60/322, 511 filed September 13,2001 entitled"Novel Nucleic Acids and Polypeptides", Attorney Docket No. 807, which in turn is a continuation-in-part application of PCT Application Serial No. PCT/US00/35017 filed December 22,2000 entitled"Novel Contigs Obtained from Various Libraries", 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/US01/02623 filed January 25,2001 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/USO 1/03 800 filed February 5,2001 entitled"Novel Contigs Obtained from Various Libraries", Attorney Docket No. 787CIP3/PCT, 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/US01/04927 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/USOI/04941 filed March 5,2001 entitled"Novel Contigs Obtained from Various Libraries", Attorney Docket 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/USO1/08631 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/USO 1/08656 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.

791CIP, 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/US01/14827 filed Mayl6, 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.

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, chemokines, 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 occurring 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 (SBH), 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: 1-336, or 673-873 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: 1-336, or 673-873 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: 1-336, or 673-873. A polynucleotide comprising a nucleotide sequence having at least 90% identity to an identifying sequence of SEQ ID NO: 1-336, or 673-873 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: 1-336, or 673-873. The sequence information can be a segment of any one of SEQ ID NO: 1-336, or 673-873 that uniquely identifies or represents the sequence information of SEQ ID NO: 1-336, or 673-873.

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 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: 1-336, or 673- 873 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 : 1-336, or 673-873 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: 1-336, or 673-873; a polynucleotide comprising any of the full length protein coding sequences of SEQ ID NO: 1-336, or 673-873; and a polynucleotide comprising any of the nucleotide sequences of the mature protein coding sequences of SEQ ID NO: 1-336, or 673-873. 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: 1-336, or 673-873; (b) a nucleotide sequence encoding any one of the amino acid sequences set forth in SEQ ID NO: 1-336, or 673-873; (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 ID NO: 337-672, or 874-1074, or Tables 3,4A, 4B, 5, 6, or 8.

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 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: 1-336, or 673-873; 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 <BR> <BR> 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 <BR> <BR> 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 and the polynucleotides encoding them 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 Table 3); 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 DESCRIPTION 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 trafficking, 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 portion (s) 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 <BR> <BR> 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 <BR> <BR> "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 "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 thymine, G is guanine and 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: 1-336, or 673-873.

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 <BR> <BR> 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 <BR> <BR> elaborated in Sambrook, J. et al. , 1989, Molecular Cloning: A Laboratory Manual, Cold<BR> 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: 1-336, or 673-873. The sequence information can be a segment of any one of SEQ ID NO: 1-336, or 673-873 that uniquely identifies or represents the sequence information of that sequence of SEQ ID NO: 1-336, or 673-873, or those segments identified in Tables 3,4A, 4B, 5,6, or 8. 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 420 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 five 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 (1-425) 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 leader/signal 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, e 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 <BR> <BR> another amino acid having similar structural and/or chemical properties, i. e. , conservative<BR> 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 glutamin ; 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 <BR> <BR> 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. <BR> <BR> <P>The term"recombinant, "when used herein to refer to a polypeptide or protein, means<BR> that a polypeptide or protein is derived from recombinant (e. g. , microbial, insect, or<BR> mammalian) expression systems. "Microbial"refers to recombinant polypeptides or proteins<BR> 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.

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 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

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 <BR> <BR> when it is expressed in a suitable host cell. "Secreted"proteins include without limitation<BR> proteins secreted wholly (e. g. , soluble proteins) or partially (e. g., receptors) from the cell in<BR> which they are expressed. "Secreted"proteins also include without limitation proteins that<BR> 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 0. 1X SSC/0. 1% SDS at 68°C), and moderately stringent <BR> <BR> 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 <BR> <BR> 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 (Hein, 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: 1-336, or 673-873; a polynucleotide encoding any one of the peptide sequences of SEQ ID NO: 1-336, or 673-873; and a polynucleotide comprising the nucleotide sequence encoding the mature protein coding sequence of the polynucleotides of any one of SEQ ID NO: 1-336, or 673-873. 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: 1-336, or 673-873; (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: 337-672, or 874-1074 (for example, as set forth in Tables 3,4A, 4B, 5,6, or 8). 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 genomic DNA that corresponds to any of the polynucleotides of SEQ ID NO: 1-336, or 673-873 can be obtained by screening appropriate cDNA or genomic DNA libraries under suitable hybridization conditions using any of the polynucleotides of SEQ ID NO: 1-336, or 673-873 or a portion thereof as a probe. Alternatively, the polynucleotides of SEQ ID NO: 1-336, or 673-873 may be used as the basis for suitable primer (s) 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: 1-336, or 673-873, 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- 336, or 673-873, a representative fragment thereof, or a nucleotide sequence at least 90% identical, preferably 95% identical, to SEQ ID NO: 1-336, or 673-873 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 for 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: 1-336, or 673-873 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 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.

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 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, primer (s) 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., Gene 34: 315 (1985); and other mutagenesis techniques <BR> <BR> well known in the art, such as, for example, the techniques in Sambrook et al. , supra, and Current Protocols in 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. The 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: 1-336, or 673-873, 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: 1-336, or 673-873 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: 1-336, or 673- 873 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, pNH8a, pNH16a, pNH18a, pNH46a (Stratagene), pTrc99A, pKK223-3, pKK233-3, pDR540, pRIT5 (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, Methods in Enzymology 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 lacl, lacZ, T3, T7, gpt, lambda PR, and trc. Eukaryotic promoters include CMV immediate early, HSV thymidine 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 TRP1 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 3- 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 typhimurium and various species within the genera Pseudomonas, Streptomyces, 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, pKK223-3 (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 <BR> <BR> 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 intra-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: 1-336, or 673-873, 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: 1-336, or 673-873 or antisense nucleic acids complementary to a nucleic acid sequence of SEQ ID NO : 1-336, or 673-873 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 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., SEQ ID NO: 1-336, or 673-873, 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 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 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 between 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-mannosylqueosine, 5'-methoxycarboxymethyluracil, 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 <BR> <BR> 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 a-anomeric nucleic acid molecule. An a-anomeric nucleic acid molecule forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual a-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 (Inoue et al. (1987) Nucleic Acids Res 15: 6131-6148) or a chimeric RNA-DNA analogue (Inoue et al. (1987) FEBS Lett 215 : 327-330).

4.4 RIBOZYMES AND PNA MOIETIES In still another embodiment, an antisense nucleic acid of the invention is a ribozyme.

Ribozymes 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) Nature 334: 585-591)) can be used to catalytically cleave mRNA 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: 1-336, or 673-873). For example, a derivative of Tetrahymena L-19 IVS RNA can be constructed in which the nucleotide sequence of the <BR> <BR> 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) AnticancerDrugDes. 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) Bioorg Med Chem 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 <BR> <BR> of gene expression by, e. g. , inducing transcription or translation arrest or inhibiting<BR> replication. PNAs of the invention can also be used, e. g. , in the analysis of single base pair<BR> 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) Bioorg Med Chem Lett 5: 1119-11124.

In other embodiments, the oligonucleotide may include other appended groups such as peptides (e. g. , for targeting host cell receptors in vivo), or agents facilitating transport<BR> 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 barrier (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, BioTechniques 6: 958-976) or intercalating agents. (See, e. g., Zon, 1988, Pharm. 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 <BR> <BR> (Davis, L. et al., Basic Methods in 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 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 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 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 of monkey kidney fibroblasts, described by Gluzman, Cell 23: 175 (1981). Other cell lines capable of expressing a compatible vector are, for example, the C127, monkey COS cells, Chinese Hamster Ovary (CHO) cells, human kidney 293 cells, human epidermal A431 cells, human Colo205 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, HeLa cells, mouse L cells, BHK, HL-60, U937, 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, and polyadenylation sites may be used to provide the required nontranscribed genetic elements. Recombinant 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 Saccharomyces cerevisiae, Schizosaccharomyces pombe, Kluyveromyces strains, Candida, or any yeast strain capable of expressing heterologous proteins. Potentially suitable bacterial strains include Escherichia coli, Bacillus subtilis, Salmonella typhimurium, 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 (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/US90/06436 (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: 337- 672, or 874-1074 or an amino acid sequence encoded by any one of the nucleotide sequences SEQ ID NO: 1-336, or 673-873 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: 1-336, or 673-873 or (b) polynucleotides encoding any one of the amino acid sequences set forth as SEQ ID NO: 337-672, or 874- 1074 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: 337-672, or 874-1074 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: 337-672, or 874-1074.

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. Chem. Soc. 114,9245-9253 (1992), both of which are incorporated herein by reference. Such fragments may 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 3,4A, 4B, 5,6, or 8.

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 may further comprise an acceptable carrier, 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 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, Protein<BR> Purification : Principles and Practice, Springer-Verlag (1994); Sambrook, et al. , in Molecular Cloning: A Laboratory Manual ; Ausubel et al., Current Protocols in Molecular 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.

The purified polypeptides can be used in in 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 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.

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 cell by the specificity of the binding molecule for SEQ ID NO: 337-672, or 874-1074.

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.

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 acid (s) 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 baculovirus/insect cell expression systems are commercially available in kit form from, e. g., Invitrogen, San Diego, Calif., U. S. A. (the MaxBatT 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-toyopearlT or Cibacrom blue 3GA Sepharose ; 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 may 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 or more 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,<BR> 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 Vu. l 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. expasy. ch/sprot). Predictions are based upon the maximum likelihood estimation.

Pesence of transmembrane region (s) was detected using the TMpred program (http ://www. ch. embnet. org/software/TMPRED form. html).

. The BLAST programs are publicly available from the National Center for <BR> <BR> Biotechnology Information (NCBI) and other sources (BLAST Manual, Altschul, S. , et al.<BR> <P>NCBI NLM NIH Bethesda, MD 20894; Altschul, S. , et al. , J. Mol. Biol. 215: 403-410 (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 fusion 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 <BR> <BR> both the treatment of proliferative and differentiative disorders, e. g. , cancer as well as<BR> 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 <BR> <BR> 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 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 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 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, in situ, or in vivo by use of vectors, and more particularly viral vectors (e. g. , adenovirus, adeno-associated virus, or a retrovirus), or ex vivo<BR> 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: 1275-1281 (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 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 in vivo for therapeutic purposes. Alternatively, it is contemplated that in other 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 in 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 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 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/US90/06436 (W091/06667) by Skoultchi et al. , each of which is incorporated by reference herein in its entirety.

4.9 TRANSGENIC ANIMALS 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 referenee.

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 in 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 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 <BR> <BR> 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 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.

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 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 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 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), 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 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 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.<BR> <P>Fritsch and T. Maniatis eds. , 1989, and"Methods in Enzymology: Guide to Molecular<BR> Cloning Techniques", Academic Press, Berger, 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-or cell lines including, without limitation, 32D, DA2, DA1G, T10, B9, B9/11, BaF3, MC9/G, M+ (preB M+), 2E8, RB5, 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 thymocyte 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, 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 ; Bertagnolli et al., J. Immunol. 145: 1706-1712,1990 ; Bertagnolli et al., Cellular Immunology 133: 327-341,1991 ; Bertagnolli, et al., 1. 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, Bottomly, 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<BR> Interleukin l l--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 in 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 (TPO), 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 <BR> <BR> cardiomyocytes (Wobus et al., Differentiation, 48: 173-182, (1991); Klug et al. , J. Clin.<BR> <P>Invest. , 98 (1) : 216-224, (1998) ) or skeletal muscle cells (Browder, L. W. In: Principles of<BR> Tissue Engineering 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.

In vitro cultures of stem cells can be used to determine if the polypeptide of the 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

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 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 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 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 with transplantation, including, without limitation, aplastic anemia and paroxysmal nocturnal hemoglobinuria), as well as in repopulating the stem cell compartment post irradiation/chemotherapy, either in-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. 1. Freshney, et al. eds. Vol pp. 265-268, Wiley-Liss, Inc. , New York, N. Y. 1994;<BR> Hirayama et al. , Proc. Natl. Acad. Sci. USA 89: 5907-5911,1992 ; Primitive hematopoietic colony forming cells with high proliferative potential, McNiece, 1. 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<BR> bone marrow cultures in the presence of stromal cells, Spooncer, E. , Dexter, M. and Allen, T. In Culture of Hematopoietic Cells. R. 1. 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. 1. 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 of bone 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/ligament-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 vivo for return in 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. W095/16035 (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. 1. and Rovee, D. T. , eds.),<BR> Year Book Medical Publishers, Inc. , Chicago, as modified by Eaglstein and Mertz, J. Invest.

Dermatol 71: 382-84 (1978).

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 immunodeficiency (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 autoimmune 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<BR> prick test (Hoffmann et al. , Allergy 54: 446-54,1999), guinea pig skin sensitization test<BR> (Vohr et al. , Arch. Toxocol. 73: 501-9), and murine local lymph node assay (Kimber 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 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 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 <BR> <BR> 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 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 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 <BR> <BR> 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, murine 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 efficacy 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 murine experimental autoimmune encephalitis, systemic lupus erythmatosis in MRL/lpr/lpr mice or NZB hybrid mice, murine autoimmune collagen arthritis, diabetes mellitus in NOD mice and BB rats, and murine 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 ß2 microglobulin protein or an MHC class II alpha chain protein and an MHC class 11 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 sufficient 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); Herrmann 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 ;<BR> 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<BR> 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<BR> et al. , Cellular Immunology 155: 111-122,1994 ; Galy et al. , Blood 85: 2770-2778,1995 ;<BR> 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<BR> 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.

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

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 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 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. Kruisbeek, D. H. Marguiles, E. M. Shevach, W. Strober, Pub. Greene 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.

4.10. 10 HEMOSTATIC 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 thrombolytic 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 Karposi's sarcoma.

Polypeptides, polynucleotides, or modulators of polypeptides of the invention

(including inhibitors and simulators 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 HCI (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-2a, Interferon Alpha-2b, Leuprolide acetate (LHRH-releasing factor analog), Lomustine, Mechlorethamine HCI (nitrogen mustard), Melphalan, Mercaptopurine, Mesna, Methotrexate (MTX), Mitomycin, Mitoxantrone HCI, 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.

In vitro models can be used to determine the effective doses of the polypeptide of the invention as a potential cancer treatment. These in 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 (1997), 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.<BR> <P>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 of polypeptides 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.

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 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 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 Myers, Curr. Opin. Biotechnol. 8: 701-707 (1997). For reviews and examples of peptidomimetic libraries, see Al-Obeidi et al., Mol. Biotechnol, 9 (3): 205-23 (1998) ; Hruby et al., Curr Opin Chem Biol, 1 (1) : 114-19 (1997); Dorner et al., BioorgMed Chem, 4 (5): 709-15 (1996) (alkylated dipeptides).

Identification of modulators through use of the various libraries described herein 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.

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, myeloblastic, 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 B12 deficiency, folic acid deficiency, Wernicke disease, tobacco-alcohol amblyopia, Marchiafava-Bignami disease (primary degeneration of the corpus callosum), and alcoholic cerebella 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 in 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, etc., depending on the molecule to be measured; and motor neuron dysfunction may be measured by assessing the physical manifestation of motor <BR> <BR> 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, 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; 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 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 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 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 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.<BR> <P>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 pg/kg to 100 mg/kg of body weight, with the preferred dose being about 0. 1 llg/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-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-14, IL-15, IFN, TNF0, 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-ß), 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, lymphokine, 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 <BR> <BR> (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 multimeric 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 <BR> <BR> 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 <BR> <BR> 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), thrombolytic 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

fibrotic tissue, often in a depot or sustained release formulation. In order to prevent the scarring process frequently occurring 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 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 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.

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 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 permeated 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-fit 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, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol the dosage unit may be determined <BR> <BR> 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 <BR> <BR> formulated for parenteral administration by injection, e. g. , by bolus injection or continuous<BR> 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: 5W) 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 carriers or excipients. Examples of such carriers 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 form of a complex of the protein (s) or other active ingredient (s) 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 antigen (s) 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,

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 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 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 ßg to about 100 mg (preferably about 0.1 zg to about 10 mg, more preferably about 0.1 Fg 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 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 polyanhydrides.

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, poly (ethylene glycol), polyoxyethylene oxide, carboxyvinyl polymer and poly (vinyl 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-ß), 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, the 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 IC50 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 used 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 LD50 (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 LD50 and ED50. 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 <BR> <BR> condition. See, e. g., Fingl et al. , 1975, in"The Pharmacological Basis of Therapeutics", Ch.

1 p. 1. 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 in vitro 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 pLg/kg 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 be 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 immunoglobulin 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 F (ab) 2 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 IgG,, 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.

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 immunospecifically 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 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: 337-672, or 874-1074, or Tables 3,4A, 4B, 5,6, or 8, or 9, 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.

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.

In certain embodiments of the invention, at least one epitope encompassed by the 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 generated by any method well known in the art, including, for example, the Kyte 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 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 in vitro, in 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., Blackwell 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 in vitro, in vivo, and in. 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 affinity 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 immunoaffinity 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 (Kozbor, 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 <BR> <BR> 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 <BR> <BR> 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 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 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 ANTIBODIES 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') Z 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,<BR> 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 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<BR> (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 antibodies" herein. Human monoclonal antibodies can be prepared by the trioma technique; the human B-cell hybridoma technique (see Kozbor, et al. , 1983 Immunol Today 4: 72) and the EBV<BR> hybridoma technique to produce human monoclonal antibodies (see Cole, et al. , 1985 In:<BR> 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) ;<BR> Marks et al. , J. Mol. Biol. , 222: 581 (1991) ). Similarly, human antibodies can be made by<BR> 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<BR> (1994) ); Fishwild et al, (Nature Biotechnology 14,845-51 (1996) ); Neuberger (Nature<BR> Biotechnology 14,826 (1996) ); and Lonberg and Huszar (Intern. Rev. Immunol. 13,65-93<BR> (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 XenomouseTM 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 FAB 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 immunoglobulin 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 chain (s) 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') 2 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') 2 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) 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.

Various techniques for making and isolating bispecific antibody fragments directly from recombinant cell culture have also been described. For example, bispecific antibodies have been produced using leucine zippers. Kostelny et al., J. Immunol. 148 (5), 1547-1553 (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 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 bispecific antibody fragments. The fragments comprise a heavy-chain variable domain (VH) connected to a 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 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 arm 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 (FcyR), such as FcyRI (CD64), FcyRII (CD32) and FcyRIII (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 bispecific 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 residue (s) 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 Wolf 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 immunoconjugates 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 2l2Bi, 13 3lIn, 90Y, and l86Re.

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 (MX-DTPA) is an exemplary cheating 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: 1-336, or 673-873 or a representative fragment thereof ; or a nucleotide sequence at least 95% identical to any of the nucleotide sequences of SEQ ID NO: 1-336, or 673-873 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))<BR> 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), BLASTN 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 sequence (s) 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. I (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. Specifically, 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 ASSAYS 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: 1-336, or 673-873, 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 activity/expression.

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<BR> Guide, W. H. Freeman, NY (1992), pp. 289-307, and Kaspczak 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 sulfhydryl 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<BR> 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: 1-336, or 673-873. 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: 1-336, or 673-873 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 in vitro by means of the addition of the appropriate RNA polymerase as T7 or SP6 RNA polymerase 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 in 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: 1981 f). 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, carrier 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 (Keller 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 terminus 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/pl) 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-MeIm7), is then added to a final concentration of 10 mM I-MeIm7.

A ss DNA solution is then dispensed into CovaLink NH strips (75 pLI/well) standing on ice.

Carbodiimide 0.2 M I-ethyl-3- (3-dimethylaminopropyl)-carbodiimide (EDC), dissolved in 10 mM 1-MeIm7, is made fresh and 25 1 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; <BR> <BR> 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 <BR> <BR> 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. Nat'l. 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-acyl-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 Sambrook 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 pUC19 (2688 base pairs). Fitzgerald et al. (1992) quantitatively evaluated the randomness of this fragmentation strategy, using a CviJI** digest of pUC19 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 ig 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 EXAMPLES 5.1 EXAMPLE 1 Novel Nucleic Acid Sequences 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 Contigs The contigs of the present invention, designated as SEQ ID NO: 673-873 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 <BR> <BR> 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 SEQ ID NO: 1-336 were assembled from Hyseq's proprietary EST sequences as described in Example 1 and human genome sequences that are available from the public databases (http : //www. ncbi. nlm. nih. gov/).

Exons were predicted from human genome sequences using GenScan (http ://genes. mit. edu/GENSCANinfo. html) ; HMMgene (http : //www. cbs. dtu. dk/services/HMMgene/hmmgenel l. html), and GenMark. hmm (http ://genemark. biology. gatech. edu/GeneMark/whmm info. html). The Hyseq proprietary EST sequences and the predicted exons were assembled based on a BLASTN hit to the extending assemblage with BLAST score greater than 300 and percent identity greater than 95%. Then, the predicted genes were analyzed using Neural Network SignalP V 1. 1 program (from Center for Biological Sequence Analysis, The Technical University of Denmark) for presence of a signal peptide. These sequences were further analyzed for presence of transmembrane region (s) using the TMpred program (http :/www. ch. embnet. org/software/TMPR. ED fonn. htm)).

Table I shows the various tissue sources of SEQ ID NO: 1-336.

The homologs for polypeptides SEQ ID NO: 337-672, that correspond to nucleotide sequences SEQ ID NO: 1-336 were obtained by a BLASTP search against Genpept release 124 and Geneseq (Derwent) release 200117 and against Genpept release 129 and Geneseq (Derwent) release (July 18,2002). The results showing homologues for SEQ ID NO: 337- 672 from Genpept 124 are shown in Table 2A. The results showing homologues for SEQ ID NO: 337-672 from Genpept 129 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.

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 as described in United States priority application serial number 60/322,511, filed September 13, 2001, herein incorporated by reference in its entirety. 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 7.2.

Further description of the Pfam models can be found at http ://pfam. 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: 1-336 (i. e. SEQ ID NO: 337-672). 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<BR> (HTM) (Molecular Simulations Inc. (MSI) San Diego, CA, ) which is an automated sequence and structure searching procedure (http://www. msi. com/), and (3) SeqFold'M 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. org/PDB/) ; start and end amino acid position of the protein sequence aligned; PSI-BLAST score, the verify score, the SeqFold score, and the Potential (s) of Mean Force (PMF). The verify score is produced by GeneAtlaslM 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 V 1. 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 each of SEQ ID NO: 1-336 to a specific chromosomal location.

Table 8 shows the number of transmembrane regions, their location (s), and TMPred score obtained, for each of the SEQ ID NO: 337-672 that had a TMPred score of 800 or greater, using the TMpred program (http://www. ch. embnet. org/software/TMPRED form. html).

Table 9 is a correlation table of the novel polynucleotide sequences SEQ ID NO: 1- 336, their corresponding polypeptide sequences SEQ ID NO: 337-672, their corresponding priority nucleotide sequences SEQ ID NO: 673-873, their corresponding priority polypeptide sequences SEQ ID NO: 874-1074, and the US serial number of the priority application in which the sequence was filed.

Table 10 is a correlation table of the novel polynucleotide sequences SEQ ID NO: I- 336, the novel polypeptide sequences SEQ ID NO: 337-672, and the corresponding SEQ ID NO in which the sequence was filed in priority US application bearing serial number 60/322, 511, filed September 13,2001.

Table 1 Tissue Origin Library/RNA Source HYSEQ Library Name SEQ ID NOS : adrenal gland Clontech ADR002 25 29 72 79 176 220 233 246 270 285 287 298- 299 306 adult bladder Invitrogen BLD001 317 321 331 adult brain Clontech ABR001 29 176 207 211 288 306 332 adult brain Clontech ABR006 3 35 49 59 62 69 71 73- 74 96 98-99 101-102 108 111 129 161-166 168-172 185-186 196 201 211 283 316 321 adult brain Clontech ABR008 13 15-20 24 43 57-59 63 65 74 83 96 105 108 125 129 135 158 162 193 201 207 218-219 248- 249 261 263 274 278 285 289-292 294-297 312-313 316-317 321- 324330332 adultbrain GIBCO AB3001 78 123 134 182265318 adult brain GIBCO ABD003 9-10 24 64-65 102 108 119 145 149 182 211 253 263 265 296 318 adult brain Invitrogen ABR014 207 248 318 adult brain Invitrogen ABRO15 296318 adult brain Invitrogen ABR016 228 296 adult brain Invitrogen ABT004 4 72 81 193 196 207 274-275 295 306-307 adult cervix BioChain Cox001 22 24 69 72 75 83 102 111 149 185 265 278 287 291 303 306 318 331 adult colon Invitrogen CLN001 144 175 182-183 245 adult heart GIBCO AHR001 13 16 23-24 31 34 57 65 71 96 185 195 236 257 265-266 277 306-307 318 321 326 336 adult kidney GIBCO AKD001 12 45 57 65 72 83 106 149 175 178 182 202 205 207 234 265 278 285-287 300 307 318 326 adult kidney Invitrogen AKT002 10 25 29 65 72 82-83 l l9 142 166 175-176 205 211 224 236 270 272 278 287 326 adult liver Clontech ALV003 222 adult liver Invitrogen ALV002 21 44 46 49 65 72 83 130 149 182 197 234 240 277 308 adult lung GIBCO ALG001 10 234 adult ovary Invitrogen AOV001 4 10 25 29 37 46 65 70 72 124 129 131142 149- 150 154 156 176 178 188 206-207 211 219 230 245 265 270 276- 278 283-284 287 318 Table I Tissue Origin Library/RNA Source HYSEQ Library Name SEQ ID NOS : 321 adult placenta Clontech APL001 129 194 318 adult spleen Clontech SPLc01 13 46 69 143 152 179 300 317 adult spleen GIBCO ASP001 46 79 182 207 317-318 adult testis GIBCO ATS001 167 236 269 318 bone marrow Clontech BMD001 6 56 69 78 129 267 277- 279 282 304 315 318 bone marrow GF BMD002 1 6 13 39-40 48-49 60 91-94 102-103 136 143 234 236 277-279 285 291 297 330 336 cultured preadipocytes Stratagene ADP001 41-43 182 275 277 314 326 endothelial cells Stratagene EDT001 10 25 49 72 105 110 130 206-207 236 270 272 277-278 310 312 8- 319 fetal brain Clontech FBR001 164 185 fetal brain Clontech FBR004 184-185 fetal brain Clontech FBR006 6 13 15 46 49 61-63 72 83 96 100 102 107-108 110 135 146 162 186- 188 190-194 203 207 219 224 236 262 274 284 291 303 316 323 331-334 fetal brain GIBCO HFB001 43 47 64 71-72 100 1 12 130 154 178 182 189 236 245 265 277 293 296 318 fetal brain Invitrogen FBT002 47 49 72 207 276 287 291 fetal heart Invitrogen FHR001 6 17 19 31 49 108 113- 114 126-128 142 177 182 201 207 243 279 284 300 316 fetal kidney Clontech FKD001 5 25 270 fetal kidney Clontech FKD002 13 70 96 115-116 136 138 164 193 201 205 292 317 324 fetal liver Clontech FLV002 17 222 292 326 fetal liver Clontech FLV004 1 49 96 117 137-138 186 222 236 239 263 303 324 fetal liver Invitrogen FLV001 72 207 233 273 310 331 fetal liver-spleen Columbia University FLS001 10 13 25 31-32 43 67 69 80 83-85 89 111 123- 124 129-130 132 150 186 201 207 222 245 254 257 270-272 277- 279 281 287 302-303 306 314 318 fetal liver-spleen Columbia University FLS002 12 25 32-33 35-36 43 46 48-49 65 69 72 77 83-84 124 129-131 142 148 174 198 206-207 222 Table 1 Tissue Origin Library/RNA Source HYSEQ Library Name SEQ ID NOS : 229 231 239 244-245 254 257 270 272 277 279 302 314 318 327 fetal liver-spleen Columbia University FLS003 31-32 46 70 87-88 90 123 132-133 142 222 fetal lung Clontech FLGOOI 4 112 fetal lung Invitrogen FLG003 30 335-336 fetal muscle Invitrogen FMSOOI 72 182 207 236 310 fetal muscle Invitrogen FMS002 46 57 104-106 139-140 236 318 fetal skin Invitrogen FSKOOI 2 17 30 43 65-66 125 166 172 182 207 236 255 300 314 fetal skin Invitrogen FSK002 8 13 17 19 43 49 57 75- 76 108 118-120 141-144 146-148 177 186 236 255 297 324 326 331 fibroblast Stratagene LFBOO] 318 induced neuron-cells Stratagene NTDOO1 185 236 283 infant brain Columbia University IB2002 8-10 43 65 71 152 157 162 182 189 211 248 263 280 285 309 328 infant brain Columbia University IB2003 21 47 153-155 157-158 169 185 188 211 268 278 306 309 314 infant brain Columbia University IBM002 182 331 infant brain Columbia University IBSOOI 72 211 268 278 leukocyte Clontech LUC003 149 221 leukocyte GIBCO LUC001 I 1 1 49 68 96 149 176 182 189 223 232 236 245 273 278-279 287 291 314 318 325-326 331 lung 318 lung tumor Invitrogen LGT002 21 24-28 46 49 72 89 175 193 200 205-207 223 236 241 245 256 277 292 294 307 310- 312 314 318 326 329 Iymph node Clontech ALNOO 1 169 263 318 lymphocytes ATCC LPCOO1 1937496877 123 143 149-151 189 207 260 263 278 325 330-331 macrophage Invitrogen HMPOOI 202 251 mammarygland Invitrogen MMGOOI 21 6783 125 131 174 182 193 205 211 223 234 238 263 265 277 287 300-302 313-314 318 321 melanoma from-cell-line-Clontech MEL004 7 203-204 207 287 ATCC-#CRL-1424 *Mixture of 16 tissues-Various Vendors CGdO10 227 mRNA *Mixture of 16 tissues-Various Vendors CGdOl l 124 182 302 mRNA *Mixture of 16 tissues-Various Vendors CGdO12 14 17 32 42 107 119 124 MARNA 146 162 206 228-230 Table 1 Tissue Origin Library/RNA Source HYSEQ Library Name SEQ ID NOS : 236 239-244 246-247 256 265 272 302 *Mixture of 16 tissues-Various Vendors CGdO 13 18 229-230 311 mRNA *Mixture of 16 tissues-Various Vendors CGdO15 32 231 252-253 272 307 MARNA 310 *Mixture of 16 tissues-Various Vendors Cd016 25 39 161 178 236 248- mRNA 250 neuronal cells Stratagene NTUOO1 174 207 pituitary gland Clontech PIT004 180 207 236 283 291 placenta Clontech PLA003 19 96 119 121-122 143 148 161 255 placenta Invitrogen APL002 207314 prostate Clontech PRTOOI 131 136 149 181 292 307 327 rectum. Invitrogen RECOO1 338 131 166 182324 retinoic acid-induced-Stratagene NTROOI 11 1 130 173 207 287 neuronal-cells salivary gland Clontech SALOOI 130 skeletal muscle Clontech SKMOOI 10 188 small intestine Clontech SINOOI 10 49 59 70 86 94-96 102 l l9 159-160 i64 183 189 268 272 300 303 307 318 spinal cord Clontech SPCOOI 4 29 43 65 79 83 106 149 158 172 176-177 189211 265324 stomach Clontech STO001 10 292 thalamus Clontech THA002 13 245 278 295 314 thymus Clontech THMOOI 4-5 149 258 302 325 thymus Clontech THMc02 6 13-14 25 96 125 151- 152 211 221 243 258 270 303 306 314 317 325 330-331 thyroid g) and Oontech THROO) 25 65 75 108 149 172 182 189 193 236 270 291 303 305-306 312 320 324 326 trachea Clontech TRCOO I 1 142 297 303 317 umbilical cord BioChain FUCOO1 24 31 70 130 193 207 257 300 318 332 uterus Clontech UTROO 1 29 149 185 207 236 young liver GIBCO ALVOOI 182 314 331 *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), I I) Human thymus mRNA (Clontech), 12) human lymph node mRNA (Clontech), 13) human so\spinal cord mRNA (Clontech), 14) human thyroid mRNA (Clontech), 15) human esophagus mRNA (BioChain), 16) human conceptional umbilical cord mRNA (BioChain).

Table 2A SEQ Accession No. Species Description Score % ID Identity NO : 337 gil2580867 Picea abies 60S ribosomal protein L13E 83 33 337 gi3127821 Drosophila Sex-Peptide 66 41 subobscura 337 gi3549864 Drosophila Sex-peptide 66 41 subobscura 338 AAY57951 Homo sapiens Human transmembrane protein 77 33 HTMPN-75. 338 gi642017 Hordeum vulgare phospholipid transfer protein 72 30 precursor 338 gi 11037708 Triticum aestivum lipid transfer protein precursor 72 34 339 AAY20852 Homo sapiens Human neurofilament-H mutant 108 38 protein fragment 11. 339 gi 1888411 Homo sapiens mRNA encoding chimaeric 80 30 transcript of collagen type I alpha I and platelet derived growth factor beta, 314 bp. 339 AAW18664 Homo sapiens Fragmented human NF-H gene 100 38 +I frameshift mutant product. 340 AAB08912 Homo sapiens Human secreted protein 251 100 sequence encoded by gene 22 SEQ ID NO : 69. 340 gi12248917 Homo sapiens mRNA for spinesin, complete 251 100 cds. 340 AAB 11699 Homo sapiens Human serine protease BSSP2 251 100 (hBSSP2), SEQ ID NO : 10. 341 gi 13990776 Gallus gallus immunoglobulin lambda chain 67 43 341. gi1086714 Caenorhabditis coded for by C. elegans cDNA 55 45 elegans yk74c8. 5 ; Similar to small type- 11 membrane antigen 341 gil469906 Gallus gallus beta-1, 4-galactosyltransferase 56 46 342 AAY 17526 Homo sapiens Human secreted protein clone 1 131 100 AM349 2 protein. 342 AAY02361 Homo sapiens Polypeptide identified by the 1131 100 signal sequence trap method. 342 AAW52834 Homo sapiens Secreted protein encoded by 664 100 clone AM349 2. 343 gi5579130 Hepatitis E virus non-structural polyprotein 71 37 343 gi330005 Hepatitis E virus poly-proline hinge 58 35 343 gi7768740 Homo sapiens genomic DNA, chromosome 82 29 21 q, section 89/105. 344 AAY86234 Homo sapiens Human secreted protein 476 60 HNTNC20, SEQ ID NO : 149. 344 AAB24074 Homo sapiens Human PRO1153 protein 111 46 sequence SEQ ID NO : 49. 344 AAY66735 Homo sapiens Membrane-bound protein 111 46 PROI 153. 345 gi 12836893 Gallus gallus IPR328-like protein 165 30 345 gi 13357180 Homo sapiens calcium channel gamma subunit 125 28 8 (CACNG8) mRNA, partial cds. 345 gi4558766 Homo sapiens neuronal voltage gated calcium 158 30 channel gamma-3 subunit mRNA, complete cds. 346 AAY79384 Homo sapiens Human G protein coupled 396 100 Table 2A SEQ Accession No. Species Description Score % ID Identity NO : receptor SLGP 7 transmembrane region. 346 gi 225483Homo sapiens ETL protein (ETL) mRNA, 396 100 complete cds. 346 AAB61144 Homo sapiens Human NOV14 protein. 396 100 347 gil 3195147 Mus musculus HCH 209 77 347 gil339910 Homo sapiens Human DOCK180 protein 95 43 mRNA, complete cds. 347 AAW03515 Homo sapiens Human DOCK 180 protein. 95 43 348 gil0176829 Arabidopsisthaliana gene id : MBB18. 16~ 79 32 349 gi 10438431 Homo sapiens cDNA : FLJ22155 fis, clone 518 34 H RC00205. 349 gi 10437336 Homo sapiens cDNA : FLJ21267 fis, clone 506 36 COL01717. 349 AAY07754 Homo sapiens Human secreted protein 291 37 fragment encoded from gene 11. 350 grils52496 Homo sapiens Human germline T-cell receptor 614 100 beta chain Dopamine-beta- hydroxylase-like, TRY1, TRY2, TRY3, TCRBV27S I P, TCRBV22S I A2N I T, TCRBV9S I A 1 T, TCRBV7S 1 A 1 N2T, TCRB V5 S 1 A 1 T, TC RBV 13 S3, TCRBV6S7P, TCRBV7S3A2T, TCRBV13S2AIT, TCRBV9S2A2PT, TCRBV7S2A I N4T, TCRBV13S9/13S2AIT, TCRBV6SSAINI, TCRBV30S I P, TCRBV31 S 1, TCRBV 13S5, TCRBV6SlAlNl, TCRBV32S I P, TCRBV5S5P, TCRBVISIAINI, TCRBV12S2A1T, TCRBV21S1, TCRBV8S4P, TCRBV 12S3, TCRBV21 S3A2N2T, TCRBV8SSP, TCRBV13S1 genes from bases I to 267156 (section 1 of 3). 350 gi33560 Homo sapiens Human mRNA for T-cell 609 100 receptor V beta gene segment V- beta-9, clone IGRb20. 350 gi37634 Homo sapiens H. sapiens rearranged TCR Vbeta 609 100 9. 1 mRNA forTcell receptor. 351 gi 13960126 Homo sapiens Similar to leucine-rich neuronal 162 80 protein, clone MGC : 4126, mRNA, complete cds. 351 gi 14043281 Homo sapiens clone IMAGE : 3528313, 133 64 mRNA, partial cds. 351 gi3135309 Homo sapiens chromosome 7q22 sequence, 133 64 complete sequence. 352 AAB61141 Homo sapiens Human NOV 11 protein. 370 86 Table 2A SEQ Accession No. Species Description Score % ID Identity NO : 352 gi4760778 Mus musculus Ten-m2 369 100 352 gi5712201 Rattus norvegicus neurestin alpha 369 100 353 AAW88628 Homo sapiens Secreted protein encoded by 78 30 gene 95 clone HPWAN23. 353 AAY57923 Homo sapiens Human transmembrane protein 78 30 HTMPN-47. 353 gi7109072 Plasmodium PfEMPI protein 78 37 falciparum 354 gi1061424 Homo sapiens Human PMS2 related (hPMSR3) 194 48 gene, complete cds. 354 gi5738553 Homo sapiens mRNA for zinc finger protein, 175 48 clone cZNF41. 5, partial. 354 gi5738547 Homo sapiens mRNA for zinc finger protein, 174 71 clone cZNF41. 2, partial. 355 girl4161140 Streptococcus M protein 75 35 pyogenes 355 gi472917 Enterococcus hirae v-type Na-ATPase 64 37 355 AAW00946 Homo sapiens Human c-Fos protein. 63 40 356 gi6088092 Mesocricetus auratus cytochrome P450 92 47 356 AAY91348 Homo sapiens Human secreted protein 130 40 sequence encoded by gene 3 SEQ ID NO : 69. 356 gi4249595 Mus musculus CYP2C40 115 34 357 gi12053357 Homo sapiens mRNA ; cDNA 488 67 DKFZp586G2122 (from clone DKFZp586G2122) ; complete cds. 357 AAY27649 Homo sapiens Human secreted protein encoded 62 35 by gene No. 83. 357 gi9755390 Arabidopsis thaliana F 17F8. 22 81 46 358 gi6273399 Homo sapiens melanoma-associated antigen 359 95 MG50 mRNA, partial cds. 358 AAW81030 Homo sapiens Melanoma associated antigen 359 95 MG50. 358 AAY70469 Homo sapiens Human p53 target molecule, 359 95 PRG2 protein. 359 gi7380324 Neisseria CIpB protein 91 32 meningitidis Z2491 359 gi7226713 Neisseria pB protein 91 32 meningitidis MC58 359 gi9658311 Vibrio cholerae integrase-related protein 61 34 360 AAB24074 Homo sapiens Human PRO1153 protein 1023 99 sequence SEQ ID NO : 49. 360 AAY66735 Homo sapiens Membrane-bound protein 1023 99 PRO1 153. 360 AAB65258 Homo sapiens Human PRO1153 (UNQ583) 1023 99 protein sequence SEQ ID NO : 351. 361 gi 1364247 Sus scrofa Ca (2+)-transport ATPase (AA 57 38 989-1042) ; non-muscle isoform (1 is 3rd base in codon) 361 AAB65991 Homo sapiens Human secreted protein BLAST 73 34 search protein SEQ ID NO : 131. 361 AAB65992 Homo sapiens Human secreted protein BLAST 73 34 Table 2A SEQ Accession No. Species Description Score % ID Identity NO : search protein SEQ ID NO : 132. 362 gi2150146 Mus musculus sulfonylurea receptor 2A 634 73 362 gi8843832 Rattus norvegicus sulphonylurea receptor 2b 375 73 362 gi3127175 Homo sapiens sulfonylurea receptor 2A 372 74 (SUR2) gene, alternatively spliced product, exon 38a and complete cds. 363 gi4467773 Helicobacter pylori cytotoxin associated protein A 60 34 363. gi7248699 Helicobacter pylori cytotoxin associated protein 60 34 CagA w 363 i5851989 Helicobacter lori cytotoxin associated protein A 59 31 364 gi 13278675 Homo sapiens clone MGC : 11170, mRNA, 77 41 complete cds. 364 gi6457690 Deinococcus 2-oxo acid dehydrogenase, E2 90 31 radiodurans component 364 gi 179521 Homo sapiens Human bullous pemphigoid 72 36 (BP 180) m RNA, partial cds. 365 AAB52176 Homo sapiens Human secreted protein BLAST 468 95 search protein SEQ ID NO : 132. 365 AAR27651 Homo sapiens Human calcium channel 117 26 27980/13. 365 gi 179764 Homo sapiens Human neuronal DHP-sensitive, 117 26 voltage-dependent, calcium channel alpha-1 D subunit mRNA, complete cds. 366 gi 13623421 Homo sapiens Similarto RIKEN cDNA 495 98 5730589L02 gene, clone MGC : 13124, mRNA, complete cds. 366 gil2803383 Homo sapiens clone MGC : 2099, mRNA, 189 100 complete cds. 366 gi 13111983 Homo sapiens clone MGC : 4221, mRNA, 189 100 complete cds. 367 AAW75100 Homo sapiens Human secreted protein encoded 121 83 by gene 44 clone HE8CJ26. 367 gi 11275978 Homo sapiens NOTCH 2 (N2) mRNA, 125 87 complete cds. 367 AAY06816 Homo sapiens Human Notch2 (humN2) protein 125 87 sequence. 368 gi2696709 Mus musculus RST 258 43 368 gi2687858 Pseudopleuronectes renal organic anion transporter 236 40 americanus 368 gi4586315 Homo sapiens ORCTL3 mRNA for organic-232 37 cation transporter like 3, complete cds. 369 gil 1463949 Homo sapiens hUGTrel7 mRNA for UDP-256 100 glucuronic acid, complete cds. 369 AAB60119 Homo sapiens Human transport protein TPPT-175 63 39. 369 AAB56473 Homo sapiens Human prostate cancer antigen 175 63 protein sequence SEQ ID NO : 1051. 370 gi3986168 Lentinula edodes SHP1 55 31 370 gi 12805659 Mus musculus Similar to syndecan 4 53 34 Table 2A SEQ Accession No. Species Description Score % ID Identity NO : 371 AAB88377 Homo sapiens Human membrane or secretory 370 94 protein clone PSEC0113. 371 gi 12656637 Mus musculus equilibrative nucleoside 109 25 transporter 3 371 gi3877156 Caenorhabditis F44D12. 9 92 32 elegans 372 gi9828006 Leishmania major probable ctg26 alteRNAte open 60 40 reading frame 372 gi4096496 Homo sapiens Human pre-B cell Ig heavy 55 47 chain mRNA, third complementarity-determining region, clone PBT-55, partial cds. 372 gi3005708 Homo sapiens clone 23619 phosphoprotein 66 33 mRNA, partial cds. 373 gi 1339910 Homo sapiens Human DOCK 180 protein 121 54 mRNA, complete cds. 373 AAW03515 Homo sapiens Human DOCK 180 protein. 121 54 373 gi 13195147 Mus musculus HCH 107 61 374'gi11036344 Pichia canadensis NADH dehydrogenase subunit 69 38 4L 374 gi 10175432 Bacillus halodurans D-alanine aminotransferase 87 35 374 gi10639223 Thermoplasma ethanolamine permease related 88 27 acidophilum protein 375 AAB90654 Homo sapiens Human secreted protein, SEQ ID 58 29 NO : 197. 375 AAY36085 Homo sapiens Extended human secreted 56 34 protein sequence, SEQ ID NO. 470. 375 gi3617829 Gallusgallus gailinacin I prepropeptide 55 42 376 girl4189735 Homo sapiens ATP-binding cassette transporter 251 43 family A member 12 (ABC12) mRNA, complete cds. 376 gi 14209834 Mus musculus ATP-binding cassette transporter 199 39 sub-family A member 7 376 gi9211112 Homo sapiens macrophage ABC transporter 196 40 (ABCA7) mRNA, complete cds 377 gi8919747 Cottontail rabbit e8 65 36 papillomavirus 377 gi8919568 Cottontail rabbit E8 64 36 papillomavirus 377 gi5679184 Xanthomonas HrcU homolog 80 25 campestris pv. glycines 378 AAY30817 Homo sapiens Human secreted protein encoded 569 98 from gene 7. 378 gi341 1233 Mus musculus IER5 107 37 378 AAG02396 Homo sapiens Human secreted protein, SEQ ID 85 61 NO : 6477. 379 AAY99353 Homo sapiens Human PR01415 (UNQ731) 1435 99 amino acid sequence SEQ ID NO : 50. 379 AAB88426 Homo sapiens Human membrane or secretory 1428 99 protein clone PSEC0199.

Table 2A SEQ Accession No. Species Description Score % ID Identity NO : 379 gil 230635 Homo sapiens CD30 gene for cytokine receptor 106 29 CD30, exons 1-8. 380 gi6636340 Rattus norvegicus myosin heavy chain Myr 8 157 61 380 gi10863773 Rattus norvegicus myosin heavy chain Myr 8b 157 61 380 AAB51865 Homo sapiens Human secreted protein 71 31 sequence encoded by gene 39 SEQ ID NO : 98. 381 gi9789476 Mus musculus claudin-19 98 41 381 gi3335182 Mus musculus claudin-1 98 32 381 gi 12805093 Mus musculus claudin 1 98 32 382 gi213109 Discopyge ommata synaptic vesicle protein 75 36 382 gil679584 Cavia porcellus membrane cofactor protein 80 37 precursor 382 gil655471 Cavia porcellus membrane cofactor 80 37 protein (GMP 1-full) 383 gil4330016 Musmusculus bM401L17. 2. 1 (cholinergic 164 50 receptor, nicotinic, alpha polypeptide 4 (isoform 1)) 383 gi9886085 Mus musculus nicotinic acetlycholine receptor 164 50 alpha 4 subunit 383 gil4330017 Mus musculus bM401L17. 2. 2 (cholinergic 164 50 receptor, nicotinic, alpha polypeptide 4 (isoform 2)) 384 gi409995 Rattus sp. mucin 137 47 384 gi4995986 Human herpesvirus 6 13. 6% identical to DR8 gene of 135 32 strain U1102 of HHV-6 384 gi2388546 Homo sapiens Human Xq28 BAC RP 1-15918 118 37 (Roswell Park Cancer Institute Human BAC Library), Cosmid LLOXNCO1-3C3 (LLNL X Chromsome Library), and BAC GS1-92B2 (Genome Systems Human BAC Library) complete sequence. 385 AAY58174 Homo sapiens Human embryogenesis protein, 872 96 EMPRO. 385 gi3879940 Caenorhabditis Similarity to Mouse H (beta) 58 650 67 elegans protein (SW : HB58_MOUSE) 385 gi3342000 Homo sapiens H beta 58 homolog 666 70 386 gi 13359817 Escherichia coli high-affinity choline transport 1021 100 0157 : H7 386 gi1657512 Escherichia coli high-affinity choline transport 1021 100 protein 386 gil786506 Escherichia coli K12 high-affinity choline transport 1021 100 387 gi10584129 Halobacterium sp. Vng6071c 81 27 NRC-1 387 gi10584473 Halobacterium sp. Vng6455c 81 27 NRC-1 387 gi 12723038 Lactococcus lactis UNKNOWN PROTEIN 58 28 subsp. lactis 388 gil3364609 Escherichia coli fumarate reductase FrdD 515 96 0157 : H7 388 gil45266 Escherichiacoli gl3 protein 515 96 388. gil790594 Escherichia coli K12 fumarate reductase, anaerobic, 515 96 Table 2A SEQ Accession No. Species Description Score % ID Identity NO : membrane anchor polypeptide 389 gi 1160319 Escherichia coli aldohexuronate transport system 928 96 389 gi13363448 Escherichia coli transport protein of hexuronates 928 96 0157 : H7 389 gi2367193 Escherichia coli K12 transport of hexuronates 928 96 390 gi395270 Escherichia coli FepE 402 100 390 go) 786802 Escherichia coli K12 ferric enterobactin (enterochelin) 402 100 transport 390 gil778503 Escherichia coli ferric enterobactin transport 402 100 protein 391 gil45521 Escherichia coli methyl-accepting chemotaxis 411 73 protein 11 391 gil736539 Escherichia coli Methyl-accepting chemotaxis 411 73 protein If (MCP-II) (Aspartate chemoreceptor protein). 391 gui 1788195 Escherichia coli K12 methyl-accepting chemotaxis 411 73 protein 11, aspartate sensor receptor 392 AAB37990 Homo sapiens Human secreted protein encoded 303 98 by gene 7 clone HWLHH 15. 392 gi312188 Bovineherpesvirus I glycoproteingD 85 29 392 gi5668989 Bovine herpesvirus glycoprotein D precursor 76 29 type 1. 1 393 gi14456429 Equus caballus galanin receptor 1 69 28 393 gi3282259 Cucumaria ND4L 69 30 pseudocurata 393 gi3282257 Cucumaria miniata ND4L 68 30 394 gi3702702 bacteriophage Vf33 Vpf77 65 30 394 gl37027 11 bacteriophage Vfl 2 Vpf77 65 30 394 gil742947 Alcaligenessp. urf-l (merE) 64 31 395 gi263516 Azospirillum NifB {N-terminal} 58 39 brasilense, Sp7, Peptide Partial, 70 aa 395 gi9622741 Conus catus four-loop conotoxin precursor 57 33 395 gil49569 Lactobacillus sp. lactacin F 56 40 396 gi896286 Leishmania NH2 terminus uncertain 123 19 tarentolae 396 gi4155384 Helicobacter pylori IRON (III) DICITRATE 120 27 J99 TRANSPORT SYSTEM PERMEASE PROTEIN 396 gilS42807 Asterina pectinifera NADH-dehydrogenase subunit 98 27 4L 397 AAB88433 Homo sapiens Human membrane or secretory 299 55 protein clone PSEC0210. 397 gi6996444 Homo sapiens CTL2 gene. 299 55 397 AAB24284 Homo sapiens Human H38087 (clone GTB6) 295 54 protein sequence SEQ ID NO : 7. 398 gi6807868 Homo sapiens mRNA ; cDNA 324 68 DKFZp434G0625 (from clone DKFZp434G0625) ; partial cds. 398 AAY 13373 Homo sapiens Amino acid sequence of protein 209 62 PR0235. 398 AAB33420 Homo sapiens Human PR0235 protein 209 62 _ UNQ209 SEQ ID NO : 3 1.

Table 2A SEQ Accession No. Species Description Score % ID Identity NO : 399 gi10434911 Homo sapiens cDNA FLJ13068 fis, clone 573 100 NT2RP3001739, weakly similar to HYPOTHETICAL 72. 5 KD PROTEIN C2F7 10 IN CHROMOSOME 1. 399 gi7022673 Homo sapiens cDNA FLJ 10562 fis, clone 109 43 NT2RP2002701. 399 AAY87090 Homo sapiens Human secreted protein 109 43 sequence SEQ ID NO : 129. 400 AAB63630 Homo sapiens Human gastric cancer associated 165 55 antigen protein sequence SEQ ID NO : 992. 400 AAB63629 Homo sapiens Human gastric cancer associated 170 55 antigen protein sequence SEQ ID NO : 991. 400 AAR06471 Homo sapiens Derived protein from clone 172 55 ICA525 (ATCC 40704). 401 gil3543949 Homo sapiens Similarto RIKEN cDNA 2104 100 2810432L12 gene, clone MGC : 12992, mRNA, complete cds. 401 AAY87340 Homo sapiens Human signal peptide containing 2104 100 protein HSPP-117 SEQ ID NO : 117. 401 gi3876730 Caenorhabditis F35C 11. 4 181 27 elegans 402 gi5001993 Dissostichus chimeric AFGP/trypsinogen-like 199 49 mawsoni serine protease precursor 402 gi295736 Dictyostelium spore coat protein sp96 189 48 discoideum 402 gi2114321 Equine herpesvirus I membrane glycoprotein 186 39 403 gi7239364 Homo sapiens acetylcholinesterase collagen-136 29 like tail subunit (COLQ) gene, exon 17 ; and complete cds, alternatively spliced. 403 gi3599478 Acanthamoeba Myosin-IA 137 35 castellanii 403 gi3858883 Acanthamoeba myosin I heavy chain kinase 133 30 castellanii 404 AAB66272 Homo sapiens Human TANGO 378 SEQ ID 664 89 NO : 29. 404 gi6006811 Mus musculus serpentine receptor 261 40 404 AAB01247 Homo sapiens Human HE6 receptor. 263 38 405 gi 136235 15 Homo sapiens clone MGC : 12705, mRNA, 94 87 complete cds. 405 gi1017781 bacteriophage lambda Rzl protein precursor 44 41 405 gi6599136 Homo sapiens mRNA ; cDNA DKFZp434F216 94 87 (from clone DKFZp434F216) ; partial cds. 406 AAC84384 aal Homo sapiens Human A236 polypeptide 693 100 coding sequence. 406 gi 10438797 Homo sapiens cDNA : FLJ22415 fis, clone'692 100 HRC08561. 406 AAY41692 Homo sapiens Human PRO 363 protein 692 100 sequence.

