1394 68 norvegicus 1571 AAG89290 Homo SapiensHuman secreted protein,198 97 SEQ ID

NO: 410.

1571 gi15487674Homo SapiensOSBP-related protein204 100 1 mRNA, complete cds.

1571 AAB38248 Homo SapiensHuman secreted protein62 51 sequence encoded by gene 46 SEQ ID

NO:104.

1572 gi4263739Homo SapiensBAC clone GS1-489L14594 68 from 7p14-p12, complete sequence.

1572 gi6102812Homo SapiensGLI3 gene for GLI3 594 68 protein.

1572 gi183248 Homo SapiensHuman DNA-binding 594 68 protein (GLI3) mRNA, complete cds.

1573 gi1019435Trypanosomamucin-like protein 133 37 cruzi 1573 gi1019433Trypanosomamucin-lilee protein;114 38 Method:

cruzi conceptual translation supplied by author 1573 gi1280434Drosophilahemomucin 127 33 melanogaster 1574 AAB76873 Homo SapiensHuman lung tumour 141 37 protein related protein sequence SEQ ID N0:798.

1574 gi6015472Hylobates dopamine receptor 133 34 muelleri Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID ~

1574 gi13421134Caulobactertranslation initiation155 34 factor IF-2 crescentus 1575 AAB74709 Homo SapiensHuman membrane associated1294 100 protein MEMAP-15.

1575 gi14495648Homo Sapiensclone MGC:15606 334 36 IMAGE:3163718, mRNA, complete cds.

1575 gi15721997Homo sapienszonadhesin (ZAN) 173 20 gene, complete cds, alternatively spliced.

1576 gil 181628Homo SapiensH.sapiens APXL mRNA.1624 78 1576 gi1773381Homo Sapienschromosome X clone 1624 78 U177G4, U152H5, U168D5, 174A6, U172D6, and U186B3 from Xp22, complete sequence.

1576 AAW58988 Homo SapiensHomo Sapiens fetal 317 71 kidney clone BD335 14 encoded protein.

1577 gi6979943Homo Sapienstype 1 tumor necrosis1499 86 factor receptor shedding aminopeptidase regulator mRNA, complete cds.

1577 gi6381989Homo Sapiensadipocyte-derived 1492 86 leucine aminopeptidase mRNA, complete cds.

1577 gi6642987Homo Sapiensaminopeptidase PILS 1492 86 (APPILS) mRNA, complete cds.

1578 gi14626461Rhizobium HupE 82 28 leguminosarum 1578 i897 Canis familiarisendothelin-2 64 36 1579 gi7657864Homo SapiensBAC clone RP11-236P24025 98 from 2, complete sequence.

1579 gi1374698Homo sapiensmRNA for nuclear 4014 98 protein, NP220, complete cds.

1579 AAY07032 Homo SapiensBreast cancer associated4014 98 antigen precursorsequence.

1580 gi551065 Mus musculusprotease-nexin 1 995 83 1580 gi14715029Mus musculusserine (or cysteine)995 83 proteinase inhibitor, Glade E (nexin, plasminogen activator inhibitor type 1), member 2 1580 gi412265 Rattus glia-derived neurite-promoting994 82 norve icusfactor (GdNPF) 1581 1499184 Felis catusneuronal protein 305 93 1581 gi10433455Homo SapienscDNA FLJ12066 fis, 286 65 clone HEMBB1002266, moderately similar to NEURONAL

PROTEIN.

1581 AAB95041 Homo SapiensHuman protein sequence286 65 SEQ ID

N0:16804.

1582 AAY13385 Homo SapiensAmino acid sequence 3183 99 of protein PR0293.

1582 AAB80253 Homo SapiensHuman PR0293 protein.3183 99 1582 AAB33472 Homo SapiensHuman PR01338 protein1676 55 SEQ ID N0:279.

1583 gi12803185Homo Sapiensnucleophosmin (nucleolar268 75 phosphoprotein B23, numatrin), clone MGC:8463 IMAGE:2821577, mRNA, complete Gds.

Table 2A

SE ID Hit ID S ecies Descri ~tion S score% Identi 1583 gi14250152Homo Sapiensnucleophosmin (nucleolar268 75 phosphoprotein B23, numatrin), clone MGC:14826 IMAGE:4276604, mRNA, complete cds.

1583 gi15214852Homo Sapiensnucleophosmin (nucleolar268 75 phosphoprotein B23, numatrin), clone MGC:13433 IMAGE:4097025, mRNA, complete cds.

1584 gi4406691Homo Sapiensclone 24922 mRNA 697 100 sequence, complete cds.

1584 gi7023544Homo SapienscDNA FLJ11094 fis, 697 100 clone PLACE 1005373, weakly similar to TRNA PSEUDOURIDINE

SYNTHASE B (EC 4.2.1.70).

1584 AAB93492Homo SapiensHuman protein sequence697 100 SEQ ID

N0:12796.

1585 gi155999Bombyx morisilk fibroin 147 39 1585 gi930003Bombyx morisilk fibroin (AA 147 39 37 - 252) 158 gi765323Bombyx morisilk fibroin heavy 158 39 chain _ gi12002682Homo SapiensPERM-containing protein1282 89 1586 (CGl) mRNA, alternative splice product, complete cds.

1586 gi7669988Homo SapiensmRNA; cDNA DKFZp761N18141090 86 (from clone DKFZp761N1814).

1586 AAB 12318Homo SapiensHuman secreted protein189 100 encoded by gene 18 clone HE2FL70.

1587 gi5019618Homo SapiensHFB30 mRNA, com fete1005 90 cds.

_ gi4530066Homo sapiensandrogen receptor 1005 90 1587 associated protein 54 (A1tA54) mRNA, complete cds.

1587 AAY78418Homo sapiensHuman androgen receptor1005 90 coactivator ARA54 SEQ ID N0:2.

1588 AAG73501Homo sapiensHuman secreted protein285 94 fragment, SEQ ID N0:277.

1588 gi1196432Homo SapiensHuman factor VIII 285 94 gene Ll element insertion DNA.

1588 gi339771Homo sapiensHuman transposon 285 94 Ll.l with a base deletion relative to L1.2B

resulting in a premature stop codon in the coding region, 1589 AAB94900Homo SapiensHuman protein sequence287 67 SEQ ID

N0:16288.

1589 gi1196433Homo SapiensHuman factor VIII 289 70 gene Ll element insertion DNA.

1589 gi1916229Homo SapiensHuman line-1 reverse278 70 transcriptase gene, partial cds, and granulocyte chemotactic protein-2 (GCP-2) gene, complete cds.

1590 gi6562173Homo SapiensmRNA; cDNA DKFZp566H033227 88 (from clone DKFZp566H033);

partial cds.

1590 gi1335199Homo SapiensHuman I~pnI repetitive227 86 sequence .

(T-betaG41) 3kb downstream of beta- lobin gene.

1590 AAB38280Homo SapiensHuman secreted protein226 88 sequence Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

encoded by gene 20 SEQ ID

N0:136.

1591 gi10436007Homo SapienscDNA FLJ13859 fis, 1794 80 clone THYR01001033, weakly similar to TRANSFORMATION-SENSITIVE PROTEIN
IEF SSP

3521.

1591 AAB95593 Homo SapiensHuman protein sequence1794 80 SEQ ID

N0:18273.

1591 gi7020708Homo SapienscDNA FLJ20535 fis, 1789 79 clone KAT11013.

1592 gi6599260Homo SapiensmRNA; cDNA DI~FZp434P17211184 76 (from clone DKFZp434P1721);

partial cds.

1592 gi10567164Homo SapiensGASC-1 mRNA, complete561 59 cds.

1592 AAR66461 Homo SapiensAF-17 protein, N-terminal181 34 region with similarity to peregrin.

1593 gi182020 Homo SapiensHuman elastin gene, 2405 89 exon 1.

1593 AAB08630 Homo SapiensAmino acid sequence 2392 88 of a human elastin polypeptide.

1593 gi182062 Homo SapiensHuman elastin mRNA, 2386 88 complete cds.

1594 gi14424570Homo Sapiensclone MGC:16614 349 88 IMAGE:4111344, mRNA, complete cds.

1594 gi1196433Homo SapiensHuman factor VIII 349 89 gene Ll element insertion DNA.

1594 AAB38012 Homo SapiensHuman secreted protein349 89 encoded by gene 3 clone HNHCT15.

1595 gi291854 Homo Sapiensaminopeptidase A 934 100 mRNA, complete cds.

1595 gi1518865Susscrofa aminopeptidase A 876 89 1595 gi7673021Rattus aminopeptidase A 847 85 norvegicus 1598 gi7288173Homo Sapiensgene for alphal,6 367 100 fucosyltransferase, exon 5.

1598 gi2055307Homo SapiensmRNA for N-Acetyl-beta-D-367 100 glucosaminide, complete cds.

1598 gi3451263Homo SapiensmRNA for glycoprotein367 100 6-alpha-L-fucosyltransferase, transcript B1.

1599 AAB93267 Homo SapiensHuman protein sequence149 46 SEQ ID

N0:12300.

1599 gi295671 Saccharomycesselected as a weak 123 25 suppressor of a cerevisiaemutant of the subunit AC40 of DNA dependant RNA
polymerise I and III

1599 gi11559313Halocynthiasynaptotagmin 121 24 roretzi 1600 AAB48139 Homo SapiensHuman TANGO 209 variant219 79 polypeptide.

1600 AAB48140 Homo SapiensHuman TANGO 209 variant219 79 polypeptide.

1600 AAB48141 Homo SapiensHuman TANGO 209 variant224 51 polypeptide.

1602 gi12053353Homo SapiensmRNA; cDNA DKFZp586D0222548 82 (from clone DI~FZp586D0222);

complete cds.

Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

1602 gi7023456Homo SapienscDNA FLJ11040 fis, 548 82 clone PLACE1004388.

1602 gi10434241Homo SapienscDNA FLJ12633 fis, 548 82 clone NT2RM4001856.

1603 gi15082532Homo Sapiensclone MGC:20434 212 85 IMAGE:4650497, mRNA, complete cds.

1603 gi13096814Mus musculusRIKEN cDNA 4932442K08165 72 ene 1603 gi9622395Plasmodiumvariant surface protein66 44 falciparum 1604 gi1321596Homo SapiensHuman (clone HSLV2132)374 100 Ig lambda light chain V region, subgroup II, partial sequence.

1604 AAG76014 Homo SapiensHuman colon cancer 362 97 antigen protein SEQ ID N0:6778.

1604 AAB36212 Homo SapiensHuman immune system 342 91 associated protein HISAP-10.

1605 gi10434674Homo SapienscDNA FLJ12911 fis, 2340 94 clone NT2RP2004425, highly similar to ' Mus musculus axotrophin mRNA.

1605 AAB95234 Homo SapiensHuman protein sequence2340 94 SEQ ID

NO:17375.

1605 AAB27239 Homo SapiensHuman EXMAD-17 SEQ 2340 94 ID NO:

17.

1606 gi8918522Homo SapiensPCCX2 mRNA for protein2200 84 containing CXXC domain 2, partial cds.

1606 gi14042116Homo sapienscDNA FLJ14534 fis, 2446 78 clone NT2RM2000599, weakly similar to Homo Sapiens F-box protein Lilina (LILINA) mRNA.

1606 AAB92702 Homo SapiensHuman protein sequence2446 78 SEQ ID

N0:11102.

1607 gi3176762Homo Sapiensreceptor for viral 807 100 semaphorin protein (VESPR) mRNA, complete cds.

1607 AAY13462 Homo SapiensViral-encoded semaphorin807 100 protein receptor (VESPR) polypeptide.

1607 AAB28522 Homo SapiensHuman VESPR. 807 100 ' 1608 gi1373425Homo SapiensHuman bumetanide-sensitive1295 99 Na-K-2Cl cotransporter (NKCC2) mRNA, complete cds.

1608 AAW29683 Homo SapiensHuman Na-K-2CI cotransporter1295 99 NKCC2.

1608 gi516000 Oryctolagusbumetanide-sensitive1244 95 Na-K-Cl cuniculus cotransport protein splice isoform B

1609 AAB95655 Homo SapiensHuman protein sequence229 61 SEQ ID

N0:18417.

1609 AAB64943 Homo SapiensHuman secreted protein221 58 sequence encoded by gene 7 SEQ ID

N0:121.

1609 gi1196433Homo SapiensHuman factor VIII 226 60 gene Ll element insertion DNA.

1610 AAB88388 Homo SapiensHuman membrane or 923 100 secretory protein clone PSEC0131.

1610 AAB25719 Homo SapiensHuman secreted protein114 100 sequence Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

encoded by gene 6 SEQ ID

N0:108.

1610 AAB25718Homo SapiensHuman secreted protein73 100 sequence encoded by gene 6 ' SEQ ID

N0:107.

1611 AAY04734Homo SapiensProtein containing 269 98 , PDZ domain from clone 38-2-lc.

1611 AAY04732Homo SapiensProtein containing 269 98 PDZ domain from clone 38-2-la.

1611 AAY53753Homo SapiensAmino acid sequence 269 98 of the MMSC2 protein.

1612 gi1794211Homo SapiensHuman oncostatin-M 1127 92 specific receptor beta subunit (OSMRB) mRNA, complete cds.

1612 AAR85912Homo SapiensOncostatin M receptor-beta1127 92 subunit.

1612 gi15012082Homo SapiensSimilar to oncostatin1127 92 M receptor, clone MGC:13583 IMAGE:4043935, mRNA, com lete cds.

1613 gi12803103Homo Sapiensheterogeneous nuclear406 82 ribonucleoprotein A1, clone MGC:8473 IMAGE:2821751, mRNA, complete cds.

1613 gi15082486Homo SapiensSimilar to heterogeneous406 82 nuclear ribonucleoprotein A1, clone MGC:20389 IMAGE:4564655, mRNA, complete cds.

1613 gi496898Homo SapiensH.sapiens mRNA for 406 82 hnRNPcore protein Al.

1614 gi12653633Homo sapienslysyl oxidase-like 898 99 2, clone MGC:1709 IMAGE:3347512, mRNA, complete cds.

1614 gi1890108Homo SapiensHuman lysyl oxidase-related898 99 protein (WS9-14) mRNA, complete cds.

1614 AAB00077Homo SapiensHuman lysyl oxidase 898 99 related protein (Lor).

1615 gi12803157Homo SapiensCOX15 (yeast) homolog,159 52 cytochrome c oxidase assembly protein, clone MGC:8634 IMAGE:2961532, mRNA, complete cds.

1615 gi15426569Homo Sapiensclone MGC:4234 159 52 IMAGE:2961532, mItNA, complete cds.

1615 gi3603230Homo Sapienscytochrome oxidase 159 52 assembly factor (COX15) mRNA, nuclear gene encoding mitochondria) protein, complete cds.

1616 gi1215746Bos taurus vacuolar system associated1309 67 protein-60 1616 gi7672979Homo Sapiensglucosidase II beta 1656 71 subunit mRNA, complete cds.

1616 gi1293640Homo SapiensHuman protein kinase1652 70 C substrate 80K-H (PRI~CSH) gene, exon 15-17.

Table 2A

SE Hit ID S oecies Descri tion ~ S score% Identi ID

1617 gi1418820Homo SapiensH.sapiens mRNA for 355 100 gamma 1 isoform of 6lkDa regulatory subunit of PP2A.

1617 gi1203812Homo SapiensHuman protein phosphatase355 100 B'alphal regulatory subunit mRNA, complete cds.

1617 gi1000892Homo Sapiensprotein phosphatase 355 100 gammal (PP2A) mRNA, 3' end of cds.

1618 gi14010930Homo SapiensBAC clone RP11-576F11868 100 from 2, complete sequence.

1618 gi7022375Homo SapienscDNA FLJ10379 fis, 1863 99 clone NT2RM2002014.

1618 AAB92758 Homo SapiensHuman protein sequence1863 99 SEQ ID

N0:11220.

1619 gi296665 Homo sapiensHuman bone marrow 629 93 serine protease gene (medullasin) (leukocyte neutrophil elastase ene).

1619 gi34533 Homo SapiensHuman mRNA for medullasin629 93 (leukocyte (neutrophil) elastase.

1619 gi307123 Homo SapiensHuman elastase/medullasin629 93 mRNA, complete cds.

1620 gi9965989Homo Sapienscalcineurin A catalytic1650 97 subunit gamma isoform mRNA, complete cds.

1620 gi258001 human, calcineurin A catalytic1639 96 testis, subunit mRNA, 2134 nt].

[Homo Sapiens 1620 gi13436077Homo Sapiensclone MGC:10576 1623 94 IMAGE:3677098, mRNA, complete cds.

1621 gi1429374EscherichiaDcuC protein 739 100 coli 1621 gi13360118Escherichiac4-dicarboxylate 739 100 coli anaerobic carrier 0157:H7 DcuC

1621 gi1786839Escherichiatransport of dicarboxylates739 100 coli 1622 AAB82485 Homo SapiensHuman secretin-like 271 94 receptor Zgpr 1.

1622 AAB66272 Homo SapiensHuman TANGO 378 SEQ 271 94 ID NO:

29.

1622 AAB82487 Homo SapiensHuman secretin-like 271 94 receptor Zgprl splice variant.

1623 gi4062658EscherichiaFlagellar basal body752 87 coli P-ring protein precursor 1623 gi1787320Escherichiahomolog of Salmonella752 87 coli P-ring of K12 flagella basal body 1623 gi13360922Escherichiaflagellar basal body751 86 coli P-ring protein 0157:H7 FIgI

1624 11773192 Escherichiasimilar to S. cerevisiae334 98 coli dal l 1624 12735238 EscherichiaGlxB3 334 98 coli 1624 gi13360031Escherichiaallantoinase 333 96 coli 0157:H7 1625 gi40992 Escherichiadehydrogenase 1481 93 coli 1625 gi13363752Escherichiaaspartate-semialdehyde1481 93 coli 0157: H7 dehydrogenase Table 2A

SE(~ Hit ID S ecies Descri tion S score% Identi ID

1625 gi3859587Shigella aspartate semialdehyde1481 93 sonnei dehydrogenase 1626 gi146346 Escherichiaphenylalanyl-tRNA 735 94 coli synthetase beta-subunit 1626 gi1742793EscherichiaPhenylalanine--tRNA 735 94 coli ligase (EC

6.1.1.20) b chain 1626 gi13361887Escherichiaphenylalanine tRNA 735 94 coli synthetase 0157:H7 beta-subunit 1627 AAB49502 Homo SapiensClone HYASC03. 310 98 1627 gi7020468Homo SapienscDNA FLJ20396 ~s, 144 48 clone KAT00561.

