VANILREP1 polynucleotides and VANILREP1 polypeptides

Abstract

VANILREP 1 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing VANILREP 1 polypeptides and polynucleotides in therapy, and diagnostic assays for such.

What is claimed is:  
     
         1 . An isolated polypeptide selected from the group consisting of: 
 (i) an isolated polypeptide comprising an amino acid sequence selected from the group having at least:    (a) 90% identity; or    (b) 95% identity to the amino acid sequence of SEQ ID NO:2 over the entire length of SEQ ID NO:2;    (ii) an isolated polypeptide comprising the amino acid sequence of SEQ ID NO:2;    (iii) an isolated polypeptide which is the amino acid sequence of SEQ ID NO:2;    (iv) an isolated polypeptide comprising an amino acid sequence selected from the group having at least: 
 (a) 90% identity; or  
 (b) 95% identity to the amino acid sequence of SEQ ID NO:8 over the entire length of SEQ ID NO:8;  
   (v) an isolated polypeptide comprising the amino acid sequence of SEQ ID NO:8 or    (vi) an isolated polypeptide which is the amino acid sequence of SEQ ID NO: 8.    
     
     
         2 . An isolated polynucleotide selece from the group consisting of 
 (i) an isolated polynucleotide compriin a nuclecoide sequence encoding a polypeptide that has at least 
 (a) 90% identit; or  
 (b) 95% identity; to the amino acid sequence of SEQ ID NO:2, over the entire length of SEQ ID NO:2; (ii) an isolated polynucleotde comprising a nucleotide sequence that has at least:  
   (a) 85% identitv;    (b) 90% identity. or    (c) 95% identity; over its entire length to a nucleotide sequence encoding the polypeptide of SEQ ID NO:2;    (iii) an isolated polynucleotide comprising a nucleotide sequence which has at least: 
 (a) 85%identity;  
 (b) 90% identity; or  
 (c) 95% identity; to that of SEQ ID NO: 1 over the entire length of SEQ ID NO: 1;  
   (iv) an isolated polynucleotide comprising a nucleotide sequence encoding the polypeptide of SEQ ID NO:2;    (v) an isolated polynucleotide which is the polynucleotide of SEQ ID NO: 1; or    (vi) an isolated polynucleotide obtainable by screeni an appropriate library under stringent hybridization conditions with a labeled probe having the sequence of SEQ ID NO: I or a fragment thereof;    or a nucleotide sequence complementary to said isolated polynucleotide.    
     
     
         3 . An isolated polynucleotide selected from the group consisting of. 
 (i) an isolated polynucleotide comprising a nucleotide sequence encoding a polypeptide that has at least 
 (a) 90%identity; or  
 (b) 95%identity;  
   to the anmino acid sequence of SEQ ID NO:8, over the entire length of SEQ ID NO:8;    (ii) an isolated polynucleotide comprising a nucleotide sequence that has at least: 
 (a) 85%identity;  
 (b) 90% identity; or  
 (c) 95% identity;  
   over its entire length to a nucleotide sequence encoding the polypeptide of SEQ ID NO:8;    (iii) an isolated polynucleotide comprising a nucleotide sequence which has at least: 
 (a) 85% identity;  
 (b) 90% identity; or  
 (c) 95% identity;  
   to that of SEQ ID NO:7 over the entire length of SEQ ID NO:7;    (iv) an isolated polynucleotide comprising a nucleotide sequence encoding the polypeptide of SEQ ID NO:8;    (v) an isolated polynucleotide which is the polynucleotide of SEQ ID NO:7; or    (vi) an isolated polynucleotide obtainable by screening an appropriate library under stringent hybridization conditions with a labeled probe having the sequence of SEQ ID NO:7 or a fragment thereof;    or a nucleotide sequence complementary to said isolated polynucleotide.    
     
     
         4 . An antibody immunospecific for the polypeptide of    claim 1   .  
     
     
         5 . A method for the treatment of a subject: 
 (i) in need of enhanced activity or expression of the polypeptide of    claim 1    comprising: 
 (a) administering to the subject a therapeutically effective amount of an agonist to said polypeptide; and/or  
 (b) providing to the subject an isolated polynucleotide comprising a nucleotide sequence encoding said polypetide in a form so as to effect production of said polypeptide activity  in vivo ; or  
   (ii) having need to inhibit activity or expression of the polypeptide of    claim 1    comprising: 
 (a) administering to the subject a therapeutically effective amount of an antagonist to said polypeptide; and/or  
 (b) administering to the subject a nucleic acid molecule that inhibits the expression of a nucleotide sequence encoding said polypeptide; and/or  
 (c) administering to the subject a therapeutically effective amount of a polypeptide that competes with said polypeptide for its ligand, substrate , or receptor.  
   
     
     
         6 . A process for diagnosing a disease or a susceptibility to a disease in a subject related to expression or activity of the polypeptide of    claim 1    in a subject comprising: 
 (a) determining the presence or absence of a mutation in the nucleotide sequence encoding said polypeptide in the genome of said subject; and/or  
 (b) analyzing for the presence or amount of said polypeptide expression in a sample derived from said subject.  
 
