SECRETED PROTEINS AND POLYNUCLEOTIDES ENCODING THEM

Abstract: Novel polynucleotides and the proteins encoded thereby are disclosed.

Description: SECRETED PROTEINS AND POLYNUCLEOTIDES ENCODING THEM This application is a continuation-in-part of application Ser No 08/667,2 1 , filed July 9, 1996 FIELD OF THE INVENTION The present invention provides novel polynucleotides and proteins encoded by such polynucleotides, along with therapeutic, diagnostic and research utilities for these polynucleotides and proteins BACKGROUND OF THE INVENTION Technology aimed at the discovery of protein factors (including e g , cytokines, such as lymphokines, interferons, CSFs and interleukins) has matured rapidly over the past decade The now routine hybπdization cloning and expression cloning techniques clone novel polynucleotides "directly" m the sense that they rely on information directly related to the discovered protein (i e , partial DNA/amino acid sequence of the protein in the case of hybridization cloning, activity of the protein in the case of expression cloning) More recent ' indirect" cloning techniques such as signal sequence cloning, which isolates DNA sequences based on the presence of a now well-recognized secretory leader sequence motif, as well as vaπous PCR-based or low stπngency hybridization cloning techniques, have advanced the state of the art by making available large numbers of DNA amino acid sequences for proteins that are known to have biological activity by virtue of their secreted nature in the case of leader sequence cloning, or by virtue of the cell or tissue source in the case of PCR-based techniques It is to these proteins and the polynucleotides encoding them that the present invention is directed SUMMARY OF THE INVENTION In one embodiment, the present invention provides a composition compπsing an isolated polynucleotide selected from the group consisting of (a) a polynucleotide compnsing the nucleotide sequence of SEQ ID NO 2, (b) a polynucleotide compπsing the nucleotide sequence of SEQ ID NO 2 from nucleotide 210 to nucleotide 552, (c) a polynucleotide compπsing the nucleotide sequence of SEQ ID NO 2 from nucleotide 297 to nucleotide 552, (d) a polynucleotide compπsing the nucleotide sequence of the full length protein coding sequence of clone BF245_1 deposited under accession number ATCC 98101 , (e) a polynucleotide encoding the full length protein encoded by the cDNA insert of clone BF245_1 deposited under accession number ATCC 98101 , (f) a polynucleotide compπsing the nucleotide sequence of the mature protein coding sequence of clone BF245_I deposited under accession number ATCC 98101 , (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone BF245_ 1 deposited under accession number ATCC 98101 , (h) a polynucleotide encoding a protein compπsing the amino acid sequence of SEQ ID NO 3, (0 a polynucleotide encoding a protein compπsing a fragment of the amino acid sequence of SEQ ID NO 3 having biological activity, (j) a polynucleotide which is an allelic vaπant of a polynucleotide of (a)- (g) above; (k) a polynucleotide which encodes a species homologue of the protein of (h) or (l) above Preferably, such polynucleotide compπses the nucleotide sequence of SEQ ID NO 2 from nucleotide 210 to nucleotide 552, the nucleotide sequence of SEQ ID NO 2 from nucleotide 297 to nucleotide 552, the nucleotide sequence of the full length protein coding sequence of clone BF245_1 deposited under accession number ATCC 98101 , or the nucleotide sequence of the mature protein coding sequence of clone BF245_1 deposited under accession number ATCC 98101 In other preferred embodiments, the polynucleotide encodes the full length or mature protein encoded by the cDNA insert of clone BF245_1 deposited under accession number ATCC 98101. Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO 2, SEQ ID NO.l or SEQ ID NO 4 In other embodiments, the present invention provides a composition compπsing a protein, wherein said protein compπses an amino acid sequence selected from the group consisting of (a) the ammo acid sequence of SEQ ID NO 3, (b) fragments of the amino acid sequence of SEQ ID NO 3, and (c) the amino acid sequence encoded by the cDNA insert of clone BF245_1 deposited under accession number ATCC 98101 , the protein being substantially free from other mammalian proteins Preferably such protein comprises the amino acid sequence of SEQ ID NO 3 In one embodiment, the present invention provides a composition compπsing an isolated polynucleotide selected from the group consisting of (a) a polynucleotide compπsing the nucleotide sequence of SEQ ID NO 5, (b) a polynucleotide compπsing the nucleotide sequence of SEQ ID NO 5 from nucleotide 477 to nucleotide 752, (c) a polynucleotide compπsing the nucleotide sequence of the full length protein coding sequence of clone AX56_8 deposited under accession number ATCC 98101 , (d) a polynucleotide encoding the full length protein encoded by the cDN A insert of clone AX56_8 deposited under accession number ATCC 98101 , (e) a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of clone AX56_8 deposited under accession number ATCC 98101 , (f) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone AX56_8 deposited under accession number ATCC 98101 , (g) a polynucleotide encoding a protein compπsing the amino acid sequence of SEQ ID N0 6, (h) a polynucleotide encoding a protein compnsing a fragment of the amino acid sequence of SEQ ID NO-6 having biological activity, (I) a polynucleotide compnsing the nucleotide sequence of the full length protein coding sequence of isolate AX56_28 deposited under accession number ATCC 98180, (j) a polynucleotide encoding the full length protein encoded by the cDNA insert of isolate AX56_28 deposited under accession number ATCC 98180, (k) a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of isolate AX56_28 deposited under accession number ATCC 98180, (1) a polynucleotide encoding the mature protein encoded by the cDNA insert of isolate AX56_28 deposited under accession number ATCC 98180, ( ) a polynucleotide which is an allehc vaπant of a polynucleotide of (a)- (e) or (ι)-(l) above, (n) a polynucleotide which encodes a species homologue of the protein of (g) or (h) above Preferably, such polynucleotide compπses the nucleotide sequence of SEQ ID NO 5 from nucleotide 477 to nucleotide 752, the nucleotide sequence of the full length protein coding sequence of clone AX56_8 deposited under accession number ATCC 98101 , or the nucleotide sequence of the mature protein coding sequence of clone AX56_8 deposited under accession number ATCC 98101 In other preferred embodiments, the polynucleotide encodes the full length or mature protein encoded by the cDNA insert of clone AX56_8 deposited under accession number ATCC 98101 Other embodiments provide the gene coπesponding to the cDNA sequence of SEQ ID NO 5 In other embodiments, the present invention provides a composition compπsing a protein, wherein said protein compπses an amino acid sequence selected from the group consisting of (a) the amino acid sequence of SEQ ID NO 6, (b) fragments of the amino acid sequence of SEQ ID NO 6, (c) the ammo acid sequence encoded by the cDNA insert of clone AX56_8 deposited under accession number ATCC 98101 , and (d) the ammo acid sequence encoded by the cDNA mseπ of isolate AX56_28 deposited under accession number ATCC 98180, the protein being substantially free from other mammalian proteins Preferably such protein comprises the amino acid sequence of SEQ ID NO 6 In one embodiment, the present invention provides a composition compπsing an isolated polynucleotide selected from the group consisting of (a) a polynucleotide compπsing the nucleotide sequence of SEQ ID NO 7, (b) a polynucleotide compnsing the nucleotide sequence of SEQ ID NO 7 from nucleotide 161 to nucleotide 553, (c) a polynucleotide compπsing the nucleotide sequence of SEQ ID NO 7 from nucleotide 218 to nucleotide 553, (d) a polynucleotide compπsing the nucleotide sequence of the full length protein coding sequence of clone AC222_I deposited under accession number ATCC 98101 , (e) a polynucleotide encoding the full length protein encoded by the cDN A insert of clone AC222_ 1 deposited under accession number ATCC 98101 , (f) a polynucleotide compnsing the nucleotide sequence of the mature protein coding sequence of clone AC222_1 deposited under accession number ATCC 98101 , (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone AC222_1 deposited under accession number ATCC 98101 , (h) a polynucleotide encoding a protein compnsing the amino acid sequence of SEQ ID NO 8, (l) a polynucleotide encoding a protein compπsing a fragment of the amino acid sequence of SEQ ID NO 8 having biological activity, (j) a polynucleotide which is an alle c vaπant of a polynucleotide of (a)- (g) above, (k) a polynucleotide which encodes a species homologue of the protein of (h) or (0 above Preferably, such polynucleotide compπses the nucleotide sequence of SEQ ID NO 7 from nucleotide 161 to nucleotide 553, the nucleotide sequence of SEQ ID NO 7 from nucleotide 218 to nucleotide 553, the nucleotide sequence of the full length protein coding sequence of clone AC222_1 deposited under accession number ATCC 98101 , or the nucleotide sequence of the mature protein coding sequence of clone AC222_1 deposited under accession number ATCC 98101 In other preferred embodiments, the polynucleotide encodes the full length or mature protein encoded by the cDNA insert of clone AC222_1 deposited under accession number ATCC 98101 In yet other preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising the am o acid sequence of SEQ ID NO 8 from ammo acid 1 to amino acid 92 Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO 7 or SEQ ID NO 9 In other embodiments, the present invention provides a composition compπsing a protein, wherein said protein compπses an amino acid sequence selected from the group consisting of (a) the am o acid sequence of SEQ ID NO 8, (b) the amino acid sequence of SEQ ID NO.8 from amino acid 1 to am o acid 92, (c) fragments of the amino acid sequence of SEQ ID NO 8; and (d) the amino acid sequence encoded by the cDNA insert of clone AC222_1 deposited under accession number ATCC 98101, the protein being substantially free from other mammalian proteins Preferably such protein compπses the ammo acid sequence of SEQ ID NO 8 or the amino dcid sequence of SEQ ID NO 8 from amino acid 1 to amino acid 92 In one embodiment, the present invention provides a composition compπsing an isolated polynucleotide selected from the group consisting of (a) a polynucleotide compnsing the nucleotide sequence of SEQ ID NO 10, (b) a polynucleotide compπsing the nucleotide sequence of SEQ ID NO 10 from nucleotide 61 to nucleotide 693, (c) a polynucleotide compπsing the nucleotide sequence of the full length protein coding sequence of clone 0289_1 deposited under accession number ATCC 98101 , (d) a polynucleotide encoding the full length protein encoded by the cDNA insert of clone 0289_1 deposited under accession number ATCC 98101 , (e) a polynucleotide compπsing the nucleotide sequence of the mature protein coding sequence of clone 0289_1 deposited under accession number ATCC 98101 , (f) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone 0289_1 deposited under accession number ATCC 98101 , (g) a polynucleotide encoding a protein compπsing the amino acid sequence of SEQ ID NO 1 1 , (h) a polynucleotide encoding a protein compπsing a fragment of the amino acid sequence of SEQ ID NO 1 1 having biological activity, (0 a polynucleotide which is an alleiic vanant of a polynucleotide of (a)- (d) above, 0) a polynucleotide which encodes a species homologue of the protein of (g) or (h) above Preferably, such polynucleotide compπses the nucleotide sequence of SEQ ID NO 10 from nucleotide 61 to nucleotide 693, the nucleotide sequence of the full length protein coding sequence of clone 0289_1 deposited under accession number ATCC 98101 , or the nucleotide sequence of the mature protein coding sequence of clone 0289_1 deposited under accession number ATCC 98101 In other preferred embodiments, the polynucleotide encodes the full length or mature protein encoded by the cDNA insert of clone 0289_1 deposited under accession number ATCC 98101 In yet other preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:l 1 from amino acid 91 to amino acid 130. Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO: 10 or SEQ ID NO: 12. In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO: 1 1 ; (b) the amino acid sequence of SEQ ID NO:l 1 from amino acid 91 to amino acid 130; (c) fragments of the amino acid sequence of SEQ ID NO: 11 ; and (d) the amino acid sequence encoded by the cDNA insert of clone 0289_1 deposited under accession number ATCC 98101 ; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO: 11 or the amino acid sequence of SEQ ID NO: l 1 from amino acid 91 to amino acid 130. In certain preferred embodiments, the polynucleotide is operably linked to an expression control sequence. The invention also provides a host cell, including bacterial, yeast, insect and mammalian cells, transformed with such polynucleotide compositions. Processes are also provided for producing a protein, which comprise: (a) growing a culture of the host cell transformed with such polynucleotide compositions in a suitable culture medium; and (b) purifying the protein from the culture. The protein produced according to such methods is also provided by the present invention. Preferred embodiments include those in which the protein produced by such process is a mature form of the protein. Protein compositions of the present invention may further comprise a pharmaceutically acceptable carrier. Compositions comprising an antibody which specifically reacts with such protein are also provided by the present invention. Methods are also provided for preventing, treating or ameliorating a medical condition which comprises administering to a mammalian subject a therapeutically effective amount of a composition comprising a protein of the present invention and a pharmaceutically acceptable carrier. BRIEF DESCRIPTION OF THE FIGURES Figure 1 is a schematic representation of the pED6 and pNotS vectors used for deposit of clones disclosed herein DETAILED DESCRIPTION ISOLATED PROTEINS AND POLYNUCLEOTIDES Nucleotide and amino acid sequences are reported below for each clone and protein disclosed in the present application In some instances the sequences are preliminary and may include some incorrect or ambiguous bases or amino acids The actual nucleotide sequence of each clone can readily be determined by sequencing of the deposited clone in accordance with known methods The predicted amino acid sequence (both full length and mature) can then be determined from such nucleotide sequence The amino acid sequence of the protein encoded by a particular clone can also be determined by expression of the clone in a suitable host cell, collecting the protein and determining its sequence For each disclosed protein applicants have identified what they have determined to be the reading frame best identifiable with sequence information available at the time of filing Because of the partial ambiguity in reported sequence information, reported protein sequences include "Xaa" designators These "Xaa" designators indicate either ( 1 ) a residue which cannot be identified because of nucleotide sequence ambiguity or (2) a stop codon in the determined nucleotide sequence where applicants believe one should not exist (if the nucleotide sequence were determined more accurately) As used herein a "secreted" protein is one which, when expressed in a suitable host cell, is transported across or through a membrane, including transport as a result of signal sequences in its amino acid sequence "Secreted" proteins include without limitation proteins secreted wholly (e g , soluble proteins) or partially (e g , receptors) from the cell in which they are expressed "Secreted" proteins also include without limitation proteins which are transported across the membrane of the endoplpasmic reticulum Clone "BF245 1 " A polynucleotide of the present invention has been identified as clone "BF245_1 " BF245_1 was isolated from a human fetal brain cDNA library using methods which are selective for cDNAs encoding secreted proteins BF245_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "BF245_1 protein") The nucleotide sequence of the 5' portion of BF245_1 as presently determined is reported in SEQ ID NO 1 An additional internal nucleotide sequence from BF245_1 as presently determined is reported in SEQ ID NO 2 What applicants believe is the proper reading frame and the predicted amino acid sequence encoded by such internal sequence is reported in SEQ ID NO 3 Amino acids 1 to 29 of SEQ ID NO 3 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 30 Additional nucleotide sequence from the 3' portion of BF245_1 , including the polyA tail, is reported in SEQ ID NO 4 The EcoRI/NotI restπction fragment obtainable from the deposit containing clone BF245_1 should be approximately 1500 bp The nucleotide sequence disclosed herein for BF245_1 was searched against the GenBank database using BLASTA/BLASTX and FASTA search protocols BF245 demonstrated at least some homology with an EST identified as "yc91 04 i Homo sapiens cDNA clone 23509 3"' (R39256, BlastN) and a human mRNA identified as "KIAA0052" (D29641 (Fasta) Based upon homology, BF245_1 proteins and each homologous protein or peptide may share at least some activity Clone "AX56 8" A polynucleotide of the present invention has been identified as clone "AX56_8" AX56_8 was isolated from a human adult testes cDNA library using methods which are selective for cDNAs encoding secreted proteins AX56_8 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "AX56_8 protein") The nucleotide sequence of AX56_8 as presently determined is reported in SEQ ID NO 5 What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the AX56_8 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO 6 The EcoRI/NotI restπction fragment obtainable from the deposit containing clone AX56_8 should be approximately 730 bp The nucleotide sequence disclosed herein for AX56_8 was searched against the GenBank database using BLASTA/BLASTX and FASTA search protocols No hits were found in the database The ammo acid sequence of AX56_8 indicates that it may have some homology with chicken cytotactin Clone "AC222 1 " A polynucleotide of the present invention has been identified as clone "AC222_1 " AC222_1 was isolated from a human adult placenta cDNA library using methods which are selective for cDNAs encoding secreted proteins AC222_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "AC222_1 protein") The nucleotide sequence of the 5' portion of AC222_1 as presently determined is reported in SEQ ID NO 7 What applicants presently believe is the proper reading frame for the coding region is indicated in SEQ ID NO 8 The predicted acid sequence of the AC222_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO 8 Amino acids 1 to 19 are the predicted leader/signal sequence, with the predicted mature am o acid sequence beginning at amino acid 20 Additional nucleotide sequence from the 3' portion of AC222_1 , including the polyA tail, is reported in SEQ ID NO 9 The EcoRI/NotI restnction fragment obtainable from the deposit containing clone AC222_I should be approximately 1400 bp The nucleotide sequence disclosed herein for AC222_1 was searched against the GenBank database using BLASTA BLASTX and FASTA search protocols AC222J demonstrated at least some homology with a chicken proteoglycan core protein, proteoglycan- Lb (D10485, BlastX) Based upon homology, AC222_1 proteins and each homologous protein or peptide may share at least some activity Clone "Q289 1 " A polynucleotide of the present invention has been identified as clone "0289_1 " 0289_1 was isolated from a human dendπtic cell cDNA library using methods which are selective for cDNAs encoding secreted proteins 0289_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "0289_1 protein") The nucleotide sequence of the 5' portion of 0289_1 as presently determined is reported m SEQ ID NO: 10 What applicants presently believe is the proper reading frame for the coding region is indicated in SEQ ID NO: 1 1 The predicted acid sequence of the 0289_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO 1 1 Additional nucleotide sequence from the 3' portion of 0289_1, including the polyA tail, is reported in SEQ ID NO: 12. The EcoRI/NotI restπction fragment obtainable from the deposit containing clone 0289_1 should be approximately 800 bp The nucleotide sequence disclosed herein for 0289_1 was searched against the GenBank database using BLASTA/BLASTX and FASTA search protocols No hits were found in the database Deposit of Clones Clones BF245J , AX56_8, AC222_1 and 0289_1 were deposited on July 9, 1996 with the Amencan Type Culture Collection under accession number ATCC 98101 , from which each clone compnsing a particular polynucleotide is obtainable Each clone has been transfected into separate bacteπal cells (E coll) in this composite deposit An additional isolate of AX56_8 (identified as "AX56_28") was deposited on September 26, 1996 with the Ameπcan Type Culture Collection under accession number ATCC 98180, from which the clone is also obtainable Each clone can be removed from the vector in which it was deposited by performing an EcoRI/NotI digestion (5' cite, EcoRl, 3' cite, NotI) to produce the appropπately sized fragment for such clone (approximate clone size fragment are identified below) Each clone was deposited in either the pED6 or pNotS vector depicted in Fig 1 In some instances, the deposited clone can become "flipped" (i e , in the reverse onentation) in the deposited isolate In such instances, the cDNA insert can still be isolated by digestion with EcoRI and NotI However, NotI will then produce the 5' cite and EcoRI will produce the 3' cite for placement of the cDNA m proper oπentation for expression in a suitable vector The cDNA may also be expressed from the vectors in which they were deposited 0289_1 may be deposited in the Bluescπpt vector In such instance, the cDNA insert can be removed from the vector by digestion with Xhol (5' cite) and NotI (3' cite) Bactenal cells containing a particular clone can be obtained from the composite deposit as follows An ohgonucleotide probe or probes should be designed to the sequence that is known for that particular clone This sequence can be deπved from the sequences provided herein, or from a combination of those sequences The sequence of the ohgonucleotide probe that was used to isolate each full-length clone is identified below, and should be most reliable in isolating the clone of interest Clone Probe Sequence BF245 SEQ ID NO 13 AX56_8 SEQ ID NO 14 AC222 SEQ ID NO: 15 0289_1 SEQ ID NO 16 In the sequences listed above which include an N at position 2, that position is occupied in preferred probes/pnmers by a biotinylated phosphoaramidite residue rather than a nucleotide (such as , for example, that produced by use of biotin phosphoramidite (1-dιmethoxytπtyloxy- 2-(N-bιotιnyl-4-amιnobutyl)-propyl-3-0-(2-cyanoethyl)-(N,N-dnsopropyl)-phosphoramadιte) (Glen Research, cat no 10-1953)) The design of the ohgonucleotide probe should preferably follow these parameters (a) It should be designed to an area of the sequence which has the fewest ambiguous bases ("N's"), if any, (b) It should be designed to have a T m of approx 80 ° C (assuming 2° for each A or T and 4 degrees for each G or C) The ohgonucleotide should preferably be labeled with g- 32 P ATP (specific activity 6000 Ci mmole) and T4 polynucleotide kinase using commonly employed techniques for labeling o gonucleotides Other labeling techniques can also be used Unincorporated label should preferably be removed by gel filtration chromatography or other established methods The amount of radioactivity incorporated into the probe should be quantitated by measurement in a scintillation counter Preferably, specific activity of the resulting probe should be approximately 4e+6 dpm/pmole The bacterial culture containing the pool of full-length clones should preferably be thawed and 100 μl of the stock used to inoculate a steπle culture flask containing 25 ml of steπle L-broth containing ampicillm at 100 μg/ml The culture should preferably be grown to saturation at 37°C, and the saturated culture should preferably be diluted in fresh L-broth Aliquots of these dilutions should preferably be plated to determine the dilution and volume which will yield approximately 5000 distinct and well-separated colonies on solid bacteπological media containing L-broth containing ampicillm at 100 μg/ml and agar at 1 5% in a 150 mm petn dish when grown overnight at 37°C Other known methods of obtaining distinct, well-separated colonies can also be employed Standard colony hybndization procedures should then be used to transfer the colonies to nitrocellulose filters and lyse, denature and bake them The filter is then preferably incubated at 65°C for 1 hour with gentle agitation in 6X SSC (20X stock is 175 3 g NaCl/hter, 88 2 g Na citrate/liter, adjusted to pH 7 0 with NaOH) containing 0 5% SDS, 100 μg/ml of yeast RNA, and 10 mM EDTA (approximately 10 mL per 150 mm filter) Preferably, the probe is then added to the hybndization mix at a concentration greater than or equal to le+6 dpm/mL The filter is then preferably incubated at 65°C with gentle agitation overnight The filter is then preferably washed in 500 mL of 2X SSC/0 5% SDS at room temperature without agitation, preferably followed by 500 mL of 2X SSC/0 1 % SDS at room temperature with gentle shaking for 15 minutes A third wash with 0 IX SSC/0 5% SDS at 65°C for 30 minutes to 1 hour is optional The filter is then preferably dπed and subjected to autoradiography for sufficient time to visualize the positives on the X-ray film Other known hybridization methods can also be employed The positive colonies are picked, grown in culture, and piasmid DNA isolated using standard procedures. The clones can then be verified by restriction analysis, hybridization analysis, or DNA sequencing. Fragments of the proteins of the present invention which are capable of exhibiting biological activity are also encompassed by the present invention. Fragments of the protein may be in linear form or they may be cyclized using known methods, for example, as described in H.U. Saragovi, etal., Bio/Technology H), 773-778 (1992) and in R.S. McDowell, et al., J. Amer. Chem. Soc. 114, 9245-9253 (1992), both of which are incorporated herein by reference. Such fragments may be fused to carrier molecules such as immunoglobulins for many purposes, including increasing the valency of protein binding sites. For example, fragments of the protein may be fused through "linker" sequences to the Fc portion of an immunogiobulin. For a bivalent form of the protein, such a fusion could be to the Fc portion of an IgG molecule. Other immunogiobulin isotypes may also be used to generate such fusions. For example, a protein - IgM fusion would generate a decavalent form of the protein of the invention. The present invention also provides both full-length and mature forms of the disclosed proteins. The full-length form of the such proteins is identified in the sequence listing by translation of the nucleotide sequence of each disclosed clone. The mature form of such protein may be obtained by expression of the disclosed full-length polynucleotide (preferably those deposited with ATCC) in a suitable mammalian cell or other host cell. The sequence of the mature form of the protein may also be determinable from the amino acid sequence of the full-length form. The present invention also provides genes corresponding to the cDNA sequences disclosed herein. The corresponding genes can be isolated in accordance with known methods using the sequence information disclosed herein. Such methods include the preparation of probes or primers from the disclosed sequence information for identification and/or amplification of genes in appropriate genomic libraries or other sources of genomic materials. Where the protein of the present invention is membrane-bound (e.g., is a receptor), the