The bovine chromogranin A gene: structural basis for hormone regulation and generation of biologically active peptides.
The structure of the gene encoding bovine chromogranin-A has been determined by characterization of two isolated genomic clones. Chromogranin-A is encoded by eight exons, which organize the coding region into several distinct structural and functional domains. Exons 1-5 represent the highly conserved signal peptide and N-terminal domain, which are separated into regions corresponding to the signal peptide, N-terminal sequence, disulfide-bonded loop, and remainder of the conserved N-terminal domain. Exon 6 represents the variable domain and encodes a region that is identical to the novel chromogranin-A-derived peptide chromostatin. Exon 7 encodes the biologically active peptide pancreastatin as well as most of the conserved C-terminal domain, with the remainder found on exon 8. The mRNA sequence obtained from the gene contains five nucleotide differences from the consensus sequence of four reported bovine chromogranin-A cDNA clones. Two of the differences in the gene result in two amino acid changes in the region encoded by exon 6. The structural organization of the chromogranin-A gene resembles that of the chromogranin-B gene in the exons corresponding to the signal peptide, N-terminal sequence, disulfide loop, and C-terminal sequence.(ABSTRACT TRUNCATED AT 250 WORDS)
Iacangelo
A L
AL
Unit on Molecular and Cellular Neurobiology, National Institute of Mental Health, Bethesda, Maryland 20892.
Grimes
M
M
Eiden
L E
LE
D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D015139:Blotting, Southern; D002417:Cattle; D002460:Cell Line; D002478:Cells, Cultured; D053379:Chromogranin A; D002864:Chromogranins / Q000235:genetics*; D003001:Cloning, Molecular; D005576:Colforsin / Q000494:pharmacology; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation; D015698:Genomic Library; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D016385:TATA Box; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic
D053379:Chromogranin A; D002864:Chromogranins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; C506155:chromogranin A, mouse; D005576:Colforsin; D003907:Dexamethasone; D004247:DNA; D013755:Tetradecanoylphorbol Acetate