EGFR

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. [provided by RefSeq, Jun 2016]

Epidermal Growth Factor Receptor

Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:2790960, PubMed:10805725, PubMed:27153536).

Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF (PubMed:2790960, PubMed:7679104, PubMed:8144591, PubMed:9419975, PubMed:15611079, PubMed:12297049, PubMed:27153536, PubMed:20837704, PubMed:17909029).

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 (PubMed:27153536).

May also activate the NF-kappa-B signaling cascade (PubMed:11116146).

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 (PubMed:11602604).

Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin (PubMed:11483589).

Positively regulates cell migration via interaction with CCDC88A/GIV which retains EGFR at the cell membrane following ligand stimulation, promoting EGFR signaling which triggers cell migration (PubMed:20462955).

Plays a role in enhancing learning and memory performance (By similarity).

Isoform 2 may act as an antagonist of EGF action.

(Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins.

Activation of phospholipase A2 activity by calcium-mediated signaling Source: UniProtKB
Activation of phospholipase C activity Source: UniProtKB
Astrocyte activation Source: Ensembl
Cell-cell adhesion Source: UniProtKB
Cell differentiation Source: GO_Central
Cell surface receptor signaling pathway Source: MGI
Cellular response to cadmium ion Source: CAFA
Cellular response to dexamethasone stimulus Source: Ensembl
Cellular response to drug Source: Ensembl
Cellular response to epidermal growth factor stimulus Source: UniProtKB
Cellular response to estradiol stimulus Source: UniProtKB
Cellular response to mechanical stimulus Source: Ensembl
Cellular response to reactive oxygen species Source: CAFA
Circadian rhythm Source: Ensembl
Diterpenoid metabolic process Source: Ensembl
Epidermal growth factor receptor signaling pathway Source: UniProtKB
Hair follicle development Source: Ensembl
Hydrogen peroxide metabolic process Source: Ensembl
Learning or memory Source: UniProtKB
Liver regeneration Source: Ensembl
Lung development Source: Ensembl
Magnesium ion homeostasis Source: Ensembl
Midgut development Source: Ensembl
Negative regulation of apoptotic process Source: UniProtKB
Negative regulation of cardiocyte differentiation Source: BHF-UCL
Negative regulation of epidermal growth factor receptor signaling pathway Source: Reactome
Negative regulation of mitotic cell cycle Source: Ensembl
Negative regulation of protein catabolic process Source: UniProtKB
Neuron projection morphogenesis Source: Ensembl
Ossification Source: UniProtKB
Ovulation cycle Source: Ensembl
Peptidyl-tyrosine autophosphorylation Source: UniProtKB
Peptidyl-tyrosine phosphorylation Source: ParkinsonsUK-UCL
Positive regulation of bone resorption Source: Ensembl
Positive regulation of canonical Wnt signaling pathway Source: BHF-UCL
Positive regulation of cell growth Source: UniProtKB
Positive regulation of cell migration Source: UniProtKB
Positive regulation of cell population proliferation Source: MGI
Positive regulation of cyclin-dependent protein serine/threonine kinase activity Source: BHF-UCL
Positive regulation of DNA repair Source: UniProtKB
Positive regulation of DNA replication Source: UniProtKB
Positive regulation of epithelial cell proliferation Source: UniProtKB
Positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
Positive regulation of G1/S transition of mitotic cell cycle Source: BHF-UCL
Positive regulation of glial cell proliferation Source: Ensembl
Positive regulation of inflammatory response Source: Ensembl
Positive regulation of kinase activity Source: GO_Central
Positive regulation of MAP kinase activity Source: UniProtKB
Positive regulation of mucus secretion Source: Ensembl
Positive regulation of NIK/NF-kappaB signaling Source: CAFA
Positive regulation of nitric oxide mediated signal transduction Source: UniProtKB
Positive regulation of peptidyl-serine phosphorylation Source: UniProtKB
Positive regulation of phosphorylation Source: UniProtKB
Positive regulation of production of miRNAs involved in gene silencing by miRNA Source: BHF-UCL
Positive regulation of prolactin secretion Source: Ensembl
Positive regulation of protein kinase B signaling Source: BHF-UCL
Positive regulation of protein kinase C activity Source: ParkinsonsUK-UCL
Positive regulation of protein localization to plasma membrane Source: ParkinsonsUK-UCL
Positive regulation of protein phosphorylation Source: UniProtKB
Positive regulation of smooth muscle cell proliferation Source: Ensembl
Positive regulation of superoxide anion generation Source: Ensembl
Positive regulation of synaptic transmission, glutamatergic Source: Ensembl
Positive regulation of transcription, DNA-templated Source: CAFA
Positive regulation of transcription by RNA polymerase II Source: UniProtKB
Positive regulation of vasoconstriction Source: Ensembl
Protein autophosphorylation Source: UniProtKB
Protein insertion into membrane Source: UniProtKB
Regulation of ERK1 and ERK2 cascade Source: CAFA
Regulation of JNK cascade Source: CAFA
Regulation of nitric-oxide synthase activity Source: UniProtKB
Regulation of peptidyl-tyrosine phosphorylation Source: UniProtKB
Regulation of phosphatidylinositol 3-kinase signaling Source: CAFA
Response to calcium ion Source: Ensembl
Response to cobalamin Source: Ensembl
Response to hydroxyisoflavone Source: Ensembl
Response to osmotic stress Source: Ensembl
Response to UV-A Source: BHF-UCL
Signal transduction Source: UniProtKB
Tongue development Source: Ensembl
Translation Source: Ensembl
Transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
Vasodilation Source: Ensembl
Wound healing Source: Ensembl