present invention also provides for soluble forms of such protein. In such forms part or all of the intracellular and transmembrane domains of the protein are deleted such that the protein is fully secreted from the cell in which it is expressed. The intracellular and transmembrane domains of proteins of the invention can be identified in accordance with known techniques for determination of such domains from sequence information. Species homologs of the disclosed polynucleotides and proteins are also provided by the present invention Species homologs may be isolated and identified by making suitable probes or pnmers from the sequences provided herein and screening a suitable nucleic acid source from the desired species The invention also encompasses alle c variants of the disclosed polynucleotides or proteins, that is, naturally-occurπng alternative forms of the isolated polynucleotide which also encode proteins which are identical, homologous or related to that encoded by the polynucleotides The isolated polynucleotide of the invention may be operably linked to an expression control sequence such as the pMT2 or pED expression vectors disclosed in Kaufman et al , Nucleic Acids Res J_9, 4485-4490 (1991 ), in order to produce the protein recombinantly Many suitable expression control sequences are known in the art General methods of expressing recombinant proteins are also known and are exemplified in R Kaufman, Methods in Enzymology JJ55, 537-566 (1990) As defined herein "operably linked" means that the isolated polynucleotide of the invention and an expression control sequence are situated within a vector or cell in such a way that the protein is expressed by a host cell which has been transformed (transfected) with the gated polynucleotide/exprcssion control sequence A number of types of cells may act as suitable host cells for expression of the protein Mammalian host cells include, for example, monkey COS cells, Chinese Hamster Ovary (CHO) cells, human kidney 293 cells, human epidermal A431 cells, human Colo205 cells, 3T3 cells, CV-1 cells, other transformed pnmate cell lines, normal dφloid cells, cell strains deπved from in vitro culture of pπmary tissue, pπmary explants, HeLa cells, mouse L cells, BHK, HL- 60, U937, HaK or Jurkat cells Alternatively, it may be possible to produce the protein in lower eukaryotes such as yeast or in prokaryotes such as bacteπa Potentially suitable yeast strains include Saccharomyces cerevtsiae, Schizosaccharomyces pombe, Kluyvewmyces strains, Candida, or any yeast strain capable of expressing heterologous proteins Potentially suitable bacteπal strains include Eschertchia colt, Bacillus subtihs, Salmonella typhimurium, or any bacteπal strain capable of expressing heterologous proteins If the protein is made in yeast or bacteπa, it may be necessary to modify the protein produced therein, for example by phosphorylation or glycosylation of the appropnate sites, in order to obtain the functional protein Such covalent attachments may be accomplished using known chemical or enzymatic methods The protein may also be produced by operably linking the isolated polynucleotide of the invention to suitable control sequences in one or more insect expression vectors, and employing an insect expression system Mateπals and methods for baculovirus/insect cell expression systems are commercially available in kit form from, e g , Invitrogen San Diego California, U S A (the MaxBac® kit), and such methods are well known in the art, as descnbed in Summers and Smith, Texas Agncultural Expeπment Station Bulletin No 1555 (1987), incorporated herein by reference As used herein, an insect cell capable of expressing a polynucleotide of the present invention is "transformed " The protein of the invention may be prepared by cultuπng transformed host cells under culture conditions suitable to express the recombinant protein The resulting expressed protein may then be punfied from such culture (1 e , from culture medium or cell extracts) using known puπfication processes, such as gel filtration and ion exchange chromatography The puπfication of the protein may also include an affinity column containing agents which will bind to the protein, one or more column steps over such affinity resins as concanava n A- agarose, hepann-toyopearl® or Cibacrom blue 3GA Sepharose®, one or more steps involving hydrophobic interaction chromatography using such resms as phenyl ether, butyl ether, or propyl ether, or immunoaffinity chromatography Alternatively, the protein of the invention may also be expressed in a form which will facilitate puπfication For example, it may be expressed as a fusion protein, such as those of maltose binding protein (MBP), glutathione-S-transferase (GST) or thioredoxin (TRX) Kits for expression and puπfication of such fusion proteins are commercially available from New England BioLab (Beverly, MA), Pharmacia (Piscataway, NJ) and InVitrogen, respectively The protein can also be tagged with an epitope and subsequently punfied by using a specific antibody directed to such epitope One such epitope ("Flag") is commercially available from Kodak (New Haven, CT) Finally, one or more reverse-phase high performance liquid chromatography (RP- HPLC) steps employing hydrophobic RP-HPLC media, e g , silica gel having pendant methyl or other aliphatic groups, can be employed to further puπfy the protein Some or all of the foregoing puπfication steps, in vanous combinations, can also be employed to provide a substantially homogeneous isolated recombinant protein The protein thus punfied is substantially free of other mammalian proteins and is defined in accordance with the present invention as an "isolated protein " The protein of the invention may also be expressed as a product of transgenic animals e g , ds d component of the milk of transgenic cows, goats, pigs, or sheep which are charactenzed by somatic or germ cells containing a nucleotide sequence encoding the protein The protein may also be produced by known conventional chemical synthesis Methods for constructing the proteins of the present invention by synthetic means are known to those skilled in the art The synthetically-constructed protein sequences, by virtue of shaπng pπmary, secondary or tertiary structural and/or conformational characteπstics with proteins may possess biological properties in common therewith, including protein activity. Thus, they may be employed as biologically active or immunological substitutes for natural, purified proteins in screening of therapeutic compounds and in immunological processes for the development of antibodies. The proteins provided herein also include proteins characteπzed by amino acid sequences similar to those of purified proteins but into which modification are naturally provided or deliberately engineered. For example, modifications in the peptide or DNA sequences can be made by those skilled in the art using known techniques. Modifications of interest in the protein sequences may include the alteration, substitution, replacement, insertion or deletion of a selected amino acid residue in the coding sequence. For example, one or more of the cysteine residues may be deleted or replaced with another amino acid to alter the conformation of the molecule. Techniques for such alteration, substitution, replacement, insertion or deletion are well known to those skilled in the art (see, e.g., U.S. Patent No 4,518,584). Preferably, such alteration, substitution, replacement, insertion or deletion retains the desired activity of the protein. Other fragments and deπvatives of the sequences of proteins which would be expected to retain protein activity in whole or in part and may thus be useful for screening or other immunological methodologies may also be easily made by those skilled in the art given the disclosures herein. Such modifications are believed to be encompassed by the present invention. USES AND BIOLOGICAL ACTIVITY The polynucleotides and proteins of the present invention are expected to exhibit one or more of the uses or biological activities (including those associated with assays cited herein) identified below. Uses or activities descnbed for proteins of the present invention may be provided by administration or use of such proteins or by administration or use of polynucleotides encoding such proteins (such as, for example, in gene therapies or vectors suitable for introduction of DNA). Research Uses and Utilities The polynucleotides provided by the present invention can be used by the research community for various purposes. The polynucleotides can be used to express recombinant protein for analysis, characteπzation or therapeutic use; as markers for tissues in which the corresponding protein is preferentially expressed (either constitutively or at a particular stage of tissue differentiation or development or in disease states); as molecular weight markers on Southern gels, as chromosome markers or tags (when labeled) to identify chromosomes or to map related gene positions, to compare with endogenous DNA sequences in patients to identify potential genetic disorders, as probes to hybridize and thus discover novel, related DNA sequences, as a source of information to derive PCR primers for genetic fingerpnnting; as a probe to "subtract-out" known sequences in the process of discovenng other novel polynucleotides, for selecting and making ohgomers for attachment to a "gene chip" or other support, including for examination of expression patterns; to raise anti-protein antibodies using DNA immunization techniques, and as an antigen to raise anti-DNA antibodies or elicit another immune response Where the polynucleotide encodes a protein which binds or potentially binds to another protein (such as, for example, in a receptor-ligand interaction), the polynucleotide can also be used in interaction trap assays (such as, for example, that descnbed in Gyuns et al.. Cell 75 791-803 (1993)) to identify polynucleotides encoding the other protein with which binding occurs or to identify inhibitors of the binding interaction The proteins provided by the present invention can similarly be used in assay to determine biological activity, including in a panel of multiple proteins for high-throughput screening; to raise antibodies or to elicit another immune response, as a reagent (including the labeled reagent) in assays designed to quantitatively determine levels of the protein (or its receptor) in biological fluids; as markers for tissues in which the corresponding protein is preferentially expressed (either constitutively or at a particular stage of tissue differentiation or development or in a disease state); and, of course, to isolate correlative receptors or ligands Where the protein binds or potentially binds to another protein (such as, for example, in a receptor-ligand interaction), the protein can be used to identify the other protein with which binding occurs or to identify inhibitors of the binding interaction. Proteins involved in these binding interactions can also be used to screen for peptide or small molecule inhibitors or agonists of the binding interaction. Any or all of these research utilities are capable of being developed into reagent grade or kit format for commercialization as research products. Methods for performing the uses listed above are well known to those skilled in the art References disclosing such methods include without limitation "Molecular Cloning: A Laboratory Manual", 2d ed., Cold Spnng Harbor Laboratory Press, Sambrook, J., E.F. Fntsch and T. Maniatis eds., 1989, and "Methods in Enzymology Guide to Molecular Cloning Techniques", Academic Press, Berger, S L and A.R Kimmel eds., 1987 Nutritional Uses Polynucleotides and proteins of the present invention can also be used as nutritional sources or supplements. Such uses include without limitation use as a protein or amino acid supplement, use as a carbon source, use as a nitrogen source and use as a source of carbohydrate. In such cases the protein or polynucleotide of the invention can be added to the feed of a particular organism or can be administered as a separate solid or liquid preparation, such as in the form of powder, pills, solutions, suspensions or capsules. In the case of microorganisms, the protein or polynucleotide of the invention can be added to the medium in or on which the microorganism is cultured. Cytokine and Cell Proliferation/Differentiation Activity A protein of the present invention may exhibit cytokine, cell proliferation (either inducing or inhibiting) or cell differentiation (either inducing or inhibiting) activity or may induce production of other cytokines in certain cell populations. Many protein factors discovered to date, including all known cytokines, have exhibited activity in one or more factor dependent cell proliferation assays, and hence the assays serve as a convenient confirmation of cytokine activity. The activity of a protein of the present invention is evidenced by any one of a number of routine factor dependent cell proliferation assays for cell lines including, without limitation, 32D, DA2, DA1G, T10, B9, B9/1 1 , BaF3, MC9/G, M+ (preB M+), 2E8, RB5, DAI, 123, Tl 165, HT2, CTLL2, TF-1, Mo7e and CMK. The activity of a protein of the invention may, among other means, be measured by the following methods: Assays for T-cell or thymocyte proliferation include without limitation those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A.M. Kruisbeek, D.H. Marguhes, E.M. Shevach, W Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, Immunologic studies in Humans); Takai et al., J. Immunol. 137:3494-3500, 1986; Bertagnolli et al., J. Immunol. 145:1706-1712, 1990; Bertagnolli et al., Cellular Immunology 133:327-341 , 1991 ; Bertagnolli, et al., J. Immunol. 149:3778-3783, 1992; Bowman et al., J. Immunol. 152: 1756- 1761 , 1994. Assays for cytokine production and/or proliferation of spleen cells, lymph node cells or thymocytes include, without limitation, those described in: Polyclonal T cell stimulation, Kruisbeek, A.M. and Shevach, E.M. In Current Protocols in Immunology. J.E.e.a. Coligan eds. Vol 1 pp. 3.12.1-3.12.14, John Wiley and Sons, Toronto. 