Insulin

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functionⁱ

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• hormone activity Source: BHF-UCL <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • "A structurally abnormal insulin causing human diabetes."
    Tager H., Given B., Baldwin D., Mako M., Markese J., Rubenstein A., Olefsky J., Kobayashi M., Kolterman O., Poucher R.
    Nature 281:122-125(1979) [PubMed] [Europe PMC] [Abstract]
• identical protein binding Source: IntAct <p>Inferred from Physical Interaction</p> <p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ipi">GO evidence code guide</a></p> Inferred from physical interactionⁱ
  • "A helical structural nucleus is the primary elongating unit of insulin amyloid fibrils."
    Vestergaard B., Groenning M., Roessle M., Kastrup J.S., van de Weert M., Flink J.M., Frokjaer S., Gajhede M., Svergun D.I.
    PLoS Biol 5:e134-e134(2007) [PubMed] [Europe PMC] [Abstract]
  • "Structural features of proinsulin C-peptide oligomeric and amyloid states."
    Lind J., Lindahl E., Peralvarez-Marin A., Holmlund A., Jornvall H., Maler L.
    FEBS J 277:3759-3768(2010) [PubMed] [Europe PMC] [Abstract]
  • "SERF protein is a direct modifier of amyloid fiber assembly."
    Falsone S.F., Meyer N.H., Schrank E., Leitinger G., Pham C.L., Fodero-Tavoletti M.T., Holmberg M., Dulle M., Scicluna B., Gesslbauer B., Rueckert H.M., Wagner G.E., Merle D.A., Nollen E.A., Kungl A.J., Hill A.F., Cappai R., Zangger K.
    Cell Rep. 2:358-371(2012) [PubMed] [Europe PMC] [Abstract]
  • "Insulin solubility transitions by pH-dependent interactions with proinsulin C-peptide."
    Landreh M., Alvelius G., Willander H., Stukenborg J.B., Soder O., Johansson J., Jornvall H.
    FEBS J 279:4589-4597(2012) [PubMed] [Europe PMC] [Abstract]
  • "Amino acid sequence determinants in self-assembly of insulin chiral amyloid superstructures: role of C-terminus of B-chain in association of fibrils."
    Babenko V., Dzwolak W.
    FEBS Lett 587:625-630(2013) [PubMed] [Europe PMC] [Abstract]
  • "Peptides that form beta-sheets on hydrophobic surfaces accelerate surface-induced insulin amyloidal aggregation."
    Nault L., Vendrely C., Brechet Y., Bruckert F., Weidenhaupt M.
    FEBS Lett 587:1281-1286(2013) [PubMed] [Europe PMC] [Abstract]
• insulin-like growth factor receptor binding Source: BHF-UCLInferred from physical interactionⁱ
  • "Purified hybrid insulin/insulin-like growth factor-I receptors bind insulin-like growth factor-I, but not insulin, with high affinity."
    Soos M.A., Field C.E., Siddle K.
    Biochem. J. 290:419-426(1993) [PubMed] [Europe PMC] [Abstract]
• insulin receptor binding Source: UniProtKB <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ
  • "Binding of human, porcine and bovine insulin to insulin receptors from human brain, muscle and adipocytes and to expressed recombinant alternatively spliced insulin receptor isoforms."
    Kotzke G., Schutt M., Missler U., Moller D.E., Fehm H.L., Klein H.H.
    Diabetologia 38:757-763(1995) [PubMed] [Europe PMC] [Abstract]
• protease binding Source: UniProtKBInferred from physical interactionⁱ
  • "In vitro degradation of insulin-like peptide 3 by insulin-degrading enzyme."
    Zhang W.J., Luo X., Guo Z.Y.
    Protein J 29:93-98(2010) [PubMed] [Europe PMC] [Abstract]

