Therapeutic polypeptides, nucleic acids encoding same, and methods of use

Abstract

Disclosed herein are nucleic acid sequences that encode G-coupled protein-receptor related polypeptides. Also disclosed are polypeptides encoded by these nucleic acid sequences, and antibodies, which immunospecifically-bind to the polypeptide, as well as derivatives, variants, mutants, or fragments of the aforementioned polypeptide, polynucleotide, or antibody. The invention further discloses therapeutic, diagnostic and research methods for diagnosis, treatment, and prevention of disorders involving any one of these novel human nucleic acids and proteins.

1 . An isolated polypeptide comprising an amino acid sequence selected from the group consisting of: 
 (a) a mature form of an amino acid sequence of SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, or 30;    (b) an amino acid sequence of SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, or 30;    (c) an amino acid sequence which is at least 95% identical to an amino acid sequence of SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, or 30; and    (d) an amino acid sequence comprising one or more conservative substitutions in the amino acid sequence of SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, or 30.    
     
     
         2 . The polypeptide of  claim 1 , wherein said polypeptide is naturally occurring.  
     
     
         3 . The polypeptide of  claim 1 , wherein said polypeptide comprises the amino acid sequence of SEQ ID NO: 6.  
     
     
         4 . The polypeptide of  claim 1  comprising an amin acid sequence having one or more amino acid substitutions to SEQ ID NO: 6, wherein said substitutions are selected from the group consisting of: 
 (a) Gly to Arg at amino acid 60; and    (b) Ser to Arg at amino acid 184.    
     
     
         5 . The polypeptide of  claim 1 , wherein said polypeptide comprises amino acids 4-195 of SEQ ID NO: 12.  
     
     
         6 . A composition comprising the polypeptide of  claim 1  and a pharmaceutically acceptable carrier.  
     
     
         7 . An isolated nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of 
 (a) SEQ ID NOs: 1, 3, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, and 29;    (b) a nucleotide sequence encoding the mature form of a polypeptide having an amino acid sequence of SEQ ID NO: 2, 4, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, or 30;    (c) a nucleotide sequence hybridizing under stringent conditions to the nucleotide sequence of SEQ ID NO: 1, 3, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, or 29; and    (d) a nucleotide sequence has at least 98% identity to SEQ ID NO: 1, 3, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, or 29;    or a complement of said nucleotide sequence    
     
     
         8 . The nucleic acid molecule of  claim 7 , wherein the nucleic acid molecule differs by a single nucleotide from a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1, 3, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, and 29.  
     
     
         9 . The nucleic acid molecule of  claim 7  comprising a nucletode sequence encoding an amimo acid sequence of SEQ ID NO: 28 or 30.  
     
     
         10 . The nucleic acid molecule of  claim 9  comprising SEQ ID NO: 27 or 29.  
     
     
         11 . The nucleic acid molecule of  claim 7  consisting of SEQ ID NO: 1, 3, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, or 29.  
     
     
         12 . A vector comprising the nucleic acid molecule of  claim 7 .  
     
     
         13 . The vector of  claim 12 , further comprising a promoter operably linked to said nucleic acid molecule.  
     
     
         14 . A cell comprising the vector of  claim 12 .  
     
     
         15 . An antibody that immunospecifically binds to the polypeptide of  claim 1 .  
     
     
         16 . The antibody of  claim 15 , wherein the antibody is a monoclonal antibody.  
     
     
         17 . The antibody of  claim 15 , wherein the antibody is a humanized antibody.  
     
     
         18 . A method of producing the polypeptide of  claim 1 , the method comprising culturing a cell under conditions that lead to expression of the polypeptide, wherein said cell comprises a vector comprising an isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, and 29.  
     
     
         19 . The method of  claim 18 , wherein the cell is a bacterial cell, an insect cell, a yeast cell, or a mammalian cell.