1627 AAB18980 Homo SapiensAmino acid sequence 144 48 of a human transmembrane protein.

1628 gi14021587Mesorhizobiumtranscriptional regulator333 38 loti 1628 gi14523075Sinorhizobiumprobable LysR-family329 39 protein meliloti 1628 gi9949248Pseudomonasprobable transcriptional327 37 regulator aeru 'nosa 1629 gi311422 EscherichiaORF-2 282 100 coli 1629 gi15081358unculturedPufM 53 41 bacterium 1629 gi13362968Escherichiaholin protein 52 33 coli 0157:H7 1630 gi159333 Leishmaniaglycoprotein 96-92 101 28 ma'or 1630 AAY91958 Homo SapiensHuman cytoskeleton 100 28 associated protein 13 (CYSKP-13).

1630 gi8163686Streptococcussurface protein PspC105 29 pneumoniae 1632 gi887820 EscherichiaIJiJG start; possible820 71 coli frameshift at end?

1632 gi466651 EscherichiaNo definition line 343 82 coli found 1632 gi1742360EscherichiaPhosphinothricin 248 83 coli acetyltransferase (EC 2.3.1.-).

1633 gi7022678Homo SapienscDNA FLJ10565 fis, 290 100 clone NT2RP2002954.

1633 AAB92950 Homo SapiensHuman protein sequence290 100 SEQ ID

N0:11629.

1633 gi1755198Cavia porcellusnitric oxide synthase71 33 1634 AAY48563 Homo SapiensHuman breast tumour-associated342 100 protein 24.

1634 gi12804499Homo Sapiensribonuclease 6 precursor,440 66 clone MGC:1360 IMAGE:2959583, mRNA, complete cds.

1634 gi12804759Homo Sapiensribonuclease 6 precursor,440 66 clone MGC:3554 IMAGE:2959583, mRNA, complete cds.

1635 gi10438872Homo SapienscDNA: FLJ22471 fis, 1620 100 clone HRC 10529.

1635 AAY86509 Homo SapiensHuman gene 70-encoded696 100 protein fragment, SEQ ID
NO:424.

1635 AAY86510 Homo SapiensHuman gene 70-encoded436 100 protein fra ent, SEQ ID NO:425.

1636 gi8096340Homo SapiensmRNA for RERE, complete365 97 cds.

1636 gi7413896group A NSP3 protein 71 29 Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

rotavirus 1636 gi9368393Human rotavirusNSP3 protein 65 27 1637 AAB58426 Homo SapiensLung cancer associated514 94 polypeptide sequence SEQ ID 764.

1637 AAB00191 Homo sapiensBreast cancer protein514 94 BCNS.

1637 AAB85481 Homo SapiensHuman 23553 sulfatase514 94 polypeptide.

1638 AAY42750 Homo SapiensHuman calcium binding741 100 protein 1 (CaBP-1).

1638 gi12060826Homo Sapiensserologically defined673 89 breast cancer antigen NY-BR-20 mRNA, partial cds.

1638 AAY07006 Homo SapiensBreast cancer associated637 88 antigen precursorsequence.

1639 gi10434205Homo sapienscDNA FLJ12612 fis, 908 86 clone NT2RM4001582, highly similar to Mus musculus COP9 complex subunit 7b (COPS7b) mRNA.

1639 AAB94175 Homo SapiensHuman protein sequence908 86 SEQ ID

N0:14484.

1639 gi15215085Mus musculusSimilar to COP9 (constitutive900 85 photomorphogenic), subunit 7b (Arabidopsis) 1640 gi1334836Human BCRF2 3072 repeat, 98 29 reading frame herpesvirus1 1640 gi1334837Human BWRFl reading frame 98 29 herpesvirus 1640 gi1334838Human BWRF1 reading frame 98 29 herpesvirus 1641 gi13161011Homo Sapienssclerostin gene, 758 100 complete cds.

1641 gi13161020Homo Sapienssclerostin mRNA, 758 100 complete cds.

1641 gi13236418Homo SapiensSOST (SOST) mRNA, 758 100 complete cds.

1642 '13436023Mus musculusRIKEN cDNA B230114J08279 94 gene 1642 AAY36125 Homo SapiensExtended human secreted279 94 protein se uence, SEQ ID
NO. 510.

1642 AAY99458 Homo SapiensHuman PRO193 amino 279 94 acid sequence SEQ ID N0:410.

1643 gi15680215Homo SapiensSimilar to ribosomal428 76 protein L23a, clone MGC:23063 IMAGE:4872948, mRNA, complete cds.

1643 gi15990426Homo SapiensSimilar to cadherin 428 76 1, type 1, E-cadherin (epithelial), clone MGC:23017 IMAGE:3959042, mRNA, complete cds.

1643 gi404015 Homo sapiensHuman ribosomal protein428 76 L23a mRNA, partial cds.

1644 gi12653271Homo Sapiensthyroid hormone receptor514 82 interactor 13, clone MGC:8565 IMAGE:2822981, mRNA, complete cds.

1644 gi2232019Homo SapiensHPV16 E1 protein 514 82 binding protein mRNA, complete cds.

1644 gi703102 Homo Sapiensthyroid receptor 513 82 interactor (TRIP 13) mRNA, partial cds.

Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

1646 gi13544066Homo SapiensSimilar to mini chromosome273 98 maintenance deficient 2 (S.

cerevisiae), clone MGC:13220 IMAGE:3959276, mRNA, complete cds.

1646 gi14043350Homo sapiensclone MGC:2123 273 98 IMAGE:3143264, mRNA, complete cds.

1646 gi14044016Homo Sapiensclone MGC:14281 273 98 IMAGE:4131943, mRNA, complete cds.

1648 gi7960207Oncorhynchusvitelline envelope 252 43 protein alpha mykiss 1648 gi160198Plasmodium circumsporozoite 191 43 protein knowlesi 1648 gi15384295Mycoplasma variable surface 177 34 lipoprotein bovis Vsp422-8 1650 gi474280Mus musculusmannosyl-oligosaccharide911 88 alpha-1,2-mannosidase 1650 gi15929672Mus musculusSimilar to mannosidase911 88 1, al ha 1650 gi2154997Sus scrofa Man9-mannosidase 869 83 _ gi5915662Homo Sapiensintegrin alpha 11 542 84 1651 subunit precursor (ITGA11) mRNA, complete cds.

1651 AAB30929Homo sapiensAmino acid sequence 542 84 ~ of a human alphal l integrin chain.

1651 AAB50085Homo SapiensHuman A259. 542 84 1652 gi4512295Homo SapiensDNA for immunoglobulin619 100 heavy-chain variable region, complete sequence, 3 of 5.

1652 gi296657Homo SapiensHuman Ig heavy chain613 99 gene variable region V(12G-1) (v(h)-iv family).

1652 gi185579Homo SapiensH.sapiens immunoglobulin601 97 germline heavy chain gene, V

region.

1654 AAE04841Homo SapiensHuman SGP039 phosphatase667 92 polypeptide.

1654 gi2582800Medica o protein hosphatase 107 41 sativa 2C

1654 gi8778653ArabidopsisF9C16.6 107 40 thaliana 1655 gi9928511MycobacteriumSEQ ID NO 18B' 89 27 tuberculosis 1655 gi13897999Galleria silk protease inhibitor50 40 2 precursor mellonella 1655 gi204419Itattus glycam 1 85 24 norvegicus 1656 gi12653509Homo sapiensDKFZP564K1964 protein,227 95 clone MGC:8605 IMAGE:2961267, mRNA, complete cds.

1656 gi5912199Homo SapiensmRNA; cDNA DKFZp564K1964227 95 (from clone DKFZp564K1964);

complete cds.

1656 gi4530587Homo SapiensTADAl protein mRNA, 227 95 complete cds.

1658 gi12654931Homo Sapiensprotein disulfide 2281 100 isomerase-related protein, clone MGC:5517 IMAGE:3454007, mRNA, Table 2A

SEQ Hit ID S ecies Description S score% Identi ID

_ complete cds.

1658 gi1136743Homo SapiensHuman mRNA for protein2281 100 disulfide isomerase-related protein P5, complete cds.

1658 AAW25154Homo SapiensHuman disulphide 2281 100 epimerase like enzyme, EP52.

1659 gi6694278Homo Sapienscell recognition 356 95 molecule Caspr2 (CASPR2) mRNA, complete cds.

1659 gi13624214Homo Sapienscontactin-associated356 95 protein 2 (CNTNAP2) mRNA, complete cds.

1659 gi1857708Homo Sapienscontactin associated140 37 protein (Caspr) mRNA, complete cds.

1660 AAG02922Homo SapiensHuman secreted protein,136 96 SEQ ID

NO: 7003.

1660 gi34373 Homo SapiensHuman DNA for LINE-1135 96 transposable element ORFI and II.

1660 gi7959889Homo SapiensPR02221 127 88 1661 gi4588087Homo SapiensPTH-responsive osteosarcoma569 87 protein (B1) mRNA, complete cds.

1661 AAG74841Homo SapiensHuman colon cancer 569 87 antigen protein SEQ ID N0:5605.

1661 gi4588085Homo SapiensPTH-responsive osteosarcoma312 84 Dl protein (Dl) mRNA, partial cds.

1662 gi4754907Homo Sapienshistone deacetylase 2090 94 4 mRNA, complete cds.

1662 AAB49957Homo SapiensHuman histone deacetylase2090 94 HDAC-4.

1662 114495171Gallus histone deacetylase-41790 78 allus 1663 AAB74704Homo SapiensHuman membrane associated183 100 protein MEMAP-10.

1663 gi2621542Methanothermobconserved protein 83 70 acter thennautotrophic us 1663 gi10440349Homo SapiensmRNA for FLJ00009 82 35 protein, partial cds.

1664 gi15159543AgrobacteriumAGR_L_2143p 99 27 tumefaciens 1664 gi5360174Gallus NOTCH-1 98 31 gallus 1664 gi4960212Bostaurus cone-rod homeobox 85 27 1665 AAB32388Homo SapiensHuman secreted protein359 100 sequence encoded by gene 18 SEQ ID

N0:74.

1665 AAY91419Homo SapiensHuman secreted protein83 36 sequence encoded by gene 6 SEQ ID

N0:140.

1665 gi860970Homo SapiensH.sapiens mRNA for 84 35 HP8 protein.

1666 gi15012095Homo SapiensSimilar to protease 621 100 inhibitor 3, skin-derived (SKALP), clone MGC:13613 IMAGE:4083155, mRNA, com fete cds.

1666 gi28712 Homo sapiensH.sapiens encoding 621 100 skin-derived antileukoproteinase.

1666 gi219615Homo SapiensHuman gene for elafin,621 100 complete cds.

Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

1667 gi6650233Homo Sapienszinc finger protein 259 58 74 (ZNF74) gene, exon 3, alternative splice products and complete cds.

1667 gi15081398Homo Sapienskruppel-like zinc 246 73 finger protein (ZNF300) mRNA, complete cds.

1667 gi1769491Homo SapiensHuman kruppel-related246 64 zinc finger protein (ZNFl84) mRNA, partial cds.

1668 AAB38280Homo SapiensHuman secreted protein142 62 sequence encoded by gene 20 SEQ ID

N0:136.

1668 gi1196431Homo SapiensHuman factor VIII 131 58 gene Ll element insertion DNA.

1668 gi6562173Homo SapiensmRNA; cDNA DI~FZp566H033147 60 (from clone DI~FZp566H033);

partial cds.

1669 AAG03136Homo SapiensHuman secreted protein,179 75 SEQ ID

NO: 7217.

1669 AAG02563Homo SapiensHuman secreted protein,77 60 SEQ ID

NO: 6644.

1669 AAG73365Homo SapiensHuman gene 20-encoded76 63 secreted protein HFCAA91, SEQ ID

N0:136.

1670 gi12804499Homo Sapiensribonuclease 6 precursor,376 83 clone MGC:1360 IMAGE:2959583, mRNA, complete cds.

1670 gi12804759Homo Sapiensribonuclease 6 precursor,376 83 clone MGC:3554 IMAGE:2959583, mRNA, complete cds.

1670 gi5091495Homo Sapiensribonuclease 6 precursor,376 83 mRNA, complete cds.

1672 AAG63163Homo sapiensAmino acid sequence 2187 99 of carcinoembryonic antigen-like polypeptide.

1672 AAR54714Homo SapiensCarcinoembryonic 463 34 antigen CEA-(c).

1672 AAB43688Homo SapiensHuman cancer associated466 31 protein sequence SEQ ID NO:1133.

1673 gi13097624Homo Sapiensclone IMAGE:3608084,760 89 mRNA, partial cds.

1673 gi10438279Homo SapienscDNA: FLJ22029 fis, 411 51 clone HEP08661.

1673 AAB93267Homo SapiensHuman protein sequence379 47 SEQ ID

NO:12300.

1674 gi339776Homo SapiensHuman transposon 686 85 L1.2.

1674 gi5070621Homo Sapiensretrotransposon Ll 686 85 insertion in X-linked retinitis pigmentosa locus, complete sequence.

1674 gi5052950Homo SapiensLINE1 element inserted684 85 in B-lobin gene intron 2.

1675 AAB56206Homo SapiensHuman secreted protein44 43 sequence encoded by gene 130 SEQ ID

N0:300.

1675 AAB56350Homo SapiensHuman secreted protein52 39 sequence encoded by gene 130 SEQ ID

N0:444.

1675 AAW33908Homo sapiensPeptide analo a of 57 31 human insulin-Table 2A

SEQ Hit ID S ecies Descri ~tion S score% Identi ID

like owth factor-1 (IGF-1).

1676 gi34234 Homo SapiensH.sapiens mRNA for 290 67 laminin-binding protein.

1676 gi13529269Homo Sapienslaminin receptor 289 67 1 (67kD, ribosomal protein SA), clone MGC:12521 IMAGE:3997019, mRNA, complete cds.

1676 gi14250794Homo Sapienslaminin receptor 289 67 1 (67kD, ribosomal protein SA), clone MGC:16750 IMAGE:4130936, mRNA, complete cds.

1677 gi475782 Homo SapiensHuman GS2 gene, exon1249 97 7 and complete cds.

1677 1458226 Homo sa Human GS2 mRNA, complete1249 97 iens cds.

1677 AAG00737 Homo SapiensHuman secreted protein,531 94 SEQ ID

NO: 4818.

1678 gi3089427Homo SapiensSSC6 rearranged T 444 100 cell receptor beta chain (TCRBV17) gene, complete cds.

1678 gi3089433Homo SapiensSSC9 rearranged T 444 100 cell receptor beta chain (TCRBV17) gene, complete cds.

1678 gi3002927Homo SapiensT cell receptor beta444 100 chain (TCRBV 17S 1-TCRBJl SS) mRNA, complete cds.

1679 gi15929119Homo Sapiensclone MGC:8834 455 100 IMAGE:3920437, mRNA, complete cds.

1679 gi7022159Homo SapienscDNA FLJ10242 iis, 455 100 clone HEMBB 1000630.

1679 AAB92624 Homo SapiensHuman protein sequence455 100 SEQ ID

N0:10919.

1680 gi10186503Homo Sapienssialic acid-specific817 100 acetylesterase II

mRNA, complete cds, alternatively spliced.

1680 gi6808138Homo SapiensmRNA; cDNA DI~FZp761A051817 100 (from clone DKFZp761A051);

partial cds.

1680 gi10242345Homo Sapienssialic acid-specific753 100 acetylesterase I
mRNA, complete cds.

1681 gi4768463Homo Sapiensclone 118 T-cell 76 44 receptor beta chain (TCRBV10S1P) mRNA, partial cds.

1681 gi4768574Homo Sapiensclone 179 T-cell 71 42 receptor beta chain (TCRBV10S1P) mRNA, partial cds.

1681 gi4768459Homo Sapiensclone 115 T-cell 69 44 receptor beta chain (TCRBV10S1P) mRNA, partial cds.

1682 gi4097459Elephantulusreverse transcriptase68 48 edwardii 1683 gi1220315Homo Sapiensearly placenta insulin-like349 100 peptide EPIL (INSL4) mRNA, complete cds.

1683 AAR89134 Homo SapiensHuman early placental349 100 insulin-like protein.

Table 2A

SE ID Hit ID S ecies Descri tion S score% Identi 1683 AAW17676 Homo SapiensHuman relaxin-related349 100 factor-2 (RRF-2).

1684 gi23365 Homo sapiensHuman mRNA for 17-beta-800 83 hydroxysteroid dehydrogenase(17-HSD) (EC 1.1.1.62).

1684 gi975895 Homo SapiensHuman 17-beta-hydroxysteroid800 83 dehydrogenase (EDH17B2) gene, complete cds.

1684 gi177127 Homo SapiensHuman 17-beta-hydroxysteroid800 83 dehydrogenase (EDH17B1 and EDH17B2) genes, complete coding regions and flanks.

1685 AAB18919 Homo SapiensA novel polypeptide 1336 99 designated PR04356.

1685 AAB31206 Homo SapiensAmino acid sequence 1336 99 of human polypeptide PR04356.

1685 gi5834584Homo SapiensmRNA encoding rat 231 31 C4.4-like protein.

1686 gi1655963Homo SapiensHuman transforming 1634 99 growth factor-beta type II receptor gene, exon 7 and complete cds.

1686 gi339570 Homo SapiensHuman TGF-beta type 1634 99 II receptor mRNA, com lete cds.

1686 AAR36601 Homo SapiensTGF-betal receptor 1634 99 type II (clone 3FF).

1687 gi508260 Homo SapiensHuman type 1 vasoactive390 76 intestinal peptide receptor (V1RG) gene, exon 13 and complete cds.

1687 gi407462 Homo SapiensH.sapiens HIVR mRNA 390 76 for vasoactive intestinal peptide (VIP) receptor.

1687 gi292904 Homo SapiensHuman vasoactive 390 76 intestial peptide rece for mRNA, complete cds.

1688 gi181268 Homo SapiensHuman c-yes-1 mRNA. 520 90 1688 AAY24421 Homo SapiensHuman yesl protein. 520 90 1688 AAB84663 Homo sapiensAmino acid sequence 520 90 of human tyrosine kinase protein Yes.

1689 AAG02314 Homo SapiensHuman secreted protein,139 55 SEQ ID

NO: 6395.

1689 gi13325174Homo Sapiensclone MGC:10997 104 70 IMAGE:3638158, mRNA, complete cds.

1689 gi9652123Mus musculusdisrupter of silencing86 40 1690 gi13516467Homo SapiensHDNB1(homzygously 1217 89 deleted in neuroblastoma-1)/UFD2 mRNA, complete cds.

1690 gi4104976Homo Sapiensubiquitin-fusion 1217 89 degradation protein 2 (iJFD2) mRNA, complete cds.

