Human adenylate cyclase and use therefor

Abstract

There is provided a novel adenylate cyclase enzyme, the nucleotide sequence of which is set out in SEQ ID NO: 98 . The activity of the adenylate cyclase is uniquely regulated by calcineurin, a protein phosphatase. The calcineurin binding site has been identified at amino acids 503 to 610 of the novel adenylate cyclase. Regulation of the novel adenylate cycalse may be useful in treating certain disorders. Suitable regulators include agents which bind to the 503 - 610 amino acid site and include calcineurin, its activators, inhibitors and competitors and antibodies specific to that site. Specific disorders include neurological disorders such as Parkinsons' disease, cardiovascular disorders such as angina pectoris and tumours, especially ovarian tumours.

1 . A protein or polypeptide having adenylate cyclase activity, said activity being regulatable by calcineurin.  
     
     
         2 . A protein or polypeptide as claimed in  claim 1  which is encoded by a polynucleotide comprising a nucleotide sequence derived from the sequence set out in SEQ ID NO: 1 or in SEQ ID NO: 98, or a part thereof.  
     
     
         3 . A protein or polypeptide as claimed in either one of claims  1  and  2  comprising the amino acid sequence as set out in SEQ ID NO: 2 or in SEQ ID NO: 99, a functional equivalent or part thereof.  
     
     
         4 . A protein or polypeptide as claimed in any one of  claims 1  to  3  which includes amino acid Nos 503-570 of SEQ ID NO: 2 or which includes amino acid Nos 503-570 of SEQ ID NO: 99.  
     
     
         5 . An isolated polynucleotide comprising a nucleotide sequence as set out in SEQ ID NO: 98, or a part thereof.  
     
     
         6 . A recombinant polynucleotide construct comprising a polynucleotide as claimed in  claim 5 .  
     
     
         7 . A vector comprising a polynucleotide as claimed in  claim 5  or a construct as claimed in  claim 6 .  
     
     
         8 . A host cell transformed with a vector as claimed in  claim 7 .  
     
     
         9 . A host cell as claimed in  claim 8  which is derived from the Human Embryonic Kidney Cell line 293.  
     
     
         10 . The use of a regulator of a protein or polypeptide as claimed in any one of  claims 1  to  4  to influence cellular metalbolism by affecting the adenylate cyclase activity or the amount of said protein or polypeptide.  
     
     
         11 . The use as claimed in  claim 10  wherein said regulator is calcineurin, its activators, inhibitors and competitors; antibodies to amino acids 503-570; or β-adrenergic agonists and β-adrenergic antagonists.  
     
     
         12 . The use as claimed in either one of claims  10  and  11  wherein said regulator is an antibody to amino acids 503-570 of SEQ ID NOS: 2 or 99.  
     
     
         13 . A method of treating a human or non-human animal body, said method comprising administrating an agent to affect the adenylate cyclase activity of, or the amount of a protein or polypeptide as claimed in any one of  claims 1  to  4 , said protein or polypeptide being present within said body.  
     
     
         14 . A method as claimed in  claim 13  wherein said protein or polypeptide is naturally present within said body.  
     
     
         15 . A method as claimed in either one of claims  13  and  14  to affect or combat neurological-based disorders; psychiatrically-based disorders; endocrine-based disorders; cardiovascular-based disorders; pregnancy-based disorders; respiratory-based disorders; bone-based disorders; kidney-based disorders; gut-based disorders; or tumours.  
     
     
         16 . The use of a protein or polypeptide as claimed in any one of  claims 1  to  4  or a polynucleotide as claimed in  claim 5  to design or test for a therapeutic agent which influences cellular metabolism.