GO - Biological processⁱ

• activation of protein kinase B activity Source: BHF-UCLInferred from direct assayⁱ
  • "Akt, a pleckstrin homology domain containing kinase, is activated primarily by phosphorylation."
    Kohn A.D., Takeuchi F., Roth R.A.
    J Biol Chem 271:21920-21926(1996) [PubMed] [Europe PMC] [Abstract]
• acute-phase response Source: BHF-UCLInferred from direct assayⁱ
  • "Insulin decreases hepatic acute phase protein levels in severely burned children."
    Wu X., Thomas S.J., Herndon D.N., Sanford A.P., Wolf S.E.
    Surgery 135:196-202(2004) [PubMed] [Europe PMC] [Abstract]
• alpha-beta T cell activation Source: UniProtKBInferred from direct assayⁱ
  • "Bovine and human insulin activate CD8+-autoreactive CTL expressing both type 1 and type 2 cytokines in C57BL/6 mice."
    Ma H., Ke Y., Li Q., Kapp J.A.
    J Immunol 164:86-92(2000) [PubMed] [Europe PMC] [Abstract]
• amyloid fibril formation Source: Reactome
• cell-cell signaling Source: UniProtKB <p>Inferred by Curator</p> <p>Used for cases where an annotation is not supported by any evidence but can be reasonably inferred by a curator from other GO annotations for which evidence<br />is available.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ic">GO evidence code guide</a></p> Inferred by curatorⁱ
  • "Binding of human, porcine and bovine insulin to insulin receptors from human brain, muscle and adipocytes and to expressed recombinant alternatively spliced insulin receptor isoforms."
    Kotzke G., Schutt M., Missler U., Moller D.E., Fehm H.L., Klein H.H.
    Diabetologia 38:757-763(1995) [PubMed] [Europe PMC] [Abstract]
• cognition Source: ARUK-UCL <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#tas">GO evidence code guide</a></p> Traceable author statementⁱ
  • "Protection of synapses against Alzheimer's-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers."
    De Felice F.G., Vieira M.N., Bomfim T.R., Decker H., Velasco P.T., Lambert M.P., Viola K.L., Zhao W.Q., Ferreira S.T., Klein W.L.
    Proc Natl Acad Sci U S A 106:1971-1976(2009) [PubMed] [Europe PMC] [Abstract]
• endoplasmic reticulum to Golgi vesicle-mediated transport Source: Reactome
• fatty acid homeostasis Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "Glucagon regulation of plasma ketone body concentration in human diabetes."
    Schade D.S., Eaton R.P.
    J Clin Invest 56:1340-1344(1975) [PubMed] [Europe PMC] [Abstract]
• glucose homeostasis Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "A structurally abnormal insulin causing human diabetes."
    Tager H., Given B., Baldwin D., Mako M., Markese J., Rubenstein A., Olefsky J., Kobayashi M., Kolterman O., Poucher R.
    Nature 281:122-125(1979) [PubMed] [Europe PMC] [Abstract]
• glucose metabolic process Source: UniProtKB-KW
• G protein-coupled receptor signaling pathway Source: BHF-UCLInferred from direct assayⁱ
  • "Insulin-induced activation of NADPH-dependent H2O2 generation in human adipocyte plasma membranes is mediated by Galphai2."
    Krieger-Brauer H.I., Medda P.K., Kather H.
    J Biol Chem 272:10135-10143(1997) [PubMed] [Europe PMC] [Abstract]
• insulin receptor signaling pathway Source: BHF-UCLInferred from direct assayⁱ
  • "A novel domain of caveolin-2 that controls nuclear targeting: regulation of insulin-specific ERK activation and nuclear translocation by caveolin-2."
    Kwon H., Jeong K., Hwang E.M., Park J.Y., Pak Y.
    J Cell Mol Med 15:888-908(2011) [PubMed] [Europe PMC] [Abstract]
• negative regulation of acute inflammatory response Source: BHF-UCLInferred from direct assayⁱ
  • "Insulin inhibits intranuclear nuclear factor kappaB and stimulates IkappaB in mononuclear cells in obese subjects: evidence for an anti-inflammatory effect?"
    Dandona P., Aljada A., Mohanty P., Ghanim H., Hamouda W., Assian E., Ahmad S.
