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 18.104.22.168; InsR family; Kinase, protein; Membrane protein, integral; Protein kinase, TK; Protein kinase, tyrosine (receptor); TK group
Cellular Component: caveola; endosome membrane; integral to plasma membrane; intracellular membrane-bound organelle; membrane; plasma membrane; receptor complex
Molecular Function: ATP binding; GTP binding; insulin binding; insulin receptor activity; insulin receptor substrate binding; insulin-like growth factor I binding; insulin-like growth factor II binding; insulin-like growth factor receptor binding; phosphoinositide 3-kinase binding; protein binding; protein-tyrosine kinase activity; PTB domain binding; receptor signaling protein tyrosine kinase activity
Biological Process: activation of MAPK activity; activation of protein kinase activity; activation of protein kinase B; cellular response to insulin stimulus; G-protein coupled receptor protein signaling pathway; glucose homeostasis; heart morphogenesis; insulin receptor signaling pathway; peptidyl-tyrosine 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 MAPKKK cascade; positive regulation of mitosis; positive regulation of nitric oxide biosynthetic process; positive regulation of protein amino acid phosphorylation; positive regulation of protein kinase B signaling cascade; protein amino acid autophosphorylation; protein heterotetramerization; regulation of embryonic development; regulation of transcription, DNA-dependent; transformation of host cell by virus