title: Primary structure of the major human pituitary pro-opiomelanocortin NH2-terminal glycopeptide. Evidence for an aldosterone-stimulating activity.
abstract: The isolation and complete purification of a human glycopeptide representing the major immunoreactive form of the pituitary NH2-terminal segment of pro-opiomelanocortin is presented. The complete sequence of this peptide was determined following CNBr fragmentation and it is shown to be 76 amino acids long. It bears an O-glycosylation site at Thr 45 and an N-glycosidic linkage at Asn 65. Compared to the reported genomic DNA sequence (Chang, A. C. Y., Cochet, M., and Cohen, S. N. (1980) Proc. Natl. Acad. Sci. U. S. A. 77, 4890-4894), one variation exists, namely Arg 22 replacing Gly 22. Two disulfide bridges linking Cys 2 to 8 and Cys 20 to 24 have been determined. Based on the sequence and disulfide bridge localization, a large degree of homology exists between the NH2-terminal sequence of the human peptide and all calcitonins, especially porcine calcitonin. The human NH2-terminal peptide is shown to stimulate the release of aldosterone from isolated cells of a human adrenal tumor, in at least equipotency to adrenocorticotropic hormone and the porcine NH2-terminal analogue, which is 100 times more potent than angiotensin II. Finally, this reported sequence completes that of the human DNA which was lacking the first 19 amino acids due to the presence of a 2-kilobase intron.
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003488:Cyanogen Bromide; D004247:DNA; D005796:Genes; D006020:Glycopeptides / Q000494:pharmacology; D006801:Humans; D007460:Iodoacetamide; D010446:Peptide Fragments; D010902:Pituitary Gland / Q000032:analysis*; D010908:Pituitary Hormones, Anterior / Q000494:pharmacology; D011333:Pro-Opiomelanocortin; D013045:Species Specificity; D013552:Swine
chemical_list: D006020:Glycopeptides; D010446:Peptide Fragments; D010908:Pituitary Hormones, Anterior; C031562:pro-opiomelanocortin amino-terminal glycopeptide; D000450:Aldosterone; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D004247:DNA; D003488:Cyanogen Bromide; D007460:Iodoacetamide