JP2002513294A - Secreted proteins and polynucleotides encoding them - Google Patents

Abstract

(57) Abstract Disclosed are novel polynucleotides and proteins encoded by them.

Description

DETAILED DESCRIPTION OF THE INVENTION             Secreted proteins and polynucleotides encoding them   No. 60 / XXXXXX filed on June 19, 1997 (not a provisional application) No. 08 / 888,715 (changed to provisional application). And all are considered to be as described herein.                                Field of the invention   The present invention relates to novel polynucleotides and the use of such polynucleotides. Proteins, and therapeutic and diagnostic methods for these polynucleotides and proteins Provides catastrophic and research utility.                                Background of the Invention   Protein factors such as lymphokines, interferons, CSFs and The method aimed at the discovery of cytokines such as Matured rapidly over the years. Nowadays conventional hybridization cloning And expression cloning methods provide information directly related to the discovered protein (ie, In the case of hybridization cloning, the partial DNA / amino acid sequence of the protein Column; the activity of the protein in the case of expression cloning) The new polypeptide is cloned "directly". Signal sequence cloning (now DNA sequences based on the presence of a well-recognized secretory leader sequence motif Isolate), as well as hybridizers by various PCR or with low stringency More recent "indirect" cloning methods, such as the cloning method, Due to its secreted nature in the case of cloning of the leader sequence, or In the case of the method by PCR, depending on the cell or tissue source, it may have biological activity. Make available a large number of DNA / amino acid sequences for known proteins This has improved the current situation. The present invention relates to these proteins and their encoding. Which are directed to the polynucleotide.                                Summary of the Invention   In one specific example, The present invention An isolation port selected from the group consisting of: Provide a composition comprising a renucleotide:   (A) SEQ ID NO: A polynucleotide comprising one nucleotide sequence;   (B) SEQ ID NO: A nucleotide from nucleotide 185 to nucleotide 1600 of 1 A polynucleotide comprising a nucleotide sequence;   (C) SEQ ID NO: 1 from nucleotide 1403 to nucleotide 1600 A polynucleotide comprising a nucleotide sequence;   (D) SEQ ID NO: Nucleotide from nucleotide 1 to nucleotide 850 of 1 A polynucleotide comprising a nucleotide sequence;   (E) of clone do154 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence;   (F) of clone do154 deposited under accession number ATCC 98468 Polynucleotide encoding full-length protein encoded by cDNA insert Tide;   (G) of clone do154 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence;   (H) of clone do154 deposited under accession number ATCC 98468 Polynucleotide encoding mature protein encoded by cDNA insert Tide;   (I) SEQ ID NO: Polynucleotide encoding a protein comprising amino acid sequence 2 Tide;   (J) SEQ ID NO: having biological activity: 2 A polynucleotide encoding the protein (the fragment is SEQ ID NO: 2 of 8 Contiguous amino acids);   (K) a polynucleotide that is an allelic variant of the polynucleotide of (a) to (h) above Nucleotides;   (L) A polynucleotide encoding a species homolog of the protein of (i) or (j) above Otide; and   (M) any one of the polynucleotides (a) to (j) under strict conditions A polynucleotide capable of hybridizing to   Preferably, Such a polynucleotide is SEQ ID NO: One nucleotide 185 A nucleotide sequence from to nucleotide 1600; SEQ ID NO: 1 nucleotchi A nucleotide sequence from nucleotide 1403 to nucleotide 1600; SEQ ID NO: One A nucleotide sequence from nucleotide 1 to nucleotide 850; Accession number AT Full length protein coding of clone do154 deposited as CC98468 Nucleotide sequence of the sequence; Or deposited under accession number ATCC 98468 Contains the nucleotide sequence of the mature protein coding sequence of clone do154. In another preferred embodiment, The polynucleotide is Accession number ATCC 9846 8, encoded by the cDNA insert of clone do154 deposited as Encodes the full-length or mature protein to be derived. In still other preferred embodiments, The present invention SEQ ID NO: The amino acid sequence from amino acid 1 to amino acid 222 of A polynucleotide encoding the protein. In a further preferred embodiment And The present invention SEQ ID NO: with biological activity 2 amino acid sequence flags Polynucleotide encoding the protein containing the fragment (the fragment issue: 2, Preferably eight, More preferably 20, Most preferably 30 runs Followed by amino acids), Alternatively, SEQ ID NO: having biological activity 2 amino A polynucleotide encoding a protein containing a fragment of an acid sequence (the fragment Is the sequence number: 2 contains the amino acid sequence from amino acid 231 to amino acid 240. ).   Another specific example is SEQ ID NO: A gene corresponding to one cDNA sequence is provided.   In another embodiment, The present invention A composition comprising a protein, The protein is   (A) SEQ ID NO: The amino acid sequence of 2;   (B) SEQ ID NO: An amino acid sequence of two amino acids 1 to 222;   (C) SEQ ID NO: Comprising two eight consecutive amino acids, SEQ ID NO: 2 amino Fragments of an acid sequence; and   (D) of clone do154 deposited under accession number ATCC 98468 Amino acid sequence encoded by cDNA insert Comprising an amino acid sequence selected from the group consisting of: Other mammalian proteins A composition is provided that is substantially free. Preferably, Such proteins have the sequence number: Amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 2 amino acids 1 to 222 Includes the amino acid sequence at In a further preferred embodiment, The present invention biology Having active activity: Protein containing a fragment of the amino acid sequence of Segment is SEQ ID NO: 2, Preferably eight, More preferably 20, Most preferred Or 30 consecutive amino acids) Alternatively, a sequence number having biological activity issue: A protein comprising a fragment of the amino acid sequence of SEQ ID NO: 2 (Including the amino acid sequence from amino acid 231 to amino acid 240).   In one specific example, The present invention An isolation port selected from the group consisting of: Provide a composition comprising a renucleotide:   (A) SEQ ID NO: A polynucleotide comprising the nucleotide sequence of 3;   (B) SEQ ID NO: Contain 3 nucleotides 47 to 2065 A polynucleotide;   (C) SEQ ID NO: 3 from nucleotide 1086 to nucleotide 1848 A polynucleotide comprising;   (D) Clone dx2901 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of   (E) Clone dx2901 deposited under accession number ATCC 98468 Encoding a full-length protein encoded by a cDNA insert Do;   (F) clone dx290 1 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of   (G) Clone dx2901 deposited under accession number ATCC 98468 Encoding a mature protein encoded by a cDNA insert Do;   (H) SEQ ID NO: Polynucleotide encoding a protein containing amino acid sequence 4 ;   (I) SEQ ID NO: having biological activity: 4 including a fragment of the amino acid sequence A polynucleotide encoding the protein (the fragment is SEQ ID NO: 4 of 8 Contiguous amino acid sequences);   (J) Polynucleic acid which is an allelic variant of the polynucleotide of (a) to (g) above Nucleotides;   (K) a polynucleotide encoding a species homolog of the protein of (h) or (i) above Do; and   (L) any one of the polynucleotides (a) to (i) under strict conditions A polynucleotide capable of hybridizing to   Preferably, Such a polynucleotide is SEQ ID NO: 3 nucleotides 47 A nucleotide sequence from to nucleotide 2065; SEQ ID NO: 3 nucleotides A nucleotide sequence from 1086 to nucleotide 1848; Accession number ATCC Full length protein coding sequence of clone dx2901 deposited as 98468 Sequence nucleotide sequence; Or the deposit deposited under accession number ATCC 98468. Contains the nucleotide sequence of the mature protein coding sequence for lawn dx2901. In another preferred embodiment, The polynucleotide is Accession number ATCC 9846 Coded by cDNA insert of clone dx2901 deposited as No. 8 Encodes the full-length or mature protein to be produced. In still other preferred embodiments , The present invention SEQ ID NO: 4 amino acids from amino acid 312 to amino acid 600 A polynucleotide encoding a protein comprising the sequence is provided. Even better In a specific example, The present invention SEQ ID NO: with biological activity 4 amino acids A polynucleotide encoding a protein containing a fragment of the sequence (the fragment Is the sequence number: 4, Preferably eight, More preferably 20, Most preferably Containing 30 consecutive amino acids), Alternatively, SEQ ID NO: having biological activity Polynucleotide encoding a protein containing a fragment of amino acid sequence 4 Tide (the fragment is SEQ ID NO: 4 amino acids 331 to 340 Comprising the amino acid sequence of   Another specific example is SEQ ID NO: 3 provide the genes corresponding to the cDNA sequences.   In another embodiment, The present invention A composition comprising a protein, The protein is   (A) SEQ ID NO: The amino acid sequence of 4;   (B) SEQ ID NO: 4 amino acid sequences from amino acid 312 to amino acid 600;   (C) SEQ ID NO: Comprising four consecutive eight amino acids; SEQ ID NO: Amino of 4 Fragments of an acid sequence; and   (D) Clone dx2901 deposited under accession number ATCC 98468 Amino acid sequence encoded by the cDNA insert of Comprising an amino acid sequence selected from the group consisting of: Other mammalian proteins A composition is provided that is substantially free. Preferably, Such proteins have the sequence number: Amino acid sequence of SEQ ID NO: 4 or SEQ ID NO: 4 amino acids 312 to 60 amino acids Includes up to 0 amino acid sequences. In a further preferred embodiment, The present invention Raw SEQ ID NO: with physical activity Protein containing a fragment of the amino acid sequence of The fragment is SEQ ID NO: 4, Preferably eight, More preferably 20, Most favorable Preferably containing 30 consecutive amino acids), Alternatively, a biologically active Column index: Protein containing a fragment of the amino acid sequence of SEQ ID NO: 4 issue: 4 including the amino acid sequence from amino acid 331 to amino acid 340) I do.   In one specific example, The present invention An isolation port selected from the group consisting of: Provide a composition comprising a renucleotide:   (A) SEQ ID NO: A polynucleotide comprising the nucleotide sequence of 5;   (B) SEQ ID NO: Nucleotide 5 from nucleotide 107 to nucleotide 724 A polynucleotide comprising a reotide sequence;   (C) SEQ ID NO: 5 nucleotides from nucleotide 218 to nucleotide 724 A polynucleotide comprising a reotide sequence;   (D) SEQ ID NO: 5 nucleotides from nucleotide 536 to nucleotide 866 A polynucleotide comprising a reotide sequence;   (E) clone ek3904 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of   (F) Clone ek3904 deposited under accession number ATCC 98468 Polynucleotide encoding the full-length protein encoded by the cDNA insert of Otide;   (G) Clone ek3904 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of   (H) clone ek3904 deposited under accession number ATCC 98468 Encoding a mature protein encoded by a cDNA insert Otide;   (I) SEQ ID NO: Polynucleotide encoding a protein containing the amino acid sequence of SEQ ID NO: 6 Tide;   (J) SEQ ID NO: having biological activity: 6 amino acid sequence fragments A polynucleotide encoding the protein (the fragment is SEQ ID NO: 6 of 8 Contiguous amino acids);   (K) a polynucleotide which is an allelic variant of the polynucleotide of (a) to (k) above Nucleotides;   (L) A polynucleotide encoding a species homolog of the protein of (i) or (j) above Otide; and   (M) any one of the polynucleotides (a) to (j) under strict conditions A polynucleotide capable of hybridizing to   Preferably, Such a polynucleotide is SEQ ID NO: 5 nucleotides 107 A nucleotide sequence from to nucleotide 724; SEQ ID NO: 5 nucleotides A nucleotide sequence from 218 to nucleotide 724; SEQ ID NO: 5 Nucles A nucleotide sequence from otide 536 to nucleotide 866; Accession number ATC Full length protein coding of clone ek3904 deposited as C98468 Nucleotide sequence of the sequence; Or deposited under accession number ATCC 98468. The nucleotide sequence of the mature protein coding sequence of clone ek3904 Including. In another preferred embodiment, The polynucleotide is Accession number ATCC9 With the cDNA insert of clone ek3904 deposited as 8468 Encodes the encoded full-length or mature protein. In yet another preferred embodiment And The present invention SEQ ID NO: Amino acids from amino acid 6 to amino acid 92 A polynucleotide encoding a protein comprising the sequence is provided. Further preferred equipment In the example, The present invention SEQ ID NO: with biological activity 6 of the amino acid sequence A polynucleotide encoding a protein containing the fragment (the fragment SEQ ID NO: 6, Preferably eight, More preferably 20, Most preferably 30 Contiguous amino acids), Alternatively, SEQ ID NO: having biological activity Six A polynucleotide encoding a protein containing a fragment of the amino acid sequence Segment is SEQ ID NO: Amino acid sequence from amino acid 97 to amino acid 106 of 6 Including).   Another specific example is SEQ ID NO: Genes corresponding to 5 cDNA sequences are provided.   In another embodiment, The present invention A composition comprising a protein, The protein is   (A) SEQ ID NO: The amino acid sequence of 6;   (B) SEQ ID NO: An amino acid sequence of 6 amino acids 6 to 92;   (C) SEQ ID NO: Comprising 6 eight consecutive amino acids, SEQ ID NO: Amino 6 Fragments of an acid sequence; and   (D) Clone ek3904 deposited under accession number ATCC 98468 Amino acid sequence encoded by the cDNA insert of Comprising an amino acid sequence selected from the group consisting of: Other mammalian proteins A composition is provided that is substantially free. Preferably, Such proteins are Distribution Column index: Amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 6 amino acids 6 to 92 Includes the amino acid sequence at In a further preferred embodiment, The present invention biology Having active activity: Protein containing a fragment of the amino acid sequence of Segment is SEQ ID NO: 6, Preferably eight, More preferably 20, Most preferred Or 30 consecutive amino acids), Or a sequence having biological activity number: A protein comprising a fragment of the amino acid sequence of SEQ ID NO: 6 6 including the amino acid sequence from amino acid 97 to amino acid 106).   In one specific example, The present invention An isolation port selected from the group consisting of: Provide a composition comprising a renucleotide:   (A) SEQ ID NO: A polynucleotide comprising the nucleotide sequence of SEQ ID NO: 7;   (B) SEQ ID NO: 7 nucleotides from nucleotide 31 to nucleotide 1230 A polynucleotide comprising a reotide sequence;   (C) SEQ ID NO: The nucleotides from nucleotide 289 to nucleotide 1230 of 7 A polynucleotide comprising a nucleotide sequence;   (D) SEQ ID NO: The nucleotides from nucleotide 344 of nucleotide 7 to nucleotide 1119 A polynucleotide comprising a nucleotide sequence;   (E) Clone er471 7 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of   (F) Clone er471 7 deposited under accession number ATCC 98468 Polynucleotide encoding the full-length protein encoded by the cDNA insert of Otide;   (G) Clone er471 7 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of   (H) clone er471 7 deposited under accession number ATCC 98468 Encoding a mature protein encoded by a cDNA insert Otide;   (I) SEQ ID NO: Polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 8 Tide;   (J) SEQ ID NO: having biological activity: 8 amino acid sequence fragments A polynucleotide encoding the protein (the fragment is SEQ ID NO: 8 of 8 Contiguous amino acids);   (K) a polynucleotide that is an allelic variant of the polynucleotide of (a) to (h) above Nucleotides;   (L) A polynucleotide encoding a species homolog of the protein of (i) or (j) above Otide; and   (M) any one of the polynucleotides (a) to (j) under strict conditions A polynucleotide capable of hybridizing to   Preferably, Such a polynucleotide is SEQ ID NO: Is nucleotide 31 of 7 A nucleotide sequence from to nucleotide 1230; SEQ ID NO: 7 nucleotides A nucleotide sequence from 289 to nucleotide 1230; SEQ ID NO: 7 Nuku A nucleotide sequence from leotide 344 to nucleotide 1119; Accession number A Full length protein codey of clone er4717 deposited as TCC98468 Nucleotide sequence of the signaling sequence; Or deposited under accession number ATCC 98468. The nucleotide sequence of the mature protein coding sequence of clone er471 7 Including. In another preferred embodiment, The polynucleotide is Accession number ATCC9 With the cDNA insert of clone er4717 deposited as 8468 Encodes the encoded full-length or mature protein. In yet another preferred embodiment And The present invention SEQ ID NO: 8 amino acids 111 to 363 A polynucleotide encoding a protein comprising a amino acid sequence is provided. Yet another In a preferred embodiment, SEQ ID NO: with biological activity 8 of the amino acid sequence A polynucleotide encoding a protein containing the fragment (the fragment SEQ ID NO: 8, Preferably eight, More preferably 20, Most preferably 30 Contiguous amino acids), Alternatively, SEQ ID NO: having biological activity 8 of A polynucleotide encoding a protein containing a fragment of the amino acid sequence Segment is SEQ ID NO: Amino acid sequence from amino acid 195 to amino acid 204 Including columns).   Another specific example is SEQ ID NO: 7 corresponding to the cDNA sequence.   In another embodiment, The present invention A composition comprising a protein, The protein is   (A) SEQ ID NO: The amino acid sequence of 8;   (B) SEQ ID NO: 8 amino acid sequences from amino acid 111 to amino acid 363;   (C) SEQ ID NO: Comprising eight consecutive amino acids of eight, SEQ ID NO: 8 amino Fragments of an acid sequence; and   (D) Clone er471 7 deposited under accession number ATCC 98468 Amino acid sequence encoded by the cDNA insert of Comprising an amino acid sequence selected from the group consisting of: Other mammalian proteins A composition is provided that is substantially free. Preferably, Such proteins are Distribution Column index: Amino acid sequence of SEQ ID NO: 8 or SEQ ID NO: 8 amino acids 111 to 3 Includes up to 63 amino acid sequences. In a further preferred embodiment, The present invention SEQ ID NO: with biological activity A protein containing a fragment of the amino acid sequence of The fragment is SEQ ID NO: 8, Preferably eight, More preferably 20, most Preferably containing 30 consecutive amino acids), Or have biological activity SEQ ID NO: A protein comprising a fragment of the amino acid sequence of number: 8 (including the amino acid sequence from amino acid 195 to amino acid 204). Offer.   In one specific example, The present invention An isolation port selected from the group consisting of: Provide a composition comprising a renucleotide:   (A) SEQ ID NO: A polynucleotide comprising the nucleotide sequence of 9;   (B) SEQ ID NO: A nucleotide from nucleotide 62 to nucleotide 322 of nucleotide 9 A polynucleotide comprising an otide sequence;   (C) SEQ ID NO: A nucleotide from nucleotide 571 to nucleotide 878 of nucleotide 9 A polynucleotide comprising a reotide sequence;   (D) of clone fs403 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence;   (E) of clone fs403 deposited under accession number ATCC 98468 Polynucleotide encoding full-length protein encoded by cDNA insert Tide;   (F) of clone fs403 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence;   (G) of clone fs403 deposited under accession number ATCC 98468 Polynucleotide encoding mature protein encoded by cDNA insert Tide;   (H) SEQ ID NO: Polynucleotide encoding a protein containing 10 amino acid sequences Otide;   (I) SEQ ID NO: having biological activity: Fragments of 10 amino acid sequences A polynucleotide encoding the protein comprising the fragment (the fragment is SEQ ID NO: 10 Of 8 amino acids);   (J) Polynucleic acid which is an allelic variant of the polynucleotide of (a) to (g) above Nucleotides;   (K) a polynucleotide encoding a species homolog of the protein of (h) or (i) above Otide; and   (L) any one of the polynucleotides (a) to (i) under strict conditions A polynucleotide capable of hybridizing to   Preferably, Such a polynucleotide is SEQ ID NO: Nucleotide 62 at 9 A nucleotide sequence from to nucleotide 322; SEQ ID NO: Nucleotide 5 of 9 A nucleotide sequence from 71 to nucleotide 878; Accession number ATCC 984 No. 68 of the full length protein coding sequence of clone fs403 deposited as No. 68 Leotide sequence; Or clone f deposited under accession number ATCC 98468 s403 contains the nucleotide sequence of the mature protein coding sequence. Other favors In a specific example, The polynucleotide is Deposit No. ATCC 98468 Up to the full length encoded by the cDNA insert of the deposited clone fs403. Or a mature protein. In a further preferred embodiment, The present invention Creature SEQ ID NO: with biological activity A protein containing 10 amino acid sequence fragments Encoding polynucleotide (the fragment is SEQ ID NO: Ten of Preferably Are eight, More preferably 20, Most preferably contains 30 consecutive amino acids. Mu), Alternatively, SEQ ID NO: having biological activity Fragment of 10 amino acid sequences A polynucleotide encoding a protein containing the fragment (the fragment is SEQ ID NO: 1 0 amino acid 38 to amino acid 47).   Another specific example is SEQ ID NO: Genes corresponding to 9 cDNA sequences are provided.   In another embodiment, The present invention A composition comprising a protein, The protein is   (A) SEQ ID NO: 10 amino acid sequences;   (B) SEQ ID NO: Comprising 10 eight consecutive amino acids SEQ ID NO: Ten of a Fragments of the amino acid sequence; and   (C) of clone fs403 deposited under accession number ATCC 98468 Amino acid sequence encoded by cDNA insert Comprising an amino acid sequence selected from the group consisting of: Other mammalian proteins A composition is provided that is substantially free. Preferably, Such proteins are Distribution Column index: Contains 10 amino acid sequences. In a further preferred embodiment, The present invention Is SEQ ID NO: with biological activity Contains fragments of 10 amino acid sequences Protein (the fragment is SEQ ID NO: Ten of Preferably eight, More preferably 2 0, Most preferably contains 30 consecutive amino acids), Or biological activity SEQ ID NO: A protein containing a fragment of 10 amino acid sequences (the flag Mention is SEQ ID NO: Amino acid sequence from amino acid 38 to amino acid 47 of 10 Including).   