Table 2A SEQ Accession No. Species Description Score % ID Identity NO : 407 gi8515813 Rattus norvegicus RSD-6 84 25 407 gi 12657809 Simian gag protein 83 25 immunodeficiency virus 407 gi9454456 Human pol protein 60 35 immunodeficiency virus type 1 408 AAY71056 Homo sapiens Human membrane transport 143 76 protein, MTRP-1. 408 gi] 3096889 Mus musculus Similar to ATPas, class 11, type 142 68 9B 408. gi13905302 Mus musculus Similar to ATPase, class 11, type 119 63 9A 409 gi2384752 Paracentrotus lividus transcription factor ; PaxA 56 47 409 gi6601486 Ovis aries pulmonary surfactant protein B 76 30 409 AAR41266 Homo sapiens vWF fragment Arg441-Tyr508, 56 47 deltaCys474-Pro488. 410 AAY99420 Homo sapiens Human PRO1486 (UNQ755) 1082 100 amino acid sequence SEQ ID NO : 287. 410 AAW88747 Homo sapiens Secreted protein encoded by 1069 99 gene 45 clone HCESF40. 410 gi6942096 Mus musculus CBLN3 942 94 411 gi11558496 Sus scrofa sodium iodide symporter 170 51 411 gi 12642414 Mus musculus sodium iodide symporter NIS 184 39 411 gil4290145 Mus musculus sodium iodide symporter 184 39 412 AAY66645 Homo sapiens Membrane-bound protein 554 100 PRO1310. 412 AAB65168 Homo sapiens Human PRO1310 protein 554 100 sequence SEQ ID NO : 62. 412 gi2921092 Mus musculus carboxypeptidase X2 281 58 414 gi5901822 Drosophila EG : 118B3. 2 160 70 melanogaster 414 AAB29877 Homo sapiens Human secreted protein BLAST 127 52 search protein SEQ ID NO : 135. 414 AAB29878 Homo sapiens Human secreted protein BLAST 121 41 search protein SEQ ID NO : 136. 415 gi58442 Human adenovirus 8. 0K protein (AA 1-74) 56 44 type 41 415 gi388253 Trifolium repens ribulose bisphosphate 54 32 carboxylase 415 gil345574 Sinapisalba small subunitribulose 1, 5-57 36 bisphosphate carboxylase (AA 1-82) 416 gi3047402 Homo sapiens monocarboxylate transporter 2 539 34 (hMCT2) mRNA, complete cds. 416 gi7688756 Mus musculus monocarboxylate transporter 4 296 48 416 gi3834395 Homo sapiens monocarboxylate transporter 2 528 33 (MCT2) mRNA, complete cds. 417 gi6136782 Mus musculus synaptotagmin V 595 91 417 gi 14210264 Rattus norvegicus synaptotagmin 5 592 91 417 gi6136792 Mus musculus synaptotagmin X 268 43 418 AAB53400 Homo sapiens Human colon cancer antigen 493 100 protein sequence SEQ ID Table 2A SEQ Accession No. Species Description Score % ID Identity NO : NO : 940. 418 gi6760350 Homo sapiens cytomegalovirus partial fusion 348 98 receptor mRNA, partial cds. 418 gi603380 Saccharomyces Yer 140wp 106 30 cerevisiae 419 AAB12136 Homo sapiens Hydrophobic domain protein 1142 100 from clone HP10625 isolated from Liver cells. 419 AAB24036 Homo sapiens Human PR04407 protein 1142 100 sequence SEQ ID NO : 47. 419 AAY57952 Homo sapiens Human transmembrane protein 1142 100 HTMPN-76. 420 gi2654984 Hepatitis GB virus C polyprotein 50 38 420 gi861305 Caenorhabditis similar to C. elegans protein 75 32 elegans F59B2. 2 420 AAW75055 Homo sapiens Fragment of human secreted 52 38 protein encoded by gene 18. 421 gi2696709 Mus musculus RST 95 47 421 gi 1293672 Mus musculus kidney-specific transport protein 93 40 421 gi7707622 Homo sapiens hOAT4 mRNA for organic 93 37 anion transporter 4, complete cds. 422 gil7829 Brassica napus LEA76 peptide (AA 1-280) 137 27 422 gi 11994339 Arabidopsis thaliana embryonic abundant protein 119 28 LEA-like 422 gi3873646 Caenorhabditis AC3. 3 123 27 elegans 423 AAB74753 Homo sapiens Human secreted protein 38 54 sequence encoded by gene 21 SEQ ID NO : 62. 423 gi2369777 Drosophila sex-peptide 39 53 mauritiana 423 gi2369804 Drosophila simulans sex-peptide 39 53 424 gi 13959739 Caprine arthritis-envelope glycoprotein 87 33 encephalitis virus 424 gi5732606 Hepatitis B virus precore/core mutant protein 74 33 424 gi4033542 Hepatitis B virus truncated pre-core-protein 72 34 425 AAB53400 Homo sapiens Human colon cancer antigen 220 91 protein sequence SEQ ID NO : 940. 425 gil 177469 Homo sapiens gene for interleukin-10. 37 46 425 AAB62192 Homo sapiens Human interleukin-10 (IL-10) 37 46 protein. 426 go) 336041 Homo sapiens Human olfactory receptor 482 50 (OLFI) gene, complete cds. 426 gi1246530 Gallus gallus olfactory receptor 2 474 50 426 gi 1246534 Gallus gallus olfactory receptor 4 474 50 427 AAY36243 Homo sapiens Human secreted protein encoded 64 48 by gene 20. 427 gi409995 Rattus sp. mucin 65 57 427 gil l 14i770 Bostaurus Toll-like receptor4 80 29 428 gi8918871 Plasmid F 96 pct identical to 288 98 gp : AB021078_30 428 gi4512467 Plasmid Collb-P9 100 pct identical to 25 residues 256 93 Table 2A SEQ Accession No. Species Description Score % ID Identity NO : of 79 aa protein sp : YPF8_ECOLI 428 gi47517 Synechocystis sp. ATPase subunit epsilon 72 45 PCC 6803 429 gi5139695 Cucumis sativus expressed in cucumber 85 28 hypocotyls 429 gi3406819 Mus musculus growth factor receptor 63 47 429 AAG03497 Homo sapiens Human secreted protein, SEQ ID 61 51 NO : 7578. 430 AAB) 8985 Homo sapiens Amino acid sequence of a 251 35 human transmembrane protein. 430 gi6013381 Rattus norvegicus TM6P1 246 33 430 AAE00330 Homo sapiens Human membrane-bound 251 35 protein-60 (Zsig60). 432 gi1046315 Plasmodium vivax merozoite surface protein-1 88 34 432 gi2213834 Plasmodium vivax merozite surface protein 1 85 29 432 giS37916 Lilium longiflorum meiotin-l 87 32 433 AAY91618 Homo sapiens Human secreted protein 63 29 sequence encoded by gene 20 SEQ ID NO : 291. 433 AAG02988 Homo sapiens Human secreted protein, SEQ ID 58 29 NO : 7069. 434 gi220411 Mus musculus N-methyl-D-aspartate receptor 159 100 channel subunit epsilon 1 434 gi286234 Rattus norvegicus N-methyl-D-aspartate receptor 159 100 subunit 434 gi2155310 Rattus norvegicus N-methyl-D-aspartate receptor 159 100 NMDAR2A subunit ; NMDA receptor NMDAR2A subunit 435 AAB66267 Homo sapiens Human TANGO 272 SEQ ID 697 50 NO : 14. 435 AAY72712 Homo sapiens HTLIH44 clone human attractin-570 47 like protein. 435 AAY72715 Homo sapiens HFICU08 clone human attractin-565 47 like protein. 436 gi2589210 Mus musculus calcium-sensing receptor related 105 35 protein 3 436 gi3130157 Takifugu rubripes pheromone receptor 106 34 436 gi2589208 Mus musculus calcium-sensing receptor related 99 33 protein 2 437 gi2384746 Mus musculus testicular condensing enzyme 681 52 437 gi4633135 Mus musculus condensing enzyme 681 52 437 girl2652723 Homo sapiens clone MGC : 3295, mRNA, 276 29 complete cds. 438 gi 12224992 Homo sapiens mRNA ; cDNA 877 100 DKFZp66702416 (from clone DKFZp66702416). 438 gi4929647 Homo sapiens CGI-89 protein mRNA, 603 61 complete cds. 438 gil2652585 Homo sapiens CGI-89 protein, clone 602 60 MGC : 845, mRNA, complete cds. 439 AAY36047 Homo sapiens Extended human secreted 61 57 protein sequence, SEQ ID NO.

Table 2A SEQ Accession No. Species Description Score % ID Identity NO : 432. 439 AAG01318 Homo sapiens Human secreted protein, SEQ ID 59 44 NO : 5399. 439 AAW74979 Homo sapiens Human secreted protein encoded 58 35 by gene 105 clone HSVAF07. 440 gi12314108 Homo sapiens Human DNA sequence from 634 100 clone RP1-23013 on chromosome 6q22. 1-22. 33 Contains part of a gene for a novel protein, STSs and GSSs, complete sequence. 440 gi10434835 Homo sapiens cDNA FLJ13018 fis, clone 435 68 NT2RP3000685. 440 gui 1491712 Homo sapiens H. sapiens mRNA for novel 95 56 protein. 442 gi861305 Caenorhabditis similar to C. elegans protein 124 30 elegans F59B2. 2 442 gilO177114 Arabidopsis thaliana amino acid transporter protein-91 34 like 442 gi2576363 Arabidopsis thaliana amino acid transport protein 79 29 443 AAY28678 Homo sapiens Human cw272-7 secreted 324 38 protein. 443 gil3185723 Homosaniens n 1755canbeA G C orT 248 30 443 AAB70537 Homo sapiens Human PR07 protein sequence 248 30 SEQ ID NO : 14. 444 gi 10186503 Homo sapiens sialic acid-specific acetylesterase 932 100 11 mRNA, complete cds, alternatively spliced. 444 gi6808138 Homo sapiens mRNA ; cDNA DKFZp761A051 923 100 (from clone DKFZp761A051) ; partial cds. 444 gi10242345 Homo sapiens sialic acid-specific 9-0-753 100 acetylesterase I mRNA, complete cds. 445 gi7328084 Homo sapiens mRNA ; cDNA 225 82 DKFZp761 L0812 (from clone DKFZp761 L0812) ; partial cds. 445 gi7576817 Plasmodium merozoite surface protein 2 94 38 falciparum 445 gi3261822 Mycobacterium PEPGRS 103 36 tuberculosis 446 gi3165565 Caenorhabditis contains similarity to 129 25 elegans transmembrane domains found in HMG CoA reductases and drosophiia patched protein (SW : P18502) 446 gi 1825729 Caenorhabditis similar to drosophila membrane 125 26 elegans protein PATCHED SP : P18502 (Pi : g129645) 446 gi 15120 enterobacteria phage unidentified reading frame 67 31 PI 447 AAB88481 Homo sapiens Human membrane or secretory 254 73 protein clone PSEC0251. 447 gi57115 Rattus norvegicus ribosomal protein L31 (AA 1-175 67 125) Table 2A SEQ Accession No. Species Description Score o/« ID Identity NO : 447 gil4198321 Mus musculus ribosomal protein L31 175 67 448 gi3130189 Takifugu rubripes pheromone receptor 212 63 448 gi2589208 Mus musculus calcium-sensing receptor related 205 50 protein 2 448. gi2589210 Mus musculus calcium-sensing receptor related 203 48 protein 3 449 gi13452508 Mus musculus claudin 14 438 40 449 gi 12597447 Homo sapiens claudin 14 (CLDN 14) mRNA, 438 39 complete cds. 449 gi7768724 Homo sapiens genomic DNA, chromosome 438 39 21 q, section 70/105. 450 AAR12603 Homo sapiens SIB 121 intestinal mucin. 148 53 450 AAW36946 Homo sapiens Protein encoded by 5'fragment 92 35 of clone M8 2. 450 AAY91378 Homo sapiens Human secreted protein 86 45 sequence encoded by gene 33 SEQ ID NO : 99. 451 gi 13561518 Homo sapiens GalNAc-4-sulfotransferase 2 213 97 mRNA, complete cds, alternatively spliced. 451 gil2711481 Homo sapiens N-acetylgalactosamine 4-O-187 97 sulfotransferase 2 GaINAc4ST-2 mRNA, complete cds. 451 AAY86315 Homo sapiens Human secreted protein 63 27 HNTMX29, SEQ ID NO : 230. 452 gi3150438 Human endogenous pol-env 264 51 retrovirus K 452 gi3150441 Human endogenous envelope protein 258 50 retrovirus K 452 giS802817 Homo sapiens endogenous retrovirus HERV-258 51 K 104 long terminal repeat, complete sequence ; and Gag protein (gag) and envelope protein (env) genes, complete cds. 453 AAY91625 Homo sapiens Human secreted protein 547 97 sequence encoded by gene 22 SEQ ID NO : 298. 453 AAU00437 Homo sapiens Human dendritic cell membrane 547 97 protein FIRE. 453 AAW30638 Homo sapiens Partial human 7-transmembrane 374 66 rece tor HAP0167 rotein. 454 AAY96963 Homo sapiens Wound healing tissue 1811 92 peptidoglycan recognition protein-like protein. 454 AAY96962 Homo sapiens Keratinocyte peptidoglycan 768 62 recognition protein-like protein. 454 AAY76124 Homo sapiens Human secreted protein encoded 768 62 by gene 1. 455 AAB72286 Homo sapiens Human ADAMTS-9 amino acid 1009 100 sequence. 455 AAB72301 Homo sapiens Human ADAMTS-9 alternative 1009 100 amino acid sequence. 455 AAB90617 Homo sapiens Human secreted protein, SEQ ID 358 39 NO : 155.

Table 2A SEQ Accession IVo. Species Description Score'% u ID Identity NO : 456 gi4323581 Homo sapiens senescence-associated epithelial 150 100 membrane protein (SEMPI) mRNA, complete cds. 456 gi4559278 Homo sapiens claudin-l (CLDNI) mRNA, 150 100 complete cds. 456 gil3383364 Homo sapiens claudin-1 (CLDNI) gene, exon 4 150 100 and complete cds. 457 AAW93960 Homo sapiens Human 53BP2 : IP-2 protein 59 45 fragment. 457 AAY19607 Homo sapiens SEQ ID NO 325 from 57 64 W09922243. 457 AAY07942 Homo sapiens Human secreted protein 55 42 fragment encoded from gene 91. 458 gi4406172 Human herpesvirus 4 latent membrane protein-1 159 37 458 gi475574 Human herpesvirus 4 latent membrane protein 1 153 39 type 2 458 gi2736358 Caenorhabditis Contains similarity to Pfam 155 51 elegans domain : PF00069 (pkinase), Score=214. 7, E-value=4. 3e-61, Nul 459 AAB43892 Homo sapiens Human cancer associated protein 253 83 sequence SEQ ID NO : 1337. 459 gi6456100 Mus musculus F-box rotein FBLIO 247 83 459 girl4250563 Homo sapiens clone IMAGE : 3163445, 253 83 mRNA, partial cds. 460 gi552087 Drosophila crumbs protein 127 45 melanogaster 460 AAY66747 Homo sapiens Membrane-bound protein 67 46 PRO1158. 460 AAB87559 Homo sapiens Human PRO1158. 67 46 461 AAB39181 Homo sapiens Human secreted protein 57 41 sequence encoded by gene 3 SEQ ID NO : 61. 462 AAW71565 Homo sapiens Hepatocyte nuclear factor 4 44 36 alpha polypeptide (exon 2 product). 462 gi2804240 Rattus norvegicus histidase 56 42 462 gil49163 Plasmid pJHC-MWI streptomycin-spectinomycin 65 71 resistance protein 463 gil0435833 Homo sapiens cDNA FLJ13729 fis, clone 233 100 PLACE3000121, weakly similar to VESICULAR TRAFFIC CONTROL PROTEIN SEC 15. 463 gi6807998 Homo sapiens mRNA ; cDNA DKFZp76112124 195 80 (from clone DKFZp76112124) ; partial cds. 463 gi7023795 Homo sapiens cDNA FLJ 11251 fis, clone 195 80 PLACE 1008813. 464 gi5668598 Homo sapiens Wiskott-Aldrich syndrome 156 33 protein interacting protein (WASPIP) mRNA, partial cds. 464 gil314755 Mus musculus Wiskott-Aldrich Syndrome 140 33 Protein 464 gi4096355 Mus musculus Wiskott-Aldrich syndrome 140 33 protein (WASP) Table 2A SEQ Accession No. Species Description Score % ID Identity NO : 465 gi4886381 Human E5 protein 54 36 papillomavirus type 16 465 AAB28331 Homo sapiens Human secreted protein BLAST 54 36 search protein SEQ ID NO : 1 15. 465 gi4886413 Human E5 protein 53 26 papillomavirus type 16 466 gi 12276062 Homo sapiens group Xi I secreted 354 100 phospholipase A2 mRNA, complete cds. 466 gil2276193 Homo sapiens FKSG38 (FKSG38) mRNA, 354 100 complete cds. 466 AAY88271 Homo sapiens Human TANGO 180 protein. 354 100 467 gi4885010 Conus textile O-superfamily conotoxin Tx05 73 26 precursor 467 gi6409400 Conus textile conotoxin scaffold VI/VII 71 25 precursor 467 AAW78192 Homo sapiens Human secreted protein encoded 67 39 by gene 67 clone HTOFC34. 468 AAB38330 Homo sapiens Human secreted protein encoded 214 97 by gene 10 clone HTEBV72. 468 gi2335059 Mus musculus IgG receptor 76 52 x 468 gi969034 Mus musculus Fc gamma receptor llbl 76 52 469 gil3311009 Homo sapiens NYD-SP16 mRNA, complete 488 100 cds. 469 gi3287162 Human vpu 69 26 immunodeficiency virus type 1 469 gi 1303982 Bacillus subtilis YqkE 59 40 470 AAB13343 Homo sapiens Human cortexin-like protein. 204 53 470 AAB38538 Homo sapiens Human secreted protein 57 39 sequence encoded by gene 17 SEQ ID NO : 75. 470 AAB34316 Homo sapiens Human secreted protein 54 34 sequence encoded by gene 18 SEQ ID NO : 77. 471 gil3938651 Mus musculus Similar to conserved membrane 502 83 protein at 44E 471 gi 14194169 Arabidopsis thaliana At IgO5960/T21 E18_20 124 30 471 gi265786 human, mRNA, 1271 betacellulin. [Homo 75 57 nt 472 gi310100 Rattus norvegicus developmentally regulated 539 80 protein 472 AAW52812 Homo sapiens Human induced tumour protein. 227 37 472 AAY07771 Homo sapiens Human secreted protein 221 40 fragment encoded from gene 28. 473 AAY71294 Homo sapiens Human orphan G protein-1711 100 coupled receptor hRUP3. 473 AAB02828 Homo sapiens Human G protein coupled 1711 100 receptor hRUP3 protein SEQ ID NO : 8. 473 gi 1204095 Takifugu rubripes dopamine receptor 237 28 474 gi3041879 Mus musculus LNXp80 556 54 Table 2A SEQ Accession No. Species Description Score % Identity NO : 474 gi3041881 Mus musculus LNXp70 556 54 474 gi13183073 Homo sapiens multi-PDZ-domain-containing 539 56 protein mRNA, complete cds. 475 AAB08872 Homo sapiens Amino acid sequence of a 77 93 human secretory protein. 475 gi5734537 Methanothermobacter transmembrane protein 9. 0 kDa 62 43 thermautotrophicus 475 gil3357178 Homo sapiens calcium channel gamma subunit 78 38 7 (CACNG7) mRNA, complete cds. 476 gi5070458 tomato yellow leaf BV2 protein 60 33 curl virus 476 gi9944667 Amsacta moorei AMV144 60 26 entomopoxvirus 476 gi293853 Mus musculus betacellulin 48 25 477 gi 10799398 Homo sapiens chromosome 19, BAC 1513 100 BC349142 (CTC-518B2), complete sequence. 477 gi6063386 Homo sapiens kallikrein-like protein 4 KLK-L4 1513 100 gene, complete cds. 477 gi4884462 Homo sapiens mRNA ; cDNA 912 98 DKFZp586J 1923 (from clone DKFZp586J1923) ; partial cds. 478 AAB90602 Homo sapiens Human secreted protein, SEQ ID 704 100 NO : 140. 478 AAB90662 Homo sapiens Human secreted protein, SEQ ID 704 100 NO : 205. 478 AAB90571 Homo sapiens Human secreted protein, SEQ ID 700 99 NO : 109. 479 AAB53436 Homo sapiens Human colon cancer antigen 82 33 protein sequence SEQ ID NO : 976. 479 AAG02279 Homo sapiens Human secreted protein, SEQ ID 82 61 NO : 6360. 479 gi3879077 Caenorhabditis R1 OEl l. 9 81 35 elegans 480'gi581191 Escherichia coli unidentified reading frame (AA 64 36 1-79) 480 gi929915 synthetic construct insulin C chain 61 58 480 AAP60248 Homo sapiens Human proinsulin. 61 58 481 AAB24074 Homo sapiens Human PRO1153 protein 136 42 sequence SEQ ID NO : 49. 481 AAY66735 Homo sapiens Membrane-bound protein 136 42 PRO1153. 481 AAB65258 Homo sapiens Human PRO1 153 (UNQ583) 136 42 protein sequence SEQ ID NO : 351. 482 AAB08854 Homo sapiens Amino acid sequence of a 787 100 human secretory protein. 482 AAY87268 Homo sapiens Human signal peptide containing 787 100 protein HSPP-45 SEQ ID NO : 45. 482 AAY66723 Homo sapiens Membrane-bound protein 787 100 PRO) 100.

Table 2A SEQ Accession No. Species Description Score % ID Identity NO : 483 gil4211714 Homo sapiens naked cuticle-l (NKDI) mRNA, 193 92 complete cds. 483 AAB08216 Homo sapiens A protein related to Drosophila 193 92 naked cuticle polypeptide. 483 gi 13487305 Mus musculus Nkd 151 62 484 gi3452275 Pleuronectes aminopeptidase N 215 28 americanus 484 gi2766187 Gallus gallus aminopeptidase Ey 178 32 484 gi3776238 Rattus norvegicus aminopeptidase N 151 29 485 AAB58305 Homo sapiens Lung cancer associated 273 100 polypeptide sequence SEQ ID 643. 485 gi5830684 variola minor virus A20L protein 57 24 485 gi297302 Variola virus A 19L 57 24 486 AAB38019 Homo sapiens Human secreted protein encoded 583 99 by gene 27 clone HPJBF63. 486 AAB38010 Homo sapiens Human secreted protein encoded 576 98 by gene 27 clone HOUHD63. 486 gil67020 Hordeum vulgare C-hordein storage protein 47 27 487 AAY91385 Homo sapiens Human secreted protein 969 100 sequence encoded by gene 40 SEQ ID NO : 106. 487 gi4126441 Homo sapiens CD22 gene variant 6, partial cds. 68 34 487 gi201798 Mus musculus T-cell receptor beta 95 29 488 gi9971734 Galleria mellonella heavy-chain fibroin 121 34 488 gi3002791 Homo sapiens macrophage receptor MARCO 81 28 mRNA, complete cds. 488 gi5231092 Homo sapiens macrophage receptor (MARCO) 81 28 gene, exon 17 and complete cds. 489 gi409995 Rattus sp. mucin 173 64 489 gi4063042 Cryptosporidium GP900 ; mucin-like glycoprotein 134 38 parvum 489 gi5732924 Toxocara canis excretory/secretory mucin 112 29 MUC-4 490 git84) 555 Homo sapiens HLA class II region containing 422 100 NOTCH4 gene, partial sequence, homeobox PBX2 (HPBX) gene, receptor for advanced glycosylation end products (RAGE) gene, complete cds, and 6 unidentified cds, complete sequence. 490 AAB25697 Homo sapiens Human secreted protein 122 40 sequence encoded by gene 33 SEQ ID NO : 86. 490 AAB25755 Homo sapiens Human secreted protein 122 40 sequence encoded by gene 33 SEQ ID NO : 144. 491 gi5732924 Toxocara canis excretory/secretory mucin 114 34 MUC-4 491 gi5732920 Toxocara canis excretory/secretory mucin 113 32 M UC-2 491 gi409995 Rattus sp. mucin 95 29 492 AAB70534 Homo sapiens Human PR04 protein sequence 395 100 Table 2A SEQ Accession No. Species Description Score % ID Identity NO : SEQ ID NO : 8. 492 AAY 13377 Homo sapiens Amino acid sequence of protein 395 100 PR0257. 492 AAB80245 Homo sapiens Human PR0257 protein. 395 100 493 gi12656447 Plasmodium erythrocyte membrane protein 1 73 33 falciparum 493 AAG04067 Homo sapiens Human secreted protein, SEQ ID 73 51 NO : 8148. 493 gi4200249 Homo sapiens H. sapiens gene from PAC 76 32 747L4. 494 i12003279 Perilla frutescens 15kD oleosin-like protein 1 77 36 w 494 gi409424 Homo sapiens Human carboxyl ester lipase like 59 32 protein (CELL) mRNA, complete cds. 494 gi609286 Xenopus laevis xsna 79 30 495 girl841555 Homo sapiens HLA class III region containing 80 42 NOTCH4 gene, partial sequence, homeobox PBX2 (HPBX) gene, receptor for advanced glycosylation end products (RAGE) gene, complete cds, and 6 unidentified cds, complete sequence. 495 AAB 18976 Homo sapiens Amino acid sequence of a 69 40 human transmembrane protein. 495 AAW73192 Homo sapiens Human vesicle trafficking 43 38 protein. 496 gi 13241972 Mus musculus SugarCrisp 841 56 496 gi 13241970 Gallus gallus SugarCrisp 840 59 496 gi2943716 Homo sapiens mRNA for 25 kDa trypsin 840 63 inhibitor, complete cds. 497 gi4584539 Arabidopsis thaliana extensin-like protein 138 34 497 gi306316 Herpesvirus papio EBNA-2 171 38 497 gi1632787 Human herpesvirus 4 BYRFI, encodes EBNA-2 142 35 (Dambaugh et al, 1984 ; Dillner et al, 1984) 498 gi 13185723 Homo sapiens n 1755 can be A, G, C, or T 373 100 498 AAB70537 Homo sapiens Human PR07 protein sequence 373 100 SEQIDNO 14 498 gil 3185725 Homo sapiens n 1755 can be A, G, C, or T. 373 100 499 gi202752 Rattus norvegicus adenylyl cyclase type 11 261 59 499 AAB02006 Homo sapiens Adenylyl cyclase type ll-C2 C2 261 59 alpha domain. 499 gi2204110 Bos taurus adenylyl cyclase type Vll 138 50 = 500 gi 10433645 Homo sapiens cDNA FLJ 12221 fis, clone 1086 69 MAMMA 1001091. 500 gi 10440418 Homo sapiens mRNA for FLJ00044 protein, 1086 69 partial cds. 500 AAB56941 Homo sapiens Human prostate cancer antigen 126 28 protein sequence SEQ ID NO : 1519. 501 AAY99402 Homo sapiens Human PRO1382 (UNQ718) 492 98 amino acid sequence SEQ ID NO : 220.

Table 2A SEQ Accession No. Species Description Score % ID Identity NO : 501 AAY32937 Homo sapiens Human cerebellin-2 protein 300 70 sequence. 501 gi5702371 Mus musculus precerebellin-I 284 66 502 AAB44681 Homo sapiens Human secreted protein 361 63 sequence encoded by gene 41 SEQ ID NO : 146. 502 gi 1293734 Saccharomyces 03635p 279 34 cerevisiae 502 gi 13877141 Homo sapiens FKSG89 162 33 503 gi4731216 Boophilus microplus NADH dehydrogenase subunit 2 52 25 503 gi6180101 Cafeteria NADH dehydrogenase subunit 2 71 48 roenbergensis 503 gi5869819 Globodera pallida NADH-ubiquinone 82 35 oxidoreductase subunit 1 504 AAY34120 Homo sapiens Human potassium channel 1597 99 K+Hnov4. 504 gi206044 Rattus norvegicus potassium channel Kv3. 2b 1582 98 504 gi206914 Rattus norvegicus K+ channel protein 1582 98 505 gi3790674 Caenorhabditis contains similarity to a 449 54 elegans vacl/fabl-type domain 506 AAB53626 Homo sapiens Human colon cancer antigen 55 47 protein sequence SEQ ID NO : 1166. 506 gi 1049106 Homo sapiens Human dystonin isoform 2 63 100 mRNA, partial cds. 506 gi470480 Homo sapiens Human clone JL8 58 34 immunoglobulin kappa chain (IgK) mRNA, VKIII-JK3 region, partial cds. 507 AAY44985 Homo sapiens Human epidermal protein-2. 82 37 507 gi 11073 Drosophila Mst84Da 75 37 melanogaster 507 gi8571115 Homo sapiens human endogenous retrovirus 75 40 HRES-1 p8 protein (p8) and p 15 protein (plu) genes, complete cds. 508 gil3676322 Homo sapiens chromosome 1 open reading 230 31 frame 2, clone MGC : 1298, mRNA, complete cds. 508 gil3938585 Homo sapiens clone MGC : 4509, mRNA, 230 31 complete cds. 508 gi2564916 Homo sapiens clk2 kinase (CLK2), propin, 229 31 cotel, glucocerebrosidase (GBA), and metaxin genes, complete cds ; metaxin pseudogene and glucocerebrosidase pseudogene ; and thrombospondin3 (THBS3) gene, partial cds. 509 gi56463 Rattus norvegicus gp210 (AA 1-1886) 363 79 509 gi6650678 Mus musculus nuclear pore membrane 358 78 glycoprotein POM210 509 gi 1703554 Caenorhabditis strong similarity to rat integral 143 32 elegans membrane glycoprotein GP 120 precursor (SP : P)) 654) Table 2A SEQ Accession No. Species Description Score % ID Identity NO : 510 AAB73355 Homo sapiens Human mesangial cell meg-1 317 52 protein. 510 gi4191594 Homo sapiens protein serine/threonine 292 52 phosphatase 4 regulatory subunit 1 (PP4R1) mRNA, complete cds. 510 gi10120321 Salmo trutta MHC class 11 alpha chain 58 30 511 gi 11320944 Homo sapiens peptide deformylase-like protein 1300 100 mRNA, complete cds. 511 girl3195254 Homo sapiens polypeptide deformylase-like 1300 100 protein (PDF) mRNA, complete cds. 511 gil 1320968 Lycopersicon peptide deformylase-like protein 346 40 esculentum 512 gil3279254 Homosapiens Similarto RIKEN cDNA 417 94 2610207116 gene, clone MGC : 10940, mRNA, complete cds. 512 i5869811 Glomus mosseae Fox2 rotein 187 30 512 gi432977 Homo sapiens Human sterol carrier protein 2 174 32 mRNA, complete cds. 513 gi 10803406 Homo sapiens mRNA for cadherin-19 (CDH 19 863 100 gene). 513 AAY41725 Homo sapiens Human PRO941 protein 863 100 sequence. 513 AAB44281 Homo sapiens Human PR0941 (UNQ478) 863 100 protein sequence SEQ ID NO : 264. 514 AAB08944 Homo sapiens Human secreted protein 206 83 sequence encoded by gene 19 SEQ ID NO : 101. 514 AAB08909 Homo sapiens Human secreted protein 159 80 sequence encoded by gene 19 SEQ ID NO : 66. 514 gril4029247 Gnorimosphaeroma cytochrome oxidase subunit I 66 53 oregonense 515 AAG02731 Homo sapiens Human secreted protein, SEQ ID 67 38 NO : 6812. 515 gi 1841964 Toxocara canis TcH SLdT. 460 63 37 515 gi3986598 Ginglymostoma antigen receptor 58 47 cirratum 516 gi575501 Homo sapiens thyrotropin beta-subunit (TSHB) 739 99 gene, exon 3. 516 gi339998 Homo sapiens Human thyrotropin beta (TSH-739 99 beta) subunit gene, exons 2 and 3. 516 gi340002 Homo sapiens Human thyrotropin beta subunit 739 99 gene, exons 2 and 3. 517 AAB53436 Homo sapiens Human colon cancer antigen 368 97 protein sequence SEQ ID NO : 976. 517 AAB25691 Homo sapiens Human secreted protein 168 93 sequence encoded by gene 27 SEQ ID NO : 80. 517 AAY01428 Homo sapiens Secreted protein encoded by 81 42 Table 2A SEQ Accession No. Species Description Score % Identity NO : gene 46 clone HAQBT52. 518 AAB54178 Homo sapiens Human pancreatic cancer 1025 99 antigen protein sequence SEQ ID NO : 630. 518 gi7321824 Drosophila out at first 510 38 melanogaster 518 gi2443448 Drosophila virilis out at first 508 39 519 AAW75178 Homo sapiens Human secreted protein encoded 45 47 by gene 69 clone HPEBD70. 519 gi6466876 Kashmir bee virus RNA polymerase 72 43 519 gi6646671 cloudy wing virus RNA polymerase 72 43 520 AAB88377 Homo sapiens Human membrane or secretory 379 91 protein clone PSEC0113. 520 gui) 90506 Homo sapiens Human PRB1 locus salivary 111 32 proline-rich protein mRNA, clone cP5, complete cds. 520 gi 190475 Homo sapiens Human salivary proline-rich 84 34 protein 1 gene, segment 2. 521 gi 1235645 Cladomyrma cryptata cytochrome oxidase subunit 11 57 50 521 gi4981606 Thermotoga maritima oligopeptide ABC transporter, 43 31 permease protein 521 gi6681644 Yaba monkey tumor similar to vaccinia A 14. 5L 55 45 virus 522 gi7020918 Homo sapiens cDNA FLJ20668 fis, clone 461 66 KAIA585. 522 AAB54305 Homo sapiens Human pancreatic cancer 62 33 antigen protein sequence SEQ ID NO : 757. 522 AAY41352 Homo sapiens Human secreted protein encoded 58 21 by gene 45 clone HTXFH55. 523 AAY54054 Homo sapiens Angiostatin-binding domain of 137 39 ABP-I, designated Big-3. 523 gi9887326 Homo sapiens angiomotin mRNA, complete 155 37 cds. 523 AAY54052 Homo sapiens An angiogenesis-associated 155 37 protein which binds plasminogen. 524 gi 11072097 Homo sapiens MLL/GAS7 fusion protein 83 25 (MLL/GAS7) mRNA, partial cds. 524 gi7331837 Caenorhabditis contains similarity to human X-60 25 elegans linked deafness dystonia protein (GB : U66035) 524 AAG02452 Homo sapiens Human secreted protein, SEQ ID 59 44 NO : 6533. 525 gi 13195147 Mus musculus HCH 953 77 525 gil339910 Homo sapiens Human DOCK180 protein 203 32 mRNA, complete cds. 525 AAW03515 Homo sapiens Human DOCK 180 protein. 203 32 526 gi854065 Human herpesvirus 6 U88 305 47 526 gi9757150 Leishmania major extremely cysteine/valine rich 284 50 protein 526 gil0434098 Homo sapiens cDNA FLJ12547 fis, clone 219 38 NT2RM4000634.

Table 2A SEQ Accession No. Species Description Score % ID Identity NO : 527 AAY48278 Homo sapiens Human prostate cancer-98 89 associated protein 64. 527 AAB58446 Homo sapiens Lung cancer associated 98 89 polypeptide sequence SEQ ID 784. 527 AAG00214 Homo sapiens Human secreted protein, SEQ ID 98 89 NO : 4295. 529 AAB61421 Homo sapiens Human TANGO 300 protein. 1583 99 529 AAB23618 Homo sapiens Human secreted protein SEQ ID 1581 99 NO : 36. 529 AAB87592 Homo sapiens Human PRO1925. 1354 98 530 gi6841194 Homo sapiens HSPC272 421 66 530 gi 12248392 Mus musculus transcriptional inhibitory factor 90 28 530 gi2853265 Rattus norvegicus jun dimerization protein 2 90 28 531 gi9964124 Helicobacter pylori HP0519-like protein 54 45 531 gi6970424 Human start codon is not identified 59 29 papillomavirus type 69 532 gil4330385 Homo sapiens mRNA for sodium/calcium 178 92 exchanger, SCL8A3, alternative splice form B (SCL8A3 gene). 532 gil4330383 Homo sapiens mRNA for sodium/calcium 193 60 exchanger SCL8A3, alternative splice form A (SCL8A3 gene). 532 go) 552526 Rattus norvegicus sodium-calcium exchanger form 178 92 3 533 giS8028 synthetic construct suef protein 148 32 533 gi2447210 Paramecium bursaria a312aR 67 35 Chlorella virus I 534 gi8100892 Human protease 76 30 immunodeficiency virus type 1 534 gi 14281259 Human HIV Protease 71 28 immunodeficiency virus 534 gi 10504617 Human protease 71 31 immunodeficiency virus type 1 535 gi4128041 Homo sapiens claudin-9 (CLDN9) gene. 146 37 535 AAB64401 Homo sapiens Amino acid sequence of human 146 37 intracellular signalling molecule INTRA33. 535 gi4325296 Mus musculus claudin-9 143 36 536 gi 10433539 Homo sapiens cDNA FLJ12133 fis, clone 224 35 MAMMA 1000278. 536 AAW64461 Homo sapiens Human secreted protein from 218 35 clone B121. 536 gi4406644 Homo sapiens clone 25130 mRNA sequence, 223 41 complete cds. 537. AAY05376 Homo sapiens Human HCMV inducible gene 974 90 protein, SEQ ID NO 20. 537 AAB60496 Homo sapiens Human cell cycle and 974 90 proliferation protein CCYPR-44, SEQ ID NO : 44.

Table 2A SEQ Accession No. Species Description Score % ID Identity NO : 537 gil3879501 Mus musculus RIKEN cDNA 4933419D20 348 41 gene 538 AAY25451 Homo sapiens Human secreted protein 2 123 53 derived from extended cDNA. 538 AAY35882 Homo sapiens Extended human secreted 123 53 protein sequence, SEQ ID NO. 19. 538 AAY66636 Homo sapiens Membrane-bound protein 126 47 PRO180. 539 girl4042279 Homo sapiens cDNA FLJ14627 fis, clone 208 82 NT2RP2000289. 539 AAW78193 Homo sapiens Human secreted protein encoded 103 46 by gene 68 clone H2CBJ08. 540 gi 10579884 Halobacterium sp. Vng0244h 68 32 NRC-I 541 AAY 19740 Homo sapiens SEQ ID NO 458 from 60 36 W09922243. 541 gi5911915 Homo sapiens mRNA ; cDNA 68 31 DKFZp586M0622 (from clone DKFZp586M0622) ; partial cds. 541 gi4574260 Haemophilus outer membrane protein 26 70 29 influenzae 542 gil3543049 Mus musculus Similar to RIKEN cDNA 1147 87 0610030G03 gene 542 gi5263332 Arabidopsis thaliana F8K7. 23 123 24 542 gi6552728 Arabidopsis thaliana T26F17. 1 123 24 543 gil4290586 Homo sapiens Similarto RIKEN cDNA 1809 100 2810403L02 gene, clone IMAGE : 3868486, mRNA, partial cds. 543 gilt493522 Homo sapiens PRO 1512 1512 100 543 AAB58871 Homo sapiens Breast and ovarian cancer 1412 92 associated antigen protein sequence SEQ ID 579. 544 gi2114213 Homo sapiens immunoglobulin lambda gene 788 100 locus DNA, clone : 123E I upstream contig. 544 gi21 14308 Homo sapiens immunoglobulin lambda gene 788 100 locus DNA, clone : 123E I. 544 gi693811 human, chromosome Vpre-B=VPre-B protein 788 100 22, Gnomic, 1100 nt]. [Homo sapiens 545 gil4250299 Homo sapiens Similar to RIKEN cDNA 686 87 C030006KI I gene, clone MGC : 18180, mRNA, complete cds. 545 gi7230571 Mus musculus lim homeodomain-containing 87 26 transcription factor 545 i587461 Mesocricetus auratus lmxl. l 83 25 546 AAB24074 Homo sapiens Human PROI 153 protein 130 34 sequence SEQ ID NO : 49. 546 AAY66735 Homo sapiens Membrane-bound protein 130 34 PRO1153. 546 AAB65258 Homo sapiens Human PRO1153 (UNQ583) 130 34 protein sequence SEQ ID Table 2A SEQ Accession No. Species Description Score % ID Identity NO : NO : 351. 547 gilS37002 Hepatitis C virus envelope glycoprotein E2/NSI 61 32 547 gi3153687 Hepatitis C virus genome polyprotein 60 41 547 AAB45374 Homo sapiens Human secreted protein 58 50 sequence encoded by gene 36 SEQ ID NO : 126. 548 gi405956 Escherichia coli yeeE 1138 93 548 gi405954 Escherichia coli exonuclease I 1014 86 548 gui) 736685 Escherichia coli Exodeoxyribonuclease I (EC 1014 86 3. 1. 11. 1) (Exonuclease I) (DNA deoxyribophosphodiesterase) (DRPase). 549 gi295196 Salmonella level of amino acid identity 699 86 typhimurium between E. coli and S. typhimurium strongly suggests authentic gene w 549 gi405956 Escherichia coli yeeE 96 36 549 AAG01568 Homo sapiens Human secreted protein, SEQ ID 65 25 NO : 5649. 550 AAW67894 Homo sapiens Human secreted protein encoded 60 28 by gene 2 clone HBMCF37. 550 AAY87145 Homo sapiens Human secreted protein 60 28 sequence SEQ ID NO : 184. 550 AAY87182 Homo sapiens Human secreted protein 60 28 sequence SEQ ID NO : 221. 551 gi216539 Escherichia coli BasS 825 98 551 gi 1790551 Escherichia coli K 12 sensor protein for basR 825 98 551 gi536956 Escherichia coli basS 825 98 552 gui 1786804 Escherichia coli K12 ferric enterobactin transport 1021 100 protein 552 go) 778505 Escherichia coli ferric enterobactin transport 1021 100 protein 552 gui13360086 Escherichia coli ferric enterobactin transport 1020 99 O 157 : H7 protein 553 gi349227 Escherichia coli transmembrane protein 1114 100 553 gi466681 Escherichia coli dppC 1114 100 553 girl3363896 Escherichia coli dipeptide transport system 1 1 14 100 0157 : H7 permease protein 2 554 gi4063042 Cryptosporidium GP900 ; mucin-like glycoprotein 359 57 parvum 554 gi2827460 Cercopithecus hepatitis A virus cellular 324 56 aethiops receptor I short form 554 gi2827462 Cercopithecus hepatitis A virus cellular 324 56 aethiops receptor I long form 555 gil3959789 Homo sapiens lung alpha/beta hydrolase 203 88 protein I mRNA, complete cds. 555 gi13784946 Mus musculus al ha/beta h drolase-1 175 77 555 gi7545019 Neurospora crassa apocytochrome b 47 41 556 AAB87774 Homo sapiens Human T2R44 amino acid 364 91 sequence SEQ ID NO : 70. 556 AAB87780 Homo sapiens Human T2R50 amino acid 363 89 sequence SEQ I D NO : 76. 556 AAB87745 Homo sapiens Human T2R 15 amino acid 343 85 sequence SEQ ID NO : 28.

Table 2A SEQ Accession No. Species Description Score % ID Identity NO : 557 gi2275592 Homo sapiens T cell receptor beta locus, 534 100 TCRBV8SSP to TCRBV21 S2A2 region. 557 gi2275570 Homo sapiens T cell receptor beta locus, 534 100 TCRBV6S4A 1 to TCRBV8S 1 region. 557 gi2218039 Homo sapiens Human germline T-cell receptor 534 100 beta chain TCRBV13S 1, TCRBV6S8A2T, TCRBVSS6A3N2T, TCRBV 13S6A2T, TCRBV6S9P, TCRBV5S3A2T, TCRBV13S8P, T CRBV6S3A I N I T, TCRBV5S2, TCRBV6S6A2T, TCRBV5S7P, TCRBV13S4, TCRBV6S2AI N1T, TCRBV5S4A2T, TCRBV6S4A 1, TCRBV23S 1 A2T, TCRBV 12S 1 A 1 N2, TCRBV21 S2A2, TCRBV8S 1, TCRBV8S2A IT, TCRBV8S3, TCRBV16SlAlNI, TCRBV24S 1 A3T, TCRBV25S I A2PT, TCRBV26S I P, TCRBV 18S 1, TCRBV17S1A1T, TCRBV2S1, TCRBV 1 OS 1 P genes from bases 257519 to 472940 (section 2 of 3). 558 gi3093754 Neurospora crassa AR2 78 28 558 gi3776090 Mus musculus wolframin 76 29 558 gi3777585 Mus musculus transmembrane protein 76 29 559 gi2935614 Homo sapiens PAC clone RP1-102K2 from 1306 100 22q12. 1-qter, complete sequence. 559 gi386988 Homo sapiens Human oncostatin M gene, exon 1306 100 3. 559 AAR33380 Homo sapiens Cytokine hOSM. 1306 100 560 AAB49502 Homo sapiens Clone HYASC03. 310 98 560 gi7020468 Homo sapiens cDNA FLJ20396 fis, clone 145 39 KAT00561. 560 AAB18980 Homo sapiens Amino acid sequence of a 145 39 human transmembrane protein. 561 AAY38432 Homo sapiens Human secreted protein encoded 81 46 by gene No. 3. 561 AAY73420 Homo sapiens Human secreted protein clone 75 33 ye22_1 protein sequence SEQ ID NO : 62. 561 AAY20298 Homo sapiens Human apolipoprotein E mutant 77 30 protein fragment 11. 562 gi9948048 Pseudomonas probable transporter (membrane 557 63 aeruginosa subunit) 562 gi7227389 Neisseria sodium/dicarboxylate symporter 492 58 Table 2A SEQ Accession No. Species Description Score % ID Identity NO : meningitidis MC58 family protein 562 gi9657417 Vibrio cholerae sodium/dicarboxylate symporter 474 55 563 gi 13111711 Homo sapiens solute carrier family 2 1273 60 (facilitated glucose transporter), member 5, clone MGC : 1619, mRNA, complete cds. 563 gi12804761 Homo sapiens solute carrier family 2 1273 60 (facilitated glucose transporter), member 5, clone MGC : 3654, mRNA, complete cds. 563 gi 183298 Homo sapiens Human glucose transport-like 5 1273 60 (GLUT5) mRNA, complete cds. 564 gi14336709 Homo sapiens 16p13. 3 sequence section 3 of 8. 358 57 564 gi9621664 Homo sapiens RHBDL gene for rhomboid-358 57 related protein. 564 gi3287191 Homo sapiens mRNA for rhomboid-related 358 57 protein, complete CDS. 565 AAY45023 Homo sapiens Human sensory transduction G-968 100 . protein coupled receptor-B3. 565 gi 13785657 Mus musculus candidate taste receptor T I R 1 786 77 565 gi 13785659 Mus musculus candidate taste receptor T1 R2 303 36 566 gi871498 Oryza sativa DNA binding protein 86 35 566 gi7160630 Bordetella pertactin (P. 68) 86 39 bronchiseptica 566 gi9049498 Bordetella pertacti n 86 39 bronchiseptica 567 gi591 1988 Homo sapiens mRNA ; cDNA 164 73 DKFZp434H2235 (from clone DKFZp434H2235) ; partial cds. 567 gi5262574 Homo sapiens mRNA ; cDNA DKFZp434G173 164 73 (from clone DKFZp434G173) ; complete cds. 567 AAW89030 Homo sapiens Polypeptide fragment encoded 147 64 by gene 165. 568 gi10437864 Homo sapiens cDNA : FLJ21709 fis, clone 429 74 COL 10077. 568 AAY91433 Homo sapiens Human secreted protein 412 76 sequence encoded by gene 33 SEQ ID NO : 154. 568 girl4042074 Homo sapiens DNA FLJ14508 fis, clone 411 80 NT2RM1000421, weakly similar to R1BONUCLEASE INHIBITOR. 569 gi9280561 Mus musculus elafin-like protein 1 66 30 569 AAY99453 Homo sapiens Human PRO) 784 (UNQ846) 77 31 amino acid sequence SEQ ID NO : 390. 569 gilO176740 Arabidopsis thaliana RING zinc finger protein-like 76 33 570 AAB87396 Homo sapiens Human gene 8 encoded secreted 440 89 protein HMAM121, SEQ ID NO : 137. 570 AAY95967 Homo sapiens Human TANGO 240. 436 88 570 AAB88402 Homo sapiens Human membrane or secretory 434 88 protein clone PSEC0152.

