Insulin

NameInsulin
Synonyms
  • Insulin precursor
Gene NameINS
OrganismHuman
Amino acid sequence
>lcl|BSEQ0006763|Insulin
MALWMRLLPLLALLALWGPDPAAAFVNQHLCGSHLVEALYLVCGERGFFYTPKTRREAED
LQVGQVELGGGPGAGSLQPLALEGSLQKRGIVEQCCTSICSLYQLENYCN
Number of residues110
Molecular Weight11980.795
Theoretical pI5.01
GO Classification
Functions
  • identical protein binding
  • protease binding
  • hormone activity
  • insulin receptor binding
  • insulin-like growth factor receptor binding
Processes
  • glucose metabolic process
  • positive regulation of glycolytic process
  • positive regulation of brown fat cell differentiation
  • positive regulation of cell growth
  • positive regulation of glucose import
  • positive regulation of peptidyl-tyrosine phosphorylation
  • positive regulation of protein kinase B signaling
  • regulation of transmembrane transporter activity
  • positive regulation of cell proliferation
  • positive regulation of glycogen biosynthetic process
  • regulation of transcription, DNA-templated
  • positive regulation of vasodilation
  • positive regulation of phosphatidylinositol 3-kinase signaling
  • positive regulation of insulin receptor signaling pathway
  • activation of protein kinase B activity
  • positive regulation of cellular protein metabolic process
  • positive regulation of lipid biosynthetic process
  • negative regulation of protein secretion
  • positive regulation of DNA replication
  • positive regulation of cell differentiation
  • positive regulation of cell migration
  • negative regulation of protein oligomerization
  • negative regulation of NAD(P)H oxidase activity
  • positive regulation of cytokine secretion
  • positive regulation of protein autophosphorylation
  • cellular protein metabolic process
  • negative regulation of protein catabolic process
  • positive regulation of nitric-oxide synthase activity
  • positive regulation of peptide hormone secretion
  • insulin receptor signaling pathway
  • glucose transport
  • positive regulation of mitotic nuclear division
  • MAPK cascade
  • fatty acid homeostasis
  • negative regulation of fatty acid metabolic process
  • wound healing
  • negative regulation of glycogen catabolic process
  • regulation of cellular amino acid metabolic process
  • negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
  • energy reserve metabolic process
  • positive regulation of nitric oxide biosynthetic process
  • negative regulation of acute inflammatory response
  • positive regulation of respiratory burst
  • G-protein coupled receptor signaling pathway
  • regulation of protein localization
  • negative regulation of lipid catabolic process
  • negative regulation of gluconeogenesis
  • regulation of insulin secretion
  • positive regulation of NF-kappaB transcription factor activity
  • cell-cell signaling
  • regulation of protein secretion
  • negative regulation of vasodilation
  • negative regulation of respiratory burst involved in inflammatory response
  • positive regulation of protein localization to nucleus
  • small molecule metabolic process
  • positive regulation of MAPK cascade
  • alpha-beta T cell activation
  • acute-phase response
  • glucose homeostasis
  • endocrine pancreas development
  • negative regulation of feeding behavior
  • negative regulation of proteolysis
Components
  • endoplasmic reticulum lumen
  • secretory granule lumen
  • extracellular region
  • endosome lumen
  • extracellular space
  • Golgi lumen
General FunctionProtease binding
Specific FunctionInsulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDP01308
UniProtKB Entry NameINS_HUMAN
Cellular LocationSecreted
Gene sequence
>lcl|BSEQ0017117|Insulin (INS)
ATGGCCCTGTGGATGCGCCTCCTGCCCCTGCTGGCGCTGCTGGCCCTCTGGGGACCTGAC