In one specific example, The present invention An isolation port selected from the group consisting of: Provide a composition comprising a renucleotide:   (A) SEQ ID NO: A polynucleotide comprising 11 nucleotide sequences;   (B) SEQ ID NO: 11 nucleotides 43 to 1671 A polynucleotide comprising a nucleotide sequence;   (C) SEQ ID NO: 11 nucleotides 112 to 1671 A polynucleotide comprising a nucleotide sequence;   (D) SEQ ID NO: 11 nucleotides from nucleotide 224 to nucleotide 679 A polynucleotide comprising a nucleotide sequence;   (E) of clone ga636 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence;   (F) of clone ga636 deposited under accession number ATCC 98468; Polynucleotide encoding full-length protein encoded by cDNA insert Tide;   (G) of clone ga636 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence;   (H) of clone ga636 deposited under accession number ATCC 98468; Polynucleotide encoding mature protein encoded by cDNA insert Tide;   (I) SEQ ID NO: Polynucleotide encoding a protein containing 12 amino acid sequences Otide;   (J) SEQ ID NO: having biological activity: 12 amino acid sequence fragments A polynucleotide encoding the protein comprising the fragment (the fragment is SEQ ID NO: 12 8 contiguous amino acids);   (K) a polynucleotide that is an allelic variant of the polynucleotide of (a) to (h) above Nucleotides;   (L) A polynucleotide encoding a species homolog of the protein of (i) or (j) above Otide; and   (M) any one of the polynucleotides (a) to (j) under strict conditions A polynucleotide capable of hybridizing to   Preferably, Such a polynucleotide is SEQ ID NO: 11 nucleotides 43 A nucleotide sequence from to nucleotide 1671; SEQ ID NO: 11 nucleos A nucleotide sequence from nucleotide 112 to nucleotide 1671; SEQ ID NO: 11 A nucleotide sequence from nucleotide 224 to nucleotide 679 of; Trust number No. ATCC 98468, full length protein code for clone ga636 The nucleotide sequence of the signaling sequence; Or deposited under accession number ATCC 98468 The nucleotide sequence of the mature protein coding sequence of clone ga636 was cloned. Including. In another preferred embodiment, The polynucleotide is Accession number ATCC9 The cDNA insert of clone ga636 deposited as 8468 Encodes the full-length or mature protein to be loaded. Still other preferred In a specific example, The present invention SEQ ID NO: 12 amino acids 62 to 212 A polynucleotide encoding a protein comprising the amino acid sequence of Further In some preferred embodiments, The present invention SEQ ID NO: with biological activity 12 Polynucleotide encoding a protein comprising a fragment of the amino acid sequence of The fragment has SEQ ID NO: 12 of Preferably eight, More preferably 20, Most preferably contains 30 consecutive amino acids), Or have biological activity SEQ ID NO: Polypeptide encoding a protein containing fragments of 12 amino acid sequences Nucleotides (the fragment is SEQ ID NO: 12 amino acids from 266 to amino acids 275 amino acid sequences).   Another specific example is SEQ ID NO: Genes corresponding to 11 cDNA sequences are provided.   In another embodiment, The present invention A composition comprising a protein, The protein is   (A) SEQ ID NO: 12 amino acid sequences;   (B) SEQ ID NO: 12 amino acid sequences from amino acid 62 to amino acid 212;   (C) SEQ ID NO: Comprising 12 eight consecutive amino acids, SEQ ID NO: 12 a Fragments of the amino acid sequence; and   (D) of clone ga636 deposited under accession number ATCC 98468 Amino acid sequence encoded by cDNA insert Comprising an amino acid sequence selected from the group consisting of: Other mammalian proteins A composition is provided that is substantially free. Preferably, Such proteins are Distribution Column index: 12 amino acid sequences or SEQ ID NO: 12 amino acids to 62 amino acids Includes up to 212 amino acid sequences. In a further preferred embodiment, The present invention , SEQ ID NO: with biological activity A protein containing a fragment of the 12 amino acid sequence White (the fragment is SEQ ID NO: 12 of Preferably eight, More preferably 20 Pieces, Most preferably contains 30 consecutive amino acids), Or biological activity SEQ ID NO: having A protein containing a fragment of the 12 amino acid sequence (the fragment Is the sequence number: Amino acid sequence from 12 amino acids 266 to 275 Including).   In one specific example, The present invention An isolation port selected from the group consisting of: Provide a composition comprising a renucleotide:   (A) SEQ ID NO: A polynucleotide comprising the nucleotide sequence of 13;   (B) SEQ ID NO: Nuku from nucleotide 17 to nucleotide 523 of 13 A polynucleotide comprising a reotide sequence;   (C) SEQ ID NO: Nuku from nucleotide 77 to nucleotide 523 of 13 A polynucleotide comprising a reotide sequence;   (D) SEQ ID NO: 13 nucleotides from nucleotide 1 to nucleotide 392 A polynucleotide comprising an otide sequence;   (E) clone gm3354 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of   (F) Clone gm3354 deposited under accession number ATCC 98468 Polynucleotide encoding the full-length protein encoded by the cDNA insert of Otide;   (G) Clone gm3354 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of   (H) clone gm3354 deposited under accession number ATCC 98468 Encoding a mature protein encoded by a cDNA insert Otide;   (I) SEQ ID NO: Polynucleotide encoding a protein containing 14 amino acid sequences Otide;   (J) SEQ ID NO: having biological activity: Fragment of 14 amino acid sequence A polynucleotide encoding the protein comprising the fragment (the fragment is SEQ ID NO: 14 8 contiguous amino acids);   (K) a polynucleotide that is an allelic variant of the polynucleotide of (a) to (h) above Nucleotides;   (L) A polynucleotide encoding a species homolog of the protein of (i) or (j) above Otide; and   (M) any one of the polynucleotides (a) to (j) under strict conditions A polynucleotide capable of hybridizing to   Preferably, Such a polynucleotide is SEQ ID NO: 13 nucleotides 17 A nucleotide sequence from to nucleotide 523; SEQ ID NO: 13 nucleoti Nucleotide sequence from nucleotide 77 to nucleotide 523; SEQ ID NO: 13 Nuku A nucleotide sequence from Reotide 1 to nucleotide 392; Accession number ATCC Full length protein coding sequence of clone gm3354 deposited as 98468 Sequence nucleotide sequence; Or the deposit deposited under accession number ATCC 98468. Contains the nucleotide sequence of the mature protein coding sequence of lawn gm3354. In another preferred embodiment, The polynucleotide is Accession number ATCC 9846 Coded by cDNA insert of clone gm3354 deposited as No. 8 Encodes the full-length or mature protein to be produced. In a further preferred embodiment, Book The invention is SEQ ID NO: The amino acid sequence from amino acid 1 to amino acid 125 of 14 A polynucleotide encoding the protein. In a further preferred embodiment And The present invention SEQ ID NO: with biological activity 14 amino acid sequence Polynucleotide encoding the protein containing the fragment (the fragment has the sequence number: 14 of Preferably eight, More preferably 20, Most preferably 30 Of consecutive amino acids), Alternatively, SEQ ID NO: having biological activity 14 of A polynucleotide encoding a protein containing a fragment of the amino acid sequence (the fragment Segment is SEQ ID NO: Amino acid sequence from amino acid 79 to amino acid 88 of 14 Including).   Another specific example is SEQ ID NO: Genes corresponding to 13 cDNA sequences are provided.   In another embodiment, The present invention A composition comprising a protein, The protein is   (A) SEQ ID NO: 14 amino acid sequences;   (B) SEQ ID NO: An amino acid sequence of 14 amino acids 1 to 125;   (C) SEQ ID NO: Comprising 14 eight consecutive amino acids, SEQ ID NO: 14 a Fragments of the amino acid sequence; and   (D) Clone gm3354 deposited under accession number ATCC 98468 Amino acid sequence encoded by the cDNA insert of Comprising an amino acid sequence selected from the group consisting of: Other mammalian proteins A composition is provided that is substantially free. Preferably, Such proteins are Distribution Column index: 14 amino acid sequence or SEQ ID NO: 14 amino acids 1 to 1 Includes up to 25 amino acid sequences. In a further preferred embodiment, The present invention SEQ ID NO: with biological activity Protein containing a fragment of 14 amino acid sequences (The fragment has SEQ ID NO: 14 of Preferably eight, More preferably 20 , Most preferably contains 30 consecutive amino acids), Or biological activity SEQ ID NO: Protein containing a fragment of the amino acid sequence of 14 (the fragment Is the sequence number: Includes amino acid sequence from 14 amino acids 79 to 88 )I will provide a.   In one specific example, The present invention An isolation port selected from the group consisting of: Provide a composition comprising a renucleotide:   (A) SEQ ID NO: A polynucleotide comprising 15 nucleotide sequences;   (B) SEQ ID NO: 15 nucleotides from nucleotide 2 to nucleotide 991 A polynucleotide comprising an otide sequence;   (C) SEQ ID NO: A nucleotide from 15 nucleotides 62 to 991 A polynucleotide comprising a reotide sequence;   (D) SEQ ID NO: 15 nucleotides from nucleotide 2 to nucleotide 504 A polynucleotide comprising an otide sequence;   (E) Clone hy370 9 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of   (F) Clone hy370 9 deposited under accession number ATCC 98468 Polynucleotide encoding the full-length protein encoded by the cDNA insert of Otide;   (G) Clone hy370 9 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of   (H) clone hy370 9 deposited under accession number ATCC 98468 Encoding a mature protein encoded by a cDNA insert Otide;   (I) SEQ ID NO: Polynucleotide encoding a protein containing 16 amino acid sequences Otide;   (J) SEQ ID NO: having biological activity: Fragment of 16 amino acid sequence A polynucleotide encoding the protein comprising the fragment (the fragment is SEQ ID NO: 16 8 contiguous amino acids);   (K) a polynucleotide that is an allelic variant of the polynucleotide of (a) to (h) above Nucleotides;   (L) A polynucleotide encoding a species homolog of the protein of (i) or (j) above Otide; and   (M) any one of the polynucleotides (a) to (j) under strict conditions A polynucleotide capable of hybridizing to   Preferably, Such a polynucleotide is SEQ ID NO: 15 nucleotides 2 A nucleotide sequence from to nucleotide 991; SEQ ID NO: 15 nucleotides A nucleotide sequence from 62 to nucleotide 991; SEQ ID NO: 15 Nucles A nucleotide sequence from Otide 2 to nucleotide 504; Accession number ATCC9 Full length protein coding sequence of clone hy3709 deposited as 8468 A nucleotide sequence of Or a black deposit deposited under accession number ATCC 98468. And the nucleotide sequence of the mature protein coding sequence of hy3709. other In a preferred embodiment of The polynucleotide is Accession number ATCC 98468 Encoded by the cDNA insert of clone hy3709 deposited as Encodes the full-length or mature protein to be derived. In still other preferred embodiments, The present invention SEQ ID NO: Amino acid sequence from 16 amino acids 1 to 167 And a polynucleotide encoding a protein comprising: Further preferred embodiments At The present invention SEQ ID NO: with biological activity Of the 16 amino acid sequence A polynucleotide encoding a fragment-containing protein (the fragment Column index: 16 of Preferably eight, More preferably 20, Most preferably 30 Contiguous amino acids), Or have biological activity SEQ ID NO: Polynucleic acid encoding a protein containing a fragment of 16 amino acid sequences Nucleotides (the fragment is SEQ ID NO: 16 amino acids 160 to amino acids 1 Up to 69 amino acid sequences).   Another specific example is SEQ ID NO: Genes corresponding to the 15 cDNA sequences are provided.   In another embodiment, The present invention A composition comprising a protein, The protein is   (A) SEQ ID NO: 16 amino acid sequences;   (B) SEQ ID NO: An amino acid sequence of 16 amino acids 1 to 167;   (C) SEQ ID NO: Comprising 16 eight consecutive amino acids, SEQ ID NO: 16 a Fragments of the amino acid sequence; and   (D) Clone hy370 9 deposited under accession number ATCC 98468 Amino acid sequence encoded by the cDNA insert of Comprising an amino acid sequence selected from the group consisting of: Other mammalian proteins A composition is provided that is substantially free. Preferably, Such proteins have the sequence number: 16 amino acid sequences or SEQ ID NO: 16 amino acids 1 to 16 Includes up to 7 amino acid sequences. In a further preferred embodiment, The present invention Raw SEQ ID NO: with physical activity: Protein containing a fragment of 16 amino acid sequences ( The fragment has SEQ ID NO: 16 of Preferably eight, More preferably 20, Most preferably contains 30 consecutive amino acids), Or have biological activity SEQ ID NO: A protein comprising a fragment of 16 amino acid sequences (the fragment Is the sequence number: Includes the amino acid sequence from amino acid 160 to amino acid 169 ).   In one specific example, The present invention An isolation port selected from the group consisting of: Provide a composition comprising a renucleotide:   (A) SEQ ID NO: A polynucleotide comprising the nucleotide sequence of 17;   (B) SEQ ID NO: Nuku from nucleotide 77 to nucleotide 616 of 17 A polynucleotide comprising a reotide sequence;   (C) SEQ ID NO: The nucleotides from nucleotide 164 to nucleotide 616 of 17 A polynucleotide comprising a nucleotide sequence;   (D) SEQ ID NO: 17 nucleotides from nucleotide 1 to nucleotide 415 A polynucleotide comprising an otide sequence;   (E) of clone ie474 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence;   (F) of clone ie474 deposited under accession number ATCC 98468; Polynucleotide encoding full-length protein encoded by cDNA insert Tide;   (G) of clone ie474 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence;   (H) of clone ie474 deposited under accession number ATCC 98468; Polynucleotide encoding mature protein encoded by cDNA insert Tide;   (I) SEQ ID NO: Polynucleotide encoding a protein containing 18 amino acid sequences Otide;   (J) SEQ ID NO: having biological activity: Fragment of 18 amino acid sequence A polynucleotide encoding the protein comprising the fragment (the fragment is SEQ ID NO: 18 8 contiguous amino acids);   (K) a polynucleotide that is an allelic variant of the polynucleotide of (a) to (h) above Nucleotides;   (L) A polynucleotide encoding a species homolog of the protein of (i) or (j) above Otide; and   (M) any one of the polynucleotides (a) to (j) under strict conditions A polynucleotide capable of hybridizing to   Preferably, Such a polynucleotide is SEQ ID NO: 17 nucleotides 77 A nucleotide sequence from to nucleotide 616; SEQ ID NO: 17 nucleoti A nucleotide sequence from nucleotide 164 to nucleotide 616; SEQ ID NO: 17 Nu A nucleotide sequence from nucleotide 1 to nucleotide 415; Accession number ATC Full length protein codey of clone ie474 deposited as C98468 Nucleotide sequence of the signaling sequence; Or deposited under accession number ATCC 98468. Containing the nucleotide sequence of the mature protein coding sequence of clone IE474. No. In another preferred embodiment, The polynucleotide is Accession number ATCC98 468 deposited with the cDNA insert of clone ie474. Encodes the full-length or mature protein to be encoded. In still other preferred embodiments hand, The present invention SEQ ID NO: 18 amino acids 1 to 113 A polynucleotide encoding a protein comprising the sequence is provided. Further preferred equipment In the example, The present invention SEQ ID NO: with biological activity 18 amino acid sequences A polynucleotide encoding a protein comprising a fragment of Is the sequence number: 18 of Preferably eight, More preferably 20, Most preferably Containing 30 consecutive amino acids), Alternatively, SEQ ID NO: having biological activity A polynucleotide encoding a protein comprising a fragment of 18 amino acid sequences ( The fragment has SEQ ID NO: Amino acids from amino acid 85 to amino acid 94 of 18 Including an acid sequence).   Another specific example is SEQ ID NO: The gene corresponding to the 17 cDNA sequences is provided.   In another embodiment, The present invention A composition comprising a protein, The protein is   (A) SEQ ID NO: 18 amino acid sequences;   (B) SEQ ID NO: An amino acid sequence of 18 amino acids 1 to 113;   (C) SEQ ID NO: Comprising 18 eight consecutive amino acids SEQ ID NO: 18 a Fragments of the amino acid sequence; and   (D) of clone ie474 deposited under accession number ATCC 98468; Amino acid sequence encoded by cDNA insert Comprising an amino acid sequence selected from the group consisting of: Other mammalian proteins A composition is provided that is substantially free. Preferably, Such proteins are Distribution Column index: 18 amino acid sequence or SEQ ID NO: 18 amino acids 1 to 1 Includes up to 13 amino acid sequences. In a further preferred embodiment, The present invention SEQ ID NO: with biological activity Protein containing a fragment of 18 amino acid sequences (The fragment has SEQ ID NO: 18 of Preferably eight, More preferably 20 pieces, Most preferably contains 30 consecutive amino acids), Or biological SEQ ID NO: A protein containing a fragment of the amino acid sequence of Segment is SEQ ID NO: Amino acid sequence from 18 amino acids 85 to 94 Including).   In one specific example, The present invention An isolation port selected from the group consisting of: Provide a composition comprising a renucleotide:   (A) SEQ ID NO: A polynucleotide comprising the nucleotide sequence of 19;   (B) SEQ ID NO: 19 nucleotides 564 to 2813 A polynucleotide comprising a nucleotide sequence;   (C) SEQ ID NO: 19 nucleotides 705 to 2813 A polynucleotide comprising a nucleotide sequence;   (D) SEQ ID NO: 19 nucleotides 793 to 1628 A polynucleotide comprising a nucleotide sequence;   (E) clone s195 10 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of   (F) Clone s195 10 deposited under accession number ATCC 98468 Polynucleotide encoding the full-length protein encoded by the cDNA insert of Otide;   (G) Clone s195 10 deposited under accession number @ TCC98468 A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of   (H) clone s195 10 deposited under accession number ATCC 98468 Encoding a mature protein encoded by a cDNA insert Otide;   (I) SEQ ID NO: Polynucleotide encoding a protein containing 20 amino acid sequences Otide;   (J) SEQ ID NO: having biological activity: Fragments of 20 amino acid sequences A polynucleotide encoding the protein comprising the fragment (the fragment is SEQ ID NO: 20 8 contiguous amino acids);   (K) a polynucleotide that is an allelic variant of the polynucleotide of (a) to (h) above Nucleotides;   (L) A polynucleotide encoding a species homolog of the protein of (i) or (j) above Otide; and   (M) any one of the polynucleotides (a) to (j) under strict conditions A polynucleotide capable of hybridizing to   Preferably, Such a polynucleotide is SEQ ID NO: 19 nucleotides 56 A nucleotide sequence from 4 to nucleotide 2813; SEQ ID NO: Nuke of 19 A nucleotide sequence from Otide 705 to nucleotide 2813; SEQ ID NO: 1 A nucleotide sequence from nucleotide 793 to nucleotide 1628 of 9; Receiving Full length protein of clone s19510 deposited under accession number ATCC 98468 Nucleotide sequence of coding sequence: Or accession number ATCC 98468 Of the mature protein coding sequence of clone s19510 deposited by Includes code array. In another preferred embodiment, The polynucleotide is Accession number A CDNA insert of clone s19510 deposited as TCC98468 Encodes the full-length or mature protein encoded by the protein. Still other preferred In a specific example, The present invention SEQ ID NO: 20 amino acids 78 to 355 A polynucleotide encoding a protein comprising the amino acid sequence of Further In some preferred embodiments, The present invention SEQ ID NO: with biological activity 20 Polynucleotide encoding a protein comprising a fragment of the amino acid sequence of The fragment has SEQ ID NO: 20 of Preferably eight, More preferably 20, Most preferably contains 30 consecutive amino acids), Or have biological activity SEQ ID NO: Polycoding protein containing a fragment of 20 amino acid sequences Nucleotides (the fragment is SEQ ID NO: 20 amino acids from 370 to amino acids Up to 379 amino acid sequences).   Another specific example is SEQ ID NO: The gene corresponding to the 19 cDNA sequences is provided.   In another embodiment, The present invention A composition comprising a protein, The protein is   (A) SEQ ID NO: 20 amino acid sequences;   (B) SEQ ID NO: An amino acid sequence of 20 amino acids 78 to 355;   (C) SEQ ID NO: Comprising 20 eight consecutive amino acids, SEQ ID NO: 20 a Fragments of the amino acid sequence; and   (D) Clone s195 10 deposited under accession number ATCC 98468 Amino acid sequence encoded by the cDNA insert of Comprising an amino acid sequence selected from the group consisting of: Other mammalian proteins A composition is provided that is substantially free. Preferably, Such proteins have the sequence number: 20 amino acid sequences or SEQ ID NO: Amino acid 78 of the amino acid sequence of 20 From 355 to 355 amino acids. In a further preferred embodiment hand, The present invention SEQ ID NO: with biological activity Fragment of 20 amino acid sequences Protein (the fragment is SEQ ID NO: 20 of Preferably eight, Better Preferably 20 Most preferably contains 30 consecutive amino acids), Or SEQ ID NO: with biological activity Protein containing fragments of 20 amino acid sequences (The fragment has SEQ ID NO: 20 amino acids 370 to 379 Including an amino acid sequence).   In certain preferred embodiments, Polynucleotide can act on expression control sequences Linked to Noh. The present invention also provides Transformed with such a polynucleotide composition Was Bacteria, yeast, Host cells are provided, including insect and mammalian cells. Also , Of the gene corresponding to the polynucleotide sequence disclosed herein, Promotion, Decline, Also Is provided by the present invention for organisms having modified expression.   