Epidermal growth factor receptor
Also known as: EGFR, ERBB, ERBB1, HER1
Function
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, AREG, 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. 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. Plays a role in enhancing learning and memory performance (By similarity). Plays a role in mammalian pain signaling (long-lasting hypersensitivity) (By similarity).
Classification
- Family (Pfam)
- PF00757 Furin-like, PF14843 GF_recep_IV, PF07714 PK_Tyr_Ser-Thr, PF01030 Recep_L_domain, PF21314 TM_ErbB1
- InterPro
- Furin-like_Cys-rich_dom, Furin_repeat, GF_recep_IV, Growth_fac_rcpt_cys_sf, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, Rcpt_L-dom, Rcpt_L-dom_sf, RTK, Ser-Thr/Tyr_kinase_cat_dom, TM_ErbB1, Tyr_kinase_AS, Tyr_kinase_cat_dom, Tyr_kinase_EGF/ERB/XmrK_rcpt
- Functional cluster
- Immunoglobulin-Domain Cell Adhesion Proteins
Experimental structures · PDB · 354
- 1IVO X-ray 3.30A
- 1M14 X-ray 2.60A
- 1M17 X-ray 2.60A
- 1MOX X-ray 2.50A
- 1NQL X-ray 2.80A
- 1XKK X-ray 2.40A
- 1YY9 X-ray 2.60A
- 1Z9I NMR
- 2EB2 X-ray 2.50A
- 2EB3 X-ray 2.84A
- 2GS2 X-ray 2.80A
- 2GS6 X-ray 2.60A
- … and 342 more
A predicted model is available from AlphaFold.
Gene Ontology · 83
- GO:0009925 basal plasma membrane
- GO:0016323 basolateral plasma membrane
- GO:0030054 cell junction
- GO:0009986 cell surface
- GO:0030669 clathrin-coated endocytic vesicle membrane
- GO:0005737 cytoplasm
- GO:0031901 early endosome membrane
- GO:0005789 endoplasmic reticulum membrane
- GO:0005768 endosome
- GO:0010008 endosome membrane
- GO:0005615 extracellular space
- GO:0005925 focal adhesion
- GO:0005794 Golgi apparatus
- GO:0000139 Golgi membrane
- GO:0097708 intracellular vesicle
- GO:0016020 membrane
- GO:0045121 membrane raft
- GO:0097489 multivesicular body, internal vesicle lumen
- GO:0031965 nuclear membrane
- GO:0005634 nucleus
- GO:0048471 perinuclear region of cytoplasm
- GO:0005886 plasma membrane
- GO:0032991 protein-containing complex
- GO:0043235 receptor complex
- GO:0032587 ruffle membrane
- GO:0070435 Shc-EGFR complex
- GO:0051015 actin filament binding
- GO:0005524 ATP binding
- GO:0051117 ATPase binding
- GO:0045296 cadherin binding
- GO:0003682 chromatin binding
- GO:0003690 double-stranded DNA binding
- GO:0019899 enzyme binding
- GO:0048408 epidermal growth factor binding
- GO:0005006 epidermal growth factor receptor activity
- GO:0042802 identical protein binding
- GO:0019900 kinase binding
- GO:0004709 MAP kinase kinase kinase activity
- GO:0019903 protein phosphatase binding
- GO:0030296 protein tyrosine kinase activator activity
- GO:0004713 protein tyrosine kinase activity
- GO:0004714 transmembrane receptor protein tyrosine kinase activity
- GO:0004888 transmembrane signaling receptor activity
- GO:0031625 ubiquitin protein ligase binding
- GO:0001618 virus receptor activity
- GO:0007166 cell surface receptor signaling pathway
- GO:0098609 cell-cell adhesion
- GO:0071230 cellular response to amino acid stimulus
- GO:0071364 cellular response to epidermal growth factor stimulus
- GO:0071392 cellular response to estradiol stimulus
- GO:0007173 epidermal growth factor receptor signaling pathway
- GO:0038134 ERBB2-EGFR signaling pathway
- GO:0007611 learning or memory
- GO:0043066 negative regulation of apoptotic process
- GO:1905208 negative regulation of cardiocyte differentiation
- GO:0042059 negative regulation of epidermal growth factor receptor signaling pathway
- GO:0042177 negative regulation of protein catabolic process
- GO:0030182 neuron differentiation
- GO:0001503 ossification
- GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction
- GO:0090263 positive regulation of canonical Wnt signaling pathway
- GO:0030307 positive regulation of cell growth
- GO:0030335 positive regulation of cell migration
- GO:0008284 positive regulation of cell population proliferation
- GO:0045739 positive regulation of DNA repair
- GO:0045740 positive regulation of DNA replication
- GO:0050679 positive regulation of epithelial cell proliferation
- GO:0070374 positive regulation of ERK1 and ERK2 cascade
- GO:0048146 positive regulation of fibroblast proliferation
- GO:1900087 positive regulation of G1/S transition of mitotic cell cycle
- GO:0043410 positive regulation of MAPK cascade
- GO:1902895 positive regulation of miRNA transcription
- GO:0033138 positive regulation of peptidyl-serine phosphorylation
- GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
- GO:0042327 positive regulation of phosphorylation
- GO:0090037 positive regulation of protein kinase C signaling