1690 gi14582754Homo Sapiensubiquitin-fusion 1217 89 degradation protein 2 mRNA, complete cds.

1691 gi2463632Homo Sapiensmonocarboxylate transporter326 96 homologue MCT6 mRNA, complete cds.

1691 AAG73420 Homo SapiensHuman gene 21-encoded63 35 secreted protein HBWBR94, SEQ ID

N0:192.

Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

1691 gi9246437StaphylococcusfmtA-like protein 83 26 aureus 1692 AAB58175 Homo SapiensLung cancer associated394 98 polypeptide se uence SEQ ID 513.

1692 gi14211500Homo Sapienssecretory protein 394 98 SEC8 mRNA, complete cds.

1692 gi14042555Homo SapienscDNA FLJ14782 fis, 394 98 clone NT2RP4000524, highly similar to Mus musculus Sec8 mRNA.

1693 gi3786312Homo SapiensmRNA for extracellular498 39 matrix protein, complete cds.

1693 gi13937865Homo Sapienslumican, clone MGC:12410312 29 IMAGE:3950745, mRNA, complete cds.

1693 gi699577 Homo SapiensHuman lumican mRNA, 312 29 complete cds.

1694 gi3002588Mus musculusPlenty of SH3s; POSH219 93 1694 gi7230620Rattus SH3 domain-containing130 34 adapter norvegicusprotein isoform SETA-1x23 1694 AAW34246 Homo SapiensSH3 domain of human 114 50 clone 53 protein.

1695 gi10645308LeishmaniaL8453.1 151 27 major 1695 gi15419013Toxoplasmasubtilisin-like protein147 30 ondii 1695 gi12018147Chlamydomonasvegetative cell wall143 30 protein gpl reinhardtii 1696 AAB43791 Homo SapiensHuman cancer associated353 98 protein sequence SEQ ID N0:1236.

1697 gi156368 Caenorhabditismetallothionein-2 56 39 elegans 1697 gi156381 Caenorhabditismetallothionein-like56 39 protein elegans 1697 gi6782 Caenorhabditismetallothionein-II 56 39 ele ans 1698 gi9858855Homo SapiensHPT protein (HPT) 1318 85 mRNA, complete cds; nuclear gene for mitochondrial product.

1698 AAB29653 Homo SapiensHuman membrane-associated1318 85 protein HUMAP-10.

1698 AAB32389 Homo SapiensHuman secreted protein1318 85 sequence encoded by gene 19 SEQ ID

N0:75.

1699 gi6841138Homo SapiensHSPC099 mRNA, partial275 100 cds.

1699 gi7022824Homo SapienscDNA FLJ10656 fis, 123 23 clone NT2RP2006038.

1699 AAB93037 Homo SapiensHuman protein sequence123 23 SEQ ID

N0:11816.

1700 AAB36587 Homo SapiensHuman FLEXHT-9 protein585 53 sequence SEQ ID N0:9.

1700 gi7023841Homo SapienscDNA FLJ11280 ~s, 581 54 clone PLACE 1009459.

1700 AAB93652 Homo sapiensHuman protein sequence581 54 SEQ ID

N0:13161.

1702 gi12330618Human envelope glycoprotein71 29 immunodeficienc Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID _ . y virus type 1 1703 AAR48975Homo SapiensHuman betal,6-N- 413 100 acetylglucosaminyltransferase protein.

1703 gi870752Homo SapiensHuman mRNA for N- 413 100 acetylglucosaminyltransferase V, complete cds.

1703 gi4545222Homo Sapiensalpha-1,3(6)-mannosylglycoprotein413 100 beta-1,6-N-acetyl-glucosaminyltransferase (MGATS) mRNA, complete cds.

1704 gi12654535Homo SapiensHSPC025, clone MGC:7351251 81 IMAGE:3507964, mRNA, complete cds.

1704 gi13960140Homo SapiensHSPC025, clone MGC:42231251 81 IMAGE:2959747, mRNA, complete cds.

1704 gi4679028Homo SapiensHSPC021 1251 81 1706 gi14250636Homo Sapiensnuclear factor of 2605 86 kappa light polypeptide gene enhancer in B-cells inhibitor-like 2, clone MGC:3398 IMAGE:3628374, mRNA, complete cds.

1706 gi6580428Homo Sapienspartial NFKBIL2 gene2751 95 for IkappaBR, exons 1-13.

1706 gi746415Homo SapiensHuman I kappa BR 1668 72 mRNA, complete cds.

1707 AAB95830Homo sapiensHuman protein sequence219 72 SEQ ID

N0:18850.

1707 gi7959889Homo SapiensPR02221 137 49 1707 gi2072969Homo SapiensHuman Ll element 133 48 L1.24 p40 ene, complete cds.

1708 gi5901529Homo SapiensC2H2 type Kruppel-like565 99 zinc finger protein splice variant b (ZNF236) mRNA, complete cds.

1708 gi5705917human, MOLTHKR-Tl=Kruppel-like 223 45 ' 4 zinc finger T-cells, protein mRNA, 798 nt].
[Homo Sapiens 1708 gi498736Homo SapiensH.sapiens HZF9 mRNA 220 48 for zinc finger protein.

1709 gi1865716Bos taurus procollagen I N-proteinase265 42 1709 AAW47029Homo SapiensHuman N-proteinase 254 43 (70 kDa short form).

1709 AAW47030Homo sapiensBovine N-proteinase.254 42 1710 gi12862392Mus musculusD86 1379 78 171 '76 Homo SapiensH.sapiens ERK3 mRNA.872 92 _ _ Homo SapiensERK3 protein kinase 872 92 _ _ mRNA, 1710 gi1294779 complete cds.

1711 gi572680Escherichiabeta ketoacyl-acyl 315 91 coli carrier protein synthase 1711 gi664870Escherichiabeta-ketoacyl-acyl 315 91 coli carrier protein synthase II

1711 gi4062664Escherichia3-oxoacyl- synthase 315 91 coli (EC 2.3.1.41) II

1712 AAR89952Homo sapiens~ Insulin-like growth726 95 factor binding ~ ~ protein-3. ~ ~

Table 2A

SEQ Hit ID S ecies Descri tion _ S score% Identi ID

1712 gi12652547Homo Sapiensinsulin-like growth 722 95 factor binding protein 3, clone MGC:2305 IMAGE:3506666, mRNA, complete cds.

1712 gi398164 Homo SapiensH.sapiens mRNA for 722 95 insulin-like growth factor binding protein-3.

1713 gi10435700Homo SapienscDNA FLJ13633 fis, 710 97 clone PLACE1011114, weakly similar to PROBABLE ATP-DEPENDENT

RNA HELICASE HAS1.

1713 AAB99891 Homo SapiensHuman RNA helicase 710 97 gene helicain B protein sequence SEQ

ID N0:4.

1713 AAB99892 Homo SapiensHuman RNA helicase 710 97 gene helicain C protein sequence SEQ

ID N0:6.

1714 gi15384740Homo SapiensmRNA for Paralemmin-21652 100 (PALM2 gene).

1714 gi15384742Homo SapiensmRNA for Palm2-AKAP21577 100 fusion protein (PALM2/AKAP2 gene).

1714 gi14041780Homo SapiensmRNA for AKAP-2 protein.415 60 1715 gi3600073Homo SapiensHuman endogenous 573 48 retrovirus K

clone 7.1 polymerise mRNA, partial cds.

1715 gi3600067Homo SapiensHuman endogenous 572 48 retrovirus K

clone 10.9 polymerise mRNA, partial cds.

1715 gi1780973Human pol protein 572 48 endogenous retrovirus K

1716 AAU00025 Homo SapiensHuman activated T-lymphocyte315 74 associated sequence 4, ATLAS-4.

1716 gi5880909DrosophilaRNA-binding protein 87 29 Smaug melanogaster 1716 gi7380929Drosophilasmaug protein 87 29 melanogaster 1717 gi35825 Homo SapiensHuman mRNA for pregnancy3998 93 zone protein.

1717 gi579594 Homo Sapiensalpha 2-macroglobulin2841 64 1717 AAR11749 Homo SapiensHuman alpha-2 macroglobulin2832 64 bait region mutant.

1718 gi4760578Mus musculusPB-Cadherin 1033 84 1718 gi1398906Rattus long type PB-cadherin1027 84 norvegicus 1718 gi1398912Rattus short type PB-cadherin1027 84 norve icus 1719 1339776 Homo SapiensHuman transposon 312 62 L1.2.

1719 gi5070621Homo Sapiensretrotransposon Ll 312 62 insertion in X-linked retinitis pigmentosa locus, complete sequence.

1719 17959889 Homo sapiensPR02221 308 71 1720 AAE06588 Homo SapiensHuman protein having687 100 hydrophobic domain, HP10778.

1720 gi15072402Raja erinaceaorganic solute transporter357 45 alpha 1720 AAB38348 Homo SapiensHuman secreted protein328 100 encoded by gene 28 clone HLDOW79.

Table 2A

SEQ Hit ID S ecies Descri ~tion S score% Identi ID

1721 AAG81345Homo SapiensHuman AFP protein 525 90 sequence SEQ

ID N0:208.

1721 AAB93797Homo SapiensHuman protein sequence525 90 SEQ ID

N0:13560.

1721 AAB44681Homo SapiensHuman secreted protein199 100 sequence encoded by gene 41 SEQ ID

N0:146.

1722 gi1809225Homo SapiensHuman BAC clone RG161K232183 83 from 7q21, complete sequence.

1722 gi1698396Homo SapiensHuman lanosterol 2183 83 14-demethylase cytochrome P450 (CYP51) mRNA, complete cds.

1722 gi871883Homo SapiensHuman mRNA for lanosterol2183 83 demethylase, complete cds.

1723 gi16182326Drosophila GH01206p 108 29 melanogaster 1723 AAG77172Homo SapiensHuman colon cancer 90 39 antigen protein SEQ ID N0:7938.

1723 gi3878064CaenorhabditisH19J13.1 72 25 elegans 1724 AAY53040Homo SapiensHuman secreted protein2480 100 clone kj320_1 protein sequence SEQ ID

N0:86.

1724 gi3510639Rattus UDP-GaINAc:polypeptide1351 59 N-norvegicus acetylgalactosaminyltransferase 1724 gi6688167Homo Sapienspartial mRNA for 1082 100 GaINAc-TS

(GALNTS gene).

1725 gi14603092Homo SapiensSimilar to CD47 antigen1329 97 (Rh-related antigen, integrin-associated signal transducer), clone MGC:15298 IMAGE:4303534, mRNA, complete cds.

1725 gi15277580Homo Sapiensclone MGC:9240 1329 97 IMAGE:3857911, mRNA, complete cds.

1725 gi396705Homo SapiensH.sapiens integrin 1329 97 associated protein mRNA, complete CDS,.

1726 gi1864011Homo SapiensmRNA for SHPS-1, 858 98 complete cds.

1726 gi2052056Homo SapiensH.sapiens mRNA for 858 98 SIRP-alphal.

1726 gi6518913Homo SapiensBit mRNA, complete 858 98 cds.

1727 gi2707601Homo SapiensA4 differentiation-dependent1656 100 protein (A4), triple LIM domain protein (LM06), and synaptophysin (SYP) genes, complete cds; and calcium channel alpha-1 subunit (CACNA1F) gene, partial cds.

1727 gi6180176Homo Sapienstranscription factor1656 100 IGHM

enhancer 3, JMl l protein, JM4 protein, JMS protein, T54 protein, JM10 protein, A4 differentiation-dependent protein, triple LIM

domain protein 6, and synaptophysin genes, complete cds; and L-type calcium channel alpha-1 subunit gene, partial cds, complete sequence.

Table 2A
21~
SEQ Hit ID S ecies Descri tion S score% Identi ID

1727 gi899301Homo SapiensHuman mRNA for synaptophysin1602 100 ( 38).

1728 gi15590682Homo Sapienshistone deacetylase 629 96 9a (HDAC9) mRNA, complete cds, alternatively spliced.

1728 gi12060992Mus musculusMEF2-interacting 626 95 transcription repressor MITR

1728 gi13183017Mus musculushistone deacetylase-related623 94 protein _ gi5911884Homo SapiensmRNA; cDNA DKFZp434N1261605 99 (from clone DI~FZp434N126).

1729 gi15912209ArabidopsisAt1g27520/T17H3_2 228 34 thaliana 1729 gi14164377Mus musculusType II membrane 216 38 protein of ER~mouse gene similar to alpha-mannosidase 1730 gi21842 Triticum proline-rich protein403 33 aestivum 1730 gi4138732Zea mays proline-rich protein398 30 1730 gi11610622Rattus GABA-A epsilon subunit411 32 splice norvegicus variant 1731 gi189222Homo SapiensHuman neurokinin-2 1733 95 receptor (TAC2R) gene, exon 5.

1731 AAW80135Homo SapiensHuman recombinant 1733 95 neurokinin-2 (NK-2) receptor protein.

1731 gi189135Homo sapiensHuman neurokinin 1732 95 A receptor (NIA-2R) mRNA, complete cds.

1732 AAB75594Homo SapiensHuman secreted protein678 99 sequence encoded by gene 37 SEQ ID

N0:148.

1732 AAB75542Homo sapiensHuman secreted protein294 100 sequence encoded by gene 37 SEQ ID

NO:96.

1732 11864011Homo SapiensmRNA for SHPS-1, 261 43 complete cds.

1733 AAY66648Homo SapiensMembrane-bound protein294 93 PR01120.

1733 AAB65171Homo SapiensHuman PR01120 (UNQ559)294 93 protein sequence SEQ ID N0:84.

1733 AAE01440Homo SapiensHuman gene 5 encoded294 93 secreted protein HE9QN39, SEQ ID

N0:95.

1734 gi13161409Mus musculusfamily 4 cytochrome 539 78 1734 gi155947Blaberus cytochrome P450 248 43 discoidalis 1734 gi3249041Diploptera corpora allata cytochrome233 42 punctata 1735 AAY71159Homo SapiensHuman phosphodiesterase682 45 interacting protein, myomegalin.

1735 gi4761644Rattus myomegalin 484 55 norve icus 1735 gi53782 Mus musculusprofilin (AA 1-140) 414 74 1736 gi4959382Homo Sapienshuman endogenous 301 39 retrovirus HERV-H19 pol protein (pol) gene, partial cds; env protein (env) gene, complete cds; and 3' LTR, complete sequence.

1736 gi8439396HERV-H/env62envelope protein 301 39 Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

1736 gi5442112Simian envelope glycoprotein296 42 retrovirus type 2 1737 AAY76177 Homo SapiensHuman secreted protein288 100 encoded by gene 54.

1738 gi3688630Homo Sapienshdkk-4 gene, exon3, 759 100 exon4 and complete cds.

1738 gi6049610Homo Sapiensdickkopf 4 (DKK-4) 759 100 mRNA, complete cds.

1738 AAW73017 Homo sapiensHuman cysteine-rich 759 100 secreted protein CRSP-2.

1739 gi10439926Homo SapienscDNA: FLJ23293 fis, 1786 99 clone HEP10514.

1739 gi4406632Homo Sapiensclone 25221 mRNA 1253 64 sequence, complete cds.

1739 gi10435296Homo SapienscDNA FLJ13321 fis, 1084 62 clone OVARC1001703, weakly similar to Mus musculus ARL-6 interacting protein-2 (Aip-2) mRNA.

1740 AAB49278 Homo SapiensProtein encoded by 755 94 zsig8l cDNA

fragment.

1740 gi1335033Homo SapiensHuman mRNA for collagen69 24 VI

alpha-2 alternative C-terminal domain.

1740 AAY40063 Homo SapiensPeptide sequence 63 35 derived from a human secreted protein.

1741 gi14714807Mus musculusSimilar to transporter-like565 83 protein 1741 AAG81264 Homo SapiensHuman AFP protein 657 100 sequence SEQ

ID N0:46.

1741 AAY66673 Homo SapiensMembrane-bound protein657 100 PRO1115.

1742 gi14583077Homo SapiensPAS-kinase (PASK) 2227 99 mRNA, complete cds.

1742 AAB65630 Homo SapiensNovel protein kinase,2223 99 SEQ ID NO:

156.

1742 gi15487238Mus musculusPASKIN protein 1632 72 1743 gi13879899MycobacteriumPPE family protein 118 31 tuberculosis 1743 gi1334643Xenopus APEG precursor protein90 34 laevis 1743 gi184511 Homo SapiensHuman zinc-finger 86 32 DNA-binding motifs (IA-1) mRNA, complete cds.

1744 gi5931718Chlamydomonas1-alpha dynein heavy1874 62 chain reinhardtii 1744 gi9409781Chlamydomonas1 beta dynein heavy 986 36 chain reinhardtii 1744 gi514215 Chlamydomonasdynein beta heavy 978 36 chain reinhardtii 1745 AAY13392 Homo SapiensAmino acid sequence 1168 57 of protein PR0328.

1745 AAB01373 Homo SapiensNeuron-associated 1168 57 protein.

1745 AAY95343 Homo SapiensHuman PR0328 antitumour1168 57 protein.

1746 AAY99398 Homo SapiensHuman PR01301 (LJNQ667)677 94 amino acid sequence SEQ ID

Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

N0:212.

1746 AAW88501 Homo SapiensHuman stomach carcinoma675 94 clone HP10415-encoded protein.

1746 AAB24255 Homo SapiensHuman cytochrome 675 94 (HUCYP) rotein SEQ
ID NO:1.

1747 AAG02314 Homo SapiensHuman secreted protein,78 66 SEQ ID

NO: 6395.

1747 AAB45051 Homo SapiensHuman secreted protein60 30 encoded by gene 27.

1747 gi2585662Human envelope glycoprotein58 38 immunodeficienc y virus type 1 1748 AAE03560 Homo SapiensHuman differentially1142 88 expressed kidney cDNA 22360 encoded protein.

1748 gi15637151Beta vulgarisglycine decarboxylase62 36 subunit P

1749 gi13506805Homo sapiensthymic stromal co-transporter2309 100 mRNA, complete cds.

1749 gi13506808Mus musculusthymic stromal co-transporter1789 77 1749 AAE04906 Homo SapiensHuman transporter 305 34 and ion channel-19 (TRICH-19) protein.

1750 gi10438815Homo SapienscDNA: FLJ22427 fis, 4170 98 clone HRC09013.

1750 AAB01381 Homo SapiensNeuron-associated 2964 95 protein.

1750 gi6650377Mus musculuspecanex 1 2288 73 1751 gi825663 Homo SapiensH.sapiens GLAST1 411 100 gene for glilial glutamate transporter, exonl, exon 2.

1751 gi487339 Homo SapiensHuman excitatory 411 100 amino acid transported mRNA, complete cds.