1994; and Measurement of mouse and human Interferon γ, Schreiber, R.D. In Current Protocols in Immunology. J.E.e.a. Coligan eds. Vol 1 pp. 6.8.1 -6.8.8, John Wiley and Sons, Toronto. 1994. Assays for proliferation and differentiation of hematopoietic and lymphopoietic cells include, without limitation, those descπbed in- Measurement of Human and Muπne Interleukin 2 and Interleukin 4, Bottomly, K., Davis, L.S. and Lipsky, P E In Current Protocols in Immunology J E e a. Coligan eds. Vol 1 pp 6 3 1 -6.3 12, John Wiley and Sons, Toronto 1991 ; deVπes et al., J. Exp. Med 173:1205-121 1 , 1991 , Moreau et al , Nature 336 690-692, 1988, Greenberger et al., Proc. Natl. Acad Sci U.S A 80.2931 -2938, 1983, Measurement of mouse and human interleukin 6 - Nordan, R. In Current Protocols in Immunology J.E e.a Cohgan 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 Immunology 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., Giannotti, J , Clark, S.C. and Turner, K J. In Current Protocols in Immunology J.E.e.a. Coligan eds. Vol 1 pp. 6.13.1 , John Wiley and Sons, Toronto. 1991 Assays for T-cell clone responses to antigens (which will identify, among others, proteins that affect APC-T cell interactions as well as direct T-cell effects by measunng proliferation and cytokine production) include, without limitation, those descπbed in Current Protocols m Immunology, Ed by J. E. Coligan, A M. Kruisbeek, D.H Marguhes, E M Shevach, W Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function; Chapter 6, Cytokines and their cellular receptors; Chapter 7, Immunologic studies in Humans); Weinberger et al., Proc. Natl Acad Sci USA 77:6091-6095, 1980; Weinberger et al., Eur. J. Immun. 11 :405-41 1 , 1981 , Takai et al., J. Immunol. 137:3494-3500, 1986, Takai et al , J. Immunol 140:508-512, 1988 Immune Stimulating or Suppressing Activity A protein of the present invention may also exhibit immune stimulating or immune suppressing activity, including without limitation the activities for which assays are descπbed herein. A protein may be useful in the treatment of vaπous immune deficiencies and disorders (including severe combined immunodeficiency (SCID)), e.g., in regulating (up or down) growth and proliferation of T and or B lymphocytes, as well as effecting the cytolytic activity of NK cells and other cell populations. These immune deficiencies may be genetic or be caused by viral (e g., HIV) as well as bacteπal or fungal infections, or may result from autoimmune disorders. More specifically, infectious diseases causes by viral, bactenal, fungal or other infection may be treatable using a protein of the present invention, including infections by HIV, hepatitis viruses, heφesviruses, mycobacteπa, Leishmania spp., malana spp and vdπous fungal infections such as candidiasis Of course, in this regard, a protein of the present invention may also be useful where a boost to the immune system generally ma be desirable, i e , in the treatment of cancer Autoimmune disorders which may be treated using a protein of the present invention include, for example, connective tissue disease, multiple sclerosis, systemic lupus erythematosus, rheumatoid arthπtis, autoimmune pulmonary inflammation, Guillain-Barre syndrome, autoimmune thyroiditis, insulin dependent diabetes mel tis, myasthenia gravis, graft-versus-host disease and autoimmune inflammatory eye disease Such a protein of the present invention may also to be useful in the treatment of allergic reactions and conditions, such as asthma (particularly allergic asthma) or other respiratory problems Other conditions, in which immune suppression is desired (including, for example, organ transplantation), may also be treatable using a protein of the present invention Using the proteins of the invention it may also be possible to immune responses, in a number of ways Down regulation may be in the form of inhibiting or blocking an immune response already m progress or may involve preventing the induction of an immune response The functions of activated T cells may be inhibited by suppressing T cell responses or by inducing specific tolerance in T cells, or both Immunosuppression of T cell responses is generally an active, non-antigen-specific, process which requires continuous exposure of the T cells to the suppressive agent Tolerance, which involves inducing non-responsiveness or anergy in T cells, is distinguishable from immunosuppression in that it is generally antigen- specific and persists after exposure to the toleπzing agent has ceased Operationally, tolerance can be demonstrated by the lack of a T cell response upon reexposure to specific antigen in the absence of the tolenzmg agent Down regulating or preventing one or more antigen functions (including without limitation B lymphocyte antigen functions (such as , for example, B7)), e g , preventing high level lymphokine synthesis by activated T cells, will be useful in situations of tissue, skin and organ transplantation and in graft-versus-host disease (GVHD) For example, blockage of T cell function should result in reduced tissue destruction in tissue transplantation Typically, in tissue transplants, rejection of the transplant is initiated through its recognition as foreign by T cells, followed by an immune reaction that destroys the transplant The administration of a molecule which inhibits or blocks interaction of a B7 lymphocyte antigen with its natural hgand(s) on immune cells (such as a soluble, monomeric form of a peptide having B7-2 activity alone or in conjunction with a onomeπc form of a peptide having an activity of another B lymphocyte antigen (e g , B7-1 , B7-3) or blocking antibody), pπor to transplantation can lead to the binding of the molecule to the natural iιgand(s) on the immune cells without transmitting the corresponding costimulatory signal. Blocking B lymphocyte antigen function in this matter prevents cytokine synthesis by immune cells, such as T cells, and thus acts as an immunosuppressant. Moreover, the lack of costimulation may also be sufficient to anergize the T cells, thereby inducing tolerance in a subject. Induction of long-term tolerance by B lymphocyte antigen-blocking reagents may avoid the necessity of repeated administration of these blocking reagents. To achieve sufficient immunosuppression or tolerance in a subject, it may also be necessary to block the function of a combination of B lymphocyte antigens. The efficacy of particular blocking reagents in preventing organ transplant rejection or GVHD can be assessed using animal models that are predictive of efficacy in humans. Examples of appropriate systems which can be used include allogeneic cardiac grafts in rats and xenogeneic pancreatic islet cell grafts in mice, both of which have been used to examine the immunosuppressive effects of CTLA4Ig fusion proteins in vivo as described in Lenschow et al., Science 257:789-792 (1992) and Turka et al., Proc. Natl. Acad. Sci USA, 89: 1 1 102- 11105 (1992). In addition, murine models of GVHD (see Paul ed., Fundamental Immunology, Raven Press, New York, 1989, pp. 846-847) can be used to determine the effect of blocking B lymphocyte antigen function in vivo on the development of that disease. Blocking antigen function may also be therapeutically useful for treating autoimmune diseases. Many autoimmune disorders are the result of inappropriate activation of T cells that are reactive against self tissue and which promote the production of cytokines and autoantibodies involved in the pathology of the diseases. Preventing the activation of autoreactive T cells may reduce or eliminate disease symptoms. Administration of reagents which block costimulation of T cells by disrupting receptor: ligand interactions of B lymphocyte antigens can be used to inhibit T cell activation and prevent production of autoantibodies or T cell-derived cytokines which may be involved in the disease process. Additionally, blocking reagents may induce antigen-specific tolerance of autoreactive T cells which could lead to long-term relief from the disease. The efficacy of blocking reagents in preventing or alleviating autoimmune disorders can be determined using a number of well- characterized animal models of human autoimmune diseases. Examples include murine experimental autoimmune encephalitis, systemic lupus erythmatosis in MRL/lpr/lpr mice or NZB hybrid mice, murine autoimmune collagen arthritis, diabetes mellitus in NOD mice and BB rats, and murine experimental myasthenia gravis (see Paul ed., Fundamental Immunology, Raven Press, New York, 1989, pp. 840-856). Upregulation of an antigen function (preferably a B lymphocyte antigen function), as a means of up regulating immune responses, may also be useful in therapy. Upregulation of immune responses may be in the form of enhancing an existing immune response or eliciting an initial immune response For example, enhancing an immune response through stimulating B lymphocyte antigen function may be useful in cases of viral infection In addition, systemic viral diseases such as influenza, the common cold, and encephalitis might be allevidted by the administration of stimulatory forms of B lymphocyte antigens systemically Alternatively, anti-viral immune responses may be enhanced in an infected patient by removing T cells from the patient, costimulating the T cells in vitro with viral antigen-pulsed APCs either expressing a peptide of the present invention or together with a stimulatory form of a soluble peptide of the present invention and reintroducmg the in vitro activated T cells into the patient Another method of enhancing anti-viral immune responses would be to isolate infected cells from a patient, transfect them with a nucleic acid encoding a protein of the present invention as descπbed herein such that the cells express all or a portion of the protein on their surface, and reintroduce the transfected cells into the patient The infected cells would now be capable of de veπng a costimulatory signal to, and thereby activate, T cells in vivo In another application, up regulation or enhancement of antigen function (preferably B lymphocyte antigen function) may be useful in the induction of tumor immunity Tumor cells (e g , sarcoma, melanoma, lymphoma. leukemia, neuroblastoma, carcinoma) transfected with a nucleic acid encoding at least one peptide of the present invention can be administered to a subject to overcome tumor-specific tolerance in the subject If desired, the tumor cell can be transfected to express a combination of peptides For example, tumor cells obtained from a patient can be transfected ex vivo with an expression vector directing the expression of a peptide having B7-2-hke activity alone, or in conjunction with a peptide having B7-l-hke activity and/or B7-3-lιke activity. The transfected tumor cells are returned to the patient to result in expression of the peptides on the surface of the transfected cell Alternatively, gene therapy techniques can be used to target a tumor cell for transfection in vivo The presence of the peptide of the present invention having the activity of a B lymphocyte antιgen(s) on the surface of the tumor cell provides the necessary costimulation signal to T cells to induce a T cell mediated immune response against the transfected tumor cells In addition, tumor cells which lack MHC class I or MHC class II molecules, or which fail to reexpress sufficient amounts of MHC class I or MHC class II molecules, can be transfected with nucleic acid encoding all or a portion of (e g , a cytoplasmic-doma truncated portion) of an MHC class I α chain protein and β 2 microglobu n protein or an MHC class II chain protein and an MHC class II β chain protein to thereby express MHC class I or MHC class II proteins on the cell surface Expression of the appropπate class I or class II MHC in conjunction with a peptide having the activity of a B lymphocyte antigen (e g , B7- 1 , B7-2, B7- 3) induces a T cell mediated immune response against the transfected tumor cell Optionally, a gene encoding an antisense construct which blocks expression of an MHC class π associated protein, such as the invaπant chain, can also be cotransfected with a DNA encoding a peptide having the activity of a B lymphocyte antigen to promote presentation of tumor associated antigens and induce tumor specific immunity Thus, the induction of a T cell mediated immune response in a human subject may be sufficient to overcome tumor-specific tolerance in the subject The activity of a protein of the invention may, among other means, be measured by the following methods Suitable assays for thymocyte or splenocyte cytotoxicity include, without limitation, those descnbed in Current Protocols in Immunology, Ed by J. E. Coligan, A.M Kruisbeek, D.H Marguhes, E.M. Shevach, W Strober, Pub Greene Publishing Associates and Wiley- lntcrscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19, Chapter 7, Immunologic studies in Humans); Herrmann et al., Proc. Natl. Acad. Sci. USA 78:2488-2492, 1981 , Herrmann et al., J. Immunol. 128:1968-1974, 1982; Handa et al , J Immunol 135:1564-1572, 1985, Takai et al., J. Immunol. 137:3494-3500, 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. Immunol. 128: 1968-1974, 1982; Handa et al., J. Immunol 135.1564-1572, 1985, Takai et al., J. Immunol. 137:3494-3500, 1986, Bowmanet al , J Virology 61 1992-1998; Takai et al , J Immunol 140.508-512, 1988, Bertagnolli et al , Cellular Immunology 133:327-341 , 1991 ; Brown et al., J. Immunol 153:3079-3092, 1994 Assays for T-cell-dependent immunogiobulin responses and isotype switching (which will identify, among others, proteins that modulate T-cell dependent antibody responses and that affect Thl/Th2 profiles) include, without limitation, those described in. Maliszewski, J Immunol. 144:3028-3033, 1990; and Assays for B cell function: In vitro antibody production, Mond, J.J. and Brunswick, M. In Current Protocols in Immunology. J.E.e.a Coligan eds Vol 1 pp 3 8.1-3 8.16, John Wiley and Sons, Toronto. 