Table 2A SEQ Accession No. Species Description Score O/o ID Identity NO : 571 AAY 19485 Homo sapiens Amino acid sequence of a 53 52 human secreted protein. 572 gi6900006 Ceratitis ca itata chorion rotein st 8 95 31 572 gui 1491621 Bovine herpesvirus I UL36 104 35 572 gi2653311 Bovine herpesvirus very large virion protein 104 35 type 1. 1 (tegument) 573 gi4877582 Homo sapiens lipoma HMGIC fusion partner 72 34 (LHFP) mRNA, complete cds. 573 AAY87336 Homo sapiens Human signal peptide containing 72 34 protein HSPP-113 SEQ ID NO : 113. 573 gi9658445 Vibrio cholerae AzIC family protein 49 38 574 gi6899191 Ureaplasma amino acid antiporter 67 33 ureal icum 574 gi5708228 Rhodopseudomonas LH2alpha7 62 35 acidophila 574 gi7211354 Saimiri boliviensis olfactory receptor 77 34 575 AAB) 9403 Homo sapiens Amino acid sequence of a 7) 2 89 human secreted protein. 575 gi387048 Cricetus cricetus DHFR-coamplified protein 230 47 575 gi3261597 Mycobacterium lprA 77 29 tuberculosis 576 gil2718841 Mus musculus Skullin 310 38 576 gi4191356 Mus musculus claudin-6 308 38 576 gil 3543081 Mus musculus claudin 6 308 38 577 gi801882 Vibrio alginolyticus FkuB 83 31 577 gi2795895 Homo sapiens clone 23819 white protein 71 30 homolog mRNA, partial cds. 577 gi5777942 Equus caballus fL-1ra 52 25 578 gi9872 Plasmodium ATPase I 116 41 falciparum 578 gi7688148 Homo sapiens Novel human gene mapping to 119 42 chomosome 1. 578 gi3451312 Schizosaccharomyces membrane atpase 116 41 pombe 579 gi6682873 Homo sapiens rec mRNA, complete cds. 200 90 579 gi7230612 Rattus norvegicus small rec 197 87 579 gi4959442 Drosophi ! a DNZDHHC/NEW) zinc finger 93 41 melanogaster protein 11 580 gi2204110 Bos taurus adenylyl cyclase type Vl l 233 69 580 gi602412 Mus musculus adenylyl cyclase type Vil 209 66 580 AAB02011 Homo sapiens Type Vll adenylyl cyclase. 209 66 581 AAB24476 Homo sapiens Human secreted protein 241 69 sequence encoded by gene 40 SEQ ID NO : 101. 581 gui52414 Mus musculus mPit-IR 69 31 581 gi7769944 Leishmania major L354. 10 87 25 582 gi3297936 Rattus norvegicus rhomboid-related protein 267 71 582 gi9621664 Homo sapiens RHBDL gene for rhomboid-266 71 related protein. 582 gil4336709 Homo sapiens 16p13. 3 sequence section 3 of 8. 266 71 583 gi10437529 Homo sapiens cDNA : FLJ21432 fis, clone 145 25 . COL04219. 583 AAY76136 Homo sapiens Human secreted protein encoded 113 28 Table 2A SEQ Accession No. Species Description Score ID Identity NO : by gene 13. 583 gi4929559 Homo sapiens CGI-45 protein mRNA, 113 28 complete cds. 584 gi2429362 Santalum album proline rich protein 137 34 584 gi5139695 Cucumis sativus expressed in cucumber 127 28 hypocotyls 584 gi7671460 Arabidonsis thaliana AtAGP4 37 585 gi3165565 Caenorhabditis contains similarity to 94 23 elegans transmembrane domains found in HMG CoA reductases and drosophila patched protein (SW : P18502) 585 gi 160281 Plasmodium erythrocyte binding protein 64 35 falciparum 585. AAY28686 Homo sapiens Human yb39_1 secreted protein. 57 43 587 AAY71948 Homo sapiens Human ion channel protein 1195 99 (ICP). 587 AAY71949 Homo sapiens Human alternative ion channel i 195 99 protein (ICP). 587 AAR27654 Homo sapiens Human calcium channel 149 27 27980/16. 588 gi478889 Rana catesbeiana transcription factor RcC/EPB-I 82 33 588 gi4098456 Sus scrofa follicle-stimulating hormone 60 38 beta subunit 588 AAR56767 Homo sapiens Human FSH beta subunit 58 33 fragment with residues-18 to 35. 589 gi5578778 Homo sapiens mRNA for G 18. 2 protein (G 18. 2 73 41 gene, located in the class 111 region of the major histocompatibility complex). 589 gi213591 Pseudopleuronectes HPLC6 65 43 americanus 589 gil 1345434 Thermus competence factor ComEA 79 43 thermophilus 590 gui13111831 Homo sapiens clone IMAGE : 3451448, 606 60 mRNA, partial cds. 590 AAW78128 Homo sapiens Human secreted protein encoded 606 60 by gene 3 clone HOSB196. 590 AAB 18993 Homo sapiens Amino acid sequence of a 606 60 human transmembrane protein. 591 gi14249886 Homo sapiens clone MGC : 15763, mRNA, 196 77 complete cds. 591 gi217554 Bos taurus endothelin receptor 50 32 591 gi3299894 Equus caballus endothelin-B receptor 50 32 592 gi36853 Homo sapiens Human mRNA for T-cell 585 100 receptor alpha-chain HAVP02 (V (a) I I. I-J (a) l). 592 gi2358022 Homo sapiens T-cell receptor alpha delta locus 585 100 from bases I to 250529 (section 1 of 5) of the Complete Nucleotide Sequence. 592 gi404055 Macaca mulatta T-cell receptor alpha chain 568 97 593 AAW52812 Homo sapiens Human induced tumour protein. 123 38 593 gi8895091 Homo sapiens Diff33 protein homolog mRNA, 123 38 Table 2A SEQ Accession No. Species Description Score % ID Identity NO : complete cds. 593 AAY95015 Homo sapiens Human secreted protein vc61_1, 123 38 SEQ ID NO : 70. 594 gi32093 Homo sapiens H. sapiens HGMP07J gene for 849 54 olfactory receptor. 594 AAF61 132 aal Homo sapiens Human OLFXY cDNA. 802 49 594 AAB46999 Homo sapiens Human OLFXY protein. 799 49 595 gi9081843 Prunus dulcis self incompatibility associated 79 44 ribonuclease 595 gi6539444 Prunus avium S6-RNase 79 44 595 gi6539438 Prunus avium Sl-RNase 78 44 596 AAB66272 Homo sapiens Human TANGO 378 SEQ ID 581 loo NO : 29. 596 AAB61166 Homo sapiens Human BBSR seven 168 39 transmembrane receptor protein. 596 gi6006811 Mus musculus serpentine receptor 168 41 597 AAY66750 Homo sapiens Membrane-bound protein 785 98 PRO1287. 597 AAB87561 Homo sapiens Human PRO1287. 785 98 597 AAB65273 Homo sapiens Human PRO1287 (UNQ656) 785 98 protein sequence SEQ ID NO : 381. 598 AAY99421 Homo sapiens Human PRO1433 (UNQ738) 915 48 amino acid sequence SEQ ID NO : 292. 598 gi) 3537297 Homo sapiens GS1999full mRNA, complete 879 51 cds. 598 AAY94889 Homo sapiens Human protein clone HP02485. 723 43 599 gi 10435844 Homo sapiens cDNA FLJ 13737 fis, clone 93 28 PLACE3000157. 599 gi205752 Rattus norvegicus Nopp 140 95 27 599 AAY53800 Homo sapiens Amino acids 145-197 of the 63 40 mature human chromogranin A (CgA) protein. 600 gi7717312 Homo sapiens chromosome 21 segment 422 97 HS21 C049. 600 AAB18666 Homo sapiens A human regulator of 115 92 intracellular phosphorylation. 600 gi 1 1342496 Bacteriophage phi-holin 77 27 Ealh 601 gi9963895 Homo sapiens HT021 (HT021) mRNA, 255 94 complete cds. r 601 AAW54455 Homo sapiens Mouse novel secreted protein 255 94 isolated from clone BF290 li. 601 AAB59017 Homo sapiens Breast and ovarian cancer 255 94 associated antigen protein sequence SEQ ID 725. 602 gi2055228 Glycine max SRCI 76 26 602 gi204144 Rattus norvegicus profilaggrin 97 25 602 gi3820941 Hepatitis B virus core antigen 24 603 gi 1234787 Xenopus laevis up-regulated by thyroid hormone 1115 58 in tadpoles ; expressed specifically in the tail and only at metamorphosis ; membrane Table 2A SEQ Accession No. Species Description Score % ID Identity NO : bound or extracellular protein ; C-terminal basic region 603 gi 10435980 Homo sapiens cDNA FLJ 13840 fis, clone 699 72 THYRO1000783, moderately similar to Xenopus laevis tail- specific thyroid hormone up- regulated (gene 5) mRNA. 603 gi4868122 Mus musculus hedgehog-interacting protein 405 33 604 gi1181494 Paramecium bursaria a331L 61 46 Chlorella virus 1 604 AAY91469 Homo sapiens Human secreted protein 57 40 sequence encoded by gene 19 SEQ ID NO : 142. 604 AAY91617 Homo sapiens Human secreted protein 57 40 sequence encoded by gene 19 SEQ ID NO : 290. 605 gi 12007419 Mus musculus B4 olfactory receptor 285 60 605 gi 12007420 Mus musculus B5 olfactory receptor 285 60 605 girl2007421 Mus musculus B6 olfactory receptor 285 60 606 AAB20695 Homo sapiens Polymeric immunoglobulin 60 55 receptor binding domain peptide SEQ ID NO : 1 1. 606 gi1181346 Paramecium bursaria a183L 56 28 Chlorella virus 1 606 gil4030701 Arabidopsis thaliana At2g28370/TIB3. 11 72 27 607 git 3507259 Homo sapiens amnionless mRNA, complete 1167 99 cds. 607 gi 13649780 Mus musculus amnionless precursor protein 840 71 607 AAY66714 Homo sapiens Membrane-bound protein 1167 99 PRO1028. 609 gi 1296632 Homo sapiens H. sapiens gene encoding G 104 37 protein coupled receptor. 609 gil 124905 Homo sapiens H. sapiens P2Y4 gene. 104 37 609 AAW23606 Homo sapiens Human P2Y4 receptor 104 37 polypeptide. 610 gi4877582 Homo sapiens lipoma HMGIC fusion partner 110 25 (LHFP) mRNA, complete cds. 610 AAY87336 Homo sapiens Human signal peptide containing 110 25 protein HSPP-113 SEQ ID NO : 113. 611 AAY27721 Homo sapiens Human secreted protein encoded 1118 88 by gene No. 29. 611 AAB87068 Homo sapiens Human secreted protein 621 99 TANGO 365, SEQ ID NO : 46. 611 AAB87146 Homo sapiens Human secreted protein 617 98 TANGO 365 A5V variant, SEQ ID NO : 161. 612 gi7208423 Caulobacter CpaA 65 36 crescentus 612 gi 13424575 Caulobacter pilus assembly protein CpaA 65 36 crescentus 613 AAY28917 Homo sapiens Human regulatory protein 267 100 H RGP-3. 613 AAB53312 Homo sapiens Human colon cancer antigen 267 100 Table 2A SEQ Accession No. Species Description Score O ; ID Identity NO : protein sequence SEQ ID NO : 852. 613 gil 1526789 Homo sapiens inorganic pyrophosphatase 2 258 98 (PPA2) mRNA, complete cds, nuclear gene for mitochondrial product. 614 gi13938575 Homo sapiens Similar to RIKEN cDNA 655 89 2610511 E22 gene, clone MGC : 4251, mRNA, complete cds. 614 AAY91458 Homo sapiens Human secreted protein 655 89 sequence encoded by gene 8 SEQ ID NO : 131. 614 AAY91598 Homo sapiens Human secreted protein 655 89 sequence encoded by gene 8 SEQ ID NO : 271 615 gi2065210 Mus musculus Pro-Pol-dUTPase polyprotein 1026 82 615 gi3860513 Mus famulus reverse transcriptase 482 84 615 gi4379237 Mus musculus reverse transcriptase 477 83 616 gil4190365 Arabidopsisthaliana AT5gl7300/MKP11_15 64 32 616 gi 11275913 Protophormia cytochrome oxidase subunit 1 55 44 atriceps 616 AAY29337 Homo sapiens Human secreted protein clone 63 28 gg894_13 alternate reading frame protein. 617 AAY20840 Homo sapiens Human neurofilament-H wild 67 38 type protein fragment 1. 617 gi 10584099 Halobacterium sp. Vng6036h 61 28 NRC-1 617 gi7739781 Rattus norvegicus CCN family protein COP-1 80 26 618 gi 13183881 Homo sapiens Fanconi anemia 657 90 complementation group D2 protein (FANCD2) mRNA, complete cds, alternatively spliced. 618 gil3324523 Homo sapiens Fanconi anemia 657 90 complementation group D2 protein (FANCD2) gene, exons 43, 44, and complete cds, alternatively spliced. 618 gi 10434106 Homo sapiens cDNA FLJ12551 fis, clone 175 100 NT2RM4000700. 619 gil4042550 Homo sapiens cDNA FLJ14779 fis, clone 242 66 NT2RP4000398, moderately similar to ZINC FINGER PROTEIN 140. 619 gi456269 Mus musculus zinc finger protein 30 242 70 domesticus 619 gi5080758 Homo sapiens chromosome 19, BAC 331191 244 69 (CIT-B-471 f3), complete sequence. 620 AAB47106 Homo sapiens Sccond splice variant of MAPP. 223 97 620 AAB47105 Homo sapiens First splice variant of MAPP. 200 90 620 AAW25722 Homo sapiens Human partial beta meltrin 184 66 protein fragment 2.

Table 2A SEQ Accession No. Species Description Score % ID Identity NO : 621 AAB90649 Homo sapiens Human secreted protein, SEQ ID 563 92 NO : 192. 621 AAB90565 Homo sapiens Human secreted protein, SEQ ID 472 100 NO : 103. 621 AAB90651 Homo sapiens Human secreted protein, SEQ ID 203 97 NO : 194. 622 AAY87335 Homo sapiens Human signal peptide containing 623 99 protein HSPP-112 SEQ ID NO : 112. 622 gi2292988 Rattus norvegicus Inter-alpha-inhibitor H4 heavy 87 32 chain 622 AAY90288 Homo sapiens Human peptidase, HPEP-5 63 36 protein sequence. 623 AAY92710 Homo sapiens Human membrane-associated 230 100 protein Zsig24. 623 AAY87250 Homo sapiens Human signal peptide containing 230 100 protein HSPP-27 SEQ ID NO : 27. 623 AAG00627 Homo sapiens Human secreted protein, SEQ ID 93 100 NO : 4708. 624 gi 10441465 Homo sapiens actin filament associated protein 274 90 (AFAP) mRNA, complete cds. 624 gi l3129531 Gallus gallus actin filament-associated protein 204 71 624 gi13129529 Gallus gallus neural actin filament protein 204 71 625 AAB64802 Homo sapiens Human secreted protein 58 41 sequence encoded by gene 30 SEQ ID NO : 88. 625 gi 1711217 Caenorhabditis F58A3. 1 b 77 30 elegans 625 gi 1711215 Cacnorhabditis F58A3. 1 a 77 30 elegans 626 AAB12121 Homo sapiens Hydrophobic domain protein 153 68 from clone HP02962 isolated from KB cells. 626 AAY30812 Homo sapiens Human secreted protein encoded 149 65 from gene 2. 626 AAB88452 Homo sapiens Human membrane or secretory 144 66 protein clone PSEC0241. 627 gi 13623237 Homo sapiens clone MGC : 10671, mRNA, 146 57 complete cds. 627 gi13310191 multiple sclerosis recombinant envelope protein 126 35 associated retrovirus element 627 gi4262296 Homo sapiens endogenous retrovirus W 117 35 envelope protein mRNA, partial cds. 628 gi10437485 Homo sapiens cDNA : FLJ21394 fis, clone 65 30 COL03536. 628 AAG02270 Homo sapiens Human secreted protein, SEQ ID 59 44 NO : 6351. 629 gi4200216 Homo sapiens H. sapiens gene from PAC 475 100 1026E2, partial. 629 gi 14141674 Rattus norvegicus BMP/retinoic acid-inducible 54 neural-specific protein Table 2A SEQ Accession No. Species Description Score «, I D Identity NO : 629 gi3041877 Homo sapiens IB3089A (IB3089A) mRNA, 151 54 complete cds. 630 AAY20292 Homo sapiens Human apolipoprotein E wild 63 51 type protein fragment 2. 630 AAB32406 Homo sapiens Human secreted protein 62 36 sequence encoded by gene 5 SEQ ID NO : 92. 630 gi 12667610 uncultured sulfate-dissimilatory sulfite reductase 72 39 reducing bacterium subunit A UMTRAdsr648-22 631 gi 12053099 Homo sapiens mRNA ; cDNA DKFZp434A 171 172 65 (from clone DKFZp434A 171) ; complete cds. 631 gi3002799 Pseudomonas 2-aminomuconic acid 118 29 pseudoalcaligenes semialdehyde dehydrogenase 631 gi5821145 Homo sapiens mRNA for RNA binding 120 22 protein, partial cds, clone : RI 1. 632 gi 14249823 Homo sapiens cholecystokinin, clone 356 100 MGC : 10571, mRNA, complete cds. 632 gi 179996 Homo sapiens Human cholecystokinin (CCK) 356 100 gene, exon 3. 632 AAB24381 Homo sapiens Human procholecystokinin 356 100 amino acid sequence SEQ ID NO : I. 633 gi 1870554 Saguinus oedipus T-cell receptor beta 79 32 633 gi 1150925 Bovine herpesvirus I glycoprotein B 65 38 633 gi 159250 Holothuria tubulosa sperm specific protein phi-0 60 30 634 gi4097231 Ureaplasma multiple banded antigen 395 23 urealyticum 634 gi560649 Neocallimastix Xylanase B, XYLB {EC 330 20 patriciarum, Peptide, 3. 2. 1. 8} 860 aa 634 gi600118 Zea mays extensin-like protein 331 35 635 AAB12140 Homo sapiens Hydrophobic domain protein 172 51 isolated from WERI-RB cells. 635 AAY25806 Homo sapiens Human secreted protein 130 46 fragment encoded from gene 23. 635 gi5901846 Drosophila BcDNA. GH12144 124 39 melanogaster 636 AAB66267 Homo sapiens Human TANGO 272 SEQ ID 1329 97 NO : 14. 636 gi2289904 Mus musculus DRPLA 125 28 636 gi1549217 Mus musculus DRPLA rotein 124 28 637 gi4705 Saccharomyces Ty protein 58 51 cerevisiae 637 gi 11139690 Ovis aries muscle specific calpain 3 54 41 637 AAY41363 Homo sapiens Human secreted protein encoded 54 55 by gene 56 clone HNGFE55. 638 gi 139261 1 I Homo sapiens 2P domain potassium channel 1430 100 Talk-2 (KCNK 17) mRNA, complete cds. 638 AAY90354 Homo sapiens Human TWIK-3 protein. 1426 99 638 gil3507377 Homo sapiens potassium channel TASK-4 1364 99 Table 2A SEQ Accession No. Species Description Score % ID Identity NO : mRNA, complete cds. 639 gi514916 Bos taurus tau protei n 91 36 639 gi437055 Macaca mulatta mucin 95 28 639 gi2754696 Gallus gallus high molecular mass nuclear 103 28 antigen 640 girl4193307 Candidatus ATP synthase beta subunit 61 35 Carsonella ruddii 640 gi2688677 Borrelia burgdorferi oligopeptide ABC transporter, 65 28 permease protein (oppC-2) 640 girl4193323 Candidatus ATP synthase beta subunit 59 31 Carsonella ruddii 641 gi3127175 Homo sapiens sulfonylurea receptor 2A 713 98 (SUR2) gene, alternatively spliced product, exon 38a and complete cds. 641 gi3127176 Homo sapiens sulfonylurea receptor 2B 713 98 (SUR2) gene, alternatively spliced product, exon 38b and complete cds. 641 gi5814019 Oryctolagus cardiac ventricle sulfonyl urea 678 93 cuniculus receptor 642 AAB24035 Homo sapiens Human PR04397 protein 1894 100 sequence SEQ ID NO : 42. 642 AAY93951 Homo sapiens Amino acid sequence of a 1241 100 Brainiac-5 polypeptide. 642 AAY06462 Homo sapiens Human Brainiac-3. 553 48 643 AAW88708 Homo sapiens Secreted protein encoded by 747 87 gene 175 clone HEMAM41. 643 gi 159655 Asearis suum collagen 94 36 643 gi289662 Caenorhabditis col-36 collagen 109 41 elegans 644 gi975893 Homo sapiens Human apolipoprotein apoC-IV 693 100 (APOC4) gene, complete cds. 644 AAG03772 Homo sapiens Human secreted protein, SEQ ID 669 96 NO : 7853. 644 gil 85465 Oryctolagus Apolipoprotein C-IV 379 55 cuniculus 645 AAY57878 Homo sapiens Human transmembrane protein 101 86 HTM PN-2 645 gi4406500 Carassius auratus gonadotropin releasing hormone 72 31 receptor type A 646 AAY59682 Homo sapiens Secreted protein 108-009-5-0-488 100 A2-FL. 646 AAY01635 Homo sapiens Human PS214 derived 488 100 polypeptide. 646 AAY64650 Homo sapiens Human luman homology 488 100 protein. 647 gi13442978 Mus musculus D-lucuron I CS-e imerase 1001 94 647 gi 11935177 Mus musculus heparin/heparan 1001 94 sulfate : glucuronic acid C5 epimerase 647 i13654639 Bos taurus D-glucuronyl C5 epimerase 972 92 648 AAG00122 Homo sapiens Human secreted protein, SEQ ID 102 100 NO : 4203.

Table 2A SEQ Accession No. Species Description Score'1/ ID Identity NO : 648 gi4583535 Homo sapiens integrin alpha 2 subunit (ITGA2) 99 95 DNA, 5'UTR and promoter region. 648 AAW70542 Homo sapiens Integrin alpha-2 chain. 102 100 649 AAY01387 Homo sapiens Secreted protein encoded by 60 40 gene 5 clone HTLFE42. 649 gi3406819 Mus musculus growth factor receptor 58 38 649 AAG02139 Homo sapiens Human secreted protein, SEQ ID 53 40 NO : 6220. 650 AAB12150 Homo sapiens Hydrophobic domain protein 683 100 isolated from HT-1080 cells. 650 gil3096862 Mus musculus RIKEN cDNA 9430096L06 634 90 gene 650 AAB29651 Homo sapiens Human membrane-associated 502 loo protein HUMAP-8. 651 gi 14250140 Homo sapiens clone MGC : 14809, mRNA, 173 100 complete cds. 651 gi561639 Homo sapiens IgE receptor beta chain (HTm4) 173 100 mRNA, complete cds. 651 AAW06503 Homo sapicns HTm4 protein. 173 100 652 AAY41428 Homo sapiens Fragment of human secreted 107 43 protein encoded by gene 17. 652 AAY41324 Homo sapiens Human secreted protein encoded 108 40 by gene 17 clone HNFIY77. 652 AAB67576 Homo sapiens Amino acid sequence of a 108 40 human hydrolytic enzyme HYENZ8. 653 gi7209315 Homo sapiens mRNA for FLJ00007 protein, 1024 79 partial cds. 653 AAY99428 Homo sapiens Human PRO1431 (UNQ737) 430 93 amino acid sequence SEQ ID NO : 315. 653 gi6599145 Homo sapiens mRNA ; cDNA DKFZp434L127 320 33 (from clone DKFZp434L127) ; partial cds. 654 gi297172 Rattus rattus ribosomal protein S7 432 93 654 gi2811284 Mus musculus ribosomal protein S7 432 93 654 gi12804027 Homo sapiens ribosomal protein S7, clone 432 93 MGC : 10268, mRNA, complete cds. 655 AAB68888 Homo sapiens Human RECAP polypeptide, 277 64 SEQ ID NO : 18. 655 AAB08944 Homo sapiens Human secreted protein 74 72 sequence encoded by gene 19 SEQ ID NO : 10 1. 655 AAY76198 Homo sapiens Human secreted protein encoded 67 59 by gene 75. 656 gi4096055 Homo sapiens chromosome 19, cosmid 136 100 R28379, complete sequence. 656 gi9950071 Pseudomonas probable permease of ABC 81 39 aeruginosa transporter 656 gi2113989 Mycobacterium ccsA 79 34 tuberculosis 657 gi10438804 Homo sapiens cDNA : FLJ22419 fis, clone 26292 Table 2A SEQ Accession No. Species Description Score % ID Identity NO : HRC08593. 657 gi 10436785 Homo sapiens cDNA FLJ 14342 fis, clone 98 42 THYRO1000569, highly similar to Mus musculus hematopoietic zinc finger protein mRNA. 657 gi6690339 Mus musculus hematopoietic zinc finger 96 40 protein 658 gi9963845 Homo sapiens HT017 mRNA, complete cds. 558 38 658 AAW09405 Homo sapiens Pineal gland specific gene-) 558 38 protein. 658 AAB69185 Homo sapiens Human hiSLR-isoprotein SEQ 558 38 ID NO : 7. 659 gi475542 Rattus norvegicus glutamate receptor delta-1 505 98 subunit 659 gi220418 Mus musculus glutamate receptor channel 505 98 subunit delta-l 659 gi56286 Rattus norvegicus glutamate receptor subtype 482 98 delta-1 660 AAB61880 Homo sapiens Human cytokine receptor 163 28 Zcytor 14. 660 AAB61881 Homo sapiens Human variantZcytorl4protein 137 32 Zc ytor I 4-1. 660 AAB87606 Homo sapiens Human PR020040. 143 28 661 gi 13195147 Mus musculus HCH 413 86 661. gi 1339910 Homo sapiens Human DOCK180 protein 373 78 mRNA, complete cds. 661 AAW03515 Homo sapiens Human DOCK180 protein. 366 76 662 AAY27669 Homo sapiens Human secreted protein encoded 255 100 by gene No. 103. 662 gi3719255 Mus musculus Clq/MBL/SPA receptor ClqRp 50 35 662 gi5714405 Musmusculus Clq/MBL/SP-Aphagocytic 50 35 receptor C 1 qRp 663 gi12724402 Lactococcus lactis prophage pi3 protein 41 58 36 subsp. lactis 663 gi 155287 Vibrio cholerae disulfide isomerase 73 29 664 gi6822060 Arabidopsis thaliana peptide transport-like protein 93 31 664 gi206311 Rattus norve icus rotein hos hatase-2Bc 58 30 665 gi14042519 Homo sapiens cDNA FLJ14763 fis, clone 2026 99 NT2RP3003621. 665 gi 13097630 Homo sapiens clone MGC : 10791, mRNA, 2026 99 complete cds. 665 gi 13591620 Homo sapiens kremen mRNA for kringle-860 49 containing transmembrane protein, complete cds. 666 gil3161409 Mus musculus family4 cytochrome P450 437 73 666 gi7331756 Caenorhabditis contains similarity to Pfam 139 37 elegans family PF00067 (Cytochrome P450), score=356. 1, E=3. 6e-103, N=l 666 gi3876203 Caenorhabditis contains similarity to Pfam 135 37 elegans domain : PF00067 (Cytochrome P450), Score=347. 4, E- value=5. le-101, N=1 667 AAB08862 Homo sapiens Amino acid sequence of a 958 100 Table 2A SEQ Accession No. Species Description Score % 1 D Identity NO : human secretory protein. 667 girl2654587 Homo sapiens clone MGC : 2463, mRNA, 953 99 complete cds. 667 AAB12163 Homo sapiens Hydrophobic domain protein 953 99 from clone HP 10671 isolated from Thymus cells. 668 gi4877582 Homo sapiens lipoma HMGIC fusion partner 195 30 (LHFP) mRNA, complete cds. 668 AAY87336 Homo sapiens Human signal peptide containing 195 30 protein HSPP-113 SEQ ID NO : 113. 668 gi7529641 Schizosaccharomyces calcium permease family 28 pombe membrane transporter 669 gi3598974 Rattus norvegicus protein tyrosine phosphatase 105 38 TD 14 669 gi6625751 Mink enteritis virus capsid protein VP2 50 34 669 gi5442034 Mus musculus calmodulin-dependent protein 66 37 kinase 11 beta M isoform 670 AAB33892 Homo sapiens Human secreted protein BLAST 43 60 search protein SEQ ID NO : 107. 670 AAB54248 Homo sapiens Human pancreatic cancer 62 42 antigen protein sequence SEQ ID NO : 700. 670 gi683548 Chironomus gamma protein constant region 62 38 pallidivittatus 671 gi41077 Escherichia coli cal protein precursor (aa 1-51) 63 42 671 gi2995968 Leontopithecus NADH dehydrogenase subunit 4 76 28 rosalia 671 gi2995972 Leontopithecus NADH dehydrogenase subunit 4 76 28 chrysomelas 672 gil 196439 Homo sapiens (clone H 4. 4) latent transforming 291 98 growth factor-beta binding protein (LTBP-I L) gene, partial cds. 672 gi207286 Rattus norvegicus TGF-beta masking protein large 226 77 subunit 672 gi3493176 Mus musculus latent TGF beta binding protein 217 73 Table 2B SEQ Accession No. Species Description Score % 1 D Identity NO : 337 AAG81442 Homo sapiens ZYMO Human AFP protein 844 100 'sequence SEQ ID N0 : 402. 337 AA012909 Homo sapiens HYSE-Human polypeptide SEQ 526 100 ID NO 26801. 337 gil2580867 Picea abies 60S ribosomal protein L13E 80 33 338 gi8953907 Mus musculus thymic stromal lymphopoietin 79 30 receptor 338 AAY57951 Homo sapiens INCY-Human transmembrane 76 33 protein HTMPN-75. 338 gi7243288 Mus musculus cytokine receptor like molecule 75 29 2 339 AAR91305 Homo sapiens SAKA Transcription factor-IIIA. 96 45 339 gi 1616942 Homo sapiens Xenopus transcription factor 96 45 IIIA homologue 339 gi7417372 Homo sapiens intracellular hyaluronan-binding 93 40 protein 340 AAE14342 Homo sapiens INCY-Human protease PRTS-7 251 100 protein. 340 AAB08950 Homo sapiens HUMA-Human secreted protein 251 100 sequence encoded by gene 22 SEQ ID NO 107. 340 AAB08912 Homo sapiens HUMA-Human secreted protein 251 100 sequence encoded by gene 22 SEQ ID NO : 69. 341 gill88672lgblA Homo sapiens mannose 6-phosphate receptor 65 44 AA59866. I b 341 gil70254 1 6Igbl Solanum NADH dehydrogenase subunit 65 31 AAF35878. I | campechiense AF224071 1 342 AAY02361 Homo sapiens ONOY Polypeptide identified by 1131 100 the signal sequence trap method. 342 AAY 17526 Homo sapiens GEMY Human secreted protein 1131 100 clone AM349 2 protein. 342 gi20988438 Homo sapiens Similar to chondroitin betal, 4 N-1131 100 acetylgalactosaminyltransferase 343 gi7768740 Homo sapiens similar to zinc finger 5 protein 79 29 343 gi20809693 Homo sapiens Similar to RIKEN cDNA 73 32 4933432E21 gene 343 girl4329696 Homo sapiens Doublesex-mab-3 (DM) domain 73 32 344 ABB85001 Homo sapiens GETH Human PR028631 1576 99 protein sequence SEQ ID NO : 370. 344 AAY86234 Homo sapiens HUMA-Human secreted protein 475 60 HNTNC20, SEQ ID NO : 149. 344 AAB65258 Homo sapiens GETH Human PROD53) 09 30 (UNQ583) protein sequence SEQ ID NO : 35 1. 345 gi20072551 Mus musculus RIKEN cDNA 493051 IJI I gene 431 45 345 gi12836893 Gallus gallus IPR328-like protein 151 30 345 gi 17974542 Homosapiens vottage-dependentcatcium i50 26 channel gamma-8 subunit 346 AAA54097_aa Homo sapiens GETH PR0228 cDNA. 396 100 I 346 AAE17037 Homo sapiens MILL-Human G protein-396 100 Table 2B SEQ Accession No. Species Description Score % ID Identity NO : coupled receptor, SLGP 7 transmembrane receptor profile. 346 AAE17031 Homo sapiens MILL-Human G protein-396 100 coupled receptor (GPCR), SLGP. 347 gi 1504002 Homo sapiens similar to a human major CRK-252 100 binding protein DOCK180. 347 gi 13195147 Mus musculus HCH 206 77 347 AAW03515 Homo sapiens SHKJ Human DOCK180 95 43 protein. 348 gil21291633lg Anopheles agCP14673 73 25 blEAA03778. 1 gambiae str. PEST 349 gi 16359249 Mus musculus RIKEN cDNA 130001 OM03 1854 gene 349 AAU28182 Homo sapiens HYSE-Novel human secretory 574 38 protein, Seq ID No 351. 349 ABB89832 Homo sapiens HUMA-Human polypeptide 522 39 SEQ ID NO 2208. 350 ABB 11722 Homo sapiens HYSE-Human Vsegment 856 99 homologue, SEQ ID NO : 2092. 350 gi 1552496 Homo sapiens V segment translation product 614 100 350 AAR26977 Homo sapiens ROUS Human T lymphocyte 609 100 receptor V-bcta 9 subfamily segment. 351 AAU20502 Homo sapiens HUMA-Human secreted 162 80 protein, Seq ID No 494. 351 gi 13960126 Homo sapiens Similar to leucine-rich neuronal 162 80 protein 351 AAU20424 Homo sapiens HUMA-Human secreted 133 64 protein, Seq ID No 416. 352 AAB61141 Homo sapiens CURA-Human NOVI I protein. 370 86 352 AAU00392 Homo sapiens CURA-Human secreted protein, 370 86 POLY4. 352 AAU08681 Homo sapiens CURA-Human FCTR3f 370 86 polypeptide sequence. 353 AAE01313 Homo sapiens HUMA-Human gene 2 encoded 499 69 secreted protein fragment, SEQ I D NO : 178. 353 AAE01233 Homo sapiens HUMA-Human gene 2 encoded 482 69 secreted protein HMVAV54, SEQ ID NO : 95. 353 AAE01259 Homo sapiens HUMA-Human gene 2 encoded 476 68 secreted protein HMVAV54, SEQ ID NO : 121. 354 AAM95682 Homo sapiens HUMA-Human reproductive 254 72 system related antigen SEQ ID NO : 4340. 354 AAU 16249 Homo sapiens HUMA-Human novel secreted 224 95 protein, Seq ID 1202. 354 ABB06198 Homo sapiens BIOW-Human DNA 193 78 methylation protein 13 SEQ ID NO : 2. 355 AAE07054 Homo sapiens HUMA-Human gene 4 encoded 680 82 Table 2B SEQ Accession No. Species Description Score % ID Identity NO : secreted protein HSYAB05, SEQ ID NO : 71. 355 AAE07077 Homo sapiens HUMA-Human gene 4 encoded 608 76 secreted protein HSYAB05, SEQ ID NO : 94. 355 ABB89204 Homo sapiens HUMA-Human polypeptide 456 73 SEQ ID NO 1580. 356 AAU91320 Homo sapiens CYTO-Human P450TEC 865 100 protein. 356 gui15080572 Homo sapiens Similar to Ri KEN CDNA 859 100 8430436A 10 gene 356 AAE05183 Homo sapiens INCY-Human drug 168 35 metabolising enzyme (DME-14) protein. 357 AAU81988 Homo sapiens INCY-Human secreted protein 484 66 SECP) 4. 357 AAE06581 Homo sapiens SAGA Human protein having 484 66 hydrophobic domain, HP03727. 357 AAM41951 Homo sapiens HYSE-Human polypeptide SEQ 181 94 ID NO 6882. 358 AAE03888 Homo sapiens HUMA-Human gene 19 359 95 encoded secreted protein fragment, SEQ ID NO : 140. 358 AAE03836 Homo sapiens HUMA-Human gene 19 359 95 encoded secreted protein HOGCE48, SEQ ID NO : 82. 35S ABB11587 Homo sapiens HYSE-Human peroxidasin 359 95 homologue, SEQ ID NO : 1957. 359 AAM77193 Homo sapiens MOLE-Human bone marrow 112 56 expressed probe encoded protein SEQ ID NO : 37499. 359 AAM64370 Homo sapiens MOLE-Human brain expressed 112 56 single exon probe encoded protein SEQ ID NO : 36475. 359 gi7380324 Neisseria CUB protein 83 32 meningitidis Z2491 360 AAE06576 Homo sapiens SAGA Human protein having 1041 79 hydrophobic domain, HP 10764. 360 AAB65258 Homo sapiens GETH Human PRO1153 1038 79 (UNQ583) protein sequence SEQ ID NO : 351. 360 AAG81325 Homo sapiens ZYMO Human AFP protein 1038 79 sequence SEQ ID NO : 168. 361 gi 15919295 human UL97 protein 71 34 herpesvirus 5 361 gi221797 Human LMPI 70 31 herpesvirus 4 361 gi22938 Human latent membrane protein LMP1 70 31 herpesvirus 4 362 gi3127176 Homo sapiens sulfonylurea receptor 2B 886 67 362 gi3127175 Homo sapiens sulfonylurea receptor 2A 886 67 362 gil5778680 Oryctolagus sulphonylurea receptor 2B 873 66 cuniculus Table 2B SEQ Accession No. Species Description Score % ! D identity NO : 364 girl8077667 Homo sapiens bA 115 P 16. 2 (inositol 1, 4, 5- 88 32 trisphosphate 3-kinase B) 364 girl4329672 Homo sapiens inositol 1, 4, 5-trisphosphate 3-88 32 kinase, isoform B 364 AAE04364 Homo sapiens INCY-Human kinase (IN)-5. 85 32 365 ABB89967 Homo sapiens HUMA-Human polypeptide 462 95 SEQ ID NO 2343. 365 AAV42697_aa Homo sapiens SIBI-DNA encoding human 114 27 1 calcium channel alpha-1 D subunit. 365 AAQ84653 aa Homo sapiens SALK Human neuronal calcium 114 27 1 channel subunit alpha I D. 366 gi 13623421 Homo sapiens Similar to R I KEN cDNA 571 73 5730589L02 gene 366 gi 19484086 Mus musculus RIKEN CDNA 5730589LO2 543 69 gene 366 gi3875896 Caenorhabditi weak similarity to chalcone 118 28 s elegans flavone isomerase (Swiss Prot accession number P 11651) 367 AAE 18208 Homo sapiens CURA-Human MOL I b Drotein. 125 87 367 AAY06816 Homo sapiens UYYA Human Notch2 (humN2) 125 87 protein sequence. 367 gi 1275978 Homo sapiens NOTCH 2 125 87 368 AAB47275 Homo sapiens META-hOAT4. 652 99 368 ABB11750 Homo sapiens HYSE-Human integral 646 98 membrane transport protein homologue, SEQ ID NO : 2120. 368 gi 18148873 Homo sapiens hUST3 645 98 369 gil665787 Homo sapiens Similar to a C. elegans protein 256 100 encoded in cosmid C52E12 (U50135) 369 gil 1463949 Homo sapiens UDP-glucuronic acid 256 100 369 gi 14971008 Drosophila UDP-sugar transporter 195 71 melanogaster 370 AAW61626 Homo sapiens HUMA-Clone HUVBB80 of 75 26 TM4SF superfamily. 370 gi 15680044 Homo sapiens Similar to transmembrane 4 75 26 superfamily member 1 370 AAW80948 Homo sapiens INCY-Amino acid sequence of 73 26 the human integral membrane protein-2. 371 ABB06152 Homo sapiens COMP-Human NS protein 905 94 sequence SEQ ID NO : 244. 371 AAB88377 Homo sapiens HELI-Human membrane or 370 94 secretory protein clone PSEC0113. 371 gi 15291323 Drosophila GH 15686p 315 36 melanogaster 372 AAM40758 Homo sapiens HYSE-Human polypeptide SEQ 80 34 ID NO 5689. 373 AAW03515 Homo sapiens SHKJ Human DOCK180 120 54 protein. 373 gi1339910 Homo sapiens DOCK180 rotein 120 54 373 AAM90486 Homo sapiens HUMA-Human 118 95 Table 2B SEQ Accession No. Species Description Score % ID Identity NO : immune/haematopoietic antigen SEQ ID NO : 18079. 374 AAG77172 Homo sapiens HUMA-Human colon cancer 215 72 antigen protein SEQ ID NO : 7938. 374 gi 17946183 Drosophila RE56564p 37 melanogaster 374 gi 16182326 Drosophila GH01206p 116 20 melanogaster 375 AAB71871 Homo sapiens MILL-Human GLRP seven 73 30 transmembrane domain. 375 AAR70006 Homo sapiens MERI Human glucagon-like 1 73 30 peptide (GLP-1) receptor. 375 gi717034 Homo sapiens glucagon-like peptide-l receptor 73 30 376 gi 14189735 Homo sapiens ATP-binding cassette transporter 251 43 family A member 12 376 gi 14209836 Mus musculus ATP-binding cassette transporter 199 39 sub-family A member 7 376 AAU09174 Homo sapiens MILL-Human transporter 196 40 molecule, MTP-I. 377 AAM92700 Homo sapiens HUMA-Human digestive 208 67 system antigen SEQ ID NO : . 2049. 377 AAB60501 Homo sapiens INCY-Human cell cycle and 74 27 proliferation protein CCYPR-49, SEQ ID NO : 49. 377 AAM40936 Homo sapiens HYSE-Human polypeptide SEQ 74 27 ID NO 5867. 378 AAY30817 Homo sapiens HUMA-Human secreted protein 569 98 encoded from gene 7. 378 gi3184264 Homo sapiens F02569 2 101 29 378 gi3386544 Mus musculus IER5 98 37 379 AAU83223 Homo sapiens ZYMO Novel secreted protein 1440 100 Z930582G 14P. 379 AAU83150 Homo sapiens ZYMO Novel secreted protein 1440 100 Z849065G4P. 379 ABB84889 Homo sapiens GETH Human PRO1415 protein 1435 99 sequence SEQ ID NO : 146. 380 AAU 19385 Homo sapiens PHAA Human G protein-219 95 coupled receptor nGPCR-2318. 380 gi6636340 Rattus myosin heavy chain Myr 8 157 61 norvegicus 380 gi10863773 Rattus myosin heavy chain Myr 8b 157 61 norvegicus 381 gi18256029 Mus musculus Similarto RIKEN cDNA 270 85 6720456116 gene 381 gi20988563 Homo sapiens similar to claudin 19 97 36 381 gi20148965 Mus musculus claudin 19 97 36 382 gi 1679584 Cavia membrane cofactor protein 77 37 porcellus precursor 382 gi 1655471 Cavia membrane cofactor 77 37 porcellus-full) 382 AAV27592 aa Homo sapiens I MMV Human interleukin-17 73 31 1 receptor cDNA.