1751 gi825504 Homo SapiensHuman mRNA for glutamate411 100 transporter, complete cds.

1752 gi1621607Homo SapiensHuman neogenin mRNA,593 100 complete cds.

1752 gi641966 Gallus neogenin 591 98 gallus 1752 gi1785999Rattus neogenin 586 97 norvegicus 1753 gi7020927Homo SapienscDNA FLJ20674 fis, 293 25 clone ICAIA4450.

1753 AAP94014 Homo SapiensCarcinoembryonic 254 27 cell surface antigen.

1753 AAR60619 Homo SapiensCarcinoembryonic 250 27 antigen glycoprotein.

1754 AAY19507 Homo SapiensAmino acid sequence 343 91 of a human secreted protein.

1754 AAY19654 Homo SapiensSEQ ID NO 372 from 85 100 W09922243.

1754 gi15075730SinorhizobiumHYPOTHETICAL 65 30 meliloti TRANSMEMBRANE PROTEIN

1755 gi2506078Mus musculustetracycline transporter-like1120 99 protein 1755 AAY29332 Homo SapiensHuman secreted protein806 78 clone pe584 2 protein sequence.

1755 AAB75295 Homo SapiensHuman secreted protein806 78 sequence encoded by gene 7 SEQ ID

N0:114.

~ 1756 AAE06608 Homo SapiensHuman protein having1065 98 ~ ~ ~

Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

hydro hobic domain, HP10798.

1756 AAB88469 Homo SapiensHuman membrane or 1065 98 secretory protein clone PSEC0027.

1756 gi9664030Drosophilaaquaporin 115 22 melanogaster 1757 gi8925284Homo Sapiensphosphatidylinositol2598 99 polyphosphate 5-phosphatase type IV mRNA, complete cds.

1757 gi9295353Mus musculusinositol polyphosphate1993 74 phosphatase 1757 gi5360761Rattus pharbin 1933 77 norvegicus 1758 gi395207 Bos tauruspotassium channel 757 83 (BGKS) 1758 gi186669 Homo SapiensHuman potassium channel754 83 mRNA, complete cds.

1758 gi304652 Canis familiarisdelayed rectifier 750 82 K+ channel 1759 gi7023003Homo sapienscDNA FLJ10769 fis, 647 85 clone NT2RP4000151.

1759 AAB93147 Homo SapiensHuman protein sequence647 85 SEQ ID

N0:12057.

1759 AAB38451 Homo SapiensFragment of human 484 84 secreted protein encoded by gene 23 clone HEGAK44.

1760 AAB87763 Homo SapiensHuman T2R33 amino 693 83 acid sequence SEQ ID N0:56.

1760 AAB87780 Homo SapiensHuman T2R50 amino 671 82 acid sequence SEQ ID N0:76.

1760 AAE03828 Homo SapiensHuman gene 11 encoded656 89 secreted protein HHAUQ28, SEQ ID NO:

74.

1761 gi13543624Homo Sapiensuncharacterized hematopoietic514 87 stem/progenitor cells protein MDS029, clone MGC:14612 IMAGE:4051044, mRNA, complete cds.

1761 gi13937872Homo Sapiensuncharacterized hematopoietic514 87 stem/progenitor cells protein MDS029, clone MGC:12437 IMAGE:3930701, mRNA, complete cds.

1761 gi14250122Homo Sapiensuncharacterized hematopoietic514 87 stem/progenitor cells protein MDS029, clone MGC:14755 IMAGE:4283253, mRNA, complete cds.

1762 gi2739094Homo Sapienssodium/myo-inositol 3621 100 cotransporter (SLC5A3) gene, complete cds.

1762 gi662843 Homo SapiensNa+/myo-inositol 3616 99 cotransporter (SLC5A3) gene, complete cds.

1762 gi1237437Bos taurusNa+/myo-inositol 3486 95 cotransporter 1763 AAW84596 Homo SapiensAmino acid sequence 1212 44 of the human Tango-79 protein.

1763 gi15029689Homo Sapiensclone MGC:17422 1209 44 IMAGE:4214343, mRNA, complete cds.

1763 AAB74705 Homo sapiensHuman membrane associated1209 44 protein MEMAP-11.

Table 2A

SE ID Hit ID S ecies Description S score% Identi 1764 gi5923786Homo Sapienszinc metalloprotease614 43 (ADAMTS6) mRNA, complete cds.

1764 AAB72282Homo SapiensHuman ADAMTS-6 amino614 43 acid sequence.

1764 gi 12053709Homo SapiensmRNA for ADAMTS 12. 1078 41 1765 gi1695682Homo SapiensmRNA for hepatic 152 64 triglyceride lipase, complete cds.

1765 gi32498 Homo SapiensHuman mRNA for hepatic152 64 triglyceride lipase (HTGL).

1765 gi307129Homo SapiensHuman hepatic lipase152 64 mRNA, complete cds.

1766 gi886282Homo Sapiensglycoprotein Ib alpha48 42 (GPIb) gene, partial cds.

1766 AAB64868Homo SapiensHuman secreted protein66 39 sequence encoded by gene 43 SEQ ID

N0:154.

1766 gi10798865Homo Sapienszinc finger transcription65 29 factor BTEB2 gene, partial cds.

1767 gi8886005Homo Sapienslysophosphatidic 324 90 acid acyltransferase-delta (LPAAT-delta) mRNA, complete cds.

1767 AAY96592Homo SapiensHuman lysophosphatidic324 90 acid acyltransferase delta.

1767 AAY66665Homo SapiensMembrane-bound protein324 90 PR01016.

1768 gi1160183Homo SapiensH.sapiens mRNA for 926 99 metabotropic glutamate receptor type 4.

1768 gi1935039Homo SapiensHuman metabotropic 926 99 glutamate receptor 4 mRNA, complete cds.

1768 gi2298840unidentifiedHMGLUR4 926 99 1769 gi13279140Homo SapiensSimilar to synaptotagmin2210 99 11, clone MGC:10881 IMAGE:3621175, mRNA, complete cds.

1769 gi15489165Homo Sapiensclone MGC:17226 2210 99 IMAGE:4179089, mRNA, complete cds.

1769 gi14042290Homo sapienscDNA FLJ14634 fis, 2201 98 clone NT2RP2001081, moderately similar to SYNAPTOTAGMIN

IV.

1770 gi14249942Homo SapiensSimilar to RII~EN 239 78 cDNA

0610008P16 gene, clone MGC:15937 IMAGE:3537224, mRNA, complete cds.

1770 AAB56487Homo SapiensHuman prostate cancer239 78 antigen protein sequence SEQ ID

N0:1065.

1770 AAB73512Homo SapiensHuman transferase 239 78 HTFS-19, SEQ

ID N0:19.

1771 gi7678873Homo SapiensmRNA for vascular 5369 99 cadherin-2, complete cds.

1771 gi7407150Homo Sapiensprotocadherin 12 5369 99 (PCDH12) mRNA, complete cds.

1771 gi8164037Homo Sapiensvascular endothelial5369 99 cadherin 2 mRNA, complete cds.

Table 2A

SE ID Hit ID S ecies Descri tion S score% Identi 1772 gi15082281Homo sapiensSimilar to steroid 231 93 dehydrogenase homolog, clone MGC:10252 IMAGE:3622879, mRNA, complete cds.

1772 gi15214803Homo SapiensSimilar to steroid 231 93 dehydrogenase homolog, clone MGC:13329 IMAGE:4281565, mRNA, complete cds.

1772 gi5531815Homo Sapienssteroid dehydrogenase231 93 homolog 1773 AAG73650Homo SapiensHuman colon cancer 265 58 antigen protein SEQ ID N0:4414.

1773 AAB94891Homo SapiensHuman protein sequence265 64 SEQ ID

N0:16231.

1773 gi1335205Homo SapiensHuman DNA for LINE-1273 48 transposable element ORFI and II.

1774 AAW71708Homo SapiensHuman integral membrane657 50 protein TMP-1.

1774 gi3603459Homo Sapienstetraspan NET-5 mRNA,626 90 complete cds.

1774 AAB93885Homo SapiensHuman protein sequence626 90 SEQ ID

NO:13815.

1775 AAG71597Homo SapiensHuman olfactory receptor981 99 polypeptide, SEQ
ID NO: 1278.

1775 AAG71587Homo SapiensHuman olfactory receptor746 75 polypeptide, SEQ
ID NO: 1268.

1775 gi15293749Homo sapiensclone OR10R2 olfactory725 75 receptor gene, partial cds.

1776 AAB38011Homo SapiensHuman secreted protein252 85 encoded by gene 3 clone HPJCX13.

1776 AAB64888Homo SapiensHuman secreted protein252 85 sequence encoded by gene 7 SEQ ID N0:66.

1776 gi10432803Homo SapienscDNA FLJ11531 ~s, 192 54 clone HEMBA1002661.

1777 gi182851Homo SapiensHuman GOS2 protein 497 100 gene, complete cds.

1777 gi182853Homo SapiensHuman GOS2 gene, 497 100 5' flank and cds.

1777 11213013Mus musculusGOS2-like protein 377 77 1778 14027903Homo SapiensVAMPS mRNA, complete473 100 cds.

1778 gi4679008Homo SapiensVAMPS-like protein 473 100 1778 AAW04181Homo sapiensCellubrevin-2. 473 100 1779 gi5326919Bos taurus SCO-spondin 75 30 1779 gi3059229AspergillusHAPB 74 35 oryzae 1779 AAY84596Homo SapiensFragment of human 48 40 pre-pro-artemin polypeptide.

1780 gi1399321Macaca mulattaMHC class I anti 679 72 en Mamu B*08 1780 ' 1399319Macaca mulattaMHC class I anti 674 67 en Mamu B*07 1780 gi8117799Pan troglodytesMHC class I antigen 677 70 1781 gi15929602Homo Sapiensclone MGC:17861 607 51 IMAGE:3903313, mRNA, complete cds.

1781 gi15099953Homo Sapiensdiacylglycerol acyltransferase607 51 mRNA, complete cds.

1781 AAY99421Homo SapiensHuman PR01433 (UNQ738)607 51 amino acid sequence SEQ ID

Table 2A

SEQ Hit H) S ecies Descri tion S score% Identi ID

N0:292.

1782 gi2706518Homo SapiensPMP69 gene, exon 1602 98 1 (and joined CDS).

1782 gi2343157Homo Sapiensperoxisomal membrane1602 98 protein 69 PMP69) mRNA, complete cds.

1782 gi15215442Homo SapiensSimilar to ATP-binding1594 98 cassette, sub-family D (ALD), member 4, clone MGC:4125 IMAGE:2960427, mRNA, complete cds.

1783 AAB35235Homo SapiensHuman neurotransmitter3571 98 transporter protein GC42.

1783 gi546769human, glycine transporter 3557 98 type lb substantia nigra, mRNA, 2364 nt].

[Homo Sapiens 1783 AAB35236Homo SapiensHuman lycine transporter3557 98 type lc.

1784 AAU00017Homo SapiensHuman Plexin-D1. 3361 97 1784 gi13097621Homo Sapiensclone IMAGE:3607457,2470 100 mRNA, partial cds.

1784 AAU00015Homo SapiensHuman Plexin-B2. 1290 47 1785 gi619726Homo SapiensHuman nuclear factor953 99 I (NFI) mRNA, clone ATl, complete cds.

1785 gi619730Homo SapiensHuman nuclear factor953 99 I (NFI) mRNA, clone CTl, partial cds.

1785 gi305357Mesocricetusnuclear factor 1-like953 99 protein auratus 1786 gi13810568Homo SapiensTLRS mRNA for Toll-like4482 100 receptor 5, complete cds.

1786 gi3132526Homo SapiensToll/interleukin-1 4464 99 receptor-like protein 3 (TIL3) mRNA, complete cds.

1786 gi7648687Mus musculustoll-like receptor 3235 72 1787 AAB56473Homo SapiensHuman prostate cancer474 100 antigen protein sequence SEQ ID

NO:1051.

1787 AAB60119Homo SapiensHuman transport protein456 98 TPPT-39.

1787 gi11463949Homo SapienshUGTrel7 mRNA for 308 62 UDP-glucuronic acid, complete cds.

1788 gi4929765Homo SapiensCGI-148 protein mRNA,744 89 complete cds.

1788 gi7578785Homo SapiensNPD008 protein (NPD008)744 89 mRNA, complete cds.

1788 gi14250060Homo Sapiensclone MGC:14598 737 88 IMAGE:4292664, mRNA, complete cds.

1789 gi1736785EscherichiaAcriflavin resistance2265 100 coli protein F

(EnvD protein).

1789 gi15980819Yersinia AcrB/AcrD/AcrF family1854 79 pestis membrane protein 1789 gi1736782EscherichiaAcriflavin resistance1821 100 coli protein F

(EnvD protein).

1790 gi15160166AgrobacteriumAGR_L 3181p 549 59 tumefaciens 1790 gi4981492Thermotogaribose ABC transporter,316 40 permease maritima protein Table 2A

SE Hit ID S ecies Descri tion S score% Identi ~
ID

1790 gi12724646Lactococcusribose ABC transporter314 35 permease lactic subsp.protein lactis 1791 gi41587 Escherichiaglycerol-3-phosphatase1073 100 coli transporter (AA 1 - 452, glpT) 1791 gi1799587Escherichiaglycerol-3-phosphate1073 100 coli transport protein 1791 gi1788573Escherichiasn-glycerol-3-phosphate1073 100 coli permease 1792 gi148200Escherichiasimilar to arylsulfatases679 98 coli of Klebsiella pneumoniae and Homo Sapiens 1792 gi13364207Escherichiaarylsulfatase 679 98 coli 0157:H7 1792 gi1790233Escherichiaarylsulfatase 679 98 coli Kl2 1793 gi9657461Vibrio choleraesulfate permease 267 51 family protein 1793 12635979Bacillus similar to franc 249 46 subtilis otter 1793 gi14024597Mesorhizobiumsulfate transporter 231 45 family protein loti 1794 gi1799719Escherichiasimilar to 922 100 coli 1794 gi15156677AgrobacteriumAGR C 2926p 452 50 tumefaciens 1794 gi15074970SinorhizobiumHYPOTHETICAL 414 47 meliloti TRANSMEMBItANE PROTEIN

1795 gi13325242Homo Sapiensclone MGC:4033 228 81 IMAGE:2820092, mRNA, complete cds.

1795 gi1644366Rattus ninjurinl 228 81 norvegicus 1795 gi3077901Mus musculusninjurin 228 81 1796 gi15987491Homo Sapienstumor endothelial 5742 89 marker 5 precursor ITEMS) mRNA, complete cds.

1796 AAB71863Homo SapiensHuman h15571 GPCR. 5742 89 1796 gi15987499Mus musculustumor endothelial 5030 79 marker 5 precursor 1797 gi13938575Homo SapiensSimilar to RIKEN 1331 100 cDNA

2610511E22 gene, clone MGC:4251 IMAGE:3028940, mRNA, complete cds.

1797 AAY91598Homo SapiensHuman secreted protein1322 100 sequence encoded by gene 8 SEQ ID

N0:271.

1797 115029776Mus musculusRIKEN cDNA 2610511E221317 98 gene 1798 gi42989 EscherichiaSect (PrlA) polypeptide953 100 coli (aa 1-443) 1798 gi606234Escherichiasect 953 100 coli 1798 gi15978329Yersinia preprotein translocase941 97 pestis Sect subunit 1800 gi10435708Homo SapienscDNA FLJ13639 fis, 289 84 clone PLACE1011219, weakly similar to PROBABLE

OXIDOREDiJCTASE (EC
l.-.-.-).

1800 AAB94698Homo SapiensHuman protein sequence289 84 SEQ ID

N0:15680.

Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

1800 gi15292559Drosophila SD07613p 101 67 melanogaster 1801 gi7415511Homo SapiensmRNA for peptide 1281 89 transporter 3, complete cds.

1801 gi13810437Rattus peptide histidine 1066 83 transporter 1 norvegicus homolog rPHT2 1801 AAY86224Homo SapiensHuman secreted protein1280 100 HDPWU34, SEQ ID N0:139.

1802 gi387012Homo SapiensHuman pepsinogen 615 97 gene, exon 9.

1802 gi387013Homo SapiensHuman pepsinogen 615 97 A (15.0) gene, exon 9, clone cgHGP2.

1802 AAB66589Homo SapiensHuman pepsin. 615 97 1803 gi15680159Homo SapiensSimilar to claudin 1113 99 2, clone MGC:20191 IMAGE:4645075, mRNA, complete cds.

1803 gi10503980Homo Sapiensclone SP82 claudin 1113 99 2 mRNA, complete cds.

1803 gi9755009Homo Sapiensclaudin-2 mRNA, complete1113 99 cds.

1804 gi476222Homo SapiensHuman anion exchanger317 74 3 brain isoform (bAE3) mRNA, complete cds.

1804 gi10953762Mus musculusanion exchan er 3 317 74 cardiac isoform 1804 gi309095Mus musculusAE3 protein 317 74 1805 AAB29632Homo SapiensHuman pollinosis-associated2518 55 gene 581-encoded protein, SEQ ID

NO:12.

1805 AAY70023Homo SapiensHuman Protease and 2068 58 associated protein-17 (PPRG-17).

1805 gi13529590Mus musculusSimilar to ubiquitin1924 56 specific protease 20 1806 AAY99363Homo SapiensHuman PRO1380 (UNQ717)1773 98 amino acid sequence SEQ ID

N0:79.

1806 gi12656639Homo Sapiensequilibrative nucleoside1767 98 transporter 3 (ENT3) mRNA, complete cds.

1806 AAY82285Homo SapiensHuman ENTl receptor 1767 98 SEQ ID

NO:1.

1807 AAG81410Homo SapiensHuman AFP protein 155 27 sequence SEQ

ID N0:338.

1807 gi9623190Mus musculussphingosine-1-phosphate159 30 phosphohydrolase 1807 gi15778670Mus musculussphingosine-1-phosphate159 30 phosphatase 1808 gi15082281Homo SapiensSimilar to steroid 231 .93 dehydrogenase homolog, clone MGC:10252 IMAGE:3622879, mRNA, complete cds.

1808 gi15214803Homo SapiensSimilar to steroid 231 93 dehydrogenase homolog, clone MGC:13329 IMAGE:4281565, mRNA, complete cds.

1808 gi5531815Homo Sapienssteroid dehydrogenase231 93 homolo 1810 gi14270513Homo Sapienspartial SLC22A3 gene775 99 for organic cation transporter 3, exon 1 and joined CDS.

1810 gi3581982Homo SapiensmRNA for extraneuronal775 99 Table 2A

SEQ Hit ID S ecies Descri tion S score% Identi ID

monoamine transporter.

