Secreted proteins and polynucleotides encoding them

Abstract

Novel polynucleotides and the proteins encoded thereby are disclosed.

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:1;    (b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:1 from nucleotide 44 to nucleotide 1204;    (c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:1 from nucleotide 1 to nucleotide 403;    (d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone AJ26 — 3 deposited under accession number ATCC 98115;    (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AJ26 — 3 deposited under accession number ATCC 98115;    (f) a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of clone AJ26 — 3 deposited under accession number ATCC 98115;    (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone AJ26 — 3 deposited under accession number ATCC 98115;    (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:2;    (i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:2 having biological activity;    (j) a polynucleotide which is an allelic 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    (l) 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 at least one 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 encoded by a composition of  claim 2 , which process comprises: 
 (a) growing a culture of the host cell of  claim 3  in a suitable culture medium; and    (b) purifying said protein from the culture.    
     
     
         6 . A protein produced according to the process of  claim 5 .  
     
     
         7 . The protein of  claim 6  comprising a mature protein.  
     
     
         8 . 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:2;    (b) the amino acid sequence of SEQ ID NO:2 from amino acid 1 to amino acid 120;    (c) fragments of the amino acid sequence of SEQ ID NO:2; and    (d) the amino acid sequence encoded by the cDNA insert of clone AJ26 — 3 deposited under accession number ATCC 98115;    the protein being substantially free from other mammalian proteins.    
     
     
         9 . The composition of  claim 8 , wherein said protein comprises the amino acid sequence of SEQ ID NO:2.  
     
     
         10 . The composition of  claim 8 , wherein said protein comprises the amino acid sequence of SEQ ID NO:2 from amino acid 1 to amino acid 120.  
     
     
         11 . The composition of  claim 8 , further comprising a pharmaceutically acceptable carrier.  
     
     
         12 . A method for preventing, treating or ameliorating a medical condition which comprises administering to a mammalian subject a therapeutically effective amount of a composition of  claim 11 .  
     
     
         13 . An isolated gene corresponding to the cDNA sequence of SEQ ID NO:1.  
     
     
         14 . A composition comprising an isolated polynucleotide selected from the group consisting of: 
 (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:3;    (b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:3 from nucleotide 928 to nucleotide 2541;    (c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:3 from nucleotide 988 to nucleotide 2541;    (d) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:3 from nucleotide 684 to nucleotide 1128;    (e) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone AJ172 — 2 deposited under accession number ATCC 98115;    (f) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AJ172 — 2 deposited under accession number ATCC 98115;    (g) a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of clone AJ172 — 2 deposited under accession number ATCC 98115;    (h) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone AJ172 — 2 deposited under accession number ATCC 98115;    (i) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:4;    a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:4 having biological activity;    (k) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(h) above;    (l) a polynucleotide which encodes a species homologue of the protein of (i) or (j) above; and    (m) a polynucleotide capable of hybridizing under stringent conditions to any one of the polynucleotides specified in (a)-(j).    
     
     
         15 . 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:4;    (b) the amino acid sequence of SEQ ID NO:4 from amino acid 1 to amino acid 67;    (c) fragments of the amino acid sequence of SEQ ID NO:4; and    (d) the amino acid sequence encoded by the cDNA insert of clone AJ172 — 2 deposited under accession number ATCC 98115;    the protein being substantially free from other mammalian proteins.    
     
     
         16 . An isolated gene corresponding to the cDNA sequence of SEQ ID NO:3.  
     
     
         17 . An isolated gene corresponding to the cDNA sequence of SEQ ID NO:6, SEQ ID NO:5 or SEQ ID NO:8.  
     
     
         18 . A composition comprising an isolated polynucleotide selected from the group consisting of: 
 (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:9;    (b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:9 from nucleotide 6 to nucleotide 2408;    (c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:9 from nucleotide 1295 to nucleotide 1705;    (d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone BL89 — 13 deposited under accession number ATCC 98115;    (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone BL89 — 13 deposited under accession number ATCC 98115;    (f) a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of clone BL89 — 13 deposited under accession number ATCC 98115;    (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone BL89 — 13 deposited under accession number ATCC 98115;    (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:10;    (i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:10 having biological activity;    (j) a polynucleotide which is an allelic 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    (l) a polynucleotide capable of hybridizing under stringent conditions to any one of the polynucleotides specified in (a)-(i).    
     
     
         19 . 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:10;    (b) the amino acid sequence of SEQ ID NO:10 from amino acid 431 to amino acid 567;    (c) fragments of the amino acid sequence of SEQ ID NO:10; and    (d) the amino acid sequence encoded by the cDNA insert of clone BL89 — 13 deposited under accession number ATCC 98115;    the protein being substantially free from other mammalian proteins.    
     