Table 2B SEQ Accession No. Species Description Score % ID Identity NO : 383 gi2764507 Locusta nicotinic acetylcholine receptor, 158 38 migratoria alphal subunit 383 gi9886085 Mus musculus nicotinic acetlycholine receptor 155 46 alpha 4 subunit 383 girl4330017 Mus musculus bM401L17. 2. 2 (cholinergic 155 46 receptor, nicotinic, alpha polypeptide 4 (isoform 2)) 384 gi4995986 Human 13. 6% identical to DR8 gene of 134 41 herpesvirus 6 strain U 1102 of HHV-6 384 gi409995 Rattus sp. mucin 129 42 384 AAM65950 Homo sapiens MOLE-Human bone marrow 123 44 expressed probe encoded protein SEQ ID NO : 26256. 385 ABB06082 Homo sapiens COMP-Human NS protein 870 99 sequence SEQ ID NO : 174. 385 AAY58174 Homo sapiens INCY-Human embryogenesis 870 99 protein, EMPRO. 385 AAB94377 Homo sapiens HELI-Human protein sequence 664 73 SEQ ID NO : 14922. 386 gi 13359817 Escherichia high-affinity choline transport 1021 100 coli 0157 : H7 386 gi 1657512 Escherichia high-affinity choline transport 1021 100 coli protein 386 gi 12513126 Escherichia high-affinity choline transport 1021 100 coli 0157 : H7 EDL933 387 gi 10584473 Halobacterium Vng6455c 79 27 sp. NRC-1 387 gi10584129 Halobacterium Vng6071c 79 27 sp. NRC-1 387 gi 12721708 Pasteurella UhpB 78 19 multocida 388 gi 13364609 Escherichia fumarate reductase FrdD 515 96 coli 0157 : H7 388 go) 45266 Escherichia gl3 protein 515 96 coli 388 gi 12519135 Escherichia fumarate reductase, anaerobic, 515 96 coli 0157 : H7 membrane anchor polypeptide EDL933 389 gi 13363448 Escherichia transport protein of hexuronates 928 96 coli 0157 : H7 389 go 1160319 Escherichia aldohexuronate transport system 928 96 coli 389 gi 12517683 Escherichia transport of hexuronates 928 96 coli 0157 : H7 EDL933 390 gi395270 Escherichia FepE 402 100 coli 390 gui 1778503 Escherichia ferric enterobactin transport 402 100 coli protein 390 gi) 786802 Escherichia ferric enterobactin (enterochelin) 402 100 coli K12 transport 391 gi 13362064 Escherichia methyl-accepting chemotaxis 648 83 coli 0157 : H7 protein II Table 2B SEQ Accession No. Species Description Score % ID Identity NO : 391 gi 1736545 Escherichia Methyl-accepting chemotaxis 648 83 coli protein 11 (MCP-II) (Aspartate chemoreceptor protein). 391 gi 145521 Escherichia methyl-accepting chemotaxis 648 83 coli protein 11 392 AAM72391 Homo sapiens MOLE-Human bone marrow 307 100 expressed probe encoded protein SEQ ID NO : 32697. 392 AAM59804 Homo sapiens MOLE-Human brain expressed 307 100 single exon probe encoded protein SEQ ID NO : 31909. 392 AAB37990 Homo sapiens HUMA-Human secreted protein 303 98 encoded by gene 7 clone HWLHH15. 393 gi3282259 Cucumaria ND4L 68 30 pseudocurata 393 gil20876844lre Mus musculus similar to ring finger protein 26 68 26 flXP_127831. I I 393 gil3282259lgbl Cucumaria ND4L 68 30 AAC69448. 11 pseudocurata 394 gi 13881068 Mycobacteriu sugar transporter family protein 83 26 m tuberculosis CD055) 394 gi 15074628 Sinorhizobium PUTATIVE 82 26 meliloti TRANSMEMBRANE PROTEIN 394 gi 15723037 Burkholderia multidrug efflux protein 81 26 cepacia 395 AAY90272. Homo sapiens LUDW-Human PTPLI 81 34 phosphatase. 395 AAB 19343 Homo sapiens ISIS-Amino acid sequence of a 81 34 human Fap-I (Fas associated protein 1). 395 AAW75999 Homo sapiens LUDW-Intracellular protein 81 34 tyrosine phosphatase, PTPLI. 396 AAM65947 Homo sapiens MOLE-Human bone marrow 215 25 expressed probe encoded protein SEQ ID NO : 26253. 396 AAM53564 Homo sapiens MOLE-Human brain expressed 215 25 single exon probe encoded protein SEQ ID NO : 25669. 396 gi16412587 Listeria similar to bacteriophage minor 123 14 innocua tail proteins 397 AA002567 Homo sapiens HYSE-Human polypeptide SEQ 351 94 I D NO 16459. 397 AAB88433 Homo sapiens HELI-Human membrane or 299 55 secretory protein clone PSEC0210. 397 AAB95155 Homo sapiens HELI-Human protein sequence 299 55 SEQ ID NO : 17188. 398 gil655432 Mus musculus plexin 2 211 32 398 AAB80241 Homo sapiens GETH Human PR0235 protein. 208 62 398 AAU 12337 Homo sapiens GETH Human PR0235 208 62 Table 2B SEQ Accession No. species Description Score ID Identity NO : polypeptide sequence. 399 AAU81997 Homo sapiens INCY-Human secreted protein 573 100 SECP23. 399 ABB94017 Homo sapiens HUMA-Human secreted protein 573 100 SEQ ID NO : 60. 399 AAB95289 Homo sapiens HELI-Human protein sequence 573 100 SEQ DNO :] 7509. 400 AAZ09920_aa Homo sapiens FARB Human islet cell antigen 241 40 1 clone ICA-525 cDNA. 400 AAV63558_aa Homo sapiens FARB Islet cell antibody antigen 241 40 1 cDNA from clone ICA-525. 400 AAB48573 Homo sapiens LUDW-Human breast cancer 241 40 MO-BC-416 polypeptide. 401 AAY87340 Homo sapiens INCY-Human signal peptide 2104 100 containing protein HSPP-1 17 SEQ ID NO : 117. 401 gi 13543949 Homo sapiens Similar to RIKEN cDNA 2104 100 2810432L12 gene 401 gi 15489421 Mus musculus RIKEN CDNA 2810432L 12 2083 98 gene 402 gi5001993 Dissostichus chimeric AFGP/trypsinogen-like 195 46 mawsoni serine protease precursor 402 gi295736 Dictyostelium spore coat protein sp96 186 48 discoideum 402 gi 19570090 Dictyostelium Spore coat protein SP96. 186 48 discoideum 403 gi4206769 Acanthamoeb myosin I heavy chain kinase 131 26 a castellanii 403 gi3599478 Acanthamoeb Myosin-lA 127 34 a castellanii 403 gi2723935 Turnip yellow No definition line found 116 29 mosaic virus 404 AAF90612_aa Homo sapiens ZYMO Human secretin-like 663 100 I receptor Zgprl cDNA. 404 AAE15635 Homo sapiens INCY-Human G-protein 663 100 coupled receptor-5 (GCREC-5) protein. 404 AAB66272 Homo sapiens MILL-Human TANGO 378 663 100 SEQ ID NO : 29. 405 gi3850044 Homo sapiens beta-tubulin cofactor D 94 87 405 girl3111855 Homo sapiens tubulin-specific chaperone d 94 87 405 gi 1465770 Bos taurus cofactor D 89 75 406 AAC84384_aa Homo sapiens MILL-Human A236 692 100 I polypeptide coding sequence. 406 AAU83656 Homo sapiens GETH Human PRO protein, Seq 692 100 ID No 130. 406 ABB84848 Homo sapiens GETH Human PR0363 protein 692 100 sequence SEQ ID NO : 64. 407 AAH77291_aa Homo sapiens MILL-Human ion channel 791 99 I protein IC23949 cDNA coding region. 407 AAG77968 Homo sapiens MILL-Human ion channel 791 99 protein IC23949. 407 AAO14211 Homo sapiens INCY-Human transporter and 791 99 Table 2B SEQ Accession No. Species Description Score % ID Identity NO : ion channel TRICH-28. 408 AAM40199 Homo sapiens HYSE-Human polypeptide SEQ 142 76 ID NO 3344. 408 AAM40198 Homo sapiens HYSE-Human polypeptide SEQ 142 76 I D NO 3343. 408 AAM41986 Homo sapiens HYSE-Human polypeptide SEQ 141 100 ID NO 6917. 409 AAM69908 Homo sapiens MOLE-Human bone marrow 201 100 expressed probe encoded protein SEQ ID NO : 30214. 409 AAM57504 Homo sapiens MOLE-Human brain expressed 201 100 single exon probe encoded protein SEQ ID NO : 29609. 409 gui 172177 Saccharomyce protein kinase C-like protein 81 23 s cerevisiae (PKC 1) 410 AAY99420 Homo sapiens GETH Human PRO1486 1082 100 (UNQ755) amino acid sequence SEQ ID NO : 287. 410 ABB50515 Homo sapiens HUMA-Human secreted protein 1069 99 encoded by gene 45 SEQ ID NO : 463. 410 AAW88747 Homo sapiens HUMA-Secreted protein 1069 99 encoded by gene 45 clone HCESF40. AAM93655 Homo sapiens HELI-Human polypeptide, SEQ 621 59 ID NO : 3524. 411 AAO14195 Homo sapiens INCY-Human transporter and 303 32 ion channel TRICH-12. 411 AAE06584 Homo sapiens SAGA Human protein having 303 32 hydrophobic domain, HP03913. 412 AAE14336 Homo sapiens INCY-Human protease PRTS-1 554 100 protein. 412 AAB65168 Homo sapiens GETH Human PRO) 3) 0 protein 554 100 sequence SEQ ID NO : 62. 412 AAU 12367 Homo sapiens GETH Human PRO1310 554 100 polypeptide sequence. 413 gi 14794894 Streptomyces AmphJ 73 28 nodosus 413 gil20833284lre Mus musculus RIKEN cDNA 9130404HI I 185 97 flXP_131474. 1 I 413 gill4794894lg Streptomyces AmphJ 73 28 blAAK73502. 1 nodosus IAF357202 5 414 AAM80242 Homo sapiens HYSE-Human protein SEQ ID 206 92 NO 3888. 414 AAM79258 Homo sapiens HYSE-Human protein SEQ ID 206 92 NO 1920. 414 gi5901822 Drosophila EG : 118B3. 2 160 70 melanogaster 415 gi 1834503 Homo sapiens mucin M UC5 B 72 38 416 gi3047402 Homo sapiens monocarboxylate transporter 2 524 32 416 gi21265165 Homo sapiens solute carrier family 16 523 32 (monocarboxylic acid Table 2B SEQ Accession No. Species Description Score % ID Identity NO : transporters), member 7 416 gi2198807 Gallus gallus monocarboxylate transporter 3 522 34 417 gi6136782 Mus musculus synaptotagmin V 595 91 417 gi 14210264 Rattus synaptotagmin 5 592 91 norvegicus 417 gi 1932801 Rattus synaptotagmin X 263 45 norvegicus 418 AAM93692 Homo sapiens HELI-Human polypeptide, SEQ 493 100 I D NO : 3602. 418 AAB53400 Homo sapiens HUMA-Human colon cancer 493 100 antigen protein sequence SEQ I D NO : 940. 418 ABB89424 Homo sapiens HUMA-Human polypeptide 489 100 SEQ ID NO 1800. 419 AAY57952 Homo sapiens INCY-Human transmembrane 1142 100 protein HTMPN-76. 419 AAB24036 Homo sapiens GETH Human PR04407 protein 1142 100 sequence SEQ ID NO : 47. 419 AAB12136 Homo sapiens PROT-Hydrophobic domain 1142 100 protein from clone HP10625 isolated from Liver cells. 420 gil 175324051re Cacnorhabditi C44B7. 6. p 72 32 flNP 495405. 1 s elegans 1 421 AAO14215 Homo sapiens INCY-Human transporter and 213 73 ion channel TRICH-32. 421 AAB47276 Homo sapiens META-hOAT5. 213 73 421 AAO14213 Homo sapiens INCY-Human transporter and 136 57 ion channel TRICH-30. 422 gi 17829 Brassica LEA76 peptide (AA 1-280) 124 26 napus 422 gi 13421492 Caulobacter methyl-accepting chemotaxis 118 20 crescentus protein McpC CB15 422 gi20126722 Brassica late embryogenesis-abundant 116 25 napus protein 424 gi 13959739 Caprine envelope glycoprotein 81 33 arthritis- encephalitis virus 424 gi323299 Caprine envelope polyprotein 77 32 arthritis- encephalitis virus 424 gi 15042572 Ovine variant envelope glycoprotein 77 30 lentivirus precursor 425 ABB89424 Homo sapiens HUMA-Human polypeptide 220 91 SEQ I D NO 1800. 425 AAM93692 Homo sapiens HELI-Human polypeptide, SEQ 220 91 ID NO : 3602. 425 AAB53400 Homo sapiens HUMA-Human colon cancer 220 91 antigen protein sequence SEQ ID NO : 940. 426 AAG72312 Homo sapiens YEDA Human olfactory 868 92 Table 2B SEQ Accession No. Species Description Score % ID Identity NO : receptor polypeptide, SEQ ID NO : 1993. 426 AAU24606 Homo sapiens SENO-Human olfactory 868 92 receptor AOLFR97. 426 git 8480638 Musmuscuius otfactory receptor MOR205-) 76580 427 AAG75482 Homo sapiens HUMA-Human colon cancer 90 66 antigen protein SEQ ID NO : 6246. 427 AAM67622 Homo sapiens MOLE-Human bone marrow 76 57 expressed probe encoded protein SEQ ID NO : 27928. 427 AAM55226 Homo sapiens MOLE-Human brain expressed 76 57 single exon probe encoded protein SEQ ID NO : 27331. 428 gi8918871 YccA of 96 pct identical to 288 98 plasmid gp : AB021078_30 Col I b-P9] plasmid F 428 gil7524597lrefl Pinus protochlorophyllide reductase 70 37 NP 042351. 11 thunbergii 58kDachain 428 gil 6330680 ! re Synechocystis ATP synthase e subunit 69 45 f NP 441408. 1 sp. PCC 6803 I 429 AAM79503 Homo sapiens HYSE-Human protein SEQ ID 81 41 NO 3149. 429 AAM78519 Homo sapiens HYSE-Human protein SEQ ID 81 41 NO 1181. 429 AAW40058 Homo sapiens USSH Cellular transcriptional 81 29 factor CBP. 430 AAB 18985 Homo sapiens INCY-Amino acid sequence of 284 31 a human transmembrane protein. 430 AAE00330 Homo sapiens ZYMO Human membrane-279 31 bound protein-60 (Zsig60). 430 xi6013381 Rattus TM6P1 279 30 norvegicus 431 AAU 16923 Homo sapiens HUMA-Human novel secreted 346 94 protein, SEQ ID 164. 431 gui 1934847 Caenorhabditi DNA topoisomerase 1 79 33 s elegans 431 gi 119348471em Caenorhabditi DNA topoisomerase ; DNA 79 33 blCAA65537. 1 s elegans topoisomerase I I 432 gi 1913791 Plasmodium merozoite surface protein 85 30 vivax 432 gi537916 6 Li) ium meiotin-t 84 32 longiflorum 432 gi2213848 Plasmodium merozite surface protein 1 82 30 vivax 433 gi 17429346 Ralstonia PUTATIVE LIPOPROTEIN 71 36 solanacearum 434 AAU77226 Homo sapiens DAMB/Human NR2A N-159 100 methyl D-aspartate (NMDA) receptor protein sequence. 434 AAR80970 Homo sapiens ALLX Human excitatory amino 159 100 Table 2B SEQ Accession No. Species Description Score % I Identity NO : acid receptor modulator protein N R2A-1. 434 AAR55529 Homo sapiens MERI Human NMDA R2A 159 100 receptor subunit. 435 gi 18044366 Homo sapiens Similar to MEGF10 protein 1166 90 435 AAG75479 Homo sapiens HUMA-Human colon cancer 817 62 antigen protein SEQ ID NO : 6243. 435 AAB66267 Homo sapiens MILL-Human TANGO 272 695 50 SEQ ID NO : 14. 436 gi3130157 Takifugu pheromone receptor 106 34 rubripes 436 gi2589210 Mus musculus calcium-sensing receptor related 105 35 protein 3 436 gi2589208 Mus musculus calcium-sensing receptor related 99 33 protein 2 437 gi 16605472 Homo sapiens acyl-malonyl condensing 1074 99 enzyme 437 gi4633135 Mus musculus condensing enzyme 679 50 437 gi2384746 Mus musculus testicular condensing enzyme 679 50 438 AAG81254 Homo sapiens ZYMO Human AFP protein 1195 86 sequence SEQ ID NO : 26. 438 gi7981261 Homo sapiens dJ50024. 4 (novel protein with 1195 86 DHHC zinc finger domain) 438 AAG74779 Homo sapiens HUMA-Human colon cancer 882 64 antigen protein SEQ ID NO : 5543. 439 AAO12277 Homo sapiens HYSE-Human polypeptide SEQ 74 44 I D NO 26169. 439 gi2209081 Rhytidoponera cytochrome b 73 25 sp. 440 gi 12314108 Homo sapiens dJ23013. 1 (novel protein) 868 84 440 AAB94417 Homo sapiens HELI-Human protein sequence 578 55 SEQ ID NO : 15016. 440 gil6416385 Arabidopsis anthocyanin-related membrane 330 33 thaliana protein 2 441 gi20988467 Mus musculus similar to LD47277p 1185 88 441 AAU91305 Homo sapiens CORT-Human protein 419 94 NOV 10c. 441 AAU91304 Homo sapiens CORT-Human protein 347 93 NOV l Ob. 442 gi21263092 Mus musculus tramdorin I 403 64 442 gi21263094 Rattus tramdorin 1 395 62 norvegicus 442 gi 14571904 Rattus lysosomal amino acid transporter 358 56 norvegicus 1 443 AAU 11817 Homo sapiens UYLE-Cancer and neurogenesis 877 72 associated gene, variant 5R23V2. 443 AAU 11816 Homo sapiens UYLE-Cancer and neurogenesis 877 72 associated gene, variant 5R-3V2. 443 AAU I 1815 Homo sapiens UYLE-Cancer and neurogenesis 877 72 associated gene, variant 5G-3V3. 444 gi 10 86503 Homo sapiens sialic acid-specific acetylesterase 932 100 Table 2B SEQ Accession No. Species Description Score % ID Identity NO : It 444 gi 10242345 Homo sapiens sialic acid-specific 9-O-753 100 acetylesterase I 444 gil628565 Mus musculus sialic acid-specific 9-O-751 81 acetylesterase 445 gill 8087335lg Homo sapiens serine/threonine protein kinase 222 54 blAAL58838. 1 kkialre-like 1 IAF390028_1 445 gill5609263lre Mycobacteriu PE_PGRS 100 36 flNP_216642. 1 m tuberculosis JH37Rv 445 gi 11425 1041 Ire Tupaia T49 93 33 pNP_116403. 1 herpesvirus I 446 gi3165565 Caenorhabditi C. elegans PTR-15 protein 114 23 s elegans (corresponding sequence T07H8. 6) 446 gil825729 Caenorhabditi C. elegans PTR-2 protein 110 25 s elegans (corresponding sequence C32E8. 8) 446 gi1255388 Caenorhabditi C. elegans PTR-I protein 83 25 s elegans (corresponding sequence C24B5. 3) 447 AAB88481 Homo sapiens HELI-Human membrane or 252 73 secretory protein clone PSEC0251. 447 AAE03835 Homo sapiens HUMA-Human gene 18 252 73 encoded secreted protein HFKHW50, SEQ ID NO : 81. 447 AAM78797 Homo sapiens HYSE-Human protein SEQ ID 170 67 NO 1459. 448 gi3130159 Takifugu pheromone receptor 210 63 rubripes 448 gill7482335lre Homo sapiens similar to vomeronasal 2, 448 76 f XP_064863 1 receptor, 4 ; vomeronasal organ family 2, receptor, 4 448 gil20948634lre Mus musculus similtr to vomeronasal 2, 260 79 fXP_142573. 1 receptor, 2 ; vomeronasal organ family 2 receptor 2 449 gi 13452508 Mus musculus claudin 14 438 39 449 AAU77764 Homo sapiens GETH Tumour associated 437 39 antigenic target polypeptide (TAT) 155. 449 AAY99431 Homo sapiens GETH Human PRO1571 437 39 (UNQ777) amino acid sequence SEQ ID NO : 324. 450 AAM65951 Homo sapiens MOLE-Human bone marrow 206 61 expressed probe encoded protein SEQ ID NO : 26257. 450 AAM53568 Homo sapiens MOLE-Human brain expressed 206 61 single exon probe encoded protein SEQ ID NO : 25673. 450 AAM73342 Homo sapiens MOLE-Human bone marrow 184 54 expressed probe encoded protein Table 2B SEQ Accession No. Species Description Score % ID Identity NO : SEQ ID NO : 33648. 451 gi 19343983 Homo sapiens GalNAc-4-sulfotransferase 2 213 97 451 gi 12711481 Homo sapiens N-acetylgalactosamine 4-O-187 97 sulfotransferase 2 GaINAc4ST-2 451 AAM69697 Homo sapiens MOLE-Human bone marrow 99 54 expressed probe encoded protein SEQ ID NO : 30003. 452 gi3150438 Human pol-env 258 55 endogenous retrovirus K 452 gi 1469243 Human pol/env 258 55 endogenous retrovirus K 452 gi4185944 Human env protein 258 55 endogenous retrovirus K 453 gi20563599 Homo sapiens methyl-CpG binding domain 982 98 protein 3-like protein 2 453. AAU00437 Homo sapiens COUN-Human dendritic cell 547 97 membrane protein FIRE. 453 AAY91625 Homo sapiens HUMA-Human secreted protein 547 97 sequence encoded by gene 22 SEQ ID NO : 298. 454 gi 15590686 Homo sapiens peptidoglycan recognition 1960 98 protein-l-beta precursor 454 AAY96963 Homo sapiens HUMA-Wound healing tissue 1810 92 peptidoglycan recognition protein-like protein. 454 gui15590684 Homo sapiens peptidoglycan recognition 1223 61 protein-l-alpha precursor 455 AAE19173 Homo sapiens INCY-Human protease, PRTS-1009 100 10 protein. 455 AAB72301 Homo sapiens HIRO/Human ADAMTS-9 1009 100 alternative amino acid sequence. 455 AAB72286 Homo sapiens HIRO/Human ADAMTS-9 1009 100 amino acid sequence. 456 ABK15497_aa Homo sapiens HOFF Human senescence 150 100 I associated epithelial membrane protein (SEMP 1) cDNA. 456 AAZ60459_aa Homo sapiens INCY-cDNA encoding a human 150 100 1 molecule associated with apoptosis 2 (MAPOP-2). 456 AAX19461 aa Homo sapiens UNIW Human senescence factor 150 100 1 p23 gene. 457 gill 1 1918231c Streptomyces elloramycin glycosyltransferase 70 47 mblCACl6413 olivaceus . 11 457 gil21301888lg Anopheles agCP8508 70 53 blEAA 14033. 1 gambiae str. PEST 457 gill7737304lre Drosophila sevenless 70 32 flNP_511114. 1 melanogaster I 458 AAM65947 Homo sapiens MOLE-Human bone marrow 158 14 Table 2B SEQ Accession No. Species Description Score % ID Identity NO : expressed probe encoded protein SEQ ID NO : 26253. 458 AAM53564 Homo sapiens MOLE-Human brain expressed 158 14 single exon probe encoded . protein SEQ ID NO : 25669. 458 gi4406172 Human latent membrane protein-1 149 36 herpesvirus 4 459 AAB93188 Homo sapiens HELI-Human protein sequence 251 83 SEQ ID NO : 12140. 459 AAB92702 Homo sapiens HELI-Human protein sequence 25 ! 83 SEQ ID NO : 11102. 459 AAM00899 Homo sapiens HYSE-Human bone marrow 251 83 protein, SEQ ID NO : 375. 460 AAG68349 Homo sapiens BODA-Human retinitis 345 100 pigmentosa related protein 14 SEQ ID NO : 2. 460 gil8175295 Homo sapiens CRBI isoform 11 precursor 345 100 460 gi 18182323 Mus musculus crumbs-like protein I precursor 247 71 461 AAM65406 Homo sapiens MOLE-Human brain expressed 277 100 single exon probe encoded protein SEQ ID NO : 37511. 461 AAM96299 Homo sapiens HUMA-Human reproductive 171 94 system related antigen SEQ ID NO : 4957. 461 gi396416 Escherichia similar to Neurospora crassa 71 37 coli phosphate-repressible phosphate permease 462 gi7677068 Homo sapiens endomembrane protein emp70 73 35 precursor isolog 463 AAB95530 Homo sapiens HEU-Human protein sequence 233 100 SEQ ID NO : 18126. 463 AAB93627 Homo sapiens HELI-Human protein sequence 195 80 SEQ ID NO : 13102. 463 gi2827162 Rattus rsec 15 195 80 norvegicus 464 gi 19171152 Homo sapiens ADAMTS-19 1321 98 464 AAE 10350 Homo sapiens PFIZ Human ADAMTS-J 1. 4 205 46 variant protein. 464 AAE10348 Homo sapiens PFIZ Human ADA MTS-J 1. 2 205 46 variant protein. 466 AAD12602_aa Homo sapiens SAGA Human protein having 354 100 I hydrophobic domain encoding cDNA clone HP10797. 466 AAB88353 Homo sapiens HELI-Human membrane or 354 100 secretory protein clone PSEC0079. 466 AAG81285 Homo sapiens ZYMO Human AFP protein 354 100 sequence SEQ ID NO : 88. 467 gil5729792lref Homo sapiens trinucleotide repeat containing 5 ; 67 39 NP 006577. 11 CAG repeat containing ; expanded repeat domain, CAG/CTG 5 ; CAG repeat domain 467 gi) 5229956re Arabidopsis omega-6 fatty acid desaturase, 67 36 Table 2B SEQ Accession No. Species Description Score % ID Identity NO : flNP_l 87819. 1 thaliana endoplasmic reticulum (FAD2) I 467 gil6969163lem Homo sapiens dJ475N 16. 1 (CTG4A) 67 39 blCAB7530 1. 1 468 AAB38330 Homo sapiens HUMA-Human secreted protein 214 97 encoded by gene 10 clone HTEBV72. 468 gil20341041lre Mus musculus RIKEN cDNA 4933424G06 109 48 flXP_110311. 1 I 469 AAM95018 Homo sapiens HUMA-Human reproductive 488 100 system related antigen SEQ ID NO : 3676. 469 gi 13311009 Homo sapiens NYD-SP 16 488 100 469 gi 1418266 Chlamydomon SF-assemblin 75 32 as eugametos 470 AAE06592 Homo sapiens SAGA Human protein having 357 100 hydrophobic domain, HP03884. 470 AAB13343 Homo sapiens LEXI-Human cortexin-like 203 59 protein. 470 ABB05043 Homo sapiens CURA-Human NOV5a protein 175 53 SEQ ID NO : 22. 471 gi 13938651 Mus musculus Similar to conserved membrane 502 83 protein at 44E 471 gi 16768782 Drosophila LD03322p 443 68 melanogaster 471 gi 14194169 Arabidopsis AtigO5960/T21 E 18_20 120 30 thaliana 472 gi310100 Rattus developmentally regulated 536 80 norvegicus protein 472 ABB17427 Homo sapiens HUMA-Human nervous system 455 100 related polypeptide SEQ ID NO 6084. 472 AAW52812 Homo sapiens INCY-Human induced tumour 227 37 protein. 473 AA167941 aa Horno sapiens FARB Human dopamine-like G 1711 100 I protein-coupled receptor (GPCR) encoding cDNA. 473 AAD30728aa Homo sapiens PFIZ Human G-protein coupled 1711 100 1 receptor (GPCR), PFI-007 cDNA. 473 AAD06020aa Homo sapiens MERE Human G-protein 1711 100 I coupled receptor, GPCR-KD5 cDNA. 474 AAE20142 Homo sapiens MERE Human protein 1593 85 containing ring finger domain, RIP4. 474 girl3872241 Homo sapiens bA400120. 1 (ligand of numb-1593 85 protein X) 474 gi 15282065 Mus musculus LNX2 1478 79 475 AAB08872 Homo sapiens INCY-Amino acid sequence of 77 93 a human secretory protein. 475 AAB73980 Homo sapiens GLAX Human stargazin-like 75 29 Table 2B SEQ Accession No. Species Description Score % ID Identity NO : protein CACNG4. 475 AAU08723 Homo sapiens GEMY Human clone hol 143 20 75 29 secretory protein. 477 gi l 0799398 Homo sapiens kallikrein 13 1513 100 477 gi6063386 Homo sapiens kallikrein-like protein 4 KLK-L4 1513 100 477 AAZ22639_aa Homo sapiens SMIK CASB 12 derived from 678 48 1 Expressed Sequence Tag sequences. 478 ABB08214 Homo sapiens ZYMO Human Zsig47 protein. 704 100 478 AAU83634 Homo sapiens GETH Human PRO protein, Seq 704 100 ID No 86. 478 AAB90662 Homo sapiens HUMA-Human secreted 704 100 protein, SEQ ID NO : 205. 479 AA000662 Homo sapiens HYSE-Human polypeptide SEQ 90 72 ID NO 14554. 479 gi6715140 Drosophila split ends 89 46 melanogaster 479 gi6979936 Drosophila split ends long isoform 89 46 melanogaster 480 gi 17944167 Drosophila GH I 0i78p 76 31 melanogaster 480 gi2340108 Zea mays starch. branching enzyme Ila 74 33 480 gi2764762 Amycolatopsi rifamycin polyketide synthase, 74 32 s mediterranei type 1 481. ABB90747 Homo sapiens UYJO Human Tumour 139 30 Endothelial Marker polypeptide SEQ ID NO 226. 481 ABB50291 Homo sapiens USSH Collagen type 111 alpha-l 139 30 ovarian tumour marker protein, SEQ ID NO : 72. 481 AAW 12843 Homo sapiens UYMA-Pro-alphal (III) : (I) CP 139 30 chimeric protein. 482 AAB65246 Homo sapiens GETH Human PRO1 100 787 100 (UNQ546) protein sequence SEQ ID NO : 299. 482 AAG81355 Homo sapiens ZYMO Human AFP protein 787 100 sequence SEQ ID NO : 228. 482 AAY66723 Homo sapiens GETH Membrane-bound protein 787 100 PRO)) 00. 483 AAB08216 Homo sapiens STRD A protein related to 247 56 Drosophila naked cuticle polypeptide. 483 gi16303260 Homo sapiens Dvl-binding protein NKD1 247 56 483 gil7978537 Homo sapiens naked protein 247 56 484 gi3452275 Pseudopleuron aminopeptidase N 210 28 ectes americanus 484 gi2766187 Gallus gallus aminopeptidase Ey 175 26 484 gi544755 Oryctolagus aminopeptidaseN ; APN 174 26 cuniculus 485 AAB58305 Homo sapiens ROSE/Lung cancer associated 273 100 polypeptide sequence SEQ ID 643. 485 gi17562350re Caenorhabditi K07C11. 10. p 103 42 Table 2B SEQ Accession No. Species Description Score % ID Identity NO : fNP_505121. 1 s elegans I 485 gill7565456lre Caenorhabditi Y38H6C. 3. p 79 29 f1NP507945. t seiegans I 486 AAB38019 Homo sapiens HUMA-Human secreted protein 583 99 encoded by gene 27 clone HPJBF63. 486 AAB38010 Homo sapiens HUMA-Human secreted protein 576 98 encoded by gene 27 clone HOUHD63. 486 gi 17742574 Agrobacteriu monooxygenase 79 41 m tumefaciens str. C58 (U. Washington) 487 AAY91385 Homo sapiens HUMA-Human secreted protein 969 100 sequence encoded by gene 40 SEQ 1D NO : 106. 487 AAU75555 Homo sapiens BIOJ Immunoglobulin 959 99 superfamily member GP286a. 487 AAU83610 Homo sapiens GETH Human PRO protein, Seq 959 99 I D No 38. 488 girl5779156 Homo sapiens Similar to RIKEN cDNA 262 96 1810073N04 gene 488 gi9971734 Galleria heavy-chain fibroin 116 34 mellonella 488 gil3880674 Mycobacteriu PE PGRS family protein 98 30 m tuberculosis CDC1551 489 gi409995 Rattus sp. mucin 167 64 489 AAM65950 Homo sapiens MOLE-Human bone marrow 146 61 expressed probe encoded protein SEQ ID NO : 26256. 489 AAM53567 Homo sapiens MOLE-Human brain expressed 146 61 single exon probe encoded protein SEQ ID NO : 25672. 490 gi 1841555 Homo sapiens NG5 422 100 490 ABB90246 Homo sapiens HUMA-Human polypeptide l l9 40 SEQ ID NO 2622. 490 ABB90038 Homo sapiens HUMA-Human polypeptide 119 28 SEQ ID NO 2414. 491 AAU07370 Homo sapiens PHAA G protein-coupled 117 30 receptor. 491 gi5732924 Toxocara excretory/secretory mucin 114 32 canis M UC-4 491 gi5732920 Toxocara excretory/secretory mucin 110 32 canis MUC-2 492 AAB80245 Homo sapiens GETH Human PR0257 protein. 395 100 492 AAB70534 Homo sapiens CURA-Human PR04 protein 395 100 sequence SEQ ID NO : 8. 492 AAU 12343 Homo sapiens GETH Human PR0257 395 100 polypeptide sequence. 493 gi 17861670 Drosophila GH20388p 159 30 melanogaster Table 2B SEQ Accession No. Species Description Score % ! D identity NO : 493 AAM76340 Homo sapiens MOLE-Human bone marrow 138 40 expressed probe encoded protein SEQ ID NO : 36646. 493 AAM63526 Homo sapiens MOLE-Human brain expressed 138 40 single exon probe encoded protein SEQ ID NO : 35631. 494 AAU83220 Homo sapiens ZYMO Novel secreted protein 1208 100 Z912187G I P. 494 AA001373 Homo sapiens HYSE-Human polypeptide SEQ 101 51 ID NO 15265. 494 AAM79091 Homo sapiens HYSE-Human protein SEQ ID 88 29 NO 1753. 495 git 841555 Homo sapiens Nos 80 42 495 AAB 18976 Homo sapiens INCY-Amino acid sequence of 67 40 a human transmembrane protein. 495 gi 1208236061re Mus musculus similar to SURF-1 protein-231 100 f XP_140861. 1 mouse I 496 gi9885193 Homo sapiens dJ881 L22. 3 (novel protein 1429 100 similar to a trypsin inhibitor) 496 gi2943716 Homo sapiens 25 kDa trypsin inhibitor 840 63 496 gi 13241970 Gallus gallus SugarCrisp 839 58 497 gi306316 Herpesvirus EBNA-2 163 36 papio 497 gi4096372 Rattus SH3 domain binding protein 158 28 norvegicus 497 gi4096360 Rattus CR 16 158 28 norvegicus 498 AAU81976 Homo sapiens INCY-Human secreted protein 373 100 SECP2. 498 ABB89091 Homo sapiens HUMA-Human polypeptide 373 100 SEQ ID NO 1467. 498 AAB70538 Homo sapiens CURA-Human PRO8 protein 373 100 sequence SEQ ID NO : 16. 499 AAE02938 Homo sapiens MILL-Human adenylate cyclase 262 100 25678. 499 AAB02006 Homo sapiens TEXA Adenylyl cyclase type Il-258 98 C2 C2 alpha domain. 499 gi202752 Rattus adenylyl cyclase type 11 258 98 norvegicus 500 AAB93931 Homo sapiens HELI-Human protein sequence 1083 70 SEQ ID NO : 13927. 500 gi 10440418 Homo sapiens FLJ00044 protein 1083 70 500 gi 16648518 Drosophila SD09360p 133 26 melanogaster 501 AA014401 Homo sapiens ELIL Novel human cerebellin-493 100 like protein (LP232). 501 AAE16346 Homo sapiens CURA-Human cerebellin-like 492 98 protein, POLY 10. 501 ABB84924 Homo sapiens GETH Human PRO1382 protein 492 98 sequence SEQ ID NO : 216. 502 gil9264106 Mus musculus RIKEN cDNA 2810049G06 1079 51 gene 502 gi) 9343843 Musmuscu) us Simitar to RIKEN cDNA 1005 46 Table 2B SEQ Accession No. Species Description Score % ID Identity NO : 2810049G06 gene 502 AAB93797 Homo sapiens HELI-Human protein sequence 956 53 SEQ ID NO : 13560. 503 AAG89306 Homo sapiens GEST Human secreted protein, 82 32 SEQ ID NO : 426. 503 gi5869819 Globodera NADH-ubiquinone 78 34 pallida oxidoreductase subunit 1 503 gi15026129 Clostridium Predicted membrane protein 78 32 acetobutylicu m 504 AA014201 Homo sapiens INCY-Human transporter and 1597 99 ion channel TRIC-18. 504 AAY34120 Homo sapiens AXYS-Human potassium 1597 99 channel K+Hnov4. 504 gi16611600 Homo sapiens voltage gated potassium channel 1597 99 Kv3. 2a 505 gi5902892 Streptomyces type 1 polyketide synthase 76 26 avermitilis AVES 2 505 AAM25582 Homo sapiens HYSE-Human protein sequence 73 27 SEQ ID NO : 1097. 505 ABB11449 Homo sapiens HYSE-Human P13-kinase 73 27 homologue, SEQ ID NO : 1819. 506 gi1049106 Homo sapiens dystonin isoform 2 76 52 506 gi904022 Mus musculus dystonin isoform 2 72 50 507 AAB94709 Homo sapiens HELI-Human protein sequence 89 29 SEQ ID NO : 15705. 507 AAU91279 Homo sapiens CURA-Human NOV3a protein. 88 33 507 gi6319138 Rattus ALG-2 interacting protein 1 84 36 norvegicus 508 gi2564916 Homo sapiens cotel 231 31 509 AAE01854 Homo sapiens HUMA-Human gene 17 371 82 encoded secreted protein fragment, SEQ ID NO : 180. 509 AAE01829 Homo sapiens HUMA-Human gene 17 371 82 encoded secreted protein HWBEM18, SEQ ID NO : 150. 509 AAE01786 Homo sapiens HUMA-Human gene 17 371 82 encoded secreted protein HWBEM18, SEQ ID NO : 107. 510 ABB04347 Homo sapiens SHAN-Human protein 614 95 phosphatase 4 regulatory subunit 37. 510 gil 1136904 Homo sapiens bA109J9. 1 (isoform 2 of 601 92 PRO1085 protein, similar to protein serine/threonine phosphatase 4 regulatory subunit I (PPP4R1)) 510 AAB73355 Homo sapiens MIYA/Human mesangial cell 312 51 meg-1 protein. 511 AAE03548 Homo sapiens FARB Human mitochondrial 1300 100 deformylase full length protein. 511 gil3195254 Homo sapiens polypeptide deformylase-like 1300 100 protein 511 gil 1320944 Homo sapiens peptide deformylase-like protein 1300 100 Table 2B 5r ; ll Accesson rvo. pecies Uescription core o ID Identity NO : 512 ABK15715 aa Homo sapiens MILL-Human 21612 alcohol 520 63 1 dehydrogenase (ADH) cDNA. 512 AAU76223 Homo sapiens MILL-Human 21612 alcohol 520 63 dehydrogenase (ADH) protein. 512 AAB84367 Homo sapiens MILL-Amino acid sequence of 520 63 human alcohol dehydrogenase 21612. 513 AAB31209 Homo sapiens GETH Amino acid sequence of 863 100 human polypeptide PRO941. 513 AAB44281 Homo sapiens GETH Human PRO941 863 too (UNQ478) protein sequence SEQ ID NO : 264. 513 AAY41725 Homo sapiens GETH Human PRO941 protein 863 100 sequence. 514 AAB08944 Homo sapiens HUMA-Human secreted protein 206 83 sequence encoded by gene 19 SEQ ID NO : 101. 514 AAB08909 Homo sapiens HUMA-Human secreted protein 159 80 sequence encoded by gene 19 SEQ ID NO : 66. 514 gi 15157368 Agrobacteriu AGR_C_4035p 68 30 m tumefaciens str. C58 (Cereon) 516 gi340002 Homo sapiens thyrotropin beta subunit 739 99 516 gi7690113 Homo sapiens thyroid-stimulating hormone 736 98 beta subunit 516 AAR99419 Homo sapiens GENZ TSH beta subunit. 723 98 517 AAB53436 Homo sapiens HUMA-Human colon cancer 368 97 antigen protein sequence SEQ ID NO : 976. 517 AAB25691 Homo sapiens HUMA-Human secreted protein 168 93 sequence encoded by gene 27 SEQ ID NO : 80. 517 AAG89263 Homo sapiens GEST Human secreted protein, 84 33 SEQ ID NO : 383. 518 AAU83188 Homo sapiens ZYMO Novel secreted protein 1443 100 Z887042G3P. 518 AAB85336 Homo sapiens CHIR Human oaf protein 1443 100 sequence. 518 AAE03851 Homo sapiens HUMA-Human gene 8 encoded 1437 99 secreted protein HBIOH81, SEQ ID NO : 97. 519 AAG76189 Homo sapiens HUMA-Human colon cancer 349 100 antigen protein SEQ ID NO : 6953. 520 AAB88377 Homo sapiens HELI-Human membrane or 379 91 secretory protein clone MEC0113. 520 ABB06152 Homo sapiens COMP-Human NS protein 137 85 sequence SEQ ID N0 : 244. 520 gill7465349lre Homo sapiens similar to solute carrier family 425 100 flXP_069720. 1 29 (nucleoside transporters), member 1 Table 2B SEQ Accession No. Species Description Score % ID Identity NO : 522 girl9263985 Homo sapiens Similar to RiKENcDNA 737 99 1300017EO9 gene 522 gi 19528309 Drosophila LD023 1 0p 269 53 melanogaster 522 gil9577352 Aspergillus probable adrenoleukodystrophy 71 31 fumigatus protein 523 AAY54053 Homo sapiens PHAA A variant of an 155 37 angiogenesis-associated protein which binds plasminogen. 523 AAY54052 Homo sapiens PHAA An angiogenesis-155 37 associated protein which binds plasminogen. 523 gi9887326 Homo sapiens angiomotin 155 37 524 gill 10720971g Homo sapiens MLL/GAS7 fusion protein 73 25 blAAG26333. 2 I 525 gi 1504002 Homo sapiens similar to a human major CRK-1040 84 binding protein DOCK180. 525 gi13195147 Mus musculus HCH 949 77 525 AAW03515 Homo sapiens SHKJ Human DOCK180 200 31 protein. 526 gi854065 Human U88 305 47 herpesvirus 6 526 AAB95124 Homo sapiens HELI-Human protein sequence 212 38 SEQ ID NO 17122. 526 AA002474 Homo sapiens HYSE-Human polypeptide SEQ 212 47 ID NO 16366. 527 AAG00214 Homo sapiens GEST Human secreted protein, 98 89 SEQ ID NO : 4295. 527 AAB58446 Homo sapiens ROSE/Lung cancer associated 98 89 polypeptide sequence SEQ ID 784. 527 AAY48278 Homo sapiens META-Human prostate cancer-98 89 associated protein 64. 528 gi15840618re Mycobacteriu 2, 4-dienoyl-coA reductase 69 34 flNP_335655. 1 m tuberculosis l CDC155 1 528 gil 1560831 5lre Mycobacteriu fadH 69 34 flNP_2 15691. 1 m tuberculosis H37Rv 529 AAU83079 Homo sapiens ZYMO Novel secreted protein 211 1 100 Z1297G2P. 529 AAB61421 Homo sapiens MILL-Human TANGO 300 1861 90 protein. 529 AAB23618 Homo sapiens ALPH-Human secreted protein 1859 90 SEQ ID NO : 36. 530 gui6841194 Homo sapiens HSPC272 418 66 530 gi3170533 Saccharomyce nucleolar protein Nop5p 93 30 s cerevisiae 530 gi 17862426 Drosophila LD27336p 90 29 melanogaster 531 gi17485716re Nomo sapiens similar to G protein-coupled 67 30 . fjXP_066655. 1 receptor 64 ; G protein-coupled receptor, epididymis-specific Table 2B SEQ Accession No. Species Description Score o ;, Identity NO : (seven transmembrane family) 532 gil4330383 Homo sapiens sodium/calcium exchanger 190 94 SCL8A3 532 AAM47745 Homo sapiens MERE Human natrium (+)- 183 100 calcium (2+) exchanger form 3 protein, HNCX3. 532 gui) 552526 Rattus sodium-calcium exchanger form 78 92 norvegicus 3 533 gi58028 synthetic suef protein 142 29 construct 533 AAM82345 Homo sapiens HUMA-Human 108 30 immune/haematopoietic antigen SEQ ID NO : 9938. 533 AAM72527 Homo sapiens MOLE-Human bone marrow 96 30 expressed probe encoded protein SEQ ID NO : 32833. 534 gi6958616 Human envelope glycoprotein 69 25 immunodefici ency virus type I 535 gi16359163 Homo sapiens Similar to RIKEN cDNA 1128 100 2310014B08 gene 535 gil8043464 Mus musculus RiKEN cDNA 2310014B08 843 75 gene 535 AAB64401 Homo sapiens INCY-Amino acid sequence of 139 37 human intracellular signalling molecule INTRA33. 536 AAE13349 Homo sapiens SENO-Human TSTP protein, 1561 91 165-015D. 536 AAE13348 Homo sapiens SENO-Human TSTP protein, 520 36 165-015C. 536 AAE13350 Homo sapiens SENO-Human TSTP protein, 249 28 165-015E. 537 AAU74622 Homo sapiens UYCA-Oestrogen-regulated 974 90 LIV-1 family protein AX078294 Hs. 537 AAU74621 Homo sapiens UYCA-Oestrogen-regulated 974 90 LIV-1 family protein Q 15043 Hs. 537 AAB60496 Homo sapiens INCY-Human cell cycle and 974 90 proliferation protein CCYPR-44, SEQ ID NO : 44. 538 AAG81279 Homo sapiens ZYMO Human AFP protein 223 100 sequence SEQ ID NO : 76. 538 ABB90338 Homo sapiens HUMA-Human polypeptide 126 47 SEQ ID NO 2714. 538 AAB65159 Homo sapiens GETH Human PRO180 126 47 (UNQ154) protein sequence SEQ ID NO : 23. 539 AAB94271 Homo sapiens HELI-Human protein sequence 207 100 SEQ ID NO : 14691. 539 AAM94001 Homo sapiens HELI-Human stomach cancer 207 100 expressed polypeptide SEQ ID NO 72.

Table 2B SEQ Accession No. Species Description Score % ID Identity NO : 539 AAW78193 Homo sapiens HUMA-Human secreted protein 103 46 encoded by gene 68 clone H2CBJ08. 541 gi4574260 Haemophilus outer membrane protein 26 70 29 influenzae 541 gi 19916386 Methanosarcin H (+)-transporting ATP synthase, 69 32 a acetivorans subunit gamma str. C2A [Methanosarcina 541 gil20916197lre Mus musculus RIKEN cDNA D630002J15 410 73 flXP_133065. 1 I 542 gil5559405 Homo sapiens Similarto RIKEN cDNA 1301 100 0610030G03 gene 542 gi13543049 Mus musculus Similar to RIKEN cDNA 1147 87 0610030G03 gene 542 gil8314524 Mus musculus Similarto RIKEN cDNA 272 31 2010305C02 gene 543 girl4789599 Homo sapiens Similarto RIKEN cDNA 1839 100 2810403L02 gene 543 gi 11493522 Homo sapiens PR01512 1512 100 543 AAB58871 Homo sapiens HUMA-Breast and ovarian 1407 93 cancer associated antigen protein sequence SEQ ID 579. 544 gi693811 Homo sapiens VPre-B protein 788 100 544 gi2114308 Homo sapiens VpreB 788 100 544 gi340305 Homo sapiens VpreB protein precursor 751 99 545 gi21430832 Drosophila SD18306p 357 41 melanogaster 545 gi 15823977 Streptomyces modular polyketide synthase 79 29 avermitilis 545 gi 19879682 Homo sapiens LIM homeobox transcription 77 31 factor 1 alpha variant 4AB 546 AAB65258 Homo sapiens GETH Human PRO1153 34 (UNQ583) protein sequence SEQ ID NO : 351. 546 AAG81325 Homo sapiens ZYMO Human AFP protein 129 34 sequence SEQ ID NO : 168. 546 AAE06576 Homo sapiens SAGA Human protein having 129 34 hydrophobic domain, HP10764. 547 gui 153366 Streptomyces methylmalonyl-CoA small 76 39 cinnamonensis subunit 547 gi 18308138 Sus scrofa CD34 antigen 74 20 547 gill7466082lre Homo sapiens similar to olfactory receptor 399 90 flXP_070192. 1 MOR 145-1 548 gi405956 Escherichia yeeE 1138 93 coli 548 gi 1736691 Escherichia Exodeoxyribonuclease I (EC 1014 86 coli 3. 1. 11. 1) (Exonuclease I) (DNA deoxyribophosphodiesterase) (DRPase). 548 gi405954 Escherichia exonuclease 1 1014 86 coli 549 gi295196 Salmonella level of amino acid identity 699 86 Table 2B SEQ Accession No. Species Description Score % ID Identity NO : typhimurium between E. coli and S. typhimurium strongly suggests authentic gene 549 gil 13541796lre Thermoplasm Predicted transporter component 137 27 flNP_I 11484. 1 a volcanium I 550 gi 17429437 Ralstonia PROBABLE 251 24 solanacearum TRANSMEMBRANE PROTEIN 550 gi 1212901 421g Anopheles ebiP 1696 121 26 blEAA02287. 1 gambiae str. PEST 550 gi !) 5964907re Sinorhizobium HYPOTHETICAL 117 27 f NP_385260. 1 meliloti TRANSMEMBRANE PROTEIN 551 gi2 16539 Escherichia BasS 825 98 coli 551 gi536956 Escherichia basS 825 98 coli 551 gill 1790551 Escherichia sensor protein for basR 825 98 coli K12 552 gi 1778505 Escherichia ferric enterobactin transport 1021 100 coli protein 552 gi 1786804 Escherichia ferric enterobactin transport 1021 100 coli K12 protein l 552 gi 13360086 Escherichia ferric enterobactin transport 1020 99 coli 0157 : H7 protein 553 girl3363896 Escherichia dipeptide transport system 1114 100 coli 0157 : H7 permease protein 2 553 gi349227 Escherichia transmembrane protein 1114 100 coli 553 gi466681 Escherichia dppC 1114 100 coli 554 gi4063042 Cryptosporidi GP900 ; mucin-like glycoprotein 359 57 um parvum 554 gi2827462 Cercopithecus hepatitis A virus cellular 314 56 aethiops receptor I long form 554 gi2827460 Cercopithecus hepatitis A virus cellular 314 56 aethiops receptor I short form 555 gi 13959789 Homo sapiens lung alpha/beta hydrolase 203 88 protein I 555 gi 13784946 Mus musculus alpha/beta hydrolase-1 175 77 555 gi 15488726 Mus musculus lung alpha/beta hydroiase I 175 77 556 AAU 11390 Homo sapiens SENO-Human T2R75 389 98 (hT2R75) polypeptide. 556 gi20336511 Homo sapiens candidate taste receptor T2RP) 7 38998 556 AAU11384 Homo sapiens SENO-Human T2R61 368 91 (hT2R61) polypeptide. 557 gi2275592 Homo sapiens TCRBV) 2S) 534) 00 557 gi2218039 Homo sapiens V segment translation product 534 100 557 gi467921 Homo sapiens T-cell receptor beta chain V 525 100 region precursor 558 gi3093754 Neurospora AR2 73 28 crassa Table 2B SEQ Accession No. Species Description Score % ! D identity NO : 558 gi 16415400 Listeria highly similar to cytochrome D 72 29 innocua ubiquinol oxidase subunit 11 558 gi 16412217 Listeria highly similar to cytochrome D 72 29 monocytogene ubiquinol oxidase subunit 11 s 559 AAD25037_aa Homo sapiens GENA-Human oncostatin M 1306 100 I (OSM) cDNA. 559 AAE 15318 Homo sapiens GENA-Human oncostatin M 1306 100 (OSM) protein. 559 AAY87820 Homo sapiens AMGE-Human oncostatin 1306 100 protein. 560 AAB49502 Homo sapiens HUMA-Clone HYASC03. 310 98 560 gi20071228 Mus musculus RIKEN cDNA 2810051A14 151 51 gene 560 AAG81365 Homo sapiens ZYMO Human AFP protein 144 48 sequence SEQ ID NO : 248. 561 AAY38432 Homo sapiens HUMA-Human secreted protein 77 47 encoded by gene No. 3. 561 gi2114473 Mus musculus pl40mDia 73 39 561 gi3638957 Homo sapiens sco-spondin-mucin-like ; similar 72 32 to P98167 (PI D : g 1711548) ; details of intron/exon structure uncertain 562 gi 16504300 Salmonella probable membrane transport 789 93 enterica subsp. protein enterica serovar Typhi 562 gi9948048 Pseudomonas probable transporter (membrane 557 63 aeruginosa subunit) 562 gi7227389 Neisseria sodium/dicarboxylate symporter 484 58 meningitidis family protein MC58 563 AA014190 Homo sapiens INCY-Human transporter and 2183 91 ion channel TRICH-7. 563 gi 183298 Homo sapiens GLUT5 protein 1329 55 563 gil2804761 Homo sapiens solute carrier family 2 1329 55 (facilitated glucose transporter), member 5 564 AAE14571 Homo sapiens EXEL-Human rhomboid related 576 100 protein, RRP3. 564 ABB75690 Homo sapiens SHAN-Human rhombus related 576 100 protein 48-35. 53. 564 gi 19171162 Homo sapiens ventrhoid transmembrane 576 100 protein 565 AAD17516 aa Homo sapiens SENO-Human taste receptor, 968 100 1 hTlRl cDNAcodingsequence. 565 ABB77319 Homo sapiens INCY-Human G-protein 968 100 coupled receptor SEQ ID NO 3. 565 AAE 10372 Homo sapiens SENO-Human taste receptor, 968 100 h l l R I protein. 566 gi20147226 Arabidopsis At2g44720/F 16B22. 21 101 38 thaliana 566 AA013099 Homo sapiens HYSE-Human polypeptide SEQ 100 40 ID NO 26991.

Table 2B SEQ Accession No. Species Description Score % ID Identity NO : 566 gi 1762434 Sus scrofa nitric oxide synthase 98 29 567 AA008397 Homo sapiens HYSE-Human polypeptide SEQ 231 93 ID NO 22289. 567 AAM41207 Homo sapiens HYSE-Human polypeptide SEQ 161 73 ID NO 6138. 567 AAM39421 Homo sapiens HYSE-Human polypeptide SEQ 161 73 ID NO 2566. 568 AAU83199 Homo sapiens ZYMO Novel secreted protein 900 100 Z891639G I P. 568 AAB95726 Homo sapiens HELI-Human protein sequence 492 75 SEQ ID NO : 18602. 568 AAB95109 Homo sapiens HELI-Human protein sequence 492 75 SEQ ID NO : 17089. 569 AAU83607 Homo sapiens GETH Human PRO protein, Seq 311 100 I D No 32. 569 girl7976983 Xenopus P8F7 196 41 laevis 569 0176740 Arabidopsis RING zinc finger protein-like 81 33 thaliana 570 AAD20624aa Homo sapiens HUMA-Human ovarian cancer 437 89 1 antigen-encoding gene 7 cDNA clone HMAM121. 570 AAB87396 Homo sapiens HUMA-Human gene 8 encoded 437 89 secreted protein HMAM121, SEQ ID NO : 137. 570 AAB85784 Homo sapiens INCY-Human kinase PKIN-3. 437 89 571 AAM86710 Homo sapiens HUMA-Human 387 97 immune/haematopoietic antigen SEQ ID NO : 14303. 571 gill9527326lre Mus musculus expressed sequence AW049604 161 96 flNP_598857. 1 I 572 gi 1491621 Bovine U L36 97 36 herpesvirus I 572 gi2653311 Bovine very large virion protein 97 36 herpesvirus (tegument) type 1. 1 572 ABB 1 1413 Homo sapiens HYSE-Human extensin 89 28 homologue, SEQ ID NO : 1783. 573 gi 15292437 Drosophila LP 10272p 39 melanogaster 573 AAY87336 Homo sapiens INCY-Human signal peptide 69 34 containing protein HSPP-113 SEQ ID NO : 113. 573 gi4877582 Homo sapiens lipoma HMGIC fusion partner 69 34 574 AAM92575 Homo sapiens HUMA-Human digestive 350 98 system antigen SEQ ID NO : 1924. 574 gi 15426530 Homo sapiens similar to RIKEN cDNA 212 29 1810006A 16 gene 574 gi 15080253 Homo sapiens Similar to RIKEN DNA 212 29 1810006A 16 gene 575 AAU83712 Homo sapiens GETH Human PRO protein, Seq 724 91 I D No 242.

Table 2B wtq Aceession lso. wpecles uescription reore/O ID Identity NO : 575 gi 16359053 Homo sapiens Similar to RIKEN DNA 724 91 2010309H 15 gene 575 AAB19403 Homo sapiens CHIR Amino acid sequence of a 712 89 human secreted protein. 576 gi12718841 Mus musculus Skullin 301 38 576 gi4191356 Mus musculus claudin-6 299 38 576 gi 13543081 Mus musculus claudin 6 299 38 577 gi801882 Vibrio FkuB 76 31 alginolyticus 578 AAO14197 Homo sapiens INCY-Human transporter and 135 44 ion channel TRICH-14. 578 AAU91185 Homo sapiens MILL-Human HEAT-2 135 44 polypeptide. 578 gi 19527485 Drosophila LD19039p 119 41 melanogaster 579 gil8044066 Mus musculus RIKEN cDNA 5033406L14 342 84 gene 579 gi6682873 Homo sapiens reduced expression in cancer 200 90 579 gi7230612 Rattus small rec 197 87 norvegicus 580 AAM25339 Homo sapiens HYSE-Human protein sequence 351 100 SEQ ID NO : 854. 580 ABB89642 Homo sapiens HUMA-Human polypeptide 291 84 SEQ ID NO 2018. 580 gi22041 10 Bos taurus adenylyl cyclase t e VII 233 69 581 AAB24476 Homo sapiens HUMA-Human secreted protein 238 69 sequence encoded by gene 40 SEQ ID NO : 101. 581 AAM82470 Homo sapiens HUMA-Human 122 71 immune/haematopoietic antigen SEQ ID NO : 10063. 581 gil8461301 Oryza sativa similar to 26S proteasome 86 24 (japonica subunit4 cultivar- group) 582 AAE14571 Homo sapiens EXEL-Human rhomboid related 341 100 protein, RRP3. 582 ABB75690 Homo sapiens SHAN-Human rhombus related 341 100 protein 48-35. 53. 582 gil9171162 Homo sapiens ventrhoid transmembrane 341 100 protein 583. AAU18887 Homo sapiens HUMA-Novel prostate gland 348 95 antigen, Seq ID No 186. 583 AAM96039 Homo sapiens HUMA-Human reproductive 348 95 system related antigen SEQ I D NO : 4697. 583 gi 16648412 Drosophila LD44720p 160 33 melanogaster 584 gi5305335 Mycobacteriu proline-rich mucin homolog 132 29 m tuberculosis 584 gi2429362 Santalum proline rich protein 126 28 album 584 gi12018147 Chlamydomon vegetative cell wall protein gpl 124 30 as reinhardtii Table 2B SEQ Accession No. Species Description Score % ID Identity NO : 585 gi3165565 Caenorhabditi C. elegans PTR-15 protein 89 29 s elegans (corresponding sequence T07H8. 6) 585 gi 1825729 Caenorhabditi C. elegans PTR-2 protein 79 20 s elegans (corresponding sequence C32E8. 8) 585 gi 15824031 Streptomyces modular polyketide synthase 75 30 avermitilis 586 gi8919836 Blumeria GTPase activating protein 76 23 graminis f. sp. hordei 586 gi21064465 Drosophila RE36839p 75 41 melanogaster 586 gi2558537 Fossombronia NADH dehydrogenase subunit 5 74 26 pusilla 587 AAD02051 aa Homo sapiens LEXI-Human ion channel 1195 99 1 protein (ICP) cDNA. 587 AAE17448 Homo sapiens MILL-Human sodium ion 1195 99 channel family protein, 56201. 587 AAY71949 Homo sapiens LEXI-Human alternative ion 1195 99 channel protein (ICP). 588 gi478889 Rana transcription factor RcC/EPB-1 78 33 catesbeiana 588 gi 15912317 Arabidopsis AT4g00090/F6N 15 8 75 30 thaliana 588 git20853571 Ire Mus musculus similar to human 74 34 fXP_121991. 1 immunodeficiency virus type I enhancer binding protein 2 ; human immunodeficiency virus type I enhancer-binding protein 2 589 Axa001188 Homo sapiens HYSE-Human polypeptide SEQ 248 86 I D NO 15080. 589 AAY73334 Homo sapiens INCY-H lRM clone 1805061 79 35 protein sequence. 589 gi I i 345434 Therrnus competence factor ComEA 78 35 thermophilus 590 ABB84982 Homo sapiens GETH Human PR05730 protein 603 60 sequence SEQ ID NO : 332. 590 AAM39990 Homo sapiens HYSE-Human polypeptide SEQ 603 60 ID NO 3135. 590 AAM38999 Homo sapiens HYSE-Human polypeptide SEQ 603 60 ID NO 2144. 591 AAB73674 Homo sapiens INCY-Human oxidoreductase 193 77 protein ORP-7. 592 gi36853 Homo sapiens T-cell receptor alpha-chain (413 585 100 is 2nd base in codon) 592 gi2358022 Homo sapiens TCRAV2S 1 585 100 592 ABB11158 Homo sapiens HYSE-Human TCR alpha chain 576 99 homologue, SEQ ID NO : 1528. 593 ABB90299 Homo sapiens HUMA-Human polypeptide 121 38 SEQ ID NO 2675. 593 AAM41275 Homo sapiens HYSE-Human polypeptide SEQ 121 38 ID NO 6206.

