| Description | The protein encoded by this gene is a transmembrane glycoprotein that is a member of the protein kinase superfamily. This protein is a receptor for members of the epidermal growth factor family. EGFR is a cell surface protein that binds to epidermal growth factor. Binding of the protein to a ligand induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation. Mutations in this gene are associated with lung cancer. Multiple alternatively spliced transcript variants that encode different protein isoforms have been found for this gene. [provided by RefSeq, Jul 2010]Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin. Subunit structure: Binding of the ligand triggers homo- and/or heterodimerization of the receptor triggering its autophosphorylation. Heterodimer with ERBB2. Interacts with ERRFI1, inhibits dimerization of the kinase domain and autophosphorylation. Part of a complex with ERBB2 and either PIK3C2A or PIK3C2B. Interacts with GRB2, an adapter protein coupling the receptor to downstream signaling pathways. Interacts with GAB2, involved in signaling downstream of EGFR. Interacts with STAT3, mediates EGFR downstream signaling in cell proliferation. Interacts with RIPK1, involved in NF-kappa-B activation. Interacts (autophosphorylated) with CBL, CBLB and CBLC, involved in EGFR ubiquitination and regulation. Interacts with SOCS5, regulates EGFR degradation through TCEB1- and TCEB2-mediated ubiquitination and proteasomal degradation. Interacts with PRMT5, methylates EGFR and enhances interaction with PTPN6. Interacts (phosphorylated) with PTPN6, inhibits EGFR-dependent activation of MAPK/ERK. Interacts with COPG1, essential for regulation of EGF-dependent nuclear transport of EGFR by retrograde trafficking from the Golgi to the ER. Interacts with TNK2, this interaction is dependent on EGF stimulation and kinase activity of EGFR. Interacts with PCNA, positively regulates PCNA. Interacts with PELP1. Interacts with MUC1. Interacts with AP2M1. Interacts with FER. May interact with EPS8, mediates EPS8 phosphorylation. Interacts (via SH2 domains) with GRB2, NCK1 and NCK2. Interacts with ATX2. Interacts with GAREM. Interacts (ubiquitinated) with ANKRD13A/B/D, the interaction is direct and may regulate EGFR internalization after EGF stimulation. Interacts with GPER1, the interaction occurs in an estrogen-dependent manner. Subcellular location: Cell membrane, Single-pass type I membrane protein. Endoplasmic reticulum membrane, Single-pass type I membrane protein. Golgi apparatus membrane, Single-pass type I membrane protein. Nucleus membrane, Single-pass type I membrane protein. Endosome. Endosome membrane. Nucleus. Note: In response to EGF, translocated from the cell membrane to the nucleus via Golgi and ER. Endocytosed upon activation by ligand. Colocalized with GPER1 in the nucleus of estrogen agonist-induced cancer-associated fibroblasts (CAF). Isoform 2: Secreted. Sequence similarities: Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily. Contains 1 protein kinase domain. |
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