1994 Mixed lymphocyte reaction (MLR) assays (which will identify, among others, proteins that generate predominantly Thl and CTL responses) include, without limitation, those descnbed in- Current Protocols in Immunology, Ed by J E Coligan, A.M. Kruisbeek, D.H Marguhes, E.M. Shevach, W Strober, Pub. Greene Publishing Associates and Wiley- Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1 -3.19; Chapter 7, Immunologic studies m Humans); Takai et al., J. Immunol. 137.3494-3500, 1986; Takai et al , J. Immunol 140:508-512, 1988; Bertagnolli et al., J. Immunol 149:3778-3783, 1992 Dendπtic cell-dependent assays (which will identify, among others, proteins expressed by dendntic cells that activate naive T-cells) include, without limitation, those descπbed in Guery et al , J Immunol 134 536-544, 1995, Inaba et al , Journal of Expeπmental Medicine 173 549-559, 1991 , Macatonia et al . Journal of Immunology 154 5071 5079 1995 Porgador et al , Journal of Experimental Medicine 182 255-260, 1995, Nair et al , Journal of Virology 67 4062-4069, 1993, Huang et al , Science 264 961-965, 1 94, Macato a et al , Journal of Expenmental Medicine 169 1255-1264, 1989, Bhardwaj et al , Journal of Clinical Investigation 94 797-807, 1994, and Inaba et al , Journal of Expenmental Medicine 172 631 - 640, 1990 Assays for lymphocyte survival/apoptosis (which will identify, among others, proteins that prevent apoptosis after superantigen induction and proteins that regulate lymphocyte homeostasis) include, without limitation, those descnbed m Darzynkiewicz et al , Cytometry 13 795-808, 1992, Gorczyca et al , Leukemia 7 659-670, 1993, Gorczyca et al Cancer Research 53 1945-1951 , 1993, Itoh et al , Cell 66 233-243, 1991 , Zacharchuk, Journal of Immunology 145 4037-4045, 1990, Zamai et al , Cytometry 14 891 -897, 1993, Gorczyca et al , International Journal of Oncology 1 639-648, 1992 Assays for proteins that influence early steps of T-cell commitment and development include, without limitation, those descnbed in Antica et al , Blood 84 1 1 1-1 17, 1994, Fine et al , Cellular Immunology 155 111-122, 1994, Galy et al , Blood 85 2770-2778, 1995, Toki et al , Proc Nat Acad Sci USA 88 7548-7551 , 1991 Hematopoiesis Regulating Activity A protein of the present invention may be useful in regulation of hematopoiesis and, consequently, in the treatment of myeloid or lymphoid cell deficiencies Even marginal biological activity in support of colony forming cells or of factor-dependent cell lines indicates involvement in regulating hematopoiesis, e g in supporting the growth and proliferation of erythroid progenitor cells alone or in combination with other cytokines, thereby indicating utility, for example, in treating vaπous anemias or for use in conjunction with irradiation/chemotherapy to stimulate the production of erythroid precursors and or erythroid cells, in supporting the growth and proliferation of myeloid cells such as granulocytes and monocytes/macrophages (l e , traditional CSF activity) useful, for example, in conjunction with chemotherapy to prevent or treat consequent myelo-suppression, in supporting the growth and proliferation of megakaryocytes and consequently of platelets thereby allowing prevention or treatment of vaπous platelet disorders such as thrombocytopenia, and generally for use in place of or complimentary to platelet transfusions, and/or in supporting the growth and proliferation of hematopoietic stem cells which are capable of matuπng to any and all of the above- mentioned hematopoietic cells and therefore find therapeutic utility m vaπous stem cell disorders (such as those usually treated with transplantation, including, without limitation, aplastic anemia and paroxysmal nocturnal hemoglobinuπa), as well as in repopulating the stem cell compartment post irradiation/chemotherapy, either in-vivo or ex-vivo (i.e., in conjunction with bone marrow transplantation or with peπpheral progenitor cell transplantation (homologous or heterologous)) as normal cells or genetically manipulated for gene therapy The activity of a protein of the invention may, among other means, be measured by the following methods Suitable assays for proliferation and differentiation of vaπous hematopoietic lines are cited above. Assays for embryonic stem cell differentiation (which will identify, among others, proteins that influence embryonic differentiation hematopoiesis) include, without limitation, those descπbed in Johansson et al Cellular Biology 15 141-151, 1995, Kelleret al . Molecular and Cellular Biology 13 473-486, 1993; McClanahan et al , Blood 81 :2903-2915, 1993 Assays for stem cell survival and differentiation (which will identify, among others, proteins that regulate lympho-hematopoiesis) include, without limitation, those descnbed in- Methylcellulose colony forming assays, Freshney, M G. In Culture of Hematopoietic Cells. R I Freshney, et al. eds. Vol pp. 265-268, Wiley-Liss, Inc , New York, NY. 1994, Hirayama et al., Proc Natl. Acad Sci USA 89:5907-5911 , 1992, Pnmitive hematopoietic colony forming cells with high pro ferative potential, McNiece, I.K. and Bπddell, 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 , Expenmental Hematology 22 353-359, 1994; Cobblestone area forming cell assay, Ploemacher, R.E In Culture of Hematopoietic Cells. R.I Freshney, et al eds Vol pp. 1-21, Wiley-Liss, Inc., New York, NY. 1994; Long term bone marrow cultures in the presence of stromal cells, Spooncer, E., Dexter, M. and Allen, T In Culture of Hematopoietic Cells. R I Freshney, et al. eds Vol pp. 163-179, Wiley-Liss, Inc., New York, 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 1994 Tissue Growth Activity A protein of the present invention also may have utility in compositions used for bone, cartilage, tendon, ligament and/or nerve tissue growth or regeneration, as well as for wound healing and tissue repair and replacement, and in the treatment of burns, incisions and ulcers. A protein of the present invention, which induces cartilage and/or bone growth in circumstances where bone is not normally formed, has application in the healing of bone fractures and cartilage damage or defects in humans and other animals. Such a preparation employing a protein of the invention may have prophylactic use in closed as well as open fracture reduction and also in the improved fixation of artificial joints. De novo bone formation induced by an osteogenic agent contributes to the repair of congenital, trauma induced, or oncologic resection induced craniofaciai defects, and also is useful in cosmetic plastic surgery. A protein of this invention may also be used in the treatment of periodontal disease, and in other tooth repair processes. Such agents may provide an environment to attract bone- forming cells, stimulate growth of bone-forming cells or induce differentiation of progenitors of bone-forming cells. A protein of the invention may also be useful in the treatment of osteoporosis or osteoarthritis, such as through stimulation of bone and/or cartilage repair or by blocking inflammation or processes of tissue destruction (collagenase activity, osteoclast activity, etc.) mediated by inflammatory processes. Another category of tissue regeneration activity that may be attributable to the protein of the present invention is tendon/ligament formation. A protein of the present invention, which induces tendon/ligament-like tissue or other tissue formation in circumstances where such tissue is not normally formed, has application in the healing of tendon or ligament tears, deformities and other tendon or ligament defects in humans and other animals. Such a preparation employing a tendon/ligament-like tissue inducing protein may have prophylactic use in preventing damage to tendon or ligament tissue, as well as use in the improved fixation of tendon or ligament to bone or other tissues, and in repairing defects to tendon or ligament tissue. De novo tendon/ligament-like tissue formation induced by a composition of the present invention contributes to the repair of congenital, trauma induced, or other tendon or ligament defects of other origin, and is also useful in cosmetic plastic surgery for attachment or repair of tendons or ligaments. The compositions of the present invention may provide an environment to attract tendon- or ligament-forming cells, stimulate growth of tendon- or ligament-forming cells, induce differentiation of progenitors of tendon- or ligament-forming cells, or induce growth of tendon/ligament cells or progenitors ex vivo for return in vivo to effect tissue repair. The compositions of the invention may also be useful in the treatment of tendinitis, caφal tunnel syndrome and other tendon or ligament defects The compositions may also include an appropπate matπx and/or sequesteπng agent as a earner as is well known in the art The protein of the present invention may also be useful for proliferation of neural cells and for regeneration of nerve and brain tissue, i e for the treatment of central and peripheral nervous system diseases and neuropathies, as well as mechanical and traumatic disorders, which involve degeneration, death or trauma to neural cells or nerve tissue More specifically, a protein may be used in the treatment of diseases of the penpheral nervous system, such as penpheral nerve mjuπes, penpheral neuropathy and localized neuropathies, and central nervous system diseases, such as Alzheimer's, Parkinson's disease, Huntington s disease, amyotrophic lateral sclerosis, and Shy-Drager syndrome Further conditions which may be treated in accordance with the present invention include mechanical and traumatic disorders, such as spinal cord disorders, head trauma and cerebrovascular diseases such as stroke Penpheral neuropathies resulting from chemotherapy or other medical therapies may also be treatable using a protein of the invention Proteins of the invention may also be useful to promote better or faster closure of non- healing wounds, including without limitation pressure ulcers, ulcers associated with vascular insufficiency, surgical and traumatic wounds, and the like It is expected that a protein of the present invention may also exhibit activity for generation or regeneration of other tissues, such as organs (including, for example, pancreas, liver, intestine, kidney, skin, endothelium), muscle (smooth, skeletal or cardiac) and vascular (including vascular endothelium) tissue, or for promoting the growth of cells compπsing such tissues Part of the desired effects may be by inhibition or modulation of fibrotic scarπng to allow normal tissue to regenerate A protein of the invention may also exhibit angiogenic activity A protein of the present invention may also be useful for gut protection or regeneration and treatment of lung or liver fibrosis, reperfusion injury in vaπous tissues, and conditions resulting from systemic cytokine damage A protein of the present invention may also be useful for promoting or inhibiting differentiation of tissues descπbed above from precursor tissues or cells, or for inhibiting the growth of tissues descπbed above The activity of a protein of the invention may, among other means, be measured by the following methods Assays for tissue generation activity include, without limitation, those described in International Patent Publication No WO95/16035 (bone, cartilage, tendon), International Patent Publication No. WO95/05846 (nerve, neuronal); International Patent Publication No. W091/07491 (skin, endothelium ). Assays for wound healing activity include, without limitation, those described in: Winter, Epidermal Wound Healing, pps. 71 -1 12 (Maibach, HI and Rovee, DT, eds.), Year Book Medical Publishers, Inc., Chicago, as modified by Eaglstein and Mertz, J. Invest. Dermatol 71 :382-84 (1978). Activin/Inhibin Activity A protein of the present invention may also exhibit activin- or inhi bin -related activities. Inhibins are characterized by their ability to inhibit the release of follicle stimulating hormone (FSH), while activins and are characterized by their ability to stimulate the release of follicle stimulating hormone (FSH). Thus, a protein of the present invention, alone or in heterodimers with a member of the inhibin family, may be useful as a contraceptive based on the ability of inhibins to decrease fertility in female mammals and decrease spermatogenesis in male mammals. Administration of sufficient amounts of other inhibins can induce infertility in these mammals. Alternatively, the protein of the invention, as a homodimer or as a heterodimer with other protein subunits of the inhibin-β group, may be useful as a fertility inducing therapeutic, based upon the ability of activin molecules in stimulating FSH release from cells of the anterior pituitary. See, for example, United States Patent 4,798,885. A protein of the invention may also be useful for advancement of the onset of fertility in sexually immature mammals, so as to increase the lifetime reproductive performance of domestic animals such as cows, sheep and pigs. The activity of a protein of the invention may, among other means, be measured by the following methods: Assays for activin/inhibin activity include, without limitation, those described in: Vale et al., Endocrinology 91:562-572, 1972; Ling et al., Nature 321:779-782, 1986; Vale et al., Nature 321 :776-779, 1986; Mason et al., Nature 318:659-663, 1985; Forage et al., Proc. Natl. Acad. Sci. USA 83:3091-3095, 1986. Chemotactic/Chemokinetic Activity A protein of the present invention may have chemotactic or chemokinetic activity (e.g., act as a chemokine) for mammalian cells, including, for example, monocytes, fibroblasts, neutrophils, T-cells, mast cells, eosinophils, epithelial and/or endothelial cells. Chemotactic and chemokinetic proteins can be used to mobilize or attract a desired cell population to a desired site of action. Chemotactic or chemokinetic proteins provide particular advantages in treatment of wounds and other trauma to tissues, as well as in treatment of localized infections. For example, attraction of lymphocytes, monocytes or neutrophils to tumors or sites of infection may result in improved immune responses against the tumor or infecting agent. A protein or peptide has chemotactic activity for a particular cell population if it can stimulate, directly or indirectly, the directed orientation or movement of such cell population. Preferably, the protein or peptide has the ability to directly stimulate directed movement of cells. Whether a particular protein has chemotactic activity for a population of cells can be readily determined by employing such protein or peptide in any known assay for cell chemotaxis. The activity of a protein of the invention may, among other means, be measured by the following methods: Assays for chemotactic activity (which will identify proteins that induce or prevent chemotaxis) consist of assays that measure the ability of a protein to induce the migration of cells across a membrane as well as the ability of a protein to induce the adhesion of one cell population to another cell population. Suitable assays for movement and adhesion include, without limitation, those described in: Current Protocols in Immunology, Ed by J.E. Coligan, A.M. Kruisbeek, D.H. Marguhes, E.M. Shevach, W.Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 6.12, Measurement of alpha and beta Chemokines 6.12.1 -6.12.28; Taub et al. J. Clin. Invest. 95:1370-1376, 1995; Lind et al. APMIS 103:140-146, 1995; Muller et al Eur. J. Immunol. 25: 1744-1748; Gruber et al. J. of Immunol. 152:5860-5867, 1994; Johnston et al. J. of Immunol. 153: 1762-1768, 1994. Hemostatic and Thrombolytic Activity A protein of the invention may also exhibit hemostatic or thrombolytic activity. As a result, such a protein is expected to be useful in treatment of various coagulation disorders (including hereditary disorders, such as hemophilias) or to enhance coagulation and other hemostatic events in treating wounds resulting from trauma, surgery or other causes. A protein of the invention may also be useful for dissolving or inhibiting formation of thromboses and for treatment and prevention of conditions resulting therefrom (such as, for example, infarction of cardiac and central nervous system vessels (e.g., stroke). The activity of a protein of the invention may, among other means, be measured by the following methods: Assay for hemostatic and thrombolytic activity include, without limitation, those described in: Linet et al., J. Clin. Pharmacol. 26:131-140, 1986; Burdick et al. Thrombosis Res 45 413-419, 1987; Humphrey et al , Fibπnolysis 5 71-79 (1991 ), Schaub, Prostaglandins 35 467-474, 1988 Receptor/Ligand Activity A protein of the present invention may also demonstrate activity as receptors, receptor ligands or inhibitors or agonists of receptor/ligand interactions Examples of such receptors and ligands include, without limitation, cytokine receptors and their ligands, receptor kinases and their ligands, receptor phosphatases and their ligands, receptors involved in cell-cell interactions and their ligands (including without limitation, cellular adhesion molecules (such as selectins, integπns and their ligands) and receptor/ligand pairs involved in antigen presentation, antigen recognition and development of cellular and humoral immune responses) Receptors and ligands are also useful for screening of potential peptide or small molecule inhibitors of the relevant receptor/ligand interaction A protein of the present invention (including, without limitation, fragments of receptors and ligands) may themselves be useful as inhibitors of receptor/ligand interactions The activity of a protein of the invention may, among other means, be measured by the following methods Suitable assays for receptor-ligand activity include without limitation those descπbed in Current Protocols in Immunology, Ed by J E Coligan, A.M. Kruisbeek, D H. Marguhes, E.M Shevach, W.Strober, Pub Greene Publishing Associates and Wiley-Interscience (Chapter 7.28, Measurement of Cellular Adhesion under static conditions 7.28 1 -7 28 22), Takai et al , Proc Natl Acad. Sci USA 84:6864-6868, 1987, Bierer et al , J Exp Med 168 1 145-1 156, 1988, Rosenstein et al , J. Exp Med. 169.149-160 1989, Stoltenborg et al , J Immunol Methods 175 59-68, 1994, Stitt et al , Cell 80 661 -670, 1995 Anti-Inflammatory Activity Proteins of the present invention may also exhibit anti-inflammatory activity The anti- lnflammatory activity may be achieved by providing a stimulus to cells involved in the inflammatory response, by inhibiting or promoting cell-cell interactions (such as, for example, cell adhesion), by inhibiting or promoting chemotaxis of cells involved in the inflammatory process, inhibiting or promoting cell extravasation, or by stimulating or suppressing production of other factors which more directly inhibit or promote an inflammatory response. Proteins exhibiting such activities can be used to treat inflammatory conditions including chronic or acute conditions), including without limitation inflammation associated with infection (such as septic shock, sepsis or systemic inflammatory response syndrome (SIRS)), lschemia- reperfusion injury, endotoxin lethality, arthπtis, complement-mediated hyperacute rejection, nephntis, cytokine or chemokine-induced lung injury, inflammatory bowel disease, Crohn s disease or resulting from over production of cytokines such as TNF or IL-1 Proteins of the invention may also be useful to treat anaphylaxis and hypersensitivity to an antigenic substance or matenal Tumor Inhibition Activity In addition to the activities descnbed above for immunological treatment or prevention of tumors, a protein of the invention may exhibit other anti-tumor activities A protein may inhibit tumor growth directly or indirectly (such as, for example, via ADCC) A protein may exhibit its tumor inhibitory activity by acting on tumor tissue or tumor precursor tissue, by inhibiting formation of tissues necessary to support tumor growth (such as, for example, by inhibiting angiogenesis), by causing production of other factors, agents or cell types which inhibit tumor growth, or by suppressing, eliminating or inhibiting factors, agents or cell types which promote tumor growth Other Activities A protein of the invention may also exhibit one or more of the following additional activities or effects inhibiting the growth, infection or function of, or killing, infectious agents, including, without limitation, bacteπa, viruses, fungi and other parasites, effecting (suppressing or enhancing) bodily characteπ sties, including, without limitation, height, weight, hair color, eye color, skin, fat to lean ratio or other tissue pigmentation, or organ or body part size or shape (such as, for example, breast augmentation or diminution, change in bone form or shape), effecting biorhythms or cancadic cycles or rhythms, effecting the fertility of male or female subjects, effecting the metabolism, catabo sm, anabohsm, processing, utilization, storage or elimination of dietary fat, hpid, protein, carbohydrate, vitamins, minerals, cofactors or other nutπtional factors or component(s), effecting behavioral charactenstics, including, without limitation, appetite, libido, stress, cognition (including cognitive disorders), depression (including depressive disorders) and violent behaviors, providing analgesic effects or other pain reducing effects, promoting differentiation and growth of embryonic stem cells in lineages other than hematopoietic lineages, hormonal or endoenne activity, in the case of enzymes, correcting deficiencies of the enzyme and treating deficiency-related diseases, treatment of hypeφro ferative disorders (such as, for example, psoπasis), lmmunoglobu n-hke activity (such as, for example, the ability to bind antigens or complement), and the ability to act as an antigen in a vaccine composition to raise an immune response against such protein or another material or entity which is cross-reactive with such protein. ADMINISTRATION AND DOSING A protein of the present invention (from whatever source derived, including without limitation from recombinant and non-recombinant sources) may be used in a pharmaceutical composition when combined with a pharmaceutically acceptable carrier. Such a composition may also contain (in addition to protein and a carrier) diluents, fillers, salts, buffers, stabilizers, solubilizers, and other materials well known in the art. The term "pharmaceutically acceptable" means a non-toxic material that does not interfere with the effectiveness of the biological activity of the active ingredient(s). The characteristics of the carrier will depend on the route of administration. The pharmaceutical composition of the invention may also contain cytokines, lymphokines, or other hematopoietic factors such as M-CSF, GM-CSF, TNF, JL-1 , IL-2, IL-3, IL-4, IL-5, EL-6, IL-7, IL-8, IL-9, IL-10, IL-1 1 , IL-12, IL-13, IL-14, EL-15, IFN, TNFO, TNF1, TNF2, G-CSF, Meg-CSF, thrombopoietin, stem cell factor, and erythropoietin. The pharmaceutical composition may further contain other agents which either enhance the activity of the protein or compliment its activity or use in treatment. Such additional factors and/or agents may be included in the pharmaceutical composition to produce a synergistic effect with protein of the invention, or to minimize side effects. Conversely, protein of the present invention may be included in formulations of the particular cytokine, lymphokine, other hematopoietic factor, thrombolytic or anti-thrombotic factor, or anti -inflammatory agent to minimize side effects of the cytokine, lymphokine, other hematopoietic factor, thrombolytic or anti-thrombotic factor, or anti-inflammatory agent. A protein of the present invention may be active in multimers (e.g., heterodimers or homodimers) or complexes with itself or other proteins. As a result, pharmaceutical compositions of the invention may comprise a protein of the invention in such multimeric or complexed form. The pharmaceutical composition of the invention may be in the form of a complex of the protein(s) of present invention along with protein or peptide antigens. The protein and/or peptide antigen will deliver a stimulatory signal to both B and T lymphocytes. B lymphocytes will respond to antigen through their surface immunogiobulin receptor. T lymphocytes will respond to antigen through the T cell receptor (TCR) following presentation of the antigen by MHC proteins. MHC and structurally related proteins including those encoded by class I and class π MHC genes on host cells will serve to present the peptide antigen(s) to T lymphocytes. The antigen components could also be supplied as purified MHC-peptide complexes alone or with co-stimulatory molecules that can directly signal T cells. Alternatively antibodies able to bind surface immunolgobulin and other molecules on B cells as well as antibodies able to bind the TCR and other molecules on T cells can be combined with the pharmaceutical composition of the invention. The pharmaceutical composition of the invention may be in the form of a liposome in which protein of the present invention is combined, in addition to other pharmaceutically acceptable carriers, with amphipathic agents such as lipids which exist in aggregated form as micelles, insoluble monolayers, liquid crystals, or lamellar layers in aqueous solution. Suitable lipids for hposomal formulation include, without limitation, monoglycerides, diglycerides, sulfatides, lysolecithin, phospholipids, saponin, bile acids, and the like. Preparation of such hposomal formulations is within the level of skill in the art, as disclosed, for example, in U.S. Patent No. 4,235,871 ; U.S. Patent No. 4,501,728; U.S. Patent No. 4,837,028; and U.S. Patent No. 4,737,323, all of which are incoφorated herein by reference. As used herein, the term "therapeutically effective amount" means the total amount of each active component of the pharmaceutical composition or method that is sufficient to show a meaningful patient benefit, i.e., treatment, healing, prevention or amelioration of the relevant medical condition, or an increase in rate of treatment, healing, prevention or amelioration of such conditions. When applied to an individual active ingredient, administered alone, the term refers to that ingredient alone. When applied to a combination, the term refers to combined amounts of the active ingredients that result in the therapeutic effect, whether administered in combination, serially or simultaneously. In practicing the method of treatment or use of the present invention, a therapeutically effective amount of protein of the present invention is administered to a mammal having a condition to be treated. Protein of the present invention may be administered in accordance with the method of the invention either alone or in combination with other therapies such as treatments employing cytokines, lymphokines or other hematopoietic factors. When co- administered with one or more cytokines, lymphokines or other hematopoietic factors, protein of the present invention may be administered either simultaneously with the cytokine(s), lymphokine(s), other hematopoietic factor(s), thrombolytic or anti-thrombotic factors, or sequentially. If administered sequentially, the attending physician will decide on the appropriate sequence of administering protein of the present invention in combination with cytokine(s), lymphokine(s), other hematopoietic factor(s), thrombolytic or anti-thrombotic factors. Administration of protein of the present invention used in the pharmaceutical composition or to practice the method of the present invention can be carried out in a vanety of conventional ways, such as oral mgestion, inhalation, topical application or cutaneous, subcutaneous, intrapeπtoneal, parenteral or intravenous injection Intravenous administration to the patient is preferred When a therapeutically effective amount of protein of the present invention is administered orally, protein of the present invention will be in the form of a tablet, capsule, powder, solution or elixir When administered in tablet form, the pharmaceutical composition of the invention may additionally contain a solid earner such ds a gelatin or an adjuvant The tablet, capsule, and powder contain from about 5 to 95% protein of the present invention, and preferably from about 25 to 90% protein of the present