CCAGCCGCAGCCTTTGTGAACCAACACCTGTGCGGCTCACACCTGGTGGAAGCTCTCTAC
CTAGTGTGCGGGGAACGAGGCTTCTTCTACACACCCAAGACCCGCCGGGAGGCAGAGGAC
CTGCAGGTGGGGCAGGTGGAGCTGGGCGGGGGCCCTGGTGCAGGCAGCCTGCAGCCCTTG
GCCCTGGAGGGGTCCCTGCAGAAGCGTGGCATTGTGGAACAATGCTGTACCAGCATCTGC
TCCCTCTACCAGCTGGAGAACTACTGCAACTAG
GenBank Gene IDAJ009655
GeneCard IDNot Available
GenAtlas IDINS
HGNC IDHGNC:6081
Chromosome Location11
LocusNot Available
References
  1. Bell GI, Pictet RL, Rutter WJ, Cordell B, Tischer E, Goodman HM: Sequence of the human insulin gene. Nature. 1980 Mar 6;284(5751):26-32. 6243748
  2. Ullrich A, Dull TJ, Gray A, Brosius J, Sures I: Genetic variation in the human insulin gene. Science. 1980 Aug 1;209(4456):612-5. 6248962
  3. Bell GI, Swain WF, Pictet R, Cordell B, Goodman HM, Rutter WJ: Nucleotide sequence of a cDNA clone encoding human preproinsulin. Nature. 1979 Nov 29;282(5738):525-7. 503234
  4. Sures I, Goeddel DV, Gray A, Ullrich A: Nucleotide sequence of human preproinsulin complementary DNA. Science. 1980 Apr 4;208(4439):57-9. 6927840
  5. Lucassen AM, Julier C, Beressi JP, Boitard C, Froguel P, Lathrop M, Bell JI: Susceptibility to insulin dependent diabetes mellitus maps to a 4.1 kb segment of DNA spanning the insulin gene and associated VNTR. Nat Genet. 1993 Jul;4(3):305-10. 8358440
  6. Minn AH, Kayton M, Lorang D, Hoffmann SC, Harlan DM, Libutti SK, Shalev A: Insulinomas and expression of an insulin splice variant. Lancet. 2004 Jan 31;363(9406):363-7. 15070567
  7. Stead JD, Hurles ME, Jeffreys AJ: Global haplotype diversity in the human insulin gene region. Genome Res. 2003 Sep;13(9):2101-11. 12952878
  8. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  9. NICOL DS, SMITH LF: Amino-acid sequence of human insulin. Nature. 1960 Aug 6;187:483-5. 14426955
  10. Oyer PE, Cho S, Peterson JD, Steiner DF: Studies on human proinsulin. Isolation and amino acid sequence of the human pancreatic C-peptide. J Biol Chem. 1971 Mar 10;246(5):1375-86. 5101771
  11. Ko AS, Smyth DG, Marktussen J, Sundby F: The amino acid sequence of the C-peptide of human proinsulin. Eur J Biochem. 1971 May 28;20(2):190-9. 5560404
  12. Sieber P, Kamber B, Hartmann A, Johl A, Riniker B, Rittel W: [Total synthesis of human insulin under directed formation of the disulfide bonds]. Helv Chim Acta. 1974;57(8):2617-21. 4443293
  13. Naithani VK: Studies on polypeptides, IV. The synthesis of C-peptide of human proinsulin. Hoppe Seylers Z Physiol Chem. 1973 Jun;354(6):659-72. 4803504
  14. Geiger R, Volk A: [Synthesis of peptides with the properties of human proinsulin C peptides ( h C peptide). 3. Synthesis of the sequences 14-17 and 9-13 of human proinsulin C peptides]. Chem Ber. 1973;106(1):199-205. 4698555
  15. Geiger R, Jager G, Konig W, Treuth G: [Synthesis of peptides with the properties of human proinsulin C peptides (hC peptide). I. Scheme for the synthesis and preparation of the sequence 28-31 of human proinsulin C peptide]. Chem Ber. 1973;106(1):188-92. 4698553
  16. Haneda M, Chan SJ, Kwok SC, Rubenstein AH, Steiner DF: Studies on mutant human insulin genes: identification and sequence analysis of a gene encoding [SerB24]insulin. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6366-70. 6312455
  17. Shoelson S, Fickova M, Haneda M, Nahum A, Musso G, Kaiser ET, Rubenstein AH, Tager H: Identification of a mutant human insulin predicted to contain a serine-for-phenylalanine substitution. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7390-4. 6424111
  18. Chan SJ, Seino S, Gruppuso PA, Schwartz R, Steiner DF: A mutation in the B chain coding region is associated with impaired proinsulin conversion in a family with hyperproinsulinemia. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2194-7. 3470784