    J Clin Endocrinol Metab 86:3257-3265(2001) [PubMed] [Europe PMC] [Abstract]
• negative regulation of fatty acid metabolic process Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "Glucagon regulation of plasma ketone body concentration in human diabetes."
    Schade D.S., Eaton R.P.
    J Clin Invest 56:1340-1344(1975) [PubMed] [Europe PMC] [Abstract]
• negative regulation of feeding behavior Source: DFLATInferred from direct assayⁱ
  • "Milk intake and feeding behavior in the first week of life and its relationship to cord blood ghrelin, leptin, and insulin concentrations."
    James R.J., James A., Drewett R.F., Cheetham T.D.
    Pediatr Res 62:695-699(2007) [PubMed] [Europe PMC] [Abstract]
• negative regulation of gluconeogenesis Source: BHF-UCL <p>Non-traceable Author Statement</p> <p>Used for statements in the abstract, introduction or discussion of a paper that cannot be traced back to another publication.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#nas">GO evidence code guide</a></p> Non-traceable author statementⁱ
  • "Insulin signalling and the regulation of glucose and lipid metabolism."
    Saltiel A.R., Kahn C.R.
    Nature 414:799-806(2001) [PubMed] [Europe PMC] [Abstract]
• negative regulation of glycogen catabolic process Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "A structurally abnormal insulin causing human diabetes."
    Tager H., Given B., Baldwin D., Mako M., Markese J., Rubenstein A., Olefsky J., Kobayashi M., Kolterman O., Poucher R.
    Nature 281:122-125(1979) [PubMed] [Europe PMC] [Abstract]
• negative regulation of lipid catabolic process Source: AgBaseInferred from mutant phenotypeⁱ
  • "Resistin in dairy cows: plasma concentrations during early lactation, expression and potential role in adipose tissue."
    Reverchon M., Rame C., Cognie J., Briant E., Elis S., Guillaume D., Dupont J.
    PLoS One 9:e93198-e93198(2014) [PubMed] [Europe PMC] [Abstract]
• negative regulation of NAD(P)H oxidase activity Source: BHF-UCLInferred from direct assayⁱ
  • "Insulin inhibits intranuclear nuclear factor kappaB and stimulates IkappaB in mononuclear cells in obese subjects: evidence for an anti-inflammatory effect?"
    Dandona P., Aljada A., Mohanty P., Ghanim H., Hamouda W., Assian E., Ahmad S.
    J Clin Endocrinol Metab 86:3257-3265(2001) [PubMed] [Europe PMC] [Abstract]
• negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway Source: BHF-UCLNon-traceable author statementⁱ
  • "Neuroprotection of insulin against oxidative stress-induced apoptosis in cultured retinal neurons: involvement of phosphoinositide 3-kinase/Akt signal pathway."
    Yu X.R., Jia G.R., Gao G.D., Wang S.H., Han Y., Cao W.
    Acta Biochim Biophys Sin (Shanghai) 38:241-248(2006) [PubMed] [Europe PMC] [Abstract]
• negative regulation of protein catabolic process Source: UniProtKBInferred from direct assayⁱ
  • "Intravenous insulin decreases protein breakdown in infants on extracorporeal membrane oxygenation."
    Agus M.S., Javid P.J., Ryan D.P., Jaksic T.
    J Pediatr Surg 39:839-844(2004) [PubMed] [Europe PMC] [Abstract]
• negative regulation of protein secretion Source: BHF-UCLInferred from direct assayⁱ
  • "Insulin decreases hepatic acute phase protein levels in severely burned children."
    Wu X., Thomas S.J., Herndon D.N., Sanford A.P., Wolf S.E.
    Surgery 135:196-202(2004) [PubMed] [Europe PMC] [Abstract]
• negative regulation of proteolysis Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "Effect of intravenous insulin treatment on in vivo whole body leucine kinetics and oxygen consumption in insulin-deprived type I diabetic patients."
    Nair K.S., Ford G.C., Halliday D.
    Metabolism 36:491-495(1987) [PubMed] [Europe PMC] [Abstract]
