The primary structure of human secretogranin I (chromogranin B): comparison with chromogranin A reveals homologous terminal domains and a large intervening variable region.
We have determined and analyzed the primary structure of human secretogranin I (chromogranin B), a tyrosine-sulfated secretory protein found in a wide variety of peptidergic endocrine cells. A 2.5-kb cDNA clone, hybridizing to an mRNA of similar length, was isolated from a cDNA library of human pheochromocytoma. The identity of the clone was established by comparison of its deduced amino acid sequence with N-terminal and several internal secretogranin I sequences as well as by immunoprecipitation of the protein produced by in vitro transcription-translation of the cloned cDNA. Secretogranin I is a 657 amino acid long polypeptide of 76 kd and is preceded by a cleaved N-terminal signal peptide of 20 residues. Comparison of the predicted amino acid sequence of human secretogranin I with that of bovine chromogranin A reveals significant homologies near the N termini and at the C termini. The N-terminal homologous domains contain the only two cysteine residues of both proteins and form disulfide-stabilized loop structures. The sequences between the homologous terminal domains in both proteins differ but are characterized by a remarkable hydrophilicity, an abundance of acidic amino acids and potential dibasic cleavage sites for the generation of smaller, perhaps hormone-like, peptides.
D000310:Adrenal Gland Neoplasms; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D053379:Chromogranin A; D053378:Chromogranin B; D002864:Chromogranins / Q000235:genetics* / Q000302:isolation & purification; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D014644:Genetic Variation; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D010673:Pheochromocytoma; D012333:RNA, Messenger / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid
C506150:CHGA protein, human; C506134:CHGB protein, human; D053379:Chromogranin A; D053378:Chromogranin B; D002864:Chromogranins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D004247:DNA