further, A method for producing a protein,   (A) culturing a host cell culture transformed with such a polynucleotide composition; Grown in the appropriate medium; Incidentally   (B) purifying the protein from the culture There is also provided a method comprising: Proteins produced by such methods are also Departure It is provided by Ming. As a preferred specific example, Manufactured by such a method And the protein to be produced is a mature form of the protein.   The protein composition of the present invention, It may further contain a pharmaceutically acceptable carrier. Or A composition comprising an antibody that specifically reacts with the protein, Provided by the present invention.   Administering a therapeutically effective amount of a composition comprising a protein of the invention and a pharmaceutically acceptable carrier. Administering to an animal subject, Prevention of medical conditions, For treatment or improvement A law is also provided.BRIEF DESCRIPTION OF THE FIGURES   1A and 1B show pED6 and pED6 used for depositing the clones disclosed herein. And pNOTs vectors are shown schematically.                                Detailed description Isolated proteins and polynucleotides   Nucleotides for each of the clones and proteins disclosed herein And amino acid sequences are reported below. Sequencing of the deposited clone by a known method To easily determine the actual nucleotide sequence of each clone Can be. The deduced amino acid sequence (both full length and mature) is then It can be determined from the leotide sequence. Express the clone in a suitable host cell. And collect the protein, then determine its sequence to determine The amino acid sequence of the encoded protein can also be determined. Each disclosed For proteins, applicants best identify using sequence information available at the time of filing Those determined to be possible reading frames were identified.   As used herein, the term "secreted" protein refers to a membrane when expressed in a suitable host cell. Refers to those that are transported through, and the result of the signal sequence in that amino acid sequence Transportation is also included. "Secreted" proteins are secreted entirely by the cells in which they are expressed. Proteins (eg, soluble proteins) or partially secreted proteins (eg, receptors) ), But not limited thereto. Also, "secreted" proteins pass through the membrane of the endoplasmic reticulum Including but not limited to those transported byClone "do154"   The polynucleotide of the present invention has been identified as clone "do154". do 154 describes a method selective for cDNA encoding a secreted protein (US Pat. 536637)) from an adult testis cDNA library. Or secretion based on computer analysis of the amino acid sequence of the encoded protein. It was identified as encoding a protein or transmembrane protein. do154 is full length black And all of the secreted proteins (also referred to herein as "do154 proteins"). Contains the coding sequence.   The nucleotide sequence of do154 determined this time is shown in SEQ ID NO: 1. this time Applicant has determined that the correct reading frame and do154 protein for do154 And those considered to be deduced amino acid sequences are shown in SEQ ID NO: 2. Amino acid 39 4 to 406 are putative leader / signal sequences and putative mature amino acid sequences Starts at amino acid 407 or transmembrane from amino acids 394 to 406 Domain.   EcoRI / Not obtainable from the deposit containing clone do154 The I restriction fragment should be approximately 1900 bp in length.   The nucleotide sequence of do154 disclosed herein can be modified using BLASTN / BLASTX and GenBank and GenSeq nucleotide sequence data using the Searched against the database. do154 is AA113909 (zm80f12.r1 Stratagene  neuroepithelium (# 937231) Homo sapiens cDNA clone 531983 5 '), AA189888 ( mu55h06.r1 Soares mouse 1ymph node NbMLN Mus musculus cDNA clone 643355 5 '), and and U52052 (Human S6 A-8 mRNA expressed in chromosome 6-suppre ssed melanoma cells) Showed sex. Based on sequence similarity, do154 protein and each similar protein or Peptides may share at least some activity.Clone "dx290 1"   The polynucleotide of the present invention has been identified as clone "dx2901". d x2901 is a method selective for cDNA encoding a secreted protein (US No. 5,536,637) from an adult testis cDNA library. Or computer analysis of the amino acid sequence of the encoded protein Encoding a secretory or transmembrane protein. dx290-1 is It is a full-length clone and is a secreted protein (also referred to herein as "dx290_1 protein"). ) Contains the entire coding sequence.   The nucleotide sequence of dx2901 determined this time is shown in SEQ ID NO: 3. now Applicants have determined that the correct reading of the dx290-1 protein corresponding to the above nucleotide sequence The frame and what is considered the deduced amino acid sequence are shown in SEQ ID NO: 4.   EcoRI / No obtainable from the deposit containing clone dx2901 The tI restriction fragment should be approximately 2300 bp in length.   The nucleotide sequence of dx290_1 disclosed herein can be obtained using BLASTA / BLASTX and Against GenBank and GeneSeq databases using FAST and FASTA search protocols And searched. dx2901 is AA064383 (m147h02.r1 Stratagene mouse tes tis (# 937308) to the sequence identified as Mus musculus cDNA clone 515187 5 '). Showed at least some similarity. Based on sequence similarity, dx290   One protein and each similar protein or peptide share at least some activity Could be.Clone "ek390 4"   The polynucleotide of the present invention has been identified as clone ek3904. e k3904 is a method selective for cDNA encoding secreted proteins (US Pat. No. 5,536,637) from a human fetal brain cDNA library. Or computer analysis of the amino acid sequence of the encoded protein Encoding a secretory or transmembrane protein. ek390 4 is It is a full-length clone and is a secreted protein (also referred to herein as "ek3904 protein"). ) Contains the entire coding sequence.   The nucleotide sequence of ek3904 determined this time is shown in SEQ ID NO: 5. now Applicants have read the correct reading of the ek3904 protein corresponding to the above nucleotide sequence. The frame and what is considered the deduced amino acid sequence are shown in SEQ ID NO: 6. 25 amino acids To 37 are putative leader / signal sequences, and the predicted mature amino acid sequence is No. 38, or amino acids 25 to 37 are transmembrane domains. You.   EcoRI / No obtainable from the deposit containing clone ek3904 The tI restriction fragment should be approximately 1000 bp in length.   The nucleotide sequence of ek3904 disclosed herein can be modified using BLASTA / BLASTX and Against GenBank and GeneSeq databases using FAST and FASTA search protocols And searched. ek3904 is AA075783 (zm89h02.r1 Stratagene ovarian c ancer (# 937219) Homo sapiens cDNA clone 545139 5 '), AA427538 (zw32g04.r1 Soares ovary tumor NbHOT Homo sapiens cDNA clone 771030 5 '), AA427539 (zw 32g04.s1 Soares ovary tumor NbHOT Homo sapiens cDNA clone 771030 3 '), AA 453353 (zx47a06.r1 Soares testis NHT Homo sapiens cDNA clone 795346 5 '), C20637 (HUMGS0004639, Human Gene Signature, 3'-directed cDNA sequence), R7 4326 (y101c07.s1 Homo sapiens cDNA clone 156972 3 '), R74420 (y101c07.r1 Ho mo sapiens cDNA clone 156972 5 '), T22914 (Human gene signature), U41197 (H uman [TTTC] 10 short tandem repeat polymorphism UM65, D17S1340), and X58 237 (Human mRNA for anti-lectin antibody epitope (clone p36 / 8-6)) It showed at least some similarity to the defined sequences. Based on sequence similarity In short, the ek3904 protein and each similar protein or peptide are at least to some extent Degree activity may be shared. TopPredII computer program Thus, in the ek3904 protein sequence, the region around amino acid 160 of SEQ ID NO: 6 Potential transmembrane domains are estimated. Nucleotide sequence of ek3904 May contain GGGA repeats.Clone "er471 7"   The polynucleotide of the present invention has been identified as clone er471-7. e r4717 is a method selective for cDNA encoding a secreted protein (US No. 5,536,637) from a human fetal brain cDNA library. Or based on computer analysis of the amino acid sequence of the encoded protein Thus, it was identified as encoding a secretory protein or a transmembrane protein. er471 7 Is a full-length clone and is a secreted protein (also referred to herein as "er471 7 protein"). ) Contains the entire coding sequence.   The nucleotide sequence of er471 7 determined this time is shown in SEQ ID NO: 7. now Applicants have read the correct reading of the er471 7 protein corresponding to the above nucleotide sequence. The frame and what is considered the deduced amino acid sequence are shown in SEQ ID NO: 8. Amino acid 74 86 to 86 are putative leader / signal sequences, and the predicted mature amino acid sequence is Starting from amino acid 87 or amino acids 74 to 86 are transmembrane domains. You.   EcoRI / No obtainable from the deposit containing clone er4717 The tI restriction fragment should be approximately 2250 bp in length.   The nucleotide sequence of er4717 disclosed herein can be modified using BLASTA / BLASTX and Against GenBank and GeneSeq databases using FAST and FASTA search protocols And searched. er471 7 is AA039137 (mi98h06.r1 Soares mouse embryo) NbME13.5 14.5 Mus musculus cDNA clone 474683 5 '), AA066962 (mm38g05.r1 St ratagene mouse melanoma (# 937312) Mus musculus cDNA clone 523832 5 '), AA 189170 (zq47h05.s1 Stratagene hNT neuron (# 937233) Homo sapiens cDNA clone 632889 3 '), AA609188 (af12c1O.s1 Soares testis NHT Homo sapiens cDNA clon e 1031442 3 '), and WO7704 (zb02e02.r1 Soares fetal lung NbHL19W Homo sa piens cDNA clone 300890 5 'similar to SW: YN66_YEAST P40164 HYPOTHETICAL 98.1 KD PROTEIN IN SPX19-GCR2 INTERGENIC REGION) Showed at least some similarity. er471 7 The deduced amino acid sequence shown was compared to GenPept and GeneSeq using the BLASTX search protocol. A search was performed against the amino acid sequence database. The putative er471 7 protein is AF01 6448 (Cosmid F41E6 [Caenorhabditis elegans]) and L08407 (collagen type XVII [ Mus musculus]) show at least some similarity to sequences identified as did. Based on sequence similarity, the er471 7 protein and each similar protein or peptide It may share at least some activity. TopPredII computer According to the program, in the er471 7 protein sequence, amino acid 4 of SEQ ID NO: 8 Three potential transmembrane domains centered around 0, 80, and 110, respectively Is estimated.Clone “fs40 3”   The polynucleotide of the present invention has been identified as clone fs403. fs 403 is a method selective for cDNA encoding a secretory protein (US Pat. 536637)) from an adult testis cDNA library. Or secretion based on computer analysis of the amino acid sequence of the encoded protein. It was identified as encoding a protein or transmembrane protein. fs403 is full length black And the entire code of secreted protein (also referred to herein as "fs403 protein"). Includes a printing array.   The nucleotide sequence of fs403 determined this time is shown in SEQ ID NO: 9. the above Correct reading frame and predicted amino acid of fs403 protein corresponding to nucleotide sequence SEQ ID NO: 10 shows what the applicant considers to be the acid sequence.   EcoRI / Not obtainable from the deposit containing clone fs403 The I restriction fragment should be approximately 1000 bp in length.   The nucleotide sequence of fs403 disclosed herein was used for BLASTA / BLASTX and GenBank and GeneSeq databases using the I searched. fs403 is AA411142 (zt37g01.r1 Soares ovary tumor NbHOT  Homo sapiens cDNA clone 724560 5 '), AA412527 (zu12a03.s1 Soares testis N HT Homo sapiens cDNA clone 731596 3 '), AA565855 (nj32d09.s1 NCI_CGAP_AA1 Homo sapiens cDNA clone IMAGE: 994193), H17042 (ym39f12.s1 Homo sapiens cDN A clone 50584 3 '), and T33280 (EST57284 Homo sapiens cDNA 3' end similar  at least some similarity to sequences identified as . Based on sequence similarity, the fs403 protein and each protein with similarity or Peptide It may share at least some activity. TopPredII computer According to the program, a latent sequence was found at the C-terminal of SEQ ID NO: 10 in the fs403 protein sequence. Putative transmembrane domains are predicted.Clone "ga63 6"   The polynucleotide of the present invention has been identified as clone ga636. ga 636 describes a method that is selective for cDNAs encoding secreted proteins (US Pat. 536637)) from an adult testis cDNA library. Or secretion based on computer analysis of the amino acid sequence of the encoded protein. It was identified as encoding a protein or transmembrane protein. ga 636 is full length black And all the secretory proteins (also referred to herein as "ga636 proteins"). Contains the coding sequence.   The nucleotide sequence of ga636 determined this time is shown in SEQ ID NO: 11. now Applicant has determined that the correct reading frame of the ga636 protein corresponding to the above nucleotide sequence. And what is considered the deduced amino acid sequence is shown in SEQ ID NO: 12. 11 amino acids To 23 are putative leader / signal sequences and the putative mature amino acid sequence is Starting from amino acid 24, or amino acids 11 to 23 are transmembrane domains. You.   EcoRI / Not obtainable from the deposit containing clone ga636 The I restriction fragment should be approximately 2300 bp in length.   The nucleotide sequence of ga636 disclosed herein was modified using BLASTA / BLASTX and GenBank and GeneSeq databases using the I searched. ga636 is AA405433 (zu13h10.r1 Soares testis NHT Homo s apiens cDNA clone 731779 5 'similar to TR G474970 G474970 SP32 PRECURSOR ), AA406076 (zu67c02.s1 Soares testis NHT Homo sapiens cDNA clone 743042 3 'similar to TR: G475021 G475021 SP32 PRECURSOR), AA424694 (zu13h10.s1 So ares testis NHT Homo sapiens cDNA clone 731779 3 'similar to TRG475021 G 475021 SP32 PRECURSOR; contains element TAR1 repetitive element), D16200 ( Pig mRNA for sp32, partial sequence), D16203 (Guinea pig mRNA for sp32, complete cds) , And D17573 (Mouse mRNA for proacrosin-binding protein (sp32), completec It showed at least some similarity to the sequence identified as ds). ga The deduced amino acid sequence disclosed herein as 636 was compared to the BALSTX search protocol. Against the GenPept and GeneSeq amino acid sequence databases . The putative ga636 protein is D16200 (sp32 precursor [Sus scrofa]), and D175 74 (alternative splicing product for proacrosin-binding protein (sp32) [Mus  musculus]) has at least some similarity to the sequence identified as Was. The sp32 protein is found in the sperm acrosome and is involved in egg-sperm fusion in reproduction. Are involved. This protein first has a putative signal peptide at the amino terminus It is synthesized as a 61 kDa precursor protein. Carboxy-terminal half of precursor molecule Corresponds to the mature sp32 protein. Thus, sp32 is involved in post-translational modification of the precursor. Generated. Binding of sp32 to proacrosin is dependent on the binding of acrosin zymogen. It may be related to packing into the acrosome matrix (Bada, et al., 1994, J.M. Biol. Chem. 269 (13): 10133-10140, described herein by reference. Is considered to have been done). Based on sequence similarity, the ga636 protein and class Similar proteins or peptides may share at least some activity There is a potential.Clone "gm335 4"   The polynucleotide of the present invention has been identified as clone "gm3354". g m3354 is a method selective for cDNAs encoding secreted proteins (US Pat. No. 5,536,637) from an adult uterine cDNA library. Or based on computer analysis of the amino acid sequence of the encoded protein, It was identified as encoding a secreted or transmembrane protein. gm335 4 is all Long clone, secreted protein (also referred to herein as "gm3354 protein") Contains the entire coding sequence.   The nucleotide sequence of gm3354 determined this time is shown in SEQ ID NO: 13. The applicant has now read the gm3354 protein corresponding to the above nucleotide sequence correctly. The sequence considered as the open frame and deduced amino acid sequence is shown in SEQ ID NO: 14. Amino acid 8 To 20 are deduced leader / signal sequences and the deduced amino acid sequence is amino acid Starting from acid 21 or amino acids 8 to 20 are transmembrane domains.   EcoRI / No obtainable from the deposit containing clone gm3354 The tI restriction fragment should be approximately 800 bp in length.   The nucleotide sequence of gm3354 disclosed herein can be modified using BLASTA / BLASTX and Against GenBank and GeneSeq databases using FAST and FASTA search protocols And searched. gm3354 is AA055367 (zf20b05.r1 Soares fetal heart N bHH19W Homo sapiens cDNA clone 377457 5 '), AC002389 (Human DNA from chromosome osome 19 specific cosmid R28461, genomic sequence, complete sequence), W O8522 (mb46h10.r1 Soares mouse p3NMF 19.5 Mus musculus cDNA clone 332515 5 '), and X93916 (S. scrofa mRNA (clone VIB11; expressed sequence tag)) Showed at least some similarity to the identified sequences. Sequence similarity Based on this, the gm3354 protein and each protein or peptide with similarity are low. They may share at least some activity.Clone "hy370 9"   The polynucleotide of the present invention has been identified as clone "hy3709". h y3709 is a method selective for cDNA encoding a secreted protein (US Pat. No. 5,536,637). Or based on computer analysis of the amino acid sequence of the encoded protein, It was identified as encoding a secreted or transmembrane protein. hy370 9 is all Long clone and secreted protein (also referred to herein as "hy3709 protein") Contains the entire coding sequence.   The nucleotide sequence of hy3709 determined this time is shown in SEQ ID NO: 15. The applicant has now read the correct hy3709 protein corresponding to the above nucleotide sequence. The open frame and deduced amino acid sequence are shown in SEQ ID NO: 16. Amino acids 8 to 20 Is the predicted leader / signal sequence, and the deduced amino acid sequence starts at amino acid 21. Beginning or alternatively, amino acids 8 to 20 are transmembrane domains.   EcoRI / No obtainable from the deposit containing clone hy3709 The tI restriction fragment should be approximately 1200 bp long.   The nucleotide sequence of hy3709 disclosed herein can be modified using BLASTA / BLASTX and Against GenBank and GeneSeq databases using FAST and FASTA search protocols And searched. hy3709 is AA763313 (vv89h07.r1 Stratagene mouse ski n (# 937313) Mus musculus cDNA clone 1229629 5 ') Showed at least some similarity. Based on sequence similarity, hy370 9 proteins and each similar protein or peptide have at least some activity May be shared. According to the TopPredII computer program, h In the y3709 protein sequence, a latent region centered around amino acid 140 of SEQ ID NO: 16 Putative transmembrane domains are predicted.Clone "ie47 4"   The polynucleotide of the present invention has been identified as clone ie474. ie 474 describes a method selective for cDNA encoding a secreted protein (US Pat. No. 5,366,637) from a human fetal brain cDNA library; Alternatively, based on computer analysis of the amino acid sequence of the encoded protein, It was identified as encoding a secretory or transmembrane protein. ie474 is full length Loan, which contains all of the secreted proteins (also referred to herein as "ie474 proteins"). Contains the coding sequence.   The nucleotide sequence of ie474 determined this time is shown in SEQ ID NO: 17. now Applicants have determined that the correct reading frame of the ie474 protein corresponding to the above nucleotide sequence. And those considered to be deduced amino acid sequences are shown in SEQ ID NO: 18. amino acid 17 to 29 are putative leader / signal sequences and putative mature amino acid sequences Starts at amino acid 30. Alternatively, amino acids 17 to 29 are transmembrane Inn.   EcoRI / Not obtainable from the deposit containing clone ie474 The I restriction fragment should be approximately 2300 bp in length.   The nucleotide sequence of ie474 disclosed herein can be compared with the BLASTX search protocol. Against the GenPept and GeneSeq amino acid sequence databases . Estimated ie474 is AA071953 (mf17h08.r1 Life Tech mouse brain Mus musc ulus cDNA clone 405375 5 'similar to TR G304421 G304421 SILENCER ELEMENT ), AA207250 (zq82d05.s1 Stratagene hNT neuron (# 937233) Homo sapiens cDNA c lone 648105 3 'similar to TR G304421 G304421 SILENCER ELEMENT), L14938 (C hicken SCG10 protein mRNA, complete cds), L20260 (Mouse SCG10 gene sequen ce), R49053 (yg58c05.s1 Homo sapiens cDNA clone 37017 3 '), S82024 (SCG10 n euron-specific growth-associated protein / stathmin homolog [human, embryo, InRNA]), T25428 (Human gene signature HUMGS07594, T25428 standard; cDNA to  mRNA), W54204 (md04a12.r1 Soares mouse embryo NbME13.5 14.5 Mus musculus  cDNA clone 367390 5 'similar to SW: SCGB_XENLA Q09002 SCG10 PROTEIN HOMO LOG A), X71433 (X. laevis SCG10 mRNA), and Z99916 (Human DNA sequence ***  SEQUENCING IN PROGRESS *** from clone 221G9; HTGS phase 1) Showed at least some similarity to the sequence. Honmei as ie47 4 The deduced amino acid sequence disclosed in the specification was compared to GenPep using the BALSTX search protocol. Searches were performed against the t and GeneSeq amino acid sequence databases. Estimated ie47 4 Proteins are L14938 (SCG10 protein [Gallus gallus]) and S82024 (SCG10 neuron-sp ecific growth-associated protein / stathmin homolog [human, embryo, Peptide ] [Homo sapiens]) has at least some similarity to the sequence identified as Indicated. SCG10 protein is found in neuronal growth cones and growing neurons. It is thought to be an existing membrane-bound protein (Maucuer et al., 1993, J. Biol. C hem. 268: 16420-16429; Stein et al., 1988, Neuron 1: 463-476; As described herein). Based on sequence similarity, ie4 The 74 proteins and each similar protein or peptide are at least partially active. May share a gender.Clone "s195 10"   The polynucleotide of the present invention has been identified as clone "s19510". s 19510 describes a method selective for cDNA encoding a secreted protein (US Pat. No. 5,536,637) using an adult neuron tissue cDNA library. Computer analysis of the amino acid sequence of the isolated or encoded protein Based on this, it was identified as encoding a secreted or transmembrane protein. s195 10 is a full-length clone and has a secreted protein (here, "s195 10 Protein)).   