• negative regulation of reactive oxygen species biosynthetic process Source: ARUK-UCL <p>Inferred from Genetic Interaction</p> <p>Used to describe "traditional" genetic interactions such as suppressors and synthetic lethals as well as other techniques such as functional complementation, rescue experiments, or inferences about a gene drawn from the phenotype of a mutation in a different gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#igi">GO evidence code guide</a></p> Inferred from genetic interactionⁱ
  • "Protection of synapses against Alzheimer's-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers."
    De Felice F.G., Vieira M.N., Bomfim T.R., Decker H., Velasco P.T., Lambert M.P., Viola K.L., Zhao W.Q., Ferreira S.T., Klein W.L.
    Proc Natl Acad Sci U S A 106:1971-1976(2009) [PubMed] [Europe PMC] [Abstract]
• negative regulation of respiratory burst involved in inflammatory response Source: BHF-UCLInferred from direct assayⁱ
  • "Insulin inhibits intranuclear nuclear factor kappaB and stimulates IkappaB in mononuclear cells in obese subjects: evidence for an anti-inflammatory effect?"
    Dandona P., Aljada A., Mohanty P., Ghanim H., Hamouda W., Assian E., Ahmad S.
    J Clin Endocrinol Metab 86:3257-3265(2001) [PubMed] [Europe PMC] [Abstract]
• neuron projection maintenance Source: ARUK-UCLInferred from genetic interactionⁱ
  • "Protection of synapses against Alzheimer's-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers."
    De Felice F.G., Vieira M.N., Bomfim T.R., Decker H., Velasco P.T., Lambert M.P., Viola K.L., Zhao W.Q., Ferreira S.T., Klein W.L.
    Proc Natl Acad Sci U S A 106:1971-1976(2009) [PubMed] [Europe PMC] [Abstract]
• nitric oxide-cGMP-mediated signaling pathway Source: UniProtKBInferred from direct assayⁱ
  • "Insulin induces the release of vasodilator compounds from platelets by a nitric oxide-G kinase-VAMP-3-dependent pathway."
    Randriamboavonjy V., Schrader J., Busse R., Fleming I.
    J Exp Med 199:347-356(2004) [PubMed] [Europe PMC] [Abstract]
• positive regulation of brown fat cell differentiation Source: BHF-UCLTraceable author statementⁱ
  • "Insulin and glucocorticoids differentially regulate leptin transcription and secretion in brown adipocytes."
    Buyse M., Viengchareun S., Bado A., Lombes M.
    FASEB J 15:1357-1366(2001) [PubMed] [Europe PMC] [Abstract]
• positive regulation of cell differentiation Source: BHF-UCLNon-traceable author statementⁱ
  • "Insulin signalling and the regulation of glucose and lipid metabolism."
    Saltiel A.R., Kahn C.R.
    Nature 414:799-806(2001) [PubMed] [Europe PMC] [Abstract]
• positive regulation of cell growth Source: BHF-UCLNon-traceable author statementⁱ
  • "Insulin signalling and the regulation of glucose and lipid metabolism."
    Saltiel A.R., Kahn C.R.
    Nature 414:799-806(2001) [PubMed] [Europe PMC] [Abstract]
• positive regulation of cell migration Source: BHF-UCL <p>Inferred from Sequence or Structural Similarity<br />Used for any analysis based on sequence alignment, structure comparison, or evaluation of sequence features such as composition.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#iss">GO evidence code guide</a></p> Inferred from sequence or structural similarityⁱ
  • "Insulin/insulin-like growth factor I hybrid receptors have different biological characteristics depending on the insulin receptor isoform involved."
    Pandini G., Frasca F., Mineo R., Sciacca L., Vigneri R., Belfiore A.
    J. Biol. Chem. 277:39684-39695(2002) [PubMed] [Europe PMC] [Abstract]
• positive regulation of cell population proliferation Source: BHF-UCLInferred from direct assayⁱ
  • "Activation of the insulin receptor by insulin and a synthetic peptide leads to divergent metabolic and mitogenic signaling and responses."
    Jensen M., Hansen B., De Meyts P., Schaffer L., Urso B.
    J Biol Chem 282:35179-35186(2007) [PubMed] [Europe PMC] [Abstract]
