Human stanniocalcin-alpha

Abstract

A human stanniocalcin-alpha polypeptide and DNA (RNA) encoding such polypeptide and a procedure for producing such polypeptide by recombinant techniques is disclosed. Also disclosed are methods for utilizing such polypeptide for the regulation of electrolyte imbalances which can lead to renal, bone and heart diseases and osteoporosis and Paget's Disease. Antagonists against such polypeptides and their use in the regulation of electrolyte imbalances which can lead to hypocalcemia and osteoporosis are also disclosed. Use of the stanniocalcin-alpha sequence as a diagnostic to detect diseases or the susceptibility to diseases related to a mutated form of stanniocalcin-alpha sequences is also disclosed.

1 . An isolated polynucleotide comprising a member selected from the group consisting of: 
 (a) a polynucleotide encoding a mature polypeptide having the deduced amino acid sequence of SEQ ID NO:2 or a fragment, analog or derivative of said polypeptide;    (b) a polynucleotide encoding a mature polypeptide having the amino acid sequence encoded by the cDNA contained in ATCC Deposit No. 75831 or a fragment, analog or derivative of said polypeptide.    
     
     
         2 . The polynucleotide of  claim 1  wherein the polynucleotide is RNA.  
     
     
         3 . The polynucleotide of  claim 1  wherein the polynucleotide is genomic DNA.  
     
     
         4 . The polynucleotide of  claim 1  wherein said polynucleotide encodes a mature polypeptide having the deduced amino acid sequence of SEQ ID NO:2.  
     
     
         5 . The polynucleotide of  claim 1  wherein said polynucleotide encodes a mature polypeptide encoded by the cDNA of ATCC Deposit No. 75831.  
     
     
         6 . The polynucleotide of  claim 1  comprising the DNA sequence of Sequence ID No. 1 encoding the mature polypeptide of Sequence ID No. 2.  
     
     
         7 . A vector containing the DNA of  claim 2 .  
     
     
         8 . A host cell genetically engineered with the vector of  claim 7 .  
     
     
         9 . A process for producing a polypeptide comprising: expressing from the host cell of  claim 8  the polypeptide encoded by said DNA.  
     
     
         10 . A process for producing cells capable of expressing a polypeptide comprising genetically engineering cells with the vector of  claim 7 .  
     
     
         11 . An isolated polynucleotide hybridizable to the polynucleotide of  claim 1  and having at least a 70% identity thereto.  
     
     
         12 . A polypeptide comprising a member selected from the group consisting of (i) a mature polypeptide having the deduced amino acid sequence of Sequence ID No. 2 and fragments, analogs and derivatives thereof; and (ii) a mature polypeptide encoded by the cDNA of ATCC Deposit No. 75831 and fragments, analogs and derivatives of said polypeptide.  
     
     
         13 . An antibody against the polypeptide of  claim 12 .  
     
     
         14 . An antagonist against the polypeptide of  claim 12 .  
     
     
         15 . An agonist to the polypeptide of  claim 12 .  
     
     
         16 . A method for the treatment of a patient having need of human stanniocalcin-alpha comprising: administering to the patient a therapeutically effective amount of the polypeptide of  claim 12 .  
     
     
         17 . A method for the treatment of a patient having need to inhibit stanniocalcin-alpha comprising: administering to the patient a therapeutically effective amount of the antagonist of  claim 15 .  
     
     
         18 . The method of  claim 16  wherein said therapeutically effective amount of the polypeptide is administered by providing to the patient DNA encoding said polypeptide and expressing said polypeptide in vivo.  
     
     
         19 . A process for identifying agonists or antagonists comprising: 
 combining a mammalian cell which expresses a stanniocalcin-alpha receptor on the surface thereof, labeled calcium and the compound to be screened and further in the presence of stanniocalcin-alpha when the screening is for an antagonist; and    determining whether the compound stimulates or inhibits calcium uptake.    
     
     
         20 . A process for diagnosing a disease or a susceptibility to a disease related to an under-expression of human stanniocalcin-alpha polypeptide the polypeptide of  claim 12  in a host comprising: 
 determining in a sample derived from a host a mutation in the human stanniocalcin-alpha nucleic acid sequence encoding the mature polypeptide of Sequence ID No. 2.