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INSR a receptor tyrosine kinase that 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 phosphotyrosines 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 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. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). The holoenzyme is cleaved into two chains, the alpha and beta subunits. The active complex is a tetramer containing 2 alpha and 2 beta chains linked by disulfide bonds. The alpha chains constitute the ligand- binding domain, while the beta chains carry the kinase domain. Interacts with SORBS1 but dissociates from it following insulin stimulation. Familial mutations associated with insulin resistant diabetes, acanthosis nigricans, pineal hyperplasia, and polycystic ovary syndrome. SNP variants may be associated with polycystic ovary syndrome, atypical migraine and diabetic hyperlipidemia. Mutations also cause leprechaunism, a severe insulin resistance syndrome causing growth retardation and death in early infancy. Two isoforms of the human protein are produced by alternative splicing. The Short isoform has a higher affinity for insulin than the longer. Isoform Long and isoform Short are predominantly expressed in tissue targets of insulin metabolic effects: liver, adipose tissue and skeletal muscle but are also expressed in the peripheral nerve, kidney, pulmonary alveoli, pancreatic acini, placenta vascular endothelium, fibroblasts, monocytes, granulocytes, erythrocytes and skin. Isoform Short is preferentially expressed in fetal cells such as fetal fibroblasts, muscle, liver and kidney. Found as a hybrid receptor with IGF1R in muscle, heart, kidney, adipose tissue, skeletal muscle, hepatoma, fibroblasts, spleen and placenta. Overexpressed in several tumors, including breast, colon, lung, ovary, and thyroid carcinomas. Note: This description may include information from UniProtKB.
Protein type: EC; InsR family; Kinase, protein; Membrane protein, integral; Protein kinase, TK; Protein kinase, tyrosine (receptor); TK group
Chromosomal Location of Human Ortholog: 8 A1.1|8 1.82 cM
Cellular Component: caveola; cell soma; cytosol; endosome; external side of plasma membrane; extracellular exosome; insulin receptor complex; integral component of membrane; integral component of plasma membrane; intracellular; intracellular membrane-bound organelle; membrane; nuclear envelope; nuclear lumen; nucleus; plasma membrane; receptor complex; synapse
Molecular Function: 3-phosphoinositide-dependent protein kinase binding; amyloid-beta binding; ATP binding; GTP binding; identical protein binding; insulin binding; insulin receptor substrate binding; insulin-activated receptor activity; insulin-like growth factor I binding; insulin-like growth factor II binding; insulin-like growth factor receptor binding; kinase activity; lipoic acid binding; nucleotide binding; phosphoinositide 3-kinase binding; protein binding; protein complex binding; protein domain specific binding; protein kinase activity; protein kinase binding; protein phosphatase binding; protein tyrosine kinase activity; PTB domain binding; signal transducer, downstream of receptor, with protein tyrosine kinase activity; transferase activity; transmembrane receptor protein tyrosine kinase activity
Biological Process: activation of MAPK activity; activation of protein kinase activity; activation of protein kinase B activity; adrenal gland development; cellular response to growth factor stimulus; cellular response to insulin stimulus; epidermis development; exocrine pancreas development; G-protein coupled receptor signaling pathway; glucose homeostasis; heart morphogenesis; insulin receptor signaling pathway; male gonad development; male sex determination; negative regulation of gene expression; negative regulation of protein phosphorylation; negative regulation of transporter activity; organ morphogenesis; peptidyl-tyrosine autophosphorylation; peptidyl-tyrosine phosphorylation; phosphorylation; positive regulation of cell migration; positive regulation of cell proliferation; positive regulation of developmental growth; positive regulation of DNA replication; positive regulation of glucose import; positive regulation of glycogen biosynthetic process; positive regulation of glycolysis; positive regulation of glycoprotein biosynthetic process; 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 phosphorylation; positive regulation of protein complex disassembly; positive regulation of protein kinase B signaling; positive regulation of protein phosphorylation; positive regulation of transcription, DNA-templated; protein amino acid phosphorylation; protein autophosphorylation; protein heterotetramerization; regulation of embryonic development; regulation of female gonad development; regulation of hydrogen peroxide metabolic process; regulation of transcription, DNA-templated; response to tumor necrosis factor; transformation of host cell by virus; transmembrane receptor protein tyrosine kinase signaling pathway
Reference #:  P15208 (UniProtKB)
Alt. Names/Synonyms: 4932439J01Rik; CD220; D630014A15Rik; Insr; Insulin receptor; Insulin receptor subunit alpha; Insulin receptor subunit beta; IR
Gene Symbols: Insr
Molecular weight: 155,610 Da
Basal Isoelectric point: 5.64  Predict pI for various phosphorylation states
CST Pathways:  AMPK Signaling  |  Insulin Receptor Signaling  |  Tyrosine Kinases & Substrates
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