  • "Insulin and IGF-1 increase mitogenesis and glucose metabolism in the multiple myeloma cell line, RPMI 8226."
    Freund G.G., Kulas D.T., Mooney R.A.
    J Immunol 151:1811-1820(1993) [PubMed] [Europe PMC] [Abstract]
• positive regulation of cellular protein metabolic process Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "Effect of intravenous insulin treatment on in vivo whole body leucine kinetics and oxygen consumption in insulin-deprived type I diabetic patients."
    Nair K.S., Ford G.C., Halliday D.
    Metabolism 36:491-495(1987) [PubMed] [Europe PMC] [Abstract]
• positive regulation of cytokine production Source: UniProtKBInferred from direct assayⁱ
  • "Insulin activates vascular endothelial growth factor in vascular smooth muscle cells: influence of nitric oxide and of insulin resistance."
    Doronzo G., Russo I., Mattiello L., Anfossi G., Bosia A., Trovati M.
    Eur J Clin Invest 34:664-673(2004) [PubMed] [Europe PMC] [Abstract]
• positive regulation of dendritic spine maintenance Source: ARUK-UCLInferred from genetic interactionⁱ
  • "Protection of synapses against Alzheimer's-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers."
    De Felice F.G., Vieira M.N., Bomfim T.R., Decker H., Velasco P.T., Lambert M.P., Viola K.L., Zhao W.Q., Ferreira S.T., Klein W.L.
    Proc Natl Acad Sci U S A 106:1971-1976(2009) [PubMed] [Europe PMC] [Abstract]
• positive regulation of gene expression Source: BHF-UCLInferred from genetic interactionⁱ
  • "Glucose tolerance is associated with differential expression of microRNAs in skeletal muscle: results from studies of twins with and without type 2 diabetes."
    Bork-Jensen J., Scheele C., Christophersen D.V., Nilsson E., Friedrichsen M., Fernandez-Twinn D.S., Grunnet L.G., Litman T., Holmstrom K., Vind B., Hojlund K., Beck-Nielsen H., Wojtaszewski J., Ozanne S.E., Pedersen B.K., Poulsen P., Vaag A.
    Diabetologia 58:363-373(2015) [PubMed] [Europe PMC] [Abstract]
• positive regulation of glucose import Source: UniProtKBInferred from direct assayⁱ
  • "Insulin and nitric oxide stimulates glucose transport in human placenta."
    Acevedo C.G., Marquez J.L., Rojas S., Bravo I.
    Life Sci 76:2643-2653(2005) [PubMed] [Europe PMC] [Abstract]
• positive regulation of glycogen biosynthetic process Source: BHF-UCLInferred from direct assayⁱ
  • "Activation of the insulin receptor by insulin and a synthetic peptide leads to divergent metabolic and mitogenic signaling and responses."
    Jensen M., Hansen B., De Meyts P., Schaffer L., Urso B.
    J Biol Chem 282:35179-35186(2007) [PubMed] [Europe PMC] [Abstract]
• positive regulation of glycolytic process Source: BHF-UCLInferred from direct assayⁱ
  • "Insulin and IGF-1 increase mitogenesis and glucose metabolism in the multiple myeloma cell line, RPMI 8226."
    Freund G.G., Kulas D.T., Mooney R.A.
    J Immunol 151:1811-1820(1993) [PubMed] [Europe PMC] [Abstract]
• positive regulation of insulin receptor signaling pathway Source: UniProtKBInferred from direct assayⁱ
  • "Insulin and nitric oxide stimulates glucose transport in human placenta."
    Acevedo C.G., Marquez J.L., Rojas S., Bravo I.
    Life Sci 76:2643-2653(2005) [PubMed] [Europe PMC] [Abstract]
• positive regulation of lipid biosynthetic process Source: BHF-UCLNon-traceable author statementⁱ
  • "Insulin signalling and the regulation of glucose and lipid metabolism."
    Saltiel A.R., Kahn C.R.
    Nature 414:799-806(2001) [PubMed] [Europe PMC] [Abstract]
• positive regulation of long-term synaptic potentiation Source: ARUK-UCLTraceable author statementⁱ
  • "Protection of synapses against Alzheimer's-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers."
    De Felice F.G., Vieira M.N., Bomfim T.R., Decker H., Velasco P.T., Lambert M.P., Viola K.L., Zhao W.Q., Ferreira S.T., Klein W.L.