The nucleotide sequence of s195 10 determined this time is shown in SEQ ID NO: 19. Applicants have now correctly read the s195 10 protein corresponding to the above nucleotide sequence. The frame and the deduced amino acid sequence are shown in SEQ ID NO: 20. Amino acid 35 To 47 are predicted leader / signal sequences, and the predicted mature amino acid sequence is Starting with amino acid 48. Alternatively, amino acids 35 to 47 are transmembrane domains It is.   EcoRI / No obtainable from the deposit containing clone s19510 The tI restriction fragment should be approximately 3500 bp in length.   The nucleotide sequence of s19510 disclosed herein can be modified using BLASTA / BLASTX and Against GenBank and GeneSeq databases using FAST and FASTA search protocols And searched. s195 10 is AA113800 (zn65b05.s1 Stratagene HeLa cell  s3 937216 Homo sapiens cDNA clone 563025 3 'similar to TR: G600018 G6000 18SSM4P), AA114062 (zn65b05.r1 Stratagene HeLa cell s3 937216 Homo sapiens  cDNA clone 563025 5 '), AA280316 (zt10f06.s1 Soares NbHTGBC Homo sapiens cDNA clone 712739 3 '), AF009301 (Homo sapiens TEB4 protein mRNA, complete  cds), N70344 (za60f10.s1 Homo sapiens cDNA clone 296971 3 '), R60474 (yh13 g07.r1 Homo sapiens cDNA clone 43058 5 '), and T26266 (standard; cDNA to mRNA; 148 BP, Human gene signature HUMGS08505) Showed at least some similarity. disclosed herein as s195-10 Estimated net The amino acid sequence was compared to GenPept and GeneSeq amino acid sequences using the BALSTX search protocol. Searched against the column database. The putative s195 10 protein is AF009301 (TEB4p rotein [Homo sapiens]), X76715 (SSM4 gene product [Saccharomyces cerevisiae ]), Z46861 (Ssm4p [Saccharomyces cerevisiae]), and Z47047 (Ssm4p [Saccharo myces cerevisiae]) to at least some similarity to the sequence identified as showed that. Based on sequence similarity, s195 10 proteins and each with similarity Proteins or peptides may share at least some activity. To According to the pPredII computer program, in the s195 10 protein sequence, No. 20 amino acids 130, 170, 210, 260, 320, 470, 52 0, 560, 600, 650 and 690 Putative transmembrane domains are predicted.   Depositing clones   Clones do154, dx2901, ek3904, er471 7, fs40 3, ga63 6, gm335 4, hy370 9, ie47 4 And s195 10 entered into force on June 19, 1997 under the Budapest Treaty. American Type Culture Collection (10801 University Boulevard, Manassas, Virginia 20110-2209 U.S.A.) with accession number ATCC 98468, From there, the clone is available. All public access to the deposited material The limit is 37C. F. R. Except for the provisions of § 1.808 (b) And the deposit period is 37 C.E. F. R. Will follow § 1.806 .   Each clone is transfected into a separate bacterial cell (E. coli) as this complex deposit. Sfected. EcoRI / NotI digestion (5 'site, EcoRI; 3 'Site, NotI) to obtain an appropriately sized fragment for such a clone. Each clone can be taken from the deposited vector . Each clone was inserted into either the pED6 or pNOTs vector shown in FIG. And deposited. Insert a new polylinker to facilitate cDNA cloning Thus, the pED6dpc2 vector (pED6) is derived from pED6dpc1. Guidance (Kaufman et al. (1991). NAR 19: 4485-4490). DHFR is deleted and new Insertion of the M13 replication origin into the ClaI site. The pNOTs vector was converted to pMT2 (Kaufman et al. 1989. Mol. Cell. Biol. 9: 1). 741-1750). In some cases, the deposited clones are identified as "F Lip "(ie, in the opposite direction). Even in such a case, , EcoRI and NotI digestion can be used to isolate cDNA inserts. Only However, in that case, the cDNA must be in the correct orientation for expression in a suitable vector. NotI creates a 5 'site and EcoRI creates a 3' site to place Will do. Even if cDNA is expressed from the vector where the cDNA is deposited Good.   Obtaining bacterial cells, including individual clones, from the complex deposit as follows Can:   Oligonucleotides should be against known sequences for individual clones. Otide probes or probes should be designed. This sequence is It can be derived from a sequence, or a combination of those sequences. Each full length claw The oligonucleotide probe sequences used to isolate the , They should be the most reliable in isolating the clone of interest.clone Probe sequence do15 4 SEQ ID NO: 21 dx290 1 SEQ ID NO: 22 ek390 4 SEQ ID NO: 23 er471 7 SEQ ID NO: 24 fs40 3 SEQ ID NO: 25 ga63 6 SEQ ID NO: 26 gm335 4 SEQ ID NO: 27 hy370 9 SEQ ID NO: 28 ie47 4 SEQ ID NO: 29 s195 10 SEQ ID NO: 30   The sequence listed above contains an N at position 2, which position is a preferred probe / pump. Biotinylated phosphoramidites rather than nucleotides in primers Residues such as biotin phosphoramidite (1-dimethoxytrityloxy-2 -(N-biotinyl-4-aminobutyl) -propyl-3-O- (2-cyanoe Tyl)-(N, N'-diisopropyl) -phosphoramidite (Glen Research Obtained by the use of catalog number 10-1953)).   Preferably, the design of the oligonucleotide probe follows these parameters. Should be:   (A) The region of the sequence where the number of unclear bases (N), if any, is minimal Should be designed to:   (B) Tm is about 80 ° C. (2 ° C. for A or T, 4 ° C. for G or C) (Assume ° C).   Preferably, a method widely used for oligonucleotide labeling is used, Oligonucleotides are converted to γ-³²P-ATP (specific activity 6000 Ci / mmole). Other labeling methods may be used it can. Preferably, the unincorporated label is gel filtered or otherwise established. Should be removed by any method The amount of radioactivity incorporated into the probe It should be quantified by measuring with a titration counter. Preferably, The specific activity of the probe obtained should be about 4e + 6 dpm / pmole .   Preferably, a bacterial culture containing a pool of full-length clones is thawed and 100 pl Stock was added to 25 ml of sterile L-broth containing 100 μg / ml ampicillin Should be used to inoculate sterile culture flasks containing. Preferably, the culture is It should be grown at 37 ° C. to saturation, and preferably, the saturated culture should be fresh L Should be diluted with broth. Preferably, some of these dilutions are plated 100 μg / ml ampicillin in a 150 mm Petri dish and Grow overnight at 37 ° C. on solid bacterial culture medium containing L-broth containing 5% agar The dilution ratio yields 5000 distinct and well-separated colonies. And volume should be determined. To get clear, well-separated colonies Other known methods can also be used.   The colonies are then nitted using standard colony hybridization techniques. Transfer to a low cellulose filter for dissolution, denaturation and baking. You.   Then, preferably, 0.5% SDS, 100 μg / ml yeast RNA, and 6X SSC containing 10 mM EDTA (205.3 x 175.3 gN aCl / liter, 88.2 g sodium citrate, pH 7.0 with NaOH ) (About 10 ml per 150 mm filter) with gentle stirring Incubate at 65 ° C for 1 hour. The probe is then preferably hived. Add to the redidation mix and add a concentration greater than 1e + 6 dpm / ml Should be equal to this. Then, preferably the filter is at room temperature Wash without stirring with 500 ml of 2X SSC / 0.5% SDS, preferably After that, 500 ml of 2 × SSC / 0.1% with gentle shaking at room temperature Wash with SDS. 65 ° C, 30 minutes to 1 hour, 0.1X SSC / 0.5% A third wash with SDS is optimal. Then preferably dry the filter After sufficient time for autoradiography, positives were visualized on X-ray film. Let Other known hybridization methods can also be used.   Positive colonies are picked, grown in medium, and then positively added using standard procedures. Isolate the mid DNA. Then, restriction analysis, hybridization analysis or Clones can be verified by DNA sequencing.   A fragment of the protein of the present invention that can exhibit biological activity is also included in the present invention. You. Protein fragments may be linear or, for example, H.U.Saragovi , et al., Bio / Technology 10,773-778 (1992) and R.S.McDowell, et al., J. Amer. C hem. Soc. 114, 9245-9253 (1992) (both references are incorporated herein by reference). May be cyclized using known methods such as those described in Many For many purposes, including increasing the number of valencies at the protein binding site. The fragment may be fused to a carrier molecule along with the immunoglobulin. For example, A protein fragment is fused to the Fc portion of an immunoglobulin via a "linker". You may let it. For a bivalent form of the protein, such a fusion could be made to the Fc portion of an IgG molecule. Can be done against Such fusions using other immunoglobulin isotypes May be obtained. For example, a protein-IgM fusion yields a decavalent form of the protein of the invention. Will be.   The invention also provides the full length and mature forms of the disclosed proteins. Full length form of such a protein Is identified in the sequence listing by translation of the nucleotide sequence of the disclosed clone. I have. The mature form of such a protein can be found in a suitable mammalian cell or other host cell. To release the disclosed full-length polynucleotides (preferably those deposited with the ATCC). It may be obtained by exposing. Amino acid sequence of full-length form It may be determined from the column.   The present invention also provides a gene corresponding to the cDNA sequence disclosed herein. " A "corresponding gene" is a region of the genome that is transcribed to produce mRNA, A genome from which cDNA is derived from RNA and required for regulated expression of such genes Flanking regions (including coding sequences, 5 'and 3' untranslated regions), or Spliced exons, introns, promoters, enhancers, It also includes silencer or suppressor elements. Of the present disclosure The corresponding gene can be isolated using the sequence information. Of the sequences disclosed herein The information can be used to isolate the corresponding gene. Such a method is compatible with the disclosed distribution. Prepare a probe or primer from the information in the column and prepare an appropriate genomic library. Or performing the identification and / or amplification of genes in other sources of genomic material. You. An "isolated gene" is defined as an adjacent gene in the genome of the organism from which the gene was isolated. A gene that has been separated from the contiguous coding sequence (if present).   Enhance, decrease, or increase the gene corresponding to the polynucleotide sequence disclosed herein. Provides an organism having an altered expression. Antisense polynucleotide Or to bind and / or bind mRNA transcribed from the gene. The desired change in gene expression is achieved by using a ribozyme that cleaves (Albert and Morris, 1994, Trends Phalmacol. Sci. 15 (7): 250-25 4; Lavarosky et al., 1997, Bjochem. Mol. Med62 (1): 11-22; and Hampel, 1998 , PrQg. Nucleic Acid Res. Mol. Biol. 58: 1-39; all of which are book by reference It is regarded as described in the specification). For the polynucleotides disclosed herein, A transgenic animal having a corresponding multicopy gene, preferably a transformed cell. Transform cells with genetic constructs that are stably maintained in cells and their progeny A transgenic animal obtained by the conversion is provided. Gene expression Increase or decrease levels, or the temporal or spatial pattern of gene expression Transgenic animals having altered genetic control regions that alter the genes (See European Patent No. 0 649 464 B1; see all of these As described herein). Furthermore, by inserting an external sequence Or the deletion of all or part of the corresponding gene, Provided by organisms in which the gene corresponding to the leotide sequence is incomplete or completely inactivated Is done. Insertion, preferably after incorrect resection of the transposable element (Plasterk, 1992, Bioessays 14 (9): 629-633; Zwaal et al., 1993, Proc. . Natl. Acad Sci. USA 90 (16): 7431-7435; Clark et al., 1994, Proc. Natl. Acad. . Sci. USA 91 (2): 719-722; all of which are incorporated herein by reference. Or by homologous recombination, preferably positive / negative genetics (Mansour et al., 1988, Nature 336: 348-352; U.S. Patent Nos. 5,464,764; 5,487,992; 5,627,059; 5,631,153; 5,6 14,396; 5,616,491; and 5,679,523; all of which are incorporated herein by reference. Incomplete or complete gene inactivation. Wear. These organisms with altered gene expression are preferably eukaryotes And more preferably a mammal. Such organisms may have disease associated with the corresponding gene. Develop non-human models for research and interact with protein products from the corresponding gene It is useful for developing assay systems for identifying working molecules.   When the protein of the present invention is membrane-bound (eg, a receptor), the present invention Soluble forms are also provided. In such a form, the intracellular and transmembrane domains of the protein And remove all or part of the protein so that it is sufficiently secreted from the host where the protein was expressed. To do. Intracellular and transmembrane domains of the protein of the present invention are determined from sequence information. The domain can be identified by a known method for determining the domain.   The proteins and protein fragments of the present invention have at least the amino acid sequence of the disclosed protein. 25% (more preferably at least 50%, most preferably at least 75%) At least 60% sequence identity to the disclosed proteins. (More preferably at least 75% identity, most preferably at least 90% Or 95% identity). Sequence identity is a measure of sequence gap. When sequences are juxtaposed to maximize overlap and identity while minimizing It is determined by comparing the amino acid sequences of the proteins. Seg of any disclosed protein At least 75% sequence identity (more preferably at least 75% 85% identity, most preferably at least 95% identity). 8 or more (more preferably 20 or more, most preferably Is a protein containing a segment containing 30 or more contiguous amino acids Alternatively, protein fragments are also included in the present invention.   Species homologs of the disclosed polynucleotides and proteins are also provided by the invention. Book The term "species homolog" as used herein refers to a species different from the source of the protein or polynucleotide. A protein or polynucleotide, but as determined by one skilled in the art, Those having significant sequence similarity. Preferably, a polynucleotide species homolog Is at least 60% (more preferably less Both have a sequence identity of 75%, and most preferably at least 90%). Isozymes should have at least 30% (more preferably at least 45%) %, Most preferably at least 60%). Sequence identical here Sex is aligned so that overlap and identity are maximized and sequence gaps are minimized The nucleotide sequence of the polynucleotide or the amino acid sequence of the protein Is determined by Suitable probes or primers from the sequences provided herein And then screening for an appropriate nucleic acid source from the desired species. More species homologs may be isolated and identified. Preferably, the species homolog is from a mammalian species Isolated It was a thing. Most preferably, the species homolog is, for example, Pan troglodytes, Gor illa gorilla, Pongo pygmaeus, Hylobates concolor, Macaca mulatta, Papio papio, Papio hamadryas, Cercopithecus aethiops, Cebus capucinus, Aotus t rivirgatus, Sanguinus oedipus, Microcebus murinus, Mus musculus, Rattus norvegicus, Crisetulus griseus, Felis catus, Mustela vison, Canis famili aris, Oryctolagus cuniculus, Bos taurus, Ovis aries, Sus scrofa and Equ isolated from certain mammals, such as us caballus, whose genetics Genomic organization of genes in one species and genetic mapping in another species It is possible to identify the association of gene sequence order with genomic organization of related genes. (O'Brien and Seuanez, 1988, Ann. Rev. Genet. 22: 323-351; O'Brien et al., 1993, Nature Genetics 3: 103-112; Johansson et al., 1995, Genomics  25: 682-690; Lyonsetal., 1997, Nature Genetics 15: 47-56; O'Brien et al., 19 97, Trends in Genetics 13 (10): 393-399; Carver and Stubbs, 1997, Genome Re search 7: 1123-1137 (all of which are described herein by reference) Is considered))).   The invention also relates to allelic variants of the disclosed polynucleotides, i.e., the disclosed polynucleotides. Identical, homologous or related to the protein encoded by the nucleotide Includes naturally occurring alternative forms of the isolated polynucleotide encoding the protein. Preferred Alternatively, an allelic variant has at least 60% (for a particular polynucleotide) More preferably at least 75%, most preferably at least 90%) identity Where the sequence identity is the maximum overlap and identity, Compare nucleotide sequences of aligned polynucleotides to minimize It is determined by Suitable probes or primers from the sequences described herein And screen for appropriate sources of nucleic acids from individuals of appropriate species. And the allelic variant may be isolated and identified.   Also, the present invention has a sequence complementary to the sequence of the polynucleotide disclosed herein. Also encompasses polynucleotides.   The invention also relates to the use of the present invention under reduced stringency conditions, more preferably under stringent conditions. The polynucleotides described herein may also be hybridized, preferably under very stringent conditions. Also encompasses polynucleotides that can be redistributed. The following table shows examples of strictness conditions. Shown in The very strict conditions are, for example, at least as strict as conditions A to F. Yes, the strict conditions are, for example, at least as strict as the conditions GL, The condition for reducing the density is, for example, at least as strict as the conditions M to R. ^‡: The hybrid length is the length of the hybridizing polynucleotide. Expected length for hybridized region (s). Polinu Hybridize a nucleotide to a target polynucleotide of unknown sequence If so, the hybrid length is the length of the polynucleotide to be hybridized. Suppose When a polynucleotide of known sequence hybridizes Aligns polynucleotide sequences to identify region (s) of optimal sequence complementarity By doing so, the hybrid length can be determined.^† : SSPE (1 × SS) in hybridization and wash buffer PE was 0.15 M NaCl, 10 mM NaH_TwoPO_Four, And 1.25 mM ED TA, pH 7.4, is converted to SSC (1 × SSC is 0.15 M NaCl and 15 mM sodium citrate). Hybridization After the completion of the washing, the washing is performed for 15 minutes. * T_B-T_R: For hybrids that are expected to be shorter than 50 base pairs in length The hybridization temperature is the melting temperature of the hybrid (T_m5) than 10) C should be lowered. T by the following equation_mIs determined. Less than 18 base pairs in length For hybrids, T_m(° C.) = 2 (number of A + T bases) +4 (number of G + C bases). Length 18 For a 49 base pair hybrid, T_m(° C) = 81.5 + 16.6 (log_Ten[Na⁺]) + 0.41 (% G + C)-(600 / N), where N is a hybrid Number of bases, and the sodium ion concentration in the hybridization buffer ([Na for 1 × SSC]⁺] = 0.165M).   Further examples of stringency conditions for polynucleotide hybridization Is Sambrook, J., E.F. Fritsch, and T.W. Maniatis, 1989, Molecular Cloning: A  Laboratmry Manual, Cold Spring Harbor Laboratory Press, Cold Spring Har bor, NY, chapters 9 and 11, and Current Protocols in Molecu1ar Biology, 1 995, F.M.Ausubel et al., Eds., John Wiley & Sons, Inc., sections 2.10 and  6.3-6.4 and are deemed to be described herein by reference .   Preferably, each of such hybridizing polynucleotides Is at least 25% of the polynucleotide of the invention to be hybridized (More preferably at least 50%, most preferably at least 75%) A length that is small relative to the polynucleotide of the invention to be hybridized. At least 60% sequence identity (more preferably, at least 75% identity; And preferably also at least 90% or 95% identity). Sequence identity Are sequenced to maximize overlap and identity, while minimizing sequence gaps. Are determined by comparing the amino acid sequences of the proteins when are aligned.   An isolated polynucleotide encoding the protein of the present invention is described in Kaufman et al., Nucleic Acid. ic Acids Res. PMT2 or pED expression vector disclosed in 19, 4485-4490 (1991) Operably linked to an expression control sequence such as Good. Many suitable expression control sequences are known in the art. Many fit Various expression control sequences are known in the art. One for recombinant protein expression General methods are also known. Kaufman, Methods in Enzymology 185, 537-566 ( 1990) is a typical example. “Operably linked,” as defined herein, refers to the isolation port of the present invention. The polynucleotide and the expression control sequence are placed and ligated into a vector or cell. (Transfection) with the polynucleotide / expression control sequence It is meant to be expressed by a host cell.   Many types of cells can serve as suitable host cells for expression of the proteins of the present invention. Mammalian cells include, for example, monkey COS cells, Chinese hamster ovary (CH O) cells, human kidney 293 cells, human epidermal A431 cells, human Colo205 cells Vesicles, 3T3 cells, CV-1 cells, other transformed primate cell lines, normal diploid Cells, cell lines obtained from in vitro culture of primary tissues, primary explants, H eLa cells, mouse cells, BHK, HL-60, U937HaK or Jurkat cells Vesicles.   Alternatively, in lower eukaryotic cells such as yeast or prokaryotic cells such as bacteria. It is possible to produce proteins. A potentially suitable yeast strain is Saccharomyces ce revisiae, Schizosaccharomyces pombe, Kluyveromyces strain, Candida, or Includes yeast strains capable of expressing the seed protein. A potentially suitable bacterial strain is Escherichia capable of expressing E. coli, Bacillus subtilis, Salmonella typhimurium, or heterologous proteins Functional bacterial strains. If the protein is produced in yeast or bacteria, so The resulting protein is converted, for example, by phosphorylation or glycosylation of the appropriate site. It may need to be modified to obtain a functional protein. Known chemical or enzymatic method The covalent bonding may be performed using a method.   