1810 14454795Mus musculusorganic cation trans720 89 orter 3 1811 gi1212965Homo SapiensH.sapiens mRNA for 266 91 ~transmembrane protein rnp24.

1811 AAB74750Homo SapiensHuman secreted protein266 91 sequence encoded by gene 18 SEQ ID

N0:59.

1811 AAB74759Homo SapiensHuman secreted protein266 91 sequence encoded by gene 18 SEQ ID

N0:68.

1812 gi15082375Homo SapiensSimilar to transmembrane711 98 superfamily member (upregulated in kidney), clone MGC:20076 IMAGE:4643216, mRNA, complete cds.

1812 gi13096836Mus musculusSimilar to transmembrane690 95 superfamily member (upregulated in kidney) 1812 AAY69992Homo SapiensHuman receptor-associated412 72 protein from Incyte clone 786873.

1813 gi12653811Homo Sapienszinc finger protein 500 38 219, clone MGC:1124 IMAGE:3347777, mRNA, complete cds.

1813 gi6899807Homo SapiensmRNA for zinc finger496 38 protein 219, complete cds.

1813 gi14549186Mus musculuszinc finger protein 490 36 1814 gi4324468Homo SapiensLAGl protein (LAG1) 1385 93 gene, exon 7 and complete cds.

1814 gi183051Homo SapiensHuman growth/differentiation1385 93 factor 1 (GDF-1) mRNA, complete cds.

1814 AAR20230Homo SapienshUOG-1. 1385 93 1815 gi6009515Xenopus epidermis specific 338 41 laevis serine protease 1815 gi9757698Xenopus embryonic serine 314 46 laevis protease-1 1815 gi13277969Mus musculusSimilar to protease,310 38 serine, 8 (prostasin) 1816 gi41875 EscherichiaI~efC potassium efflux706 100 coli system 1816 1216472 Escherichiakefc potassium efflux706 100 coli system 1816 gi1786232EscherichiaIC+ efflux antiporter,706 100 coli glutathione-Kl2 re Mated 1817 gi1054578Escherichiadioxygenase 1510 100 coli _ gi1786565Escherichiataurine dioxygenase,1510 100 1817 coli 2-K12 oxoglutarate-dependent 1817 gi13359879Escherichiataurine dioxygenase 1506 99 coli 0157:H7 1818 gi1279401EscherichiaSapB protein 928 98 coli 1818 gi1742115EscherichiaPeptide transport 928 98 coli system permease protein SapB.

1818 gi13361335Escherichiahomolog of Salmonella928 98 coli peptide 0157:H7 transport permease protein 1819 gi9652147Homo Sapienstransmembrane-type 4639 100 protein tyrosine phosphatase H (PTPRH) ene, exon 20 and complete cds.

1819 gi475004Homo SapiensmRNA for protein 4308 93 tyrosine phosphatase precursor, complete cds.

Table 2A

SEQ Hit ID S ecies Description S score% Identi ID

1819 gi1321659Rattus brain-enriched membrane-920 77 norvegicus associated protein tyrosine phosphatase (BEM)-2 1820 gi7141125Homo Sapienstissue-type heart 1277 100 Ellis-van Creveld syndrome protein (EVC) mRNA, complete cds.

1820 gi7141127Homo Sapienstissue-type brain 1277 100 Ellis-van Creveld syndrome protein (EVC) mRNA, complete cds.

1820 gi7271903Homo SapiensDWF-1 mRNA, complete1271 99 cds.

1821 AAG71453Homo SapiensHuman olfactory receptor568 98 polypeptide, SEQ
ID NO: 1134.

1821 AAG72370Homo SapiensHuman OR-like polypeptide568 98 query sequence, SEQ ID
NO: 2051.

1821 AAE04556Homo SapiensHuman G-protein coupled558 100 receptor-12 (GCREC-12) protein.

1822 gi10440040Homo SapienscDNA: FLJ23375 fis, 757 98 clone HEP 16206.

1822 AAB95094Homo SapiensHuman protein sequence98 43 SEQ ID

N0:17042.

1822 16002197Homo sa H.sapiens NDUFV3 78 34 iens gene, exon 1.

Table 2~

SEQ Hit ID Species Description S
ID scoreIdenti 912 gi601918 Homo Sapiensglutathione S-transferase1263 100 theta 2 912 gi769703 Rattus glutathione S-transferase995 78 norvegicus subunit Yrs 912 gi220757 Rattus glutathione S-transferase995 78 norvegicus Yrs-Yrs 913 gi13872813Homo Sapiensfibulin-6 4538 93 913 gi14575679Homo Sapienshemicentin 4533 93 913 ABB10492 Homo SapiensHuman cDNA SEQ ID 3343 90 NO: 800.

914 AAU80378 Homo SapiensHuman DOPD-like protein465 98 NOV 1.

914 AAR83048 Homo SapiensHuman macrophage migration450 94 inhibitory factor-3 (MIF-3).

914 gi2104581Homo Sapiensphenylpyruvate tautomerase450 94 II

915 AAR83048 Homo SapiensHuman macrophage migration546 86 inhibitory factor-3 (MIF-3).

915 gi2104581Homo Sapiensphenylpyruvate tautomerase546 86 II

915 gi3047378Homo SapiensD-dopachrome tautomerase546 86 916 AAR89197 Homo SapiensHuman hepatocellular 3466 91 growth factor single chain precursor protein.

916 gi219681 Homo SapiensHGF activator precursor3466 91 916 gi4190954Homo Sapienshepatocyte growth 3466 91 factor activator 917 gi5441937Homo Sapienslaminin beta precursor;8964 100 similar to AAB92586 (PID:g2708707) 917 AAY15457 Homo SapiensHuman laminin beta 8838 93 4 protein.

917 AAY15459 Homo SapiensSEQ ID 5 of W09919347.6042 97 918 AAG65887 Homo SapiensAmino acid sequence 5050 100 of GSK gene Id 14936.

918 AAG65888 Homo SapiensAmino acid sequence 4582 84 of GSK gene Id 14936.

918 AAG68261 Homo SapiensHuman POLY8 protein 4543 83 sequence SEQ ID NO:16.

919 ABB74955 Homo SapiensHuman lung tumour 905 100 L524S variant protein sequence SEQ
ID N0:166.

919 ABB74954 Homo SapiensHuman lung tumour 905 100 L524S variant protein sequence SEQ
ID NO:165.

919 AAE23751 Homo SapiensHuman parathyroid 905 100 related peptide, PTHrP (1-173).

920 gi20269129Homo SapiensMEGF6 2584 95 920 AAE17919 Homo SapiensHuman gene 1 encoded 2468 99 serine protease, HMGBM65.

920 AAY72091 Homo SapiensHuman serine protease2468 99 #2 encoded by clone HMGBM65.

921 ABB90774 Homo SapiensHuman Tumour Endothelial346 100 Marker polypeptide SEQ ID
NO 281.

921 ABB90773 Homo SapiensHuman Tumour Endothelial346 100 Marker polypeptide SEQ ID
NO 279.

921 ABB90772 Homo SapiensHuman Tumour Endothelial346 100 Marlcer polypeptide SEQ ID
NO 277.

922 AAU97039 Homo SapiensHuman LP protein LP 2054 89 190.

922 ABG30500 Homo SapiensHuman Carboxypeptidase2054 89 A.

922 AAB47565 Homo SapiensProtease PRTS-7. 2054 89 923 AAM52240 Homo SapiensHuman MFAP4 SEQ ID 1198 99 NO 3.

923 '790817 Homo Sapiensmicrofibril-associated1198 99 glycoprotein 4 923 AAM52239 Homo sapiensHuman MAG4V SEQ ID 1197 100 NO 1.

924 AAU81960 Homo SapiensHuman PR0536. 1648 100 924 AAB65173 Homo SapiensHuman PR0536 (UNQ337)1648 100 protein Table 2B

SEQ Hit ID Species Description S

ID scoreIdenti sequence SEQ ID N0:97.

924 AAB94830 Homo SapiensHuman protein sequence1648 100 SEQ ID

N0:15991.

925 AAU10497 Homo SapiensHuman Apolipoprotein 438 90 A-II, APOA2.

925 gi13528981Homo Sapiensapolipoprotein A-II 438 90 925 gi21429231Homo Sapiensapolipoprotein All 438 90 926 AAY76156 Homo SapiensHuman secreted protein419 90 encoded by gene 33.

927 gi13097252Homo sapiensSimilar to FK506 binding648 91 protein 2 (13 kDa) 927 gi337370 Homo Sapiensrapamycin- and FK506-binding648 91 protein 927 AAR93551 Homo SapiensHuman FKBP-13 immunophilin628 90 protein.

928 AAG73789 Homo SapiensHuman colon cancer 230 95 antigen protein SEQ ID N0:4553.

928 AAB53360 Homo sapiensHuman colon cancer 230 95 antigen protein sequence SEQ ID N0:900.

930 gi17982522Brucella (S)-2-hydroxy-acid 1151 49 oxidase chain D

melitensis 930 gi17740510AgrobacteriumFAD dependent oxidoreductase1149 49 tumefaciens str.

C58 (U.

Washington) 930 gi15157181AgrobacteriumAGR C 3718p 1149 49 tumefaciens str.

C58 (Cereon) 931 ABB89770 Homo SapiensHuman polypeptide 366 70 SEQ ID NO

2146.

931 AAB75367 Homo SapiensHuman secreted protein366 70 #26.

931 AAU04353 Homo SapiensMammalian toxicological366 70 response marker protein #5.

932 ABB55723 Homo SapiensHuman polypeptide 1107 99 SEQ ID NO 52.

932 AAU39014 Homo sapiensHuman secreted protein1107 99 yc2 1.

_ AAM94621 Homo SapiensHuman reproductive 203 67 932 system related antigen SEQ ID NO:
3279.

933 gi16648246Drosophila GH27263p 228 33 melanogaster 933 gi1711197Xenopus Xfringe2 184 25 laevis 933 gi1679784Xenopus radical fringe 184 26 laevis _ AAY73383 Homo SapiensHTRM clone 2280456 1571 100 934 protein sequence.

934 AAG75282 Homo SapiensHuman colon cancer 619 99 antigen protein SEQ ID N0:6046.

934 AAM41045 Homo SapiensHuman polypeptide 89 29 SEQ ID NO

5976.

935 AAG65916 Homo SapiensAmino acid sequence 3041 99 of GSK gene Id 239881.

935 gi15705411Homo Sapienspeptidoglycan recognition3041 99 protein L

precursor 935 AAG65915 Homo SapiensAmino acid sequence 2892 99 of GSK gene Id 239881.

936 AAU97218 Homo sapiensHuman G protein-coupled850 99 receptor, TGR25.

Table 2B

SEQ Hit ID Species Description S

ID scoreIdenti 936 AAE23415 Homo SapiensHuman G-protein coupled850 99 receptor-7 (GCREC-7).

936 ABB12463 Homo SapiensHuman bone marrow 769 100 expressed protein SEQ ID NO:
302.

937 gi1711232Homo Sapiens14-3-3 protein eta 1094 94 chain 937 gi460779 Homo Sapiens14-3-3 eta subtype 1094 94 937 11477931 Homo Sapiens14.3.3 eta chain 1094 94 938 gi16118441OryctolagusS-100 calcium-binding479 100 protein beta cuniculus subunit 938 gi12804681Homo SapiensS100 calcium-binding 479 100 protein, beta (neural) 938 gi337730 Homo SapiensS100 protein beta 479 100 subunit 939 AAW75082 Homo SapiensHuman secreted protein392 92 encoded by gene 26 clone HTLEV12.

939 AAM95398 Homo SapiensHuman reproductive 71 50 system related antigen SEQ ID NO:
4056.

939 AAU29184 Homo SapiensHuman PRO polypeptide71 50 sequence #161.

940 AAU29315 Homo SapiensHuman PRO polypeptide3743 99 sequence #292.

940 ABB75753 Homo SapiensHuman pancreas GP354.3104 100 940 ABB75751 Homo SapiensHuman immunoglobulin 3073 99 superfamily member GP354.

941 AA021477 Homo sapiensHuman NgR2 protein 2133 100 sequence.

941 AA021482 Homo SapiensMature human NgR2 2082 100 protein sequence.

941 gi20987877Mus musculussimilar to Nogo receptor885 58 942 AAB25674 Homo SapiensHuman secreted protein768 98 sequence encoded by gene 10 SEQ ID N0:63.

942 AAB36613 Homo SapiensHuman FLEXHT-35 protein238 90 sequence SEQ ID N0:35.

942 gi14603247Homo SapiensSimilar to RII~EN 238 90 cDNA

5730409615 gene 943 AAE22093 Homo SapiensHuman kidney specific851 98 renal cell carcinoma (KSRCC) protein.

943 AAY85678 Homo SapiensHuman kidney disease 751 98 associated protein SEQ ID 10.

943 gi3127193Rattus kidney-specific protein686 75 ' norvegicus 944 ABP41513 Homo SapiensHuman ovarian antigen2558 100 HCOOX52, SEQ ID N0:2645.

944 gi1197499Homo SapiensC1 inhibitor 2527 100 944 AAW18207 Homo SapiensWild-type C1 inhibitor.2524 99 945 gi17982052Brucella RIBOSOMAL PROTEIN 241 36 Ll l melitensis METHYLTRANSFERASE

945 gi15157854AgrobacteriumAGR C~4799p 207 36 tumefaciens str.

C58 (Cereon) 945 gi18145768Clostridiumprobable ribosomal 118 37 protein Ll l perfringensmethyltransferase str.

946 AAB03948 Homo SapiensHuman mesenchymal 462 98 stem cell polypeptide.

946 AAB64909 Homo SapiensHuman secreted protein165 63 sequence encoded by gene 28 SEQ ID N0:87.

Table 2B

SEQ Hit ID Species Description S
~

ID scoreIdenti 946 AAU01649 Homo SapiensHuman secreted protein165 63 immunogenic epitope encoded by gene #12.

947 AAE13809 Homo sapiensHuman lung tumour-specific2906 99 protein SAL-82.

947 AAB44467 Homo SapiensHuman lung tumour-specific2906 99 antigen encoded by cDNA #103.

9 gi13958036Homo SapiensRUFY1 2906 99 _ AAB88326 Homo sapiensHuman membrane or 541 74 949 secretory protein clone PSEC0021.

949 AAB92475 Homo SapiensHuman protein sequence541 74 SEQ ID

NO:10549.

949 AAE03226 Homo SapiensHuman gene 7 encoded 541 74 secreted protein HNTDL21, SEQ
ID N0:76.

950 ABP47877 Homo SapiensHuman polypeptide 1303 100 SEQ ID NO 307.

950 ABP47870 Homo SapiensHuman polypeptide 959 99 SEQ ID NO 300.

950 ABP48038 Homo SapiensHuman polypeptide 835 98 SEQ ID NO 468.

951 AAU12382 Homo SapiensHuman PR0792 polypeptide1138 87 sequence.

951 AAB24416 Homo SapiensHuman PRO792 protein 1138 87 sequence SEQ ID N0:155.

951 AAB24055 Homo sapiensHuman PR0792 protein 1138 87 sequence SEQ ID N0:31.

952 gi7670746Homo SapiensUDP-glucose:glycoprotein7974 98 glucosyltransferase 1 precursor 952 gi13275621synthetic Rat RUGT 7317 91 construct 952 gi7677176Rattus UDP-glucose 7317 91 norvegicus glycoprotein:glucosyltransferase precursor 953 gi20810499Homo SapiensSimilar to RIKEN cDNA1237 100 2900074C 18 gene 953 AAM42005 Homo SapiensHuman polypeptide 404 48 SEQ ID NO

6936.

953 AAB64390 Homo SapiensAmino acid sequence 402 50 of human intracellular signalling molecule INTRA22.

954 gi18676660Homo SapiensFLJ00229 protein 2292 98 954 AAM40342 Homo SapiensHuman polypeptide 1454 60 SEQ ID NO

3487.

954 AAM42128 Homo SapiensHuman polypeptide 765 60 SEQ ID NO

7059.

955 gi21707216Homo sapiensLOC146556 2100 99 955 AAG81399 Homo SapiensHuman AFP protein 1910 100 sequence SEQ

ID NO:316.

955 AAB61421 Homo SapiensHuman TANGO 300 protein.1904 99 956 gi21667020Homo sapiensmutant I beta-1,6-N- 1637 99 acetylglucosaminyltransferase C

form 956 gi21667011Homo SapiensI beta-1,6-N- 1637 99 acetylglucosaminyltransferase C

form 956 gi21667015Homo Sapiensmutant I beta-1,6-N- 1633 99 acetylglucosaminyltransferase C

form Table 2B

SEQ Hit ID Species Description S
ID scoreIdenti 957 gi2065165Homo Sapienscollagen type XIV 773 93 957 AAG00322 Homo SapiensHuman secreted protein,482 98 SEQ ID
NO: 4403.

957 1288875 Gallus galluscolla en XIV 461 63 958 AAG75509 Homo SapiensHuman colon cancer 2482 94 antigen protein SEQ ID N0:6273.

958 AAB84606 Homo SapiensAmino acid sequence 2482 94 of matrix metalloproteinase collagenase 1.

958 AAE10415 Homo SapiensHuman matrix metalloprotinase-12482 94 (MMP-1) protein.

959 AAY25868 Homo SapiensHuman secreted protein993 99 fragment encoded from gene 57.

959 gi15145797Sus scrofa basic proline-rich 88 42 protein 959 '3413810 Mus musculusBassoon 84 31 960 AAG77807 Homo SapiensHuman HSIFL59 serine/threonine473 98 phosphatase protein sequence.

960 AAB58288 Homo SapiensLung cancer associated473 98 polypeptide sequence SEQ ID 626.

960 AAY59744 Homo SapiensHuman normal ovarian 473 98 tissue derived protein 21.

961 gi4019247Ateline thymidine kinase 71 46 herpesvirus 962 gi9956936Mus musculusSu(var)3-9 homolog 1310 86 Suv39h2 962 AAM78701 Homo SapiensHuman protein SEQ 1236 100 ID NO 1363.

962 AAW05261 Homo SapiensChromatin regulator 814 55 protein SUV39H.

963 AAG03840 Homo SapiensHuman secreted protein,439 80 SEQ ID
NO: 7921.

963 gi1698653Homo SapiensNADPH:ubiquinone oxidoreductase439 80 subunit B 13 963 gi12654023Homo SapiensNADH dehydrogenase 439 80 (ubiquinone) 1 alpha subcomplex, 5 (l3kD, B13) 964 gi37347 Homo SapiensTRG gamma chain (AA 1657 94 1-340) 964 gi339407 Homo SapiensTi antigen CD3-associated1627 93 protein precursor 964 gi37018 Homo Sapienspre-gamma-chain (AA 1436 87 -14 to 309) 965 AAE06606 Homo SapiensHuman protein having 566 96 hydrophobic domain, HP 10794.