    Proc Natl Acad Sci U S A 106:1971-1976(2009) [PubMed] [Europe PMC] [Abstract]
• positive regulation of MAPK cascade Source: BHF-UCLInferred from direct assayⁱ
  • "Regulation of the Akt/Glycogen synthase kinase-3 axis by insulin-like growth factor-II via activation of the human insulin receptor isoform-A."
    Scalia P., Heart E., Comai L., Vigneri R., Sung C.K.
    J Cell Biochem 82:610-618(2001) [PubMed] [Europe PMC] [Abstract]
  • "A novel domain of caveolin-2 that controls nuclear targeting: regulation of insulin-specific ERK activation and nuclear translocation by caveolin-2."
    Kwon H., Jeong K., Hwang E.M., Park J.Y., Pak Y.
    J Cell Mol Med 15:888-908(2011) [PubMed] [Europe PMC] [Abstract]
• positive regulation of mitotic nuclear division Source: UniProtKBInferred from direct assayⁱ
  • "PSM, a mediator of PDGF-BB-, IGF-I-, and insulin-stimulated mitogenesis."
    Riedel H., Yousaf N., Zhao Y., Dai H., Deng Y., Wang J.
    Oncogene 19:39-50(2000) [PubMed] [Europe PMC] [Abstract]
• positive regulation of NF-kappaB transcription factor activity Source: BHF-UCLInferred from direct assayⁱ
  • "Extracellular PBEF/NAMPT/visfatin activates pro-inflammatory signalling in human vascular smooth muscle cells through nicotinamide phosphoribosyltransferase activity."
    Romacho T., Azcutia V., Vazquez-Bella M., Matesanz N., Cercas E., Nevado J., Carraro R., Rodriguez-Manas L., Sanchez-Ferrer C.F., Peiro C.
    Diabetologia 52:2455-2463(2009) [PubMed] [Europe PMC] [Abstract]
• positive regulation of nitric oxide mediated signal transduction Source: UniProtKBInferred from direct assayⁱ
  • "Insulin and nitric oxide stimulates glucose transport in human placenta."
    Acevedo C.G., Marquez J.L., Rojas S., Bravo I.
    Life Sci 76:2643-2653(2005) [PubMed] [Europe PMC] [Abstract]
• positive regulation of nitric-oxide synthase activity Source: UniProtKBNon-traceable author statementⁱ
  • "Insulin-dependent activation of endothelial nitric oxide synthase is impaired by O-linked glycosylation modification of signaling proteins in human coronary endothelial cells."
    Federici M., Menghini R., Mauriello A., Hribal M.L., Ferrelli F., Lauro D., Sbraccia P., Spagnoli L.G., Sesti G., Lauro R.
    Circulation 106:466-472(2002) [PubMed] [Europe PMC] [Abstract]
• positive regulation of peptide hormone secretion Source: BHF-UCLTraceable author statementⁱ
  • "Insulin and glucocorticoids differentially regulate leptin transcription and secretion in brown adipocytes."
    Buyse M., Viengchareun S., Bado A., Lombes M.
    FASEB J 15:1357-1366(2001) [PubMed] [Europe PMC] [Abstract]
• positive regulation of phosphatidylinositol 3-kinase signaling Source: BHF-UCLInferred from direct assayⁱ
  • "Insulin and IGF-1 increase mitogenesis and glucose metabolism in the multiple myeloma cell line, RPMI 8226."
    Freund G.G., Kulas D.T., Mooney R.A.
    J Immunol 151:1811-1820(1993) [PubMed] [Europe PMC] [Abstract]
• positive regulation of protein autophosphorylation Source: BHF-UCLInferred from sequence or structural similarityⁱ
  • "Replacement of insulin receptor tyrosine residues 1162 and 1163 compromises insulin-stimulated kinase activity and uptake of 2-deoxyglucose."
    Ellis L., Clauser E., Morgan D.O., Edery M., Roth R.A., Rutter W.J.
    Cell 45:721-732(1986) [PubMed] [Europe PMC] [Abstract]
• positive regulation of protein kinase B signaling Source: BHF-UCLInferred from direct assayⁱ
  • "Regulation of the Akt/Glycogen synthase kinase-3 axis by insulin-like growth factor-II via activation of the human insulin receptor isoform-A."
    Scalia P., Heart E., Comai L., Vigneri R., Sung C.K.
    J Cell Biochem 82:610-618(2001) [PubMed] [Europe PMC] [Abstract]
• positive regulation of protein localization to nucleus Source: BHF-UCLInferred from direct assayⁱ