     
     
         7 . A method for screening to identify compounds which stimulate or which inhibit the fliction of the polypeptide of    claim 1    which comprises a method selected from the group consisting of. 
 (a) measuring the binding of a candidate compound to the polypeptide (or to the cells or membranes bearing the polypeptide) or a fusion protein thereof by means of a label directly or indirectly associated with the candidate compound;  
 (b) measuring the binding of a candidate compound to the polypeptide (or to the cells or membranes bearing the polypeptide) or a fusion protein thereof in the presense of a labeled competitior;  
 (c) testing whether the candidate compound results in a signal generated by activation or inhibition of the polypeptide, using detection systems appropriate to the cells or cell membranes bearing the polypeptide;  
 (d) mixing a candidate compound with a solution containing a polypeptide of    claim 1   , to form a mixture, measuring activity of the polypeptide in the mixture, and comparing the activity of the mixture to a standard; or  
 (e) detecting the effect of a candidate compound on the production of mRNA encoding said polypeptide and said polypeptide in cells, using for instance, an ELISA assay.  
 
     
     
         8 . An agonist or an antagonist of the polypeptide of    claim 1   .  
     
     
         9 . An expression system comprising a polynucleotide capable of producing a polypeptide of    claim 1    when said expression system is present in a compatible host cell.  
     
     
         10 . A process for producing a recombinant host cell comprising transforming or transfecting a cell with the expression system of    claim 9    such the the host cell, under appropriate culture conditions, produces a polypeptide selected from the group consisting of: 
 (a) a polypeptide comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO:2 over the entire length of SEQ ID NO:2; or  
 (b) a polypeptide comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO:8 over the entire length of SEQ ID NO:8.  
 
     
     
         11 . A recombinant host cell produced by the process of    claim 10   .  
     
     
         12 . A membrane of a recombinant host cell of    claim 11    expressing a polypeptide selected from the group consisting of: 
 (a) a polypeptide comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO:2 over the entire length of SEQ ID NO:2; or  
 (b) a polypeptide comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO:8 over the entire length of SEQ ID NO:8.  
 
     
     
         13 . A process for producing a polypeptide comprising culturing a host cell of claim II under conditions sufficient for the production of said polypeptide and recovering the polypeptide from the culture.  
     
     
         14 . An isolated polynucleotide selected form the group consisting of 
 (a) an isolated polynucleotide comprising a nucleotide sequence which has at least 85%, 90%, 95%, 97% identity to SEQ ID NO:3 over the entire length of SEQ ID NO:3;    (b) an isolated polynucleotide comprising the polynucleotide of SEQ ID NO:3;    (c) the polynucleotide of SEQ ID NO:3;    (d) an isolated polynucleotide comprising a nucleotide sequence encoding a polypeptide which has at least 90%/o, 95%, 97-99% identity to the amino acid sequence of SEQ ID NO:4, over the entire length of SEQ ID NO:4;    (e) an isolated polynucleotide comprising a nucleotide sequence which has at least 85%, 90%, 95%, 97% identity to SEQ ID NO:5 over the entire length of SEQ ID NO:5;    (f) an isolated polynucleotide comprising the polynucleotide of SEQ ID NO:5;    (g) the polynucleotide of SEQ ID NO:5; or    (h) an isolated polynucleotide comprising a nucleotide sequence encoding a polypeptide which has at least 90%, 95%, 97-99% identity to the amino acid sequence of SEQ ID NO:6, over the entire length of SEQ ID NO:6.    
     
     
         15 . A polypeptide selected from the group consisting of: 
 (a) a polypeptide which comprises an amino acid sequence which has at least 90%, 95%, 97-99% identity to that of SEQ ID NO:4 over the entire length of SEQ ID NO:4;    (b) a polypeptide which has an amino acid sequence which is at least 90%, 95%, 9799% identity to the amino acid sequence of SEQ ID NO:4 over the entire length of SEQ ID NO:4;    (c) a polypeptide which comprises the amino acid of SEQ ID NO:4;    (d) a polypeptide which is the polypeptide of SEQ ID NO:4;    (e) a polypeptide which is encoded by a polynucleotide comprising the sequence contained in SEQ ID NO:3;    (f) a polypeptide which comprises an amino acid sequence which has at least 90%, 95%, 97-99% identity to that of SEQ ID NO:6 over the entire length of SEQ ID NO:6;    (g) a polypeptide which has an amino acid sequence which is at least 90%, 95%, 97-99% identity to the amino acid sequence of SEQ ID NO:6 over the entire length of SEQ ID NO:6;    (h) a polypeptide which comprises the amino acid of SEQ ID NO:6;    (i) a polypeptide which is the polypeptide of SEQ ID NO:6; or    (j) a polypeptide which is encoded by a polynucleotide comprising the sequence contained in SEQ ID NO:5.