Table 2B SEQ Accession No. Species Description Score % ID Identity NO : 593 AAM39489 Homo sapiens HYSE-Human polypeptide SEQ 121 38 (D NO 2634. 594 ABB06606 Homo sapiens CURA-G protein-coupled 1583 100 receptor GPCR4c protein SEQ ID NO : 22. 594 ABB06605 Homo sapiens CURA-G protein-coupled 1583 100 receptor GPCR4a protein SEQ ID NO : 20. 594 ABB06604 Homo sapiens CURA-G protein-coupled 1583 100 receptor GPCR4a protein SEQ I D NO : 18. 595 gi6539444 Prunus avium S6-RNase 77 40 595 gi9957252 Prunus dulcis Sg-RNase 77 40 595 gi9081843 Prunus dulcis self-incompatibility associated 77 40 ribonuclease 596 AAF90612_aa Homo sapiens ZYMO Human secretin-like 581 100 1 receptor Zgprl cDNA. 596 AAE15635 Homo sapiens INCY-Human G-protein 581 100 coupled receptor-5 (GCREC-5) protein. 596 AAB66272 Homo sapiens MILL-Human TANGO 378 581 100 SEQ ID NO : 29. 597 ABB84906 Homo sapiens GETH Human PRO1287 protein 785 98 sequence SEQ ID NO : 180. 597 AAB65273 Homo sapiens GETH Human PRO1287 785 98 (UNQ656) protein sequence SEQ ID NO : 381. 597 AAB87561 Homo sapiens GETH Human PRO1287. 785 98 598 girl7426446 Homo sapiens bA351 K23. 5 (novel protein) 1630 100 598 ABL53627aa Homo sapiens GENO-Breast protein-909 48 1 eukaryotic conserved gene 1 (BSTP-ECGI) cDNA. 598 ABB75677 Homo sapiens GENO-Breast protein-909 48 eukaryotic conserved gene I (BSTP-ECG1) protein. 599 girls012190 Homo sapiens Similarto RIKEN cDNA 967 94 2610036L 13 gene 599 AAG89274 Homo sapiens GEST Human secreted protein, 420 98 SEQ ID NO : 394. 599 gi20987202 Mus musculus RIKEN cDNA 2610036L13 380 64 gene 600 gi7717312 Homo sapiens TGF-beta-activated kinase like 422 97 600 AAB 18666 Homo sapiens INCY-A human regulator of 115 92 intracellular phosphorylation. 600 gi11342496 Bacteriophage holin 75 26 phi-Ealh 601 AAG02869 Homo sapiens GEST Human secreted protein, 253 98 SEQ ID NO : 6950. 601 AAB10262 Homo sapiens GEMY Human fetal brain 253 98 protein fragment BF290 li. 601 AAB59017 Homo sapiens HUMA-Breast and ovarian 253 98 cancer associated antigen protein sequence SEQ ID 725. 602 gi204144 Rattus profi laggrin 82 25 Table 2B SEQ Accession No. Species Description Score % ! D Identity NO : norvegicus 602 gi7682468 Bos taurus submaxillary mucin 82 26 602 gi 14578315 Plasmodium PV I H 14175_P 80 26 vivax 603 gi 1234787 Xenopus up-regulated by thyroid hormone 1190 55 laevis in tadpoles ; expressed specifically in the tail and only at metamorphosis ; membrane bound or extracellular protein ; C-terminal basic region 603 AAU12201 Homo sapiens GETH Human PRO1779 1181 57 polypeptide sequence. 603 AAB94773 Homo sapiens HELI-Human protein sequence 771 63 SEQ ID NO : 15860. 605 ABB11373 Homo sapiens HYSE-Human olfactory 482 100 receptor homologue, SEQ ID NO : 1743. 605 gi 18479402 Mus musculus olfactory receptor MOR 160-1 384 78 605 gi 18480922 Mus musculus olfactory receptor MOR 160-4 353 74 606 gi21112746 Xanthomonas C-type cytochrome biogenesis 75 29 campestris pv. membrane protein campestris str. ATCC 33913 606 gi 15128587 Inversidens NADH dehydrogenase complex 72 32 japanensis 1 606 gil 133858221re Mus musculus RIKEN cDNA 1810059G22 727 83 ftNP_080601. 1 I 607 gui13507259 Homo sapiens amnionless 1623 75 607 AAB65237 Homo sapiens GETH Human PRO1028 1167 99 (UNQ513) protein sequence SEQ ID NO : 281. 607 AAY66714 Homo sapiens GETH Membrane-bound protein 1167 99 PRO 1028. 608 AAY76219 Homo sapiens HUMA-Human secreted protein 336 94 encoded by gene 96. 608 AAY30164 Homo sapiens ASTR-Human dorsal root 4 34 receptor 6 hDRR6. 608 gi 19338918 Homo sapiens G protein-coupled receptor 114 34 SNSR6 609 AAU74538 Homo sapiens FARB Human P2Y purinoceptor 113 34 8-like G protein-coupled receptor related protein. 609 gi 1771972 Xenopus P2Y8 nucleotide receptor 113 34 laevis 609 AAS19414_aa Homo sapiens CURA-Human cDNA encoding 102 37 1 novel G protein-coupled . receptor, GPCR9. 610 gil5292437 Drosophila LP10272p 245 38 melanogaster 610 AAY87336 Homo sapiens INCY-Human signal peptide 101 25 containing protein HSPP-113 SEQ I D NO : 113. 610 gi4877582 Homo sapiens lipoma HMGIC fusion partner 101 25 Table 2B SEQ Accession No. Species Description Score % ID Identity NO : 611 AAY27721 Homo sapiens HUMA-Human secreted protein 1114 98 encoded by gene No. 29. 611 AAB87068 Homo sapiens MILL-Human secreted protein 621 99 TANGO 365, SEQ ID NO : 46. 611 AAB87148 Homo sapiens MILL-Human secreted protein 617 98 TANGO 365 T20S variant, SEQ ID NO : 165. 613 AAM74132 Homo sapiens MOLE-Human bone marrow 267 100 expressed probe encoded protein SEQ ID NO : 34438. 613 AAM61375 Homo sapiens MOLE-Human brain expressed 267 100 single exon probe encoded protein SEQ ID NO : 33480. 613 AAB53312 Homo sapiens HUMA-Human colon cancer 267 100 antigen protein sequence SEQ ID NO : 852. 614 AAU27619 Homo sapiens ZYMO Human protein 656 89 AFP583515. 614 AAY91598 Homo sapiens HUMA-Human secreted protein 656 89 sequence encoded by gene 8 SEQ ID NO : 271. 614 AAY91458 Homo sapiens HUMA-Human secreted protein 656 89 sequence encoded by gene 8 SEQ ID NO : 131. 615 gi2065210 Mus musculus Pro-Pol-dUTPase polyprotein 1026 82 615 gi3860513em Mus famulus reverse transcriptase 482 84 blCAA 13574. 1 I 615 gil4379237lem Mus musculus reverse transcriptase 477 83 blCAA 13572. 1 I 616 AAU25709 Homo sapiens PHAA G protein-coupled 136 52 receptor, nGPCR-2123. 617 gi 13422363 Caulobacter sensor histidine kinase DivJ 76 29 crescentus CB15 617 gi699512 Mus musculus cyclin F 75 40 617 gi7272187 Caulobacter histidine protein kinase 74 29 crescentus 618 girl5718476 Homo sapiens Fanconi anemia 657 90 complementation group D2 protein 618 gi 13324523 Homo sapiens Fanconi anemia 657 90 complementation group D2 protein, isoform 2 618 gil3324522 Homo sapiens Fanconi anemia 657 90 complementation group D2 protein, isoform 1 619 AAU25447 Homo sapiens INCY-Human mddt protein 394 96 from clone LG : 1083142. 1 : 2000MAY 19. 619 AAU 16295 Homo sapiens HUMA-Human novel secreted 329 95 protein, Seq ID 1248. 619 AAM79834 Homo sapiens HYSE-Human protein SEQ ID 267 65 Table 2B SEQ Accession No. Species Description Score O ;, ID Identity NO : NO 3480. 620 AAB47106 Homo sapiens ZYMO Second splice variant of 309 51 MAPP. 620 gi 18147612 Homo sapiens metalloprotease disintegrin 309 51 620 gi 13157560 Homo sapiens dJ964F7. 1 (novel disintegrin and 309 51 reprolysin metal loproteinase family protein) 621 gil8606367 Mus musculus RIKEN cDNA 4930570C03 715 92 gene 621 AAB90649 Homo sapiens HUMA-Human secreted 562 97 protein, SEQ 1D NO : 192. 621 AAB90565 Homo sapiens HUMA-Human secreted 472 100 protein, SEQ ID NO : 103. 622 AAY87335 Homo sapiens INCY-Human signal peptide 623 99 containing protein HSPP-112 SEQ ID NO : 112. 622 gi 15149556 Drosophila junctophilin 90 26 melanogaster 622 gi21428978 Drosophila GH28348p 90 26 melanogaster # 623 ABB89722 Homo sapiens HUMA-Human polypeptide 230 100 SEQ ID NO 2098. 623 AAY87250 Homo sapiens INCY-Human signal peptide 230 100 containing protein HSPP-27 SEQ ID NO : 27. 623 AAY92710 Homo sapiens ZYMO Human membrane-230 100 associated protein Zsig24. 624 gi 10441465 Homo sapiens actin filament associated protein 274 90 624 girl7644147 Rattus actin filament associated protein 237 77 norvegicus 624 gi 13129529 Gallus gallus neural actin filament protein 201 71 625 gi 15193279 Oncorhynchus TNF decoy receptor 70 35 mykiss 626 ABBI 1417 Homo sapiens HYSE-Human secreted protein 443 98 homologue, SEQ ID NO : 1787. 626 AAG81257 Homo sapiens ZYMO Human AFP protein 148 68 sequence SEQ ID NO : 32. 626 AAB12121 Homo sapiens PROT-Hydrophobic domain 148 68 protein from clone HP02962 isolated from KB cells. 627 AAM74424 Homo sapiens MOLE-Human bone marrow 151 73 expressed probe encoded protein SEQ ID NO : 34730. 627 AAM61632 Homo sapiens MOLE-Human brain expressed 151 73 single exon probe encoded protein SEQ ID NO : 33737. 627 gui13310191 multiple recombinant envelope protein 121 35 sclerosis associated retrovirus element 628 gi 17390957 Mus musculus Similar to RIKEN cDNA 122 34 2010001 E 11 gene 628 gil20858407lre Mus musculus RIKEN cDNA 2010001EI I 129 35 Table 2B SEQ Accession No. Species Description Score % ID Identity NO : flXP_125582. 1 I 629 AAE03765 Homo sapiens HUMA-Human gene 2 encoded 194 58 secreted protein HCE3C63, SEQ ID NO : 35. 629 gi20988899 Mus musculus similar to deleted in bladder 190 56 cancer chromosome region candidate I 629 AAV83819_aa Homo sapiens CURI-Tumour suppressor gene 148 56 1 IB3089A (also known as DBCCR 1). 630 gil4276188 Desulfosarcin dissimilatory sulfite reductase 75 48 a variabilis alpha subunit 630 gi 14669513 uncultured dissimilatory sulfite reductase 74 47 bacterium alpha subunit 630 gi 14090308 Desulfovibrio sulfite reductase alpha subunit 73 48 cuneatus 631 AAM74983 Homo sapiens MOLE-Human bone marrow 269 91 expressed probe encoded protein SEQ ID NO : 35289. 631 AAM62179 Homo sapiens MOLE-Human brain expressed 269 91 single exon probe encoded protein SEQ ID NO : 34284. 631 AAU20596 Homo sapiens HUMA-Human secreted 137 50 protein, Seq ID No 588. 632 AAE10339 Homo sapiens ENGE-Human cholecystokinin 356 100 (CCK). 632 AAB24381 Homo sapiens ALLR Human 356 100 procholecystokinin amino acid sequence SEQ ID NO : 1. 632 gi 179996 Homo sapiens cholecystokinin 356 100 633 AAM69871 Homo sapiens MOLE-Human bone marrow 228 100 expressed probe encoded protein SEQ ID NO : 30177. 633 AAM57476 Homo sapiens MOLE-Human brain expressed 228 100 single exon probe encoded protein SEQ ID NO : 29581. 633 AAM68493 Homo sapiens MOLE-Human bone marrow 223 85 expressed probe encoded protein SEQ ID NO : 28799. 634 gil4456239 Homo sapiens bA74P 14. 2 (novel protein) 1684 88 634 gi4097231 Ureaplasma multiple banded antigen 395 23 urealyticum 634 gi600118 Zea mays extensin-like protein 324 35 635 AAE05188 Homo sapiens INCY-Human drug 171 51 metabol ising enzyme (DME-19) protein. 635 AAB12140 Homo sapiens PROT-Hydrophobic domain 171 51 protein isolated from WERI-RB cells. 635 ABB11624 Homo sapiens HYSE-Human secreted protein 144 52 homologue, SEQ I D NO : 1994. 636 gi 18676590 Homo sapiens FLJ00193 protein 1339 98 636 AAB66267 Homo sapiens MILL-Human TANGO 272 1326 97 Table 2B SEQ Accession No. Species Description Score % ID Identity NO : SEQ ID NO : 14. 636 gi 17386053 Mus musculus Jedi protein 987 79 637 gi7542324 Erwinia potential ORFB-specific 72 27 amylovora chaperone 638 Tao14184 Homo sapiens INCY-Human transporter and 1430 100 ion channel TRICH-1. 638 girl3926111 Homo sapiens 2P domain potassium channel 1430 100 Talk-2 638 AAE01027 Homo sapiens MILL-Human TWIK-3 protein 1426 99 from clone Athual33f10. 639 gi2754696 Gallus gallus high molecular mass nuclear 93 27 antigen 639 gi437055 Macaca mucin 92 29 mulatta 639 gi6715140 Drosophila split ends 91 30 melanogaster 641 gi3127176 Homo sapiens sulfonylurea receptor 2B 713 98 641 gi3127175 Homo sapiens sulfonylurea receptor 2A 713 98 641 gi 15778680 Oryctolagus sulphonylurea receptor 2B 678 93 cuniculus 642 AAB24035 Homo sapiens GETH Human PR04397 protein 1894 100 sequence SEQ ID NO : 42. 642 gi 17225044 Mus musculus beta-1, 3-galactosyltransferase- 1487 82 related protein 642 AAY93951 Homo sapiens HUMA-Amino acid sequence 1241 100 of a Brainiac-5 polypeptide. 643 ABB84966 Homo sapiens GETH Human PR04371 protein 758 95 sequence SEQ ID NO : 300. 643 ABB89971 Homo sapiens HUMA-Human polypeptide 758 95 SEQ ID NO 2347. 643 AAU12250 Homo sapiens GETH Human PRO4371 758 95 polypeptide sequence. 644 AAU 10355 Homo sapiens LEEH/Hhuman apolipoprotein 693 100 C-IV (APOC4). 644 gi975893 Homo sapiens apoC-IV 693 100 644 i18088771 Homo sapiens apolipoprotein C-IV 693 100 645 AAM25873 Homo sapiens HYSE-Human protein sequence 110 80 SEQ I D NO : 1388. 645 AAY57878 Homo sapiens INCY-Human transmembrane 101 86 protein HTMPN-2. 646 AAG93311 Homo sapiens NISC-Human protein HP10562. 488 100 646 AAG67820 Homo sapiens SHAN-Human leucine zipper 488 100 protein 43. 646 AAY64650 Homo sapiens GEST Human luman homology 488 100 protein. 647 gi 1 935177 Mus musculus heparin/heparan 1001 94 sulfate : glucuronic acid C5 epimerase 647 gil3442978 Mus musculus D-glucuronyl C5-epimerase 1001 | 94 647 gi 13654639 Bos taurus D-glucuronyl C5 epimerase 969 92 648 AAG00122 Homo sapiens GEST Human secreted protein, 102 100 SEQ ID NO : 4203. 648 AAW70542 Homo sapiens TORA Integrin alpha-2 chain. 102 100 648 gi33907 Homo sapiens integrin alpha-2 preprotein (AA 102 100 Table 2B SEQ Accession No. Species Description Score % ID Identity NO : .-29 to 1152) 649 gi 21107282 Xanthomonas TonB-dependent receptor 70 31 axonopodis pv. citri str. 306 650 ABB90225 Homo sapiens HUMA-Human polypeptide 683 100 SEQ ID NO 2601. 650 AAB12150 Homo sapiens PROT-Hydrophobic domain 683 100 protein isolated from HT-1080 cells. 650 ABB06157 Homo sapiens COMP-Human NS protein 675 98 sequence SEQ ID NO : 249. 651 AAV03875_aa Homo sapiens BETH-HTm4 gene. 173 100 1 651 AAW41056 Homo sapiens BETH-HTm4 protein. 173 100 651 gi561639 Homo sapiens IgE receptor beta subunit 173 100 652 gi21483462 Drosophila LD44686p 140 37 melanogaster 652 AAB67576 Homo sapiens INCY-Amino acid sequence of 104 43 a human hydrolytic enzyme HYENZ8. 652 AAM40456 Homo sapiens HYSE-Human polypeptide SEQ 104 43 ID NO 5387. 653 gi7209315 Homo sapiens FLJ00007 protein 1375 85 653 AAM90874 Homo sapiens HUMA-Human 591 99 immune/haematopoietic antigen SEQ I D NO : 18467. 653 AAY99428 Homo sapiens GETH Human PRO1431 430 93 (UNQ737) amino acid sequence SEQ ID NO : 315. 654 gi297172 Rattus rattus ribosomal protein S7 432 93 654 gi551251 Homo sapiens ribosomal protein S7 432 93 654 gi2811284 Mus musculus ribosomal protein S7 432 93 655 AAB68888 Homo sapiens INCY-Human RECAP 273 71 polypeptide, SEQ ID NO : 18. 655 AAU12284 Homo sapiens GETH Human PR05993 273 71 polypeptide sequence. 655 AAB82854 Homo sapiens FARB Human P2Y-like GPCR 164 75 polypeptide. 656 gi4096055 Homo sapiens R28379 3 136 100 656 gi9947429 Pseudomonas heme exporter protein CcmB 79 31 aeruginosa 656 gi2984101 Aquifex nodulation competitiveness 77 28 aeolicus protein NfeD 657 AAU16396 Homo sapiens HUMA-Human novel secreted 97 41 protein, Seq ID 1349. 657 AAB95861 Homo sapiens HELI-Human protein sequence 96 42 SEQ ID NO : 18926. 657 gi6690339 Mus musculus hematopoietic zinc finger protein 94 40 658 AAG67525 Homo sapiens SMIK Amino acid sequence of a 1850 100 . human secreted polypeptide. 658 ABB90207 Homo sapiens HUMA-Human polypeptide 558 38 SEQ ID NO 2583. 658 AAB69185 Homo sapiens SREN-Human hISLR-iso 558 38 Table 2B SEQ Accession No. Species Description Score % ID Identity NO : protein SEQ ID NO : 7. 659 AAH77293 aa Homo sapiens MILL-Human ion channel 505 98 I protein IC32391 cDNA coding region. 659 AAE13278 Homo sapiens INCY-Human transporters and 505 98 ion channels (TRICH)-5. 659 AAG77969 Homo sapiens MILL-Human ion channel 505 98 protein IC32391. 660 AAU 11356 Homo sapiens SCHE Human DNAX cytokine 1120 89 receptor subunit 9 (DCRS9) polypeptide. 660 AAU83601 Homo sapiens GETH Human PRO protein, Seq 1116 97 'IDNo20. 660 AAU04957 Homo sapiens GETH Human Interleukin 17 1116 97 receptor, IL-17RH3. 661 gi 1504002 Homo sapiens similar to a human major CRK-548 78 binding protein DOCK) 80. 661 gi 13195147 Mus musculus HCH 514 73 661 gui 1339910 Homo sapiens DOCK180 protein 436 60 662 AAY27669 Homo sapiens HUMA-Human secreted protein 255 100 encoded by gene No. 103. 662 gil 195273641re Mus musculus expressed sequence A1195350 ; 257 83 f1NP598894.) cDNA sequence, clone 2-37 I 663 gi9971784 Bovine protein L 73 27 ephemeral fever virus 663 gi 155287 Vibrio disulfide isomerase 70 28 cholera 663 gij 100865731re Bovine protein L 73 27 fNP065409. I ephemera) fever virus 664 gi6822060 Arabidopsis peptide transport-like protein 86 31 thaliana 664 gi20147231 Arabidopsis At) g68570/F24J57 74 36 thaliana 664 gi20453068 Arabidopsis At2g40460/T2P4. 19 72 31 thaliana 665 AAE 17537 Homo sapiens INCY-Human protein 2583 100 modification and maintenance molecule-6 (PMMM-6). 665 gi21388771 Homo sapiens kringle-containing protein 2220 100 665 gi21388540 Mus musculus Kremen2 protein 2140 85 666 ABB07527 Homo sapiens INCY-Human drug 659 87 metabolizing enzyme (DME) (I D : 564340) CD)). 666 ABB07515 Homo sapiens INCY-Human drug 565 99 metabolizing enzyme (DME) (ID : 8097779CD1). 666 gi13161409 Mus musculus famil 4 cytochrome P450 437 73 667 AAB08862 Homo sapiens INCY-Amino acid sequence of 958 100 a human secretory protein. 667 AAB12163 Homo sapiens PROT-Hydrophobic domain 953 99 protein from clone HP10671 Table 2B SEQ Accession No. Species Description Score % ID Identity NO : isolated from Thymus cells. 667 AAE10183 Homo sapiens HYSE-Human bone marrow 268 91 derived protein, SEQ ID NO : 27. 668 gi 15292437 Drosophila LP10272p 361 31 melanogaster 668 AAY87336 Homo sapiens INCY-Human signal peptide 181 28 containing protein HSPP-1 13 SEQ ID NO : 113. 668 gi4877582 Homo sapiens lipoma HMGIC fusion partner 181 28 669 gi3598974 Rattus protein tyrosine phosphatase 103 38 norvegicus TD14 669 ABB03068 Homo sapiens HUMA-Human expressed 83 35 polypeptide SEQ 1D NO 41. 669 AAB29664 Homo sapiens KYOW Human tyrosine 83 35 phosphatase HD-PTP cKALI l fragment. 670 gi 18375957 Neurospora related to 60s ribosomal protein 74 32 crassa L2 (mitochondrial) 670 gi20540703re Homo sapiens serologically defined colon 83 32 flXP_046834. 6 cancer antigen 43 I 670 gill8375957le Neurospora related to 60s ribosomal protein 74 32 mblCAD21256 crassa L2 (mitochondrial) . 11 671 gi 12656590 Danio rerio P2x purinoceptor subunit 4 72 40 671 gi2995988 Callithrix NADH dehydrogenase subunit 4 70 28 jacchus 671 gi2995982 Callithrix NADH dehydrogenase subunit 4 70 28 pygmaea 672 gi 1196439 Homo sapiens latent transforming growth 291 98 factor-binding protein 672 gi207286 Rattus TGF-beta masking protein large 226 77 norvegicus subunit 672 gi3493176 Mus musculus latent TGF beta binding protein 217 73 Table 3 SEQ ID Database entry Description *Results NO : ID 339 PR00709 AVIDIN SIGNATURE PR00709A 4. 60 1. 170e-09 16-34 340 BL01253 Type I fibronectin domain BL01253F 14. 35 5. 050e-14 78-116 proteins. 346 BL00649 G-protein coupled receptors BL00649C 17. 82 6. 339e-12 4-29 family 2 proteins. 346 PR00249 SECRETlN-LIKE GPCR PR00249C 17. 08 3. 769e-10 6-29 SUPERFAMILY SIGNATURE 354 PD01066 PROTEIN ZINC FINGER PD01066 19. 43 6. 362e-29 129-167 ZINC-FINGER METAL- BINDING NU. 354 DM01354 kwTRANSCRIPTASE DMOi354N 13. i75. 661e-12 196-240 REVERSE 11 ORF2. DM01354M 12. 50 I. OOOe-11 171-200 356 PR00463 E-CLASS P450 GROUP I PR00463B 17. 50 3. 314e-13 135-156 SIGNATURE PR00463A 11. 40 8. 568e-10 111-130 362 BL00211 ABC transporters family BL00211B 13. 37 2. 286e-13 222-253 proteins. BL00211A 12. 23 9. 550e-09 160-171 378 PR00049 WILM'S TUMOUR PR00049D 0. 00 8. 780e-09 78-92 PROTEIN SIGNATURE 384 PF00624 Flocculin repeat proteins. PF00624J 6. 21 7. 070e-09 40-94 PF00624F 11. 04 9. 056e-09 68-103 386 BL01303 BCCT family of transporters BL01303A 14. 33 5. 629e-31 89-121 proteins. BL01303B 10. 142. 250e-18 142-160 387 PR00075 FATTY ACID PR00075A 16. 97 9. 565e-09 9-29 DESATURASE FAMILY I SIGNATURE 391 BL00538 Bacterial chemotaxis sensory BL00538C 10. 61 1. OOOe-40 152-190 transducers proteins. BL00538A 23. 61 3. 647e-39 96-143 391 PR00260 BACTERIAL PR00260A 13. 20 3. 172e-24 5-30 CHEMOTAXIS SENSORY PR00260D 9. 90 4. 418e-19 143-172 TRANSDUCER PR00260C 10. 26 3. 302e-11 69-89 SIGNATURE PR00260B 8. 90 2. 220e-10 60-75 394 BL00077 Heme-copper oxidase BL00077C 18. 98 9. 697e-09 9-59 catalytic subunit, copper B binding regio. 400 PR00550 HYPERGLYCEMIC PR00550C 11. 31 9. 426e-10 29-39 HORMONE SIGNATURE 402 DM01283 A-BINDING PROTEIN DM01283A 14. 91 9. 600e-10 35-70 CHLOROPHYLL. 402 PR00456 RIBOSOMAL PROTEIN P2 PR00456E 3. 06 6. 056e-11 57-71 SIGNATURE PR00456E 3. 06 2. 367e-09 62-76 PR00456E 3. 06 3. 278e-09 56-70 PR00456E 3. 06 4. 646e-09 49-63 402 PR00833 POLLEN ALLERGEN POA PR00833H 2. 30 4. 875e-10 59-73 Pi SIGNATURE PR00833H 2. 30 2. 154e-09 38-52 PR00833H 2. 30 3. 538e-09 88-102 PR00833H 2. 30 5. 615e-09 92-106 PR00833H 2. 30 7. 692e-09 97-111 402 PD00306 PROTEIN PD00306B 5. 57 9. 000e-09 90-100 GLYCOPROTEIN PRECURSOR RE. 402 PF00624 Flocculin repeat proteins. PF00624F 11. 04 9. 347e-09 85-120 402 PD01364 MUCIN GLYCOPROTEIN PD01364B 13. 94 9. 526e-09 109-124 PRECURSOR MEM. 402 PR00308 TYPE I ANTIFREEZE PR00308A 5. 90 2. 694e-09 91-105 PROTEIN SIGNATURE PR00308A 5. 90 9. 788e-09 62-76 Table 3 SEQ ID Database entry Description *Results NO : ID 402 DM00191 w SPAC8A4. 04C DM00191 D 13. 94 9. 922e-09 86-124 RESISTANCE SPAC8A4. 05C DAUNORUBICIN. 404 BL00649 G-protein coupled receptors BL00649B 20. 68 5. 061e-i 1 23-68 family 2 proteins. BL00649C 17. 82 4. 955e-10 82-107 404 PR00249 SECRETIN-LIKE GPCR PR00249C 17. 08 5. 435e-09 84-107 SUPERFAMILY PR00249A 15. 886. 642e-09 18-42 SIGNATURE 406 BL00312 Glycophorin A proteins. BL00312B 9. 22 9. 91 le-09 2-30 408 PR00957 GENE 66 (IR5) PROTEIN PR00957A 7. 65 3. 473e-09 158-175 SIGNATURE 409 BL00479 Phorbol esters/BL00479A 19. 86 1. 220e-10 59-81 diacylglycerol binding domain proteins. 409 PD02269 CYTIDINE DEAMINASE PD02269C 16. 36 9. 735e-10 70-82 HYDROLASE ZINC AMINOHY. 410 PR00007 COMPLEMENT C 1 Q PR00007B 14. 16 7. 698e-13 116-135 DOMAIN SIGNATURE PR00007D 9. 64 9. 654e-11 193-203 PR00007A 19. 33 2. 552e-10 89-115 PR00007C 15. 60 3. 656e-10 163-184 410 BL01113 Clq domain proteins. BL01113B 18. 26 1. 563e-20 95-130 BLO1113D 7. 47 9. 308e-12 195-204 BLO1113C 13. 18 4. 750e-10 163-182 412 PR00925 NONHISTONE PR00925B 3. 73 5. 982e-10 78-90 CHROMOSOMAL PROTEIN HMG17 FAMILY SIGNATURE 414 BL00019 Actinin-type actin-binding BL00019D 15. 33 3. 948e-14 41-70 domain proteins. 426 BL00237 G-protein coupled receptors BL00237A 27. 68 7. 000e-14 67-106 proteins. 426 PR00245 OLFACTORY RECEPTOR PR00245A 18. 03 6. 143e-12 36-57 SIGNATURE PR00245B 10. 38 1. 675e-11 154-168 426 PR00237 RHODOPSIN-LIKE GPCR PR00237C 15. 69 1. 000e-09 81-103 SUPERFAMILY SIGNATURE 435 PR00011 TYPE III EGF-LIKE PR0001 IB 13. 08 5. 576e-13 76-94 SIGNATURE PR00011 D 14. 03 6. 943e-13 76-94 PR00011 B 13. 08 9. 542e-13 33-51 PR0001 ID 14. 03 3. 21 ìe-12 33-51 PR0001 IA 14. 06 6. 516e-12 33-51 PR0001 IA 14. 06 8. 548e-12 76-94 PR00011 D 14. 03 3. 213e-11 162-180 PROOOIIB 13. 082. 174e-10 162-180 PR0001 ID 14. 03 2. 523e-10 119-137 PR00011B 13. 08 2. 356e-09 119-137 PR00011 B 13. 08 5. 685e-09 205-223 PROOOlIA 14. 066. 425e-09 119-137 PROOOllA 14. 066. 671e-09 162-180 PR00011 D 14. 03 9. 870e-09 205-223 441 PR00251 BACTERIAL OPS1N PR00251 G 16. 33 4. 000e-09 176-194 SIGNATURE 441 PR00308 TYPE I ANTIFREEZE PR00308A 5. 90 6. 188e-09 51-65 PROTEIN SIGNATURE Table 3 SEQ ID Database entry Description *Results NO : ID 447 BL01144 Ribosomal protein L3 e BLO1 144 25. 07 6. 684e-17 83-134 proteins. 448 BL00979 G-proteincoupledreceptors BL00979M 14. 396. 532e-11 30-80 family 3 proteins. 448 PR00248 METABOTROPIC PR00248F) 4. 25). 923e-iO 56-78 GLUTAMATE GPCR SIGNATURE 453 BL00649 G-protein coupled receptors BL00649C 17. 82 6. 073e-13 21-46 family 2 proteins. 453 PR00249 SECRETIN-LIKE GPCR PR00249C 17. 08 9. 129e-11 23-46 SUPERFAMILY SIGNATURE 458 BL00242 Integrins alpha chain BL00242E 9. 03 8. 154e-09 82-110 proteins. 458 PR00336 LYSOSOME-ASSOCIATED PR00336D 9. 96 1. OOOe-08 133-155 MEMBRANE GLYCOPROTEIN SIGNATURE 464 DM00215 PROLINE-RICH PROTEIN DM00215 19. 43 8. 071e-10 122-154 3. 464 PR00910 LUTEOVIRUS ORF6 PR00910A 2. 51 2. 607e-09 142-154 PROTEIN SIGNATURE 464 PR00049 WILM'S TUMOUR PR00049D 0. 00 8. 714e-11 140-154 PROTEIN SIGNATURE PR00049D 0. 00 4. 356e-09 135-149 468 PR00806 VINCULIN SIGNATURE PR00806C 11. 07 8. 839e-09 13-30 473 BL00237 G-protein coupled receptors B L00237A 27. 68 9. 129e-15 71-110 proteins. BL00237C 13. 19 1. 346e-13 218-244 BL00237D 11. 23 9. 308e-11 271-287 473 PR00237 RHODOPSIN-L1KE GPCR PR00237F 13. 57 3. 520e-13 223-247 SUPERFAMILY PR00237C 15. 692. 200e-11 85-107 SIGNATURE PR00237E 13. 03 2. 588e-09 166-189 PR00237G 19. 63 3. 093e-09 261-287 477 BL00495 Apple domain proteins. BL00495N 11. 04 8. 239e-14 204-238 BL004950 13. 75 9. 000e-14 236-264 477 BL00134 Serine proteases, trypsin BL00134B 15. 99 4. 176e-22 212-235 family, histidine proteins. BL00134A 11. 96 7. 158e-19 61-77 BL00134C 13. 45 6. 850e-13 245-258 477 PR00722 CHYMOTRYPSIN SERINE PR00722A 12. 27 5. 737e-17 62-77 PROTEASE FAMILY (Sl) PR00722C 10. 87 4. 600e-15 211-223 SIGNATURE PR00722B 12. 51 4. 375e-12 120-134 477 BL01253 Type I fibronectin domain BLO1253G 11. 34 8. 352e-14 211-224 proteins. BL01253D 4. 84 7. 207e-13 61-74 BL01253H 13. 15 7. 124e-12 227-261 477 BL00021 Kringle domain proteins. BL00021 B 13. 33 2. 565e-17 61-78 BL00021 D 24. 56 1. 1 lOe-10 217-258 477 PR00839 V8 SERINE PROTEASE PR00839B 11. 20 3. 955e-10 61-78 FAMILY SIGNATURE 477 BL00672 Serine proteases, V8 family, BL00672A 9. 79 1. 120e-09 61-76 histidine proteins. 496 PR00838 VENOM ALLERGEN 5 PR00838G 16. 07 9. 760e-12 165-184 SIGNATURE PR00838D 8. 73 1. 563e-10 87-105 496 BL01009 Extracellularproteins BL01009D 14. 192. 976e-17 167-187 SCP/Tpx-1/Ag5/PR-I/Sc7 BL01009A 13. 75 3. 057e-1 1 87-104 proteins. BL01009E 13. 50 2. 125e-10 201-216 496 PR00837 ALLERGEN V5/TPX-1 PR00837C 17. 21 1. 000e-16 166-182 FAMILY SIGNATURE PR00837A 14. 77 3. 919e-13 87-105 Table 3 SEQ ID Database entry Description *Results NO : I D PR00837D 11. 12 9. 514e-10 202-215 497 PR00049 WILM'S TUMOUR PR00049D 0. 00 7. 344e-13 205-219 PROTEIN SIGNATURE PR00049D 0. 00 9. 262e-13 206-220 PR00049D 0. 00 4. 000e-12 207-221 PR00049D 0. 00 4. 000e-12 208-222 PR00049D 0. 00 7. 655e-11 202-216 PR00049D 0. 00 7. 958e-11 204-218 PR00049D 0. 00 8. 336e-11 203-217 PR00049D 0. 00 1. 214e-10 209-223 PR00049D 0. 00 1. 214e-10 210-224 PR00049D 0. 00 3. 746e-09 211-225 497 PD02059 CORE POLYPROTEIN PD02059B 24. 48 5. 056e-09 194-228 PROTEIN GAG CONTAINS : P. 497 DM00215 PROLINE-RICH PROTEIN DM00215 19. 43 7. 706e-11 193-225 3. DM00215 19. 43 5. 018e-10 195-227 DM00215 19. 43 5. 982e-10 192-224 DM00215 19. 43 7. 750e-10 188-220 DM00215 19. 43 7. 911 e-10 198-230 DM00215 19. 43 9. 839e-10 189-221 DM00215 19. 43 5. 271 e-09 191-223 497 BL00904 Protein prenyltransferases BL00904A 8. 30 4. 766e-09 205-254 alpha subunit repeat proteins BL00904A 8. 30 7. 766e-09 204-253 proteins. 501 BLOI 113 Clq domain proteins. BL0 ì I ì 3A 17. 99 3. 106c-10 22-48 501 PR00513 5 PR00513D 11. 06 8. 085e-09 50-67 HYDROXYTRYPTAMINE I B RECEPTOR SIGNATURE 502 PR00828 FORMIN SIGNATURE PR00828H 8. 87 4. 081e-09 390-411 504 PR00169 POTASSIUM CHANNEL PR00169H 8. 09 5. 696e-30 225-251 SIGNATURE PR00169E 9. 10 8. 773e-28 127-153 PR00169G 9. 39 6. 684e-27 196-218 PR00169C 16. 31 8. 714e-25 59-82 PR00169F 7. 19 6. 192e-24 156-179 PR00169D 12. 86 2. 385e-20 85-105 507 PR00451 CHITIN-BINDING PR00451A 6. 49 1. 871e-09 88-96 DOMAIN SIGNATURE 507 PR00873 ECHINOIDEA (SEA PR00873D 8. 43 9. 707e-09 78-96 URCHIN) METALLOTHIONEIN SIGNATURE 511 PF01327 Polypeptide deformylase. PF01327D 18. 82 2. 440e-20 197-228 PF01327A 18. 58 2. 187e-09 92-126 512 PD02796 PROTEIN STEROL PD02796B 20. 92 6. 507e-23 157-203 CARRIER LIPID-TRAN. 513 BL00232 Cadherins extracellular repeat BL00232A 27. 72 7. 218e-12 38-70 proteins domain proteins. 516 BL00261 Glycoprotein hormones beta BL00261 B 25. 64 I. OOOe-40 72-115 chain proteins. BL00261 A 23. 97 3. 500e-34 22-55 517 PR00796 VIRAL SPIKE PR007961 8. 96 7. 638e-11 32-57 GLYCOPROTEIN PRECURSOR SIGNATURE 520 PR00209 ALPHA/BETA GLIADIN PR00209B 4. 88 8. 594e-09 129-147 FAMILY SIGNATURE 523 PR00833 POLLEN ALLERGEN POA PR00833H 2. 30 6. 625e-10 61-75 Table 3 SEQ ID Database entry Description *Results NO : ID Pi SIGNATURE 523 PR00308 TYPE I ANTIFREEZE PR00308C 3. 83 5. 846e-10 66-75 PROTEIN SIGNATURE PR00308C 3. 83 9. 308e-10 58-67 PR00308A 5. 90 3. 859e-09 63-77 523 PR00456 RIBOSOMAL PROTEIN P2 PR00456E 3. 06 8. 685e-11 73-87 SIGNATURE PR00456E 3. 06 7. 375e-10 64-78 PR00456E 3. 06 7. 844e-10 61-75 PR00456E 3. 06 9. 625e-10 57-71 PR00456E 3. 06 9. 625e-10 58-72 PR00456E 3. 06 9. 625e-10 59-73 PR00456E 3. 06 9. 906e-10 60-74 PR00456E 3. 06 1. 228e-09 62-76 PR00456E 3. 06 2. 367e-09 56-70 PR00456E 3. 06 2. 595e-09 67-81 PR00456E 3. 06 3. 962e-09 68-82 PR00456E 3. 06 5. 443e-09 50-64 523 PF00761 Polyomavirus coat protein. PF00761 B 18. 21 6. 924e-09 51-89 523 DM01283 A-BINDING PROTEIN DM01283A 14. 91 5. 300e-10 55-90 CHLOROPHYLL. DM01283A 14. 91 5. 781 e-09 53-88 DM01283A 14. 91 8. 313e-09 50-85 542 PR00779 INOSITOL 1, 4, 5-PR00779H 8. 81 6. 909e-09 18-39 TRISPHOSPHATE- BINDING PROTEIN RECEPTOR SIGNATURE 544 DM00031 IMMUNOGLOBULIN V DM00031B 15. 41 4. 508e-15 84-117 REGION. 549 PD01736 PROTEIN PD01736B 8. 42 9. 250e-09 118-129 TRANSMEMBRANE INTERGENIC REGION RECQ-PLD. 551 PF00512 Signal carboxyl-terminal PF00512 13. 94 3. 571e-14 150-168 domain proteins. 552 PF01032 FecCD transport family. PF01032B 9. 12 7. 300e-15 i 32-146 553 BL00713 Sodium : dicarboxylate BL00713D 20. 98 6. 063e-09 24-61 symporter family proteins. 554 DM00784 APILLOMAVIRUS E4 DM00784B 17. 87 7. 492e-09 67-91 PROTEIN. 554 PF00624 Flocculin repeat proteins. PF00624J 6. 21 2. 669e-10 49-103 PF00624G 10. 91 7. 225e-1086-140 PF00624G 10. 91 2. 016e-09 78-132 PF00624G 10. 91 3. 831e-0930-84 PF00624F 11. 04 3. 976e-09 67-102 PF00624G 10. 91 4. 339e-09 60-114 PF00624F 11. 04 5. 355e-09 73-108 PF00624F 11. 04 5. 935e-09 19-54 PF00624G 10. 91 6. 589e-09 84-138 PF00624G 10. 91 6. 734e-09 62-116 PF00624G 10. 91 7. 677e-09 38-92 PF00624G 10. 91 8. 403e-09 21-75 PF00624J 6. 21 9. 023e-09 61-115 PF00624J 6. 21 9. 023e-09 65-l l 9 PF00624G 10. 91 9. 347e-09 24-78 PF00624G 10. 91 9. 710e-0992-146 559 BL00590 LIF/OSM family proteins. BL00590B 17. 36 3. 045e-19 183-200 562 BL00713 Sodium : dicarboxylate BL00713C 19. 76 1. 964e-09 100-138 symporter family proteins.