Nucleus membrane; Nucleus; Endoplasmic reticulum membrane; Golgi apparatus membrane; Endosome; Endosome membrane; Cell membrane. In response to EGF, translocated from the cell membrane to the nucleus via Golgi and ER (PubMed:20674546, PubMed:17909029). Endocytosed upon activation by ligand (PubMed:2790960, PubMed:17182860, PubMed:27153536, PubMed:17909029). Colocalized with GPER1 in the nucleus of estrogen agonist-induced cancer-associated fibroblasts (CAF) (PubMed:20551055).
Isoform 2: Secreted

Lung cancer (LNCR):
A common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis.
Inflammatory skin and bowel disease, neonatal, 2 (NISBD2):
A disorder characterized by inflammatory features with neonatal onset, involving the skin, hair, and gut. The skin lesions involve perioral and perianal erythema, psoriasiform erythroderma, with flares of erythema, scaling, and widespread pustules. Gastrointestinal symptoms include malabsorptive diarrhea that is exacerbated by intercurrent gastrointestinal infections. The hair is short or broken, and the eyelashes and eyebrows are wiry and disorganized.

Extracellular: 25-645
Helical: 646-668
Cytoplasmic: 669-1210

Phosphorylated on Tyr residues in response to EGF (PubMed:20462955, PubMed:27153536). Phosphorylation at Ser-695 is partial and occurs only if Thr-693 is phosphorylated. Phosphorylation at Thr-678 and Thr-693 by PRKD1 inhibits EGF-induced MAPK8/JNK1 activation. Dephosphorylation by PTPRJ prevents endocytosis and stabilizes the receptor at the plasma membrane. Autophosphorylation at Tyr-1197 is stimulated by methylation at Arg-1199 and enhances interaction with PTPN6. Autophosphorylation at Tyr-1092 and/or Tyr-1110 recruits STAT3. Dephosphorylated by PTPN1 and PTPN2.
Monoubiquitinated and polyubiquitinated upon EGF stimulation; which does not affect tyrosine kinase activity or signaling capacity but may play a role in lysosomal targeting (PubMed:27153536). Polyubiquitin linkage is mainly through 'Lys-63', but linkage through 'Lys-48', 'Lys-11' and 'Lys-29' also occurs. Deubiquitination by OTUD7B prevents degradation. Ubiquitinated by RNF115 and RNF126 (By similarity).
Palmitoylated on Cys residues by ZDHHC20. Palmitoylation inhibits internalization after ligand binding, and increases the persistence of tyrosine-phosphorylated EGFR at the cell membrane. Palmitoylation increases the amplitude and duration of EGFR signaling.
Methylated. Methylation at Arg-1199 by PRMT5 stimulates phosphorylation at Tyr-1197.