ID:INS_HUMAN DESCRIPTION: RecName: Full=Insulin; Contains: RecName: Full=Insulin B chain; Contains: RecName: Full=Insulin A chain; Flags: Precursor; FUNCTION: Insulin 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. SUBUNIT: Heterodimer of a B chain and an A chain linked by two disulfide bonds. SUBCELLULAR LOCATION: Secreted. DISEASE: Defects in INS are the cause of familial hyperproinsulinemia (FHPRI) [MIM:176730]. DISEASE: Defects in INS are a cause of diabetes mellitus insulin- dependent type 2 (IDDM2) [MIM:125852]. IDDM2 is a multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. DISEASE: Defects in INS are a cause of diabetes mellitus permanent neonatal (PNDM) [MIM:606176]. PNDM is a rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy. DISEASE: Defects in INS are a cause of maturity-onset diabetes of the young type 10 (MODY10) [MIM:613370]. MODY10 is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease. PHARMACEUTICAL: Available under the names Humulin or Humalog (Eli Lilly) and Novolin (Novo Nordisk). Used in the treatment of diabetes. Humalog is an insulin analog with 52-Lys-Pro-53 instead of 52-Pro-Lys-53. SIMILARITY: Belongs to the insulin family. SEQUENCE CAUTION: Sequence=AAA59179.1; Type=Erroneous gene model prediction; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/INS"; WEB RESOURCE: Name=Insulin at Eli Lilly; Note=Clinical information on Eli Lilly insulin products; URL="http://www.lillyDiabetes.com/Products/PatientInfo.cfm"; WEB RESOURCE: Name=Protein Spotlight; Note=Protein of the 20th century - Issue 9 of April 2001; URL="http://web.expasy.org/spotlight/back_issues/sptlt009.shtml"; WEB RESOURCE: Name=Wikipedia; Note=Insulin entry; URL="http://en.wikipedia.org/wiki/Insulin";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P01308
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000165 MAPK cascade GO:0002674 negative regulation of acute inflammatory response GO:0005975 carbohydrate metabolic process GO:0006006 glucose metabolic process GO:0006355 regulation of transcription, DNA-templated GO:0006521 regulation of cellular amino acid metabolic process GO:0006888 ER to Golgi vesicle-mediated transport GO:0006953 acute-phase response GO:0007186 G-protein coupled receptor signaling pathway GO:0007267 cell-cell signaling GO:0008284 positive regulation of cell proliferation GO:0008286 insulin receptor signaling pathway GO:0010469 regulation of receptor activity GO:0010628 positive regulation of gene expression GO:0010750 positive regulation of nitric oxide mediated signal transduction GO:0014068 positive regulation of phosphatidylinositol 3-kinase signaling GO:0022898 regulation of transmembrane transporter activity GO:0030307 positive regulation of cell growth GO:0030335 positive regulation of cell migration GO:0031954 positive regulation of protein autophosphorylation GO:0032148 activation of protein kinase B activity GO:0032270 positive regulation of cellular protein metabolic process GO:0032460 negative regulation of protein oligomerization GO:0032880 regulation of protein localization GO:0033861 negative regulation of NAD(P)H oxidase activity GO:0042060 wound healing GO:0042177 negative regulation of protein catabolic process GO:0042593 glucose homeostasis GO:0043410 positive regulation of MAPK cascade GO:0044267 cellular protein metabolic process GO:0045597 positive regulation of cell differentiation GO:0045721 negative regulation of gluconeogenesis GO:0045725 positive regulation of glycogen biosynthetic process GO:0045818 negative regulation of glycogen catabolic process GO:0045821 