  • "A novel domain of caveolin-2 that controls nuclear targeting: regulation of insulin-specific ERK activation and nuclear translocation by caveolin-2."
    Kwon H., Jeong K., Hwang E.M., Park J.Y., Pak Y.
    J Cell Mol Med 15:888-908(2011) [PubMed] [Europe PMC] [Abstract]
• positive regulation of respiratory burst Source: BHF-UCLInferred from direct assayⁱ
  • "Insulin-induced activation of NADPH-dependent H2O2 generation in human adipocyte plasma membranes is mediated by Galphai2."
    Krieger-Brauer H.I., Medda P.K., Kather H.
    J Biol Chem 272:10135-10143(1997) [PubMed] [Europe PMC] [Abstract]
• regulation of cellular amino acid metabolic process Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "Effect of intravenous insulin treatment on in vivo whole body leucine kinetics and oxygen consumption in insulin-deprived type I diabetic patients."
    Nair K.S., Ford G.C., Halliday D.
    Metabolism 36:491-495(1987) [PubMed] [Europe PMC] [Abstract]
• regulation of protein localization Source: BHF-UCLInferred from direct assayⁱ
  • "Insulin stimulates glucose transport via nitric oxide/cyclic GMP pathway in human vascular smooth muscle cells."
    Bergandi L., Silvagno F., Russo I., Riganti C., Anfossi G., Aldieri E., Ghigo D., Trovati M., Bosia A.
    Arterioscler Thromb Vasc Biol 23:2215-2221(2003) [PubMed] [Europe PMC] [Abstract]
• regulation of protein localization to plasma membrane Source: ARUK-UCLInferred from genetic interactionⁱ
  • "Protection of synapses against Alzheimer's-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers."
    De Felice F.G., Vieira M.N., Bomfim T.R., Decker H., Velasco P.T., Lambert M.P., Viola K.L., Zhao W.Q., Ferreira S.T., Klein W.L.
    Proc Natl Acad Sci U S A 106:1971-1976(2009) [PubMed] [Europe PMC] [Abstract]
• regulation of protein secretion Source: UniProtKBInferred from direct assayⁱ
  • "Insulin decreases the secretion of apoB-100 from hepatic HepG2 cells but does not decrease the secretion of apoB-48 from intestinal CaCo-2 cells."
    Allister E.M., Pal S., Thomson A.M., Helmerhorst E., Mamo J.C.
    J Biomed Sci 11:789-798(2004) [PubMed] [Europe PMC] [Abstract]
• regulation of synaptic plasticity Source: ARUK-UCLTraceable author statementⁱ
  • "Protection of synapses against Alzheimer's-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers."
    De Felice F.G., Vieira M.N., Bomfim T.R., Decker H., Velasco P.T., Lambert M.P., Viola K.L., Zhao W.Q., Ferreira S.T., Klein W.L.
    Proc Natl Acad Sci U S A 106:1971-1976(2009) [PubMed] [Europe PMC] [Abstract]
• regulation of transcription, DNA-templated Source: BHF-UCLNon-traceable author statementⁱ
  • "Differential gene expression induced by insulin and insulin-like growth factor-II through the insulin receptor isoform A."
    Pandini G., Medico E., Conte E., Sciacca L., Vigneri R., Belfiore A.
    J Biol Chem 278:42178-42189(2003) [PubMed] [Europe PMC] [Abstract]
• regulation of transmembrane transporter activity Source: BHF-UCLInferred from direct assayⁱ
  • "Insulin stimulates glucose transport via nitric oxide/cyclic GMP pathway in human vascular smooth muscle cells."
    Bergandi L., Silvagno F., Russo I., Riganti C., Anfossi G., Aldieri E., Ghigo D., Trovati M., Bosia A.
    Arterioscler Thromb Vasc Biol 23:2215-2221(2003) [PubMed] [Europe PMC] [Abstract]
• vasodilation Source: UniProtKBInferred from direct assayⁱ
  • "Insulin induces the release of vasodilator compounds from platelets by a nitric oxide-G kinase-VAMP-3-dependent pathway."
    Randriamboavonjy V., Schrader J., Busse R., Fleming I.
    J Exp Med 199:347-356(2004) [PubMed] [Europe PMC] [Abstract]
• wound healing Source: BHF-UCLInferred from direct assayⁱ
  • "Effects of insulin on wound healing."
    Pierre E.J., Barrow R.E., Hawkins H.K., Nguyen T.T., Sakurai Y., Desai M., Wolfe R.R., Herndon D.N.
    J Trauma 44:342-345(1998) [PubMed] [Europe PMC] [Abstract]