- GO:1903078 positive regulation of protein localization to plasma membrane
- GO:0001934 positive regulation of protein phosphorylation
- GO:0045944 positive regulation of transcription by RNA polymerase II
- GO:0051205 protein insertion into membrane
- GO:0050730 regulation of peptidyl-tyrosine phosphorylation
- GO:0070141 response to UV-A
- GO:0007165 signal transduction
Disease associations
- lung cancer MONDO:0008903
- inflammatory skin and bowel disease, neonatal, 2 MONDO:0014481
Drugs targeting this protein · 56
- ERLOTINIB HYDROCHLORIDE inhibitor
- LAPATINIB DITOSYLATE inhibitor
- TAK-285 inhibitor
- AC-480 inhibitor
- NERATINIB inhibitor
- ALLITINIB inhibitor
- PKI-166 inhibitor
- CEP-32496 inhibitor
- ICOTINIB inhibitor
- VARLITINIB inhibitor
- AFATINIB DIMALEATE inhibitor
- DACOMITINIB inhibitor
- DACOMITINIB ANHYDROUS inhibitor
- SAPITINIB inhibitor
- VANDETANIB inhibitor
- FALNIDAMOL inhibitor
- JNJ-26483327 inhibitor
- OSIMERTINIB inhibitor
- TESEVATINIB inhibitor
- OSIMERTINIB MESYLATE inhibitor
- POZIOTINIB inhibitor
- PD-0166285 HYDROCHLORIDE inhibitor
- SIMOTINIB inhibitor
- ROCILETINIB inhibitor
- BRIGATINIB inhibitor
- BMS-690514 inhibitor
- AZD-3759 inhibitor
- PYROTINIB inhibitor
- NAQUOTINIB inhibitor
- RUSERONTINIB inhibitor
- PF-06459988 inhibitor
- OLMUTINIB inhibitor
- NAZARTINIB inhibitor
- NERATINIB MALEATE inhibitor
- MAVELERTINIB inhibitor
- AZD-4769 inhibitor
- FIRMONERTINIB inhibitor
- TARLOXOTINIB inhibitor
- ABIVERTINIB inhibitor
- ABIVERTINIB MALEATE inhibitor
- PUQUITINIB MESYLATE DIHYDRATE inhibitor
- LAZERTINIB inhibitor
- TUXOBERTINIB negative allosteric modulator
- CLN-081 inhibitor
- MOBOCERTINIB inhibitor
- AUMOLERTINIB inhibitor
- MOBOCERTINIB SUCCINATE inhibitor
- THELIATINIB inhibitor
- EPITINIB inhibitor
- CANERTINIB DIHYDROCHLORIDE inhibitor
- AEE-788 inhibitor
- CUDC-101 inhibitor
- AV-412 inhibitor
- LAZERTINIB MESYLATE inhibitor
- PELITINIB inhibitor
- GEFITINIB inhibitor
Neighborhood · nearest proteins
Related proteins · sequence + function similarity
- Epidermal growth factor receptor 1.00
- Epidermal growth factor receptor 0.99
- Melanoma receptor tyrosine-protein kinase 0.85
- Receptor tyrosine-protein kinase erbB-2 0.84
- Receptor tyrosine-protein kinase erbB-2 0.82
- Receptor tyrosine-protein kinase erbB-2 0.81
- Epidermal growth factor receptor 0.81
- Epidermal growth factor receptor 0.80
- Receptor tyrosine-protein kinase erbB-2 0.80
- Epidermal growth factor receptor 0.80
- Receptor tyrosine-protein kinase erbB-4 0.79
- Receptor tyrosine-protein kinase erbB-4 0.79
Co-cited proteins · studied together in the literature
- Pro-epidermal growth factor 4 shared papers
- Leucine-rich repeats and immunoglobulin-like domains protein 1 1 shared papers
- Epigen 1 shared papers
- ERBB receptor feedback inhibitor 1 1 shared papers
- Sialidase-3 2 shared papers
- Amphiregulin 1 shared papers
- Probetacellulin 1 shared papers
- Coatomer subunit gamma-1 1 shared papers
- Protein FAM83B 1 shared papers
- Regulator of G protein signaling 16 1 shared papers
- G protein-coupled estrogen receptor 1 2 shared papers
- Beta-casein 1 shared papers
Literature · 114 cited papers
- SNX32 regulates sorting and trafficking of activated EGFR to the lysosomal degradation pathway. Traffic · 2024
- CD82 palmitoylation site mutations at Cys5+Cys74 affect EGFR internalization and metabolism through recycling pathway. Acta Biochim. Biophys. Sin. · 2022
- ZNRF1 Mediates Epidermal Growth Factor Receptor Ubiquitination to Control Receptor Lysosomal Trafficking and Degradation. Front. Cell Dev. Biol. · 2021
- TRAF4 binds to the juxtamembrane region of EGFR directly and promotes kinase activation. Proc. Natl. Acad. Sci. U.S.A. · 2018
- Landscape of the regulatory elements for lysine 2-hydroxyisobutyrylation pathway. Cell Res. · 2018
- Epidermal Growth Factor Receptor neddylation is regulated by a desmosomal-COP9 (Constitutive Photomorphogenesis 9) signalosome complex. Elife · 2017
- Beclin1 antagonizes LAPTM4B-mediated EGFR overactivation in gastric cancer cells. Gene · 2017
- Inhibition of DHHC20-Mediated EGFR Palmitoylation Creates a Dependence on EGFR Signaling. Mol. Cell · 2016
- Haem-dependent dimerization of PGRMC1/Sigma-2 receptor facilitates cancer proliferation and chemoresistance. Nat. Commun. · 2016
- c-Src/Cav1-dependent activation of the EGFR by Dsg2. Oncotarget · 2016
- NEU3 activity enhances EGFR activation without affecting EGFR expression and acts on its sialylation levels. Glycobiology · 2015
- EGFR phosphorylates and inhibits lung tumor suppressor GPRC5A in lung cancer. Mol. Cancer · 2014
- … and 102 more in the literature graph