  19. Sakura H, Iwamoto Y, Sakamoto Y, Kuzuya T, Hirata H: Structurally abnormal insulin in a diabetic patient. Characterization of the mutant insulin A3 (Val----Leu) isolated from the pancreas. J Clin Invest. 1986 Dec;78(6):1666-72. 3537011
  20. Barbetti F, Raben N, Kadowaki T, Cama A, Accili D, Gabbay KH, Merenich JA, Taylor SI, Roth J: Two unrelated patients with familial hyperproinsulinemia due to a mutation substituting histidine for arginine at position 65 in the proinsulin molecule: identification of the mutation by direct sequencing of genomic deoxyribonucleic acid amplified by polymerase chain reaction. J Clin Endocrinol Metab. 1990 Jul;71(1):164-9. 2196279
  21. Shibasaki Y, Kawakami T, Kanazawa Y, Akanuma Y, Takaku F: Posttranslational cleavage of proinsulin is blocked by a point mutation in familial hyperproinsulinemia. J Clin Invest. 1985 Jul;76(1):378-80. 4019786
  22. Yano H, Kitano N, Morimoto M, Polonsky KS, Imura H, Seino Y: A novel point mutation in the human insulin gene giving rise to hyperproinsulinemia (proinsulin Kyoto). J Clin Invest. 1992 Jun;89(6):1902-7. 1601997
  23. Hua QX, Weiss MA: Toward the solution structure of human insulin: sequential 2D 1H NMR assignment of a des-pentapeptide analogue and comparison with crystal structure. Biochemistry. 1990 Nov 20;29(46):10545-55. 2271664
  24. Hua QX, Weiss MA: Comparative 2D NMR studies of human insulin and des-pentapeptide insulin: sequential resonance assignment and implications for protein dynamics and receptor recognition. Biochemistry. 1991 Jun 4;30(22):5505-15. 2036420
  25. Hua QX, Weiss MA: Two-dimensional NMR studies of Des-(B26-B30)-insulin: sequence-specific resonance assignments and effects of solvent composition. Biochim Biophys Acta. 1991 May 30;1078(1):101-10. 1646635
  26. Jorgensen AM, Kristensen SM, Led JJ, Balschmidt P: Three-dimensional solution structure of an insulin dimer. A study of the B9(Asp) mutant of human insulin using nuclear magnetic resonance, distance geometry and restrained molecular dynamics. J Mol Biol. 1992 Oct 20;227(4):1146-63. 1433291
  27. Hua QX, Shoelson SE, Inouye K, Weiss MA: Paradoxical structure and function in a mutant human insulin associated with diabetes mellitus. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):582-6. 8421693
  28. Chang X, Jorgensen AM, Bardrum P, Led JJ: Solution structures of the R6 human insulin hexamer,. Biochemistry. 1997 Aug 5;36(31):9409-22. 9235985
  29. Stoy J, Edghill EL, Flanagan SE, Ye H, Paz VP, Pluzhnikov A, Below JE, Hayes MG, Cox NJ, Lipkind GM, Lipton RB, Greeley SA, Patch AM, Ellard S, Steiner DF, Hattersley AT, Philipson LH, Bell GI: Insulin gene mutations as a cause of permanent neonatal diabetes. Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):15040-4. Epub 2007 Sep 12. 17855560
  30. Edghill EL, Flanagan SE, Patch AM, Boustred C, Parrish A, Shields B, Shepherd MH, Hussain K, Kapoor RR, Malecki M, MacDonald MJ, Stoy J, Steiner DF, Philipson LH, Bell GI, Hattersley AT, Ellard S: Insulin mutation screening in 1,044 patients with diabetes: mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood. Diabetes. 2008 Apr;57(4):1034-42. Epub 2007 Dec 27. 18162506
  31. Molven A, Ringdal M, Nordbo AM, Raeder H, Stoy J, Lipkind GM, Steiner DF, Philipson LH, Bergmann I, Aarskog D, Undlien DE, Joner G, Sovik O, Bell GI, Njolstad PR: Mutations in the insulin gene can cause MODY and autoantibody-negative type 1 diabetes. Diabetes. 2008 Apr;57(4):1131-5. doi: 10.2337/db07-1467. Epub 2008 Jan 11. 18192540
  32. Boesgaard TW, Pruhova S, Andersson EA, Cinek O, Obermannova B, Lauenborg J, Damm P, Bergholdt R, Pociot F, Pisinger C, Barbetti F, Lebl J, Pedersen O, Hansen T: Further evidence that mutations in INS can be a rare cause of Maturity-Onset Diabetes of the Young (MODY). BMC Med Genet. 2010 Mar 12;11:42. doi: 10.1186/1471-2350-11-42. 20226046