positive regulation of glycolytic process GO:0045840 positive regulation of mitotic nuclear division GO:0045861 negative regulation of proteolysis GO:0045922 negative regulation of fatty acid metabolic process GO:0046326 positive regulation of glucose import GO:0046628 positive regulation of insulin receptor signaling pathway GO:0046631 alpha-beta T cell activation GO:0046889 positive regulation of lipid biosynthetic process GO:0048167 regulation of synaptic plasticity GO:0050708 regulation of protein secretion GO:0050709 negative regulation of protein secretion GO:0050715 positive regulation of cytokine secretion GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation GO:0050890 cognition GO:0050995 negative regulation of lipid catabolic process GO:0051000 positive regulation of nitric-oxide synthase activity GO:0051092 positive regulation of NF-kappaB transcription factor activity GO:0051897 positive regulation of protein kinase B signaling GO:0055089 fatty acid homeostasis GO:0060266 negative regulation of respiratory burst involved in inflammatory response GO:0060267 positive regulation of respiratory burst GO:0090277 positive regulation of peptide hormone secretion GO:0090336 positive regulation of brown fat cell differentiation GO:1900182 positive regulation of protein localization to nucleus GO:1900273 positive regulation of long-term synaptic potentiation GO:1902176 negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway GO:1902952 positive regulation of dendritic spine maintenance GO:1903076 regulation of protein localization to plasma membrane GO:1903427 negative regulation of reactive oxygen species biosynthetic process GO:1990535 neuron projection maintenance GO:2000252 negative regulation of feeding behavior GO:2001275 positive regulation of glucose import in response to insulin stimulus
DQ104205 - Homo sapiens INSIGF long transcript variant mRNA, complete cds, alternatively spliced. DQ104204 - Homo sapiens INSIGF short transcript variant mRNA, complete cds, alternatively spliced. BC148488 - Synthetic construct Homo sapiens clone IMAGE:100015383, MGC:183013 INS-IGF2 readthrough transcript (INS-IGF2) mRNA, encodes complete protein. BC153083 - Synthetic construct Homo sapiens clone IMAGE:100016390, MGC:184293 INS-IGF2 readthrough transcript (INS-IGF2) mRNA, encodes complete protein. E00191 - DNA coding for human proinsulin. E00011 - RNA coding for human preproinsulin. JQ951950 - Homo sapiens preproinsulin (INS) mRNA, complete cds. X70508 - Homo sapiens mRNA for insulinoma pre-proinsulin. BC005255 - Homo sapiens insulin, mRNA (cDNA clone MGC:12292 IMAGE:3950204), complete cds. AY899304 - Homo sapiens proinsulin mRNA, complete cds, alternatively spliced. BT006808 - Homo sapiens insulin mRNA, complete cds. DQ778082 - Homo sapiens clone BFC06103 insulin mRNA, complete cds. JF909299 - Homo sapiens insulin (INS) mRNA, partial cds. KJ891480 - Synthetic construct Homo sapiens clone ccsbBroadEn_00874 INS gene, encodes complete protein. KR710182 - Synthetic construct Homo sapiens clone CCSBHm_00010255 INS (INS) mRNA, encodes complete protein. KR710183 - Synthetic construct Homo sapiens clone CCSBHm_00010256 INS (INS) mRNA, encodes complete protein. KR710184 - Synthetic construct Homo sapiens clone CCSBHm_00010257 INS (INS) mRNA, encodes complete protein. KR710185 - Synthetic construct Homo sapiens clone CCSBHm_00010262 INS (INS) mRNA, encodes complete protein. DQ893040 - Synthetic construct clone IMAGE:100005670; FLH192922.01X; RZPDo839A1078D insulin (INS) gene, encodes complete protein. DQ896283 - Synthetic construct Homo sapiens clone IMAGE:100010743; FLH192918.01L; RZPDo839A1068D insulin (INS) gene, encodes complete protein. AB587580 - Synthetic construct DNA, clone: pF1KB8864, Homo sapiens INS gene for insulin, without stop codon, in Flexi system. JD521620 - Sequence 502644 from Patent EP1572962. JD363620 - Sequence 344644 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein P01308 (Reactome details) participates in the following event(s):