The isolated polynucleotides of the present invention can be used in one or more insect expression vectors to The protein can be obtained by operably linking to an appropriate control sequence and using an insect expression system. Good. Materials and methods for baculovirus / insect cell expression systems are described, for example, in In Kit form from vitrogen, San Diego, California, USA (MaxBac^RKit) Commercially available, such methods are well known in the art and include Summers and And Smith, Texas Agricultural Experiment Station Bulletin No. 1555 (1987) ( (Referred to as described herein by reference) . As used herein, an insect cell capable of expressing the polynucleotide of the present invention is " Transformation ".   Culturing transformed host cells under culture conditions suitable for expressing the recombinant protein The protein of the present invention may be produced more. Next, the obtained expressed protein was subjected to gel filtration and filtration. Such cultures using known purification processes, such as ion exchange chromatography (I.e., medium or cell extract). Also, protein purification Is an affinity column containing an agent that will bind to the protein; Valine A-agarose, Heparin-Toyopearl^ROr Cibacrom blue 3GA Sepha Loin^ROne or more column steps with an affinity column such as Use resin such as phenyl ether, butyl ether or propyl ether One or more steps using hydrophobic interaction chromatography; Or immunoaffinity chromatography.   Alternatively, the protein of the invention may be expressed in an easily purified form. For example, Lactose binding protein (MBP), glutathione-S-tonspherase (GST) Or expressed as a fusion protein such as a fusion protein with thioredoxin (TRX) You may. Kits for expression and purification of such fusion proteins are available from New En glan BioLab (Beverly, MA), Pharmacia (Piscataway, NJ) and InVitrogen Sold. Tag proteins with epitopes, and then label such epitopes. Direction Purification can also be performed by using the specific antibody thus obtained. Epitome of 1 ("Flag") is commercially available from Kodak (New Haeven, CT).   Finally, a hydrophobic RP-HPLC medium such as a pendant methyl or other aliphatic group is added. One or more reversed-phase high quality liquid chromatography using silica gel with The protein can be further purified using the-(RP-PLC) step. A few Or a substantially homogeneous isolation system using various combinations of all of the above purification steps. A recombinant protein can also be obtained. The protein thus purified can be derived from other mammalian proteins. It is not qualitatively included and is defined as "isolated protein" in the present invention.   The protein of the present invention may be used as a product of a transgenic animal. Characterized by somatic or germ cells containing the nucleotide sequence Expressed as an ingredient in milk of transgenic cows, goats, pigs, or sheep Is also good.   The protein may be produced by known conventional chemical synthesis. The present invention by synthetic means Methods for constructing proteins are known to those skilled in the art. Synthetically constructed protein sequences are primary Sharing secondary or tertiary structure and / or conformational properties Thus, they may have common biological properties, including protein activity. Yo For the screening of therapeutic compounds and the immunology for the production of antibodies. Process to replace the biological activity or immunological replacement of the naturally occurring purified protein May be used.   The protein shown in the present specification has an amino acid sequence similar to that of the purified protein. Which are modified naturally or by derivatization Is also good. For example, modification of a peptide or DNA sequence can be accomplished by one of ordinary skill in the art using known methods. More can be done. The desired modification in the protein sequence depends on the choice in the coding sequence. Includes amino acid residue changes, substitutions, exchanges, insertions or deletions. For example, up to one Or more cysteine residues have been deleted or replaced with another amino acid. The conformation of the child may be changed. Such changes, replacements, exchanges, insertions, etc. Methods for deletion or deletion are well known to those skilled in the art (see, for example, US Pat. No. 8584). Preferably, such changes, substitutions, exchanges, insertions or deletions Loss retains the desired activity of the protein.   Expected to retain protein activity in whole or in part, thus screening Or other fragments of the protein sequence that may be useful for immunological or other immunological methods. Derivatives can also be made by those skilled in the art from the disclosure herein. Such modifications are the subject of the present invention. Is believed to be encompassed byApplications and biological activities   The polynucleotides and proteins of the present invention may have one or more of the following uses or Exhibiting biological activity (including those associated with the assays cited herein) Conceivable. The uses or activities described for the proteins of the present invention may be attributed to the administration of such proteins. Supply or use, or of a polynucleotide encoding such a protein. Administration or use (eg, for any vector suitable for gene therapy or DNA transfer) C).Research applications and usefulness   The polynucleotide provided by the present invention can be used for various purposes depending on the research population. Can be used. Preferential expression of the corresponding protein for analysis, characterization or therapeutic use (Constitutively, at a specific stage of tissue differentiation or development, or As tissue markers (expressed in disease states) as well as Southern gel molecules As a quantity marker, it can be used to identify chromosomes or map related gene locations. Compared to the patient's endogenous DNA as a chromosome marker or tag (if labeled) Probes to identify potential genetic diseases Genetic fingerprinting to discover new related DNA sequences As a source of information for obtaining PCR primers for Probes to subtract known sequences in the process of nucleotide discovery And select the oligomer to bind to a “gene chip” or other support To test for expression patterns, use DNA immunization to To generate antibodies, as well as to generate anti-DNA antibodies, or Polynucleotides can be used as antigens to induce an immune response You. Binds or potentially binds another protein (e.g., If the protein encodes a protein that binds to Or interaction trap assays to identify inhibitors of binding interactions A (for example, as described in Gyuris et al., Cell 75: 791-803 (1993)). And polynucleotides can be used.   The proteins provided by the present invention are a family of multiple proteins for high-throughput screening. For assays to determine biological activity, including proteins of interest; production of antibodies or other A protein (or its receptor) in a biological fluid Reagents (including labeling reagents) in assays designed to quantitatively determine The corresponding protein is preferentially expressed (constitutively or with tissue differentiation or Is expressed at a particular stage of development or in a disease state) As well as used to, of course, isolate related receptors or ligands You may. Bind when a protein binds or potentially binds to another protein Proteins to identify other proteins and / or inhibitors of binding interactions White can be used. Using proteins involved in these binding interactions, Of peptide or small molecular inhibitors or agonists for binding interactions Training can also be performed.   Any or all of these research uses may be commercialized as research products. Can be developed into reagent grade or kit formats.   Methods for performing the above uses are well known to those skilled in the art. Open this method The literature shown is "Molecular Cloning: A Laboratory Manual", 2nd ed., Cold Spri ng Harbor Laboratory Press, Sambrook, J., E.F. Fritsch and T. Maniatis ed s., 1989, and "Methods in Enzymology: Guide to Molecular Cloning Techniqu es ", Academic Press, Berger, S.L. and A.R. Kimmel eds., 1987 However, it is not limited to these.   Nutritional uses   Use of the polynucleotide and protein of the present invention as a nutrient source or additive Can be. Such uses include the use as a protein or amino acid additive and the use as a carbon source. All uses, as a nitrogen source and as a carbohydrate source. Not limited to these. In such a case, the protein or polynucleotide of the present invention is Food, pills, solutions, suspensions or capsules. It can also be administered as a separate solid liquid formulation, such as in the form of a solid. Microbial In this case, the protein or polynucleotide of the present invention is added to the medium in which the microorganism is cultured. be able to.   Cytokines and cell proliferation / differentiation activity   The protein of the present invention has cytokine activity, cell growth activity (induction or inhibition) or cell activity. Can show blast differentiation activity (induction or inhibition) or in certain cell populations To induce the production of other cytokines. Many proteins found to date Sex factors (including all known cytokines) are dependent on one or more factors Showing activity in cell proliferation assays, and thus the assay Serves as a convenient way to confirm activity. The activity of the protein of the present invention is determined in cell lines (32D, DA 2, DA1G, T10, B9, B9 / 11, BaF3, MC9 / G, M + (pr eB M +), 2E8, RB5, DA1, 123, T1165, HT2, CTL L2, TF-1, Mo7e and CMK, but not limited to) It is confirmed by any of a number of conventional factor-dependent cell proliferation assays.   The activity of the protein of the invention may be measured, inter alia, by the following method:   Assays for T cell or thymocyte proliferation are described in Current Protocols in I mmunology, Ed by J.E.Coligan, A.M.Kruisbeek, D.H.Margulies, E.M.Shevach, W St rober, Pub.Greene Publishing Associates and Wiley-Interscience (Chapter 3 , In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, Immun ologic studies in Humans); Takai et al., J. Imnlunol. 137: 3494-3500,1986; B ertagnolli et al. Immunol. 145: 1706-1712, 1990; Bertagnolli et al., Cellular Immunology 133: 327-341, 1991; Bertagnolli, et al., J. Am. Immunol.1 49: 3778-3783, 1992; Bowman et al., J. Am. Immunol. 152: 1756-1761, described in 1994. Including, but not limited to:   Cytokine production and / or expansion of spleen cells, lymph node cells or thymocytes Assays for propagation are described in Polyclonal T cell stimulation, Kruisbeek, A.M. and  Shevach, E.M. In Current Protocols in Immunology. J.E.e.a.Coligan eds. V ol 1 pp. 3.12.1-3.12.14, John Wiley and Sons, Toronto. 1994; and Measurem ent of mouse and human Interferon γ, Schreiber, R.D. In Current Protoco ls in Immunology. J.E.e.a.Coligan eds.Vol 1 pp.6.8.1-6.8.8, John Wiley an d Sons, Toronto. Includes, but is not limited to, those described in 1994.   Assays for proliferation and differentiation of hematopoietic and lymphogenic cells ent of Human and Murine Interleukin 2 and Interleukin 4, Bottomly, K., Davi s, L.S. and Lipsky, P.E. In Current Protocols in Immunology. J.E.e.a.Coliga n eds. Vol 1 pp. 6.3.1-6.3.12, John Wiley and Sons, Toronto. 1991; deVrie s et al., J. Mol. 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: 2931-293 8,1983; Measurement of mouse and human interleukin 6-Nordan, R .; In Curren t Protocols in Immunology. J.E.e.a. Coligan eds. Vol 1 pp. 6.6.1-6.6.5, John Wiley and Sons, Toronto. 1991; Smith et al., Proc. Natl. Acad. Sci. U.S .A. 83: 1857-1861, 1986; Measurement of human Interleukin 11-Bennett, F., Giannotti, J., Clark, S.C. and Turner, K. J. In Current Protocols in Imm uno1ogy.J.E.e.a.Coligan eds.Vol 1 pp.6.15.1 John Wiley and Sons, Toronto . 1991; Measurement of mouse and human Interleukin 9-Ciarletta, A., Giann otti, J., Clark, S.C. and Turner, K.J. In Current Protocols in Immunolog y.J.E.e.a.Coligan eds.Vol 1 pp. 6.13.1, John Wiley and Sons, Toronto. 199 Includes, but is not limited to, those described in 1.   Assays for the response of T cell clones to antigens (particularly proliferation and APC-T cell interaction as well as direct To identify the effects of T cells) is described in Current Protocols in Imnlunology, Ed. E . Coligan, A.M.Kruisbeek, D.H.Margulies, E.M.Shevach, W Strober, Pub.Greene P ublishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays fo r Mouse Lymphocyte Function; Chapter 6, Cytokines and their cellular rec eptors; Chapter 7, Immunologic studies in Humans); Weinberger et al., Proc. Natl. Acad. Sci. USA 77: 6091-6095, 1980; Weinberger et al., Eur. J. Immun.1 1: 405-411, 1981; Takai et al., J. Am. Immunol. 137: 3494-3500, 1986; Takai et al. , J. Immunol. 140: 508-512, 1988, including but not limited to Absent.   Immunostimulatory or suppressive activity   Further, the protein of the present invention, the activity in the assay described herein (not limited to these) It may also exhibit immunostimulatory or immunosuppressive activity, including: Protein is a seed In various deficiencies and disorders, including severe immunodeficiency complications (SCID) For example, to enhance the proliferation of T and / or B lymphocytes. In regulating or down-regulating, as well as in NK Useful in activating the cytolytic activity of cells and other cell populations Can be. These immunodeficiencies can be genetic and can be viral (e.g., Caused by, for example, HIV) and bacterial or fungal infections. Or may be caused by an autoimmune disease. Than In particular, infections caused by viruses, bacteria, fungi or other infectious agents Sexual diseases such as HIV, hepatitis virus, herpes virus, mycobacteria, Various fungal infections, such as Leishmania, Malaria and Candida species, are It can be treated with proteins. Of course, in this regard, the booming of the immune system When a strike is required, that is, in the treatment of cancer, the protein of the present invention may be used.   Autoimmune diseases that may be treated using the protein of the present invention include, for example, multiple sclerosis, Systemic deep elitomades, rheumatoid arthritis, autoimmune pneumonia, Guilla in-Barre syndrome, autoimmune thyroiditis, insulin-dependent diabetes, severe muscle Includes asthenia, graft versus host disease and autoimmune inflammatory eye diseases. Book Such proteins can be used to treat allergic reactions such as asthma or other respiratory disorders And may be used for the treatment of symptoms. Other conditions for which immunosuppression is desired (eg, asthma (Especially allergic asthma) and related respiratory problems) And may be treated. Other conditions for which immunosuppression is desired (including, for example, organ transplantation) May be treated using the protein of the present invention.   The proteins of the present invention can also be used to enable an immune response in a number of ways. Da Unregulation can block or block an immune response already in progress Or includes interfering with the induction of an immune response. There may be. By suppressing the T cell response, or Inhibits activated T cell function by inducing resistance or both May be. Generally, immunosuppression of T cell responses is an active, non-antigen specific Process, which requires continuous exposure of T cells to the inhibitor. Resistance and Means non-responsive or anergic in T cells, generally antigen-specific In that it persists after exposure to the tolerizing agent has ceased. Operationally, the lack of a T cell response when exposed to a specific antigen in the absence of a resistance agent More resistance may be shown.   One or more antigen functions (eg, B lymphocyte antigen function (eg, B7) Including, but not limited to, down-regulating For example, blocking high levels of lymphokine synthesis by activated T cells Useful in tissue, skin and organ transplantation and graft versus host disease (GVHD) There will be. For example, blocking T cell function reduces tissue destruction in tissue transplantation Should be. Typically, in tissue transplants, graft rejection is Initiated by T cells being recognized as foreign and then breaking the graft A destructive immune response occurs. B7 Lymphocyte Antigen on Immune Cells and Its Native Riga Molecule that inhibits or blocks interaction with the second B lymphocyte antigen (e.g., B7-1, B7-3) mixed with a monomeric peptide having the activity of Or a single, soluble, monomeric peptide having B7-2 activity) The previous administration provides a natural response on immune cells without transmitting responsive costimulatory signals. May induce binding of the molecule to the ligand. In this regard, B lymphocyte anti- Blocking the primary function involves cytokine synthesis by immune cells, such as T cells. And thus acts as an immunosuppressant. Moreover, the lack of co-stimulation It may be sufficient to cause a loss of T cell response. B lymphocyte antigen blocking reagent Induction of long-term tolerance by The need can be avoided. To achieve sufficient immunosuppression or tolerance in the subject May also need to block the function of the B lymphocyte antigen combination .   Individual blocking in preventing organ transplant rejection or GVHD Evaluate the effectiveness of the reagents using animal models that can predict their effectiveness in humans be able to. Examples of suitable systems that can be used include allografts in rats and allografts. Xenogeneic pancreatic islet cell grafts in mice and Was used to test the immunosuppressive effect of the CTLA4Ig fusion protein (Lenscho w et al., Science 257: 789-792 (1992) and Turka et al., Proc Natl. Acad. Sci. USA, 89: 11102-11105 (1992)). In addition, GVHD rat model (Paul ed., Fundamental Immunology, Ravan Press, New York, 1989, pp.84 B-lymphocyte antigen machinery for the progression of the disease in vivo using The blocking effect of noh can be determined.   In addition, blocking antigen function is therapeutically useful for treating autoimmune diseases It can be. Many autoimmune diseases are responsive to self- Inappropriate activity of T cells to promote the production of cytokines and autoantibodies involved in It is the result of sexualization. Interfering with the activation of self-reactive T cells reduces the symptoms of the disease. Less or may be eliminated. Disrupting B lymphocyte antigen receptor: ligand interaction Inhibit T cell activation using administration of a reagent that blocks T cell costimulation Production of autoantibodies or T cell-derived cytokines that can harm and participate in the disease process Can interfere with life. In addition, blocking reagents can provide long-term remission of disease It may induce antigen-specific resistance of autoreactive T cells that may lead. Autoimmune disease The effectiveness of blocking reagents in the prevention or amelioration of Can be determined using a number of well-characterized animal models You. Examples are murine experimental autoimmune encephalitis, MRLlpr / lpr mice or N Systemic deep erythematosus and murine self-immunity in ZB hybrid mice Plague collagen arthritis, diabetes in NOD mice and BB rats, and Experimental rat myasthenia gravis (Paul ed., Fundamental Immunology, Raven Press, Ne. w York, 1989, pp. 840-856).   Antigen function as a means of up-regulating the immune response (preferred Alternatively, up-regulation of B lymphocyte antigen function) is also therapeutically useful. Up-regulation of the immune response may be May be in a form that eliminates the initial immune response. For example, B lymphocyte antigen function Enhancing the immune response by stimulating may be useful in the case of a viral infection. In addition, systemic viral such as influenza, common cold, and encephalitis Disease may be ameliorated by systemic administration of a stimulatory form of B lymphocyte antigen .   Alternatively, T cells are taken from a patient and tagged with ACPs that express a peptide of the invention. Co-stimulate T cells in vitro with added viral antigens, or Is combined with a stimulating form of the soluble peptide of the invention and then activated in vitro Re-introduced T cells into the patient, the anti-virus in infected patients It may enhance the immune response. Another method of promoting an antiviral immune response is Infected cells are taken from the patient and the nucleic acid encoding the protein of the invention described herein is To allow cells to express all or part of the protein on their surface. And then reintroduce the transfected cells into the patient. U. The infected cells then transmit a costimulatory signal to the T cells in vivo. Could thereby activate T cells.   In another application, antigen function (preferably B lymphocyte antigen function) Up-regulation or promotion may be useful in inducing tumor immunity . Transfection with a nucleic acid encoding at least one peptide of the invention Tumor cells (eg, sarcoma, melanoma, lymphoma, leukemia, neuroblastoma, cancer Tumor) can be administered to a subject to overcome tumor-specific resistance in the subject. Desired If you Transfect tumor cells to express a combination of peptides it can. For example, a tumor cell obtained from a patient is treated with a peptide having B7-2-like activity. Or a peptide having a B7-1-like activity and / or a B7-3-like activity Expression vector that directs expression in combination Can be sfected. Transfected tumor cells into patient To express the peptide on the surface of the transfected cells. Alternatively, for transfection in vivo using gene therapy Tumor cells can be targeted.   