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
  • positive regulation of phosphatidylinositol 3-kinase signaling
  • regulation of transcription, DNA-templated
  • positive regulation of protein autophosphorylation
  • positive regulation of vasodilation
  • positive regulation of cellular protein metabolic process
  • positive regulation of peptide hormone secretion
  • activation of protein kinase B activity
  • positive regulation of DNA replication
  • negative regulation of protein secretion
  • negative regulation of NAD(P)H oxidase activity
  • positive regulation of cell migration
  • negative regulation of fatty acid metabolic process
  • negative regulation of protein oligomerization
  • positive regulation of nitric-oxide synthase activity
  • cellular protein metabolic process
  • negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
  • negative regulation of protein catabolic process
  • positive regulation of mitotic nuclear division
  • insulin receptor signaling pathway
  • positive regulation of respiratory burst
  • glucose transport
  • fatty acid homeostasis
  • MAPK cascade
  • negative regulation of gluconeogenesis
  • negative regulation of glycogen catabolic process
  • wound healing
  • negative regulation of respiratory burst involved in inflammatory response
  • positive regulation of nitric oxide biosynthetic process
  • regulation of cellular amino acid metabolic process
  • energy reserve metabolic process
  • alpha-beta T cell activation
  • regulation of protein localization
  • negative regulation of acute inflammatory response
  • G-protein coupled receptor signaling pathway
  • negative regulation of feeding behavior
  • regulation of insulin secretion
  • positive regulation of brown fat cell differentiation
  • positive regulation of NF-kappaB transcription factor activity
  • cell-cell signaling
  • positive regulation of glucose import
  • negative regulation of lipid catabolic process
  • regulation of transmembrane transporter activity
  • positive regulation of protein localization to nucleus
  • regulation of protein secretion
  • positive regulation of glycogen biosynthetic process
  • negative regulation of vasodilation
  • acute-phase response
  • small molecule metabolic process
  • positive regulation of insulin receptor signaling pathway
  • positive regulation of MAPK cascade
  • negative regulation of proteolysis
  • glucose homeostasis
  • positive regulation of lipid biosynthetic process
  • endocrine pancreas development
  • positive regulation of cell growth
  • glucose metabolic process
  • positive regulation of cell differentiation
  • positive regulation of glycolytic process
  • positive regulation of cell proliferation
  • positive regulation of peptidyl-tyrosine phosphorylation
  • positive regulation of cytokine secretion
  • positive regulation of protein kinase B signaling
Components
  • endoplasmic reticulum lumen
  • secretory granule lumen
  • extracellular region
  • extracellular space
  • endosome lumen
  • 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
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  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
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  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
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  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
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  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