Abstract
A clone containing the complete human glucagon gene was isolated and sequenced. The gene is approximately 9.4 kilobases in length and comprises six exons and five introns. The putative preproglucagon encoded by this gene, 180 amino acids in length and containing glucagon and two glucagon-like peptides, is very similar to that of other mammalian species (greater than 90% amino acid sequence homology). There is 88% nucleotide sequence homology between the proximal 130 base pairs of the 5' flanking regions of the human and rat glucagon genes. These sequences, highly conserved throughout evolution, are likely involved in the regulation of glucagon gene transcription.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bell G. I., Sanchez-Pescador R., Laybourn P. J., Najarian R. C. Exon duplication and divergence in the human preproglucagon gene. 1983 Jul 28-Aug 3Nature. 304(5924):368–371. doi: 10.1038/304368a0. [DOI] [PubMed] [Google Scholar]
- Bell G. I., Santerre R. F., Mullenbach G. T. Hamster preproglucagon contains the sequence of glucagon and two related peptides. Nature. 1983 Apr 21;302(5910):716–718. doi: 10.1038/302716a0. [DOI] [PubMed] [Google Scholar]
- Brown J. C. A gastric inhibitory polypeptide. I. The amino acid composition and the tryptic peptides. Can J Biochem. 1971 Feb;49(2):255–261. doi: 10.1139/o71-037. [DOI] [PubMed] [Google Scholar]
- Graves B. J., Johnson P. F., McKnight S. L. Homologous recognition of a promoter domain common to the MSV LTR and the HSV tk gene. Cell. 1986 Feb 28;44(4):565–576. doi: 10.1016/0092-8674(86)90266-7. [DOI] [PubMed] [Google Scholar]
- Heinrich G., Gros P., Habener J. F. Glucagon gene sequence. Four of six exons encode separate functional domains of rat pre-proglucagon. J Biol Chem. 1984 Nov 25;259(22):14082–14087. [PubMed] [Google Scholar]
- Heinrich G., Gros P., Lund P. K., Bentley R. C., Habener J. F. Pre-proglucagon messenger ribonucleic acid: nucleotide and encoded amino acid sequences of the rat pancreatic complementary deoxyribonucleic acid. Endocrinology. 1984 Dec;115(6):2176–2181. doi: 10.1210/endo-115-6-2176. [DOI] [PubMed] [Google Scholar]
- Lawn R. M., Fritsch E. F., Parker R. C., Blake G., Maniatis T. The isolation and characterization of linked delta- and beta-globin genes from a cloned library of human DNA. Cell. 1978 Dec;15(4):1157–1174. doi: 10.1016/0092-8674(78)90043-0. [DOI] [PubMed] [Google Scholar]
- Lopez L. C., Frazier M. L., Su C. J., Kumar A., Saunders G. F. Mammalian pancreatic preproglucagon contains three glucagon-related peptides. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5485–5489. doi: 10.1073/pnas.80.18.5485. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lopez L. C., Li W. H., Frazier M. L., Luo C. C., Saunders G. F. Evolution of glucagon genes. Mol Biol Evol. 1984 Jul;1(4):335–344. doi: 10.1093/oxfordjournals.molbev.a040322. [DOI] [PubMed] [Google Scholar]
- Lund P. K., Goodman R. H., Dee P. C., Habener J. F. Pancreatic preproglucagon cDNA contains two glucagon-related coding sequences arranged in tandem. Proc Natl Acad Sci U S A. 1982 Jan;79(2):345–349. doi: 10.1073/pnas.79.2.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lund P. K., Goodman R. H., Montminy M. R., Dee P. C., Habener J. F. Anglerfish islet pre-proglucagon II. Nucleotide and corresponding amino acid sequence of the cDNA. J Biol Chem. 1983 Mar 10;258(5):3280–3284. [PubMed] [Google Scholar]
- Messing J. New M13 vectors for cloning. Methods Enzymol. 1983;101:20–78. doi: 10.1016/0076-6879(83)01005-8. [DOI] [PubMed] [Google Scholar]
- Mutt V., Jorpes J. E., Magnusson S. Structure of porcine secretin. The amino acid sequence. Eur J Biochem. 1970 Sep;15(3):513–519. doi: 10.1111/j.1432-1033.1970.tb01034.x. [DOI] [PubMed] [Google Scholar]
- Mutt V., Said S. I. Structure of the porcine vasoactive intestinal octacosapeptide. The amino-acid sequence. Use of kallikrein in its determination. Eur J Biochem. 1974 Mar 1;42(2):581–589. doi: 10.1111/j.1432-1033.1974.tb03373.x. [DOI] [PubMed] [Google Scholar]
- Patzelt C., Tager H. S., Carroll R. J., Steiner D. F. Identification and processing of proglucagon in pancreatic islets. Nature. 1979 Nov 15;282(5736):260–266. doi: 10.1038/282260a0. [DOI] [PubMed] [Google Scholar]
- Ravazzola M., Siperstein A., Moody A. J., Sundby F., Jacobsen H., Orci L. Glicentin immunoreactive cells: their relationship to glucagon-producing cells. Endocrinology. 1979 Aug;105(2):499–508. doi: 10.1210/endo-105-2-499. [DOI] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schroeder W. T., Lopez L. C., Harper M. E., Saunders G. F. Localization of the human glucagon gene (GCG) to chromosome segment 2q36----37. Cytogenet Cell Genet. 1984;38(1):76–79. doi: 10.1159/000132034. [DOI] [PubMed] [Google Scholar]
- Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
- Spiess J., Rivier J., Thorner M., Vale W. Sequence analysis of a growth hormone releasing factor from a human pancreatic islet tumor. Biochemistry. 1982 Nov 23;21(24):6037–6040. doi: 10.1021/bi00267a002. [DOI] [PubMed] [Google Scholar]
- Sundby F., Jacobsen H., Moody A. J. Purification and characterization of a protein from porcine gut with glucagon-like immunoreactivity. Horm Metab Res. 1976 Sep;8(5):366–371. doi: 10.1055/s-0028-1093615. [DOI] [PubMed] [Google Scholar]
- Swift G. H., Craik C. S., Stary S. J., Quinto C., Lahaie R. G., Rutter W. J., MacDonald R. J. Structure of the two related elastase genes expressed in the rat pancreas. J Biol Chem. 1984 Nov 25;259(22):14271–14278. [PubMed] [Google Scholar]
- Thim L., Moody A. J. The primary structure of porcine glicentin (proglucagon). Regul Pept. 1981 May;2(2):139–150. doi: 10.1016/0167-0115(81)90007-0. [DOI] [PubMed] [Google Scholar]
- Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Unger R. H., Orci L. Glucagon and the A cell: physiology and pathophysiology (first two parts). N Engl J Med. 1981 Jun 18;304(25):1518–1524. doi: 10.1056/NEJM198106183042504. [DOI] [PubMed] [Google Scholar]