Existence of the peptide of the present invention having B lymphocyte antigen activity on the surface of tumor cells Provides the necessary co-stimulatory signals for T cells to provide T cell-mediated trafficking. Induces an immune response against the transfected tumor cells. In addition, MHC Tumor cells lacking class I or MHC class II molecules, or sufficient MHC Tumor cells that cannot reexpress class I or MHC class II molecules are I α chain protein and β_TwoMicroglobulin protein or MHC class II α chain or Or all or part of the MHC class II β chain protein (eg, Transfection with the nucleic acid encoding the Class I or class II MHC proteins can be expressed on the cell surface . A marker having the activity of a B lymphocyte antigen (eg, B7-1, B7-2, B7-3) Expression of the appropriate class I or class II HMC in combination with the peptide is Elicits an immune response to transfected tumor cells mediated by vesicles Lead. If desired, expression of MHC class II binding proteins, such as invariant chains, can be blocked. The gene coding for the antisense construct to be detected can be linked to the activity of the B lymphocyte antigen. Co-transfection with DNA encoding a peptide having To promote the presentation of tumor-associated antigens and induce tumor-specific immunity. Therefore Induction of an immune response mediated by T cells in a human subject can be caused by tumors in the subject. It may be sufficient to overcome tumor-specific resistance.   The activity of the protein of the invention may be measured, inter alia, by the following method:   Suitable assays for thymocyte or spleen cell cytotoxicity are described in Current Protocols in Immunology, Edby J.E.Coligan, A.M.Kruisbeek, D.H.Margulies, E.M.Shevach, W St rober, Pub.Greene Publishing Associates and Wiley-Interscience (Chapter 3 , In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, Immun ologic studies in Humans); Herrmann et al., Proc. Natl. Acad. Sci. USA 78: 248 8-2492, 1981; Herrmann et al., J. Immunol. 128: 1968-1974, 1982; Handa et al. , J. et al. Immunol. 135: 1564-1572, 1985; Takai et al., J. Am. Immunol. 137: 3494-350 0,1986; Takai et al., J. Immunol. 140: 508-512, 1988; Herrmann et al., Proc. . Natl. Acad. Sci. USA 78: 2488-2492, 1981; Herrmann et al. , J. et al. Immunol. 128: 1968-1974, 1982; Handa et al., J. Am. Immunol. 135: 1564-1572,1985; Takai e t al., J.S. Immunol. 137: 3494-3500, 1986; Bowman et al., J. Am. Virology 61: 1992 -1998; Takai et al., J. Immunol. 140: 508-512, 1988; Bertagnolli et al., Ce llular Immunology 133: 327-341, 1991; Brown et al., J. Am. Immunol. 153: 3079-3 092, 1994, including but not limited to the assays described.   Updates for T cell-dependent immunoglobulin response and isotype switching Say (especially to modulate the T cell-dependent antibody response to a Th1 / Th2 profile Influencing proteins are identified in Maliazewski, J. Immunol. 144: 3028-3033, 1990. Includes, but is not limited to, the assays described, and further enhances B cell function Say, In vitro antibody production, Mond, J.J. and Brunswick, M. In Current  Protocols in Immunology J.E.Coligan eds.Val 1 pp.3.8.1-3.8.16, John Wile y and Sons, Tronto 1994.   Mixed lymphocyte reaction (MLR) assays (especially primarily Th1 and CTL Identify the proteins that generate the answer), Current Protocols in Immunology, Ed by J.E. Coligan, A.M. Kruisbeek, D.H. Margulies, E.M. Shevach, W Strober, P ub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vi tro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, Immunologic  studies in Humans); Takai et al. Immunol. 137: 3494-3500,1986; Takai  et al., J. Amer. Immunol. 140: 508-512, 1988; Bertagnolli et al., J. Am. Immunol. 1 49: 3778-3783, including but not limited to the assays described in 1992.   Dendritic cell-dependent assays (especially for dendritic cells that activate untreated T cells) To identify proteins that are more expressed) are described in Guery et al., J. Am. Immunol. 134: 536-544, 1995; Inaba et al., Journal of Experimental Medicine 173: 549-559, 1991; Ma catonia et al., Journal of Immunology 154: 5071-5079, 1995; Porgador et al. ., Journal of Experimental Medicine 182: 255-260, 1995; Nair et al., Journa l of Virology 67: 4062-4069,1993; Huang et al., Science 264: 961-965,1994; Ma catonia et al., Journal of Experimental Medicine 169: 1255-1264,1989; Bhard waj et al., Journal of Clinical Investigation 94: 797-807, 1994; and Inaba e t al., Journal of Experimental Medicine 172: 631-640, 1990. Includes but is not limited to Say.   Lymphocyte survival / apoptosis assays (especially apoptosis after superantibody induction) Identify Proteins That Prevent Lysis and that Regulate Lymphocyte Homeostasis ) Is Darzynkiewicz et al., Cytometry 13: 795-808, 1992; Gorczyca et al., L eukemia 7: 659-670, 1993; Gorczyca et al., Cancer Research 53: 1945-1951,199 3; 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., I Includes assay described in nternational Journal of Oncology 1: 639-648, 1992 But not limited to these.   Early stage T cell commitment and development assays Antica et al., Blood 84: 111-117, 1994; Fine et al., Cellular Immunology 155: 111-122, 1994; Galy et al., Blood 85: 2770-2778, 1995; Toki et al., Proc. Natl. A cad. Sci. USA 88: 7548-7551, 1991, including but not limited to No.   Hematopoietic regulatory activity   The proteins of the present invention are useful in regulating hematopoiesis and are therefore Useful in the treatment of bulb deficiency. Colony forming cells or factor-dependent cell lines Even minimal biological activity in support of has been implicated in regulating hematopoiesis. For example, to support the growth of erythroid progenitor cells alone, or to In combination with, for example, treatment of various anemias, or release Production of erythroid progenitors and / or erythroblasts in combination with radiation therapy / chemotherapy Stimulating viability; proliferation of bone marrow cells such as granulocytes and monocytes / macrophages Support (ie, traditional CSF activity), eg, in combination with chemotherapy In addition, it is useful in preventing subsequent myelosuppression; Breeding, then supporting platelet growth, and thereby thrombocytopenia It is useful for preventing or treating various platelet diseases, and Used instead of or in addition to platelet infusion; and / or hematopoietic stem Cells (mature to all of the above hematopoietic cells, and therefore various stem cell diseases (typically It is always a disease treated by transplantation, for example, aplastic anemia and seizures Is useful in supporting nocturnal hemoglobinuria). And after radiation / chemotherapy in vivo or ex vivo (i.e. Or combined with bone marrow transplantation) or genetically engineered for gene therapy Also useful in repopulating stem cell compartments as normal cells after .   In particular, the activity of the protein of the present invention may be measured by the following method.   Assays suitable for proliferation and differentiation of various hematopoietic cell lines have already been cited .   Assays for embryonic stem cell differentiation, specifically identifying proteins that affect embryonic hematopoiesis ) Is based on 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, including, but not limited to.   Assays for stem cell survival and differentiation, specifically identifying proteins that regulate lympho-hematopoiesis ) Is described in Methylcellulose colony forming assays, Freshney, M.G. In Culture  of Hematopoietic Cells. R.I. Freshney, et al. eds. Vol pp. 265-268, Wile y-Liss, Inc., New York, NY. 1994; Hirayama et al., Proc. Natl. Acad. Sci. USA 89: 5. 907-5911,1992; Primitive hematopoietic colony forming cells with high proliferative potential, McNiece, I.K. and Briddell, R.A. In Culture of  Hematopoietic Cells.R.I.Freshney, et al.eds.Vol pp.23-39, Wiley-Liss, Inc. , New York, NY.1994; Neben et al., Experimental Hematology 22: 353-359,1994; C obblestone area forming cell assay, Ploemacher, R.E.In Culture of Hematopo ietic Cells. R.I. Freshney, et al. eds. Vol pp. 1-21, Wiley-Liss, Inc .. New York, NY. 1994; Long term bone marrow cultures in the presence of s tromal cells, Spooncer, E., Dexter, M. and Allen, T .; In Culture of Hematopo ietic Cells. R.I. Freshney, et al. eds. Vol pp. 163-179, Wiley-Liss, Inc., New York, NY. 1994; Long term culture initiating cell assay, Sutherland, H. J. In Culture of Hematopoietic Cells. R.I. Freshney, et al. eds. Vol pp . 139-162, Wiley-Liss, Inc., New York, NY. Includes assay described in 1994 Including, but not limited to.   Tissue proliferation activity   The protein of the present invention may be used to grow or regenerate bone, cartilage, keys, ligaments and / or nerve tissue. And compositions used for wound healing and tissue repair, further including burns, lacerations And has utility in the treatment of ulcers.   Book that induces cartilage and / or bone growth in an environment where bone is not formed normally Inventive proteins cure healing of fractures and cartilage damage or defects in humans and other animals There are applications in Such formulations using the protein of the present invention include closed fractures and It is useful for reducing open fractures and improving fixation of artificial joints. Bone De novo bone formation induced by plasticizers can be congenital, traumatic or tumor Contributes to the repair of craniofacial deficits induced by radiological resection and further It is also useful in general surgery.   The proteins of the present invention may be used in the treatment of periodontal disease and other tooth restoration processes. Heel Agents provide an environment to attract osteogenic cells, stimulate the growth of osteogenic cells, Alternatively, it can induce osteogenic cell precursor differentiation. For example, the protein of the present invention And / or mediated by inflammatory or inflammatory processes Block the process of tissue destruction (collagenase activity, osteoclast activity, etc.) This may be useful in the treatment of osteoporosis or osteoarthritis.   Another category of tissue developmental activity that may be attributed to the proteins of the invention is the key. / Ligament formation. Environments where key / ligament-like or other tissues are not formed properly The protein of the present invention that induces the formation of such a tissue in humans is Applied to healing of key or ligament lacerations, deformations and other key or ligament defects You. Such a formulation using a key / ligament-like tissue-inducing protein may be used for key or ligament-like tissue. To prevent key or ligament fixation to bone or other tissue It may be. The de novo key / ligament-like tissue formation induced by the composition of the present invention Sexual, traumatic, or oncological resection-induced craniofacial defects Cosmetic surgery for contributing to the repair and also for attaching or repairing keys or ligaments It is also useful in The composition of the present invention attracts key- or ligament-forming cells Provide an environment for stimulating the growth of key- or ligament-forming cells, Induction of precursors of band-forming cells or tissue repair when returned to vivo. Ex vivo can induce the growth of key / ligament cells or progenitors ex vivo. The compositions of the present invention can be used to treat keratitis, carpal tunnel syndrome and other key or ligament defects. Is also useful. The composition of the present invention may comprise a suitable matrix and / or It may include a sequestering agent, such as a well-known carrier.   The protein of the present invention is used for proliferation of nerve cells and regeneration of nerve and brain tissue, , Central and peripheral nervous system diseases and neuropathy and mechanical diseases and Treatment of traumatic diseases (including degeneration, death or trauma to nerve cells or nerve tissue) May also be useful for treatment. More specifically, peripheral nerve injury, peripheral neuropathy and Diseases of the peripheral nervous system such as neuropathy and localized neuropathy, and Alzheimer's disease , Parkinson's disease, Huntington's disease, amyotrophic lateral spinal sclerosis and Shy-Drager Proteins may be used in the treatment of diseases of the central nervous system, such as the syndrome. By the present invention Additional conditions that may be treated include mechanical disorders such as spinal cord disorders and traumatic disorders And cerebrovascular diseases such as head trauma and stroke. Chemotherapy or other Peripheral neuropathy caused by medical therapy of Cure Can be treated.   The protein of the present invention may also be used for pressure ulcer, ulcer associated with vascular dysfunction, More preferred for non-healing wounds, including (but not limited to) wounds due to trauma It may also be useful for promoting rapid closure.   The protein of the present invention includes organs (eg, pancreas, liver, intestine, kidney, skin, endothelium). ), Muscle (smooth, skeletal or cardiac) and vascular (including vascular endothelium) tissue To promote the development of other tissues or the proliferation of cells that make up such tissues. Activity. Part of the desired effect is by inhibiting fibrotic scarring. Regeneration of normal tissue. The proteins of the present invention may also exhibit angiogenic activity.   The protein of the present invention, protection or regeneration of intestine, and fibrosis of lung or liver, various groups Treatment of tissue reperfusion injury and symptoms caused by systemic cytokine damage May also be useful for treatment.   The protein of the present invention, the promotion or suppression of the differentiation of the precursor tissue or cells from the tissue; Alternatively, it may be useful for suppressing the growth of the tissue.   The activity of the protein of the invention may be measured, inter alia, by the following method:   Assay for tissue regeneration activity is described in WO 95/16035 (bone, cartilage, key) International Publication WO95 / 05846 (nerves, neurons); International Publication WO91 / 05 7491 (skin, endothelium), including but not limited to .   Assays for wound healing activity are described in Winter, Epidermal Wound Healing, pps. 71-112 ( Maibach, HI and Rovee, DT, eds.), Year Book Medical Publishers, Inc., Ch. icago (modified by Eaglstein and Mertz, J. Invest. Dermatol 71: 382-384 (1978) (Decorated), but are not limited thereto.   Activin / inhibin activity   Also, the protein of the present invention may exhibit activin- or inhibin-related activity. I Inhibins are characterized by their ability to inhibit follicle stimulating hormone (FSH) release, Activins are characterized by their ability to stimulate the release of follicle stimulating hormone (FSH). You. Therefore, the protein of the present invention may be used alone or as a member of the inhibin α family. In the form of a heterodimer with a female mammal, which reduces the fertility of a female mammal May be useful as an infertility drug based on the ability of inhibin to reduce spermatogenesis in animals You. Administration of sufficient amounts of other inhibins may result in infertility in these mammals. Can be guided. Alternatively, the proteins of the present invention may be homodimers or Is a heterodimer with other protein subunits of the inhibin-β group Based on the ability of activin molecules to stimulate FSH release from anterior pituitary cells And may be useful as a therapeutic agent that induces fertility. For example, US Pat. See 98885. In addition, the protein of the present invention is useful for reproduction in sexually immature mammals. It may be useful for enhancement and, as a result, homes such as cattle, sheep and pigs Increased fertility during the life of the animal.   The activity of the protein of the invention may be measured, inter alia, by the following method:   Assays for activin / inhibin activity are described in Vale et al., Endocrinology 91: 5. 62-572, 1972; Ling et al., Nature 321: 779-782, 1986; Vale et al., Nature 3. 21: 776-779, 1986; Mason et al., Nature 318: 659-663,1985; Forage et al., Pr oc. Natl. Acad. Sci. USA 83: 3091-3095, 1986, including Not limited to these.   Chemotaxis / chemokinesis activity   The protein of the present invention can be used for mammalian cells such as monocytes, neutrophils, T cells, mast cells, and eosinophils. Chemotactic or chemokinetic activity of spheres and / or endothelial cells (eg, Acting as in). Uses chemotactic and chemokinetic proteins And recruit or attract the desired cell population to the desired site of action. Chemotaxis Alternatively, chemokinesis proteins may be used to treat and localize tissue injuries and other trauma. It is particularly advantageous for treating localized infections. For example, tumors of lymphocytes, monocytes or neutrophils Attraction to tumor or infected site may improve immune response to tumor or infectious agent You.   Certain proteins or peptides have chemotactic activity for specific cell populations. Direct or indirect, if stimulated, the direction or behavior of such cell populations. Command movement. Preferably, the protein or peptide has a directed movement of the cell. Have the ability to directly stimulate Specific proteins have chemotactic activity on cell populations Is used to determine whether such proteins or peptides have known chemotaxis Can be easily determined.   The activity of the protein of the invention may be measured, inter alia, by the following method:   Assay for chemotaxis activity (an assay to identify proteins that induce or interfere with chemotaxis) Say) describes the ability of the protein to induce cell translocation across the membrane as well as the Includes assays that measure the ability of a protein to induce adhesion to other cell populations. Moving Assays suitable for and adhesion are described in Current Protocols in Immunology, Ed by J.E. Coligan, A.M. Kruisbeek, D.H. Margulies, E.M. Shevach, W. Strober, Pub. G reene Publishing Associates and Wiley-Interscience (Chapter 6.12, Measurem ent of alpha and beta Chemokines 6.12.1-6.12.28; Taub et al. J. Clin. Inve st. 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, assessed in 1994 Includes, but is not limited to:   Hemostasis and thrombolytic activity   In addition, the protein of the present invention may exhibit hemostatic or thrombolytic activity. As a result Thus, such proteins are useful in the treatment of various clotting disorders, including genetic disorders such as hemophilia. Or in the treatment of injury caused by trauma, surgery or other causes. Blood clots and other hemostasis. The protein of the present invention may be used to dissolve or form a thrombus. Growth inhibition and the symptoms resulting therefrom (eg, myocardial infarction and central nervous system blood) It may be useful in the treatment and prevention of vascular infarcts (eg, stroke).   The activity of the protein of the invention may be measured, inter alia, by the following method:   Assays for haemostatic and thrombolytic activity are described by Linet et al., J. Clin. Pharmacol. 26: 1. 31-140, 1986; Burdick et al., Thrombosis Res. 45: 413-419, 1987; Humphrey et al., Fibrinolysis 5: 71-79 (1991); Schaub, Prostaglandins 35: 467-474, 1988. But not limited thereto.   Receptor / ligand activity   Further, the protein of the present invention may be a receptor, a receptor ligand or a receptor / ligand interaction. May exhibit activity as inhibitors or agonists. Such receptors and Examples of gand are cytokine receptors and their ligands, receptor kinases and And their ligands, receptor phosphatases and their ligands, cells Receptors involved in cell interactions and their ligands (cell adhesion molecules (SELEC , Integrin and their ligands) and antigen presentation, antigens Receptor / ligand pairs involved in the development of cognitive, cellular and humoral immune responses Inclusive) but not limited to. Receptors and ligands are related receptors Screening of potential peptide or small molecule inhibitors for body / ligand interactions It is also useful for training. The protein of the present invention (receptor and ligand fragments Include, but are not limited to, blocking the receptor / ligand interaction itself. May be useful as a harmful agent.   The activity of the protein of the invention may be measured, inter alia, by the following method:   Suitable assays for receptor-ligand activity are described in Current Protocols in Immunolog. y, Ed by J. E. Coligan, A.S. M. Kruisbeek, D.S. H. Margulies, E. M. Shevach , W. Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Ch apter 7.28, Measurement of Cellular Adhesion under static conditions 7.2 8.1-7.28.22), Takai et al., Proc. Natl. Acad. Sci. USA 84: 6864-6868, 1987; Bier er et al., J. Exp. Med. 168: 1145-1156, 1988; Rosenstein et al., J. Am. Exp. Me d. 169: 149-1601989; Stoltenborg et al., J. Am. Immunol. Methods 175: 59-68, 199 4; includes the assay described in Stitt et al., Cell 80: 661-670, 1995, but Not limited to them.   Anti-inflammatory activity   The protein of the present invention can exhibit anti-inflammatory activity. Anti-inflammatory activity is involved in the stimulus response By stimulating cells, cell-cell interaction (eg, attachment) Chemotaxis of cells involved in the inflammatory process by inhibiting or promoting By inhibiting or promoting, by inhibiting or promoting cell extravasation, Alternatively, it stimulates the production of other factors that more directly inhibit or promote the inflammatory response or Is exhibited by suppressing. Symptoms of inflammation ( Includes chronic or acute symptoms, infection-related inflammation (including septic shock, sepsis) Or systemic inflammatory response syndrome (SIRS)), ischemia-reperfusion injury, Fatal injury by dotoxin, arthritis, hyperacute rejection mediated by complement, Nephritis, lung injury induced by cytokines or chemokines, inflammatory bowel disease Disease, Crohn's disease or overproduction of cytokines such as TNF or IL-1 (Including, but not limited to, diseases arising from). Departure Myelin protein is a cure for anaphylaxis and hypersensitivity to antigenic substances or materials. May also be useful for treatment.   Cadherin / tumor entry inhibitory activity   Cadherin is a calcium-dependent adhesion molecule, Plays a major role in determining specific cell types, in particular I think that the. Loss or alteration of normal cadherin expression is associated with tumor growth and metastasis. It can induce a change to the relevant cell adhesion properties. Cadherin dysfunction is vulgaris Pemphigus and pemphigus foliaceus (autoimmune cutaneous blistering disease), Crohn's disease, and It is also involved in other human diseases, such as some developmental abnormalities.   