965 AAM94615 Homo SapiensHuman reproductive 566 96 system related antigen SEQ ID NO:
3273.

965 gi18490535Mus musculusRIKEN cDNA 2610528J11388 78 ene 966 113654639Bos taurus D- ucuronyl C5 epimerase3159 97 966 gi13442978Mus musculusD- lucuronyl C5-epimerase3139 95 966 gi11935177Mus musculusheparin/heparan sulfate:glucuronic3134 95 acid C5 epimerase 967 AAG72204 Homo SapiensHuman olfactory receptor1167 77 polypeptide, SEQ ID
NO: 1885.

967 AAG71875 Homo SapiensHuman olfactory receptor1138 74 polypeptide, SEQ ID
NO: 1556.

967 AAG71816 Homo sapiensHuman olfactory receptor1102 72 polypeptide, SEQ ID
NO: 1497.

968 AAB73679 Homo SapiensHuman oxidoreductase 1918 100 protein ORP-12.

968 gi12655133Homo SapiensSimilar to CGI-63 1918 100 protein 968 ABB89788 Homo SapiensHuman polypeptide 1907 99 SEQ ID NO

Table 2B

SEQ Hit ID Species Description S
ID ~ scoreIdenti __ 2164.

969 AAY28995 Homo SapiensTumour suppressor 2309 59 Del-27 protein se uence.

969 AAY15344 Homo SapiensTumour su pressor 2309 59 protein del-27.

969 gi6062874Homo Sapienscandidate tumor suppressor2309 59 protein 970 gi387011 Homo sapienspyruvate dehydrogenase2187 99 E1-alpha precursor 970 gi35381 Homo Sapienspyruvate dehydrogenase2049 100 E1' subunit (AA 1 - 390) 970 gi219982 Homo Sapiensalpha subunit 2049 100 971 12275569 Homo SapiensTCRBV23S1 660 99 971 gi2104755Homo SapiensT cell receptor V-beta660 99 971 gi495404 Pan troglodytesT cell receptor beta 657 88 chain 972 AAM95505 Homo SapiensHuman reproductive 1469 99 system related antigen SEQ ID NO:
4163.

972 ABB96188 Homo SapiensHuman testicular antigen1469 99 SEQ ID
NO: 1572.

972 AAB75360 Homo SapiensHuman secreted protein1272 100 #19.

973 AAE02937 Homo SapiensHuman TFRP protein. 3040 94 973 gi4996563Homo Sapiensprotein inhibitor 3040 94 of activatied STAT3 973 gi12654633Homo Sapiensprotein inhibitor 3040 94 of activated STAT3 974 gi15099957Homo Sapiensdiacylglycerol acyltransferase855 93 2-like protein 974 gi15099955Mus musculusdiacylglycerol acyltransferase675 59 2-like protein 974 AAY94889 Homo SapiensHuman protein clone 576 56 HP02485.

975 AAB92669 Homo SapiensHuman protein sequence1432 100 SEQ ID
NO:11033.

975 ABG40833 Homo SapiensHuman peptide encoded399 98 by genome-derived single exon probe SEQ ID
30498.

975 AAM31319 Homo SapiensPeptide #5356 encoded399 98 by probe for measuring placental gene expression.

976 gi4210474Navel orangepolyprotein 71 21 infectious mottling virus 977 11209685 Homo Sapienssalivary peroxidase 3754 96 977 gi163307 Bos taurus lactoperoxidase 3166 80 977 gi11990122Camelus peroxidase 3153 81 dromedarius 978 AAY01604 Homo SapiensAmino acid sequence 501 97 of the human defensin (Def ~ protein.

978 gi29735 Homo Sapienscorticostatin/defensin214 46 HP-4 precursor 978 AAR15222 Homo SapiensChronic myelogenous 211 47 leukaemia-derived myeloid-related protein.

979 AAG81415 Homo SapiensHuman AFP protein 848 100 sequence SEQ
ID N0:348.

980 gi6633820ArabidopsisF1N19.20 79 26 thaliana 980 gi6180001Capra hircuspregnancy-associated 73 30 lycoprotein-8 980 gi20071290Mus musculusSimilar to solute 71 25 carrier family 26, member 7 981 gi4309953Homo SapiensT cell receptor gamma951 95 chain; similar to PID:g339160 Table 2B

SEQ Hit ID Species Description S

ID scoreIdenti 981 gi4309950Homo SapiensT cell receptor gamma917 88 chain; match to 508328 (PID:g106470) 981 ABG39493 Homo SapiensHuman peptide encoded679 77 by genome-derived single exon probe SEQ ID

29158.

982 gi1223888synthetic T cell receptor alpha1066 79 chain construct 982 gi338766 Homo SapiensT-cell receptor precursor987 73 982 gi3089419Homo SapiensT cell receptor alpha974 71 chain 983 ABB07518 Homo SapiensHuman drug metabolizing418 29 enzyme (DME) (ID: 7474438CD1).

983 AAB73512 Homo sapiensHuman transferase 409 30 HTFS-19, SEQ

ID N0:19.

983 gi14249942Homo SapiensSimilar to RIKEN cDNA409 30 0610008P16 gene 984 AAG71286 Homo SapiensHuman gene 9-encoded 311 90 secreted protein HMSDL37, SE
ID N0:135.

984 AAG71251 Homo SapiensHuman gene 9-encoded 311 90 secreted protein HMSDL37, SEQ
ID N0:99.

984 gi13096922Mus musculusSimilar to nadrin 74 44 985 gi4519541Mus musculusthrombospondin type 1296 88 1 domain 985 ABP61846 Homo SapiensHuman polypeptide 644 46 SEQ ID NO 200.

985 AAB99220 Homo SapiensHuman thrombospondin-30.644 46 986 AAG81417 Homo SapiensHuman AFP protein 287 100 sequence SEQ

ID N0:352.

987 ABB53264 Homo sapiensHuman polypeptide 1904 100 #4.

987 118565270Homo SapiensLib 1904 100 987 gi18565266Rattus Lib 1621 83 norvegicus 988 AAB59022 Homo SapiensBreast and ovarian 1385 100 cancer associated antigen protein sequence SEQ ID

730.

988 gi14124958Homo Sapiensnucleotide binding 1385 100 protein 2 (E.coli MinD like) 988 gi13559170Homo SapiensC447E6.1 (nucleotide 1380 100 binding protein 1 (E.coli MinD like) ) 989 AAU99292 Homo SapiensHuman chordin-like 3916 100 associated protein #1.

989 AAU99293 Homo sapiensHuman chordin-like 3073 81 associated protein #2.

989 AAE07119 Homo SapiensHuman gene 12 encoded2411 98 secreted protein fragment, SEQ ID N0:136.

990 AAB26105 Homo SapiensHuman DAN/Cerberus-related1693 87 protein 6 (hDCR6) #1.

990 AAE17089 Homo sapiensHuman osteolevin protein.439 66 990 ABB07209 Homo SapiensHuman cloaked-2 polypeptide439 66 sequence.

991 gi9964099Chlamydia inclusion membrane 74 35 protein trachomatis 992 gi21619848Homo SapiensSimilar to immunoglobulin1002 89 lambda joining 3 992 gi4490538Homo Sapienslambda-immunoglobulin927 81 light chain 992 gi33746 Homo Sapiensimmunoglobulin lambda914 80 light chain 993 AAG03466 Homo SapiensHuman secreted protein,97 100 SEQ ID

NO: 7547.

Table 2B

SEQ Hit ID Species Description S

ID scoreIdenti 993 gi4063766Aspergilluschitinase 91 30 nidulans 993 gi3617766Anopheles ICHIT protein 88 27 gambiae 994 gi203246 Rattus cell adhesion-like 1739 97 molecule norve icus 994 gi514374 Homo Sapiensopioid-binding cell 1665 97 adhesion molecule 994 gi586 Bos taurus put. pre-OPCAM (AA 1640 93 1 - 345) 995 AAB53088 Homo SapiensHuman angiogenesis-associated2391 91 protein PR0328, SEQ
ID NO:132.

995 AAB80260 Homo SapiensHuman PR0328 protein.2391 91 995 AAU12351 Homo SapiensHuman PR0328 polypeptide2391 91 sequence.

996 AAB85144 Homo SapiensHuman NKCR polypeptide1205 83 (clone ID

HMSOM53).

996 AAY96226 Homo sapiensHuman high affinity 354 41 Fc receptor, FcgammaRI.

996 gi31332 Homo SapiensFcRI (AA 1-374) 354 41 997 ABB50835 Homo SapiensHuman secreted protein74 36 encoded by gene 80 SEQ ID N0:788.

998 ABP61434 Homo SapiensHuman NF-kB activating417 100 protein SEQ ID NO 21.

998 AAU07442 Homo SapiensHuman Wntl Upregulated417 100 protein 2 (WUP2).

998 AAU07441 Homo SapiensHuman Wntl Upregulated417 100 protein 1 (WUP1).

999 AAB08732 Homo SapiensAmino acid sequence 1671 85 of a human OLD-35 polypeptide.

999 gi20372922Homo sapienspolynucleotide phosphorylase-like1671 85 protein 999 AAB92684 Homo SapiensHuman protein sequence1265 88 SEQ ID

NO:11065.

1000gi199582 Mus musculusB(2)-microglobulin 616 95 1000gi50105 Mus musculusbeta2-microglobulin 614 95 precursor (aa -20 to 99) 1000gi199576 Mus musculusB(2)-microglobulin 609 94 1001AAB93335 Homo SapiensHuman protein sequence672 99 SEQ ID

N0:12441.

1001AAE21620 Homo SapiensHuman gene 7 encoded 427 91 secreted protein, SEQ ID N0:92.

1001AAE21604 Homo SapiensHuman gene 7 encoded 402 90 secreted protein HTFOE85, SEQ
ID NO:76.

1002gi15559608Homo SapiensSimilar to zinc finger2079 100 protein 16 (KOX 9) 1002gi488555 Homo Sapienszinc finger protein 749 65 1002AAB21006 Homo SapiensHuman nucleic acid-binding747 54 protein, NuABP-10.

1003ABB79480 Homo SapiensHuman zinc finger 1689 56 protein 75.68.

003 gi1769491Homo Sapienskruppel-related zinc 1672 53 1 finger protein _ AAM39130 Homo sapiensHuman polypeptide 1669 52 2275.

1005AAB23641 Homo SapiensHuman secreted protein609 100 SEQ ID NO:

97.

1005gi13129458Oryza sativapolyprotein 89 31 Table 2B

SEQ Hit ID Species Description S
ID scoreIdenti [Oryza sativa (japonica cultivar-group)]

1005gi7228457 Oryza sativaSimilar to Sorghum 87 29 (japonica bicolor Gypsy-cultivar- Ty3 type retrotransposon oup) RetroSorl, polyprotein. (AF098806) 1006gi11493473Homo SapiensPR02225 163 67 1007AAM52305 Homo SapiensHuman zyxine. 2815 91 1007AAG68191 Homo SapiensZyxin protein SEQ 2815 91 ID N0:107.

1007gi1545954 Homo Sapienszyxin 2815 91 1008AAM00955 Homo SapiensHuman bone marrow 704 100 protein, SEQ
ID NO: 431.

1008gi18028488Homo Sapienscytosolic leucine-rich631 99 protein 1008gi21666364Bos taurusleucine-rich rotein 588 90 1009AAE01420 Homo SapiensHuman secreted protein612 100 fragment, SEQ ID NO:144.

1009gi17225457Homo Sapiensautism-related protein76 38 1009AAM79126 Homo SapiensHuman protein SEQ 72 29 ID NO 1788.

1010gi16877231Homo SapiensSimilar to RIKEN cDNA997 100 2700019D07 gene 1010AAM39593 Homo SapiensHuman polypeptide 94 100 SEQ ID NO
2738.

1010gi7302568 DrosophilaCG15073-PA 91 19 melanogaster 1011AAB43434 Homo SapiensHuman cancer associated413 78 protein sequence SEQ ID N0:879.

1011AAY07039 Homo SapiensBreast cancer associated413 78 antigen precursorsequence.

1011gi17932966Homo Sapiensribosomal protein 413 78 1012AAW88457 Homo sa Human lysophospholipase1125 93 iens IHLP.

1012ABP51416 Homo SapiensHuman MDDT SEQ ID 843 100 NO 438.

1012AAB75386 Homo SapiensHuman secreted protein825 100 #45.

1013AAG81374 Homo SapiensHuman AFP protein 919 98 sequence SEQ
ID NO:266.

1013gi20977549Danio rerioDT1P1A10-like rotein 354 41 1013gi665970 SaccharomycesYIr435wp 169 26 cerevisiae 1014gi20988991Mus musculusRIKEN cDNA 2810405K02920 88 gene 1014AAM93895 Homo SapiensHuman polypeptide, 777 100 SEQ ID NO:
4031.

1014ABB84903 Homo sapiensHuman PR01198 protein187 36 sequence SEQ ID N0:174.

1015AAB56791 Homo SapiensHuman prostate cancer496 98 antigen protein sequence SEQ
ID N0:1369.

1015gi19401678Giardia endosomal AAA ATPase-like76 38 intestinalisprotein 1016ABB44579 Homo SapiensHuman wound healing 655 100 related polypeptide SEQ ID
NO 36.

1016AAB53427 Homo SapiensHuman colon cancer 655 100 antigen protein se uence SEQ ID N0:967.

1016gi2286227 Bos taurusmyocardial vascular 655 100 inhibition factor 1017AAB81188 Homo SapiensHuman zinc finger 2389 98 protein 52 (ZFP-52).

1017AAB95368 Homo SapiensHuman protein sequence1712 100 SEQ ID
N0:17684.

Table 2B

SEQ Hit ID Species Description S
ID scoreIdenti 1017ABP51456 Homo SapiensHuman MDDT SEQ ID 1561 99 NO 478.

1018gi6434346CaenorhabditisY105E8B.4 77 33 elegans 1019AAG66831 Homo SapiensHuman DNA-dependent 443 98 protein kinase 9.

1019AAB90816 Homo SapiensHuman shear stress-response365 100 protein SEQ ID NO: 140.

1019AAG66832 Homo SapiensHuman DNA-dependent 79 100 protein ldnase 9 N-terminal peptide.

1020gi1377897Homo Sapiensheart protein 1631 100 102017209525 Homo SapiensDRAL/Slim3/FHL2 1625 99 102015825391 Mus musculusfour and half LIM 1524 91 domain protein 2 1021gi18139947Homo SapiensHLCDGP1 893 99 1021gi7770259Homo SapiensPR02975 794 100 1021gi1237130EscherichiaO antigen polymerase 85 26 coli 1022gi19263712Homo SapiensSimilar to LOC146557 972 100 1022AAG81348 Homo SapiensHuman AFP protein 528 62 sequence SEQ
ID N0:214.

1022AAM88837 Homo SapiensHuman immune/haematopoietic179 80 antigen SEQ ID N0:16430.

1023AAG01390 Homo sapiensHuman secreted protein,297 100 SEQ ID
NO: 5471.

1023gi456681 Pseudorabieshelicase 80 25 virus 1023AAM85692 Homo SapiensHuman immune/haematopoietic78 63 antigen SEQ ID N0:13285.

1024gi4235144Homo SapiensBC39498_1 1423 62 1024gi21265141Homo SapiensSimilar to zinc finger1404 60 protein 91 (HPF7, HTF10) 1024gi14348591Homo SapiensKRAB zinc finger protein1403 58 1025gi18490643Homo SapiensSimilar to recombination2849 99 activating gene 2 1025gi165680 Oryctolagusrecombination activating2666 91 cuniculus protein 1025gi2576246Mus musculusRAG-2 protein 2594 88 1026AAG75278 Homo SapiensHuman colon cancer 1058 95 antigen protein SEQ ID N0:6042.

1026gi600255 Gallus alluscaldesmon 147 28 1026gi211896 Gallus gallush-caldesmon 147 28 1027AAY87341 Homo SapiensHuman signal peptide 699 99 containing protein HSPP-118 SEQ
ID N0:118.

1027gi12311853Leishmania possible surface antigen77 31 major 1028AAM92844 Homo SapiensHuman digestive system86 38 antigen SEQ ID N0: 2193.

1028ABB 11195Homo SapiensHuman transmembrane 82 25 protein homologue, SEQ ID
N0:1565.

1028ABG66815 Homo SapiensHuman prostate specific75 60 protein DEX0283 123.

1029AAE02058 Homo SapiensHuman four disulfide 587 41 core domain (FDCD)-containing protein.

1029AAM79986 Homo SapiensHuman protein SEQ 579 41 ID NO 3632.

1029AAM79002 Homo SapiensHuman protein SEQ 579 41 ID NO 1664.

1031ABP42929 Homo SapiensHuman ovarian antigen820 93 HPDRS87, SEQ ID N0:4061.

'Table 2B

SEQ Hit ID Species Description S

ID scoreIdenti 1031ABP41129 Homo SapiensHuman ovarian antigen820 93 HE2RG21, SEQ ID N0:2261.

1031AAU01195 Homo SapiensHuman cyclophilin 820 93 A rotein.

1032AAE06643 Homo sapiensHuman G-protein coupled671 99 receptor (NGPCR) #2, 1032AAE06642 Homo SapiensHuman G-protein coupled671 99 receptor (NGPCR) #I, 1032gi7291589Drosophila CG18679-PA 214 34 melanogaster 1033AAG03055 Homo SapiensHuman secreted protein,269 100 SEQ ID ' NO: 7136.

1034AAB38043 Homo SapiensFragment of human I25 36 secreted protein encoded by gene 10 clone HWHGP71.

1034gi5305335Mycobacteriumproline-rich mucin 105 33 homolog tuberculosis 103415917666 Zea mays extensin-like protein104 37 1035AAM93942 Homo SapiensHuman polypeptide, 3226 99 SEQ ID NO:

4126.

1035ABB 11422Homo SapiensHuman Zn finger protein2760 96 homologue, SEQ ID N0:1792.

1035gi6467206Homo Sapiensgonadotropin inducible2032 57 transcription repressor-4 1036AAB95007 Homo SapiensHuman protein sequence518 86 SEQ ID

N0:16685.

1036gi21410398Mus musculusRII~EN cDNA 26I0034EI381 32 gene 1036gi45906 Proteus hlyC protein (AA 1-54)72 45 vulgaris 1037AAY27616 Homo SapiensHuman secreted protein562 99 encoded by gene No. 50.