invention When administered in liquid form, a liquid earner such as water, petroleum, oils of animal or plant ongm such as peanut oil, mineral oil, soybean oil, or sesame oil, or synthetic oils may be added The liquid form of the pharmaceutical composition may further contain physiological saline solution, dextrose or other sacchaπde solution, or glycols such as ethylene glycol, propylene glycol or polyethylene glycol When administered in liquid form, the pharmaceutical composition contains from about 0 5 to 90% by weight of protein of the present invention, and preferably from about I to 50% protein of the present invention When a therapeutically effective amount of protein of the present invention is administered by intravenous, cutaneous or subcutaneous injection, protein of the present invention will be in the form of a pyrogen-free, parenterally acceptable aqueous solution The preparation of such parenterally acceptable protein solutions, having due regard to pH, isotonicity, stability, and the like, is within the skill m the art A preferred pharmaceutical composition for intravenous, cutaneous, or subcutaneous injection should contain, in addition to protein of the present invention, an lsotomc vehicle such as Sodium Chloπde Injection, Ringer's Injection, Dextrose Injection, Dextrose and Sodium Chlonde Injection, Lactated Ringer's Injection, or other vehicle as known in the art The pharmaceutical composition of the present invention may also contain stabilizers, preservatives, buffers, antioxidants, or other additives known to those of skill in the art The amount of protein of the present invention in the pharmaceutical composition of the present invention will depend upon the nature and seventy of the condition being treated, and on the nature of pnor treatments which the patient has undergone Ultimately, the attending physician will decide the amount of protein of the present invention with which to treat each individual patient Initially, the attending physician will administer low doses of protein of the present invention and observe the patient's response Larger doses of protein of the present invention may be administered until the optimal therapeutic effect is obtained for the patient, and at that point the dosage is not increased further. It is contemplated that the various pharmaceutical compositions used to practice the method of the present invention should contain about 0.01 μg to about 100 mg (preferably about 0.1 μg to about 10 mg, more preferably about 0.1 μg to about 1 mg) of protein of the present invention per kg body weight. The duration of intravenous therapy using the pharmaceutical composition of the present invention will vary, depending on the severity of the disease being treated and the condition and potential idiosyncratic response of each individual patient. It is contemplated that the duration of each application of the protein of the present invention will be in the range of 12 to 24 hours of continuous intravenous administration. Ultimately the attending physician will decide on the appropriate duration of intravenous therapy using the pharmaceutical composition of the present invention. Protein of the invention may also be used to immunize animals to obtain polyclonal and monoclonal antibodies which specifically react with the protein. Such antibodies may be obtained using either the entire protein or fragments thereof as an immunogen. The peptide immunogens additionally may contain a cysteine residue at the carboxyl terminus, and are conjugated to a hapten such as keyhole limpet hemocyanin (KLH). Methods for synthesizing such peptides are known in the art, for example, as in R.P. Merrifield, J. Amer.Chem.Soc. 85, 2149-2154 (1963); J.L. Krstenansky, et al., FEBS Lett. 2U_, 10 (1987). Monoclonal antibodies binding to the protein of the invention may be useful diagnostic agents for the immunodetection of the protein. Neutralizing monoclonal antibodies binding to the protein may also be useful therapeutics for both conditions associated with the protein and also in the treatment of some forms of cancer where abnormal expression of the protein is involved. In the case of cancerous cells or leukemic cells, neutralizing monoclonal antibodies against the protein may be useful in detecting and preventing the metastatic spread of the cancerous cells, which may be mediated by the protein. For compositions of the present invention which are useful for bone, cartilage, tendon or ligament regeneration, the therapeutic method includes administering the composition topically, systematically, or locally as an implant or device. When administered, the therapeutic composition for use in this invention is, of course, in a pyrogen-free, physiologically acceptable form. Further, the composition may desirably be encapsulated or injected in a viscous form for delivery to the site of bone, cartilage or tissue damage. Topical administration may be suitable for wound healing and tissue repair. Therapeutically useful agents other than a protein of the invention which may also optionally be included in the composition as described above, may alternatively or additionally, be administered simultaneously or sequentially with the composition in the methods of the invention Preferably for bone and/or cartilage formation, the composition would include a matπx capable of de veπng the protein-containing composition to the site of bone and/or cartilage damage, providing a structure for the developing bone and cartilage and optimally capable of being resorbed into the body Such matnces may be formed of mateπals presently in use lor other implanted medical applications The choice of matπx matenal is based on biocompatibi ty, biodegradabihty, mechanical properties, cosmetic appearance and interface properties The particular application of the compositions will define the appropπate formulation Potential matrices for the compositions may be biodegradable and chemically defined calcium sulfate, tπcalciumphosphate, hydroxyapatite, polylactic acid, polyglycohc acid and polyanhydπdes Other potential matenals are biodegradable and biologically well-defined, such as bone or dermal collagen Further matnces are compnsed of pure proteins or extracellular matrix components Other potential matnces are nonbiodegradable and chemically defined, such as sintered hydroxapatite, bioglass, alummates, or other ceramics Matnces may be compπsed of combinations of any of the above mentioned types of material, such as polylactic acid and hydroxyapatite or collagen and tncalciumphosphate The bioceramics may be altered in composition, such as in calcium-aluminate-phosphate and processing to alter pore size, particle size, particle shape, and biodegradabihty Presently preferred is a 50 50 (mole weight) copolymer of lactic acid and glyco c acid in the form of porous particles having diameters ranging from 150 to 800 microns In some applications, it will be useful to utilize a sequesteπng agent, such as carboxymethyl cellulose or autologous blood clot, to prevent the protein compositions from disassociating from the matπx A preferred family of sequesteπng agents is cellulosic matenals such as alkylcelluloses (including hydroxyalkylcelluloses), including methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropyl-methylcellulose, and carboxymethylcellulose, the most preferred being cationic salts of carboxymethylcellulose (CMC) Other preferred sequestenng agents include hyaluronic acid, sodium alginate, poly(ethylene glycol), polyoxyethylene oxide, carboxyvinyl polymer and poly( vinyl alcohol) The amount of sequesteπng agent useful herein is 0 5-20 wt%, preferably 1-10 wt% based on total formulation weight, which represents the amount necessary to prevent desorbtion of the protein from the polymer matnx and to provide appropnate handling of the composition, yet not so much that the progenitor cells are prevented from infiltrating the matπx, thereby providing the protein the opportunity to assist the osteogenic activity of the progenitor cells In further compositions, proteins of the invention may be combined with other agents beneficial to the treatment of the bone and/or cartilage defect, wound, or tissue in question These agents include vanous growth factors such as epidermal growth factor (EGF), platelet deπved growth factor (PDGF), transforming growth factors (TGF- and TGF-β), and lnsuhn- like growth factor (IGF). The therapeutic compositions are also presently valuable for vetcπnary applications Particularly domestic animals and thoroughbred horses, in addition to humans, are desired patients for such treatment with proteins of the present invention The dosage regimen of a protein-containing pharmaceutical composition to be used in tissue regeneration will be determined by the attending physician considenng vaπous factors which modify the action of the proteins, e g , amount of tissue weight desired to be formed, the site of damage, the condition of the damaged tissue, the size of a wound, type of damaged tissue (e.g , bone), the patient's age, sex, and diet, the seventy of any infection, time of administration and other clinical factors The dosage may vary with the type of matπx used in the reconstitution and with inclusion of other proteins in the pharmaceutical composition For example, the addition of other known growth factors, such as IGF I (insulin like growth factor I), to the final composition, may also effect the dosage Progress can be monitored by peπodic assessment of tissue/bone growth and/or repair, for example, X-rays, histomoφhometπc determinations and tetracychne labeling Polynucleotides of the present invention can also be used for gene therapy Such polynucleotides can be introduced either in vivo or ex vivo into cells for expression in a mammalian subject. Polynucleotides of the invention may also be administered by other known methods for introduction of nucleic acid into a cell or organism (including, without limitation, in the form of viral vectors or naked DNA) Cells may also be cultured ex vivo in the presence of proteins of the present invention in order to proliferate or to produce a desired effect on or activity in such cells Treated cells can then be introduced in vivo for therapeutic puφoses. Patent and literature references cited herein are incoφorated by reference as if fully set forth. SEQUENCE LISTING (1) GENERAL INFORMATION: (i) APPLICANT: Jacobs, Kenneth McCoy, John LaVallie, Edward Racie, Lisa Merberg, David Treacy, Maurice Spaulding, Vikki Bowman, Michael (ii) TITLE OF INVENTION: SECRETED PROTEINS AND POLYNUCLEOTIDES ENCODING THEM (iii) NUMBER OF SEQUENCES: 16 (iv) CORRESPONDENCE ADDRESS: (A) ADDRESSEE: Genetics Institute, Inc. (B) STREET: 87 CambridgePark Drive (C) CITY: Cambridge (D) STATE: Massachusetts ( E) COUNTRY : U.S.A. (F) ZIP: 02140 (v) COMPUTER READABLE FORM: (A) MEDIUM TYPE: Floppy disk (B) COMPUTER: IBM PC compatible (C) OPERATING SYSTEM: PC-DOS/MS-DOS (D) SOFTWARE: Patentin Release #1.0, Version #1.30 (vi) CURRENT APPLICATION DATA: (A) APPLICATION NUMBER: (B) FILING DATE: (C) CLASSIFICATION: (viii) ATTORNEY/AGENT INFORMATION: (A) NAME: Brown, Scott A. (B) REGISTRATION NUMBER: 32,724 (ix) TELECOMMUNICATION INFORMATION: (A) TELEPHONE: (617) 498-8224 (B) TELEFAX: (617) 876-5851 (2) INFORMATION FOR SEQ ID NO : 1 : (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 339 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear Iii) MOLECULE TYPE: cDNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:l: GCGGCCGCAG GTCTAGAATT CAATCGGGAG AGAGATACTG CCTGGTTCTT ACAGACACAG 60 ATTATGTCAT CCTTGCAGCC TTCACCCAAA GTTGCTCCCT CCTTCTAGGG CATTTTGTTT 120 TCCTACTTAA TACCAAGTGT CAGCATGTTA GTAATAAACA GGTGTCTCTA CCATTAGTCA 180 AAGGTGGGAG TTAAGCCTTT CATCTTTGTA GCTTTCTCCA GTACCTAACC ATGATTTACT 240 TCATGGGAAG TCCCTCAAAG TACTATTAAT TATCCTGTGT TCTCCTGCCT TGCCTCTTAA 300 CAAAAATTCT GCTGTTCCTG ATTATTTCCA TTTTACCAG 339 (2) INFORMATION FOR SEQ ID NO : 2 : (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 552 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO : 2 : AAATANAAAT ANAACAAATT NTAGGGAAGG ACTAAACTGT CTAAAGAAAT GTAAAATCCA 60 AAGACTTGGA TTTTCAACCT ATATCAGAAG ACACTTTTTT TTCAGTTCCC ATGTGAAATT 120 CTTTNTAGGC CAAGGAAGGA CAAATACAAA TTTTGATTAC AAATTATTTT TAGAACTTTG 180 ACACCTACAC TTAAATTCTG AGTCATTAAA CAGGCCTACA TTTATCAACT GTGGAAATAT 240 CAGCCAGTTT TTGCAAACCT CTTCTTAGGA CACTAAGTTG TTTGCAGAAA TCACTAGCAT 300 TGACTGACTC AGCAACAATG TGGTTATATT CTTTGATTAA CTTAGTCCTT TTTCTTGGTC 360 AAGAGTCAGT AGACAGGACT GAAGCTTATG CCCCTTGCCC CCCCACCACC ACTCCATTAC 420 TACCACCTTG GTTTAGCCAT CCTTTTCTTG ATCTGTTCTC CCCACTTCTA CTGTGCTACT 480 CTACAGACTT GCCCTGAATG TAAGAGCAAC AATTACCTTG TAAAGTCCAA GTTGGGGCAG 540 GTCACTCCCA AA 552 (2) INFORMATION FOR SEQ ID NO : 3 : (l) SEQUENCE CHARACTERISTICS: (A) LENGTH: 47 amino acids (B) TYPE- ammo acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (n) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO : 3 : Thr Gly Leu His Leu Ser Thr Val Glu He Ser Ala Ser Phe Cys Lys 1 5 10 15 Pro Leu Leu Arg Thr Leu Ser Cys Leu Gin Lys Ser Leu Ala Leu Thr 20 25 30 Asp Ser Ala Thr Met Trp Leu Tyr Ser Leu He Asn Leu Val Leu 35 40 45 (2) INFORMATION FOR SEQ ID NO : 4 : (l) SEQUENCE CHARACTERISTICS: (A) LENGTH: 308 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (n) MOLECULE TYPE: cDNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO : 4 : TTTTTTNGGA ATCACCAAAA TCAAGNGNGA TATTGTGTTT GCTGCCAGCC TNNANTTGTA 60 GAGTCAGCTA AAGGAATGTG NGATTTTAAA TTATTGACCA CCTGTTTGAT TACAGTTGAN 120 NACAAATGCC TGCAAGTGTG GATTTGGTTT TCCCANACAT TTTAATATGT ATTATATTTA 180 AATCAAACAT CATTCATAGA AAGCATATNA CANANATGTT TANACATAAG CATNACATTT 240 TTTTAATAAA AATGTANACA GGTGGGGCAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA 300 AAAAAAAA 308 (2) INFORMATION FOR SEQ ID NO : 5 : (l) SEQUENCE CHARACTERISTICS - (A) LENGTH: 1077 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 5: CATTTGATCT TTCCACNACT ATCCAACTCA CAACGTGGCA NTGGGGTTGT GCCGCCTTTG 60 CAGGTGTATA TNANACACGT GGTTTTGGCC GCAGAGGCAC CNGTCGNCAG GTGGGGGGTT 120 CCGCTGCCTG CAAAGGGTCG CTACAGACGT TGTTTGTNTT CAAGAAGCTT CCAGAGGAAN 180 TGCTTCCTTC ACGACATTCA ACAGACCTTG CATTCCTTTG GCGAGAGGGG AAAGACCCCT 240 AGGNATGNTT