The protein expressed by the EGFR gene functions as a receptor tyrosine kinase, binding with ligands from the EGF family to activate several signaling cascades that translate extracellular signals into cellular responses. Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen, BTC/betacellulin, epiregulin, and HBEGF. Ligand binding triggers receptor dimerization and autophosphorylation, recruiting adapter proteins like GRB2 and activating complex downstream signaling pathways such as RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC, and STATs, and possibly the NF-kappa-B cascade. EGFR also directly phosphorylates proteins like RGS16 and MUC1, influencing various cellular processes including its coupling with G protein-coupled receptor signaling and cell migration through interaction with CCDC88A/GIV. Isoform 2 of EGFR may act as an antagonist to EGF actions. In microbial infection, EGFR also serves as a receptor facilitating hepatitis C virus (HCV) entry into hepatocytes by promoting CD81-CLDN1 receptor complexes and enhancing membrane fusion with HCV envelope glycoproteins. This supplementary information is collated from multiple sources and compiled automatically.
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.
None
The gene represented in this entry is involved in disease pathogenesis.
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.
None
The disease is caused by variants affecting the gene represented in this entry.
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). Ubiquitinated by ZNRF1 or CBL at different lysines in response to EGF stimulation; leading to recruitment of the ESCRT machinery and subsequent degradation in the lysosomes (PubMed:33996800). Deubiquitinated by UCHL1 leading to the inhibition of its degradation (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.
Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.
Ubiquitously expressed. Isoform 2 is also expressed in ovarian cancers.
ERBB, ERBB1, HER1, EGFR, Epidermal growth factor receptor, Proto-oncogene c-ErbB-1, Receptor tyrosine-protein kinase erbB-1
Proteins
Research Tools
134277Da
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