     
         20 . An isolated gene corresponding to the cDNA sequence of SEQ ID NO:9.  
     
     
         21 . A composition comprising an isolated polynucleotide selected from the group consisting of: 
 (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:11;    (b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:11 from nucleotide 2113 to nucleotide 2337;    (c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:11 from nucleotide 2036 to nucleotide 2316;    (d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone BL341 — 4 deposited under accession number ATCC 98115;    (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone BL341 — 4 deposited under accession number ATCC 98115;    (f) a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of clone BL341 — 4 deposited under accession number ATCC 98115;    (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone BL341 — 4 deposited under accession number ATCC 98115;    (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:12;    (i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:12 having biological activity;    (j) a polynucleotide which is an allelic 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    (l) a polynucleotide capable of hybridizing under stringent conditions to any one of the polynucleotides specified in (a)-(i).    
     
     
         22 . 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:12;    (b) the amino acid sequence of SEQ ID NO:12 from amino acid 1 to amino acid 68;    (c) fragments of the amino acid sequence of SEQ ID NO:12; and    (d) the amino acid sequence encoded by the cDNA insert of clone BL341 — 4 deposited under accession number ATCC 98115;    the protein being substantially free from other mammalian proteins.    
     
     
         23 . An isolated gene corresponding to the cDNA sequence of SEQ ID NO:11.  
     
     
         24 . A composition comprising an isolated polynucleotide selected from the group consisting of: 
 (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:15;    (b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:15 from nucleotide 144 to nucleotide 257;    (c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:15 from nucleotide 30 to nucleotide 271;    (d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone CC25 — 17 deposited under accession number ATCC 98115;    (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone CC25 — 17 deposited under accession number ATCC 98115;    (f) a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of clone CC25 — 17 deposited under accession number ATCC 98115;    (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone CC25 — 17 deposited under accession number ATCC 98115;    (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:16;    (i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:16 having biological activity;    (j) a polynucleotide which is an allelic 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    (l) a polynucleotide capable of hybridizing under stringent conditions to any one of the polynucleotides specified in (a)-(i).    
     
     
         25 . 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:16;    (b) fragments of the amino acid sequence of SEQ ID NO:16; and    (c) the amino acid sequence encoded by the cDNA insert of clone CC25 — 17 deposited under accession number ATCC 98115;    the protein being substantially free from other mammalian proteins.    
     
     
         26 . An isolated gene corresponding to the cDNA sequence of SEQ ID NO:15.  
     
     
         27 . A composition comprising an isolated polynucleotide selected from the group consisting of: 
 (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:17;    (b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:17 from nucleotide 431 to nucleotide 520;    (c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:17 from nucleotide 266 to nucleotide 511;    (d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone CC397 — 19 deposited under accession number ATCC 98115;    (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone CC397 — 19 deposited under accession number ATCC 98115;    (f) a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of clone CC397 — 19 deposited under accession number ATCC 98115;    (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone CC397 — 19 deposited under accession number ATCC 98115;    (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:18;    (i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:18 having biological activity;    a polynucleotide which is an allelic 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    (l) a polynucleotide capable of hybridizing under stringent conditions to any one of the polynucleotides specified in (a)-(i).    
     
     
         28 . 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:18;    (b) the amino acid sequence of SEQ ID NO:18 from amino acid 1 to amino acid 27;    (c) fragments of the amino acid sequence of SEQ ID NO:18; and    (d) the amino acid sequence encoded by the cDNA insert of clone CC397 — 19 deposited under accession number ATCC 98115;    the protein being substantially free from other mammalian proteins.    
     
     
         29 . An isolated gene corresponding to the cDNA sequence of SEQ ID NO:17.  
     
     
         30 . A composition comprising an isolated polynucleotide selected from the group consisting of: 
 (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:41;    (b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:41 from nucleotide 218 to nucleotide 1159;    (c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:41 from nucleotide 806 to nucleotide 1159;    (d) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:41 from nucleotide 217 to nucleotide 517;    (e) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone K483 — 1 deposited under accession number ATCC 98115;    (f) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone K483 — 1 deposited under accession number ATCC 98115;    (g) a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of clone K483 — 1 deposited under accession number ATCC 98115;    (h) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone K483 — 1 deposited under accession number ATCC 98115;    (i) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:42;    (j) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:42 having biological activity;    (k) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(h) above;    (l) a polynucleotide which encodes a species homologue of the protein of (i) or (j) above; and    (m) a polynucleotide capable of hybridizing under stringent conditions to any one of the polynucleotides specified in (a)-(j).    
     