The cadherin superfamily contains over 40 members, each of which is distinct. Expression patterns. All members of the superfamily Have a common conserved extracellular repeat (cadherin domain), but There are structural differences in other parts. Cadherin domain binds to calcium Calcium is necessary for their attachment as they combine to form their tertiary structure. You. Few amino acids in the first cadherin domain are due to homophilic attachment Base Modification of this recognition site can alter the specificity of cadherin, providing a foundation As a result, the mutant molecule not only recognizes itself, but also Be able to bind to doherin. In addition, some cadherins are It is also involved in heterophilic attachment to phosphorus.   E-cadherin, one of the members of the cadherin superfamily, It is expressed in cell types. Pathologically, E-cadherin expression is If lost, the malignant cells become invasive and the cancer metastasizes. E-cadhedrine Transfection of a polynucleotide that expresses Cell morphology, restore cell-to-cell and cell-cell adhesion, By reducing the rate of cell growth and dramatically reducing the growth of anchorage-dependent cells, The changes associated with cancer were reversed. Thus, re-introducing E-cadhedrin expression Returns the carcinoma to a less advanced stage. Other cadherins are also used in other tissue It may have the same invasive inhibitory role in Ip-derived carcinomas. Soy sauce , A protein of the present invention having cadherin activity, and a gene encoding such a protein The bright polynucleotides can be used to treat cancer. Such protein or poly Introducing nucleotides into cancer cells may provide normal cadherin expression. Can reduce or eliminate the cancerous changes observed in these cells .   Cancer cells are also known to express cadherin in a different tissue type than originally intended. Therefore, these cancer cells can invade different tissues and metastasize. Mosquito The protein of the present invention having doherin activity, and the polynucleotide of the present invention encoding such a protein Nucleotide replaces cadherin, which is inappropriately expressed in these cells. Restores normal cell adhesion properties and reduces or eliminates cell propensity to metastasize sell.   Further, the protein of the present invention having cadherin activity, and encoding such a protein Antibodies that recognize and bind to cadherin using the polynucleotides of the present invention You can also get. Tumor cell cadherds inappropriately expressed using such antibodies Can block cell adhesion and prevent cells from forming tumors elsewhere. Wear. Such anti-cadhedrin antibodies can be used to evaluate cancer grade, pathological type, and prognosis. Can be used as a marker for In other words, when the cancer progresses, cadherin The expression is reduced and this cadherin expression can be Can be detected.   A fragment of the protein of the present invention having cadherin activity, preferably cadherin Of the present invention encoding such protein fragments Use polynucleotides to bind to cadherin, producing undesirable effects By blocking cadherin binding, it can also block cadherin function. Wear. Furthermore, a fragment of the protein of the present invention having cadherin activity, preferably Truncated soluble mosquitoes known to be stable in the circulatory system of cancer patients Dohedrin fragments and polynucs encoding such protein fragments Reotide can also be used to disrupt correct cell-cell attachment.   Assays for cadherin adhesion and entry inhibitory activity are described in Hortsch et al. J Bio l Chem 270 (32): 18809-18817,1995; Miyaki et al. Oncogene 11: 2547-2552,1995; Ozawa et al. Cell 63: 1033-1038, 1990. Not limited to them.   Tumor inhibitory activity   In addition to the activities described above for the immunological treatment or prevention of tumors, the protein of the present invention Can exhibit antitumor activity. Certain proteins directly or indirectly affect tumor growth (eg, (Via ADCC). Certain proteins are found in tumor or tumor precursor tissue Act to inhibit the formation of tissue necessary to support tumor growth (eg, angiogenesis) Other factors, agents or cell types that inhibit tumor growth Factors, agents or agents that cause the production of Alternatively, a tumor inhibitory activity may be exhibited by removing or inhibiting a cell type.   Other activities   The proteins of the present invention may exhibit one or more of the following additional activities or effects: : Infections, including but not limited to bacteria, viruses, fungi and other parasites Sex factor killing; height, weight, hair color, eye color, skin or other tissue pigmentation Or the size or form of an organ or body part (eg, breast augmentation or vice versa) Effects on body characteristics (suppression or promotion), including: fat, protein or charcoal consumed Effects of hydrate on digestion; appetite, libido, stress, cognition (including cognitive disorders), depression Behavioral characteristics, including (but not limited to) depressive disorders and violent behavior Effects; providing analgesic or other pain relief; in non-hematopoietic lineages Promoting differentiation and proliferation of embryonic stem cells; hormonal or endocrine activity; Correct enzyme deficiency and treat related disorders; hyperproliferative disorders (eg, such as psoriasis) ) Treatment; immunoglobulin-like activity (eg, the ability to bind antibodies or complement); And such a protein or protein acting as an antigen in a vaccine composition. Ability to generate an immune response to other substances or entities that cross react with white.Administration and dose   The protein of the invention (from any source, recombinant and non-recombinant) Methods, including, but not limited to, those described above) with a pharmaceutically acceptable carrier. They may be used together in a pharmaceutical composition. Such compositions (besides the protein and carrier) , Diluents, fillers, salts, buffers, stabilizers, solubilizers, and It may contain other well-known substances. The term "pharmaceutically acceptable" A non-toxic substance that does not interfere with the effectiveness of the biological activity of the active ingredient. Carrier properties Depends on the route of administration. The pharmaceutical composition of the present invention comprises M-CSF, GM-CSF, TN F, 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, I L-14, IL-15, IFN, TNF0, TNF1, TNF2, G-CSF, Meg-CSF, thrombopoietin, stem cell factor, and erythropoietin May contain cytokines, lymphokines, or other hematopoietic factors such as No. The pharmaceutical composition further enhances the protein activity or enhances the activity in therapy. Or may contain other agents that supplement their usefulness. Such additional factors and And / or synergistic effect with the protein of the present invention by containing an agent in a pharmaceutical composition The results may be achieved or side effects may be minimized. Conversely, certain cytokines , Lymphokines, other hematopoietic factors, thrombolytic or antithrombotic factors, or anti-inflammatory Including the protein of the present invention in the formulation of the drug, cytokines, lymphokines, other hematopoietic factors May minimize the side effects of blood, thrombolytic or antithrombotic factors, or anti-inflammatory drugs. No.   The protein of the present invention may be a multimer (for example, a heterodimer or a homodimer) or It may be active by itself or in a complex with other proteins. As a result, The pharmaceutical composition comprises such a multimeric or complexed form of the protein of the present invention. You may.   The pharmaceutical composition of the present invention may be in the form of a complex of the protein of the present invention and a protein or peptide antigen. It may be in a state. Protein and / or peptide antigens can be It will deliver a stimulus signal to the lymphocytes. B lymphocytes have their surface immunity Will respond to antigen through globulin receptors. T lymphocytes are MHC proteins Will respond to the antigen through the T cell receptor (TCR). MHC and host cell class I and class II MHC genes Structurally related proteins, including those that have been loaded, are peptide-antigens against T lymphocytes. It will help to present the original. The antigen component was a purified MHC-peptide complex only. Or with co-stimulatory molecules that can send signals directly to T cells Can be done. Alternatively, surface immunoglobulins on B cells and T cells on T cells Antibodies that can bind CR and other molecules can also be mixed with the pharmaceutical compositions of the present invention. Wear.   The pharmaceutical composition of the present invention may be in the form of liposome, in which the protein of the present invention is contained. And other pharmaceutically acceptable carriers, amphipathic agents such as lipids (mice in aqueous solution). Agglomerate form, such as insoluble monolayer, liquid crystal or lamellar layer) Have been combined. Suitable lipids for liposome formulations are monoglycerides, diglycerides , Sulfatizide, lysolecithin, phospholipids, saponins, bile acids, etc. However, it is not limited to these. The preparation of such liposome formulations is within the level of ordinary skill in the art. And, for example, U.S. Pat. Nos. 4,235,871, 4501728, 4837028, And 4737323, all of which are described herein by reference. Also And the like).   As used herein, the term "therapeutically effective amount" refers to a significant patient benefit, e.g., Sufficient pharmaceutical composition or method to show improvement in symptoms of the condition, healing, increased rate of healing It means the total amount of each active ingredient. Used for individual active ingredients administered alone When used, the term refers only to that component. When used in combinations of active ingredients, The total amount of active ingredients that produces a therapeutic effect, regardless of whether U.   In practicing the treatment method of the present invention, a disease to be treated with a therapeutically effective amount of the protein of the present invention. Administered to a mammal having a morphology. According to the method of the present invention, alone or with a cytokine The protein of the invention together with other therapeutic agents such as lymphokines or other hematopoietic factors. It may be administered. One or more cytokines, lymphokines or other When co-administered with hematopoietic factors, the protein of the present invention may be administered with cytokines, lymphokines, and other It may be administered simultaneously or sequentially with blood, thrombolytic or antithrombotic factors. Gradually When administering the next dose, the attending physician will ask for cytokines, lymphokines, other hematopoietic factors, blood Appropriate administration of thrombolytic factor or antithrombotic factor in combination with the protein of the present invention Will determine the order.   The administration of the protein of the present invention in the pharmaceutical composition of the present invention or used in the practice of the present invention can be carried out by various conventional methods. Administration methods, e.g., oral feeding, inhalation, or intradermal, subcutaneous, or intravenous injection. I can. Intravenous injection into a patient is preferred.   When a therapeutically effective amount of the protein of the present invention is orally administered, the protein of the present invention may contain , Powder, solution or elixir form. When administered in tablet form, The pharmaceutical composition may further comprise a solid carrier such as gelatin or an adjuvant. It may be. Tablets, capsules, and powders contain about 5 to 95% of a protein of the present invention, It preferably contains about 25-90% of the protein of the invention. Place to administer in liquid form Oil, water, petroleum, oils of animal or vegetable origin, such as peanut oil, mineral oil , Soybean oil, sesame oil, or synthetic fats and oils may be added. Pharmaceutical group in liquid form The composition can be a saline solution, dextrose or other saccharide solution, or glycol (E.g., ethylene glycol, propylene glycol or polyethylene glycol) Ricoh ) May further be contained. When administered in liquid form, the pharmaceutical composition comprises 0.5 to 90% by weight of the protein of the present invention, preferably about 1 to 50% of the protein of the present invention. Contains white.   When a therapeutically effective amount of the protein of the present invention is administered by intravenous, intradermal or subcutaneous injection, The protein of the present invention may be in the form of a pyrogen-free, parenterally acceptable aqueous solution . Of such a parenterally acceptable protein solution having the appropriate pH, isotonicity, and stability. Preparation is within the skill of the art. Preferred medicament for intravenous, intradermal or subcutaneous injection The composition comprises, in addition to the protein of the present invention, sodium chloride for injection, Ringer's solution, Dextrose, dextrose and sodium chloride solution for injection, lactic acid for injection Should contain Ringer's solution, or other carriers known in the art . The pharmaceutical composition of the present invention may comprise a stabilizer, a preservative, a buffer, an antioxidant, Other additives known to the consumer.   The amount of the protein of the invention in the pharmaceutical composition of the invention depends on the nature and severity of the condition to be treated, As well as the nature of the treatment the patient has already received. Ultimately, your doctor Each patient will determine the amount of the protein of the invention to be treated. First, the doctor in charge Administer an amount of the protein of the invention and observe the patient's response. Until optimal therapeutic effects are obtained Higher doses of the protein of the present invention may be administered and may be used once optimal therapeutic effect is obtained. Do not increase the volume further. Various pharmaceutical compositions for performing the methods of the present invention include About 0.01 μg to about 100 mg of the protein of the present invention (preferably, About 0.1 μg to about 10 mg / kg body weight, more preferably 1 kg / kg body weight 0.1 to about 1 mg of the protein of the present invention.   The duration of treatment by intravenous administration using the composition of the present invention depends on the severity of the disease to be treated. And will vary depending on the condition and response of each patient. Each of the proteins of the present invention The duration of application will range from 12 to 24 hours for continuous intravenous administration . Ultimately, the attending physician will determine the stage of treatment by intravenous administration using the pharmaceutical composition of the present invention. Will decide between.   Immunizing an animal with the protein of the present invention to specifically react with the protein of the present invention; And monoclonal antibodies may be obtained. Whole protein or its fragment G May be used as an immunogen to obtain such antibodies. Peptide immunogen is carboxy powder It may further contain a cysteine residue at the end, and can be Binds to haptens such as anine (KLH). Method for synthesizing such a peptide Are known in the art, for example, R.P.Merrifield, J.Amer.Chem.Soc. 8 5, 2149-2154 (1963); L. Krstenansky, et. al., FEBS Lett. 211, 10 (1987 ). Monoclonal antibodies that bind to the protein of the present invention It may be a useful diagnostic agent for immunodetection of the inventive protein. Neutralizing anti-binding to the protein of the present invention The body can be useful as a therapeutic agent for conditions associated with the protein of the present invention, and Certain tumors in the treatment of some forms of cancer involving aberrant expression of the light protein It may be useful in treating ulcers. In the case of cancer cells or white blood cells, the protein of the present invention Is a neutralizing monoclonal antibody against cancer cells that can be mediated by the protein of the present invention. It may be useful in detecting and preventing infestations.   For compositions of the invention useful for the regeneration of bone, cartilage, keys or ligaments, the method of treatment comprises: The composition can be administered locally, systemically, or locally as an implant or device. Administration. When administered, the therapeutic composition used in the present invention comprises Of course, it is a pyrogen-free, physiologically acceptable form. In addition, Alternatively, the composition may be encapsulated or injected as a viscous form to provide bone, cartilage or May be delivered to the site of tissue damage. Local administration is suitable for wound healing and tissue repair I do. Therapeutically useful action other than the protein of the present invention which may be contained in the above composition The agent is, alternatively or additionally, administered simultaneously or sequentially with the composition in the method of the present invention. May be. Preferably, for bone and / or cartilage formation, the composition comprises Delivering the white-containing composition to the site of bone and / or cartilage damage, and developing the bone and cartilage; Provides a structure for living, and optimally contains a matrix that can be absorbed into the body Will have. Such matrices are currently used for other implanted medical devices It may be made from the materials that have been used.   The choice of matrix material depends on its biocompatibility, biodegradability, mechanical properties, cosmetic Based on appearance and interface properties. The appropriate formulation will be determined by the particular application of the composition. U. Possible matrices for the composition are biodegradable, chemically known sulfuric acid Lucium, tricalcium phosphate, hydroxyapatite, polylactic acid, polyglyco It may be oleic acid and polyanhydride. Other available materials are biodegradable, Well-known in nature, for example, bone or skin collagen. further The matrix may contain pure proteins or extracellular matrix components. Other possible matrices include sintered hydroxyapatite, bioglass, aluminum Not biodegradable, such as silicates or other ceramics, It is. The matrix is a combination of materials of the above type, for example polylactic acid and Including hydroxyapatite or collagen and tricalcium phosphate It may be. Bioceramics may be added to the composition, for example, calcium-alumina. It may be altered in the to-phosphate and processed to produce pore size, particle size, The particle shape and biodegradability may be varied.   Lactic acid in the form of porous particles having a diameter in the range of 150 to 800 microns and A 50:50 (molar weight) copolymer of biglycolic acid is presently preferred. . In some applications, carboxymethylcellulose or autologous Prevent the dissociation of the protein composition from the matrix using a sequestering agent such as a clot And would be useful.   Preferred families of sequestrants are methylcellulose, ethylcellulose, Roxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl Alkyl cells containing methylcellulose and carboxymethylcellulose Cellulosic materials such as loin (including hydroxyalkylcellulose) Most preferred is a cationic salt of carboxymethylcellulose (CMC). Other preferred sequestering agents are hyaluronic acid, sodium alginate, poly (ethylene Glycol), polyoxyethylene oxide, carboxyvinyl polymer and Poly (vinyl alcohol). The amount of sequestrant useful in the present invention depends on the total formulation weight. 0.5 to 20% by weight, preferably 1 to 10% by weight, based on the amount, Prevents protein desorption from the polymer matrix and allows for proper handling of the composition The amount of progenitor cells that infiltrate the matrix To give the protein a chance to promote the osteogenic activity of cells, not much Not to be.   In a further composition, the protein of the present invention comprises a bone and / or cartilage defect, wound, Alternatively, it may be mixed with other agents that are beneficial in treating the tissue. These agents are , Epidermal growth factor (EGF), platelet-derived growth factor (PDGF), transformed growth factor (TGF-α and TGF-β) and insulin-like growth factor (IGF) Include.   At present, the therapeutic compositions are also valuable for veterinary use. For details, In addition to humans, livestock and thoroughbred horses are treated with the protein of the present invention. Is a desirable patient.   Rules of administration of protein-containing pharmaceutical compositions used for tissue regeneration alter the effect of proteins Factors, such as tissue weight, damage site, and damage desired to be formed. The condition of the tissue received, the size of the wound, the type of tissue required (eg, bone), the patient's year Consider age, gender and diet, severity of infection, duration of administration, and other clinical factors And your doctor will decide. The dose depends on the type of matrix used for reconstitution. And depending on the content of other proteins in the pharmaceutical composition. For example, IGF   Addition of other known growth factors, such as I (insulin-like growth factor I) to the final composition Addition can also affect dosage. Tissue / bone growth and / or repair, By regular assessment by morphological survey and tetracycline labeling The progress can be monitored.   The polynucleotide of the present invention can also be used for gene therapy. Such polynuks Leotide is introduced into cells in vivo or ex vivo and expressed in a mammalian subject. Can be made. Other known methods for introducing nucleic acids into cells or organisms The polynucleotide of the present invention may be administered more (in a viral vector, Or in the form of naked DNA, but is not limited thereto).   Culturing and growing the cells ex vivo in the presence of the protein of the invention, or Produce the desired effect on such cells or produce the desired activity in such cells. May be. The treated cells are then introduced in vivo for therapeutic purposes. can do.   The patents and publications cited herein are hereby incorporated by reference in their entirety. It is assumed that