1037gi17902598Rice black P6 protein 71 25 streaked dwarf virus 1038116588681Homo Sapiensanion transporter/exchanger-94295 95 1038AAE21 Homo SapiensHuman TRICH-10 protein.3612 9I

1038gi13344999Homo Sapienssolute carrier family1298 37 26 member 6 1039AAU12254 Homo SapiensHuman PRO4343 polypeptide780 100 sequence.

1039AAM40835 Homo sapiensHuman polypeptide 780 100 SEQ ID NO

5766.

1039AAY76141 Homo SapiensHuman secreted protein780 100 encoded by gene 18.

1040ABB89694 Homo SapiensHuman polypeptide 622 77 SEQ ID NO

2070.

1040AAY59672 Homo SapiensSecreted protein 108-006-5-0-E6-FL.622 77 1040AAB94543 Homo SapiensHuman protein sequence618 76 SEQ ID

N0:15290.

1041AAY92710 Homo SapiensHuman membrane-associated704 97 protein Zsig24.

1041ABB89722 Homo SapiensHuman polypeptide 566 99 SEQ ID NO

2098.

1041AAY87250 Homo SapiensHuman signal peptide 566 99 containing protein HSPP-27 SEQ
ID NO:27.

1042AAU29316 Homo SapiensHuman PRO polypeptide2932 99 sequence #293.

1042ABB05749 Homo SapiensHuman G protein-coupled1591 44 receptor Table 2B

SEQ Hit ID Species Description S
ID scoreIdenti NOVla protein SEQ
ID N0:2.

1042gi14572521Homo SapiensNEPHl 1519 51 1043AAU00688 Homo SapiensHuman CD59 protein. 710 100 1043AAW26318 Homo sapiensHuman CD59. 710 100 1043AAR80240 Homo SapiensHuman membrane attack710 100 complex inhibition factor.

1044gi17390957Mus musculusSimilar to RIKEN cDNA1455 74 2010001E11 gene 1044gi6841140 Homo SapiensHSPC100 498 100 1044gi17985273Brucella GLUCOSE/GALACTOSE 124 22 melitensisTRANSPORTER

1045AAB56632 Homo SapiensHuman prostate cancer3377 99 antigen protein sequence SEQ
ID NO:1210.

1045gi13097708Homo Sapiensribophorin II 3152 100 1045gi4730801 Homo SapiensdJ343K2.2.1 (ribophorin3152 100 II (isoform 1)) 1046AAB70690 Homo SapiensHuman hDPP protein 598 100 sequence SEQ
ID N0:7.

1046AAG89279 Homo SapiensHuman secreted protein,598 100 SEQ ID
NO: 399.

1046gi13182757Homo SapiensHTPAP 598 100 1047gi2276448 Homo SapiensMHC class I HLA-A 1794 93 1047gi6815812 Homo sapiensMHC class I antigen 1794 93 heavy chain 1047gi1245460 Homo SapiensMHC class I HLA-A 1786 92 1048ABP41629 Homo SapiensHuman ovarian antigen675 90 HOOJQ91, SEQ ID N0:2761.

1048AAB95392 Homo SapiensHuman protein sequence564 78 SEQ ID
N0:17743.

1048AAM79768 Homo SapiensHuman protein SEQ 564 78 ID NO 3414.

1049gi14017773Mus musculusCg10671-like 1517 96 1049gi14017764Mus musculusCG10671-like 1517 96 1049ABB89676 Homo SapiensHuman polypeptide 957 89 SEQ ID NO
2os2.

1050AAG81431 Homo SapiensHuman AFP protein 503 97 sequence SEQ
ID N0:380.

1050AAE23305 Homo SapiensHuman nectin-4 protein128 32 #4.

1050gi19353148Mus musculusSimilar to poliovirus127 27 receptor-related 1051gi20072551Mus musculusRIKEN cDNA 4930511J11420 45 gene 1051gi17974542Homo Sapiensvoltage-dependent 147 25 calcium chamiel gamma-8 subunit 1051112836893 Gallus IPR328-like protein 147 29 anus 1052ABB84978 Homo SapiensHuman PR04430 protein436 70 sequence SEQ ID N0:324.

1052ABB95584 Homo SapiensHuman angiogenesis 436 70 related protein PR04430 SEQ ID NO:
324.

1052AAU29273 Homo SapiensHuman PRO polypeptide436 70 sequence #250.

1053AAB88325 Homo SapiensHuman membrane or 912 99 secretory protein clone PSEC0020.

1053AAB53257 Homo SapiensHuman colon cancer 859 99 antigen protein sequence SEQ ID N0:797.

1053AAY87264 Homo sapiensHuman signal peptide 315 63 containing protein HSPP-41 SEQ
ID N0:41.

1054AAU12201 Homo SapiensHuman PR01779 polypeptide1819 54 Table 2B

SEQ Hit ID Species Description S
~ scoreIdenti ID

sequence.

1054AAB25594 Homo SapiensProtein encoded by 1819 54 human secreted protein gene #1, 1054gi1234787Xenopus up-regulated by thyroid1799 53 laevis hormone in tadpoles; expressed specifically in the tail and only at metamorphosis;
membrane bound or extracellular protein; C-terminal basic region 1055AAW55035 Homo sapiensHPURR amino acid sequence.2014 100 1055AAW47066 Homo SapiensHuman brain P2X-1 2014 100 receptor polypeptide.

1055gi4099139Homo SapiensP2X4 purinoreceptor 2014 100 1056AAE03560 Homo SapiensHuman differentially 1255 85 expressed kidney cDNA 22360 encoded protein.

1056AAM42468 Homo SapiensHuman kidney related 145 90 polypeptide SEQ ID NO 337.

1056AAM99653 Homo SapiensHuman excretory related145 90 polypeptide SEQ ID NO 390.

1057ABB53267 Homo SapiensHuman pol eptide #7. 3372 98 1057AA014449 Homo SapiensProtein of human Zona3367 98 Pellucida 1 (Zzpl).

1057gi972946 Mus musculusZP1 precursor 2216 67 1058gi15779156Homo SapiensSimilar to RIKEN cDNA1858 100 1810073N04 gene 1058gi13097045Mus musculusSimilar to RIKEN cDNA1719 91 1810073N04 gene 1058AAM79693 Homo SapiensHuman protein SEQ 1138 100 ID NO 3339.

1059AAM79993 Homo SapiensHuman protein SEQ 1736 89 ID NO 3639.

1059AAM79009 Homo SapiensHuman protein SEQ 1736 89 ID NO 1671.

1059ABB12000 Homo SapiensHuman prostaglandin 1736 89 DP receptor homolo ue, SEQ ID
N0:2370.

1060AAU79946 Homo SapiensHuman transporter 2907 99 protein sequence.

1060AAE21181 Homo SapiensHuman TRICH-25 protein.2672 91 1060gi2811122Xenopus NaDC-2 1742 54 laevis 1061AAM79483 Homo sapiensHuman protein SEQ 1698 88 ID NO 3129.

1061AAM78499 Homo SapiensHuman protein SEQ 1698 88 ID NO 1161.

1061ABB11938 Homo SapiensHuman cystinosin homologue,1698 88 SEQ
ID N0:2308.

1062gi12656590Danio rerioP2x purinoceptor subunit72 40 1063AAG68335 Homo SapiensHuman CSP2 protein 1354 99 SEQ IDNO:4.

1063gi19525540Homo Sapienslymphocyte effector 1330 98 toxicity activation ligand 1063AAY36071 Homo SapiensExtended human secreted1252 92 protein sequence, SEQ ID NO.
456.

1064gi15277509Homo sapiensSimilar to transmembrane1548 97 superfamily member 1064ABP41089 Homo SapiensHuman ovarian antigen1501 100 HSLGG58, SEQ ID NO:2221.

1064118138238Bos taurus C-14 sterol reductase1376 87 1065AAM93346 Homo SapiensHuman polypeptide, 5017 98 SEQ ID NO:
2891.

1065AAM93761 Homo SapiensHuman polypeptide, 4620 99 SEQ ID NO:
3754.

1065AAB92756 Homo SapiensHuman protein sequence2856 99 SEQ ID

Table 2B
7.4?.
SEQ Hit ID Species Description S
ID scoreIdenti N0:11216.

1066AAE23544 Homo SapiensHuman FAIL protein. 1730 99 1066AAE23554 Homo SapiensHuman FAIL protein 1728 99 #3.

1066AAE23556 Homo sapiensHuman FAIL protein 1726 99 #5.

1067gi18480772Mus musculusolfactoryreceptor 1267 82 1067gi18479346Mus musculusolfactoryreceptor 1193 79 1067AAG72119 Homo SapiensHuman olfactory receptor1043 81 polypeptide, SEQ ID
NO: 1800.

1068ABB89454 Homo sapiensHuman polypeptide 530 95 SEQ ID NO
1830.

1068ABP41764 Homo SapiensHuman ovarian antigen530 95 HE6CR19, SEQ ID N0:2896.

1068AAU04352 Homo SapiensMammalian toxicological530 95 response marker protein #4.

1069AAY33300 Homo SapiensHuman hALIC-2 clone 1572 100 HP53 protein.

1069AAR85206 Homo SapiensHuman ALIC-2. 1572 100 106911381584 Bos taurusactivin receptor type1572 100 I

1070gi16359163Homo SapiensSimilar to RIKEN cDNA1332 94 2310014808 gene 1070gi18043464Mus musculusRIKEN cDNA 23100148081226 77 gene 1070AAB64401 Homo SapiensAmino acid sequence 212 35 of human intracellular signalling molecule INTRA33.

1071AAW60043 Homo SapiensHuman MHC class I 1894 93 chain-related gene A (MICA) polypetide.

1071gi1405893 Homo SapiensMHC class I chain-related1894 93 protein A

1071gi16877353Homo SapiensMHC class I polypeptide-related1838 90 sequence A

1072gi15292437DrosophilaLP10272p 439 39 melanogaster 1072AAB80378 Homo SapiensSecreted protein encoded210 28 by gene #8.

1072AAY87336 Homo SapiensHuman signal peptide 210 28 containing protein HSPP-113 SEQ
ID N0:113.

1073AAB58289 Homo SapiensLung cancer associated2303 86 polypeptide sequence SEQ ID 627.

1073ABB55767 Homo sapiensHuman polypeptide 2163 86 SEQ ID NO 140.

1073AAU39058 Homo SapiensHuman secreted protein2163 86 pe584 2.

1074AAB58289 Homo SapiensLung cancer associated2303 86 polypeptide sequence SEQ ID 627.

1074ABB55767 Homo SapiensHuman polypeptide 2163 86 SEQ ID NO 140.

1074AAU39058 Homo SapiensHuman secreted protein2163 86 pe584 2.

1075AAM93703 Homo SapiensHuman polypeptide, 1061 93 SEQ ID NO:
3632.

1075AAE04780 Homo SapiensHuman vesicle trafficking864 100 protein-23 (VETRP-23) protein.

1075ABB08160 Homo sapiensHuman cytoskeleton-associated758 87 protein (CSAP)-4 (ID:
7472724CD1).

1076ABB06255 Homo SapiensHuman G protein-coupled1511 100 receptor TGR17-6 protein SEQ
ID N0:15.

1076ABB06254 Homo SapiensHuman G protein-coupled1511 100 receptor TGR17-5 protein SEQ
ID N0:13.

1076ABB06252 Homo SapiensHuman G protein-coupled1511 100 receptor TGR17-3 protein SEQ
ID N0:7.

1077AAE16786 Homo SapiensHuman transporter 2679 99 and ion channel-Table 2B

SEQ Hit ID Species Description S

ID scoreIdenti 23 (TRICH-23) protein.

1077ABB08218 Homo SapiensHuman membrane transporter1759 68 protein 57256.

1077AAM3869'7Homo SapiensHuman polypeptide 1249 53 SEQ ID NO

1842.

1078AAB85029 Homo SapiensProtein encoded by 3444 81 BAP28 cDNA

consisting of exons 1 to 45.

1078AAW54099 Homo SapiensHomo sapiens BAP28 2219 88 sequence.

1078AAB92729 Homo SapiensHuman protein sequence1588 92 SEQ ID

N0:11159.

1079ABB07526 Homo SapiensHuman drug metabolizing2580 99 enzyme (DME) (ID: 1962105CD1).

1079AAM93720 Homo SapiensHuman polypeptide, 2331 92 SEQ ID NO:

3669.

1079gi57806 Rattus sp. gamma-glutamyltranspeptidase236 28 (AA

1-568) 1080AAM78536 Homo SapiensHuman protein SEQ 6839 100 ID NO 1198.

1080AAM79520 Homo SapiensHuman protein SEQ 6820 99 ID NO 3166.

1080ABG40303 Homo SapiensHuman peptide encoded2092 100 by genome-derived single exon probe SEQ ID

29968.

1081gi20809440Homo Sapienssterol O-acyltransferase1783 65 (acyl-Coenzyme A: cholesterol acyltransferase) 1 1081gi4878022Homo Sapiensacyl-coenzyme A: cholesterol1779 65 acyltransferase 1081AAW38416 Homo SapiensHuman acyl-coenzyme 1774 65 A:cholesterol acyltransferase I.

1082gi22002433Homo Sapiensp150 target of rapamycin7014 100 (TOR)-scaffold protein containing WD-repeats 1082gi21979456Homosapiensraptor 7014 100 1082gi22002435Mus musculusp150 target of rapamycin6819 96 (TOR)-scaffold protein containing WD-repeats 1083AAY33301 Homo SapiensHuman hALK-3 clone 2647 89 ONFS protein.

1083AAR85207 Homo SapiensHuman ALK-3. 2647 89 1083AAR55368 Homo SapiensHuman Activin receptor-like2647 89 kinase 3 (hALK-3).

1084AAY33301 Homo SapiensHuman hALK-3 clone 1829 92 ONFS protein.

1084AAR85207 Homo SapiensHuman ALK-3. 1829 92 1084AAR55368 Homo sapiensHuman Activin receptor-like1829 92 kinase 3 (hALK-3).

1085AAW90873 Homo SapiensHuman brain-specific 1329 53 dysferlin protein.

1085AAW90868 Homo SapiensHuman dysferlin protein.1329 53 1085AAY82643 Homo SapiensHuman dysferlin protein1329 53 sequence SEQ ID N0:2.

1086gi19343765Mus musculusSimilar to dysferlin 1860 47 1086ABB89615 Homo SapiensHuman polypeptide 1853 47 SEQ ID NO

1991.

1086gi6731235Homo Sapiensmyoferlin 1853 47 1087AAY92321 Homo SapiensHuman alpha-2-delta-D5881 99 calcium channel subunit.

1087AAB62262 Homo SapiensHuman calcium channel5742 99 alpha2delta Table 2B

SEQ Hit ID Species Description ~ S

ID scoreIdenti subunit.

1087AAU01038 Homo SapiensHuman secreted soluble5742 99 alpha2delta calcium channel subunit #18 protein.

1088gi18676422Homo SapiensFLJ00088 rotein 3492 96 1088ABP51380 Homo SapiensHuman MDDT SEQ ID 2083 99 NO 402.

1088gi2104689Mus musculusalpha glucosidase 1987 53 II, alpha subunit 1089AAY01143 Homo SapiensSecreted protein encoded238 100 by gene 9 clone HSIDY06.

1090AAY81261 Homo SapiensHuman DNA structure-specific3683 100 recognition protein 1 (SSRP1).

1090AAW39212 Homo SapiensHuman SSRP1 protein. 3683 100 1090AAR38744 Homo SapiensHuman SSRP. 3683 100 1091gi177814 Homo Sapiensalpha-1-antitrypsin-related1922 90 protein 1091gi15990507Homo SapiensSimilar to serine 1408 66 (or cysteine) proteinase inhibitor, Glade A (alpha-1 antiproteinase, antitrypsin), member 1091AAY26925 Homo SapiensHuman alphal-anti-trypsin1407 66 type Ml protein.

1092gi16877139Homo SapiensSimilar to RIKEN cDNA2273 100 1300019N10 gene 1092AAB56819 Homo SapiensHuman prostate cancer1054 100 antigen protein sequence SEQ
ID N0:1397.

1092AAM95577 Homo SapiensHuman reproductive 627 91 system related antigen SEQ ID NO:
4235.

1093gi18605512Homo SapiensSimilar to CAP-binding1523 100 protein complex interacting protein 2 1093AA006814 Homo sapiensHuman polypeptide 1314 100 SEQ ID NO

20706.

1093AAY57946 Homo SapiensHuman transmembrane 1128 100 protein HTMPN-70.

1094AAM93603 Homo SapiensHuman polypeptide, 2973 99 SEQ ID NO:

3418.

1094gi19571657Caenorhabditissimilar to Yeast YEH4964 41 like protein elegans 1094ABB89291 Homo SapiensHuman polypeptide 590 85 SEQ ID NO

1667.

1095gi4959568Homo Sapiensnuclear pore complex 1650 94 interacting protein NPIP

1095AA017206 Homo SapiensHuman secreted protein1336 79 SEQ ID NO:

105.

1095ABB90262 Homo SapiensHuman polypeptide 872 69 SEQ ID NO

2638.

1096gi18031730Homo SapiensGK006 1405 98 1096AAB92609 Homo SapiensHuman protein sequence1074 99 SEQ ID

N0:10874.

1096AAM40309 Homo SapiensHuman polypeptide 1074 99 SEQ ID NO

3454.

1097AAG03767 Homo SapiensHuman secreted protein,612 90 SEQ ID

NO: 7848.

1097AAB43694 Homo SapiensHuman cancer associated612 90 protein sequence SEQ ID NO:1139.

1097gi285910 Homo SapiensATP synthase subunit 612 90 c precursor 1098gi897827 Homo Sapiensiron-responsive element-binding4968 99 protein/iron regulatory protein 2 Table 2B

SEQ Hit ID Species Description S

ID scoreIdenti 1098AAE19851 Homo SapiensHuman wild-type IRP-24909 99 protein.

1098gi897581 Homo Sapiensiron-regulatory protein4909 99 1099gi3551150 Canine immediate-early protein77 28 herpesvirus 1099gi437051 Acipenser vitellogenin 76 23 transmontanus 1099gi21539886Arabidopsistranscription activator75 26 thaliana 1100AAM84273 Homo sapiensHuman immune/haematopoietic328 92 antigen SEQ ID N0:11866.

1100gi3551150 Canine immediate-early protein77 28 herpesvirus 1100gi535260 PlasmodiumSTARP antigen 76 21 reichenowi 1101gi3551150 Canine immediate-early protein77 28 herpesvirus 1101gi437051 Acipenser vitellogenin 76 23 transmontanus 1101gi535260 PlasmodiumSTARP antigen 75 21 reichenowi 1102AAU12296 Homo SapiensHuman PR07171 polypeptide168 67 sequence.