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsⁱ

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationⁱ

• UniProt annotation
• GO - Cellular component

Keywords - Cellular componentⁱ

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechⁱ

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseaseⁱ

<p>This subsection of the 'Pathology and Biotech' section describes the use of a protein as a pharmaceutical drug. It indicates the name of the drug, the name of the firm that commercializes it and explains in a few words in which context the drug is used. In some cases, drugs that are under development are also described.<p><a href='/help/pharmaceutical_use' target='_top'>More...</a></p>Pharmaceutical useⁱ

Keywords - Diseaseⁱ

Organism-specific databases

Miscellaneous databases

Protein family/group databases

Chemistry databases

Genetic variation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingⁱ

Molecule processing

Amino acid modifications

Keywords - PTMⁱ

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressionⁱ

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsⁱ

GO - Molecular functionⁱ

• hormone activity Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "A structurally abnormal insulin causing human diabetes."
    Tager H., Given B., Baldwin D., Mako M., Markese J., Rubenstein A., Olefsky J., Kobayashi M., Kolterman O., Poucher R.
    Nature 281:122-125(1979) [PubMed] [Europe PMC] [Abstract]
• identical protein binding Source: IntActInferred from physical interactionⁱ
  • "A helical structural nucleus is the primary elongating unit of insulin amyloid fibrils."
    Vestergaard B., Groenning M., Roessle M., Kastrup J.S., van de Weert M., Flink J.M., Frokjaer S., Gajhede M., Svergun D.I.
    PLoS Biol 5:e134-e134(2007) [PubMed] [Europe PMC] [Abstract]
  • "Structural features of proinsulin C-peptide oligomeric and amyloid states."
    Lind J., Lindahl E., Peralvarez-Marin A., Holmlund A., Jornvall H., Maler L.
    FEBS J 277:3759-3768(2010) [PubMed] [Europe PMC] [Abstract]
  • "SERF protein is a direct modifier of amyloid fiber assembly."
    Falsone S.F., Meyer N.H., Schrank E., Leitinger G., Pham C.L., Fodero-Tavoletti M.T., Holmberg M., Dulle M., Scicluna B., Gesslbauer B., Rueckert H.M., Wagner G.E., Merle D.A., Nollen E.A., Kungl A.J., Hill A.F., Cappai R., Zangger K.
    Cell Rep. 2:358-371(2012) [PubMed] [Europe PMC] [Abstract]
  • "Insulin solubility transitions by pH-dependent interactions with proinsulin C-peptide."
    Landreh M., Alvelius G., Willander H., Stukenborg J.B., Soder O., Johansson J., Jornvall H.
    FEBS J 279:4589-4597(2012) [PubMed] [Europe PMC] [Abstract]
  • "Amino acid sequence determinants in self-assembly of insulin chiral amyloid superstructures: role of C-terminus of B-chain in association of fibrils."
    Babenko V., Dzwolak W.
    FEBS Lett 587:625-630(2013) [PubMed] [Europe PMC] [Abstract]
  • "Peptides that form beta-sheets on hydrophobic surfaces accelerate surface-induced insulin amyloidal aggregation."
    Nault L., Vendrely C., Brechet Y., Bruckert F., Weidenhaupt M.
    FEBS Lett 587:1281-1286(2013) [PubMed] [Europe PMC] [Abstract]
• insulin-like growth factor receptor binding Source: BHF-UCLInferred from physical interactionⁱ
  • "Purified hybrid insulin/insulin-like growth factor-I receptors bind insulin-like growth factor-I, but not insulin, with high affinity."
    Soos M.A., Field C.E., Siddle K.
    Biochem. J. 290:419-426(1993) [PubMed] [Europe PMC] [Abstract]
• insulin receptor binding Source: UniProtKBInferred from direct assayⁱ
  • "Binding of human, porcine and bovine insulin to insulin receptors from human brain, muscle and adipocytes and to expressed recombinant alternatively spliced insulin receptor isoforms."
    Kotzke G., Schutt M., Missler U., Moller D.E., Fehm H.L., Klein H.H.
    Diabetologia 38:757-763(1995) [PubMed] [Europe PMC] [Abstract]
• protease binding Source: UniProtKBInferred from physical interactionⁱ
  • "In vitro degradation of insulin-like peptide 3 by insulin-degrading enzyme."
    Zhang W.J., Luo X., Guo Z.Y.
    Protein J 29:93-98(2010) [PubMed] [Europe PMC] [Abstract]

Protein-protein interaction databases

Miscellaneous databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structureⁱ

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsⁱ

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesⁱ

Keywords - Domainⁱ

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)ⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingⁱ: The displayed sequence is further processed into a mature form.

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

        10         20         30         40         50
MALWMRLLPL LALLALWGPD PAAAFVNQHL CGSHLVEALY LVCGERGFFY 
        60         70         80         90        100
TPKTRREAED LQVGQVELGG GPGAGSLQPL ALEGSLQKRG IVEQCCTSIC 
       110
SLYQLENYCN                                             

<p>This subsection of the 'Sequence' section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautionⁱ

Natural variant