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61P 7/04 A61P 25/00 17/02 29/00 25/00 31/00 29/00 33/00 31 / 00 35/00 33/00 35/04 35/00 37/04 35/04 37/06 37/04 43/00 105 37/06 C07K 14/47 43/00 105 C12P 21/02 C C07K 14/47 C12N 15/00 ZNAA C12N 5/10 5/00 B C12P 21/02 A61K 37/02 (81) Designated countries EP (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE), OA (BF, BJ, CF, CG, CI, CM, GA, GN, ML, MR, NE, SN, TD, TG), AP (GH) , GM, KE, LS, MW, SD, SZ, UG, ZW), EA ( M, AZ, BY, KG, KZ, MD, RU, TJ, TM), AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, CA, CH, CN, CU, CZ, DE , DK, EE, ES, FI, GB, GE, GH, GM, GW, HU, ID, IL, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MD, MG, MK, MN, MW, MX, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, UA , UG, UZ, VN, YU, ZW (72) Inventor McCoy, John M. United States 01867 Massachusetts Reading, 56 Howard Street 56 (72) Inventor Ravalee, Edward Earl United States 01451 Harbour, Massachusetts L.A., Lisa A. Inventor Lacey, Lisa A. United States 01720 Acton, Mass., School Street 124 (72) Inventor Tracy, Maurice United States 02167 Chesnut Hill, Walt. No. 93 (72) Inventor Spalding, Vicky United States 01821 Billorica, Mass., Meadowbank Road No. 11 (72) Inventor Augustino, Michael Jay United States 01810 Andover, Mass., Walter Avenue 26 (72) Inventors Howes, Stephen H. United States 02144, Chester Street 44, Apartment 2, Somerville, Massachusetts. (72) Inventor Fechtel, Kim United States 02174 Arlington, MA 02174 Massachusetts. On Road No. 46

Claims (1)

[Claims]   1. (A) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 1;   (B) nucleotides from nucleotide 185 to nucleotide 1600 of SEQ ID NO: 1 A polynucleotide comprising a nucleotide sequence;   (C) the sequence from nucleotide 1403 to nucleotide 1600 of SEQ ID NO: 1 A polynucleotide comprising a nucleotide sequence;   (D) nucleotides from nucleotide 1 to nucleotide 850 of SEQ ID NO: 1 A polynucleotide comprising a nucleotide sequence;   (E) of clone do154 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence;   (F) of clone do154 deposited under accession number ATCC 98468 Polynucleotide encoding full-length protein encoded by cDNA insert Tide;   (G) of clone do154 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence;   (H) of clone do154 deposited under accession number ATCC 98468 Polynucleotide encoding mature protein encoded by cDNA insert Tide;   (I) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 2 Tide;   (J) including a fragment of the amino acid sequence of SEQ ID NO: 2 having biological activity (The fragment is SEQ ID NO: 2-8) Contiguous amino acids);   (K) a polynucleotide that is an allelic variant of the polynucleotide of (a) to (h) above Nucleotides;   (L) A polynucleotide encoding a species homolog of the protein of (i) or (j) above Otide; and   (M) any one of the polynucleotides (a) to (j) under strict conditions Polynucleotide that can hybridize to An isolated polynucleotide selected from the group consisting of:   2. 2. The method of claim 1, wherein the polypeptide is operably linked to at least one expression control sequence. Renucleotide.   3. A host cell transformed with the polynucleotide of claim 2.   4. 4. The host cell of claim 3, wherein said cell is a mammalian cell.   5. (A) growing the culture of the host cell of claim 3 in a suitable medium;   (B) Purifying the protein from the culture A method for producing a protein encoded by the polynucleotide of claim 2, comprising:   6. A protein produced by the method of claim 5.   7. (A) the amino acid sequence of SEQ ID NO: 2;   (B) an amino acid sequence from amino acid 1 to amino acid 222 of SEQ ID NO: 2;   (C) the amino acid of SEQ ID NO: 2, comprising eight consecutive amino acids of SEQ ID NO: 2 Fragments of an acid sequence; and   (D) of clone do154 deposited under accession number ATCC 98468 Amino acid sequence encoded by cDNA insert A protein comprising an amino acid sequence selected from the group consisting of: A protein substantially free of.   8. The protein of claim 7, comprising the amino acid sequence of SEQ ID NO: 2.   9. Includes amino acid sequence from amino acid 1 to amino acid 222 of SEQ ID NO: 2 The protein of claim 7.   10. A composition comprising the protein of claim 7 and a pharmaceutically acceptable carrier.   11. An isolated gene corresponding to the cDNA sequence of SEQ ID NO: 1.   12. (A) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 3;   (B) including nucleotides 47 to 2065 of SEQ ID NO: 3 A polynucleotide;   (C) SEQ ID NO: 3 from nucleotide 1086 to nucleotide 1848 A polynucleotide comprising;   (D) Clone dx2901 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of   (E) Clone dx2901 deposited under accession number ATCC 98468 Encoding a full-length protein encoded by a cDNA insert Do;   (F) clone dx290 1 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of   (G) Clone dx2901 deposited under accession number ATCC 98468 Encoding a mature protein encoded by a cDNA insert Do;   (H) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 4 ;   (I) including a fragment of the amino acid sequence of SEQ ID NO: 4 having biological activity A polynucleotide encoding the protein (the fragment comprises the eight Contiguous amino acid sequences);   (J) Polynucleic acid which is an allelic variant of the polynucleotide of (a) to (g) above Nucleotides;   (K) a polynucleotide encoding a species homolog of the protein of (h) or (i) above C; and   (L) any one of the polynucleotides (a) to (i) under strict conditions Polynucleotide that can hybridize to An isolated polynucleotide selected from the group consisting of:   13. (A) the amino acid sequence of SEQ ID NO: 4;   (B) the amino acid sequence of SEQ ID NO: 4 from amino acid 312 to amino acid 600;   (C) the amino acid of SEQ ID NO: 4, comprising eight consecutive amino acids of SEQ ID NO: 4 Fragments of an acid sequence; and   (D) Clone dx2901 deposited under accession number ATCC 98468 Amino acid sequence encoded by the cDNA insert of A protein comprising an amino acid sequence selected from the group consisting of: A protein substantially free of.   14． An isolated gene corresponding to the cDNA sequence of SEQ ID NO: 3.   15. (A) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 5;   (B) the nucleotide sequence from nucleotide 107 to nucleotide 724 of SEQ ID NO: 5 A polynucleotide comprising a reotide sequence;   (C) the nucleotide sequence from nucleotide 218 to nucleotide 724 of SEQ ID NO: 5 A polynucleotide comprising a reotide sequence;   (D) the nucleotide sequence from nucleotide 536 to nucleotide 866 of SEQ ID NO: 5 A polynucleotide comprising a reotide sequence;   (E) clone ek3904 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of   (F) Clone ek3904 deposited under accession number ATCC 98468 Polynucleotide encoding the full-length protein encoded by the cDNA insert of Otide;   (G) Clone ek3904 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of   (H) clone ek3904 deposited under accession number ATCC 98468 Encoding a mature protein encoded by a cDNA insert Otide;   (I) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 6 Tide;   (J) including a fragment of the amino acid sequence of SEQ ID NO: 6 having biological activity (The fragment is SEQ ID NO: 6 8 Contiguous amino acids);   (K) a polynucleotide which is an allelic variant of the polynucleotide of (a) to (k) above Nucleotides;   (L) A polynucleotide encoding a species homolog of the protein of (i) or (j) above Otide; and   (M) any one of the polynucleotides (a) to (j) under strict conditions Polynucleotide that can hybridize to An isolated polynucleotide selected from the group consisting of:   16. (A) the amino acid sequence of SEQ ID NO: 6;   (B) an amino acid sequence from amino acid 6 to amino acid 92 of SEQ ID NO: 6;   (C) the amino acid of SEQ ID NO: 6, comprising eight consecutive amino acids of SEQ ID NO: 6 Fragments of an acid sequence; and   (D) Clone ek3904 deposited under accession number ATCC 98468 Amino acid sequence encoded by the cDNA insert of A protein comprising an amino acid sequence selected from the group consisting of: A protein substantially free of.   17． An isolated gene corresponding to the cDNA sequence of SEQ ID NO: 5.   18. (A) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 7;   (B) the nucleotide sequence from nucleotide 31 to nucleotide 1230 of SEQ ID NO: 7 A polynucleotide comprising a reotide sequence;   (C) nucleotides from nucleotide 289 to nucleotide 1230 of SEQ ID NO: 7 A polynucleotide comprising a nucleotide sequence;   (D) nucleotides from nucleotide 344 to nucleotide 1119 of SEQ ID NO: 7 A polynucleotide comprising a nucleotide sequence;   (E) Clone er471 7 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of   (F) Clone er471 7 deposited under accession number ATCC 98468 Polynucleotide encoding the full-length protein encoded by the cDNA insert of Otide;   (G) Clone er471 7 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of   (H) clone er471 7 deposited under accession number ATCC 98468 Encoding a mature protein encoded by a cDNA insert Otide;   (I) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 8 Tide;   (J) including a fragment of the amino acid sequence of SEQ ID NO: 8 having biological activity (The fragment is SEQ ID NO: 8-8) Contiguous amino acids);   (K) a polynucleotide that is an allelic variant of the polynucleotide of (a) to (h) above Nucleotides;   (L) A polynucleotide encoding a species homolog of the protein of (i) or (j) above Otide; and   (M) any one of the polynucleotides (a) to (j) under strict conditions Polynucleotide that can hybridize to An isolated polynucleotide selected from the group consisting of:   19. (A) the amino acid sequence of SEQ ID NO: 8;   (B) the amino acid sequence of amino acid 111 to amino acid 363 of SEQ ID NO: 8;   (C) the amino acid of SEQ ID NO: 8, comprising eight consecutive amino acids of SEQ ID NO: 8 Fragments of an acid sequence; and   (D) Clone er471 7 deposited under accession number ATCC 98468 Amino acid sequence encoded by the cDNA insert of A protein comprising an amino acid sequence selected from the group consisting of: A protein substantially free of.   20. An isolated gene corresponding to the cDNA sequence of SEQ ID NO: 7.   21. (A) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 9;   (B) nucleotides from nucleotide 62 to nucleotide 322 of SEQ ID NO: 9 A polynucleotide comprising an otide sequence;   (C) the nucleotide sequence from nucleotide 571 to nucleotide 878 of SEQ ID NO: 9 A polynucleotide comprising a reotide sequence;   (D) of clone fs403 deposited under accession number $ TCC98468 A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence;   (E) of clone fs403 deposited under accession number TCC98468 Polynucleotide encoding full-length protein encoded by cDNA insert Tide;   (F) of clone fs403 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence;   (G) of clone fs403 deposited under accession number ATCC 98468 Polynucleotide encoding mature protein encoded by cDNA insert Tide;   (H) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 10 Otide;   (I) a fragment of the amino acid sequence of SEQ ID NO: 10 having biological activity A polynucleotide encoding the protein containing the fragment (the fragment is SEQ ID NO: 10 Of 8 amino acids);   (J) Polynucleic acid which is an allelic variant of the polynucleotide of (a) to (g) above Nucleotides;   (K) a polynucleotide encoding a species homolog of the protein of (h) or (i) above Otide; and   (L) any one of the polynucleotides (a) to (i) under strict conditions Polynucleotide that can hybridize to An isolated polynucleotide selected from the group consisting of:   22. (A) the amino acid sequence of SEQ ID NO: 10;   (B) an amino acid sequence of SEQ ID NO: 10 comprising eight consecutive amino acids of SEQ ID NO: 10 A fragment of the amino acid sequence; and   (C) of clone fs403 deposited under accession number ATCC 98468 Amino acid sequence encoded by cDNA insert A protein comprising an amino acid sequence selected from the group consisting of: A protein substantially free of.   23. An isolated gene corresponding to the cDNA sequence of SEQ ID NO: 9.   24. (A) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 11;   (B) nucleotides from nucleotide 43 to nucleotide 1671 of SEQ ID NO: 11 A polynucleotide comprising a nucleotide sequence;   (C) the sequence of SEQ ID NO: 11 from nucleotide 112 to nucleotide 1671 A polynucleotide comprising a nucleotide sequence;   (D) nucleotides from nucleotide 224 to nucleotide 679 of SEQ ID NO: 11 A polynucleotide comprising a nucleotide sequence;   (E) of clone ga636 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence;   (F) of clone ga636 deposited under accession number ATCC 98468; Polynucleotide encoding full-length protein encoded by cDNA insert Tide;   (G) of clone ga636 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence;   (H) of clone ga636 deposited under accession number ATCC 98468; Polynucleotide encoding mature protein encoded by cDNA insert Tide;   (I) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 12 Otide;   (J) a fragment of the amino acid sequence of SEQ ID NO: 12 having biological activity A polynucleotide encoding the protein comprising the fragment (SEQ ID NO: 12 8 contiguous amino acids);   (K) a polynucleotide that is an allelic variant of the polynucleotide of (a) to (h) above Nucleotides;   (L) A polynucleotide encoding a species homolog of the protein of (i) or (j) above Otide; and   (M) any one of the polynucleotides (a) to (j) under strict conditions Polynucleotide that can hybridize to An isolated polynucleotide selected from the group consisting of:   25. (A) the amino acid sequence of SEQ ID NO: 12;   (B) amino acid sequence from amino acid 62 to amino acid 212 of SEQ ID NO: 12 ;   (C) an amino acid sequence of SEQ ID NO: 12 comprising eight consecutive amino acids of SEQ ID NO: 12; A fragment of the amino acid sequence; and   (D) of clone ga636 deposited under accession number ATCC 98468 Amino acid sequence encoded by cDNA insert A protein comprising an amino acid sequence selected from the group consisting of: A protein substantially free of.   26. An isolated gene corresponding to the cDNA sequence of SEQ ID NO: 11.   27. (A) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 13;   (B) the nucleotide sequence from nucleotide 17 to nucleotide 523 of SEQ ID NO: 13 A polynucleotide comprising a reotide sequence;   (C) the nucleotide sequence from nucleotide 77 to nucleotide 523 of SEQ ID NO: 13 A polynucleotide comprising a reotide sequence;   (D) the nucleotide sequence from nucleotide 1 to nucleotide 392 of SEQ ID NO: 13 A polynucleotide comprising an otide sequence;   (E) clone gm3354 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of   (F) Clone gm3354 deposited under accession number ATCC 98468 Polynucleotide encoding the full-length protein encoded by the cDNA insert of Otide;   (G) Clone gm3354 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of   (H) clone gm3354 deposited under accession number ATCC 98468 Encoding a mature protein encoded by a cDNA insert Otide;   (I) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 14 Otide;   (J) a fragment of the amino acid sequence of SEQ ID NO: 14 having biological activity A polynucleotide encoding the protein comprising the fragment (SEQ ID NO: 14 8 contiguous amino acids);   (K) a polynucleotide that is an allelic variant of the polynucleotide of (a) to (h) above Nucleotides;   (L) A polynucleotide encoding a species homolog of the protein of (i) or (j) above Otide; and   (M) any one of the polynucleotides (a) to (j) under strict conditions Polynucleotide that can hybridize to An isolated polynucleotide selected from the group consisting of:   28. (A) the amino acid sequence of SEQ ID NO: 14;   (B) an amino acid sequence from amino acid 1 to amino acid 125 of SEQ ID NO: 14;   (C) an amino acid sequence of SEQ ID NO: 14 comprising eight consecutive amino acids of SEQ ID NO: 14 A fragment of the amino acid sequence; and   (D) Clone gm3354 deposited under accession number ATCC 98468 Amino acid sequence encoded by the cDNA insert of A protein comprising an amino acid sequence selected from the group consisting of: A protein substantially free of.   29. An isolated gene corresponding to the cDNA sequence of SEQ ID NO: 13.   30. (A) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 15;   (B) nucleotides from nucleotide 2 to nucleotide 991 of SEQ ID NO: 15 A polynucleotide comprising an otide sequence;   (C) the nucleotide sequence from nucleotide 62 to nucleotide 991 of SEQ ID NO: 15 A polynucleotide comprising a reotide sequence;   (D) nucleotides from nucleotide 2 to nucleotide 504 of SEQ ID NO: 15 A polynucleotide comprising an otide sequence;   (E) Clone hy370 9 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of   (F) Clone hy370 9 deposited under accession number ATCC 98468 Polynucleotide encoding the full-length protein encoded by the cDNA insert of Otide;   (G) Clone hy370 9 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of   (H) clone hy370 9 deposited under accession number ATCC 98468 Encoding a mature protein encoded by a cDNA insert Otide;   (I) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 16 Otide;   (J) a fragment of the amino acid sequence of SEQ ID NO: 16 having biological activity A polynucleotide encoding the protein comprising the fragment (SEQ ID NO: 16 8 contiguous amino acids);   (K) a polynucleotide that is an allelic variant of the polynucleotide of (a) to (h) above Nucleotides;   (L) A polynucleotide encoding a species homolog of the protein of (i) or (j) above Otide; and   (M) any one of the polynucleotides (a) to (j) under strict conditions Polynucleotide that can hybridize to An isolated polynucleotide selected from the group consisting of:   31. (A) the amino acid sequence of SEQ ID NO: 16;   (B) the amino acid sequence of SEQ ID NO: 16 from amino acid 1 to amino acid 167;   (C) SEQ ID NO: 16 comprising eight consecutive amino acids of SEQ ID NO: 16 A fragment of the amino acid sequence; and   (D) Clone hy370 9 deposited under accession number $ TCC98468 Amino acid sequence encoded by the cDNA insert of A protein comprising an amino acid sequence selected from the group consisting of: A protein substantially free of.   32. An isolated gene corresponding to the cDNA sequence of SEQ ID NO: 15.   33. (A) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 17;   (B) the nucleotide sequence from nucleotide 77 to nucleotide 616 of SEQ ID NO: 17 A polynucleotide comprising a reotide sequence;   (C) nucleotides from nucleotide 164 to nucleotide 616 of SEQ ID NO: 17 A polynucleotide comprising a nucleotide sequence;   (D) nucleotides from nucleotide 1 to nucleotide 415 of SEQ ID NO: 17 A polynucleotide comprising an otide sequence;   (E) of clone ie474 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence;   (F) of clone ie474 deposited under accession number ATCC 98468; Polynucleotide encoding full-length protein encoded by cDNA insert Tide;   (G) of clone ie474 deposited under accession number $ TCC98468 A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence;   (H) of clone ie474 deposited under accession number ATCC 98468; Polynucleotide encoding mature protein encoded by cDNA insert Tide;   (I) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 18 Otide;   (J) a fragment of the amino acid sequence of SEQ ID NO: 18 having biological activity A polynucleotide encoding the protein (the fragment is SEQ ID NO: 18 8 contiguous amino acids);   (K) a polynucleotide that is an allelic variant of the polynucleotide of (a) to (h) above Nucleotides;   (L) A polynucleotide encoding a species homolog of the protein of (i) or (j) above Otide; and   (M) any one of the polynucleotides (a) to (j) under strict conditions Polynucleotide that can hybridize to An isolated polynucleotide selected from the group consisting of:   34. (A) the amino acid sequence of SEQ ID NO: 18;   (B) the amino acid sequence of amino acid 1 to amino acid 113 of SEQ ID NO: 18;   (C) an amino acid sequence of SEQ ID NO: 18 comprising eight consecutive amino acids of SEQ ID NO: 18 A fragment of the amino acid sequence; and   (D) of clone ie474 deposited under accession number ATCC 98468; Amino acid sequence encoded by cDNA insert A protein comprising an amino acid sequence selected from the group consisting of: A protein substantially free of.   35. An isolated gene corresponding to the cDNA sequence of SEQ ID NO: 17.   36. (A) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 19;   (B) the sequence of SEQ ID NO: 19 from nucleotide 564 to nucleotide 2813 A polynucleotide comprising a nucleotide sequence;   (C) the sequence from nucleotide 705 to nucleotide 2813 of SEQ ID NO: 19 A polynucleotide comprising a nucleotide sequence;   (D) SEQ ID NO: 19 from nucleotide 793 to nucleotide 1628 A polynucleotide comprising a nucleotide sequence;   (E) clone s195 10 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of   (F) Clone s195 10 deposited under accession number ATCC 98468 Polynucleotide encoding the full-length protein encoded by the cDNA insert of Otide;   (G) Clone s195 10 deposited under accession number ATCC 98468 A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of   (H) clone s195 10 deposited under accession number ATCC 98468 Encoding a mature protein encoded by a cDNA insert Otide;   (I) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 20 Otide;   (J) a fragment of the amino acid sequence of SEQ ID NO: 20 having biological activity A polynucleotide encoding the protein (including the fragment having SEQ ID NO: 20). 8 contiguous amino acids);   (K) a polynucleotide that is an allelic variant of the polynucleotide of (a) to (h) above Nucleotides;   (L) A polynucleotide encoding a species homolog of the protein of (i) or (j) above Otide; and   (M) any one of the polynucleotides (a) to (j) under strict conditions Polynucleotide that can hybridize to An isolated polynucleotide selected from the group consisting of:   37. (A) the amino acid sequence of SEQ ID NO: 20;   (B) the amino acid sequence of SEQ ID NO: 20 from amino acid 78 to amino acid 355;   (C) an amino acid sequence of SEQ ID NO: 20 comprising eight consecutive amino acids of SEQ ID NO: 20; A fragment of the amino acid sequence; and   (D) Clone s195 10 deposited under accession number ATCC 98468 Amino acid sequence encoded by the cDNA insert of A protein comprising an amino acid sequence selected from the group consisting of: A protein substantially free of.   38. An isolated gene corresponding to the cDNA sequence of SEQ ID NO: 19.