Table 3 SEQ ID Database entry Description *Results NO : ID 563 BL00216 Sugar transport proteins. BL00216B 27. 64 8. 000e-25 108-157 563 PR00171 SUGAR TRANSPORTER PROO 171 C 10. 97 8. 714e-13 268-278 SIGNATURE PR00171 D 12. 76 1. 610e-11 357-378 PROO 171 B 14. 73 2. 019e-09 109-128 563 PR00172 GLUCOSE TRANSPORTER PR00172A 9. 82 9. 372e-20 258-279 SIGNATURE PR00172F 8. 47 6. 400e-15 420-440 PR00172B 8. 42 7. 639e-14 295-316 PR00172E 8. 29 5. 755e-13 390-408 PR00172D 9. 13 2. 227e-12 357-380 PR00172C 9. 51 2. 209e-09 326-346 563 PR00593 METABOTROP1C PR00593E 11. 51 5. 227e-09 112-126 GLUTAMATE RECEPTOR SIGNATURE 565 BL00979 G-protein coupled receptors B L00979M 14. 39 5. 114e-12 126-176 family 3 proteins. 565 PR00248 MEI'ABOTROPIC PR00248F 14. 25 8. 222e-09 152-174 GLUTAMATE GPCR SIGNATURE 566 BL00402 Binding-protein-dependent BL00402A 5. 93 7. 000e-09 55-68 transport systems inner membrane co. 568 PR00237 RHODOPSIN-LIKE GPCR PR00237F 13. 57 8. 342e-09 24-48 SUPERFAMILY SIGNATURE 568 PR00175 SODIUM/ALANINE PR00175C 11. 57 9. 753e-09 2-21 SYMPORTER SIGNATURE 587 PR00170 SODIUM CHANNEL PR00170G 7. 74 3. 374e-09 37-65 SIGNATURE 594 BL00237 G-protein coupled receptors BL00237A 27. 68 5. 974e-12 83-122 proteins. 594 PR00534 MELANOCORTIN PR00534A 11. 49 6. 123e-10 44-56 RECEPTOR FAMILY SIGNATURE 594 PR00245 OLFACTORY RECEPTOR PR00245C 7. 84 4. 484e-17 231-246 SIGNATURE PR00245A 18. 03 9. 265e-16 52-73 PR00245B 10. 38 9. 514e-12 170-184 PR00245D 10. 47 2. 465e-10 267-278 PR00245E 12. 40 8. 302e-10 284-298 594 PR00237 RHODOPSIN-LIKE GPCR PR00237E 13. 03 2. 800e-10 192-215 SUPERFAMILY PR00237A 11. 48 5. 935e-09 19-43 SIGNATURE 605 PR00245 OLFACTORY RECEPTOR PR00245A 18. 03 1. 419e-18 57-78 SIGNATURE 605 PR00237 RHODOPSIN-LIKE GPCR PR00237A 11. 48 5. 875e-11 24-48 SUPERFAMILY SIGNATURE 606 PR00927 ADENINE NUCLEOTIDE PR00927A 7. 98 9. 667e-09 14-26 TRANSLOCATORI SIGNATURE 609 PR00237 RHODOPSIN-LIKE GPCR PR00237B 13. 50 2. 250e-09 58-79 SUPERFAMILY PR00237G 19. 63 9. 372e-09 143-169 SIGNATURE 610 PR00698 C. ELEGANS SRG FAMILY PR00698E 14. 43 8. 714e-09 97-122 INTEGRAL MEMBRANE PROTEIN SIGNATURE 615 PF00075 RNase H. PF00075A 14. 44 4. 429e-09 231-247 Table 3 SEQ ID Database entry Description *Results NO : ID 618 PF01325 Iron dependant repressor. PF01325B 20. 91 5. 680e-09 34-55 619 PD01066 PROTEfN ZINC FINGER PD01066 19. 43 9. 727e-36 58-96 ZINC-FINGER METAL- BINDING NU. 620 PR00907 THROMBOMODULIN PR00907E 11. 70 2. 969e-10 49-71 SIGNATURE 632 PD01 1 15 PRECURSOR AMPHIBIAN PD01115A 12. 27 9. 750e-12 1-23 SKIN SIGNAL. 636 BL00970 Nuclear transition protein 2 BL00970B 10. 09 8. 966e-10 83-108 proteins. 638 PF01007 Inwardrectifierpotassium PF01007B 17. 48 1. 000e-0895-138 channel. 654 BL00948 Ribosomal protein S7e BL00948A 14. 13 5. 034e-20 68-90 proteins. 658 PR00019 LEUCINE-RICH REPEAT PR00019B 11. 36 4. 150e-10 70-83 SIGNATURE PR00019B 11. 36 9. 100e-10 94-107 PR00019A 11. 19 8. 000e-09 73-86 658 PR00500 POLYCYSTIC KIDNEY PR00500B 7. 74 9. 337e-09 178-198 DISEASE PROTEIN SIGNATURE 660 BL00476 Fatty acid desaturases family BL00476B 18. 34 4. 938e-09 252-295 1 proteins. 660 PR00669 INHIBIN ALPHA CHAIN PR00669B 8. 27 6. 488e-09 179-195 SIGNATURE 665 BL01253 Type I fibronectin domain BL01253C 15. 89 6. 654e-18 78-116 proteins. 665 PR00018 KRINGLE DOMAIN PR00018C 14. 30 3. 625e-21 82-102 SIGNATURE PR00018A 14. 52 3. 423e-09 36-51 670 PR00049 WILM'S TUMOUR PR00049D 0. 00 6. 034e-09 7-2 PROTEIN SIGNATURE 672 PR00591 SOMATOSTATIN PR00591 B 7. 56 4. 750e-09 117-131 RECEPTOR TYPE 5 SIGNATURE * Results include in order : Accession No. , subtype, e-value, and amino acid position of the signature in the corresponding polypeptide Table 4A SEQ ID NO : Pfam Model Description E-value Score 340 trypsin Trypsin 1. 9e-06 23. 0 345 PMP22_Claudin PMP-0. 002-5. 3 22/EMP/MP20/Claudin family 350 ig Immunoglobulin 1. 7e-08 32. 5 domain 354 KRAB KRAB box 6. 4e-22 86. 3 356 p450 Cytochrome P450 8. 3e-13 48. 0 362 ABC tran ABC transporter 0. 0016-23. 4 383 neurchan Neurotransmitter-gated 4. 8e-15 54. 0 ion-channel 386 BCCT BCCT family 8. 5e-22 85. 8 transporter 388 Fumarate-red-D 3. 4e-64 226. 7 391 HAMP 1. 1 e-11 52. 2 404 7tm2 7transmembrane 0. 0039-87. 5 receptor (Secretin family) 410 Clq Clq domain 2. 2e-45 164. 2 416 MCT Monocarboxylate 4. 4e-59 209. 7 transporter 426 7tu 1 7 transmembrane 5. 4e-22 72. 0 receptor (rhodopsin family) 435 EGF EGF-like domain 0. 00021 28. 1 437 DUF6 Integral membrane 0. 043 13. 8 protein DUF6 438 zf-DHHC DHHC zinc finger 1. 2e-32 121. 9 domain 443 CUB CUB domain 6. 9e-32 119. 4 447 Ribosomal_L3 e Ribosomal protein 0. 00061 16. 6 L31e 448 7tm3 7transmembrane 0. 0073-95. 1 receptor (metabotropic glutamate family) 449 PMP22 Claudin PMP-7. 6e-31 115. 9 22/EMP/MP20/Claudin family 453 7tm_2 7 transmembrane 3. 7e-05-46. 4 receptor (Secretin family) 455 tsp_l Thrombospondin type 0. 028 12. 1 I domain 473 7tm_1 7 transmembrane 9. 3e-40 128. 4 receptor (rhodopsin family) 474 PDZ PDZ domain (Also 2. 1e-42 154. 3 known as DHR or GLGF). 477 trypsin Trypsin 9. 8e-99 313. 5 484 Peptidase Ml Peptidase family Ml 3. 7e-11 32. 8 487 ig Immunoglobulin 1. 2e-06 26. 5 domain 496 SCP SCP-like extracellular 2. 9e-21 80. 4 protein 501 Clq Clq domain 5. 4e-08 35. 2 Table 4A SEQ ID NO : Pfam Model Description E-value Score 504 ion trans lon transport protein 3. 9e-31 116. 9 511 Pep_deformylase Polypeptide 2. 1e-20 81. 2 deformylase 512 SCP2 SCP-2 sterol transfer 5. 2e-23 89. 9 family 513 cadherin Cadherin domain 2. 9e-08 40. 9 516 Cys knot Cystine-knotdomain 3. 3e-52 186. 9 544 ig Inununoglobulin 2. 6e-09 35. 1 domain 551 HAMP 1. te-08'42. 3 552 FecCD_family FecCD transport family 7. 4e-44 159. 1 553 BPD_transp Binding-protein-6e-05 29. 9 dependent transport systems inner membrane component 557 ig Immunoglobulin 8. 8e-13 46. 2 domain 559 LIF OSM LIF/OSM family 8e-145 494. 5 562 SDF Sodium : dicarboxylate 3. 4e-58 206. 8 symporter family 563sugars Sugar (and other) 2e-99 343. 7 transporter 565 7tm_3 7 transmembrane 2. 1e-06-21. 8 receptor (metabotropic glutamate family) 576 PMP22_Claudin PMP-4. 1 e-08 40. 4 22/EMP/MP20/Claudin family 579 zf-DHHC DHHC zinc finger 0. 0085-6. 4 domain 582 Rhomboid Rhomboid family 0. 072-20. 3 592 ig Immunoglobulin I. Se-05 23. 0 domain 594 7tm_1 7 transmembrane 7. 1e-30 97. 1 receptor (rhodopsin family) 605 7tm 1 7 transmembrane 3. 8e-06 21. 7 receptor (rhodopsin family) 609 7tm_1 7 transmembrane 0. 064 8. 3 receptor (rhodopsin family) 611 DUF6 Integral membrane 1. 4e-05 32. 0 protein DUF6 615 rvt Reverse transcriptase 3e-15 61. 0 (RNA-dependent DNA polymerase) 619 KRAB KRAB box 2e-42 154. 4 632 Gastrin Gastrin/cholecystokinin 7. 5e-22 83. 9 family 634. Cornifin 0. 0031 5. 4 638 ion trans lon transport protein 0. 0034 24. 0 642 Galactosyl_T Galactosyltransferase 2. 9e-28 107. 3 654 Ribosomal S7e Ribosomal protein S7e 6. 9e-17 69. 5 658 LRR Leucine Rlch Repeat 1. 8e-15 64. 8 665 kringle Kringle domain 1. 2e-17 72. 1 Table 4A SEQ ID NO : Pfam Model Description E-value Score 666 p450 Cytochrome P450 0. 034 10. 6 Table 4B SEQ Pfam Model Description E-value Score No : of Position ID Pfam of the NO : Domains Domain 345 PMP22_Claudin PMP-0. 002-5. 3 1 4-195 22/EMP/MP20/Claudin family 350 ig Immunoglobulin domain 4. 3e-05 30. 3 1 35-112 351 LRR Leucine Rich Repeat 1. 5 15. 3 1 19-41 354 KRAB KRAB box 3. 9e-23 90. 3 1 127-167 357 MOSC N MOSC N-terminal beta 0. 00046 11. 9 1 54-165 barrel domain 358 LRRNT Leucine rich repeat N-0. 28 17. 4 1 35-62 terminal domain 360 Adeno_E3_CR2 Adenovirus E3 region 3. 9-1. 3. _ 83-130 protein CR2 362 ABC tran ABC transporter 0. 0068-28. 4 1 155-257 381 PMP22_Claudin PMP-7. 5-67. 1 1 1-134 22/EMP/MP20/Claudin family 383 Neurchanmem Neurotransmitter-gatedion-0. 28-95. 0 1 5-100 b channel tra 385 Vps26 Vacuolar protein sorting-1. 4e-92 321. 0 1 12-247 associated protein 386 Transposase 27 IS 1 transposase 1. 2e-52 188. 3 I 212-323 386 BCCT BCCT family transporter 8. 5e-22 85. 8 1 17-328 386 BCCT BCCT family transporter 8. 5e-22 85. 8 I 17-328 388 Fumarate red D Fumarate reductase subunit 1 e-63 225. 1 1 2-119 D 390 wzz Chain length determinant 0. 003 2. 8 1 1-101 protein 391 HAMP HAMP domain 1. 2e-11 52. 2 I 74-143 391 LEA Late embryogenesis 3. 5-2. 1 I 149-213 abundant protein 404 7tm_2 7 transmembrane receptor 0. 004-87. 9 I 13-153 (Secretin family) 409 DAG_PE-bind Phorbol 0. 73-6. 1 1 59-94 esters/diacylglycerol binding dom 410 Clq Clq domain 5. 9e-46 166. 1 1 73-202 416 FecCD FecCD transport family 0. 65-198. 0 1 3-224 416 UPS0118 Domain of unknown 2. 8-117. 6 4-353 function DUF20 416 sugar tr Sugar (and other) 6. 7-193. 3 I 3-355 transporter 416 TerC Integral membrane protein 8. 9-103. 2 1 26-215 TerC family 416 secY eubacterial secY protein 9. 2-248. 7 1 5-302 422 MCPsignal Methyl-accepting 0. 86-122. 1 1 265-467 chemotaxis protein (MCP) s 422 LEA Late embryogenesis 6. 5-5. 5 1 401-463 abundant protein 426 7tm_1 7 transmembrane receptor 0. 00024-17. 2 I 18-226 (rhodopsin family) 435 EGF EGF-like domain 0. 00021 28. 1 5 27-51 : 64- 94 : 107- 137 : 150- 180 : 193- 217 435 EB EB module 2. 8-6. 5 1 113-180 <BR> <BR> Table 4B SEQ Pfam Model Description E-value Score No : of Position ID Pfam of the NO : Domains Domain 435 laminin_EGF Laminin EGF-like 3. 6-9. 8 4 28-64 : 68- (Domains III and V) 107 : 111- 150 : 154- 197 437 DUF6 Integral membrane protein 0. 08 10. 6 1 160-288 DUF6 437 DUF250 Domain of unknown 9. 9-107. 0 1 142-274 function, DUF250 438 zf-DHHC DHHC zinc finger domain 1. 2e-32 121. 9 1 98-162 438 CDP-CDP-alcohol 9. 9-35. 1 1 14-188 OH P transf phosphatidyltransferase 440 DUF6 Integral membrane protein 0. 59-4. 1 1 133-264 DUF6 443 CUB CUB domain 4c-31 116. 8 1 135-240 443 sushi Sushi domain (SCR repeat) 4. 5e-06 33. 6 1 74-131 447 Ribosomal L3 e Ribosomal protein L3 e 0. 00061 16. 6 1 77-143 448 7tm 3 7 transmembrane receptor 0. 0073-95. 1 1 1-108 449 PMP22_Claudin PMP-7. 6e-31 115. 9 1 4-181 22/EMP/MP20/Claudin family 453 7tm 2 7 transmembrane receptor 3. 7e-05-46. 4 1-175 (Secretin family) 455 tsp_l Thrombospondin type 1 0. 028 12. 1 1 31-83 domain 460 Brevenin Brevenin/esculentin/gaeguri 8. 5-3. 3 1 17-61 n/rugosin family 464 Pep_M12B_prop Reprolysin family 0. 12-23. 7 179-288 ep propeptide 472 TMSTDE TMS membrane 2e-06-157. 8 1 1-193 protein/tumour differentially e 472 SPW SPW repeat 8. 5-8. 3 I 69-121 473 7tu_ 1 7 transmembrane receptor 1. 2e-32 121. 9 I 21-279 (rhodopsin family) 474 PDZ PDZ domain (Also known 1. le-41 152. 0 3 1 19- as DHR or GLGF) 211 : 233- 313 : 314- 401 474 Autoind bind Autoinducer binding 9. 3-50. 4 1 26-153 domain 477 trypsin Trypsin 8. 2e-91 315. 1 1 36-258 487 ig Immunoglobulin domain 0. 0017 25. 1 1 32-109 496 SCP SCP-like extracellular l. Se-16 68. 4 1 18-215 protein 502 MBOAT MBOAT family 7. 5e-73 255. 4 1 66-379 504 ion trans Ion transport protein 1. 4e-32 121. 7 1 56-247 504 oxidoredq3 NADH-5. 6-81. 7 1 92-242 ubiquinone/plastoquinone oxidoreduct 510 HEAT HEAT repeat 0. 39 17. 2 1 106-143 511 Pep_deformylase Polypeptide deformylase 4. 3e-19 76. 8 1 63-238 512 SCP2 SCP-2 sterol transfer family 5. 2e-23 89. 9 1 100-208 512 Uteroglobin Uteroglobin family 5. 6-26. 8 1 1-70 513 cadherin Cadherin domain le-08 42. 4 1 48-139 Table 4B SEQ Pfam Model Description E-value Score No : of Position ID Pfam of the NO : Domains Domain 516 Cys_knot Cystine-knot domain 8. 3e-53 188. 9 1 15-125 542 LAG 1 Longevity-assurance protein 3. 4-109. 3 1 60-243 (LAG)) 543 NIF NLI interacting factor 5. 3e-15 63. 3 1 120-300 544 ig Immunoglobuhn domain 1. 8e-07 38. 2 I 34-117 550 YjgP YjgQ Predicted permease 6. 5e-23 89. 6 1 1-279 YjgP/YjgQ family 550 Hexose dehydrat NDP-hexose 2, 3- 9. 5-172. 0 1 25-147 dehydratase 551 HAMP HAMP domain 1. 1 e-08 42. 3 70-138 551 signal His Kinase A 1. 5-1. 9 1 142-174 (phosphoacceptor) domain 552 FecCD FecCD transport family 7. 4e-44 159. 1 1 1-203 552 ABC-3 ABC 3 transport family 3. 1-186. 2 I 1-203 553 BPD_transp Binding-protein-dependent 6e-05 29. 9 I 108-184 transport system 553 Competence Competence protein 0. 71-84. 6 I 2-216 557 ig Immunoglobulin domain 4. 3e-07 37. 0 I 45-164 559 LIF OSM LIF/OSM family 8e-145 494. 5 1 2-209 562 SDF Sodium : dicarboxylate 8. 3e-07-83. 3 1 1-173 symporter family 563 sugartr Sugar (and other) 2. 1 e-99 343. 6 1 17-455 transporter 563 OATPC Organic Anion Transporter 5-230. 7 1 14-348 Polypeptide 563 Nuc H symport Nucleoside H+ symporter 5. 5-269. 8 I 38-445 563 COX1 Cytochrome C and Quinol 5. 6-307. 7 1 9-422 oxidase polyp 563 DUF21 Domain of unknown 7. 2-75. 4 1 22-207 function DUF21 563 PUCC PUCC protein 7. 4-280. 0 1 37-444 563 xan_ur permease Permease family 9. 7-202. 9 1 5-349 563 DUF318 Predicted permease 10-169. 2 1 82-367 565 7tu 3 7 transmembrane receptor 2. 1 e-06-22. 0 1 I-184 570 DUF323 Domain of unknown 0. 0018-58. 7 1 31-150 function (DUF323) 576 PMP22_Claudin PMP-4. 1 e-08 40. 4 1 7-183 22/EMP/MP20/Claudin family 579 zf-DHHC DHHC zinc finger domain 0. 0085-6. 4 1 5-40 582 Rhomboid Rhomboid family 0. 092-22 0 | 15-98 587 ion trans Ion transport protein 0. 18 10. 6 1 2-133 592 ig Immunoglobulin domain 0. 0031 24. 2 1 40-111 594 7tm_1 7 transmembrane receptor 1. 9e-27 104. 6 1 34-283 (rhodopsin family) 603 Folate rec Folate receptor family 0. 87-107. 5 1 6-212 DUF6 Integral membrane protein 0. 00017 28. 3 2 8- DUF6 129 : 147- 277 611 PhaC MnhG_Yu Na+/H+ antiporter subunit 2-50. 3 16-118 fB 611 DUF7 Integral membrane protein 3. 9-34. 6 1 177-268 DUF7 611 Competence Competence protein 7. 5-104. 9 1 43-280 Table 4B SEQ Pfam Model Description E-value Score No : of Position ID Pfam of the NO : Domains Domain 615 rvt Reverse transcriptase I. Se-08 41. 9 I 214-381 619 KRAB KRAB box 6. 4e-27 102. 9 1 56-96 621 MAPEG MAPEG familY 2. 1-21. 7 I 10-95 632 Gastrin Gastrin/cholecystokinin 4e-05 30. 5 1 2-74 family 634 Cornifin Cornifin (SPRR) family 0. 0031 54 1 8-221 638 ion_trans lon transport protein 0. 01 22. 4 I 101-263 642 Galactosyl T Galactosyltransferase 1. 2e-25 98. 6 1 130-334 653 DUF312 Short repeats of unknown 9. Z-2. 8 1 269-312 function (DUF312) 654 Ribosomal S7e Ribosomal protein S7e le-16 69. 0 I 66-158 658 LRR Leucine Rich Repeat 1. 2e-15 65. 5 5 48-71 : 72- 95 : 96- 119 : 120- 143 : 144- 167 658 LRRNT Leucine rich repeat N-3e-08 40. 9 1 17-46 terminal domain 658 LRRCT Leucine rich repeat C-7. 8e-07 36. 1 I 177-230 terminal domain 665 kringle Kringle domain 1. 2e-17 72. 1 36-l l 9 665 CUB CUB domain 2. 5e-12 54. 4 1 219-323 665 WSC WSC domain 2. 6e-08 41. 0 124-205 668 PMP22_Claudin PMP-8. 6-68. 2 1 25-200 22/EMP/MP20/Claudin family Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : 350 lal4 L 20 126 3. 4e-25 55. 31 NEURAMINtDASE ; CHAIN : N ; COMPLEX SINGLE CHAIN ANTIBODY ; (ANTIBODY/ANTIGEN) CHAIN : H, L ; COMPLEX (ANTIBODY/ANTIGEN), SINGLE- CHAIN ANTIBODY, 2 GLYCOSYLATED PROTEIN 350 la2y A 20 126 5. 1e-27 54. 70 MONOCLONAL ANTIBODY COMPLEX Dl. 3 ; CHAIN : A, B ; (IMMUNOGLOBULIN/HYDROLA LYSOZYME ; CHAIN : C ; SE) COMPLEX (IMMUNOGLOBULIN/HYDROLA SE), IMMUNOGLOBULIN V 2 REGION, SIGNAL, HYDROLASE, GLYCOSIDASE, BACTERIOLYTIC 3 ENZYME, EGG WHITE 350 a7q L 20 136 1. 5e-25 52. 86 MONOCLONAL ANTIBODY IMMUNOGLOBULIN Dl. 3 ; CHAIN : L, H ; IMMUNOGLOBULIN, VARIANT 350 lao7 E 22 142 3. 4e-46-0. 08 0. 06 HLA-A 0201 ; CHAIN : A ; BETA-COMPLEX (MHCNIRAL 2 MICROGLOBULIN ; CHAIN : PEPTIDE/RECEPTOR) HLA-A2 B ; TAX PEPTIDE ; CHAIN : C ; T HEAVY CHAIN ; CLASS I MHC, T- CELL RECEPTOR ALPHA ; CELL RECEPTOR, VIRAL CHAIN : D ; T CELL RECEPTOR PEPTIDE, 2 COMPLEX BETA ; CHAIN : E ; (MHC/VIRAL PEPTIDE/RECEPTOR 350 lap2 A 20 128 5. 1e-30 51. 96 MONOCLONAL ANTIBODY IMMUNOGLOBULIN VARIABLE C219 ; CHAIN : A, B, C, D ; DOMAIN ; SINGLE CHAIN FV, MONOCLONAL ANTIBODY, C219, P-GLYCOPROTEIN, 2 IMMUNOGLOBULIN 350 larl D 20 136 3. 4e-26 52. 90 CYTOCHROME C OXIDASE ; COMPLEX CHAIN : A, B ; ANTIBODY FV (OXIDOREDUCTASE/ANTIBODY FRAGMENT ; CHAIN : C, D ;) CYTOCHROME AA3, COMPLEX Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : IV, FERROCYTOCHROME C, COMPLEX (OXIDOREDUCTASE/ANTIBODY ), ELECTRON TRANSPORT, 2 TRANSMEMBRANE, CYTOCHROME OXIDASE, ANTIBODY COMPLEX 350 1 bOw A 20 127 5. 1e-27 55. 43 BENCE-JONES KAPPA I IMMUNE SYSTEM BENCE- PROTEIN BRE ; CHAIN : A, B, JONES : IMMUNOGLOBULIN, C ; AMYLOID, IMMUNE SYSTEM 350 lbd2 22 160 1. 7e-48-0. 10 0. 07 HLA-A 0201 ; CHAIN : A ; BETA-COMPLEX (MHC/VIRAL 2 MICROGLOBULIN ; CHAIN : PEPTIDE/RECEPTOR) HLA A2 B ; TAX PEPTIDE ; CHAIN : C ; T HEAVY CHAIN ; COMPLEX CELL RECEPTOR ALPHA ; (MHC/VIRAL CHAIN : D ; T CELL RECEPTOR PEPTIDE/RECEPTOR) BETA ; CHAIN : E ; 350 bec 23 143 1. 7e-46 0. 27 0. 30 14. 3. D T CELL ANTIGEN RECEPTOR T CELL RECEPTOR RECEPTOR ; 1 BEC 5 CHAIN : I BEC 14 NULL IBEC 6 350 tbfv L 20 127 1. 7e-25 51. 18 FV4155 ; CHAIN : L, H ; IMMUNOGLOBULIN IMMUNOGLOBULIN, FV FRAGMENT, STEROID HORMONE, 2 FINE SPECIFICITY 350 bvk A 20 127 1. 2e-29 57. 64 LYS11 ; CHAIN : A, B, D, E ; COMPLEX (HUMANIZED LYSOZYME ; CHAIN : C, F ; ANTIBODY/HYDROLASE) MURAMIDASE ; HUMANIZED ANTIBODY, ANTIBODY COMPLEX, FV, ANTI- LYSOZYME, 2 COMPLEX (HUMANIZED ANTIBODY/HYDROLASE) Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : 350 ibwm A 23 138 3. 4e-45 0. 06 0. 12 ALPHA-BETA T CELL IMMUNE SYSTEM RECEPTOR (TCR) (D10) ; IMMUNOGLOBULIN, CHAIN : A ; IMMUNORECEPTOR, IMMUNE SYSTEM 350 lbww A 18 126 le-28 52. 26 IG KAPPA CHAIN V-I REGtON IMMUNE SYSTEM REIV, REI ; CHAIN : A, B ; STABILIZED IMMUNOGLOBULIN FRAGMENT, BENCE-JONES 2 PROTEIN, IMMUNE SYSTEM 350 ld9k B 23 138 3. 4e-45 0. 12 0. 34 T-CELL RECEPTOR D10 IMMUNE SYSTEM MHC I-AK ; (ALPHA CHAIN) ; CHAIN : A, E ; MHC I-AK ; T-CELL RECEPTOR, T-CELL RECEPTOR D10 MHC CLASS 11, D10, I-AK (BETA CHAIN) ; CHAIN : B, F ; MHC I-AK A CHAIN (ALPHA CHAIN) ; CHAIN : C, G ; MHC I- AK B CHAIN (BETA CHAIN) ; CHAIN : D, H ; CONALBUMIN PEPTIDE ; CHAIN : P, Q ; 350 ldlf L 20 127 8. 5e-26 54. 31 ANTI-DANSYL IMMUNOGLOBULIN ANTI- IMMUNOGLOBULIN DANSYL FV FRAGMENT FV IGG2A (S) ; CHAIN : L, H. FRAGMENT, IMMUNOGLOBULIN 350 ldsf L 20 129 5. 1 e-23 53. 77 ANTICANCER ANTIBODY Bl ; IMMUNOGLOBULIN B I DSFV ; CHAIN : L, H ; MONOCLONAL ANTIBODY, ANTITUMOR, IMMUNOGLOBULIN 350 If l 1 20 159 6. 8e-34-0. 00 0. 07 F124 IMMUNOGLOBULIN IMMUNE SYSTEM (KAPPA LIGHT CHAIN) ; IMMUNOGLOBULIN, CHAIN : A, C ; F124 ANTIBODY, FAB, HEPATITIS B, IMMUNOGLOBULIN (IGGI PRES2 HEAVY CHAIN) ; CHAIN : B, D ; Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : 350 fgv L 20 136 1. 7e-31 55. 11 IMMUNOGLOBULIN FV FRAGMENT OF A HUMANIZED VERSION OF THE ANTI-CD18 1FGV 3 ANTIBODY'H52' (HUH52-AA FV) I FGV 4 350 Ifvc A 20 128 6. 8e-31 54. 26 IMMUNOGLOBULIN FV FRAGMENT OF HUMANIZED ANTIBODY 4D5, VERSION 8 1 FVC 3 350 1 fyt E 22 160 6. 8e-44 0. 05 0. 10 HLA CLASS 11 IMMUNE SYSTEM HLA-DRI, HISTOCOMPATIBILITY DRA ; HLA-DR1, DRB1 0101 ; TCR ANTIGEN, DR CHAIN : A ; HLA HAI. 7 ALPHA CHAIN ; TCR Ha. 7 CLASS 11 BETA CHAIN ; PROTEIN- HISTOCOMPATIBILITY PROTEIN COMPLEX, ANTIGEN, Dry CHAIN : B ; IMMUNOGLOBULIN FOLD HEMAGGLUTININ HA1 PEPTIDE CHAIN ; CHAIN : C ; T- CELL RECEPTOR ALPHA CHAIN ; CHAIN : D ; T-CELL RECEPTOR BETA CHAIN ; CHAIN : E ; 350 ligm L 20 134 5. lé-30 57. 34 IMMUNOGLOBULIN IMMUNOGLOBULIN M (IG-M) FV FRAGMENT I IGM 3 350 livl A 20 126 le-24 60. 97 IMMUNOGLOBULIN IMMUNOGLOBULIN VL DOMAIN (VARIABLE DOMAIN OF KAPPA LIGHT I IVL 3 CHAIN) OF DESIGNED ANTIBODY M29B I IVL 4 350 Ijhl L 20 127 3. 4e-285795 COMPLEX (ANTIBODY- Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : ANTIGEN) FV FRAGMENT (IGGI, KAPPA) (LIGHT AND HEAVY VARIABLE DOMAINS 1JHL 3 NON-COVALENTLY ASSOCIATED) OF MONOCLONAL ANTI-HEN EGG IJHL 4 LYSOZYME ANTIBODY Dol 1. 15 COMPLEX WITH PHEASANT EGG IJHL 5 LYSOZYME IJHL 6 350 1 kb5 B 21 136 1. 7e-33 50. 75 KB5-C20 T-CELL ANTIGEN COMPLEX RECEPTOR ; CHAIN : A, B ; (IMMUNOGLOBULIN/RECEPTOR ANTIBODY DESIRE-) ; CHAIN :) TCR VAPLHA VBETA DOMAIN ; L, H ; T-CELL RECEPTOR, STRAND SWITCH, FAB, ANTICLONOTYPIC, 2 (IMMUNOGLOBULIN/RECEPTOR ) 350 Imaj 20 127 6. 8e-24 50. 59 IMMUNOGLOBULIN MURINE ANTIBODY 26-10 VL DOMAIN (NMR, 15 ENERGY MINIMIZED I MAJ 3 STRUCTURES) I MAJ 4 350 nfd B 20 143 le-45 0. 08 0. 27 N15 ALPHA-BETA T-CELL COMPLEX RECEPTOR ; CHAIN : A, B, C, (IMMUNORECEPTOR/IMMUNOG D ; H57 FAB ; CHAIN : E, F, G, H LOBULIN) COMPLEX (IMMUNORECEPTOR/IMMUNOG LOBULIN) 350 Inmb L 20 128 8. Se-27 58. 89 N9NEURAMINIDASE ; INMB4 COMPLEX CHAIN : N ; INMB 5 FAB NC10 ; (HYDROLASE/IMMUNOGLOBUL INMB9CHAIN : L, H INMB 10 IN) 350 Irvf L 20 130 5. 1e-26 54. 02 HUMAN RHINOVIRUS 14 COMPLEX (COAT Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : COAT PROTEIN ; CHAIN : 1, 2, PROTEIN/IMMUNOGLOBULIN) 3, 4 ; FAB 17-IA ; CHAIN : L, H POLYPROTEIN, COAT PROTEIN, CORE PROTEIN, RNA-DIRECTED RNA 2 POLYMERASE, HYDROLASE, THIOL PROTEASE, MYRISTYLATION, 3 COMPLEX (COAT PROTEIN/IMMUNOGLOBULIN) 350 isbas 20 159 1. 2e-33 0. 10 0. 33 MONOCLONAL ANTIBODY MONOCLONAL ANTIBODY 3A2 ; CHAIN : H, L ; MONOCLONAL ANTIBODY, FAB-FRAGMENT, REPRODUCTION 350 ltcr 20 143 le-45 0. 06 0. 17 ALPHA, BETA T-CELL RECEPTOR TCR ; T-CELL, RECEPTOR CHAIN : A, B ; RECEPTOR, TRANSMEMBRANE, GLYCOPROTEIN, SIGNAL 350 lwtl A 20 127 6. 8e-28 54. 08 IMMUNOGLOBULIN WAT, A VARIABLE DOMAIN FROM IMMUNOGLOBULIN LIGHT- CHAIN I WTL 3 (BENCE- JONES PROTEIN) I WTL 4 350 2rhe 21 130 1. 7e-24 52. 52 IMMUNOGLOBULIN BENCE- *JONES PROTEIN (LAMBDA, VARIABLE DOMAIN) 2RHE 4 351 Ifol A I 53 0. 00012-0. 34 0. 12 NUCLEAR RNA EXPORT RNA BINDING PROTEIN TAP FACTOR l ; CHAIN : A, B ; (NFXI) ; RIBONUCLEOPROTEIN (RNP, RBD OR RRM) AND LEUCINE-RICH-REPEAT 2 (LRR) 356 Idt6 60 248 8. 5e-52-0. 41 0. 05 CYTOCHROME P450 2C5 ; OXIDOREDUCTASE . _ CHAIN : A ; PROGESTERONE 21- Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : HYDROXYLASE, CYPIIC5 P450 1, MEMBRANE PROTEIN, PROGESTERONE 21- HYDROXYLASE, BENZO (A) 2 PYRENE HYDROXYLASE, ESTRADIOL 2-HYDROXYLASE, P450, CYP2C5 362 IbOu 129 254 5. 1e-24 0. 37 0. 36 HISTIDINE PERMEASE ; TRANSPORT PROTEIN ABC CHAIN : A ; TRANSPORTER, HISP ; ABC TRANSPORTER, HISTIDINE PERMEASE, TRANSPORT PROTEIN 362 If2u A 141) 75 0. 0025-0. 78 0. 09 RAD50 ABC-ATPASE ; CHAIN : REPLICATION DNA DOUBLE- A, C ; RAD50 ABC-ATPASE ; STRAND BREAK REPAIR, ABC- CHAIN : B, D ; ATPASE 362 f2u A 160 213 0. 0048-0. 91 0. 12 RAD50 ABC-ATPASE ; CHAIN : REPLICATION DNA DOUBLE- A, C ; RAD50 ABC-ATPASE ; STRAND BREAK REPAIR, ABC- CHAIN : B, D ; ATPASE 362 Ig29 I 142 253 3. 4e-21-0. 28 0. 34 MALTOSE TRANSPORT SUGAR BINDING PROTEIN PROTEIN MALK ; CHAIN : 1, 2 ; MALK ; ATPASE, ACTIVE TRANSPORT, MALTOSE UPTAKE AND REGULATION 362 Igky 158 184 0. 0027-0. 82 0. 28 TRANSFERASE GUANYLATE KINASE (E. C. 2. 7. 4. 8) COMPLEX WITH IGKY 3 GUANOSINE MONOPHOSPHATE I GKY 4 364 le3y A 103 159 0. 0025 0. 21 0. 52 FADD PROTEIN. CHAIN : A ; APOPTOSIS FAS-ASSOCIATING DEATH DOMAIN-CONTAINING Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : PROTEIN ; DEATH DOMAIN, ADAPTER MOLECULE, FAS RECEPTOR DEATH INDUCING 2 SIGNALLING COMPLEX 364 lfad A 103 150 0. 00075 0. 14 1. 00 FADD PROTEIN ; CHAIN : A ; APOPTOSIS APOPTOSIS, FADD, DEATH DOMAIN 364 llrv 19 202 0. 0018 0. 32 0. 03 LEUCINE-RICH REPEAT LEUCINE-RICH REPEATS LRV ; VARIANT ; CHAIN : NULL ; LEUCINE-RICH REPEATS, REPETITIVE STRUCTURE, IRON SULFUR 2 PROTEINS, NITROGEN FIXATION 388 I fUm D 2 100 I 7e-44-0. 68 1. 00 FUMARATE REDUCTASE OXIDOREDUCTASE COMPLEX FLAVOPROTEIN SUBUNIT ; II ; COMPLEX 11 ; COMPLEX 11 ; CHAIN : A, M ; FUMARATE COMPLEX II ; FUMARATE REDUCTASE IRON-SULFUR REDUCTASE, COMPLEX 11, PROTEIN ; CHAIN : B, N ; SUCCINATE DEHYDROGENASE, FUMARATE REDUCTASE 15 2 RESPIRATION, KD HYDROPHOBIC PROTEIN ; OXIDOREDUCTASE CHAIN : C, O ; FUMARATE REDUCTASE 13 KD HYDROPHOBIC PROTEIN CHAIN : D, P ; 388 lfum D 2 117 1. 7e-44 168. 49 FUMARATE REDUCTASE OXIDOREDUCTASE COMPLEX FLAVOPROTEIN SUBUNIT ; II ; COMPLEX 11 ; COMPLEX II ; CHAIN : A, M ; FUMARATE COMPLEX If ; FUMARATE REDUCTASE IRON-SULFUR REDUCTASE, COMPLEX 11, PROTEIN ; CHAIN : B, N ; SUCCINATE DEHYDROGENASE, FUMARATE REDUCTASE 15 2 RESPIRATION, KD HYDROPHOBIC PROTEIN ; OXIDOREDUCTASE CHAIN : C. O ; FUMARATE REDUCTASE 13 KD Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : HYDROPHOBIC PROTEIN ; CHAIN : D, P ; 391 I qu7 A 154 214 2. 5e-09-0. 49 0. 90 METHYL-ACCEPTING SIGNALING PROTEIN SERINE, CHEMOTAXIS PROTEIN I ; CHEMOTAXIS, FOUR HELICAL- CHAIN : A, B ; BUNDLE 391 2asr 38 71 Se-10-0. 81 0. 51 CHEMOTAXIS ASPARTATE RECEPTOR (LIGAND BINDING DOMAIN) 2ASR 3 391 zig A 26 71 2. 5e-14-0. 79 0. 47 ASPARTATE RECEPTOR ; 2LIG CHEMOTAXIS 4 CHAIN : A, B ; 2LIG 5 396 Icl7 130 265 0. 001 73. 12 ATP SYNTHASE SUBUNIT C ; MEMBRANE PROTEIN CHAIN : A, B, C, D, E, F, G, H, I, MEMBRANE PROTEIN, HELIX, J, K, L ; ATP SYNTHASE COMPLEX SUBUNIT A ; CHAIN : M ; 402 1 dOs A 2 91 1. 3e-09 0. 26-0. 20 NICOTINATE TRANSFERASE DINUCLEOTIDE- MONONUCLEOTIDE : 5, 6- BINDING MOTIF, CHAIN : A ; PHOSPHORIBOSYL TRANSFERASE 402 leut 24 125 le-09 0. 40-0. 20 SIALIDASE ; CHAIN : NULL ; HYDROLASENEURAMINIDASE ; HYDROLASE, GLYCOSIDASE 402 2pro A 10 136 le-18 0. 12-0. 20 ALPHA-LYTIC PROTEASE ; PRO REGION PRO REGION, CHAIN : A, B, C ; FOLDASE, PROTEIN FOLDING, SERINE PROTEASE 410 Ic28 A 71 204 1. 7e-34 0. 72 0. 89 30 KD ADIPOCYTE SERUM PROTEIN ACRP30 C1Q COMPLEMENT-RELATED TNF TRIMER ALL-BETA, SERUM PROTEIN CHAIN : A, B, C ; PROTEIN 410 Ic28 A 73 203 6. 8e-33 0. 52 0. 98 30 KD ADIPOCYTE SERUM PROTEIN ACRP30 C1Q Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : COMPLEMENT-RELATED TNF TRIMER ALL-BETA, SERUM PROTEIN CHAIN : A, B, C ; PROTEIN 410 Ic28 A 77 204 1. 7e-34 64. 45 30 KD ADIPOCYTE SERUM PROTEIN ACRP30 C1Q COMPLEMENT-RELATED TNF TRIMER ALL-BETA, SERUM PROTEIN CHAIN : A, B, C ; PROTEIN 410 Ic28 B 73 203 le-30 0. 76 0. 83 30 KD ADIPOCYTE SERUM PROTEIN ACRP30 CIQ COMPLEMENT-RELATED TNF TRIMER ALL-BETA, SERUM PROTEIN CHAIN : A, B, C ; PROTEIN 410 Ic28 B 81 196 le-30 53. 80 30 KD ADIPOCYTE SERUM PROTEIN ACRP30 CIQ COMPLEMENT-RELATED TNF TRIMER ALL-BETA, SERUM PROTEIN CHAIN : A, B, C PROTEIN 410 c28 C 73 203 8. 5e-28 0. 56 0. 37 30 KD ADIPOCYTE SERUM PROTEIN ACRP30 CIQ COMPLEMENT-RELATED TNF TRIMER ALL-BETA, SERUM PROTEIN CHAIN : A, B, C ; PROTEIN 414 Ibhd A 42 87 8. 5e-18 0. 00 0. 04 UTROPHIN ; CHAIN : A, B ; STRUCTURAL PROTEIN CALPONIN HOMOLOGY, ACTIN BINDING, STRUCTURAL PROTEIN 414 Ibkr A 41 89 1. 7e-20-0. 24 0. 28 SPECTRIN BETA CHAIN ; ACTIN-BINDING CALPONIN CHAIN : A ; HOMOLOGY (CH) DOMAIN ; FILAMENTOUS ACTIN-BINDING DOMAIN, CYTOSKELETON 414 1 dxx A 26 76 le-09-0. 48 0. 41 DYSTROPHIN ; CHAIN : A, B, C, STRUCTURAL PROTEIN D ; DYSTROPHIN, MUSCULAR DYSTROPHY, CALPONIN HOMOLOGY DOMAIN, 2 ACTIN- BINDING, UTROPHIN 414 1 dix A 42 89 1. 5e-16-0. 35 0. 11 DYSTROPHIN ; CHAIN : A, B, C, STRUCTURAL PROTEIN D ; DYSTROPHIN, MUSCULAR DYSTROPHY, CALPONIN Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : HOMOLOGY DOMAIN, 2 ACTIN- BINDING, UTROPHIN 414 qag A 42 87 8. 5e-18-0. 59 0. 09 UTROPHIN ACTIN BINDING STRUCTURAL PROTEIN REGION ; CHAIN : A, B ; CALPONIN HOMOLOGY DOMAIN, DOMAIN SWAPPING, ACTIN BINDING, 2 UTROPHIN, DYSTROPHIN, STRUCTURAL PROTEIN 422 4hbl 290 328 0. 00051 0. 28 0. 53 DHPI ; CHAIN : NULL ; DESIGNED HELICAL BUNDLE DESIGNED HELICAL BUNDLE 435 lalit L 97 202 2. SC-I3 51. 11 ACTIVATED PROTEIN C ; COMPLEX (BLOOD CHAIN : C, L ; D-PHE-PRO-MAI ; COAGULATION/INHIBITOR) CHAIN : P ; AUTOPROTHROMBIN IIA ; HYDROLASE, SERINE PROTEINASE), PLASMA CALCIUM BINDING, 2 GLYCOPROTEIN, COMPLEX (BLOOD COAGULATION/INHIBITOR) 435 dan L 114 245 5e-16 53. 38 BLOOD COAGULATION BLOOD COAGULATION, SERINE FACTOR VIIA ; CHAIN : L, H ; PROTEASE, COMPLEX, CO- SOLUBLE TISSUE FACTOR ; FACTOR, 2 RECEPTOR ENZYME. CHAIN : T, U ; D-PHE-PHE-INHIBITOR, GLA, EGF, 3 ARG-COMPLEX (SERINE CHLOROMETHYLKETONE PROTEASE/COFACTOR/LIGAND) (DFFRCMK) WITH CHAIN : C ; 435 Idan L 151 232 8. 5e-12 0. 07 0. 30 BLOOD COAGULATION BLOOD COAGULATION, SERINE FACTOR VIIA ; CHAIN : L, H ; PROTEASE, COMPLEX, CO- SOLUBLE TISSUE FACTOR ; FACTOR, 2 RECEPTOR ENZYME, Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : CHAIN : T, U ; D-PHE-PHE-INHIBITOR, GLA, EGF, 3 ARG-COMPLEX (SERINE CHLOROMETHYLKETONE PROTEASE/COFACTOR/LIGAND) (DFFRCMK) WITH CHAIN : C ; 435 dan L 32 154 2. 5e-15 0. 23-0. 13 BLOOD COAGULATION BLOOD COAGULATION, SERINE FACTOR VIIA ; CHAIN : L, H ; PROTEASE, COMPLEX, CO- SOLUBLE TISSUE FACTOR ; FACTOR, 2 RECEPTOR ENZYME, CHAIN : T, U ; D-PHE-PHE-INHIBITOR, GLA, EGF, 3 ARG-COMPLEX (SERINE CHLOROMETHYLKETONE PROTEASE/COFACTOR/LIGAND) (DFFRCMK) WITH CHAIN : C ; 435 I dan 82 197 5e-i 6 0. 45-0. 12 BLOOD COAGULATION BLOOD COAGULATION, SERINE FACTOR VIIA ; CHAIN : L, H ; PROTEASE, COMPLEX, CO- SOLUBLE TISSUE FACTOR ; FACTOR, 2 RECEPTOR ENZYME, CHAIN : T, U ; D-PHE-PHE-INHIBITOR, GLA, EGF, 3 ARG-COMPLEX (SERINE CHLOROMETHYLKETONE PROTEASE/COFACTOR/LIGAND) (DFFRCMK) WITH CHAIN : C ; 435 ldva L 151 232 8. 5e-12-0. 02 0. 63 DES-GLA FACTOR VIIA HYDROLASE/HYDROLASE (HEAVY CHAIN) ; CHAIN : H, t ; INHIBITOR PROTEIN-PEPTIDE DES-GLA FACTOR VIIA COMPLEX (LIGHT CHAIN) ; CHAIN : L, M ; (DPN)-PHE-ARG ; CHAIN : C, D ; PEPTIDE E-76 ; CHAIN : X, Y ; 435 ldx5 1 107 225 2. 5e-15 0. 30 0. 04 THROMBIN LIGHT CHAIN ; SERINE PROTEINASE CHAIN : A, B, C, D ; THROMBIN COAGULATION FACTOR ll ; HEAVY CHAIN ; CHAIN : M, N, COAGULATION FACTOR 11 ; O, P ; THROMBOMODULIN ; FETOMODULIN, TM, CD141 CHAIN : 1, J, K, L ; THROMBIN ANTIGEN ; EGR-CMK SERINE INHIBITOR L-GLU-L-GLY-L-PROTEINASE, EGF-LIKE ARM ; CHAIN : E, F, G, H ; DOMAINS, ANTICOAGULANT COMPLEX, 2 Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : ANTIFIBRINOLYTIC COMPLEX 435 lux5 1 149 259 6. 8e-14-0. 00-0. 18 THROMBIN LIGHT CHAIN ; SERINE PROTEINASE CHAIN : A, B, C, D ; THROMBIN COAGULATION FACTOR 11 ; HEAVY CHAIN ; CHAIN : M, N, COAGULATION FACTOR Il ; O, P ; THROMBOMODULIN ; FETOMODULIN, TM, CD141 CHAIN : 1, J, K, L ; THROMBIN ANTIGEN ; EGR-CMK SERINE INHIBITOR L-GLU-L-GLY-L-PROTEINASE, EGF-LIKE ARM ; CHAIN : E, F, G, H ; DOMAINS, ANTICOAGULANT COMPLEX, 2 ANTIFIBRINOLYTIC COMPLEX 435 Idx5 70 193 2e-16 0. 42-0. 12 THROMBIN LIGHT CHAIN ; SERINE PROTEINASE CHAIN : A, B, C, D ; THROMBIN COAGULATION FACTOR ll ; HEAVY CHAIN ; CHAIN : M, N, COAGULATION FACTOR 11 ; O, P ; THROMBOMODULIN ; FETOMODULIN, TM, CD141 CHAIN : 1, J, K, L ; THROMBIN ANTIGEN ; EGR-CMK SERINE INHIBITOR L-GLU-L-GLY-L-PROTEINASE, EGF-LIKE ARM ; CHAIN : E, F, G, H ; DOMAINS, ANTICOAGULANT COMPLEX, 2 ANTIFIBRINOLYTIC COMPLEX 435 lext A 33 173 5e-15 0. 13-0. 15 TUMOR NECROSIS FACTOR SIGNALLING PROTEIN BINDING RECEPTOR ; CHAIN : A, B ; PROTEIN, CYTOKINE, SIGNALLING PROTEIN 435 lext A 53 203 1. 8e- 15 65. 24 TUMOR NECROSIS FACTOR SIGNALLING PROTEIN BINDING RECEPTOR ; CHAIN : A, B ; PROTEIN, CYTOKINE, SIGNALLING PROTEIN 435 text A 54 197 1. 8e-15 0. 30-0. 06 TUMOR NECROSIS FACTOR SIGNALLING PROTEIN BINDING RECEPTOR ; CHAIN : A, B ; PROTEIN, CYTOKINE, SIGNALLING PROTEIN 435 lfak L 151 232 8. 5e-12-0. 08 0. 78 BLOOD COAGULATION BLOOD CLOTTING FACTOR VIIA ; CHAIN : L ; COMPLEX (SERINE BLOOD COAGULATION PROTEASEICOFACTOR/LIGAND) Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : FACTOR VIIA ; CHAIN : H ;, BLOOD COAGULATION, 2 SOLUBLE TISSUE FACTOR ; SERINE PROTEASE, COMPLEX, CHAIN : T ; 5L15 ; CHAIN : I ; CO-FACTOR, RECEPTOR ENZYME, 3 INHIBITOR, GLA, EGF, COMPLEX (SERINE 4 PROTEASE/COFACTOR/LIGAND) , BLOOD CLOTTING 435 ligr A 8 214 le-21 0. 15-0 12 INSULIN-LIKE GROWTH HORMONE RECEPTOR FACTOR RECEPTOR 1 ; HORMONE RECEPTOR, INSULIN CHAIN : A ; RECEPTOR FAMILY 435 1 ko 111 237 3. 4e-17 0. 52 0. 88 LAMININ ; CHAIN : NULL ; GLYCOPROTEIN GLYCOPROTEIN 435 Iklo 154 268 8. 5e-16 0. 34 0. tO LAMININ ; CHAIN : NULL ; GLYCOPROTEIN GLYCOPROTEIN 435 lklo 31 198 2. 5e-29 0. 39 0. 01 LAMININ ; CHAIN : NULL ; GLYCOPROTEIN GLYCOPROTEIN 435 1 kilo 33 199 2. 5e-29 91. 67 LAMININ ; CHAIN : NULL ; GLYCOPROTEIN GLYCOPROTEIN 435 lklo 68 197 1. 2e-18 0. 51 0. 90 LAMININ ; CHAIN : NULL ; GLYCOPROTEIN GLYCOPROTEIN 435 1 klo 68 218 2. 5e-26 0. 24-0. 14 LAMININ ; CHAIN : NULL ; GLYCOPROTEIN GLYCOPROTEIN 435 Incf 39 180 5e-17 0. 23-0. 07 TUMOR NECROSIS FACTOR SIGNALLING PROTEIN TYPE I RECEPTOR ; NCF 4 CHAIN : A, RECEPTOR, STN FR l ; I NCF 8 B ; INCF 5 BINDING PROTEIN, CYTOKINE INCF 19 435 Incf 180 5e-17 54. 09 TUMOR NECROSIS FACTOR SIGNALLING PROTEIN TYPE I RECEPTOR ; INCF 4 CHAIN : A, RECEPTOR, STNFRI ; INCF 8 B ; INCF 5 BINDING PROTEIN, CYTOKINE INCF 19 435 ncf A 96 218 2. 5e-16 0. 33-0. 14 TUMOR NECROSIS FACTOR SIGNALLING PROTEIN TYPE I Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation I D I D I D AA AA Blast score score score NO : RECEPTOR ; I NCF 4 CHAIN : A, RECEPTOR, STNFR1 ; 1NCF 8 B ; INCF 5 BINDING PROTEIN, CYTOKINE INCF 19 435 Ipfx L 64 214 1. 8e-26 0. 20-0. 18 FACTOR IXA ; CHAIN : C, L, ; D-COMPLEX (BLOOD PHE-PRO-ARG ; CHAIN : I ; COAGULATION/INHIBITOR) CHRISTMAS FACTOR ; COMPLEX, INHIBITOR, HEMOPHILIA/EGF, BLOOD COAGULATION, 2 PLASMA, SERINE PROTEASE, CALCIUM- BINDING, HYDROLASE, 3 GLYCOPROTEIN 435 Ipfx L 72 208 5e-28 62. 61 FACTOR IXA ; CHAIN : C, L, ; D-COMPLEX (BLOOD PHE-PRO-ARG ; CHAIN : I ; COAGULATION/INHIBITOR) CHRISTMAS FACTOR ; COMPLEX, INHIBITOR, HEMOPHILIA/EGF, BLOOD COAGULATION, 2 PLASMA, SERINE PROTEASE, CALCIUM- BINDING, HYDROLASE, 3 GLYCOPROTEIN 435 Ipp2 R 64 184 le-17 0. 13-0. 18 HYDROLASE CALCIUM-FREE PHOSPHOLIPASE A=2= (E. C. 3. 1. 1. 4) IPP24 435 Iqfk L 107 206 75e-17 0. 34-0. 02 COAGULATION FACTOR VIIA SERINE PROTEASE FVIIA ; (LIGHT CHAIN) ; CHAIN : L ; FVIIA ; BLOOD COAGULATION, COAGULATION FACTOR VIIA SERINE PROTEASE (HEAVY CHAIN) ; CHAIN : H ; TRIPEPTIDYL INHIBITOR ; CHAIN : C ; 435 Iqfk 151 232 8. 5e-12 0. 04 0. 83 COAGULATION FACTOR VIIA SERINE PROTEASE FVIIA ; (LIGHT CHAIN) ; CHAIN : L ; FVIIA ; BLOOD COAGULATION, Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : COAGULATION FACTOR VIIA SERINE PROTEASE (HEAVY CHAIN) ; CHAIN : H ; TRIPEPTIDYL INHIBITOR ; CHAIN : C ; 435 1 qub A 11 297 2. 5e-33 60. 56 HUMAN BETA2-MEMBRANE ADHESION SHORT GLYCOPROTEIN I ; CHAIN : A ; CONSENSUS REPEAT, SUSHI, COMPLEMENT CONTROL PROTEIN, 2 N- GLYCOSYLATION, MULTI- DOMAIN, MEMBRANE ADHESION 435 skz 106 216 2. 5e-20 66. 23 ANTISTASIN ; CHAIN : NULL ; SERINE PROTEASE INHIBITOR FACTOR XA INHIBITOR ; ANTISTASIN, CRYSTAL STRUCTURE, FACTOR XA INHIBITOR, 2 SERINE PROTEASE INHIBITOR, THROMBOSIS 435 1 skz 64 216 2. 5e-20 0. 18 0. 21 ANTISTASIN ; CHAIN : NULL ; SERINE PROTEASE INHIBITOR FACTOR XA INHIBITOR ; ANTISTASIN, CRYSTAL STRUCTURE, FACTOR XA INHIBITOR, 2 SERINE PROTEASE INHIBITOR, THROMBOSiS 435 Itpg 37 143 2. 2e-18 0. 38 0. 11 T-PLASMINOGEN PLASMINOGEN ACTIVATION ACTIVATOR F1-G ; ITPG 7 CHAIN : NULL ; ITPG 8 435 tpg 81 184 5e-18 0. 49-0. 08 T-PLASMINOGEN PLASMINOGEN ACTJVATION ACTIVATOR F1-G ; ITPG 7 CHAIN : NULL ; ITPG 8 Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : 435 tvap A 70 184 1. 8e-15-0. 14 0. 00 PHOSPHOLIPASE A2 ; CHAIN : LIPID DEGRADATION A, B ; PHOSPHOLIPASE A2, LIPID DEGRADATION, HYDROLASE 435 lxka L 70 154 5e-15 0. 14 0. 18 BLOOD COAGULATION BLOOD COAGULATION FACTOR XA ; CHAIN : L, C ; FACTOR STUART FACTOR ; BLOOD COAGULATION FACTOR, SERINE PROTEINASE, EPIDERMAL 2 GROWTH FACTOR LIKE DOMAIN 435 2not 34 137 5e-15 0. 11-0. 13 PHOSPHOLIPASE A2 ; CHAIN : HYDROLASE HYDROLASE, A, B ; LIPID DEGRADATION, CALCIUM, PRESYNAPTIC 2 NEUROTOXIN, VENOM 435 9wga A 20 181 1. 7e-16 0. 20 0. 05 LECTIN (AGGLUTININ) WHEAT GERM AGGLUTININ (ISOLECTIN 2) 9WGA 3 435 9wga A 31 180 2. 5e-27 0. 32-0. 17 LECTIN (AGGLUTININ) WHEAT GERM AGGLUTININ (ISOLECTIN 2) 9WGA 3 435 9wga A 53 219 5e-30 79. 05 LECTIN (AGGLUTININ) WHEAT GERM AGGLUTININ (ISOLECTIN 2) 9WGA 3 435 9wga A 55 229 3. 4e-15 0. 39 0. 10 LECTIN (AGGLUTININ) WHEAT GERM AGGLUTININ (ISOLECTIN 2) 9WGA 3 435 9wga A 64 218 5e-30 0. 79-0. 05 LECTIN (AGGLUTININ) WHEAT GERM AGGLUTININ (ISOLECTIN 2) 9WGA 3 443 Ickl A 12 132 8. 5e-11-0. 11 0. 05 CD46 ; CHAIN : A, B, C, D, E, F ; GLYCOPROTEIN MEMBRANE COFACTOR PROTEIN (MCP) ; Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : VIRUS RECEPTOR, COMPLEMENT COFACTOR, SHORT CONSENSUS REPEAT, 2 SCR, MEASLES VIRUS, GLYCOPROTEIN 443 lckl A 67 131 5e-11 0. 36 0. 03 CD46 ; CHAIN : A, B, C, D, E, F ; GLYCOPROTEIN MEMBRANE COFACTOR PROTEIN (MCP) ; VIRUS RECEPTOR, COMPLEMENT COFACTOR, SHORT CONSENSUS REPEAT, 2 SCR, MEASLES VIRUS, GLYCOPROTEIN 443 le5g A 72 192 3. 4e-14 0. 10 0. 24 COMPLEMENT CONTROL COMPLEMENT INHIBITOR VCP, PROTEIN ; CHAIN : A ; SP35 ; COMPLEMENT, NMR, MODULES, PROTEIN STRUCTURE, VACCINIA VIRUS 443 le5g A 73 155 1. 3e-15 0. 11 0. 24 COMPLEMENT CONTROL COMPLEMENT INHIBITOR VCP, PROTEIN ; CHAIN : A ; SP35 ; COMPLEMENT, NMR, MODULES, PROTEIN STRUCTURE, VACCINIA VIRUS 443 Ihcc 73 132 5e-10 0. 35 0. 57 GLYCOPROTEIN 16TH COMPLEMENT CONTROL PROTEIN (/CCP$) OF FACTOR H 1 HCC 3 443 1 hfh 70 192 1. 3e-10 51. 85 GLYCOPROTEIN FACTOR H, 15TH AND 16TH C-MODULE PAIR (NMR, MINIMIZED I HFHA 1 AVERAGED STRUCTURE) 1 HFH 4 I HFHA 5 443 lhfh 71 155 1. 3e-10 0. 36 0. 22 GLYCOPROTEIN FACTOR H, Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : 15TH AND 16TH C-MODULE PAIR (NMR, MINIMIZED 1HFHA 1 AVERAGED STRUCTURE) IHFH4 1HFHA 5 443 Iqub A 21 297 3. 4e-27 56. 46 HUMAN BETA2-MEMBRANE ADHESION SHORT GLYCOPROTEIN 1 ; CHAIN : A ; CONSENSUS REPEAT, SUSHI, COMPLEMENT CONTROL PROTEIN, 2 N- GLYCOSYLATION, MULTI- DOMAIN, MEMBRANE ADHESION 443 Isfp 129 245 2. 3e-27 51. 76 ASFP ; CHAIN : NULL ; SPERMADHESIN ACIDIC SEMINAL PROTEIN ; SPERMADHESIN, BOVINE SEMINAL PLASMA PROTEIN, ACIDIC 2 SEMINAL FLUID PROTEIN, ASFP, CUB DOMAIN, X-RAY CRYSTAL 3 STRUCTURE, GROWTH FACTOR 443 Isfp 135 242 2. 3e-27 0. 38 0. 81 ASFP ; CHAIN : NULL ; SPERMADHESIN ACIDIC SEMINAL PROTEIN ; SPERMADHESIN, BOVINE SEMINAL PLASMA PROTEIN, ACIDIC 2 SEMINAL FLUID PROTEIN, ASFP, CUB DOMAIN, X-RAY CRYSTAL 3 STRUCTURE, GROWTH FACTOR 443 Isfp 155 244 1. 7e-07 0. 01 0. 16 ASFP ; CHAIN : NULL ; SPERMADHESIN ACIDIC SEMINAL PROTEIN ; SPERMADHESIN, BOVINE SEMINAL PLASMA PROTEIN, Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : ACIDIC 2 SEMINAL FLUID PROTEIN, ASFP, CUB DOMAIN, X-RAY CRYSTAL 3 STRUCTURE, GROWTH FACTOR 443 lspp A 135 242 5e-28 0. 38 0. 71 MAJOR SEMINAL PLASMA COMPLEX (SEMINAL PLASMA GLYCOPROTEIN PSP- ! ; PROTEIN/SPP) SEMINAL CHAIN : A ; MAJOR SEMINAL PLASMA PROTEINS, PLASMA GLYCOPROTEIN SPERMADHESINS, CUB PSP-11 ; CHAIN : B DOMAIN 2 ARCHITECTURE, COMPLEX (SEMINAL PLASMA PROTEIN/SPP) 443 1 spp B 129 242 5e-29 0. 36 0. 62 MAJOR SEMINAL PLASMA COMPLEX (SEMINAL PLASMA GLYCOPROTEIN PSP-I ; PROTEIN/SPP) SEMINAL CHAIN : A ; MAJOR SEMINAL PLASMA PROTEINS, PLASMA GLYCOPROTEIN SPERMADHESINS, CUB PSP-11 ; CHAIN : B DOMAIN 2 ARCHITECTURE, COMPLEX (SEMINAL PLASMA PROTEIN/SPP) 443 IVVC 127 3. 4e-15 0. 24-0. 14 VACCINIA VIRUS COMPLEMENT INHIBITOR SP35, COMPLEMENT CONTROL VCP, VACCINIA VIRUS SP35 ; PROTEIN ; CHAIN : NULL ; COMPLEMENT INHIBITOR, COMPLEMENT MODULE, SCR, SUSHI DOMAIN, 2 MODULE PAIR 443 Ivvc 72 194 1. 7e-12 0. 09 0. 25 VACCINIA VIRUS COMPLEMENT INHIBITOR SP35, COMPLEMENT CONTROL VCP, VACCINIA VIRUS SP35 ; PROTEIN ; CHAIN : NULL ; COMPLEMENT INHIBITOR, COMPLEMENT MODULE, SCR, SUSHI DOMAIN, 2 MODULE PAIR 443 Ivvc 72 196 1. 7e-12 50. 78 VACCINIA VIRUS COMPLEMENT INHIBITOR SP35, COMPLEMENT CONTROL VCP, VACCINIA VIRUS SP35 ; Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : PROTEIN ; CHAIN : NULL ; COMPLEMENT INHIBITOR, COMPLEMENT MODULE, SCR, SUSHI DOMAIN, 2 MODULE PAIR 454 ! lba 230 375 5e-39 0. 08 0. 05 HYDROLASE (ACTING ON LINEAR AMIDES) LYSOZYME (E. C. 3. 5. 1. 28) MUTANT WITH ALA 6 REPLACED BY LYS I LBA 3 AND RESIDUES 2-5 DELETED (DEL (2-5), A6K) 1LBA4 454 l lba 258 359 1. 7e-23 0. 03 0. 33 HYDROLASE (ACTING ON LINEAR AMIDES) LYSOZYME (E. C. 3. 5. 1. 28) MUTANT WITH ALA 6 REPLACED BY LYS I LBA 3 AND RESIDUES 2-5 DELETED (DEL (2-5), A6K) I LBA 4 454 1 lba 72 232 2. 5e-23 54. 86 HYDROLASE (ACTING ON LINEAR AMIDES) LYSOZYME (E. C. 3. 5. 1. 28) MUTANT WITH ALA 6 REPLACED BY LYS I LBA 3 AND RESIDUES 2-5 DELETED (DEL (2-5), A6K) I LBA 4 454 llba 74 214 2. 5e-23 0. 26 0. 55 HYDROLASE (ACTING ON LINEAR AMIDES) LYSOZYME (E. C. 3. 5. 1. 28) MUTANT WITH ALA 6 REPLACED BY LYS I LBA 3 AND RESIDUES 2-5 DELETED (DEL (2-5), A6K) Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : 1LBA 4 454 llba 81 175 3. 4e-23 0. 66 0. 88 HYDROLASE (ACTING ON LINEAR AMIDES) LYSOZYME (E. C. 3. 5. 1. 28) MUTANT WITH ALA 6 REPLACED BY LYS ILBA 3 AND RESIDUES 2-5 DELETED (DEL (2-5), A6K) 1 LBA 4 455 lc2a A 35 148 0. 0027-0. 45 0. 03 BOWMAN-BIRK TRYPSIN HYDROLASE INHIBITOR ALL- INHIBITOR ; CHAIN : A BETA STRUCTURE, HYDROLASE INHIBITOR 458 lcl7 M 110 248 1. 2e-07 79. 86 ATP SYNTHASE SUBUNIT C ; MEMBRANE PROTEIN CHAIN : A, B, C, D, E, F, G, H, 1, MEMBRANE PROTEIN, HELIX, J, K, L ; ATP SYNTHASE COMPLEX SUBUNIT A ; CHAIN : M ; 459 Ifqv 28 67 0. 005-0. 85 0. 43 SKP2 ; CHAIN : A, C, E, G, IF K, LIGASE CYCLIN A/CDK2- M, O ; SKPI ; CHAIN : B, D, F, H, ASSOCIATED PROTEIN P45 ; J, L, N, P ; CYCLIN A/CDK2-ASSOCIATED PROTEIN P19 ; SKPI, SKP2, F- BOX, LRR, LEUCINE-RICH REPEAT, SCF, UBIQUITIN, 2 E3, UBIQUITIN PROTEIN LIGASE 474 lb8q A 223 353 1. 2e-13 50. 34 NEURONAL NITRIC OXIDE OXIDOREDUCTASE PDZ SYNTHASE ; CHAIN : A ; DOMAIN, NNOS, NITRIC OXIDE HEPTAPEPTIDE ; CHAIN : B ; SYNTHASE 474 Ib8q A 224 302 1. 2e-13 0. 05 0. 88 NEURONAL NITRIC OXIDE OXIDOREDUCTASE PDZ SYNTHASE ; CHAIN : A ; DOMAIN, NNOS, NITRIC OXIDE Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : _ HEPTAPEPTIDE CHAIN B-SYNTHASE 474 b8q A 313 429 1. 8e-17 0. 38 0. 11 NEURONAL NITRIC OXIDE OXIDOREDUCTASE PDZ SYNTHASE ; CHAIN : A ; DOMAIN, NNOS, NITRIC OXIDE HEPTAPEPTIDE ; CHAIN : B ; SYNTHASE 474 lbe9 A 116 229 1. 7e-14-0. 22 0. 70 PSD-95 ; CHAIN : A ; CRIPT ; PEPTIDE RECOGNITION CHAIN : B ; PEPTIDE RECOGNITION, PROTEIN LOCALIZATION 474 be9 A 221 337 1. 3e-09 51. 39 PSD-95 ; CHAIN : A ; CRIPT ; PEPTIDE RECOGNITION CHAIN : B ; PEPTIDE RECOGNITION, PROTEIN LOCALIZATION 474 be9 A 230 338 1. 3e-09 0. 71 1. 00 PSD-95 ; CHAIN : A ; CRIPT ; PEPTIDE RECOGNITION CHAIN : B ; PEPTIDE RECOGNITION, PROTEIN LOCALIZATION 474 be9 A 315 380 le-10 0. 07 0. 18 PSD-95 ; CHAIN : A ; CRIPT ; PEPTIDE RECOGNITION CHAIN : B ; PEPTIDE RECOGNITION, PROTEIN LOCALIZATION 474 1 be9 A 349 413 le-10-0. 39 0. 28 PSD-95 ; CHAIN : A ; CRIPT ; PEPTIDE RECOGNITION CHAIN : B ; PEPTIDE RECOGNITION, PROTEIN LOCALIZATION 474 lit6 231 330 2e-10-0. 19 0. 01 INTERLEUKIN 16 ; CHAIN : CYTOKINE LCF ; CYTOKINE, NULS ; LYMPHOCYTE CHEMOATTRACTANT FACTOR, PDZ DOMAIN 474 lil6 282 413 2. 5e-16 52. 15 INTERLEUKIN 16 ; CHAIN : CYTOKINE LCF ; CYTOKINE, NULL ; LYMPHOCYTE CHEMOATTRACTANT FACTOR, PDZ DOMAIN 474 lil6 315 388 2. 5e-16 0. 93 1. 00 INTERLEUKIN 16 ; CHAIN : CYTOKINE LCF ; CYTOKINE, NULL ; LYMPHOCYTE CHEMOATTRACTANT FACTOR, PDZ DOMAIN Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : 474 kwa A 234 321 1. 5e-11 0. 44 1. 00 HCASK/LIN-2 PROTEIN ; KINASE HCASK, GLGF REPEAT, CHAIN : A, B ; DHR ; PDZ DOMAIN, NEUREXIN, SYNDECAN, RECEPTOR CLUSTERING, KINASE 474 Ikwa A 313 388 2. 3e-16 0. 21 1. 00 HCASK/LIN-2 PROTEIN ; KINASE HCASK. GLGF REPEAT, CHAIN : A, B ; DHR ; PDZ DOMAIN, NEUREXIN, SYNDECAN, RECEPTOR CLUSTERING, KINASE 474 lpdr 122 218 1. 2e-13-0. 25 0. 27 HUMAN DISCS LARGE SIGNAL TRANSDUCTION HDLG, PROTEIN ; CHAIN : NULL ; DHR3 DOMAIN ; SIGNAL TRANSDUCTION, SH3 DOMAIN, REPEAT 474 Ipdr 228 295 2. 5e-12 0. 23 0. 99 HUMAN DISCS LARGE SIGNAL TRANSDUCTION HDLG, PROTEIN ; CHAIN : NULL ; DHR3 DOMAIN ; SIGNAL TRANSDUCTION, SH3 DOMAIN, REPEAT 474 Ipdr 311 380 2e-12 0. 41 0. 82 HUMAN DISCS LARGE SIGNAL TRANSDUCTION HDLG, PROTEIN ; CHAIN : NULL ; DHR3 DOMAIN ; SIGNAL TRANSDUCTION, SH3 DOMAIN, REPEAT 474 lqau A 117 224 7. 5e-15 0. 12-0. 01 NEURONAL NITRIC OXIDE OXIDOREDUCTASE BETA- SYNTHASE (RESIDUES 1-130) ; FINGER CHAIN : A ; 474 Iqau A 231 346 2. 3e-13 0. 45 0. 83 NEURONAL NITRIC OXIDE OXIDOREDUCTASE BETA- SYNTHASE (RESIDUES 30) ; FINGER CHAIN : A ; 474 lqau A 313 388 5e-16 0. 88 1. 00 NEURONAL NITRIC OXIDE OXIDOREDUCTASE BETA- SYNTHASE (RESIDUES 1-130) ; FINGER CHAIN : A ; 474 I qav 114 212 1. 5e-15 0. 01 I. 00 ALPHA-) SYNTROPHIN MEMBRANE (RESIDUES 77-171) ; CHAIN : A ; PROTEIN/OXIDOREDUCTASE Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID D ID AA AA Blast score score score NO : NEURONAL NITRIC OXIDE BETA-FINGER, HETERODIMER SYNTHASE (RESIDUES 1-130) ; CHAIN : B ; 474 Iqav A 229 309 7. 5e-12 0. 68 1. 00 ALPHA-1 SYNTROPHIN MEMBRANE (RESIDUES 77-171) ; CHAIN : A ; PROTEIN/OXIDOREDUCTASE NEURONAL NITRIC OXIDE BETA-FINGER, HETERODIMER SYNTHASE (RESIDUES 1-130) ; CHAIN : B ; 474 Iqav A 311 388 2e-16 0. 66 1. 00 ALPHA-) SYNTROPHIN MEMBRANE (RESIDUES 77-171) ; CHAIN : A ; PROTEIN/OXIDOREDUCTASE NEURONAL NITRIC OXIDE BETA-FINGER, HETERODIMER SYNTHASE (RESIDUES 1-130) ; CHAIN : B ; 474 lqlc A 116 213 5e-15 0. 81 0. 89 POSTSYNAPTIC DENSITY PEPTIDE RECOGNITION PSD-95 ; PROTEIN 95 ; CHAIN : A ; PDZ DOMAIN, NEURONAL NITRIC OXIDE SYNTHASE, NMDA RECEPTOR 2 BINDING 474 lqlc A 120 213 5. le-15 0. 36 0. 22 _ POSTSYNAPTIC DENSITY PEPTIDE RECOGNITION PSD-95 ; PROTEIN 95 ; CHAIN : A ; PDZ DOMAIN, NEURONAL NITRIC OXIDE SYNTHASE, NMDA RECEPTOR 2 BINDING 474 lqic A 229 309 l. Se-09 0. 68 1. 00 POSTSYNAPTIC DENSITY PEPTIDE RECOGNITION PSD-95 ; PROTEIN 95 ; CHAIN : A ; PDZ DOMAIN, NEURONAL NITRIC OXIDE SYNTHASE, NMDA RECEPTOR 2 BINDING 474 lqlc A 31 1 388 1. 5e-14 0. 75 1. 00 POSTSYNAPTIC DENSITY PEPTIDE RECOGNITION PSD-95 ; PROTEIN 95 ; CHAIN : A ; PDZ DOMAIN, NEURONAL NITRIC OXIDE SYNTHASE, NMDA RECEPTOR 2 BINDING 474 3pdz A 113 212 5e-15 0. 36 0. 96 TYROSINE PHOSPHATASE HYDROLASE PDZ DOMAIN, (PTP-BAS, TYPE l) ; CHAIN : A ; HUMAN PHOSPHATASE, Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : HPTP1E, PTP-BAS, SPECIFICITY 2 OF BINDING 474 3pdz A 227 324 7. 5e-12 0. 47 0. 99 TYROSINE PHOSPHATASE HYDROLASE PDZ DOMAIN, (PTP-BAS, TYPE 1) ; CHAIN : A ; HUMAN PHOSPHATASE, HPTP1E, PTP-BAS, SPECIFICITY 2 OF BINDING 474 3pdz A 311 388 2. 5e-15 1. 23 1. 00 TYROSINE PHOSPHATASE HYDROLASE PDZ DOMAIN, (PTP-BAS, TYPE 1) ; CHAIN : A ; HUMAN PHOSPHATASE, HPTPIE, PTP-BAS, SPECIFICITY 2 OF BINDING 477 1a0 ; A 36 265 0 235 32 TRYPSIN ; CHAIN : A, B, C, D ; SERINE PROTEASE SERINE PROTEINASE, TRYPSIN, HYDROLASE 477 laOj A 36 265 0 1. 07 1. 00 TRYPSIN ; CHAIN : A, B, C, D ; SERINE PROTEASE SERINE PROTEINASE, TRYPSIN, HYDROLASE 477 1a01 36 264 5. le-82 167 61 BETA-TRYPTASE ; CHAIN : A, SERINE PROTEINASE TRYPSIN- B, C, D ; LIKE SERINE PROTEINASE, TETRAMER, HEPARIN, ALLERGY, 2 ASTHMA 477 la5i A 23 263 2. 5e-83 173. 85 PLASMINOGEN ACTIVATOR ; COMPLEX (SERINE CHAIN : A ; GLU-GLY-ARG PROTEASE/INHIBITOR) CHLOROMETHYL KETONE ; (DELTAFEK) DSPAALPHA1 ; CHAIN : I ; EGRCMK ; SERINE PROTEASE, FIBRINOLYTIC ENZYMES, PLASMINOGEN 2 ACTIVATORS 477 lao5 A 36 266 2. 5e-96 226. 34 GLANDULAR KALLIKREIN-SERINE PROTEASE PRORENIN 13 ; CHAIN : A, B ; CONVERTING ENZYME (PRECE), EPIDERMAL GLANDULAR KALLIKREIN, Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : SERINE PROTEASE, PROTEIN MATURATION 477 ao5 A 38 264 2. 5e-96 1. 16 1. 00 GLANDULAR KALLIKREIN-SERINE PROTEASE PRORENIN 13 ; CHAIN : A, B ; CONVERTING ENZYME (PRECE), EPIDERMAL GLANDULAR KALLIKREIN, SERINE PROTEASE, PROTEIN MATURATION 477 laut 36 263 2. 2e-88 172. 05 ACTIVATED PROTEIN C ; COMPLEX (BLOOD CHAIN : C, L ; D-PHE-PRO-MAI ; COAGULATION/INHIBITOR) CHAIN : P ; AUTOPROTHROMBIN IIA ; HYDROLASE, SERINE PROTEINASE), PLASMA CALCIUM BINDING, 2 GLYCOPROTEIN, COMPLEX (BLOOD COAGULATION/INHIBITOR) 477 lbio 36 263 5e-89 198. 56 COMPLEMENT FACTOR D : SERINE PROTEASE SERINE CHAIN : NULL ; PROTEASE, HYDROLASE, COMPLEMENT, FACTOR D, CATALYTIC 2 TRIAD, SELF- REGULATION 477 bqy A 36 271 I e-92 205. 81 PLASMINOGEN ACTIVATOR ; BLOOD CLOTTING TSV-PA ; CHAIN : A, B ; GLU-GLY-ARG-FIBRINOLYSIS, PLASMINOGEN CHLOROMETHYLKETONE ACTIVATOR, SERINE INHIBITOR ; CHAIN : E, F ; PROTEINASE, 2 SNAKE VENOM, COMPLEX (HYDROLASE/INHIBITOR), BLOOD CLOTTING 477 lcgh A 36 264 3. 4e-74 175. 67 CATHEPSIN G ; CHAIN : A ; COMPLEX (SERINE PHOSPHONATE INHIBITOR PROTEASE/INHIBITOR) SUC-VAL-PRO-PHEP- (OPH) 2 ; INFLAMMATION, INHIBITOR, Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : CHAIN : S ; SPECIFICITY, SERINE PROTEASE, 2 COMPLEX (SERINE PROTEASE/INHIBITOR) 477 dpo 36 265 le-97 226. 55 TRYPSIN ; CHAIN : NULL ; SERINE PROTEASE HYDROLASE, SERINE PROTEASE, DIGESTION, PANCREAS, ZYMOGEN, 2 SIGNAL, MULTIGENE FAMILY 477 I fxy A 36 266 1. 7e-91 218. 47 COAGULATION FACTOR XA-COMPLEX TRYPSIN CHIMERA ; CHAIN : (PROTEASE/INHIBITOR) A ; D-PHE-PRO-ARG-TRYPSIN, COAGULATION CHLOROMETHYLKETONE FACTOR XA, CHIMERA, (PPACK) WITH CHAIN : I ; PROTEASE, PPACK, 2 CHLOROMETHYLKETONE, COMPLEX (PROTEASE/INHIBITOR) 477 mct A 36 265 0 234. 27 COMPLEX (PROTEINASE/INHI BITOR) TRYPSIN (E. C. 3. 4. 21. 4) COMPLEXED WITH INHIBITOR FROM BITTER 1 MCT 3 GOURD I MCT 4 477 1 mct A 36 265 0 1. 20 1. 00 COMPLEX (PROTEINASE/INHI BITOR) TRYPSIN (E. C. 3. 4. 21. 4) COMPLEXED WITH INHIBITOR FROM BITTER I MCT 3 GOURD I MCT 4 477 lnpm A 36 263 5e-94 253. 14 NEUROPSIN ; CHAIN : A, B ; SERINE PROTEINASE SERINE PROTEINASE, GLYCOPROTEIN 477 Ipfx C 36 263 Se-91'177. 42 FACTOR IXA ; CHAIN : C, L, ; D-COMPLEX (BLOOD PHE-PRO-ARG ; CHAIN : 1 ; COAGULATION/INHIBITOR) CHRISTMAS FACTOR ; Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : COMPLEX, INHIBITOR, HEMOPHILIA/EGF, BLOOD COAGULATION, 2 PLASMA, SERINE PROTEASE, CALCIUM- BINDING, HYDROLASE, 3 GLYCOPROTEIN 477 1qrZ A 21 265 1. 7e-88 176. 03 PLASMINOGEN ; CHAIN : A, B, HYDROLASE C, D ; MICROPLASMINOGEN, SERINE PROTEASE, ZYMOGEN, CHYMOTRYPSIN 2 FAMILY, HYDROLASE 477 1 rfn A 36 263 1. 3e-90 177. 83 COAGULATION FACTOR IX ; COAGULATION FACTOR CHAIN : A ; COAGULATION SERINE PROTEINASE, BLOOD FACTOR IX ; CHAIN : B ; COAGULATION, COAGULATION FACTOR 477 Irtf B 36 264 lue-84 177. 39 TWO CHAIN TISSUE SERINE PROTEASE (TC)-T-PA ; PLASMINOGEN ACTIVATOR ; SERINE PROTEASE, CHAIN : A, B ; FIBRINOLYTIC ENZYMES 477 Isgf A 45 266 7. 5e-83 179. 65 NERVE GROWTH FACTOR ; GROWTH FACTOR 7S NGF ; CHAIN : A, B, G, X, Y, Z ; GROWTH FACTOR (BETA-NGF), HYDROLASE-SERINE PROTEINASE 2 (GAMMA-NGF), INACTIVE SERINE PROTEINASE (ALPHA-NGF) 477 Isgf G 36 265 8. Se-99 1. 03 1. 00 NERVE GROWTH FACTOR ; GROWTH FACTOR 7S NGF ; CHAIN : A, B, G, X, Y, Z ; GROWTH FACTOR (BETA-NGF), HYDROLASE-SERINE PROTEINASE 2 (GAMMA-NGF), INACTIVE SERINE PROTEINASE (ALPHA-NGF) 477 ISgf G 36 266 8. 5C-99 248. 29 NERVE GROWTH FACTOR ; GROWTH FACTOR 7S NGF ; Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : CHAIN : A, B, G, X, Y, Z ; GROWTH FACTOR (BETA-NGF), HYDROLASE-SERINE PROTEINASE 2 (GAMMA-NGF), INACTIVE SERINE PROTEINASE (ALPHA-NGF) 477 lslw B 36 265 1e-99 223 23 ECOTIN ; CHAIN : A ; ANIONIC COMPLEX (SERINE TRYPSIN ; CHAIN : B ; PROTEASE/INHIBITOR) TRYPSIN INHIBITOR ; SERINE PROTEASE, INHIBITOR, COMPLEX, METAL BINDING SITES, 2 PROTEIN ENGINEERING, PROTEASE- SUBSTRATE INTERACTIONS, 3 METALLOPROTEINS 477 low B 36 265 le-99 1. 25 1. 00 ECOTIN ; CHAIN A ; ANIONIC COMPLEX (SERINE TRYPSIN : CHAIN : B ; PROTEASE/INHIBITOR) TRYPSIN INHIBITOR ; SERINE PROTEASE, INHIBITOR, COMPLEX, METAL BINDING SITES, 2 PROTEIN ENGINEERING, PROTEASE- SUBSTRATE INTERACTIONS, 3 METALLOPROTEINS 477 ton 36 266 5e-97 232. 87 HYDROLASE (SERINE PROTEINASE) TONIN (E. C. NUMBER NOT ASSIGNED) 1 TON 4 477 ion 38 264 5e-97 1. 16 1. 00 HYDROLASE (SERINE PROTEINASE) TONIN (E. C. NUMBER NOT ASSIGNED) 1 TON 4 477 ItRn A 36 266 0 229. 81 HYDROLASE (SERINE Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : PROTEINASE) TRYPSIN (E. C. 3. 4. 21. 4) COMPLEXED WITH THE INHIBITOR ITRN 3 DIISOPROPYL- FLUOROPHOSPHOFLUORIDA TE (DFP) ITRN 4 HUMAN TRYPSIN, DFP INHIBITED INTRA 6 477 trn A 36 266 0 1. 00 1. 00 HYDROLASE (SERINE PROTEINASE) TRYPSIN (E. C. 3. 4. 21. 4) COMPLEXED WITH THE INHIBITOR ITRN 3 DIISOPROPYL- FLUOROPHOSPHOFLUORIDA TE (DFP) ITRN 4 HUMAN TRYPSIN, DFP INHIBITED ITRN 6 477 2tbs 36 265 le-99 222. 15 HYDROLASE (SERINE PROTEINASE) TRYPSIN (E. C. 3. 4. 21. 4) COMPLEXED WITH BENZAMIDINE INHIBITOR 2TBS 3 477 2tbs 36 265 le-99 1. 04 1. 00 HYDROLASE (SERINE PROTEINASE) TRYPSIN (E. C. 3. 4. 21. 4) COMPLEXED WITH BENZAMIDINE INHIBITOR 2TBS 3 477 5ptp 36 265 0 230. 52 BETA TRYPSIN ; CHAIN : SERINE PROTEASE NULL ; HYDROLASE, SERINE PROTEASE, DIGESTION, PANCREAS, 2 ZYMOGEN, SIGNAL Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : 477 5ptp 36 265 0 1. 26 1. 00 BETA TRYPSIN ; CHAIN : SERINE PROTEASE NULL ; HYDROLASE, SERINE PROTEASE, DIGESTION, PANCREAS, 2 ZYMOGEN, SIGNAL 487 lepf A 18 124 5e-07 0. 22 0. 33 NEURAL CELL ADHESION CELL ADHESION NCAM ; NCAM, MOLECULE ; CHAIN : A, B, C, IMMUNOGLOBULIN FOLD, D ; GLYCOPROTEIN 487 f5w A 15 107 le-06 0. 02 0. 36 COXSACKIE VIRUS AND VIRUS/VIRAL PROTEIN ADENOVIRUS RECEPTOR ; RECEPTOR IMMUNOGLOBULIN CHAIN : A, B ; V DOMAIN FOLD, SYMMETRIC DIMER 487 Ifhg A 22 109 2. 5e-07 0. 09 0. 06 TELOKIN ; CHAIN : A CONTRACTILE PROTEIN IMMUNOGLOBULIN FOLD, BETA BARREL 487 Itnm 22 107 2. 5e-06 0. 11 0. 11 MUSCLE PROTEIN TITIN MODULE M5 (CONNECTIN) ITNM 3 (NMR, MINIMIZED AVERAGE STRUCTURE) ITNM4 ITNM58 487 2ncm 20 109 2e-06 0. 12 0. 30 NEURAL CELL ADHESION CELL ADHESION NCAM MOLECULE ; CHAIN : NULL ; DOMAIN 1 ; CELL ADHESION, GLYCOPROTEIN, HEPARIN- BINDING, GPI-ANCHOR, 2 NEURAL ADHESION MOLECULE, IMMUNOGLOBULIN FOLD, SIGNAL 487 3ncm A 22 109 5e-07-0. 09 0. 12 NEURAL CELL ADHESION CELL ADHESION PROTEIN MOLECULE, LARGE NCAM MODULE 2 ; CELL Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : ISOFORM ; CHAIN : A ; ADHESION, GLYCOPROTEIN, HEPARIN-BINDING, GPI- ANCHOR, 2 NEURAL ADHESION MOLECULE, IMMUNOGLOBULIN FOLD, HOMOPHILIC 3 BINDING, CELL ADHESION PROTEIN 492 lsfp 38 78 0. 0015-0. 73 0. 71 ASFP ; CHAIN : NULL ; SPERMADHESIN ACIDIC SEMINAL PROTEIN ; SPERMADHESIN, BOVINE SEMINAL PLASMA PROTEIN, ACIDIC 2 SEMINAL FLUID PROTEIN, ASFP, CUB DOMAIN, X-RAY CRYSTAL 3 STRUCTURE, GROWTH FACTOR 492 spp B 24 78 0. 