R-HSA-264976 Proinsulin binds zinc and calcium forming Proinsulin:zinc:calcium R-HSA-264997 Oxidation of cysteine to cystine in Proinsulin R-HSA-9023159 Carboxypeptidase E cleaves C-peptide (Insulin(57-89)) to yield C-peptide (Insulin(57-87)) R-NUL-9023186 Carboxypeptidase E (rat Carboxypeptidase H) cleaves C-peptide (Insulin(57-89)) to yield C-peptide (Insulin(57-87)) R-HSA-9023178 PCSK2 cleaves Insulin(57-110) to yield Insulin(90-110) and C-peptide (Insulin(57-89)) R-NUL-9023180 Pcsk2 (rat) cleaves human Insulin(57-110) to yield Insulin(90-110) and C-peptide (Insulin(57-89)) R-HSA-74716 Insulin binds the insulin receptor R-HSA-74726 Dissociation of insulin from insulin receptor R-NUL-9023165 Pcsk1 (rat) cleaves human proinsulin to yield Insulin(25-56) and Insulin(57-110) R-HSA-9023196 PCSK1 cleaves proinsulin to yield Insulin(25-56) and Insulin(57-110) R-HSA-6807875 ARFGAP, cargo, v-SNAREs and p24 proteins bind nascent COPI complex R-NUL-9023166 Carboxypeptidase E (rat Carboxypeptidase H) cleaves Insulin(25-56) to yield Insulin(25-54) R-HSA-74707 Binding of IRS to insulin receptor R-HSA-74740 Binding of SHC1 to insulin receptor R-HSA-110011 Binding of Grb10 to the insulin receptor R-HSA-74712 Dissociation of IRS-P from insulin receptor R-HSA-74715 Autophosphorylation of insulin receptor R-HSA-74743 Dissociation of p-Y427-SHC1 from insulin receptor R-HSA-6807877 ARFGAPs stimulate ARF GTPase activity R-HSA-6809003 ERGIC-to-Golgi vesicles bind dynein:dynactin R-HSA-9023163 Carboxypeptidase E cleaves Insulin(25-56) to yield Insulin(25-54) R-HSA-74742 Phosphorylation of SHC1 R-HSA-74711 Phosphorylation of IRS R-HSA-6809011 cis-Golgi t-SNAREs bind YKT6 on tethered vesicle R-HSA-6809006 Vesicle is tethered through binding GOLGA2:GORASP1, GOLGB1 and the COG complex R-HSA-8857925 Inhibition of PP2A activity by phosphorylation of the catalytic subunit at tyrosine Y307 R-HSA-264876 Insulin processing R-HSA-210745 Regulation of gene expression in beta cells R-HSA-422356 Regulation of insulin secretion R-HSA-74752 Signaling by Insulin receptor R-HSA-77387 Insulin receptor recycling R-HSA-2980736 Peptide hormone metabolism R-HSA-186712 Regulation of beta-cell development R-HSA-163685 Energy Metabolism R-HSA-6807878 COPI-mediated anterograde transport R-HSA-74713 IRS activation R-HSA-74751 Insulin receptor signalling cascade R-HSA-74749 Signal attenuation R-HSA-9006934 Signaling by Receptor Tyrosine Kinases R-HSA-392499 Metabolism of proteins R-HSA-1266738 Developmental Biology R-HSA-1430728 Metabolism R-HSA-199977 ER to Golgi Anterograde Transport R-HSA-162582 Signal Transduction R-HSA-199991 Membrane Trafficking R-HSA-948021 Transport to the Golgi and subsequent modification R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-HSA-977225 Amyloid fiber formation R-HSA-5653656 Vesicle-mediated transport R-HSA-446203 Asparagine N-linked glycosylation R-HSA-199418 Negative regulation of the PI3K/AKT network R-HSA-597592 Post-translational protein modification R-HSA-1257604 PIP3 activates AKT signaling R-HSA-9006925 Intracellular signaling by second messengers
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
