Polynucleotides and polypeptides belonging to the uncoupling proteins family

Abstract

HNFCW60 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing HNFCW60 polypeptides and polynucleotides in the design of protocols for the treatment of obesity, diabetes, hyperlipademia and body weight disorder, among others, and diagnostic assays for such conditions.

1 . An isolated polynucleotide comprising: 
 (a) a nucleotide sequence which has at least 70% identity, preferably at least 80% identity, more preferably at least 90% identity, yet more preferably at least 95% identity, even more preferably at least 97-99% identity to SEQ ID NO:3 or SEQ ID NO:5 over the entire length of SEQ ID NO:3 or SEQ ID NO:5, respectively;    (b) a nucleotide sequence which has at least 70% identity, preferably at least 80% identity, more preferably at least 90% identity, yet more preferably at least 95% identity, even more preferably at least 97-99% identity, to SEQ ID NO:3 or SEQ ID NO:5 over the entire length of SEQ ID NO:3 or SEQ ID NO:5, respectively;    (c) the polynucleotide of SEQ ID NO:3 or SEQ ID NO:5; or    (d) a nucleotide sequence encoding a polypeptide which has at least 70% identity, preferably at least 80% identity, more preferably at least 90% identity, yet more preferably at least 95% identity, even more preferably at least 97-99% identity, to the amino acid sequence of SEQ ID NO:4 or SEQ ID NO:6 over the entire length of SEQ ID NO:4 or SEQ ID NO:6, respectively;    as well as the polynucleotide of SEQ ID NO:3 or SEQ ID NO:5.    
     
     
         2 . A polypeptide which: 
 (a) comprises an amino acid sequence which has at least 70% identity, preferably at least 80% identity, more preferably at least 90% identity, yet more preferably at least 95% identity, most preferably at least 97-99% identity, to that of SEQ ID NO:4 or SEQ ID NO:6 over the entire length of SEQ ID NO:4 or SEQ ID NO:6, respectively;    (b) has an amino acid sequence which is at least 70% identity, preferably at least 80% identity, more preferably at least 90% identity, yet more preferably at least 95% identity, most preferably at least 97-99% identity, to the amino acid sequence of SEQ ID NO:4 or SEQ ID NO:6 over the entire length of SEQ ID NO:4 or SEQ ID NO:6, respectively;    (c) comprises the amino acid of SEQ ID NO:4 or SEQ ID NO:6; and    (d) is the polypeptide of SEQ ID NO:4 or SEQ ID NO:6; as well as polypeptides encoded by a polynucleotide comprising the sequence contained in SEQ ID NO:3 or SEQ ID NO:5.    
     
     
         3 . An isolated polynucleotide selected from: 
 (a) a polynucleotide comprising a nucleotide sequence encoding the polypeptide of SEQ ID NO:2; and    (b) the polynucleotide of SEQ ID NO: 1;    or a nucleotide sequence complementary to said isolated polynucleotide    
     
     
         4 . An expression system comprising a polynucleotide capable of producing a polypeptide having at least 70% identity to the polypeptide of SEQ ID NO:2 over the entire length of SEQ ID NO:2 when said expression system is present in a compatible host cell.  
     
     
         5 . A host cell comprising the expression system of    claim 4    or a membrane thereof expressing a polypeptide having at least 70% identity to the polypeptide of SEQ ID NO:2 over the entire length of SEQ ID NO:2.  
     
     
         6 . A process for producing a polypeptide of having at least 70% identity to the polypeptide of SEQ ID NO:2 over the entire length of SEQ ID NO:2 comprising culturing a host cell of    claim 5    under conditions sufficient for the production of said polypeptide and recovering the polypeptide from the culture medium.  
     
     
         7 . An antibody immunospecific for a polypeptide having at least 70% identity to the polypeptide of SEQ ID NO:2 over the entire length of SEQ ID NO:2.  
     
     
         8 . A method for screening to identify compounds which stimulate or which inhibit the function of a polypeptide having at least 70% identity to the polypeptide of SEQ ID NO:2 over the entire length of SEQ ID NO:2 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.    
     
     
         9 . An agonist or antagonist to a polypeptide having at least 70% identity to the polypeptide of SEQ ID NO:2 over the entire length of SEQ ID NO:2.  
     
     
         10 . A compound which is an agonist or antagonist to: 
 (a) a polypeptide having at least 70% identity to the polypeptide of SEQ ID NO:2 over the entire length of SEQ ID NO:2;    (b) an isolated polynucleotide of    claim 3   ; or    (c) a nucleic acid molecule that modulates the expression of the nucleotide sequence encoding the polypeptide of SEQ ID NO:2;    for use in therapy.    
     
     
         11 . A process for diagnosing a disease or a susceptibility to a disease in a subject related to expression or activity of a polypeptide having at least 70% identity to the polypeptide of SEQ ID NO:2 over the entire length of SEQ ID NO:2 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.