0015-0. 08 0. 10 MAJOR SEMINAL PLASMA COMPLEX (SEMINAL PLASMA GLYCOPROTEIN PSP-1 ; PROTEIN/SPP) SEMINAL CHAIN : A ; MAJOR SEMINAL PLASMA PROTEINS, PLASMA GLYCOPROTEIN SPERMADHESINS, CUB PSP-I1 ; CHAIN : B DOMAIN 2 ARCHITECTURE, COMPLEX (SEMINAL PLASMA PROTEIN/SPP) 496 Icfe 60 219 5. 1e-42 0. 22 1. 00 PATHOGENESIS-RELATED PATHOGENESIS-RELATED PROTEIN P14A ; CHAIN : PROTEIN PATHOGENESIS- NULL ; RELATED LEAF PROTEIN 6, ETHYLENE PATHOGENESIS- RELATED PROTEIN, PR-I PROTEINS, 2 PLANT DEFENSE 496 cfeJH219 5.) e-4275. 76 PATHOGENESIS-RELATED PATHOGENESIS-RELATED Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : PROTEIN P14A ; CHAIN : PROTEIN PATHOGENESIS- NULL ; RELATED LEAF PROTEIN 6, ETHYLENE PATHOGENESIS- RELATED PROTEIN, PR-1 PROTEINS, 2 PLANT DEFENSE 496 tqnx A 58 220 1. 7e-42 0. 33 1. 00 VES V 5 ; CHAIN : A ; ALLERGEN ANTIGEN 5 ; ANTIGEN 5, ALLERGEN, VESPID VENOM 511 Idef 63 229 3. 4e-46 62. 32 PEPTIDE DEFORMYLASE ; HYDROLASE HYDROLASE, CHAIN : NULL ; ZINC METALLOPROTEASE 512 Ic44 A 92 211 8. 5e-37 0. 82 0. 99 STEROL CARRIER PROTEIN 2 ; LIPID BINDING PROTEIN NON CHAIN : A ; SPECIFIC LIPID BINDING PROTEIN ; STEROL CARRIER PROTEIN, NON SPECIFIC LIPID TRANSFER PROTEIN, 2 FATTY ACID BINDING, FATTY ACYL COA BINDING 513 ledh A 46 166 3. 4e-17-0. 18 0. 25 E-CADHERIN ; CHAIN : A, B ; CELL ADHESION PROTEIN EPITHELIAL CADHERIN DOMAINS I AND 2, ECAD12 ; CADHERIN, CELL ADHESION PROTEIN, CALCIUM BINDING PROTEIN 513 ledh A 51 164 1. 7e-23 0. 24 0. 98 E-CADHERIN ; CHAIN : A, B ; CELL ADHESION PROTEIN EPITHELIAL CADHERIN DOMAINS I AND 2, ECAD12 ; CADHERIN, CELL ADHESION PROTEIN, CALCIUM BINDING Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : PROTEIN 513 Incg 45 138 7. 5e-17 0. 44 0. 93 N-CADHERIN ; INCG 3 CELL ADHESION PROTEIN CADHERIN 1NCG 13 513 1 nci B 45 140 5e-16-0. 22 0. 63 N-CADHERIN ; INCI 3 CELL ADHESION PROTEIN CADHERIN INCI 13 513 ncj A 45 164 Se-20 0. 22 0. 86 N-CADHERIN ; CHAIN : A ; CELL ADHESION PROTEIN CELL ADHESION PROTEIN 513 Inc A 45 165 3. 4e-19-0. 11 0. 36 N-CADHERIN ; CHAIN : A ; CELL ADHESION PROTEIN CELL ADHESION PROTEIN 513 Isuh 44 144 5e-24 55. 29 EPITHELIAL CADHERIN ; CELL ADHESION CHAIN : NULL ; UVOMORULIN ; CADHERIN, CALCIUM BINDING, CELL ADHESION 513 I suh 45 144 3. 4e-09 0. 31 0. 59 EPITHELIAL CADHERIN ; CELL ADHESION CHAIN : NULL ; UVOMORULIN ; CADHERIN, CALCIUM BINDING, CELL ADHESION 513 Isuh 45 144 5e-24 0. 66 0. 98 EPITHELIAL CADHERIN ; CELL ADHESION CHAIN : NULL ; UVOMORULIN ; CADHERIN, CALCIUM BINDING, CELL ADHESION 516 ihcn B 15 126 le-45 94. 05 HORMONE HUMAN CHORIONIC GONADOTROPIN _ HCN 3 516 Ihcn B 16 125 le-45 0. 10 1. 00 HORMONE HUMAN CHORIONIC GONADOTROPIN I HCN 3 516 Ihcn B 17 126 1. 7e-43-0. 14 1. 00 HORMONE HUMAN CHORIONIC GONADOTROPIN I HCN 3 Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation 1 D 1 D ID AA AA Blast score score score NO : 544 lal4 H 20 139 5. 1e-14 61. 90 NEURAMINIDASE ; CHAIN : N ; COMPLEX SINGLE CHAIN ANTIBODY ; (ANTIBODY/ANTIGEN) CHAIN : H, L ; COMPLEX (ANTIBODY/ANTIGEN), SINGLE- CHAIN ANTIBODY, 2 GLYCOSYLATED PROTEIN 544 la2y A 19 134 3. 4e-28 57. 90 MONOCLONAL ANTIBODY COMPLEX D1. 3 ; CHAIN : A, B ; (IMMUNOGLOBULIN/HYDROLA LYSOZYME ; CHAIN : C ; SE) COMPLEX (IMMUNOGLOBULIN/HYDROLA SE), IMMUNOGLOBULIN V 2 REGION, SIGNAL, HYDROLASE, GLYCOSIDASE, BACTERIOLYTIC 3 ENZYME, EGG WHITE 544 la7q L 19 132 3. 4e-26 56. 95 MONOCLONAL ANTIBODY IMMUNOGLOBULIN Dl. 3 ; CHAIN : L, H ; IMMUNOGLOBULIN, VARIANT 544 ladq L 21 141 6. 8e-46 0. 39 0. 95 IGG4 REA ; CHAIN : A ; RF-AN COMPLEX IGM/LAMBDA ; CHAIN : H, L ; (IMMUNOGLOBULIN/AUTOANT IGEN) COMPLEX (IMMUNOGLOBULIN/AUTOANT IGEN), RHEUMATOID FACTOR 2 AUTO-ANTIBODY COMPLEX 544 lao7 20 142 2. 3e-19 59. 00 HLA-A 0201 ; CHAIN : A ; BETA-COMPLEX (MHCNIRAL 2 MICROGLOBULIN ; CHAIN : PEPTIDE/RECEPTOR) HLA-A2 B ; TAX PEPTIDE ; CHAIN : C ; T HEAVY CHAIN ; CLASS I MHC, T- CELL RECEPTOR ALPHA ; CELL RECEPTOR, VIRAL CHAIN : D ; T CELL RECEPTOR PEPTIDE, 2 COMPLEX BETA ; CHAIN : E ; (MHC/VIRAL PEPTIDE/RECEPTOR Table 5 S PUH CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : 544 lap2 19 133 3. 4e-31 57. 34 MONOCLONAL ANTIBODY IMMUNOGLOBULIN VARIABLE C219 ; CHAIN : A, B, C, D ; DOMAIN ; SINGLE CHAIN FV, MONOCLONAL ANTIBODY, C219, P-GLYCOPROTEIN, 2 IMMUNOGLOBULIN 544 laqk L 22 141 3. 4e-50 0. 07 0. 95 FAB B7-15A2 ; CHAIN : L, H ; IMMUNOGLOBULIN HUMAN FAB, ANTI-TETANUS TOXOID, HIGH AFFINITY, CRYSTAL 2 PACKING MOTIF, PROGRAMMING PROPENSITY TO CRYSTALLIZE, 3 IMMUNOGLOBULIN 544 larl D 19 129 1 e-24 57. 17 CYTOCHROME C OXIDASE ; COMPLEX CHAIN : A, B ; ANTIBODY FV (OXIDOREDUCTASE/ANTIBODY FRAGMENT ; CHAIN : C, D ;) CYTOCHROME AA3, COMPLEX IV, FERROCYTOCHROME C, COMPLEX (OXIDOREDUCTASE/ANTIBODY ), ELECTRON TRANSPORT, 2 TRANSMEMBRANE, CYTOCHROME OXIDASE, ANTIBODY COMPLEX 544 1 bOw A 19 127 1. 7e-29 58. 09 BENCE-JONES KAPPA I IMMUNE SYSTEM BENCE- PROTEIN BRE ; CHAIN : A, B, JONES ; IMMUNOGLOBULIN, C ; AMYLOID, IMMUNE SYSTEM 544 Ibfv L 19 135 8. 5e-28 57. 62 FV4155 ; CHAIN : L, H ; IMMUNOGLOBULIN IMMUNOGLOBULIN, FV FRAGMENT, STEROID HORMONE, 2 FINE SPECIFICITY 544 lbjm A 21 142 5. le-45 0. 33 0. 90 LOC-LAMBDA I TYPE IMMUNOGLOBULIN BENCE- LIGHT-CHAIN DIMER ; IBJM 6 JONES PROTEIN ; IBJM 8 BENCE CHAIN : A, B ; IBJM 7 JONES, ANTIBODY, MULTIPLE Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation I D I D I D AA AA Blast score score score NO : QUATERNARY STRUCTURES IBJM 13 544 Ibvk A 135 5. 1e-32 61. 61 HULYS I l ; CHAIN : A, B, D, E ; COMPLEX (HUMANIZED LYSOZYME ; CHAIN : C, F ; ANTIBODY/HYDROLASE) MURAMIDASE ; HUMANIZED ANTIBODY, ANTIBODY COMPLEX, FV, ANTI- LYSOZYME, 2 COMPLEX (HUMANIZED ANTIBODY/HYDROLASE) 544 lbww A 17 132 1. 7e-31 61. 59 IG KAPPA CHAIN V-1 REGION IMMUNE SYSTEM REIV, REI ; CHAIN : A, B ; STABILIZED IMMUNOGLOBULIN FRAGMENT, BENCE-JONES 2 PROTEIN, IMMUNE SYSTEM 544 IcdO A 22 122 1. 2e-46 0. 57 1. 00 JTO, A VARIABLE DOMAIN IMMUNE SYSTEM FROM LAMBDA-6 TYPE IMMUNOGLOBULIN, BENCE- CHAIN : A, B ; JONES PROTEIN, LAMDA-6 544 ldlf L 19 135 3. 4e-27 57. 84 ANTI-DANSYL IMMUNOGLOBULIN ANTI- IMMUNOGLOBULIN DANSYL FV FRAGMENT FV IGG2A (S) ; CHAIN : L, H ; FRAGMENT, IMMUNOGLOBULIN 544 Ifgv L 19 134 1. 7e-33 67. 61 IMMUNOGLOBULIN FV FRAGMENT OF A HUMANIZED VERSION OF THEANTI-CD18 lFGV3 ANTIBODY'H52' (HUH52-AA FV) 1 FGV 4 544 lfvc A 19 136 3. 4e-31 64. 02 IMMUNOGLOBULIN FV FRAGMENT OF HUMANIZED ANTIBODY 4D5, VERSION 8 Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : I FVC 3 544 igm L 19 144 le-30 62. 66 IMMUNOGLOBULIN IMMUNOGLOBULIN M (IG-M) FV FRAGMENT I IGM 3 544 Imaj 19 135 1. 2e-25 56. 76 IMMUNOGLOBULIN MURINE ANTIBODY 26-10 VL DOMAIN (NMR, 15 ENERGY MINIMIZED IMAJ 3 STRUCTURES) I MAJ 4 544 level A 22 145 3. 4e-12 58. 28 VH SINGLE-DOMAIN COMPLEX ANTIBODY ; CHAIN : A, B ; (ANTIBODY/ANTIGEN) CAB- LYSOZYME ; CHAIN : L, M ; LYS3 COMPLEX ; CAMEL SINGLE-DOMAIN ANTI- LYSOZYME, COMPLEX 2 (ANTI BODY/ANTIGEN) 544 Irvf L 20 138 1. 2e-31 62. 39 HUMAN RHINOVIRUS 14 COMPLEX (COAT COAT PROTEIN ; CHAIN : 1, 2, PROTEIN/IMMUNOGLOBULIN) 3, 4 ; FAB 17-IA ; CHAIN : L, H POLYPROTEIN, COAT PROTEIN, CORE PROTEIN, RNA-DIRECTED RNA 2 POLYMERASE, HYDROLASE, THIOL PROTEASE, MYRISTYLATION, 3 COMPLEX (COAT PROTEIN/IMMUNOGLOBULIN) 544 Iwtl A 19 127 1. 5e-31 60. 42 IMMUNOGLOBULIN WAT, A VARIABLE DOMAIN FROM IMMUNOGLOBULIN LIGHT- CHAIN I WTL 3 (BENCE- JONES PROTEIN) I WTL 4 544 2cd0 A 23 122 5. 1e-47 0. 67 1. 00 BENCE-JONES PROTEIN WIL, IMMUNE SYSTEM A VARIABLE DOMAIN FROM IMMUNOGLOBULIN, BENCE- Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : CHAIN : A, B ; JONES PROTEIN, LAMBDA-6 544 2fb4 L 20 142 1. 7e-46 0. 21 0. 86 IMMUNOGLOBULIN IMMUNOGLOBULIN FAB 2FB4 4 544 2imn 19 127 6. 8e-33 60. 82 IMUNOGLOBULIN IMMUNOGLOBULIN VL DOMAIN (VARIABLE DOMAIN OF KAPPA 21MN 3 LIGHT CHAIN) OF MCPC603 MUTANT IN WHICH 21MN 4 COMPLEMENTARITY- DETERMINING REGION I HAS BEEN REPLACED BY 21MN 5 THAT FROM MOPC167 21MN 6 544 2mcg 1 21 142 1. 7e-52 0. 32 0. 72 IMMUNOGLOBULIN IMMUNOGLOBULIN LAMBDA LIGHT CHAIN DIMER (/MCGS) 2MCG 3 (TRIGONAL FORM) 2MCG 4 544 2rhe 20 140 1. 2e-44 68. 90 IMMUNOGLOBULIN BENCE- *JONES PROTEIN (LAMBDA, VARIABLE DOMAIN) 2RHE 4 544 2rhe 21 121 1. 2e-44 0. 59 1. 00 IMMUNOGLOBULIN BENCE- *JONES PROTEIN (LAMBDA, VARIABLE DOMAIN) 2RHE 4 544 43c9 A 19 134 1. 7e-31 57. 86 IMMUNOGLOBULIN (LIGHT IMMUNOGLOBULIN CHAIN) ; CHAIN : A, C, E, G ; IMMUNOGLOBULIN IMMUNOGLOBULIN (HEAVY CHAIN) ; CHAIN : B, D, F, H ; 544 43c9 B 18 140 5. le-15 61. 03 IMMUNOGLOBULIN (LIGHT IMMUNOGLOBULIN CHAIN) ; CHAIN : A, C, E, G ; IMMUNOGLOBULIN Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : IMMUNOGLOBULIN (HEAVY CHAIN) ; CHAIN : B, D, F, H ; 544 7fab L 21 141 1. 4e-43 0. 29 0. 21 IMMUNOGLOBULIN IMMUNOGLOBULIN FAB' NEW (LAMBDA LIGHT CHAIN) 7FAB 3 544 8fab A 23 141 3. 4e-44 0. 31 0. 84 IMMUNOGLOBULIN FAB FRAGMENT FROM HUMAN IMMUNOGLOBULIN IGGI (LAMBDA, HIL) 8FAB 3 548 1 fxx A 224 454 6. 8e-97 0. 07 1. 00 EXONUCLEASE 1 ; CHAIN : A ; HYDROLASE EXODEOXYRIBONUCLEASE ! ; ALPHA-BETA DOMAIN, SH3- LIKE DOMAIN, DNAQ SUPERFAMILY 557 lao7 E 74 194 3. 4e-53 0. 46 1. 00 HLA-A 0201 ; CHAIN : A ; BETA-COMPLEX (MHCNIRAL 2 MICROGLOBULIN ; CHAIN : PEPTIDE/RECEPTOR) HLA-A2 B ; TAX PEPTIDE ; CHAIN : C ; T HEAVY CHAIN ; CLASS I MHC, T- CELL RECEPTOR ALPHA ; CELL RECEPTOR, VIRAL CHAIN : D ; T CELL RECEPTOR PEPTIDE, 2 COMPLEX BETA ; CHAIN : E ; (MHCNIRAL PEPTIDE/RECEPTOR 557 lao7 E 74 217 3. 4e-53 80. 28 HLA-A 0201 ; CHAIN : A ; BETA-COMPLEX (MHCNIRAL 2 MICROGLOBULIN ; CHAIN : PEPTIDE/RECEPTOR) HLA-A2 B ; TAX PEPTIDE ; CHAIN : C ; T HEAVY CHAIN ; CLASS I MHC, T- CELL RECEPTOR ALPHA ; CELL RECEPTOR, VIRAL CHAIN : D ; T CELL RECEPTOR PEPTIDE, 2 COMPLEX BETA ; CHAIN : E ; (MHCNIRAL PEPTIDE/RECEPTOR Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : 557 Ibd2 74 194 le-55 0. 58 1. 00 HLA-A 0201 ; CHAIN : A ; BETA-COMPLEX (MHC/VIRAL 2 MICROGLOBULIN ; CHAIN : PEPTIDE/RECEPTOR) HLA A2 B ; TAX PEPTIDE ; CHAIN : C ; T HEAVY CHAIN ; COMPLEX CELL RECEPTOR ALPHA ; (MHC/VIRAL CHAIN : D ; T CELL RECEPTOR PEPTIDE/RECEPTOR) BETA ; CHAIN : E ; 557 bd2 E 74 217 le-55 62. 05 HLA-A 0201 ; CHAIN : A ; BETA-COMPLEX (MHC/VIRAL 2 MICROGLOBULIN ; CHAIN : PEPTIDE/RECEPTOR) HLA A2 B ; TAX PEPTIDE ; CHAIN : C ; T HEAVY CHAIN ; COMPLEX CELL RECEPTOR ALPHA ; (MHC/VIRAL CHAIN : D ; T CELL RECEPTOR PEPTI DE/RECEPTOR) BETA ; CHAIN : E ; 557 Ibec 74 217 8. 5e-57 72. 58 14. 3. D T CELL ANTIGEN RECEPTOR T CELL RECEPTOR RECEPTOR ; IBEC5CHAIN : IBEC 14 NULL ; BEC 6 557 I bec 75 195 8. 5e-57 0. 51 1. 00 14. 3. D T CELL ANTIGEN RECEPTOR T CELL RECEPTOR RECEPTOR ; IBEC5 CHAIN : IBEC 14 NULL ; IBEC6 557 Ibwm A 74 217 1. 7e-48 61. 36 ALPHA-BETA T CELL IMMUNE SYSTEM RECEPTOR (TCR) (D10) ; IMMUNOGLOBULIN, CHAIN : A ; IMMUNORECEPTOR, IMMUNE SYSTEM 557 Ibwm A 75 185 1. 7e-48 0. 55 1. 00 ALPHA-BETA T CELL IMMUNE SYSTEM RECEPTOR (TCR) (D10) ; IMMUNOGLOBULIN, CHAIN : A ; IMMUNORECEPTOR, IMMUNE SYSTEM 557 d9k B 75 185 1. 7e-48 0. 63 1. 00 T-CELL RECEPTOR DIG IMMUNE SYSTEM MHC I-AK ; (ALPHA CHAIN) ; CHAIN : A, E ; MHC I-AK ; T-CELL RECEPTOR, T-CELL RECEPTOR D10 MHC CLASS 11, D10, I-AK (BETA CHAIN) ; CHAIN : B, F ; MHC I-AK A CHAIN (ALPHA Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : CHAIN) ; CHAIN : C, G ; MHC I- AK B CHAIN (BETA CHAIN) ; CHAIN : D, H ; CONALBUMIN PEPTIDE ; CHAIN : P, Q ; 557 lfyt E 74 194 3. 4e-50 0. 39 1. 00 HLA CLASS 11 IMMUNE SYSTEM HLA-DRI, HISTOCOMPATIBILITY DRA ; HLA-DRI, DRBI 0101 ; TCR ANTIGEN, DR CHAIN : A ; HLA HA1. 7 ALPHA CHAIN ; TCR HA 1. 7 CLASS 11 BETA CHAIN ; PROTEIN- HISTOCOMPATIBILITY PROTEIN COMPLEX, ANTIGEN, DR-1 CHAIN : B ; IMMUNOGLOBULIN FOLD HEMAGGLUTININ HAI PEPTIDE CHAIN ; CHAIN : C ; T- CELL RECEPTOR ALPHA CHAIN ; CHAIN : D ; T-CELL RECEPTOR BETA CHAIN ; CHAIN : E ; 557 Inct 27 93 0. 0015-0. 00 0. 11 TITIN ; CHAIN : NULL ; MUSCLE PROTEIN CONNECTIN, NEXTM5 ; CELL ADHESION, GLYCOPROTEIN, TRANSMEMBRANE, REPEAT, BRAIN, 2 IMMUNOGLOBULIN FOLD, ALTERNATIVE SPLICING, SIGNAL, 3 MUSCLE PROTEIN 557 Itcr 72 195 8. 5e-55 0. 45 1. 00 ALPHA, BETA T-CELL RECEPTOR TCR ; T-CELL, RECEPTOR CHAIN : A, B ; RECEPTOR, TRANSMEMBRANE, GLYCOPROTEIN, SIGNAL 557 Itcr B 72 217 8. 5e-55 74. 81 ALPHA, BETA T-CELL RECEPTOR TCR ; T-CELL, RECEPTOR CHAIN : A, B ; RECEPTOR, TRANSMEMBRANE, GLYCOPROTEIN, SIGNAL 559 levs A 29 212 1. 8e-78 1. 02 1. 00 ONCOSTATIN M ; CHAIN : A ; CYTOKINE 4-HELIX BUNDLE, Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : GP130 BINDING CYTOKINE 559 levs 29 212 5. 1e-76 I. 13 I. 00 ONCOSTATIN M ; CHAIN : A ; CYTOKINE 4-HELIX BUNDLE, GP130 BINDING CYTOKINE 568 I a4y A 52 166 5e-05 0. 05 0. 43 RIBONUCLEASE INHIBITOR ; COMPLEX CHAIN : A, D ; ANGIOGENIN ; (INHIBtTOR/NUCLEASE) CHAIN : B, E ; COMPLEX (INHIBITOR/NUCLEASE), COMPLEX (Rl-ANG), HYDROLASE 2 MOLECULAR RECOGNITION, EPITOPE MAPPING, LEUCINE-RICH 3 REPEATS 592 I ac6 A 27 119 1. 3e-15 56. 47 T-CELL RECEPTOR ALPHA ; RECEPTOR RECEPTOR, V CHAIN : A, B ; ALPHA DOMAIN, SITE- DIRECTED MUTAGENESIS, 2 THREE-DIMENSIONAL STRUCTURE, GLYCOPROTEIN, SIGNAL 592 lao7 D 26 119 7. 5e-21 51. 88 HLA-A 0201 ; CHAIN : A ; BETA-COMPLEX (MHCNIRAL 2 MICROGLOBULIN ; CHAIN : PEPTIDE/RECEPTOR) HLA-A2 B ; TAX PEPTIDE ; CHAIN : C ; T HEAVY CHAIN ; CLASS I MHC, T- CELL RECEPTOR ALPHA ; CELL RECEPTOR, VIRAL CHAIN : D ; T CELL RECEPTOR PEPTIDE, 2 COMPLEX BETA ; CHAIN : E ; (MHC/VIRAL PEPTIDE/RECEPTOR 592 laqk L 28 117 5. le-48 0. 35 0. 89 FAB B7-15A2 ; CHAIN : L, H ; IMMUNOGLOBULIN HUMAN FAB, ANTI-TETANUS TOXOID, HIGH AFFINITY, CRYSTAL 2 PACKING MOTIF, Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : PROGRAMMING PROPENSITY TO CRYSTALLIZE, 3 IMMUNOGLOBULIN 592 1 b6d A 25 114 1. 2e-44 0. 16 0. 60 IMMUNOGLOBULIN ; CHAIN : IMMUNOGLOBULIN A, B ; IMMUNOGLOBULIN, KAPPA LIGHT-CHAIN DIMER HEADER 592 lbjl L 25 114 5. 1 e-46 0. 37 0. 63 FAB FRAGMENT ; CHAIN : L, COMPLEX H, J, K ; VASCULAR (ANTIBODY/ANTIGEN) FAB-12 ; ENDOTHELIAL GROWTH VEGF ; COMPLEX FACTOR ; CHAIN : V, W ; (ANTIBODY/ANTIGEN), ANGIOGENIC FACTOR 592 Ibjm 27 116 5. 1e-45 0. 13 0. 83 LOC-LAMBDA I TYPE IMMUNOGLOBULIN BENCE- LIGHT-CHAIN DIMER ; IBJM 6 JONES PROTEIN ; IBJM 8 BENCE CHAIN : A, B ; 1 BJM 7 JONES, ANTIBODY, MULTIPLE QUATERNARY STRUCTURES IBJM 13 592 Ibww 23 114 1. 7e-45 0. 27 0. 31 IG KAPPA CHAIN V-l REGION IMMUNE SYSTEM REIV, REI ; CHAIN : A, B ; STABILIZED IMMUNOGLOBULIN FRAGMENT, BENCE-JONES 2 PROTEIN, IMMUNE SYSTEM 592 Idee 25 114 3. 4e-47 0. 25 0. 48 IGM RF 2A2 ; CHAIN : A, C, E ; IMMUNE SYSTEM FAB-IBP IGM RF 2A2 ; CHAIN : B, D, F ; COMPLEX CRYSTAL IMMUNOGLOBULIN G STRUCTURE 2. 7A RESOLUTION BINDING PROTEIN A ; CHAIN : BINDING 2 OUTSIDE THE G, H ; ANTIGEN COMBINING SITE SUPERANTIGEN FAB VH3 3 SPECIFICITY 592 ldfb L 25 119 8. 5e-47 0. 50 0. 64 IMMUNOGLOBULIN 3D6 FAB I DFB 3 592 Ifgv L 25 114 1. 4e-45 0. 21 0. 53 IMMUNOGLOBULIN FV Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID. ID AA AA Blast score score score NO : FRAGMENT OF A HUMANIZED VERSION OF THE ANTI-CD18 IFGV 3 ANTIBODY'H52' (HUH52-AA FV) 1 FGV 4 592 2fb4 L 26 117 1. 2e-44 0. 35 0. 82 IMMUNOGLOBULIN IMMUNOGLOBULIN FAB 2FB4 4 592 2fgw L 25 114 1. 7e-45 0. 32 0. 77 IMMUNOGLOBULIN FAB FRAGMENT OF A HUMANIZED VERSION OF THE ANTI-CD18 2FGW 3 ANTIBODY'H52' (HUH52-OZ FAB) 2FGW 4 603 Icru A 169 400 1. 5e-46 0. 13 0. 28 SOLUBLE QUINOPROTEIN OXIDOREDUCTASE BETA- GLUCOSE PROPELLER, SUPERBARREL, DEHYDROGENASE ; CHAIN : COMPLEX WITH THE A, B ; COFACTOR PQQ 2 AND THE INHIBITOR METHYLHYDRAZINE, OXIDOREDUCTASE 603 cru A 186 404 7. 5e-49 0. 01 0. 27 SOLUBLE QUINOPROTEIN OXIDOREDUCTASE BETA- GLUCOSE PROPELLER, SUPERBARREL, DEHYDROGENASE ; CHAIN : COMPLEX WITH THE A, B ; COFACTOR PQQ 2 AND THE INHIBITOR METHYLHYDRAZI NE, OXIDOREDUCTASE 615 Ic0t A 174 431 1. 7e-65-0. 24 0. 25 HIV-I REVERSE TRANSFERASE HIV-I REVERSE Table 5 SL FUH CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : TRANSCRIPTASE (A-CHAIN) ; TRANSCRIPTASE, AIDS, NON- CHAIN : A ; HIV-I REVERSE NUCLEOSID INHIBITOR, 2 TRANSCRIPTASE (B-CHAIN) ; DRUG DESIGN CHAIN : B ; 615 It 176 431 le-62-0. 31 0. 23 HIV-1 REVERSE TRANSFERASE HIV-1 REVERSE TRANSCRIPTASE (A-CHAIN) ; TRANSCRIPTASE, AIDS, NON- CHAIN : A ; HIV-1 REVERSE NUCLEOSIDE INHIBITOR, 2 TRANSCRIPTASE (B-CHAIN) ; DRUG DESIGN CHAIN : B ; 615 lclc B 175 431 le-74-0. 12 0. 39 HIV-1 REVERSE TRANSFERASE HIV-1 REVERSE TRANSCRIPTASE (A-CHAIN) ; TRANSCRIPTASE, AIDS, NON- CHAIN : A ; HIV-I REVERSE NUCLEOSID INHIBITOR, 2 TRANSCRIPTASE (B-CHAIN) ; DRUG DESIGN CHAIN : B ; 615 Ic9r A 171 431 le-70-0. 08 0. 94 HIV-1 REVERSE TRANSFERASE/IMMUNE TRANSCRIPTASE (CHAIN A) ; SYSTEM/DNA HIV-1 RT ; HIV-1 CHAIN : A ; HIV-1 REVERSE RT ; HIV, REVERSE TRANSCRIPTASE (CHAIN B) ; TRANSCRIPTASE, MET184ILE, CHAIN : B ; ANTIBODY (LIGHT 3TC, PROTEIN-DNA 2 COMPLEX, CHAIN) ; CHAIN : L ; DRUG RESISTANCE, M1841, ANTIBODY (HEAVY CHAIN) ; TRANSFERASE/IMMUNE 3 CHAIN : H ; DNA (5'-CHAIN : T ; SYSTEM/DNA DNA (5'-CHAIN : P ; 615 Ic9r B 171 431 1. 7e-79-0. 14 0. 59 HIV-1 REVERSE TRANSFERASE/IMMUNE TRANSCRIPTASE (CHAIN A) ; SYSTEM/DNA HIV-1 RT ; HIV-1 CHAIN : A ; HIV-1 REVERSE RT ; HIV, REVERSE TRANSCRIPTASE (CHAIN B) ; TRANSCRIPTASE, MET1841LE, CHAIN : B ; ANTIBODY (LIGHT 3TC, PROTEIN-DNA 2 COMPLEX, CHAIN) ; CHAIN : L ; DRUG RESISTANCE, M1841, ANTIBODY (HEAVY CHAIN) ; TRANSFERASE/IMMUNE 3 CHAIN : H ; DNA (5'-CHAIN : T ; SYSTEM/DNA DNA (5'-CHAIN : P ; Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : 615 lmml 154 396 5. le-50 116. 10 MMLV REVERSE REVERSE TRANSCRIPTASE TRANSCRIPTASE ; I MML 4 CHAIN : NULL ; I MML 5 615 1 ah A 171 431 3. 4e-86-0. 12 0. 74 HIV-1 REVERSE NUCLEOTIDYLTRANSFERASE TRANSCRIPTASE ; RTH 4 HIV-I RT ; IRTH6HIV-I CHAIN : A, B ; I RTH 5 REVERSE TRANSCRIPTASE IRTH 15 615 lrth B 173 431 le-75-0. 09 0. 23 HIV-1 REVERSE NUCLEOTIDYLTRANSFERASE TRANSCRIPTASE ; IRTH4 HIV-I RT ; I RTH 6 HIV-I CHAIN : A, B ; I RTH 5 REVERSE TRANSCRIPTASE 1RTH 15 615 Ivrt 174 431 1. 7e-85-0. 26 0. 40 HIV-I REVERSE NUCLEOTIDYLTRANSFERASE TRANSCRIPTASE ; IVRT4 HIV-I RT ; I VRT 6 HIV-I CHAIN : A, B ; I VRT 5 REVERSE TRANSCRIPTASE IVRT 15 615 1 vrt B 175 431 1. 7e-75-0. 20 0. 11 HIV-1 REVERSE NUCLEOTIDYLTRANSFERASE TRANSCRIPTASE ; I VRT 4 HIV-I RT ; I VRT 6 HIV-I CHAIN : A, B ; IVRT5 REVERSETRANSCRIPTASE ] VRT 15 615 3hvt B 172 431 3. 4e-74-0. 14 0. 00 NUCLEOTIDYLTRANSFERAS E REVERSE TRANSCRIPTASE (E. C. 2. 7. 7. 49) 3HVT 3 620 laut L 47 75 0. 00068-0. 18 0. 42 ACTIVATED PROTEIN C ; COMPLEX (BLOOD CHAIN : C, L ; D-PHE-PRO-MAI ; COAGULATION/INHIBITOR) CHAIN : P ; AUTOPROTHROMBIN IIA ; HYDROLASE, SERINE PROTEINASE), PLASMA CALCIUM BINDING, 2 GLYCOPROTEIN, COMPLEX (BLOOD Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : COAGULATION/INHIBITOR) 620 Idiy A 46 77 0. 00068 0. 69 0. 25 PROSTAGLANDIN H2 OXIDOREDUCTASE SYNTHASE-1 ; CHAIN : A ; ARACHIDONIC ACID, MEMBRANE PROTEIN, PEROXIDASE, DIOXYGENASE 620 fsb 46 75 0. 0034 1. 08 0. 34 P-SELECTIN ; CHAIN : NULL ; CELL ADHESION PROTEIN EGF- LIKE DOMAIN, CELL ADHESION PROTEIN, TRANSMEMBRANE, 2 GLYCOPROTEIN 627 lmgl A 260 376 3. 4e-28-0. 94 0. 06 HTLV-1 GP21 LEUKEMIA VIRUS TYPE I ECTODOMAIN/MALTOSE-HUMAN T CELL LEUKEMIA BINDING PROTEIN CHAIN : A ; VIRUS TYPE 1, HTLV-l, ENVELOPE 2 PROTEIN, MEMBRANE FUSION, MALTOSE-BINDING PROTEIN CHIMERA 627 2ebo A 304 376 5. 1e-22-0. 56 0. 21 EBOLA VIRUS ENVELOPE ENVELOPE GLYCOPROTEIN GLYCOPROTEIN ; CHAIN : A, ENVELOPE GLYCOPROTEIN, B, C ; FILOVIRUS, EBOLA VIRUS, GP2, COAT 2 PROTEIN 658 la9n A 27 164 2. 5e-18 0. 22 0. 69 U2 RNA HAIRPIN IV ; CHAIN : COMPLEX (NUCLEAR Q, R ; U2 A' ; CHAIN : A, C ; U2 PROTEIN/RNA) COMPLEX B"-, CHAIN : B, D ; (NUCLEAR PROTEIN/RNA), RNA, SNRNP, RIBONUCLEOPROTEIN 658 la9n 54 188 Se-24 0. 30 0. 48 U2 RNA HAIRPIN IV ; CHAIN : COMPLEX (NUCLEAR Q, R ; U2 A'; CHAIN : A, C ; U2 PROTEIN/RNA) COMPLEX B" ; CHAIN : B, D ; (NUCLEAR PROTEIN/RNA), RNA, SNRNP, RIBONUCLEOPROTEIN 658 la9n C 27 164 7. 5e-18 0. 38 0. 96 U2 RNA HAIRPIN IV ; CHAIN : COMPLEX (NUCLEAR Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : Q, R ; U2 A' ; CHAIN : A, C ; U2 PROTEIN/RNA) COMPLEX B" ; CHAIN : B, D ; (NUCLEAR PROTEIN/RNA), RNA, SNRNP, RIBONUCLEOPROTEIN 658 la9n 54 188 1. 5e-23 0. 46 0. 53 U2 RNA HAIRPIN IV ; CHAIN : COMPLEX (NUCLEAR Q, R ; U2 A' ; CHAIN : A, C ; U2 PROTEIN/RNA) COMPLEX B" ; CHAIN : B, D ; (NUCLEAR PROTEIN/RNA), RNA, SNRNP, RIBONUCLEOPROTEIN 658 IdOb A 70 237 1 7e-21-0. 00 0. 41 INTERNALIN B ; CHAIN : A ; CELL ADHESION LEUCINE RICH REPEAT, CALCIUM BINDING, CELL ADHESION 658 Idee A 98 218 1. 2e-09-0. 43 0. 30 RAB TRANSFERASE CRYSTAL GERANYLGERANYLTRANSF STRUCTURE, RAB ERASE ALPHA SUBUNIT ; GERANYLGERANYLTRANSFER CHAIN : A, C ; RAB ASE, 2. 0 A 2 RESOLUTION, N- GERANYLGERANYLTRANSF FORMYLMETHIONINE, ALPHA ERASE BETA SUBUNIT ; SUBUNIT, BETA SUBUNIT CHAIN : B, D ; 658 ! ds9 A 55 178 2. 5e-17-0. 29 0. 06 OUTER ARM DYNEIN ; CONTRACTILE PROTEIN CHAIN : A ; LEUCINE-RICH REPEAT, BETA- BETA-ALPHA CYLINDER, DYNEIN, 2 CHLAMYDOMONAS, FLAGELLA 658 2bnh 34 183 I e-21 0. 28-0. 03 RIBONUCLEASE INHIBITOR ; ACETYLATION RNASE CHAIN : NULL ; INHIBITOR, Rl BONUCLEASE/ANGIOGENIN INHIBITOR ACETYLATION, LEUCINE-RICH REPEATS 665 la0h A 30 150 2. 5e-29 0. 37 0. 65 MEIZOTHROMBIN ; CHAIN : A, COMPLEX (SERINE B, D, E ; D-PHE-PRO-ARG ; PROTEASE/INHIBITOR) DESFI ; CHAIN : C, F ; PPACK ; SERINE PROTEASE, Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : COAGULATION, THROMBIN, PROTHROMBIN, 2 MEIZOTHROMBIN, COMPLEX (SERINE PROTEASE/INHIBITOR) 665 la0h A 30 169 6. 8e-10 0. 28 0. 76 MEIZOTHROMBIN ; CHAIN : A, COMPLEX (SERINE B, D, E ; D-PHE-PRO-ARG ; PROTEASE/INHIBITOR) DESFI ; CHAIN : C, F ; PPACK ; SERINE PROTEASE, COAGULATION, THROMBIN, PROTHROMBIN, 2 MEIZOTHROMBIN, COMPLEX (SERINE PROTEASE/INHIBITOR) 665 la0h 30 201 2. 5e-29 82. 71 MEIZOTHROMBIN ; CHAIN : A, COMPLEX (SERINE B, D, E ; D-PHE-PRO-ARG ; PROTEASE/INHIBITOR) DESFI ; CHAIN : C, F ; PPACK ; SERINE PROTEASE, COAGULATION, THROMBIN, PROTHROMBIN, 2 MEIZOTHROMBIN, COMPLEX (SERINE PROTEASE/INHIBITOR) 665 Ib2 ; A 32 120 7. 5e-26 72. 58 PLASMINOGEN ; CHAIN : A ; HYDROLASE SERINE PROTEASE, FIBRINOLYSIS, LYSINE-BINDING DOMAIN, 2 PLASMINOGEN, KRINGLE 2, HYDROLASE 665 lb2i A 34 119 7. 5e-26 0. 90 0. 81 PLASMINOGEN ; CHAIN A ; HYDROLASE SERINE PROTEASE, FIBRINOLYSIS, LYSINE-BINDING DOMAIN, 2 PLASMINOGEN, KRINGLE 2, HYDROLASE 665 cea A 35 119 1 e-24 68. 58 PLASMINOGEN ; ICEA 7 SERINE PROTEASE KIPG ; ICEA CHAIN : A, B ; ICEA 8 10 665 I kdU 35 120 2. 5e-28 71. 09 PLASMINOGEN ACTIVATION Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : PLASMINOGEN ACTIVATOR (UROKINASE-TYPE, KRINGLE DOMAIN) 1 KDU 3 (U-PA K) (NMR, MINIMIZED AVERAGE STRUCTURE) I KDU 4 665 lkdu 36 119 2. 5e-28 0. 91 0. 96 PLASMINOGEN ACTIVATION PLASMINOGEN ACTIVATOR (UROKINASE-TYPE, KRINGLE DOMAIN) 1 KDU 3 (U-PA K) (NMR, MINIMIZED AVERAGE STRUCTURE) 1 KDU 4 665 Ikrn 35 Se-22 76. 76 PLASMINOGEN ; CHAIN : SERINE PROTEASE KRINGLE, NULL ; BLOOD, PLASMINOGEN, SERINE PROTEASE 665 html A 34 119 1. 3e-28 0. 89 1. 00 HYDROLASE (SERINE PROTEASE) TISSUE PLASMINOGEN ACTIVATOR KRINGLE 2 (E. C. 3. 4. 21. 68) IPML3 665 lpml A 34 121 1. 3e-28 86. 47 HYDROLASE (SERINE PROTEASE) TISSUE PLASMINOGEN ACTIVATOR KRINGLE 2 (E. C. 3. 4. 21. 68) IPML3 665 Ipml C 34 119 1 e-28 0. 94 0. 96 HYDROLASE (SERINE PROTEASE) TISSUE PLASMINOGEN ACTIVATOR KRINGLE 2 (E. C. 3. 4. 21. 68) 1 PML 3 665 lpml C 34 120 le-28 86. 67 HYDROLASE (SERINE PROTEASE) TISSUE Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : PLASMINOGEN ACTIVATOR KRINGLE 2 (E. C. 3. 4. 21. 68) IPML3 665 15fP 218 329 2. Se-17 1. 13 0. 99 ASFP ; CHAIN : NULL ; SPERMADHESIN ACIDIC SEMINAL PROTEIN ; SPERMADHESIN, BOVINE SEMINAL PLASMA PROTEIN, ACIDIC 2 SEMINAL FLUID PROTEIN, ASFP, CUB DOMAIN, X-RAY CRYSTAL 3 STRUCTURE, GROWTH FACTOR 665 Isfp 238 327 3. 4e-07 0. 62 0. 09 ASFP ; CHAIN : NULL ; SPERMADHESIN ACIDIC SEMINAL PROTEIN ; SPERMADHESIN, BOVINE SEMINAL PLASMA PROTEIN, ACIDIC 2 SEMINAL FLUID PROTEIN, ASFP, CUB DOMAIN, X-RAY CRYSTAL 3 STRUCTURE, GROWTH FACTOR 665 ISPP 218 323 2. 5e-16 0. 67 0. 11 MAJOR SEMINAL PLASMA COMPLEX (SEMINAL PLASMA GLYCOPROTEIN PSP-1 ; PROTEIN/SPP) SEMINAL CHAIN : A ; MAJOR SEMINAL PLASMA PROTEINS, PLASMA GLYCOPROTEIN SPERMADHESINS, CUB PSP-II ; CHAIN : B DOMAIN 2 ARCHITECTURE, COMPLEX (SEMINAL PLASMA PROTEIN/SPP) 665 lapp B 218 323 2. 5e-15 0. 62-0. 07 MAJOR SEMINAL PLASMA COMPLEX (SEMINAL PLASMA GLYCOPROTEIN PSP-1 ; PROTEIN/SPP) SEMINAL CHAIN : A ; MAJOR SEMINAL PLASMA PROTEINS, PLASMA GLYCOPROTEIN SPERMADHESINS, CUB PSP-II ; CHAIN : B DOMAIN 2 ARCHITECTURE, COMPLEX (SEMINAL PLASMA Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : PROTEIN/SPP) 665 spp B 245 328 6. 8e-06 0. 38 0. 09 MAJOR SEMINAL PLASMA COMPLEX (SEMINAL PLASMA GLYCOPROTEIN PSP-I ; PROTEIN/SPP) SEMINAL CHAIN : A ; MAJOR SEMINAL PLASMA PROTEINS, PLASMA GLYCOPROTEIN SPERMADHESINS, CUB PSP-II ; CHAIN : B DOMAIN 2 ARCHITECTURE, COMPLEX (SEMINAL PLASMA PROTEIN/SPP) 665 I urk l 123 2. 2e-23 69. 71 PLASMINOGEN ACTIVATION PLASMINOGEN ACTIVATOR (UROKINASE-TYPE) (AMINO TERMINAL FRAGMENT) (NMR, 15 STRUCTURES) 665 2hpp P 36 l l9 Se-25 66. 47 HYDROLASE (SERINE PROTEINASE) ALPHA- THROMBIN (E. C. 3. 4. 21. 5) COMPLEX WITH 2HPP 3 D- PHE-PRO-ARG- CHLOROMETHYLKETONE (PPACK) CHLOROMETHYLKETONE 2HPP 4 REPLACED BY A METHYLENE GROUP AND BOVINE PROTHROMBIN 2HPP 5 FRAGMENT 2 2HPP 6 665 2hpp P 36 119 5e-25 0. 71 0. 39 HYDROLASE (SERINE PROTEINASE) ALPHA- THROMBIN (E. C. 3. 4. 21. 5) COMPLEX WITH 2HPP 3 D- PHE-PRO-ARG- CHLOROMETHYLKETONE (PPACK) Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : CHLOROMETHYLKETONE 2HPP 4 REPLACED BY A METHYLENE GROUP AND BOVINE PROTHROMBIN 2HPP 5 FRAGMENT 2 2HPP 6 665 2hpq P 36 119 1. 2e-24 60. 25 HYDROLASE (SERINE PROTEINASE) ALPHA- THROMBIN (E. C. 3. 4. 21. 5) COMPLEX WITH 2HPQ 3 D- PHE-PRO-ARG- CHLOROMETHYLKETONE (PPACK) CHLOROMETHYLKETONE 2HPQ 4 REPLACED BY A METHYLENE GROUP AND HUMAN PROTHROMBIN 2HPQ 5 FRAGMENT 2 2HPQ 6 665 2pfl 20 119 2. 3e-25 0. 85 0. 71 HYDROLASE (SERINE PROTEINASE) PROTHROMBIN FRAGMENT I (RESIDUES I-156) 2PF I 3 665 2pfl 5 131 2. 3e-25 58. 78 HYDROLASE (SERINE PROTEINASE) PROTHROMBIN FRAGMENT) (RESIDUES I-156) 2PF I 3 665 2pf2 35 119 2. 5e-25 0. 82 0. 77 HYDROLASE (SERINE PROTEASE) PROTHROMBIN FRAGMENT I (RESIDUES I- 156) COMPLEX WITH 2PF2 3 CALCIUM 2PF2 4 665 3kiv 35 l l9 5e-27 76. 56 APOLIPOPROTEIN ; CHAIN : KRINGLE KRINGLE, LYSINE NULL ; BINDING SITE, Table 5 SEQ PDB CHAIN START END Psi Verify PMF SEQFOLD Compound PDB annotation ID ID ID AA AA Blast score score score NO : APOLIPOPROTEIN (A) 665 3kiv 35 119 5e-27 0. 76 0. 87 APOLIPOPROTEIN ; CHAIN : KRINGLE KRINGLE, LYSINE NULL ; BINDING SITE, APOLIPOPROTEIN (A) 665 5hpg A 35 122 le-26 77. 19 PLASMINOGEN ; CHAIN : A, B ; SERINE PROTEASE SERINE PROTEASE, KRINGLE 5, HUMAN PLASMINOGEN, FIBRINOLYSIS 665 5hpg A 35 122 le-26 0. 65 0. 70 PLASMINOGEN ; CHAIN : A, B ; SERINE PROTEASE SERINE PROTEASE, KRINGLE 5, HUMAN PLASMINOGEN, FIBRINOLYSIS 665 9wga A 21 168 1. 7e-13 0. 15-0. 12 LECTIN (AGGLUTININ) WHEAT GERM AGGLUTININ (ISOLECTIN 2) 9WGA 3 665 9wga A 51 234 3. 4e-10 0. 16-0. 19 LECTIN (AGGLUTININ) WHEAT GERM AGGLUTININ (ISOLECTIN 2) 9WGA 3 Table 6 SEQ ID NO : Position of Signal Peptide Maximum score Average score 337 29 0. 968 0. 793 338 32 0. 989 0. 841 339 37 0. 972 0. 775 341 42 0. 943 0. 626 342 34 0. 993 0. 933 344 33 0. 968 0. 827 345 28 0. 995 0. 945 346 26 0. 994 0. 932 347 41 0. 959 0. 629 348 39 0 986 0. 641 349 28 0. 988 0. 935 350 24 0 981 0. 776 351 25 0. 898 0. 612 352 14 0. 943 0. 864 353 24 0. 976 0. 925 355 21 0. 896 0. 706 357 39 0. 983 0. 710 358 26 0. 971 0. 899 359 27 0. 970 0. 898 360 27 0. 970 0. 898 362 29 0. 964 0. 562 363 33 0. 937 0. 698 364 24 0. 988 0. 952 365 18 0. 995 0. 978 366 13 0. 972 0. 733 367 25 0. 992 0. 929 368 20 0. 987 0. 963 369 41 0. 972 0. 714 370 40 0. 993 0. 805 372 40 0. 993 0. 805 373 42 0. 890 0. 551 375 21 0. 942 0. 816 376 25 0. 954 0 816 378 41 0. 983 0. 859 379 25 0. 980 0. 906 380 15 0. 953 0 860 381 22 0. 943 0. 746 382 31 0. 995 0. 895 383 17 0. 959 0. 867 385 18 0. 981 0. 858 387 22 0. 993 0. 966 388 49 0. 987 0. 594 390 25 0. 990 0. 857 391 26 0. 985 0. 956 392 19 0. 993 0. 953 393 48 0. 985 0. 571 394 17 0. 976 0. 772 395 15 0. 932 0. 796 396 40 0. 996 0. 972 398 25 0. 941 0. 656 399 16 0. 984 0. 949 401 34 0. 971 0. 910 402 42 0. 983 0. 683 403 17 0. 961 0. 884 405 17 0. 961 0. 884 Table 6 SEQ ID NO : Position of Signal Peptide Maximum score Average score 406 26 0. 996 0. 922 407 20 0. 947 0. 881 408 48 0. 940 0. 755 409 30 0. 968 0. 777 410 32 0. 953 0. 778 411 20 0. 963 0. 551 412 25 0. 958 0. 928 414 33 0. 988 0. 893 415 24 0. 933 0. 671 416 44 0. 956 0. 803 417 47 0. 967 0. 826 418 48 0. 992 0. 807 419 25 0. 976 0. 909 421 29 0. 973 0. 792 422 29 0. 922 0. 662 423 32 0. 967 0. 646 424 21 0. 933 0. 785 425 0. 894 0. 613 426 46 0. 981 0. 714 427 44 0. 955 0. 611 428 17 0. 950 0. 712 429 14 0. 989 0 917 430 27 0. 998 0. 952 431 35 0. 969 0. 716 432 17 0. 943 0. 681 433 21 0. 956 0. 879 434 25 0. 985 0. 718 435 17 0. 943 0. 794 436 29 0. 998 0. 924 437 29 0. 998 0. 924 438 21 0. 986 0. 966 442 25 0. 988 0. 947 443 18 0. 900 0. 591 444 23 0. 975 0. 884 445 18 0. 898 0. 719 446 43 0. 907 0. 701 447 29 0. 941 0. 708 448 20 0. 989 0. 960 449 20 0. 989 0. 960 450 40 0. 998 0. 990 451 35 0. 984 0. 757 452 42 0. 977 0. 671 453 0. 978 0 902 454 17 0. 976 0. 927 455 34 0. 957 0. 706 456 18 0. 978 0. 937 459 18 0. 902 0. 649 460 36 0. 978 0. 657 461 19 0. 973 0. 788 462 20 0. 964 0. 774 463 24 0. 978 0. 709 464 21 0. 968 0. 782 465 45 0. 998 0. 924 466 22 0. 989 0. 960 467 49 0. 986 0. 825 Table 6 SEQ ID NO : Position of Signal Peptide Maximum score Average score 468 38 0. 959 0. 769 469 28 0. 988 0. 744 470 24 0. 909 0. 643 471 20 0. 972 0. 830 472 48 0. 957 0. 617 473 20 0. 980 0. 902 474 17 0. 905 0. 697 475 47 0. 995 0. 684 477 20 0. 983 0. 888 478 31 0. 977 0. 806 481 38 0. 930 0. 725 482 20 0. 972 0. 888 483 10 0. 993 0. 569 484 34 0. 994 0. 867 485 23 0. 904 0. 643 486 22 0. 974 0. 877 487 17 0. 959 0. 814 488 48 0. 946 0. 768 490 19 0. 957 0. 838 491 38 0. 988 0. 950 492 24 0. 967 0. 918 494 31 0. 945 0. 695 495 46 0. 992 0. 562 496 23 0. 958 0. 866 497 25 0. 973 0. 888 498 41 0. 981 0. 577 499 43 0. 970 0. 727 500 32 0. 913 0. 607 501 27 0. 962 0. 882 502 22 0. 989 0. 887 503 22 0. 981 0. 881 504 28 0. 972 0. 825 505 31 0. 990 0. 766 506 30 0. 995 0. 964 507 24 0. 955 0. 640 508 37 0. 977 0. 860 509 38 0. 983 0. 775 510 18 0. 990 0. 922 511 24 0. 993 0. 923 512 22 0. 948 0. 754 513 22 0. 989 0. 927 514 41 0. 987 0. 895 515 31 0. 979 0. 864 516 16 0. 988 0. 968 518 27 0. 977 0. 934 519 43 0. 994 0. 918 520 45 0. 995 0. 686 522 26 0. 975 0. 807 523 30 0. 982 0. 647 524 42 0. 982 0. 664 525 15 0. 935 0. 811 526 36 0. 999 0. 992 528 41 0. 901 0. 614 529 20 0. 994 0. 976 530 21 0. 940 0. 738 Table 6 SEQ ID NO : Position of Signal Peptide Maximum score Average score 531 38 0. 991 0. 889 532 16 0. 915 0. 719 534 28 0. 974 0. 886 535 21 0. 981 0. 911 536 30 0. 993 0. 832 537 30 0. 993 0. 832 538 21 0. 993 0. 979 539 38 0. 884 0. 655 540 25 0. 963 0. 849 541 27 0. 954 0. 863 542 27 0. 961 0. 767 544 19 0. 972 0. 877 546 25 0. 986 0. 802 547 45 0. 954 0. 577 548 26 0. 895 0. 712 549 23 0. 956 0. 836 550 19 0. 989 0. 950 551 40 0. 967 0. 821 552 19 0. 968 0. 923 553 44 0. 990 0. 566 554 41 0. 922 0. 748 555 34 0. 991 0. 758 557 32 0. 968 0. 678 558 23 0. 989 0. 965 559 23 0. 989 0. 965 560 16 0. 969 0. 917 561 19 0. 978 0. 930 562 39 0. 982 0. 678 563 36 0. 987 0. 866 564 24 0. 942 0. 780 565 46 0. 963 0. 617 567 49 0. 998 0. 716 568 45 0. 996 0. 966 569 32 0. 971 0. 914 570 25 0. 998 0. 958 571 25 0. 998 0. 958 573 41 0. 962 0. 555 574 19 0. 973 0. 893 575 37 0. 968 0. 621 576 24 0. 983 0. 949 577 40 0. 980 0. 824 578 21 0. 953 0. 854 580 45 0. 987 0. 852 581 18 0. 898 0. 665 583 24 0. 959 0. 869 584 20 0. 982 0. 852 585 44 0. 894 0. 594 586 48 0. 981 0. 692 588 17 0. 992 0. 969 590 29 0. 975 0. 835 591 17 0. 924 0. 748 592 25 0. 974 0. 872 593 18 0. 943 0. 843 594 33 0. 970 0. 887 595 25 0. 980 0. 893 Table 6 SEQ ID NO : Position of Signal Peptide Maximum score Average score 596 18 0. 973 0. 922 597 26 0. 994 0. 969 598 34 0. 961 0. 562 599 39 0. 978 0. 791 600 17 0. 928 0. 753 603 19 0. 976 0. 950 605 49 0. 994 0. 792 606 24 0. 993 0. 937 607 19 0. 991 0. 956 608 39 0. 996 0. 930 611 43 0. 987 0. 765 612 41 0. 977 0. 722 613 23 0. 952 0. 651 615 19 0. 987 0. 898 617 26 0. 972 0. 732 618 20 0. 965 0. 833 619 13 0. 923 0. 755 620 25 0. 951 0. 738 622 30 0. 967 0. 769 623 48 0. 979 0. 568 625 18 0 956 0 655 626 27 0. 975 0. 831 627 44 0. 987 0. 725 628 35 0. 969 0. 616 629 33 0. 981 0. 884 630 35 0. 954 0. 759 631 20 0 926 0. 787 632 20 0. 974 0. 908 633 16 0. 888 0. 686 635 27 0. 973 0. 870 636 37 0. 956 0. 698 637 25 0. 969 0. 873 638 48 0. 985 0. 705 640 26 0. 956 0. 717 641 11 0. 977 0. 95 8 642 22 0. 953 0. 916 643 39 0. 972 0. 817 644 29 0. 983 0. 897 645 24 0. 917 0. 657 646 23 0. 967 0. 856 648 25 0. 928 0. 667 650 38 0. 966 0. 856 651 21 0. 990 0. 950 652 41 0. 971 0. 804 653 19 0. 937 0. 870 654 15 0. 987 0. 802 655 20 0. 925 0. 699 657 40 0. 977 0. 661 658 14 0. 967 0. 876 659 0. 990 0. 724 660 23 0. 968 0. 924 661 27 0. 882 0. 585 662 44 0. 990 0. 644 664 17 0. 950 0. 658 665 25 0. 971 0. 897 Table 6 SEQ ID NO : Position of Signal Peptide Maximum score Average score 666 39 0. 996 0. 868 667 20 0. 987 0. 946 669 14 0. 946 0. 864 672 26 0. 982 0. 896 Table 7 SEQ ID NO : Chromsomal location 1 5 2 6 3 3 4 17 5 11 6 10 7 3q 8 13 9 17 10 1 12 13 13 17 15 13 16 5 17 6 19 10 21 1 23 13 24 1 25 11 26 12 28 12 29 15 30 19 31 1 32 11 323 Ip31 2-32. 3 35 7 36 17 37 8 39 10 40 7 41 3 42 22 43 12 44 13 45 13 46 17 47 20 48 16 49 11 50 15 51 ils 52 15 53 15 54 15 56 16 57 15 58 22. 60 1 61 1 62 7 63 11 66 2 67 8 Table 7 SEQ ID NO : Chromsomal location 68 16 69 70 11 71 13 72 18 75 12 76 10 77 9 78 17 80 3 81 11 82 8 84 2 85 86 4 87 9 88 9 89 8 91 16 92 15 93 4 94 19 95 7 96 16 97 15 98 16 99 5 100 19 101 8 102 Ip35. 1-35. 3. 104 6 105 8 106 5 107 p34. 1-36. 11 109 4 110 6 111 1 112 19 113 6 114 10 115 18 116 6 117 19 118 1 119 3 120 3 121 13 122 3 123 12 124 1 125 6 126 13 128 5 129 16 130 4 Table 7 SEQ ID NO : Chromsomal location 131 5 133 5 134 12 137 Xq25-26 138 13 140 6pl 1. 2-12. 3 141 19 142 6q 16-21 143 I q23-24. 144 5 145 22. 146 17 147 16 148 5 151 19 152 17 153 16 154 18 155 5 156 10 157 2 158 9 159 9 160 20 161 17 162 17 163 5 165 20 166 6 167 16 168 12 170 6 172 9 173 3 174 20 175 16 176 11 177 18 178 10 179 22q 13. 1-13. 2. 181 16 182 11 183 17 184 7 185 11 186 06 187 6q 16. 2-21 188 3 190 19 191 19 192 1 193 16 194 X 195 6 197 Xpl 1. 4-21. 2 Table 7 SEQ ID NO : Chromsomal location 198 1 199 8 200 6q22. 1-22. 33 201 8 204 6 206 17 207 19 210 17 211 8 212 15 213 15 214 11 215 15 216 15 218 219 2 220 12 222 6q23. 1-24. 3 224 16 225 21 226 15 227 1 228 17 229 I 232 16 234 3 235 22 236 10 237 3 238 16 239 240 17 241 2 242 3 243 13 244 13 246 17 247 15 250 1 251 5 252 19 253 9 255 3 256 14 257 15 258 1 259 3 260 16 262 X 263 11 264 21 265 3 266 3 267 14 270 Table 7 SEQ ID NO : Chromsomal location 272 17 273 15 276 18 277 4 278 17 279 1 280 6. 281 22ql3. 1-13. 33 282 3 284 20 286 6 288 4 290 291 1 292 293 294 295 9 296 3 298 300 1 301 11 302 6p21. 1-21. 2 303 17 304 3 305 12 306 16 307 5 309 17 312 5 313 18 314 16 3) 5J ! 8 315 18 316 vil 317 5 318 1 q42. 2-43 319 11 320 19 321 3 324 3 326 5 327 8 329 16 330 4 332 6 333 12 334 12 335 18 336 2 Table 8 SEQ ID NO : Number of Position of Transmembrane Region : TMPred Score Transmembrane Domains Predicted 337 1 9-31 : 2958 338 I 15-38 : 1948 339 2 20-34 : 1518 82-98 : 1908 340 1 64-80 : 1560 341 1 24-40 : 2347 342 1 14-32 : 2720 343 1 23-44 : 1807 344 2 15-31 : 1300 118-140 : 3012 345 4 95-111 : 2524 104-139 : 1338 125-147 : 2138 174-209 : 1036 346 2 6-38 : 1711 49-67 : 1103 347 2 15-31 : 3431 69-86 : 889 348 1 28-44 : 2183 349 3 13-32 : 2547 95-110 : 1692 112-132 : 1903 353 3 41-57 : 1768 82-97 : 2647 122-136 : 968 354 1 250-265 : 1867 355 3 46-62 : 911 68-84 : 1367 154-166 : 1297 356 2 32-51 : 2342 114-130 : 1188 357 1 23-39 : 2309 359J4)-59 : 2412 360 2 85-114 : 2984 221-238 : 959 361 2 35-50 : 1595 66-85 : 2779 362 2 17-32 : 1331 57-71 : 1728 363 3 14-31 : 1963 40-58 : 1009 66-86 : 1248 364 1 226-242 : 2202 365 2 46-61 : 832 73-90 : 2191 366 1 34-56 : 1058 367 1 154-172 : 2074 368 3 34-49 : 1210 66-99 : 1252 97-113 : 2355 369 I 18-33 : 1975 370 2 34-53 : 1125 67-84 : 2061 371 4 158-174 : 1945 199-216 : 1112 225-242 : 1673 254-271 : 946 372 1 15-33 : 1775 373 1 181-199 : 1868 374 5 38-54 : 1712 67-94 : 2110 114-128 : 918 240-256 : 855 277- 292 : 1359 375 2 50-74 2625 130-149 : 1166 376 4 16-38 : 1473 43-59 : 1371 77-94 : 1851 199-214 : 1092 377 1 46-62 : 3051 378 1 17-34 : 2743 379 1 95-118 : 3033 380 1 213-230 : 985 382 1 8-31 : 3667 383 1 83-101 : 2361 384 3 47-62 : 1204 51-79 : 1625 96-109 : 1118 386 4 13-35 : 1282 58-73 : 2648 91-107 : 1319 148-165 : 1783 387 4 41-56 : 1354 62-78 : 1639 88-103 : 977 134-150 : 1946 388 2 25-462369 66-81 : 1705 389 5 20-43 : 823 51-73 : 1163 87-106 : 1827 105-125 : 1017 153- 186 : 1554 391 1 74-89 : 3414 393 l 31-57 : 2521 394 3 27-46 : 2157 130-160 : 1822 236-250 : 888 Table 8 SEQ ID NO : Number of Position of Transmembrane Region : TMPred Score Transmembrane Domains Predicted 396 10 28-44 : 2267 50-76 : 1625 68-88 : 2769 93-113 : 1629 118- 138 : 2697 153-168 : 1629 178-194 : 2313 203-238 : 1733 244-263 : 2730 269-284 : 1367 397 1 40-67 : 1986 400 3 23-40 : 2163 266-285 : 985 291-304 : 1229 401 3 18-34 : 2249 256-272 : 1362 280-299 : 167 402 1 21-39 : 2045 403 2 34-51 : 1665 133-151 : 1190 404 4 21-37 : 2440 57-74 : 1286 84-112 : 1585 122-143 : 1004 405 2 48-63 : 1829 197-216 : 1112 408 1 29-48 : 1619 410 2 16-32 : 1602 191-205 : 890 411 3 44-60 : 2409 103-123 : 941 165-185 : 2002 413 319-35 : 2) 53 38-53 : 1100 78-97 : 1064 414 1 20-39 : 1830 415 2 57-72 : 2060 93-110 : 939 416 8 23-47 : 1290 60-80 : 1779 87-106 : 1447 159-187 : 2236 202- 216 : 1085 234-249 : 981 270-299 : 1491 324-338 : 1352 467 1 21-39 : 2481 418 2 27-52 : 1562 66-84 : 864 419 2 15-31 : 1529 41-56 : 2722 420 1 21-36 : 2544 421 2 16-34 : 1960 40-55 : 951 422 1 174-191 : 1728 423 1 16-32 : 827 424 1 45-66 : 1964 425 1 75-92 : 1800 426 3 17-40 : 2165 71-83 : 1112 116-143 : 1198 427 1 23-39 : 3165 428 42-59 : 859 430 5 75-90 : 1359 107-122 : 1520 135-151 : 1967 175-191 : 1416 236-251 : 2332 431 1 14-32 : 2317 435 2 214-236 : 1046 282-294 : 966 436J48-63 : 2723 437 6 125-141 : 2144 157-173 : 1116 185-204 : 1756 223-238 : 926 243-259 : 1271 273-288 : 1225 438 2 38-55 1680 151-168 : 2550 439 2 30-51 : 2155 161-176 : 905 440 6 36-50 : 2210 58-74 : 1644 126-141 : 914 152-173 : 1406 187- 202 : 2224 221-236 : 1055 441 5 49-70 : 1075 88-104 : 1052 123-140 : 1710 157-175 : 2590 191-204 : 1390 442 2 25-45 : 1365 64-84 : 1812 444 2 46-59 : 1059 186-206 : 1046 445 1 97-112 : 1026 446 1 26-41 : 1887 448 3 28-43 : 1680 58-73 : 1675 90-105 : 1928 449 3 82-102 : 1765 119-134 : 1405 167-183 : 2521 450 4 I-45 : 1726 42-67 : 2522 207-229 : 861 274-291 : 922 451 1 13-31 : 2843 452 3 23-38 : 1889 50-66 : 831 121-137 : 1096 453 3 19-35 : 1356 72-87 : 1830 105-120 : 1373 Table 8 SEQ ID NO : Number of Position of Transmembrane Region : TMPred Score Transmembrane Domains Predicted 455 2 22-48 : 1148 384-399 : 2339 457 1 36-51 : 2076 458 6 83-100 : 2781 111-133 : 1847 157-173 : 2151 175-191 : 1172 236-251 : 3053 307-322 : 1307 460 1 14-34 : 2733 461 1 31-50 : 2047 462 1 118-137 : 812 464 1 234-248 : 948 465 1 7-41 : 2396 467 1 18-33 : 1771 468 1 15-39 : 2946 470 1 53-68 : 3633 471 1 36-51 : I : 50 472 3 30-58 : 2255 69-85 : 1303 102-116 : 965 473 7 5-33 : 2407 48-62 : 834 82-101 : 1768 116-136 : 1635 165- 185 : 2884 226-247 : 1338 263-282 : 1779 475 1 26-47 : 2958 476 43-58 : 2185 477J5)-66 : 896 478 1 20-39 : 1851 479 1 30-48 : 2719 480 2 50-67 : 1746 105-120 : 1144 481 1 142-159 : 2140 482 1 108-123 : 1623 483 1 34-48 : 2268 484 14-38 : 2868 281-297 : 941 486 1 217-239 : 1272 487 1 146-168 : 2684 488 2 90-107 : 1944 363-377 : 1338 489 64-81 : 2157 84-100 : 1243 97-133 : 1672 490 I 48-72 2661 491 3 2-38 : 971 22-46 : 1497 84-99 : 1261 493 2 34-61 : 2058 93-108 : 1716 494 2 40-59 : 1918 234-249 : 859 495 1 24-45 : 2330 497 1 296-313 : 812 498 1 2 1-44 : 2763 499 1 21-36 : 2617 500 1 26-51 : 825 502 4 34-55 : 2354 150-169 : 1592 311-333 : 1867 353-375 : 892 503 1 69-872593 504 5 59-80 : 1228 88-107 : 866 157-176 : 3161 198-216 : 1250 223-238 : 2194 505 1 195-210 : 1193 506 19-35 : 2865 507 1 69-98 : 822 508 3 18-33 : 2344 94-115 : 1093 232-249 : 1415 509 1 14-31 : 2117 510 1 166-182 : 2113 514 1 17-35 : 2291 515 1 11-31 : 871 517 1 31-53 : 2985 Table 8 SEQ ID NO : Number of Position of Transmembrane Region : TMPred Score Transmembrane Domains Predicted 519 l 20-44 : 2459 52020-37 : 2284 521 1 22-42 : 3116 52246-62 : 2496 524 1 19-33 : 1834 526 2 41-71 : 1782 65-86 : 3101 527 3 19-34 : 1101 46-62 : 1928 185-201 : 1841 528 1 17-39 : 1978 529 1 364-379 : 1065 531 1 22-40 : 1765 533 1 38-53 : 1788 534 1 14-32 : 2099 535 2 32-52 : 1769 77-102 : 2317 536 3 16-37 : 895 52-69 : 1796 100-120 : 1617 537 4 153-175 : 2138 189-204 : 1068 261-283 : 2271 290- 306 : 1112 538 1 1-34 : 1975 539 1 10-38 : 1023 540 1 15-31 : I 522 541 74-91 : 2543 542 5 49-64 : 1187 82-96 : 1485 119-140 : 1408 129-153 : 2110 206-222 : 2257 543 1 66-83 : 2200 546 2 75-94 : 924 180-195 : 1494 547 1 22-37 : 2183 548 5 43-67 : 2282 70-91 : 1282 121-137 : 2440 169-183 : 1439 197-232 : 1120 549 3 14-34 : 1791 83-97 : 1381 115-144 : 1592 550 4 43-62 : 1533 195-216 : 2160 222-237 : 1314 257-270 : 1867 551 2 13-31 : 1516 69-88 : 2277 552 5 25-42 : 1555 74-89 : 1237 114-142 : 2195 154-169 : 1023 185-200 : 2114 553 3 24-47 : 1711 61-79 : 2020 192-207 : 2454 554 2 36-56 : 1076 90-110 : 1216 555 1 16-33 : 2206 556 2 17-36 : 2654 64-76 : 932 557 l 19-34 : 1366 558 2 21-46 : 1142 54-70 : 3147 560 1 28-46 : 2247 561 2 23-43 : 1069 58-75 : 1756 562 4 21-39 : 1494 81-97 : 1518 125-143 : 1312 148-169 : 2440 563 10 7-32 : 2014 82-96 : 1124 107-123 : 1475 148-167 : 1298 170- 193 : 1565 258-273 : 1090 296-316 : 1839 324-345 : 1356 354-369 : 1159 420-437 : 1669 564 2 44-60 : 963 75-90 : 3007 565 4 29-44 : 1865 76-93 : 1315 119-138 : i894 155-176 : 1330 566 1 42-69 : 2215 567 2 36-55 : 2620 41-76 : 845 568 I 3-35 : 3176 569 I 56-73 : 3062 572 3 45-61 : 2010 110-125 : 1024 175-193 : 839 573 1 18-39 : 2254 574 3 55-76 : 2276 89-112 : 1167 148-168 : 2134 Table 8 SEQ ID NO : Number of Position of Transmembrane Region : TMPred Score Transmembrane Domains Predicted 575 1 16-36 : 2701 576 2 82-107 : 1813 168-186 : 2844 577 1 17-35 : 2449 578 1 36-53 : 2305 579 I 29-45 : 2349 580 1 26-43 : 2340 581 2 238-257 : 908 396-412 : 1281 582 2 50-68 : 1787 82-94 : 808 583 2 41-55 : 1214 76-91 : 2379 584 1 120-139 : 1924 585 2 25-41 : 2077 208-223 : 986 586 2 25-45 : 1955 167-181 : 1187 587 3 47-62 : 2783 76-92 : 1090 115-130 : 2791 589 1 58-85 : 1106 590 4 33-48 : 1166 71-88 : 2044 108-123 : 1229 134-154 : 2709 593 1 79-94 : 1909 594 6 16-33 : 2461 94-113 : 2485 137-152 : 1212 190-212 : 3236 237-253 : 971 266-285 : 1138 596 2 48-66 : 1420 56-86 : 2350 597 1 14-32 : 2650 598 2 23-42 : 2154 134-155 : 1123 599 3 16-34 : 1811 55-70 : 1301 82-99 : 1627 600 1 43-58 : 890 601 27-42 : 2043 602 3 52-75 : 2018 325-346 : 865 375-392 : 839 603 1 353-370 : 2096 604 1 25-45 : 2047 605 1 24-47 : 2800 606 2 71-86 : 1595 102-121 : 2779 607 i 297-319 : 2854 608 10 25-41 : 148954-72 : 2563 87-103 : 1436 116-134 : 2525 149- 165 : 1474 178-196 : 2516 211-227 : 1420 240-258 : 2456 273-289 : 1392 302-320 : 2395 609 2 22-48 : 2007 141-164 : 1410 610 2 21-41 : 1941 102-117 : 3056 611 8 29-44 : 1389 61-74 : 917 88-103 : 1267 115-129 : 890 179- 193 : 898 204-221 : 1978 220-238 : 1076 259-275 : 1735 612 1 26-43 : 1767 614 2 36-51 : 2233 100-113 : 2408 615 2 40-56 : 1175 69-85 : 1803 619 1 35-53 : 2023 621 4 17-32 : 2238 39-60 : 1679 79-95 : 2605 114-129 : 1098 623 1 23-42 : 2878 624 2 36-58 : 1952 189-210 : 874 627 4 25-48 : 2108 276-291 : 1253 334-351 : 1063 399-416 : 1680 628 4 22-37 : 2458 45-60 : 1250 82-98 : 1641 159-176 : 933 629 1 14-34 : 1660 630 1 12-38 : 1749 635 1 43-59 : 2213 636 1 13-34 : 2984 638 6 25-41 : 1898 103-119 : 1328 131-148 : 2506 180-203 : 1533 205-228 : 1303 245-260 : 1634 639 l 30-49 : 2416 Table 8 SEQ ID NO : Number of Position of Transmembrane Region : TMPred Score Transmembrane Domains Predicted 641 1 32-50 : 1597 642 1 284-299 : 1055 643 124-141 : 2071 645 92-108 : 1857 647 1 28-44 : 2543 649 2 43-58 : 1396 60-75 : 2059 650 3 5-35 : 1780 59-73 : 1361 80-103 : 1826 652 5 16-32 : 1576 72-87 : 1083 104-121 : 1825 145-160 : 1294 227-247 : 1337 654 1 39-53 : 1731 655 1 245-258 : 1771 656 58-81 : 2868 657 1 16-33 : 1894 658 290-310 : 2684 660 2 264-282 : 1757 383-403 : 1000 662 1 20-47 : 3001 663 2 IS-33 : 892 108-126 : 1867 664 1 37-56 : 2054 665 1 369-387 : 2530 666 2 14-34 : 1939 187-208 : 1365 667 2 43-58 : 1060 155-170 : 2602 668 4 24-45 : 2509 98-119 : 2954 129-147 : 1343 183-201 : 2141 669 I 142-157 : 1775 670 1 33-49 : 2264 671 I 43-57 : 1794 Table 9 SEQ ID SEQ ID SEQ ID SEQ ID Identification of NO : of NO : of NO : of NO : of Priority Application full-length full-length contig contig that contig nucleotide nucleotide peptide nucleotide peptide sequence was filed sequence sequence sequence sequence (Attorney Docket No. SEQ ID NO.) * 1 337 673 874 788 13033 2 338 339 340 674 875 784 3746 5 341 6 342 675 876 785 2855 7 343 8 344 9 345 676 877 785 1465 10 346 677 878 784 1644 11 347 678 879 784 4307 12 348 13 349 679 880 787 1411 14 350 680 881 787 5936 15 351 681 882 784 4781 16 352 682 883 784 2486 17 353 683 884 790 28311 18 354 684 885 787 10206 19 355 20 356 21 357 22 358 685 886 784 3665 23 359 24 360 686 887 785 1105 25 361 687 888 787 7951 26 362 688 889 785 1538 27 363 28 364 689 890 787_4539 29 365 690 891 790 26713 30 366 691 892 790 10585 31 367 32 368 692 893 785 1092 33 369 693 894 784 5400 34 370 35 371 694 895 790 17470 36 372 37 373 695 896 784 844 38 374 696 897 787 9644 39 375 697 898 789 1867 40 376 698 899 785 612 41 377 699 900 785 1054 42 378 700 901 785 852 43 379 701 902 790 5231 44 380 702 903 784 5466 45 381 46 382 703 904 790 21464 47 383 704 905 784 715 48 384 705 906 785 631 49 385 706 907 784 3853 50 386 707 908 790 10399 Table 9 SEQ ID SEQ ID SEQ ID SEQ ID Identification of NO : of NO : of NO : of NO : of Priority Application full-length full-length contig contig that contig nucleotide nucleotide peptide nucleotide peptide sequence was filed sequence sequence sequence sequence (Attorney Docket No. SEQ ID NO.) * 51 387 708 909 790 25607 52 388 709 910 790 10374 53 389 710 911 790 10504 54 390 711 912 790 21640 55 391 712 913 790 17957 56 392 713 914 787 71 57 393 714 915 791 1511 58 394 715 916 785 640 59 395 716 917 789 3732 60 396 717 918 787 5233 61 397 718 919 788 2575 62 398 719 920 790_4139 63 399 720 921 789 2499 64 400 65 401 721 922 792 4675 66 402 722 923 784 2550 67 403 723 924 784 6192 68 404 724 925 787 7445 69 405 70 406 725 926 787 5416 71 407 726 927 784 4167 72 408 727 928 784 5133 73 409 74 410 728 929 784 10126 75 411 76 412 77 413 729 930 792 932 78 414 730 931 784 4665 79 415 80 416 81 417 82 418 731 932 790 19568 83 419 84 420 85 421 86 422 87 423 88 424 89 425 732 933 784 1798 90 426 91 427 733 934 790 1155 92 428 734 935 789 5186 93 429 94 430 95 431 96 432 97 433 98 434 99 435 735 936 790 8077 loo 436 736 937 787 1058 101 437 Table 9 SEQ ID SEQ ID SEQ ID SEQ ID Identification of NO : of NO : of NO : of NO : of Priority Application full-length full-length contig contig that contig nucleotide nucleotide peptide nucleotide peptide sequence was filed sequence sequence sequence sequence (Attorney Docket No. SEQ ID NO.) * 102 438 737 938 784 929 103 439 738 939 788 10938 104 440 105 441 739 940 787 5943 106 442 740 941 785 975 107 443 741 942 787 2691 los 444 742 943 785 3660 109 445 743 944 790 13070 110 446 111 447 744 945 790 13664 112 448 745 946 790 24599 113 449 114 450 115 451 116 452 117 453 746 947 790 24595 118 454 119 455 747 948 787 4919 120 456 121 457 122 458 123 459 748 949 784 3534 124 460 749 950 784 4970 125 461 126 462 127 463 750 951 784 4845 128 464 129 465 751 952 787 7638 130 466 752 953 785 1670 131 467 753 954 790 27718 132 468 133 469 754 955 790 24877 134 470 755 956 790 9494 135 471 756 957 787 4525 136 472 757 958 784 939 137 473 138 474 139 475 140 476 141 477 142 478 758 959 784 6707 143 479 759 960 788 11952 144 480 760 961 790 12052 145 481 761 962 790 3488 146 482 762 963 787 2489 147 483 148 484 149 485 763 964 792 3487 150 486 151 487 764 965 785 395 152 488 Table 9 SEQ ID SEQ ID SEQ ID SEQ ID Identification of NO : of NO : of NO : of NO : of Priority Application full-length full-length contig contig that contig nucleotide nucleotide peptide nucleotide peptide sequence was filed sequence sequence sequence sequence (Attorney Docket No. SEQ ID NO.) * 153 489 154 490 155 491 156 492 765 966 785 3560 157 493 158 494 766 967 785 1618 159 495 160 496 161 497 162 498 767 968 787 4486 163 499 768 969 784 3498 164 500 165 501 166 502 769 970 784_5437 167 503 770 971 787 2054 168 504 169 505 771 972 787 2155 170 506 772 973 790 15300 171 507 172 508 173 509 174 510 175 511 773 974 790 11357 176 512 774 975 789 2890 177 513 178 514 179 515 180 516 181 517 775 976 790 3760 182 518 776 977 784 4787 183 519 184 520 777 978 787 4483 185 521 186 522 778 979 785 598 187 523 779 980 790 2524 188 524 780 981 791 2994 189 525 781 982 784 4307 190 526 191 527 782 983 790 11947 192 528 193 529 783 984 787 6368 194 530 784 985 790 21374 195 531 196 532 785 986 790 26925 197 533 198 534 199 535 200 536 786 987 787 2905 201 537 787 988 784 5289 202 538 788 989 784 3437 203 539 Table 9 SEQ ID SEQ ID SEQ ID SEQ ID Identification of NO : of NO : of NO : of NO : of Priority Application full-length full-length contig contig that contig nucleotide nucleotide peptide nucleotide peptide sequence was filed sequence sequence sequence sequence (Attorney Docket No. SEQ ID NO.) * 204 540 205 541 789 990 785 158 206 542 790 991 784 1021 207 543 791 992 790 16269 208 544 209 545 210 546 211 547 792 993 790 3621 212 548 213 549 793 994 790 16011 214 550 794 995 790 18251 215 551 795 996 790 26204 216 552 796 997 790 17932 217 553 797 998 790 25384 218 554 219 555 798 999 784 4771 220 556 221 557 799 1000 784 9216 222 558 800 1001 787 7102 223 559 801 1002 784 8386 224 560 802 1003 790 21024 225 561 226 562 803 1004 790 25301 227 563 804 1005 784 2437 228 564 229 565 805 1006 784 3789 230 566 806 1007 787 4340 231 567 807 1008 788_8449 232 568 808 1009 790 17189 233 569 809 1010 790 3825 234 570 810 1011 784 7233 235 571 236 572 811 1012 789 20 237 573 238 574 812 1013 784 2129 239 575 240 576 813 1014 787 5627 241 577 814 1015 787 7249 242 578 243 579 815 1016 790 301 244 580 816 1017 784 1483 245 581 817 1018 784 5156 246 582 818 1019 787 2548 247 583 248 584 819 1020 789 3213 249 585 820 1021 789 4901 250 586 251 587 821 1022 790 24517 252 588 253 589 822 1023 788 1187 254590 823) 024 7844265 Table 9 SEQ ID SEQ ID SEQ ID SEQ ID Identification of NO : of NO : of NO : of NO : of Priority Application full-length full-length contig contig that contig nucleotide nucleotide peptide nucleotide peptide sequence was filed sequence sequence sequence sequence (Attorney Docket No. SEQ ID NO.) * 255 591 824 1025 784 603 256 592 825 1026 787 2104 257 593 826 1027 784 4819 258 594 827 1028 784_3677 259 595 260 596 261 597 262 598 263 599 828 1029 790 21539 264 600 265 601 266 602 030 790935 266 602 829 1030 790 935 267 603 268 604 269 605 830 1031 787 3283 270 606 831 1032 787 7951 271 607 832 1033 790 13949 272 608 833 1034 784 2168 273 609 834 1035 785 1250 274 610 835 1036 784 9629 275 611 276 612 277 613 277 613 278 614 836 1037 785 14 279 615 837 1038 790 24168 280 616 838 1039 787 4843 281 617 282 618 839 1040 790 16366 283 619 840 1041 790 8044 284 620 841 1042 784 3590 285 621 842 1043 784 337 286 622 843 1044 785 706 287 623 844 1045 787_9834 288 624 845 1046 789 3409 289 625 290 626 846 1047 787 3554 291 627 847 1048 790 8276 292 628 848 1049 785 3232 293 629 849 1050 784 3345 294 630 850 1051 790 18037 295 631 296 632 851 1052 784 7084 297 633 298 634 299 635 852 1053 787 2278 300 636 853 1054 785 1867 301 637 302 638 854 1055 787 2310 303 639 855 1056 784 2326 304 640 641 856 1057 785 1538 Table 9 SEQ ID SEQ ID SEQ ID SEQ ID Identification of NO : of NO : of NO : of NO : of Priority Application full-length full-length contig contig that contig nucleotide nucleotide peptide nucleotide peptide sequence was filed sequence sequence sequence sequence (Attorney Docket No. SEQ ID NO.) * 306 642 857 1058 784 5007 307 643 858 1059 787 8999 308 644 309 645 310 646 311 647 859 1060 787 5698 312 648 860 1061 790 29400 313 649 314 650 861 1062 784 4813 315 651 316 652 862 1063 784 9771 317 653 863 790 10961 318 654 864 1065 790 11763 319 655 865 1066 784 5832 320 656 321 657 322 658 866 1067 790 16986 323 659 867 1068 785 3654 324 660 868 1069 785 102 325 661 869 1070 784 4307 326 662 327 663 328 664 329 665 330 666 870 1071 787 6896 331 667 871 1072 789 3174 332 668 872 1073 787 5591 333 669 334 670 335 671 873 1074 785 1003 336 672 *784 XXX = SEQ ID NO: XXX of Attorney Docket No. 784, US Serial No. 09/488,725 filed 01/21/2000, the entire disclosure of which, including sequence listing, is incorporated herein by reference.

