Molecular cloning and primary structure of human chromogranin A (secretory protein I) cDNA.
Chromogranin A (CGA), also referred to as secretory protein I, is an acidic protein that has been detected in all neuroendocrine cell types examined and is often present in large amounts relative to other secreted proteins. For example, CGA comprises at least 40% of the soluble protein of the adrenal chromaffin granule, and it appears to be the major secretory protein in the parathyroid secretory granules. CGA complementary DNAs (cDNAs) from bovine adrenal and pituitary have recently been cloned and sequenced and found to be nearly identical. A region of bovine CGA has a high degree of amino acid sequence identity to pancreastatin, a recently isolated porcine peptide that inhibits glucose-induced insulin secretion. This suggests that CGA may be a prohormone. We have cloned and sequenced a human cDNA encoding CGA. This human CGA cDNA has an overall 86% nucleic acid identity to the bovine cDNA. Like the bovine CGA cDNA, the human cDNA has little homology to pancreastatin at the 5' region of this peptide but significant amino acid homology to the carboxyl-terminal portion of pancreastatin where the biologic activity resides. There is an area within the pancreastatin region of human CGA and porcine pancreastatin with a 70% amino acid identity to the calcium-binding moiety of the E-F hand proteins such as parvalbumin and oncomodulin. These data suggest that CGA and pancreastatin may both be members of a larger family of calcium-binding proteins.
Helman
L J
LJ
Molecular Genetics Section, National Cancer Institute, Bethesda, Maryland 20892.
Ahn
T G
TG
Levine
M A
MA
Allison
A
A
Cohen
P S
PS
Cooper
M J
MJ
Cohn
D V
DV
Israel
M A
MA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D053379:Chromogranin A; D002864:Chromogranins / Q000235:genetics*; D003001:Cloning, Molecular; D004247:DNA / Q000032:analysis*; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D010187:Pancreatic Hormones / Q000032:analysis; D013552:Swine
C506150:CHGA protein, human; D053379:Chromogranin A; D002864:Chromogranins; D009419:Nerve Tissue Proteins; D010187:Pancreatic Hormones; C050836:pancreastatin; D004247:DNA; D002118:Calcium