INSR
Entrez ID: 3643
Full name: insulin receptor
External links: HGNC UniprotKB Ensembl RefSeq COSMIC
Family: TK: InsR
Chromosomal location: 19p13.2
Substructure location: Gatekeeper: 1103 A-loop: 1176...1201 G-loop: 1029...1035 αC-helix: 1065...1078
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INSR
Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins...
Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosine residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin. In adipocytes, inhibits lipolysis (By similarity).
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GO - Biological processes (BP):
activation of MAPK activity, activation of protein kinase activity, activation of protein kinase B activity, adrenal gland development, amyloid-beta clearance, anatomical structure development, carbohydrate metabolic process, cellular response to growth factor stimulus, cellular response to insulin ...
activation of MAPK activity, activation of protein kinase activity, activation of protein kinase B activity, adrenal gland development, amyloid-beta clearance, anatomical structure development, carbohydrate metabolic process, cellular response to growth factor stimulus, cellular response to insulin stimulus, dendritic spine maintenance, epidermis development, exocrine pancreas development, glucose homeostasis, G protein-coupled receptor signaling pathway, heart morphogenesis, insulin receptor signaling pathway, learning, male gonad development, male sex determination, memory, multicellular organism development, neuron projection maintenance, peptidyl-tyrosine autophosphorylation, peptidyl-tyrosine phosphorylation, positive regulation of cell migration, positive regulation of cell population proliferation, positive regulation of developmental growth, positive regulation of glucose import, positive regulation of glycogen biosynthetic process, positive regulation of glycolytic process, positive regulation of kinase activity, positive regulation of MAPK cascade, positive regulation of meiotic cell cycle, positive regulation of mitotic nuclear division, positive regulation of nitric oxide biosynthetic process, positive regulation of phosphatidylinositol 3-kinase signaling, positive regulation of protein-containing complex disassembly, positive regulation of protein kinase B signaling, positive regulation of protein phosphorylation, positive regulation of receptor internalization, positive regulation of respiratory burst, positive regulation of transcription, DNA-templated, protein autophosphorylation, protein phosphorylation, receptor-mediated endocytosis, regulation of embryonic development, regulation of female gonad development, regulation of transcription, DNA-templated, transformation of host cell by virus, transmembrane receptor protein tyrosine kinase signaling pathway
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GO - Molecular function (MF):
amyloid-beta binding, ATP binding, cargo receptor activity, GTP binding, identical protein binding, insulin-activated receptor activity, insulin binding, insulin-like growth factor I binding, insulin-like growth factor II binding, insulin-like growth factor receptor binding, insulin receptor substra...
amyloid-beta binding, ATP binding, cargo receptor activity, GTP binding, identical protein binding, insulin-activated receptor activity, insulin binding, insulin-like growth factor I binding, insulin-like growth factor II binding, insulin-like growth factor receptor binding, insulin receptor substrate binding, phosphatidylinositol 3-kinase binding, protein-containing complex binding, protein domain specific binding, protein tyrosine kinase activity, PTB domain binding, structural molecule activity, transmembrane receptor protein tyrosine kinase activity
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GO - Cellular component (CC):
endosome membrane, late endosome, extracellular exosome, lysosome, caveola, dendrite membrane, external side of plasma membrane, insulin receptor complex, integral component of plasma membrane, neuronal cell body membrane, plasma membrane, axon, membrane, receptor complex...
endosome membrane, late endosome, extracellular exosome, lysosome, caveola, dendrite membrane, external side of plasma membrane, insulin receptor complex, integral component of plasma membrane, neuronal cell body membrane, plasma membrane, axon, membrane, receptor complex
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insulin receptor
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Kaplan plot for INSR in
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*NOTE: the Kaplan plots were collected from OncoLnc