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EGFR a receptor tyrosine kinase. This is a receptor for epidermal growth factor (EGF) and related growth factors including TGF-alpha, amphiregulin, betacellulin, heparin-binding EGF-like growth factor, GP30, and vaccinia virus growth factor. EGFR is involved in the control of cell growth and differentiation. It is a single-pass transmembrane tyrosine kinase. Ligand binding to this receptor results in receptor dimerization, autophosphorylation (in trans), activation of various downstream signaling molecules and lysosomal degradation. It can be phosphorylated and activated by Src. Activated EGFR binds the SH2 domain of phospholipase C-gamma (PLC-gamma), activating PLC-gamma-mediated downstream signaling. Phosphorylated EGFR binds Cbl, leading to its ubiquitination and degradation. Grb2 and SHC bind to phospho-EGFR and are involved in the activation of MAP kinase signaling pathways. Phosphorylation on Ser and Thr residues is thought to represent a mechanism for attenuation of EGFR kinase activity. EGFR is overexpressed in breast, head and neck cancers, correlating with poor survival. Activating somatic mutations are seen in lung cancer, corresponding to the minority of patients with strong responses to the EGFR inhibitor Iressa (gefitinib). Mutations and amplifications are also seen in glioblastoma, and upregulation is seen in colon cancer and neoplasms. In xenografts, inhibitors synergize with cytotoxic drugs in the inhibition of many tumor types. Inhibitors include: Iressa/ZD1839, Erbitux, Tarceva, and lapatinib. Four alternatively spliced isoforms have been described. Note: This description may include information from UniProtKB.
Protein type: EC; EGFR family; Kinase, protein; Membrane protein, integral; Protein kinase, TK; Protein kinase, tyrosine (receptor); TK group; Tumor suppressor
Chromosomal Location of Human Ortholog: 7p11.2
Cellular Component: AP-2 adaptor complex; apical plasma membrane; basolateral plasma membrane; cell surface; clathrin-coated vesicle membrane; cytoplasm; early endosome membrane; endoplasmic reticulum membrane; endosome; endosome membrane; extracellular space; focal adhesion; Golgi membrane; integral component of membrane; membrane; membrane raft; nuclear membrane; nucleus; perinuclear region of cytoplasm; plasma membrane; protein complex; receptor complex; Shc-EGFR complex; synapse
Molecular Function: actin filament binding; ATP binding; cadherin binding; calmodulin binding; chromatin binding; double-stranded DNA binding; enzyme binding; epidermal growth factor binding; epidermal growth factor receptor activity; identical protein binding; integrin binding; MAP kinase kinase kinase activity; nitric-oxide synthase regulator activity; phosphatidylinositol-4,5-bisphosphate 3-kinase activity; protein binding; protein heterodimerization activity; protein kinase binding; protein phosphatase binding; protein tyrosine kinase activity; Ras guanyl-nucleotide exchange factor activity; signal transducer, downstream of receptor, with protein tyrosine kinase activity; transmembrane receptor activity; transmembrane receptor protein tyrosine kinase activity; ubiquitin protein ligase binding; viral receptor activity
Biological Process: activation of MAPKK activity; activation of phospholipase C activity; astrocyte activation; calcium-dependent phospholipase A2 activation; cell proliferation; cell surface receptor signaling pathway; cellular response to cadmium ion; cellular response to dexamethasone stimulus; cellular response to epidermal growth factor stimulus; cellular response to estradiol stimulus; cellular response to reactive oxygen species; cerebral cortex cell migration; circadian rhythm; digestive tract morphogenesis; diterpenoid metabolic process; embryonic placenta development; entry of virus into host cell; epidermal growth factor receptor signaling pathway; ERBB2 signaling pathway; hair follicle development; hydrogen peroxide metabolic process; learning and/or memory; lung development; magnesium ion homeostasis; MAPK cascade; midgut development; negative regulation of apoptosis; negative regulation of cardiocyte differentiation; negative regulation of epidermal growth factor receptor signaling pathway; negative regulation of ERBB signaling pathway; negative regulation of mitotic cell cycle; negative regulation of protein catabolic process; neuron projection morphogenesis; ossification; ovulation cycle; peptidyl-tyrosine autophosphorylation; peptidyl-tyrosine phosphorylation; phosphatidylinositol phosphorylation; positive regulation of blood vessel diameter; positive regulation of bone resorption; positive regulation of cell growth; positive regulation of cell migration; positive regulation of cell proliferation; positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle; positive regulation of DNA repair; positive regulation of DNA replication; positive regulation of epithelial cell proliferation; positive regulation of ERK1 and ERK2 cascade; positive regulation of fibroblast proliferation; positive regulation of inflammatory response; positive regulation of MAP kinase activity; positive regulation of NIK/NF-kappaB signaling; positive regulation of nitric oxide biosynthetic process; positive regulation of peptidyl-serine phosphorylation; positive regulation of phosphorylation; positive regulation of prolactin secretion; positive regulation of protein kinase B signaling; positive regulation of protein kinase C activity; positive regulation of protein phosphorylation; positive regulation of smooth muscle cell proliferation; positive regulation of superoxide anion generation; positive regulation of synaptic transmission, glutamatergic; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-templated; positive regulation of vasoconstriction; protein autophosphorylation; protein insertion into membrane; regulation of cell motility; regulation of ERK1 and ERK2 cascade; regulation of JNK cascade; regulation of nitric-oxide synthase activity; regulation of peptidyl-tyrosine phosphorylation; regulation of phosphatidylinositol 3-kinase signaling; regulation of transcription from RNA polymerase II promoter; response to calcium ion; response to cobalamin; response to hydroxyisoflavone; response to osmotic stress; response to stress; salivary gland morphogenesis; signal transduction; tongue development; translation; wound healing
Disease: Inflammatory Skin And Bowel Disease, Neonatal, 2; Lung Cancer
Reference #:  P00533 (UniProtKB)
Alt. Names/Synonyms: avian erythroblastic leukemia viral (v-erb-b) oncogene homolog; cell growth inhibiting protein 40; cell proliferation-inducing protein 61; EGFR; Epidermal growth factor receptor; epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian); ERBB; ERBB1; HER1; mENA; PIG61; Proto-oncogene c-ErbB-1; Receptor tyrosine-protein kinase erbB-1
Gene Symbols: EGFR
Molecular weight: 134,277 Da
Basal Isoelectric point: 6.26  Predict pI for various phosphorylation states
CST Pathways:  Angiogenesis  |  ErbB/HER Signaling  |  IL6 Signaling  |  Phospholipase Signaling  |  Tyrosine Kinases & Substrates
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