GTCAAGAAGA CAGGGNCAGG TTTTCCGGCC CTTNACATTG CCAAAAGACG 300 GCAATATGGT GGNAAATAAC ATATAGACAA ACGCACACCG GCCTTATTCC AAGCGGNTTC 360 GGCCAGTAAC GTTAGAATTG CGGCCGCAGG TCTAGAATTC AGTCTTTTCA AGAGAACAAT 420 AAAATAGGCA GTCTCCTACC TCTTGTCTTA CTCTAATATA AACTCCATGA AGATAAGTAT 480 TGTATCCATA CTGTTCATGC TGCACAGCAG TTGCCCTTAT CTGCAGGGCG ACGCATCCCA 540 AGACCCCCAG TGGATGCTTG AAACTGCAGA ANANTNACAC ACGTGATTGC CACCATCGGA 600 ACACATTTCT GTTCACGTCT TCCACCCACA GATTTAATGC CTTTTCCATC TTAACTAAGC 660 ACTCATCATG GACTGTGGCC ATAACTTTTG CAGTTTTAGA TGCAACAGCA AAACTAACAT 720 TAATTTTTTC TTCTTCTTCA CAATTTCATG GGTAGATTTG TTCTTACCGT AGATCTTAKC 780 AACCTCAGCA TATGATGTTT TTTCTTTTGA GAACTTTCAC CTTTTNTCTT AAAGAAAGCA 840 CTTTACAGCT TNTCTTTGGC ATATCTCAAC TGCCAGCATC ACTGNTCTTG AACTTTGGGG 900 CCATTATTAA GTCAGNAAAG GGTTANTTCA AACNAGCTTT TGTANTCCCA CNTACTTGGG 960 AGGNTAAGGC AGGAGAATGG NATGAACCCG AGAGGCAGAG GTTGCAGTGA GCTGAGATCG 1020 TGCCACTGCA CTCCAGCGTG GGTGACAGAG AGATTNTGTC TAAAAAAAAA AAAAAAA 1077 (2) INFORMATION FOR SEQ ID NO : 6 : (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 92 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO : 6 : Val Leu Tyr Pro Tyr Cys Ser Cys Cys Thr Ala Val Ala Leu He Cys 1 5 10 15 Arg Ala Thr His Pro Lys Thr Pro Ser Gly Cys Leu Lys Leu Gin Xaa 20 25 30 Xaa Xaa Thr Arg Asp Cys His His Arg Asn Thr Phe Leu Phe Thr Ser 35 40 45 Ser Thr His Arg Phe Asn Ala Phe Ser He Leu Thr Lys His Ser Ser 50 55 60 Trp Thr Val Ala He Thr Phe Ala Val Leu Asp Ala Thr Ala Lys Leu 65 70 75 80 Thr Leu He Phe Ser Ser Ser Ser Gin Phe His Gly 85 90 (2) INFORMATION FOR SEQ ID NO : 7 : (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 553 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO : 7 : AGGGCCAGGT TTTCCGGGCC NTCACATTGC CAAAAGACGG CAATATGGTG GGAAATAACA 60 TATAGACAAA CGCACACCGG CCTTATTCCA AGCGGNTTCG GCCAGTAACG TTAGAATTGC 120 GGCCGCAGGT YTAGGTCAGA GCCAAAGGAA AGCTTGAAAA ATGAAGACAT TAGCAGGACT 180 TGTTCTGGGA CTTGTCATCT TTGATGCTGC TGTGACTNCC CCAACTCTAG AGTCCATCAA 240 CTATGACTCA GAAACCTATG ATGCCACCTT AGAAGACCTG GATAATTTGT ACAACTATGA 300 AAACATACCT GTTGATAAAG TTGAGATTGA AATAGCCACA GTGATGCCTT CAGGGAACAG 360 AGAGCTCCTC ACTCCACCCC CACAGCCTGA GAAGGCCCAG GAAGAGGAAG AGGAGGAGGA 420 ATCTACTCCC AGGCTGATTG ATGGCTCTTC TCCCCAGGAG CCTGAATTCA CAGGGGTTCT 480 GGGGCCACAC ACAAATGAAG ACTTTCCAAC CTGTCTTTTG TGTACTTGTA TAAGTACCAC 540 CGTGTACTGT GAT 553 ( 2 ) INFORMATION FOR SEQ ID NO : 8 : ( l ) SEQUENCE CHARACTERI STICS : (A) LENGTH : 131 ammo acids (B) TYPE : ammo acid (C) STRANDEDNESS: (D) TOPOLOGY, linear (n) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO : 8 : Met Lys Thr Leu Ala Gly Leu Val Leu Gly Leu Val He Phe Asp Ala 1 5 10 15 Ala Val Thr Xaa Pro Thr Leu Glu Ser He Asn Tyr Asp Ser Glu Thr 20 25 30 Tyr Asp Ala Thr Leu Glu Asp Leu Asp Asn Leu Tyr Asn Tyr Glu Asn 35 40 45 He Pro Val Asp Lys Val Glu He Glu He Ala Thr Val Met Pro Ser 50 55 60 Gly Asn Arg Glu Leu Leu Thr Pro Pro Pro Gin Pro Glu Lys Ala Gin 65 70 75 80 Glu Glu Glu Glu Glu Glu Glu Ser Thr Pro Arg Leu He Asp Gly Ser 85 90 95 Ser Pro Gin Glu Pro Glu Phe Thr Gly Val Leu Gly Pro His Thr Asn 100 105 110 Glu Asp Phe Pro Thr Cys Leu Leu Cys Thr Cys He Ser Thr Thr Val 115 120 125 Tyr Cys Asp 130 (2) INFORMATION FOR SEQ ID NO : 9 : (l) SEQUENCE CHARACTERISTICS: (A) LENGTH: 358 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (n) MOLECULE TYPE: cDNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO : 9 : TTATAATATA ATGAAAATGT AGTAATTTAA GAAAACACCA GATGAGTTAG GAATAAACCT 60 ATAACATTTA CAAAAAGAGC AAAATTAAGT GA AGAAAAT ATTTCACACA TGTTCTTATA 120 GATCATGTAT CACTTGCAAG TTTTNGGAGT TCATATCCTA TATCATTTCA AATTAAGNAC 180 ATAATAAAGT AAAATTTTGA AATGAACACT TTAGGTATTT TTGCCAAGAT TTAGATGTTT 240 TTAATTAAAC TTTTTTCTTC CTTTTTTTTT CACTAAAGCA TGTTTATTCC CCTAATCCAT 300 TAAAGAGCAT GAAAAAAAGA ATAAATGTAT TTGAAAATTA AAAAAAAAAA AAAAAAAA 358 (2) INFORMATION FOR SEQ ID NO: 10: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 693 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 10: GCGGCCGCTC TANAACTAGT GGATCCCCCG GGCTGCAGGA ATTCGGCCAA AGAGGCCTAG 60 AATGAAAATC CAGGTGTTTG TCATTCATCA GCAACAGGTG ATCCCCATTG CAGGCAGCCG 120 GAACCGACGT CTCCTGGACC ACTGAGCTGG CTGTTCTCAT TACTGCCCTT TCCGCCCAGG 180 CTGGCGGTGA CTCACCGTGA GACAAGTCAG CTAGGTGTTC AGGACAGGGA TTTCAGAGTA 240 TTTTTGTCCA AAGAGGAAAG GGATGATTTC TACGGATCAC TACCAGTTGG TTTACTGTTA 300 GCTCATCGTG TTGATCACAC CAAGTCTTGC CAATTTGGTT TTCTAAGTAT TTTCACGCCT 360 TCTCCTCGTG TCCGCGTCAC TGCTCTGATT CAGGCCCTTG TCATTTCTCA TCTTTGCCAT 420 TTTAGTAGTT TTTGGATTGG GCTCCCGGCT GCTAATTTTG TCCCCTTTTC CACTATCTTC 480 CACATTGTCA CCGCAGTCAT GTTTCTAAGG CAGAATCTCA CTGTGCCCC CATCGTGTTG 540 CTGGGCCCTT GCATGCCGTA CCCTGGCCTT TGTGAAATGC CCTTCATCTG TGCTCTTCCC 600 TCCACCTGGA ATGTCCGTCT CTCTTTTTCT GCCAACCCAC NCGACCCCTC CCTCCTNCAA 660 GCCCGTGAGT GTCCCCNCCC TCCATGTCCT GTG 693 (2) INFORMATION FOR SEQ ID NO: 11: ( ) SEQUENCE CHARACTERISTICS: (A) LENGTH: 130 ammo acids (B) TYPE: ammo acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (n) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO : 11 : Asn Glu Asn Pro Gly Val Cys His Ser Ser Ala Thr Gly Asp Pro H s 1 5 10 15 Cys Arg Gin Pro Glu Pro Thr Ser Pro Gly Pro Leu Ser Trp Leu Phe 20 25 30 Ser Leu Leu Pro Phe Pro Pro Arg Leu Ala Val Thr His Arg Glu Thr 35 40 45 Ser Gin Leu Gly Val Gin Asp Arg Asp Phe Arg Val Phe Leu Ser Lys 50 55 60 Glu Glu Arg Asp Asp Phe Tyr Gly Ser Leu Pro Val Gly Leu Leu Leu 65 70 75 80 Ala His Arg Val Asp His Thr Lys Ser Cys Gin Phe Gly Phe Leu Ser 85 90 95 He Phe Thr Pro Ser Pro Arg Val Arg Val Thr Ala Leu He Gin Ala 100 105 110 Leu Val He Ser His Leu Cys His Phe Ser Ser Phe Trp He Gly Leu 115 120 125 Pro Ala 130 (2) INFORMATION FOR SEQ ID NO: 12: (l) SEQUENCE CHARACTERISTICS: (A) LENGTH: 327 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (n) MOLECULE TYPE: cDNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 12: TTCGTGGGGC CTGCCCGTTC NGATNTNGNT GCNGCCTCGC TGTCCCCCTC CTCCCTCCNG 60 TGGTTNATAT TCCAGGAATT CTGAATTAGT TGCACCGTGN TCTNATATTT ACTGCAAGAA 120 TAGACCAGTG GTTCTCCAGC TTTTCTGCAC TCTGGAATCA CCTGGGGGTC TTTAAAAAAC 180 ACTGCCTGGC TCCTAGTCCT AAATTTGGAG ATTTAACTGG ACTTACAGTT TTTCAAAGCA 240 CCCCAAAAGA TTNTAATGTG CAGCAAAGTT TGGGAACCAC TGGTATAGAC TGTCTTCTGC 300 TTGTTTTCTT GAAAAACACA AACACAA 327 (2) INFORMATION FOR SEQ ID NO: 13: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 29 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: other nucleic acid (A) DESCRIPTION: /desc = "oligonucleotide" (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 13: GNTAAACCAA GGTGGTAGTA ATGGAGTGG 29 (2) INFORMATION FOR SEQ ID NO: 14: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 29 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: other nucleic acid (A) DESCRIPTION: /desc = "oligonucleotide" (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 14: GNTCTTGGGA TGCGTCGCCC TGCAGATAA 29 (2) INFORMATION FOR SEQ ID NO: 15: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 29 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear In) MOLECULE TYPE: other nucleic acid (A) DESCRIPTION: /desc = "oligonucleotide" (xi ) SEQUENCE DESCRIPTION: SEQ ID NO: 15: GNAGGCATCA CTGTGGCTAT TTCAATCTC 29 (2) INFORMATION FOR SEQ ID NO: 16: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 29 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: other nucleic acid (A) DESCRIPTION: /desc = "oligonucleotide" (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 16: TNCCTTAGAA ACATGACTGC GGTGACAAT 29

Claims: What is claimed is: 1. A composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:2; (b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 2 from nucleotide 210 to nucleotide 552; (c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:2 from nucleotide 297 to nucleotide 552; (d) a polynucleotide comprising the nucleotide sequence of the full length protein coding sequence of clone BF245_1 deposited under accession number ATCC 98101 ; (e) a polynucleotide encoding the full length protein encoded by the cDNA insert of clone BF245_1 deposited under accession number ATCC 98101 ; (f) a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of clone BF245_1 deposited under accession number ATCC 98101 ; (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone BF245_1 deposited under accession number ATCC 98101 ; (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:3; (i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:3 having biological activity; (j) a polynucleotide which is an alleiic variant of a polynucleotide of (a)-(g) above; (k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ; and (I) a polynucleotide capable of hybridizing under stringent conditions to any one of the polynucleotides specified in (a)-(i). 2. A composition of claim 1 wherein said polynucleotide is operably linked to an expression control sequence. 3. A host cell transformed with a composition of claim 2. 4. The host cell of claim 3, wherein said cell is a mammalian cell. 5 A process for producing a protein, which compπses (a) growing a culture of the host cell of claim 3 in a suitable culture medium, and (b) puπfymg the protein from the culture 6 A protein produced according to the process of claim 5 7 The protein of claim 6 compπsing a mature protein 8 A composition compπsing a protein, wherein said protein compnses an amino acid sequence selected from the group consisting of (a) the ammo acid sequence of SEQ ID NO 3, (b) fragments of the ammo acid sequence of SEQ ID NO 3, and (c) the ammo acid sequence encoded by the cDNA insert of clone BF245_1 deposited under accession number ATCC 98101 , the protein being substantially free from other mammalian proteins 9 The composition of claim 8, wherein said protein compnses the amino acid sequence of SEQ ID NO 3 10 The composition of claim 8, further compπsing a pharmaceutically acceptable earner 11 A method for preventing, treating or ameliorating a medical condition which compnses administenng to a mammalian subject a therapeutically effective amount of a composition of claim 10 12 The gene corresponding to the cDNA sequence of SEQ ID NO 2, SEQ ID NO 1 or SEQ ID NO 4 13 A composition compnsing an isolated polynucleotide selected from the group consisting of (a) a polynucleotide compnsing the nucleotide sequence of SEQ ID NO 7, (b) a polynucleotide compnsing the nucleotide sequence of SEQ ID NO 7 from nucleotide 161 to nucleotide 553, (c) a polynucleotide compπsing the nucleotide sequence of SEQ ID NO 7 from nucleotide 218 to nucleotide 553, (d) a polynucleotide compnsing the nucleotide sequence of the full length protein coding sequence of clone AC222_1 deposited under accession number ATCC 98101 , (e) a polynucleotide encoding the full length protein encoded by the cDNA insert of clone AC222_1 deposited under accession number ATCC 98101 , (f) a polynucleotide compnsing the nucleotide sequence of the mature protein coding sequence of clone AC222_1 deposited under accession number ATCC 98101 , (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone AC222_1 deposited under accession number ATCC 98101 , (h) a polynucleotide encoding a protein compπsing the ammo acid sequence of SEQ ID NO:8, (0 a polynucleotide encoding a protein compπsing a fragment of the amino acid sequence of SEQ ID NO 8 having biological activity, (j) a polynucleotide which is an allelic vaπant of a polynucleotide of (a)-(g) above; (k) a polynucleotide which encodes a species homologue of the protein of (h) or (I) above ; and (1) a polynucleotide capable of hybndizing under stnngent conditions to any one of the polynucleotides specified in (a)-(ι) 14 A composition compπsing a protein, wherein said protein compnses an amino acid sequence selected from the group consisting of (a) the amino acid sequence of SEQ ID NO 8, (b) the ammo acid sequence of SEQ ID NO 8 from amino acid 1 to amino acid 92, (c) fragments of the amino acid sequence of SEQ ID NO 8, and (d) the amino acid sequence encoded by the cDNA insert of clone AC222_1 deposited under accession number ATCC 98101 , the protein being substantially free from other mammalian proteins 15 The gene corresponding to the cDN A sequence of SEQ ID NO 7 or SEQ ID NO:9 16. A composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 10; (b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 10 from nucleotide 61 to nucleotide 693; (c) a polynucleotide comprising the nucleotide sequence of the full length protein coding sequence of clone 0289_1 deposited under accession number ATCC 98101 ; (d) a polynucleotide encoding the full length protein encoded by the cDNA insert of clone 0289_1 deposited under accession number ATCC 98101 ; (e) a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of clone 0289_1 deposited under accession number ATCC 98101 ; (f) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone 0289_1 deposited under accession number ATCC 98101 ; (g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:l l ; (h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:l 1 having biological activity; (i) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(f) above; (j) a polynucleotide which encodes a species homologue of the protein of (g) or (h) above ; and (k) a polynucleotide capable of hybridizing under stringent conditions to any one of the polynucleotides specified in (a)-(h). 17. A composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO: 11 ; (b) the amino acid sequence of SEQ ID NO: 11 from amino acid 91 to amino acid 130; (c) fragments of the amino acid sequence of SEQ ID NO: 11 ; and (d) the amino acid sequence encoded by the cDNA insert of clone 0289_1 deposited under accession number ATCC 98101 ; the protein being substantially free from other mammalian proteins. 18. The gene corresponding to the cDNA sequence of SEQ ID NO: 10 or SEQ ID NO:12.

Inventors: BOWMAN MICHAEL, JACOBS KENNETH, LAVALLIE EDWARD R, MCCOY JOHN M, MERBERG DAVID, RACIE LISA A, SPAULDING VIKKI, TREACY MAURICE, BOWMAN, MICHAEL, JACOBS, KENNETH, LAVALLIE, EDWARD, R., MCCOY, JOHN, M., MERBERG, DAVID, RACIE, LISA, A., SPAULDING, VIKKI, TREACY, MAURICE
Applicants: GENETICS INST, GENETICS INSTITUTE, INC.
Application year: 1997
Main classification: C12N15
IPC codes: A61K38, A61P7, A61P19, A61P25, A61P35, A61P37, A61P43, C07K14, C12N5, C12N15, C12P21