     
         31 . 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:42;    (b) the amino acid sequence of SEQ ID NO:42 from amino acid 1 to amino acid 100;    (c) fragments of the amino acid sequence of SEQ ID NO:42; and    (d) the amino acid sequence encoded by the cDNA insert of clone K483 — 1 deposited under accession number ATCC 98115;    the protein being substantially free from other mammalian proteins.    
     
     
         32 . An isolated gene corresponding to the cDNA sequence of SEQ ID NO:41.  
     
     
         33 . A method of promoting cell-cell fusion, said method comprising contacting a first cell and a second cell, wherein said first cell expresses an AJ172 — 2 protein.  
     
     
         34 . The method of  claim 33 , wherein said first cell naturally expresses said AJ172 — 2 protein.  
     
     
         35 . The method of  claim 34 , wherein said first cell expresses said AJ172 — 2 protein as a result of transfection of said first cell.  
     
     
         36 . The method of  claim 35 , wherein said first cell is transfected with a composition of  claim 14 .  
     
     
         37 . The method of  claim 35 , wherein said first cell is transfected with a gene of  claim 16 .  
     
     
         38 . The method of  claim 33 , wherein said AJ172 — 2 protein is a protein of  claim 15 .  
     
     
         39 . The method of  claim 33 , wherein said first cell and said second cell are cells of the same type.  
     
     
         40 . The method of  claim 33 , wherein at least one of said first cell and said second cell are transfected to express an additional protein other than said AJ172 — 2 protein.  
     
     
         41 . A method of inhibiting cell-cell fusion between a first cell which expresses an AJ172 — 2 protein and a second cell, said method comprising contacting said first cell with an AJ172 — 2 protein antagonist.  
     
     
         42 . The method of  claim 41 , wherein said antagonist is selected from the group consisting of an antibody or antibody fragment directed to an AJ172 — 2 protein, an antisense polynucleotide directed to a polynucleotide expressing an AJ172 — 2 protein, a nucleotide aptamer directed to an AJ172 — 2 protein, a peptide aptamer directed to an AJ172 — 2 protein and a small molecule which blocks the fusion-inducing activity of an AJ172 — 2 protein.  
     
     
         43 . The method of  claim 41 , wherein said first cell is a placental cell.  
     
     
         44 . The method of  claim 43 , wherein said second cell is a cell from the maternal uterine lining.  
     
     
         45 . The method of  claim 41 , wherein said first cell is a cytotrophoblast.  
     
     
         46 . A method of inhibiting blastocyst implantation, said method comprising contacting a cell within said blastocyst which expresses an AJ172 — 2 protein with an AJ172 — 2 protein antagonist.  
     
     
         47 . A method of inhibiting trophoblast invasion, said method comprising contacting a first cell which expresses an AJ172 — 2 protein with an AJ172 — 2 protein antagonist.  
     
     
         48 . The method of  claim 42 , wherein said antagonist is selected from the group consisting of an antibody or antibody fragment directed to an AJ172 — 2 protein, an antisense polynucleotide directed to a polynucleotide expressing an AJ172 — 2 protein, a nucleotide aptamer directed to an AJ172 — 2 protein, and a peptide aptamer directed to an AJ172 — 2 protein.  
     
     
         49 . The method of  claim 48 , wherein said antagonist is selected from the group consisting of an antibody or antibody fragment directed to an AJ172 — 2 protein, and an antisense polynucleotide directed to a polynucleotide expressing an AJ 172 — 2 protein.  
     
     
         50 . A method of diagnosing or predicting the existence of a condition associated with disregulation of AH172 — 2 protein in a mammalian subject, said method comprising (a) determining a first level of expression of AJ172 — 2 protein in said subject, and (b) comparing said first level of expression to a second level of expression of AJ172 — 2 protein in one or more other mammalian subjects which do not have said condition.  
     
     
         51 . The method of  claim 50 , wherein said condition is selected from the group consisting of pre-eclampsia, placental pathology and cancer.  
     
     
         52 . The method of  claim 50 , wherein said first level of expression is determined in the serum of said subject.  
     
     
         53 . The method of  claim 50 , wherein said first level of expression is determined using an antibody or antibody fragment directed to AJ172 — 2 protein.  
     
     
         54 . The method of  claim 51 , wherein said cancer is choriocarcinoma.  
     
     
         55 . A method of treating a neoplastic disease in a mammalian subject, said method comprising administering to said subject a therapeutically effective amount of an agent which modulates the expression or function of AJ172 — 2.  
     
     
         56 . The method of  claim 55 , wherein said disease is choriocarcinoma.  
     
     
         57 . A method of inhibiting metastasis in a mammalina subject, said method comprising administering to said subject a therapeutically effective amount of an agent which modulates the expression or function of AJ172 — 2.