Epidermal growth factor receptor (P00533)

Uniprot ID	P00533
Protein Name	Epidermal growth factor receptor
Gene Name	EGFR
Species	Homo sapiens (Human)

Signal peptide^(a)	N	Secretome P^(b)	0.426
Function	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). 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). 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. {ECO:0000269\|PubMed:21516087}.
GO - Molecular function	actin filament binding : IDA:UniProtKB ATP binding : IEA:UniProtKB-KW ATPase binding : ISS:ARUK-UCL cadherin binding : HDA:BHF-UCL calmodulin binding : IEA:Ensembl chromatin binding : IDA:UniProtKB double-stranded DNA binding : NAS:UniProtKB enzyme binding : IPI:UniProtKB epidermal growth factor binding : IBA:GO_Central epidermal growth factor-activated receptor activity : IDA:UniProtKB identical protein binding : IPI:IntAct integrin binding : IEA:Ensembl MAP kinase kinase kinase activity : NAS:UniProtKB protein heterodimerization activity : IDA:UniProtKB protein kinase binding : IEA:Ensembl protein phosphatase binding : IPI:UniProtKB protein tyrosine kinase activity : IDA:UniProtKB transmembrane receptor protein tyrosine kinase activity : IBA:GO_Central transmembrane signaling receptor activity : IDA:MGI ubiquitin protein ligase binding : IPI:UniProtKB virus receptor activity : IEA:UniProtKB-KW
GO - Biological process	activation of phospholipase A2 activity by calcium-mediated signaling : TAS:UniProtKB activation of phospholipase C activity : TAS:UniProtKB astrocyte activation : IEA:Ensembl cell differentiation : IBA:GO_Central cell population proliferation : IDA:UniProtKB cell surface receptor signaling pathway : IDA:MGI cell-cell adhesion : IMP:UniProtKB cellular response to amino acid stimulus : IEA:Ensembl cellular response to cadmium ion : IMP:CAFA cellular response to dexamethasone stimulus : IEA:Ensembl cellular response to epidermal growth factor stimulus : ISS:UniProtKB cellular response to estradiol stimulus : IDA:UniProtKB cellular response to mechanical stimulus : IEA:Ensembl cellular response to reactive oxygen species : IMP:CAFA cerebral cortex cell migration : IEA:Ensembl circadian rhythm : IEA:Ensembl digestive tract morphogenesis : IEA:Ensembl diterpenoid metabolic process : IEA:Ensembl embryonic placenta development : IEA:Ensembl epidermal growth factor receptor signaling pathway : IDA:UniProtKB ERBB2 signaling pathway : TAS:Reactome eyelid development in camera-type eye : IEA:Ensembl hair follicle development : IEA:Ensembl hydrogen peroxide metabolic process : IEA:Ensembl learning or memory : ISS:UniProtKB liver regeneration : IEA:Ensembl lung development : IEA:Ensembl magnesium ion homeostasis : IEA:Ensembl MAPK cascade : TAS:Reactome membrane organization : TAS:Reactome midgut development : IEA:Ensembl morphogenesis of an epithelial fold : IEA:Ensembl negative regulation of apoptotic process : IMP:UniProtKB negative regulation of cardiocyte differentiation : IMP:BHF-UCL negative regulation of epidermal growth factor receptor signaling pathway : TAS:Reactome negative regulation of ERBB signaling pathway : TAS:Reactome negative regulation of mitotic cell cycle : IEA:Ensembl negative regulation of Notch signaling pathway : TAS:Reactome negative regulation of protein catabolic process : IDA:UniProtKB neuron projection morphogenesis : IEA:Ensembl ossification : NAS:UniProtKB ovulation cycle : IEA:Ensembl peptidyl-tyrosine autophosphorylation : IMP:UniProtKB peptidyl-tyrosine phosphorylation : IDA:ParkinsonsUK-UCL positive regulation of blood vessel diameter : IEA:Ensembl positive regulation of bone resorption : IEA:Ensembl positive regulation of canonical Wnt signaling pathway : IMP:BHF-UCL positive regulation of cell growth : IDA:UniProtKB positive regulation of cell migration : IMP:UniProtKB positive regulation of cell population proliferation : IDA:MGI positive regulation of cyclin-dependent protein serine/threonine kinase activity : IMP:BHF-UCL positive regulation of DNA repair : IDA:UniProtKB positive regulation of DNA replication : IDA:UniProtKB positive regulation of epithelial cell proliferation : IDA:UniProtKB positive regulation of ERK1 and ERK2 cascade : IDA:UniProtKB positive regulation of fibroblast proliferation : IEA:Ensembl positive regulation of G1/S transition of mitotic cell cycle : IMP:BHF-UCL positive regulation of inflammatory response : IEA:Ensembl positive regulation of MAP kinase activity : IDA:UniProtKB positive regulation of NIK/NF-kappaB signaling : IMP:CAFA positive regulation of nitric oxide mediated signal transduction : IDA:UniProtKB positive regulation of peptidyl-serine phosphorylation : IMP:UniProtKB positive regulation of phosphorylation : IDA:UniProtKB positive regulation of production of miRNAs involved in gene silencing by miRNA : IMP:BHF-UCL positive regulation of prolactin secretion : IEA:Ensembl positive regulation of protein kinase B signaling : IMP:BHF-UCL positive regulation of protein kinase C activity : IDA:ParkinsonsUK-UCL positive regulation of protein localization to plasma membrane : IDA:ParkinsonsUK-UCL positive regulation of protein phosphorylation : IDA:UniProtKB positive regulation of smooth muscle cell proliferation : IEA:Ensembl positive regulation of superoxide anion generation : IEA:Ensembl positive regulation of synaptic transmission, glutamatergic : IEA:Ensembl positive regulation of transcription by RNA polymerase II : IDA:UniProtKB positive regulation of transcription, DNA-templated : IMP:CAFA positive regulation of vasoconstriction : IEA:Ensembl protein autophosphorylation : IMP:UniProtKB protein insertion into membrane : TAS:UniProtKB regulation of cell motility : TAS:Reactome regulation of ERK1 and ERK2 cascade : IMP:CAFA regulation of JNK cascade : IMP:CAFA regulation of nitric-oxide synthase activity : IDA:UniProtKB regulation of peptidyl-tyrosine phosphorylation : IMP:UniProtKB regulation of phosphatidylinositol 3-kinase signaling : IMP:CAFA regulation of transcription by RNA polymerase II : TAS:Reactome response to calcium ion : IEA:Ensembl response to cobalamin : IEA:Ensembl response to hydroxyisoflavone : IEA:Ensembl response to osmotic stress : IEA:Ensembl response to UV-A : IDA:BHF-UCL salivary gland morphogenesis : IEA:Ensembl signal transduction : IDA:UniProtKB tongue development : IEA:Ensembl translation : IEA:Ensembl transmembrane receptor protein tyrosine kinase signaling pathway : IBA:GO_Central wound healing : IEA:Ensembl

^{(a) The Signal peptide D-score cutoff for "YES"(having signal peptide) is 0.45.}
^{(b) Non-classically secreted proteins should obtain an NN-score(Neural Networks score) exceeding the normal threshold of 0.5, but not at the same time be predicted to contain a signal peptide.}

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