785 XXX = SEQ ID NO: XXX of Attorney Docket No. 785, US Serial No. 09/491,404 filed 01/25/2000, the entire disclosure of which, including sequence listing, is incorporated herein by reference.

787_XXX = SEQ ID NO: XXX of Attorney Docket No. 787, US Serial No. 09/496,914 filed 02/03/2000, the entire disclosure of which, including sequence listing, is incorporated herein by reference.

788 XXX = SEQ ID NO: XXX of Attorney Docket No. 788, US Serial No. 09/515,126 filed 02/28/2000, the entire disclosure of which, including sequence listing, is incorporated herein by reference.

Table 9 789 XXX = SEQ ID NO: XXX of Attorney Docket No. 789, US Serial No. 09/519, 705 filed 03/07/2000, the entire disclosure of which, including sequence listing, is incorporated herein by reference.

790 XXX = SEQ ID NO: XXX of Attorney Docket No. 790, US Serial No. 09/540,217 filed 03/31/2000, the entire disclosure of which, including sequence listing, is incorporated herein by reference.

791 XXX = SEQ ID NO: XXX of Attorney Docket No. 791, US Serial No. 09/552,929 filed 04/18/2000, the entire disclosure of which, including sequence listing, is incorporated herein by reference.

792 XXX = SEQ ID NO: XXX of Attorney Docket No. 792, US Serial No. 09/577,408 filed 05/18/2000, the entire disclosure of which, including sequence listing, is incorporated herein by reference.

Table 10 SEQ ID NO of Full-length SEQ ID NO of Full-length SEQ ID NO in Nucleotide Sequence Peptide Sequence Priority Application USSN 60/311, 261 1 337 10 2 338 100 3 339 101 4 340 102 5 341 103 6 342 104 7 343 105 8 344 106 9 345 107 10 346 108 11 347 109 12 348 li 13 349 110 14 350 111 15 351 112 16 352 113 17 353 114 18 354 115 19 355 116 20 356 117 21 357 118 22 358 119 23 359 12 24 360 120 25 361 121 26 362 122 . 27363123 28 364 124 29 365 125 30 366 126 31 367 127 32 368 128 33 369 129 34 370 13 35 371 130 36 372 131 37 373 132 38 374 133 39 375 134 40 376 135 41 377 136 42 378 137 43 379 138 44 380 139 45 381 14 46 382 140 47 383 141 48 384 142 Table 10 SEQ ID NO of Full-length SEQ ID NO of Full-length SEQ ID NO in Nucleotide Sequence Peptide Sequence Priority Application USSN 60/311, 261 49 385 143 50 386 144 51 387 145 52 388 146 53 389 147 54 390 148 55 391 149 56 392 15 57 393 150 58 394 151 59 395 152 60 396 153 61 397 154 62 398 155 63 399 156 64 400 157 65 401 158 66 402 159 67 403 16 68 404 160 69 405 161 70 406 162 71 407 163 72 408 164 73 409 165 74 410 166 75 411 167 76 412 168 77 413 169 78 414 17 79 415 170 80 416 171 81 417 172 82 418 173 83 419 174 84 420 175 85 421 176 86 422 177 87 423 178 88 424 179 89 425 18 90 426 180 91 427 181 92 428 182 93 429 183 94 430 184 95 431 185 96 432 186 97 433 187 Table 10 SEQ ID NO of Full-length SEQ ID NO of Full-length SEQ ID NO in Nucleotide Sequence Peptide Sequence Priority Application USSN 60/311, 261 98 434 188 99 435 189 100 436 19 101 437 190 102 438 191 103 439 192 104 440 193 105 441 194 106 442 195 107 443 196 108 444 197 109 445 198 110 446 199 111 447 2 112 448 20 113 449 200 114 450 201 115 451 202 116 452 203 117 453 204 118 454 205 119 455 206 120 456 207 121 457 208 122 458 209 123 459 21 124 460 210 125 461 211 126 462 212 127 463 213 128 464 214 129 465 215 130 466 216 131 467 217 132 468 218 133 469 219 134 470 22 135 471 220 136 472 221 137 473 222 138 474 223 139 475 224 140 476 225 141 477 226 142 478 227 143 479 228 144 480 229 145 481 23 146 482 230 Table 10 SEQ ID NO of Full-length SEQ ID NO of Full-length SEQ ID NO in Nucleotide Sequence Peptide Sequence Priority Application USSN 60/311, 261 147 483 231 148 484 232 149 485 233 150 486 234 151 487 235 152 488 236 153 489 237 154 490 238 155 491 239 156 492 24 157 493 240 158 494 241 159 495 242 160 496 243 161 497 244 162 498 245 163 499 246 164 500 247 165 501 248 166 502 249 167 503 25 168 504 250 169 505 251 170 506 252 171 507 253 172 508 254 173 509 255 174 510 256 175 511 257 176 512 258 177 513 259 178 514 26 179 515 260 180 516 261 181 517 262 182 518 263 183 519 264 184 520 265 185 521 266 186 522 267 187 523 268 188 524 269 189 525 27 190 526 270 191 527 271 192 528 272 193 529 273 194 530 274 195 531 275 Table 10 SEQ ID NO of Full-length SEQ ID NO of Full-length SEQ ID NO in Nucleotide Sequence Peptide Sequence Priority Application USSN 60/311, 261 196 532 276 197 533 277 198 534 278 199 535 279 200 536 28 201 537 280 202 538 281 203 539 282 204 540 283 205 541 284 206 542 285 207 543 286 208 544 287 209 545 288 210 546 289 211 547 29 212 548 290 213 549 291 214 550 292 215 551 293 216 552 294 217 553 295 218 554 296 219 555 297 220 556 298 221 557 299 222 558 3 223 559 30 224 560 300 225 561 301 226 562 302 227 563 303 228 564 304 229 565 305 230 566 306 231 567 307 232 568 308 233 569 309 234 570 31 235 571 310 236 572 311 237 573 312 238 574 313 239 575 314 240 576 315 241 577 316 242 578 317 243 579 318 244 580 319 Table 10 SEQ ID NO of Full-length SEQ ID NO of Full-length SEQ ID NO in Nucleotide Sequence Peptide Sequence Priority Application USSN 60/311, 261 245 581 32 246 582 320 247 583 321 248 584 322 249 585 323 250 586 324 251 587 325 252 588 326 253 589 327 254 590 328 255 591 329 256 592 33 257 593 330 258 594 331 259 595 332 260 596 333 261 597 334 262 598 335 263 599 336 264 600 337 265 601 34 266 602 35 267 603 36 268 604 37 269 605 38 270 606 39 271 607 4 272 608 40 273 609 41 274 610 42 275 611 43 276 612 44 277 613 45 278 614 46 279 615 47 280 616 48 281 617 49 282 618 5 283 619 50 284 620 51 285 621 52 286 622 53 287 623 54 288 624 55 289 625 56 290 626 57 291 627 58 292 628 59 293 629 6 Table 10 SEQ ID NO of Full-length SEQ ID NO of Full-length SEQ ID NO in Nucleotide Sequence Peptide Sequence Priority Application USSN 60/311, 261 294 630 60 295 631 61 296 632 62 297 633 63 298 634 64 299 635 65 300 636 66 301 637 67 302 638 68 303 639 69 304 640 7 305 641 70 306 642 71 307 643 72 308 644 73 309 645 74 310 646 75 311 647 76 312 648 77 313 649 78 314 650 79 315 651 8 316 652 80 317 653 81 318 654 82 319 655 83 320 656 84 321 657 85 322 658 86 323 659 87 324 660 88 325 661 89 326 662 9 327 663 90 328 664 91 329 665 92 330 666 93 331 667 94 332 668 95 333 669 96 334 670 97 335 671 98 336 672 99