1102ABB85001 Homo SapiensHuman PR028631 protein90 40 sequence SEQ ID N0:370.

1102ABB95607 Homo SapiensHuman angiogenesis 90 40 related protein PR028631 SEQ ID NO:
370.

1103gi11558264Homo Sapienssphingosine-1-phosphatase2032 89 1103gi13447199Homo Sapienssphingosine-1-phosphate1994 87 phosphatase 1103gi15778670Mus musculussphingosine-1-phosphate1721 76 phosphatase 1104ABB72215 Homo SapiensHuman protein isolated1544 100 from skin cells SEQ ID NO: 331.

1104ABB72150 Homo SapiensHuman protein isolated1544 100 from skin cells SEQ ID NO: 189.

1104ABB84843 Homo SapiensHuman PR0301 protein 1544 100 sequence SEQ ID NO:54.

1105AAG03757 Homo SapiensHuman secreted protein,506 100 SEQ ID

NO: 7838.

1105gi178836 Homo Sapiensapolipoprotein C-II 506 100 11051757915 Homo SapiensapoCII protein 506 100 1106AAU97773 Homo SapiensHuman Fortilin polypeptide.794 97 1106AAR55698 Homo SapiensTumor protein p21. 794 97 1106gi18482460Sus scrofatranslationally controlled794 97 tumor protein 1107gi12082725Mus musculusB cell phosphoinositide3519 84 3-kinase adaptor 1107gi12082723Gallus B cell phosphoinositide2806 69 gallus 3-kinase adaptor 1107gi20987486Homo Sapienssimilar to B cell 1829 97 phosphoinositide kinase adaptor 1108gi21708117Homo Sapienssimilar to hepatocellular318 37 carcinoma-associated antigen HCA557b 1108gi18252514Homo Sapienshepatocellular carcinoma-associated318 37 antigen HCA557b Table 2B

SEQ Hit ID Species Description S
ID scoreIdenti 1108gi20071260Mus musculusRIKEN cDNA 2310038H17306 37 gene 1109gi15076511Homo Sapiensnonmuscle myosin light881 99 chain 2 1109gi13436446Homo Sapiensmyosin regulatory 881 99 light chain 1109gi22137716Mus musculusmyosin regulatory 881 99 light chain 1110gi17391357Homo SapiensFXYD domain-containing390 96 ion transport regulator 1110gi19354238Mus musculusFXYD domain-containing153 45 ion transport re ulator 1110gi4206711Mus musculusphospholemman precursor153 45 1111AAM49040 Homo sapiensHuman testicular development-1486 85 specific protein 10 (NYD-SP10).

1111113272522Homo sapienstranscription factor 1486 85 NYD-spl0 1111gi21040409Homo Sapiensregulatory factor 1486 85 X, 4 (influences HLA class II expression) 1112gi20269720Homo Sapiensneuropilin and tolloid1894 99 like-1 1112gi20269724Mus musculusneuropilin and tolloid1839 96 like-1 1112ABB55774 Homo SapiensHuman olypeptide SEQ 1057 58 ID NO 154.

1113AAB61150 Homo SapiensHuman NOV19 protein. 758 98 1113AAB61149 Homo SapiensHuman NOVl8 protein. 758 98 _ AAY33297 Homo SapiensHuman membrane spanning758 98 1113 protein MSP-4.

1114ABB90021 Homo SapiensHuman polypeptide 476 89 SEQ ID NO
2397.

1114ABB 11874Homo SapiensHuman secreted protein476 89 homologue, SEQ ID N0:2244.

1114AAY94914 Homo SapiensHuman secreted protein476 89 clone pw337_6 protein sequence SEQ ID
N0:34.

1115AAG72407 Homo SapiensHuman OR-like polypeptide1281 100 query sequence, SEQ ID NO:
2088.

1115AAG72267 Homo SapiensHuman olfactory receptor1281 100 polypeptide, SEQ ID
NO: 1948.

1115gi21928991Homo Sapiensseven transmembrane 1274 99 helix receptor 1116AAU80496 Homo SapiensHuman G-coupled receptor1905 98 (GCREC) protein, Seq ID No 4.

1116ABP51568 Homo SapiensHuman G protein coupled1543 98 receptor SEQ ID NO:18.

1116AAU85147 Homo sapiensG-coupled olfactory 1538 100 receptor #8.

1117gi5802817Homo Sapiensenvelope protein 479 77 1117gi3150438Human pol-env 466 77 endogenous retrovirus K

111719558705 Homo Sapiensenvelope 466 77 1118AAE15241 Homo SapiensHuman RNA metabolism 514 100 protein-4 (RMEP-4).

1118ABB89053 Homo SapiensHuman polypeptide 514 100 SEQ ID NO
1429.

1118AAG89341 Homo SapiensHuman secreted protein,501 99 SEQ ID
NO: 461.

1119AAE23979 Homo SapiensHuman LP217 secreted 4563 50 protein.

1119AAB20155 Homo SapiensSecreted protein SECP1.4522 50 1119AAM39295 Homo SapiensHuman polypeptide 4518 50 SEQ ID NO
2440.

1120AAB28199 Homo SapiensHuman HMG-17 non histone429 94 chromosomal protein.

Table 2B

SEQ Hit ID Species Description S
~

ID scoreIdenti 1120gi32329 Homo Sapiensput. HMG-17 protein 429 94 1120gi306864 Homo Sapienshigh mobility group 429 94 protein 17 1121ABP43105 Homo SapiensHuman ovarian antigen456 69 HVCBB19, SEQ ID N0:4237.

1121AAE13797 Homo SapiensHuman lung tumour-specific456 69 protein SALT-T8.

1121AAB44456 Homo SapiensHuman lung tumour-specific456 69 antigen encoded by cDNA #71.

1122AAM93711 Homo SapiensHuman polypeptide, 2974 99 SEQ ID NO:

3650.

1122ABB89767 Homo SapiensHuman polypeptide 2214 97 SEQ ID NO

2143.

1122gi7303971Drosophila 068230-PA 1154 41 melanogaster 1123AAU76036 Homo SapiensHuman sugar transporter-11055 99 (HST-1) protein sequence.

1123AAB60112 Homo SapiensHuman transport protein775 100 TPPT-32.

1123AAB61903 Homo SapiensAtherosclerosis-associated380 48 polypeptide.

1124AA1228120Homo SapiensNI~G2 transmembrane 725 95 protein-D.

1124ABB 11846Homo SapiensHuman integral membrane722 94 protein homolo ue, SEQ ID
N0:2216.

1124gi35063 Homo SapiensType II rote al membrane722 94 protein 1125AAM78418 Homo SapiensHuman protein SEQ 1878 94 ID NO 1080.

1125gi21518639Homo SapiensTSLC1-like 2 1870 97 1125gi19068139Mus musculusmembrane glycoprotein1849 96 1126AAB94738 Homo SapiensHuman protein sequence3079 99 SEQ ID

NO:15776.

1126AAM41695 Homo SapiensHuman polypeptide 2456 99 SEQ ID NO

6626.

1126AAM39909 Homo SapiensHuman polypeptide 1272 100 SEQ ID NO

3054.

1127AAB75594 Homo SapiensHuman secreted protein678 99 sequence encoded by gene 37 SEQ ID

NO:148.

1127AAB80437 Homo SapiensGene #20 associated 381 98 peptide #1.

1127AAM78175 Homo SapiensHuman bone marrow 365 100 expressed probe encoded protein SEQ ID NO:

38481.

1128gi291529 Mouse tegument protein 89 24 cytomegalovirus 1128gi14573798CaenorhabditisC. elegans SItD-60 85 28 protein elegans (corresponding sequence C13B7.3) 1128gi191992 Mus musculusAPC 79 20 1129gi20987535Mus musculusRIKEN cDNA 3300002004741 67 gene 1129gi20799661Mus musculusmucolipin-2 741 67 1129AAB93412 Homo sapiensHuman protein sequence632 55 SEQ ID

N0:12616.

1130gi19354289Mus musculusRIKEN cDNA 2010107623111 42 gene 1130ABB79328 Homo SapiensHuman ovary specific 107 42 protein SEQ

ID N0:125.

1130gi15488920Homo SapiensSimilar to RII~EN 107 42 cDNA

2010107623 gene 1131AAU70675 Homo SapiensHuman otoferlin. 2432 42 Table 2B

SEQ Hit ID Species Description S

ID scoreIdenti 1131gi4588470Homo Sapiensotoferlin 2432 42 1131AAU70673 Homo SapiensHuman otoferlin #2. 2420 42 1132gi20071179Homo Sapiensmonocyte to macrophage1032 77 differentiation-associated 1132gi1006665Homo Sapiensexpression associated1028 77 with monocyte to macrophage differentiation 1132gi18314462Mus musculusmonocyte to macrophage1028 77 differentiation-associated 1133AAU95752 Homo SapiensHuman olfactory and 1522 92 pheromone G

protein-coupled receptor #239.

1133AAU85278 Homo SapiensG-coupled olfactory 1499 91 receptor #139.

1133AAU24658 Homo SapiensHuman olfactory receptor1499 91 AOLFR156.

1134AAE13275 Homo SapiensHuman transporters 1472 80 and ion channels (TRICH)-2.

1134gi17384411Homo SapiensbA251O17.3 (similar 1469 80 to aquaporin 7) 1134AAY70455 Homo SapiensHuman membrane channel1295 73 protein-5 (MECHP-5).

1135ABG42409 Homo SapiensHuman peptide encoded317 100 by genome-derived single exon probe SEQ ID

32074.

1135AAM32826 Homo SapiensPeptide #6863 encoded317 100 by probe for measuring placental gene expression.

1135AAM19638 Homo SapiensPeptide #6072 encoded317 100 by probe for measurin cervical gene expression.

1136AAB47977 Homo SapiensBCYS. 2663 99 1136gi2463632Homo sapiensmonocarboxylate transporter2574 97 homologue MCT6 1136gi21265165Homo Sapienssolute carrier family602 31 (monocarboxylic acid transporters), member 7 1137ABB08456 Homo SapiensHuman tumour specific705 94 antigenic peptide #2.

1137AAU08592 Homo SapiensHuman V-ATPase l6kDa 705 94 subunit.

1137gi14424534Homo SapiensATPase, H+transporting,705 94 lysosomal (vacuolar proton pump) l6kD

1138gi16741167Mus musculusRII~EN cDNA 0610010D201506 87 gene 1138gi15080314Homo SapiensSimilar to RIKEN cDNA514 100 0610010D20 gene 1138gi10580053Halobacteriumdihydrodipicolinate 375 33 synthase; DapA

sp. NRC-1 1139AA014199 Homo SapiensHuman transporter 1425 85 and ion channel TRICH-16.

1139ABB80588 Homo sapiensHuman sbg1020829SGLT 1425 85 protein.

1139AAE06614 Homo SapiensHuman protein having 1425 85 hydrophobic domain, HP03974.

1140ABB90752 Homo SapiensHuman Tumour Endothelial1890 76 Marker polypeptide SEQ ID
NO 236.

1140gi6708478Mus musculusformin-like protein 1559 65 1140gi4101720Mus musculuslymphocyte specific 1532 65 formin related protein 1141AAB94131 Homo SapiensHuman protein sequence996 96 SEQ ID

N0:14389.

1141gi497984 Bostaurus Ac45 317 39 1141AAM93671 Homo SapiensHuman polypeptide, 307 36 SEQ ID NO:

Table 2B

SEQ Hit ID Species Description S

ID scoreIdenti 3556.

1142AAG67137 Homo SapiensAmino acid sequence 2701 96 of a human enzyme.

1142gi21707691Mus musculusRIKEN cDNA 15000020202645 93 ene 1142AAB94358 Homo sapiensHuman protein sequence2579 96 SEQ ID

N0:14883.

1143AAW54370 Homo SapiensG-protein coupled 1815 100 receptor HLTEX11.

1143AAB64854 Homo SapiensHuman secreted protein1792 100 sequence encoded by gene 36 SEQ ID

N0:140.

1143AAB64853 Homo SapiensGene 36 human secreted1792 100 protein homologous amino acid sequence #139.

1144ABB90324 Homo SapiensHuman polypeptide 1321 100 SEQ ID NO

2700.

1144AAU82004 Homo SapiensHuman secreted protein989 78 SECP30.

1144AAM95005 Homo SapiensHuman reproductive 548 85 system related antigen SEQ ID NO:
3663.

1145AAY13458 Homo SapiensAmino acid sequence 3759 100 of human Fe65.

1145gi2734083Homo sapiensstet-like protein 3759 100 1145gi3924936Homo SapiensFe65 protein 3759 100 1146AAB08900 Homo SapiensHuman secreted protein845 90 sequence encoded by gene 10 SEQ ID N0:57.

1146AAY27071 Homo SapiensHuman JWA protein. 845 90 1146AAW75110 Homo SapiensHuman secreted protein845 90 encoded by gene 54 clone HETGL41.

1147AAM93733 Homo sapiensHuman polypeptide, 764 87 SEQ ID N0:

3697.

1147gi2970431Florometra NADH dehydrogenase 91 31 subunit 4 serratissima 1147gi15128604InversidensNADH dehydrogenase 77 29 subunit 4 japanensis 1148AAB93562 Homo SapiensHuman protein sequence2402 100 SEQ ID

N0:12957.

1148gi21626993Drosophila CG15078-PA 990 39 melanogaster 1148gi17945442Drosophila RE18318p 990 39 melanogaster 1149ABB89832 Homo SapiensHuman polypeptide 1640 99 SEQ ID NO

2208.

1149ABB89833 Homo SapiensHuman polypeptide 838 97 SEQ ID NO

2209.

1149gi16359249Mus musculusRII~EN cDNA 1300010M03630 36 gene 1150ABB89832 Homo SapiensHuman polypeptide 1640 99 SEQ ID NO

22os.

1150ABB89833 Homo SapiensHuman polypeptide 838 97 SEQ ID NO

2209.

1150gi16359249Mus musculusRIKEN cDNA 1300010M03564 35 ene 1151ABB78999 Homo SapiensHuman 9-27 protein 569 93 sequence SEQ

ID N0:4483.

115111177476 Homo Sapiensinterferon-inducible 569 93 protein 1151gi12654159Homo Sapiensinterferon induced 569 93 transmembrane protein 1 (9-27) DEMANDE OU BREVET VOLUMINEUX
LA PRESENTE PARTIE DE CETTE DEMANDE OU CE BREVET COMPREND
PLUS D'UN TOME.

NOTE : Pour les tomes additionels, veuillez contacter le Bureau canadien des brevets JUMBO APPLICATIONS/PATENTS
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Claims (26)

WHAT IS CLAIMED IS:

1. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of SEQ ID NO: 1-911.

2. An isolated polynucleotide encoding a polypeptide with biological activity, wherein said polynucleotide hybridizes to the polynucleotide of claim 1 under stringent hybridization conditions.

3. An isolated polynucleotide encoding a polypeptide with biological activity, wherein said polynucleotide has greater than about 99% sequence identity with the polynucleotide of claim 1.

4. The polynucleotide of claim 1 wherein said polynucleotide is DNA.

5. An isolated polynucleotide of claim 1 wherein said polynucleotide comprises the complementary sequences.

6. A vector comprising the polynucleotide of claim 1.

7. An expression vector comprising the polynucleotide of claim 1.

8. A host cell genetically engineered to comprise the polynucleotide of claim 1.

9. A host cell genetically engineered to comprise the polynucleotide of claim operatively associated with a regulatory sequence that modulates expression of the polynucleotide in the host cell.

10. An isolated polypeptide, wherein the polypeptide is selected from the group consisting of:
(a) a polypeptide encoded by any one of the polynucleotides of claim 1;
and (b) a polypeptide encoded by a polynucleotide hybridizing under stringent conditions with any one of SEQ ID NO: 1-911.

11. A composition comprising the polypeptide of claim 10 and a carrier.

12. An antibody directed against the polypeptide of claim 10.

13. A method for detecting the polynucleotide of claim 1 in a sample, comprising:
a) contacting the sample with a compound that binds to and forms a complex with the polynucleotide of claim 1 for a period sufficient to form the complex; and b) detecting the complex, so that if a complex is detected, the polynucleotide of claim 1 is detected.

14. A method for detecting the polynucleotide of claim 1 in a sample, comprising:
a) contacting the sample under stringent hybridization conditions with nucleic acid primers that anneal to the polynucleotide of claim 1 under such conditions;
b) amplifying a product comprising at least a portion of the polynucleotide of claim 1; and c) detecting said product and thereby the polynucleotide of claim 1 in the sample.

15. The method of claim 14, wherein the polynucleotide is an RNA molecule and the method further comprises reverse transcribing an annealed RNA molecule into a cDNA
polynucleotide.

16. A method for detecting the polypeptide of claim 10 in a sample, comprising:
a) contacting the sample with a compound that binds to and forms a complex with the polypeptide under conditions and for a period sufficient to form the complex; and b) detecting formation of the complex, so that if a complex formation is detected, the polypeptide of claim 10 is detected.

17. A method for identifying a compound that binds to the polypeptide of claim 10, comprising:

a) contacting the compound with the polypeptide of claim 10 under conditions sufficient to form a polypeptide/compound complex; and b) detecting the complex, so that if the polypeptide/compound complex is detected, a compound that binds to the polypeptide of claim 10 is identified.

18. A method for identifying a compound that binds to the polypeptide of claim 10, comprising:

a) contacting the compound with the polypeptide of claim 10, in a cell, under conditions sufficient to form a polypeptide/compound complex, wherein the complex drives expression of a reporter gene sequence in the cell; and b) detecting the complex by detecting reporter gene sequence expression, so that if the polypeptide/compound complex is detected, a compound that binds to the polypeptide of claim 10 is identified.

19. A method of producing the polypeptide of claim 10, comprising, a) culturing a host cell comprising a polynucleotide sequence selected from the group consisting of any of the polynucleotides from SEQ ID NO: 1-911, under conditions sufficient to express the polypeptide in said cell; and b) isolating the polypeptide from the cell culture or cells of step (a).

20. An isolated polypeptide comprising an amino acid sequence selected from the group consisting of any one of the polypeptides SEQ ID NO: 912-1822.

21. The polypeptide of claim 20 wherein the polypeptide is provided on a polypeptide array.

22. A collection of polynucleotides, wherein the collection comprising of at least one of SEQ ID NO: 1-911.

23. The collection of claim 22, wherein the collection is provided on a nucleic acid array.

24. The collection of claim 23, wherein the array detects full-matches to any one of the polynucleotides in the collection.

25. The collection of claim 23, wherein the array detects mismatches to any one of the polynucleotides in the collection.

26. The collection of claim 22, wherein the collection is provided in a computer-readable format.