ID:EGFR_HUMAN DESCRIPTION: RecName: Full=Epidermal growth factor receptor; EC=2.7.10.1; AltName: Full=Proto-oncogene c-ErbB-1; AltName: Full=Receptor tyrosine-protein kinase erbB-1; Flags: Precursor; 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, 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. FUNCTION: Isoform 2 may act as an antagonist of EGF action. CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. ENZYME REGULATION: Endocytosis and inhibition of the activated EGFR by phosphatases like PTPRJ and PTPRK constitute immediate regulatory mechanisms. Upon EGF-binding phosphorylates EPS15 that regulates EGFR endocytosis and activity. Moreover, inducible feedback inhibitors including LRIG1, SOCS4, SOCS5 and ERRFI1 constitute alternative regulatory mechanisms for the EGFR signaling. SUBUNIT: 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; 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. INTERACTION: Self; NbExp=13; IntAct=EBI-297353, EBI-297353; Q02952:AKAP12; NbExp=2; IntAct=EBI-297353, EBI-2562430; P62158:CALM3; NbExp=3; IntAct=EBI-297353, EBI-397435; P62161:Calm3 (xeno); NbExp=6; IntAct=EBI-297353, EBI-397530; P22681:CBL; NbExp=4; IntAct=EBI-297353, EBI-518228; P22682:Cbl (xeno); NbExp=2; IntAct=EBI-297353, EBI-640919; Q99418:CYTH2; NbExp=5; IntAct=EBI-297353, EBI-448974; P01133:EGF; NbExp=3; IntAct=EBI-297353, EBI-640857; P04626:ERBB2; NbExp=9; IntAct=EBI-297353, EBI-641062; P21860:ERBB3; NbExp=6; IntAct=EBI-297353, EBI-720706; Q15303:ERBB4; NbExp=2; IntAct=EBI-297353, EBI-80371; Q9UJM3:ERRFI1; NbExp=2; IntAct=EBI-297353, EBI-2941912; P03372-4:ESR1; NbExp=4; IntAct=EBI-297353, EBI-4309277; Q14318:FKBP8; NbExp=3; IntAct=EBI-297353, EBI-724839; P60520:GABARAPL2; NbExp=2; IntAct=EBI-297353, EBI-720116; P04406:GAPDH; NbExp=4; IntAct=EBI-297353, EBI-354056; P62993:GRB2; NbExp=12; IntAct=EBI-297353, EBI-401755; Q9UBN7:HDAC6; NbExp=8; IntAct=EBI-297353, EBI-301697; P08107:HSPA1B; NbExp=4; IntAct=EBI-297353, EBI-629985; P46940:IQGAP1; NbExp=4; IntAct=EBI-297353, EBI-297509; Q9Y2H9:MAST1; NbExp=2; IntAct=EBI-297353, EBI-3385920; P08581:MET; NbExp=4; IntAct=EBI-297353, EBI-1039152; O00750:PIK3C2B; NbExp=7; IntAct=EBI-297353, EBI-641107; Q9UJ41:RABGEF1; NbExp=4; IntAct=EBI-297353, EBI-913954; Q13671:RIN1; NbExp=3; IntAct=EBI-297353, EBI-366017; Q01973:ROR1; NbExp=8; IntAct=EBI-297353, EBI-6082337; P29353:SHC1; NbExp=5; IntAct=EBI-297353, EBI-78835; P13866:SLC5A1; NbExp=3; IntAct=EBI-297353, EBI-1772443; P12931:SRC; NbExp=5; IntAct=EBI-297353, EBI-621482; P31948:STIP1; NbExp=2; IntAct=EBI-297353, EBI-1054052; Q8K424:Trpv3 (xeno); NbExp=2; IntAct=EBI-297353, EBI-2650739; P09936:UCHL1; NbExp=2; IntAct=EBI-297353, EBI-714860; Q9P0L0:VAPA; NbExp=2; IntAct=EBI-297353, EBI-1059156; P27348:YWHAQ; NbExp=4; IntAct=EBI-297353, EBI-359854; P63104:YWHAZ; NbExp=4; IntAct=EBI-297353, EBI-347088; 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. Note=In response to EGF, translocated from the cell membrane to the nucleus via Golgi and ER. Endocytosed upon activation by ligand. SUBCELLULAR LOCATION: Isoform 2: Secreted. TISSUE SPECIFICITY: Ubiquitously expressed. Isoform 2 is also expressed in ovarian cancers. PTM: 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. PTM: Monoubiquitinated and polyubiquitinated upon EGF stimulation; which does not affect tyrosine kinase activity or signaling capacity but may play a role in lysosomal targeting. Polyubiquitin linkage is mainly through 'Lys-63', but linkage through 'Lys-48', 'Lys-11' and 'Lys-29' also occur. PTM: Methylated. Methylation at Arg-1199 by PRMT5 positively stimulates phosphorylation at Tyr-1197. DISEASE: Defects in EGFR are associated with lung cancer (LNCR) [MIM:211980]. LNCR is 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. SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily. SIMILARITY: Contains 1 protein kinase domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/EGFR"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/egfr/"; WEB RESOURCE: Name=Wikipedia; Note=EGFR entry; URL="http://en.wikipedia.org/wiki/Epidermal_growth_factor_receptor";
ModBase Predicted Comparative 3D Structure on P00533
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Other Names for This Gene
Press "+" in the title bar above to open this section.
Methods, Credits, and Use Restrictions
Press "+" in the title bar above to open this section.
