title: The primary structure of human chromogranin A and pancreastatin.
abstract: A full-length clone encoding human chromogranin A has been isolated from a lambda gt10 cDNA library of a human pheochromocytoma. The nucleotide sequence reveals that human chromogranin A is a 439-residue protein preceded by an 18-residue signal peptide. Comparison of the protein sequence of human chromogranin A with that of bovine chromogranin A shows high conservation of the NH2-terminal and COOH-terminal domains as well as the potential dibasic cleavage sites, whereas the middle portion shows remarkable sequence variation (36%). This part of human chromogranin A contains a sequence homologous to porcine pancreastatin at residues 250-301. The sequence variation in this part of human chromogranin A compared to porcine pancreastatin is 32% and thus of the same magnitude as that between human and bovine chromogranin A. Therefore, the difference between porcine pancreastatin and the corresponding portions of bovine or human chromogranin A can be explained by species variation, suggesting that pancreastatin is derived from chromogranin A itself rather than a protein that is only similar to chromogranin A. Moreover, the pancreastatin sequence contained in human chromogranin A is flanked by sites for proteolytic processing. Together, these observations suggest that human chromogranin A may be the precursor for a human pancreastatin molecule and possibly for other, as yet unidentified, biologically active peptides.
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D053379:Chromogranin A; D002864:Chromogranins / Q000032:analysis* / Q000235:genetics; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000032:analysis*; D010187:Pancreatic Hormones / Q000032:analysis* / Q000235:genetics; D011061:Poly A / Q000032:analysis; D012313:RNA / Q000032:analysis; D012333:RNA, Messenger; D013552:Swine
chemical_list: C506150:CHGA protein, human; D053379:Chromogranin A; D002864:Chromogranins; D009419:Nerve Tissue Proteins; D010187:Pancreatic Hormones; D012333:RNA, Messenger; C050836:pancreastatin; D011061:Poly A; D012313:RNA