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Protein

Epidermal growth factor receptor

Gene

EGFR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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).By similarity20 Publications
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.1 Publication

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation6 Publications

Enzyme regulationi

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.4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei745ATPCombined sources2 Publications1
Active sitei837Proton acceptorPROSITE-ProRule annotation1
Binding sitei855ATPCombined sources2 Publications1
Sitei1016Important for interaction with PIK3C2B1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi718 – 726ATPCombined sources1 Publication9
Nucleotide bindingi790 – 791ATPCombined sources2 Publications2

GO - Molecular functioni

  • actin filament binding Source: UniProtKB
  • ATP binding Source: UniProtKB-KW
  • cadherin binding Source: BHF-UCL
  • calmodulin binding Source: Ensembl
  • chromatin binding Source: UniProtKB
  • double-stranded DNA binding Source: UniProtKB
  • enzyme binding Source: UniProtKB
  • epidermal growth factor-activated receptor activity Source: UniProtKB
  • epidermal growth factor binding Source: Ensembl
  • identical protein binding Source: IntAct
  • integrin binding Source: Ensembl
  • MAP kinase kinase kinase activity Source: UniProtKB
  • phosphatidylinositol-4,5-bisphosphate 3-kinase activity Source: Reactome
  • protein heterodimerization activity Source: UniProtKB
  • protein kinase binding Source: Ensembl
  • protein phosphatase binding Source: UniProtKB
  • protein tyrosine kinase activity Source: UniProtKB
  • Ras guanyl-nucleotide exchange factor activity Source: Reactome
  • transmembrane receptor protein tyrosine kinase activity Source: Reactome
  • transmembrane signaling receptor activity Source: MGI
  • ubiquitin protein ligase binding Source: UniProtKB
  • virus receptor activity Source: UniProtKB-KW

GO - Biological processi

  • 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 proliferation Source: UniProtKB
  • cell surface receptor signaling pathway Source: MGI
  • cellular response to amino acid stimulus Source: Ensembl
  • cellular response to cadmium ion Source: CAFA
  • cellular response to dexamethasone stimulus 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
  • cerebral cortex cell migration Source: Ensembl
  • circadian rhythm Source: Ensembl
  • digestive tract morphogenesis Source: Ensembl
  • diterpenoid metabolic process Source: Ensembl
  • embryonic placenta development Source: Ensembl
  • epidermal growth factor receptor signaling pathway Source: UniProtKB
  • ERBB2 signaling pathway Source: Reactome
  • eyelid development in camera-type eye Source: Ensembl
  • 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
  • MAPK cascade Source: Reactome
  • membrane organization Source: Reactome
  • midgut development Source: Ensembl
  • morphogenesis of an epithelial fold 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 ERBB signaling pathway Source: Reactome
  • negative regulation of mitotic cell cycle Source: Ensembl
  • negative regulation of Notch signaling pathway Source: Reactome
  • 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 blood vessel diameter Source: Ensembl
  • 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 proliferation Source: MGI
  • positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle 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 fibroblast proliferation Source: Ensembl
  • positive regulation of inflammatory response Source: Ensembl
  • positive regulation of MAP kinase activity Source: UniProtKB
  • 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 cell motility Source: Reactome
  • 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
  • regulation of transcription by RNA polymerase II Source: Reactome
  • 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
  • salivary gland morphogenesis Source: Ensembl
  • signal transduction Source: UniProtKB
  • tongue development Source: Ensembl
  • translation Source: Ensembl
  • wound healing Source: Ensembl

Keywordsi

Molecular functionDevelopmental protein, Host cell receptor for virus entry, Kinase, Receptor, Transferase, Tyrosine-protein kinase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1 2681
ReactomeiR-HSA-1227986 Signaling by ERBB2
R-HSA-1236382 Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants
R-HSA-1236394 Signaling by ERBB4
R-HSA-1250196 SHC1 events in ERBB2 signaling
R-HSA-1251932 PLCG1 events in ERBB2 signaling
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-177929 Signaling by EGFR
R-HSA-179812 GRB2 events in EGFR signaling
R-HSA-180292 GAB1 signalosome
R-HSA-180336 SHC1 events in EGFR signaling
R-HSA-182971 EGFR downregulation
R-HSA-1963640 GRB2 events in ERBB2 signaling
R-HSA-1963642 PI3K events in ERBB2 signaling
R-HSA-212718 EGFR interacts with phospholipase C-gamma
R-HSA-2179392 EGFR Transactivation by Gastrin
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-445144 Signal transduction by L1
R-HSA-5637810 Constitutive Signaling by EGFRvIII
R-HSA-5638303 Inhibition of Signaling by Overexpressed EGFR
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-6785631 ERBB2 Regulates Cell Motility
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-8847993 ERBB2 Activates PTK6 Signaling
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828 Clathrin-mediated endocytosis
R-HSA-8857538 PTK6 promotes HIF1A stabilization
R-HSA-8863795 Downregulation of ERBB2 signaling
R-HSA-8866910 TFAP2 (AP-2) family regulates transcription of growth factors and their receptors
R-HSA-9013507 NOTCH3 Activation and Transmission of Signal to the Nucleus
SignaLinkiP00533
SIGNORiP00533

Protein family/group databases

MoonDBiP00533 Predicted

Names & Taxonomyi

Protein namesi
Recommended name:
Epidermal growth factor receptor (EC:2.7.10.1)
Alternative name(s):
Proto-oncogene c-ErbB-1
Receptor tyrosine-protein kinase erbB-1
Gene namesi
Name:EGFR
Synonyms:ERBB, ERBB1, HER1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000146648.15
HGNCiHGNC:3236 EGFR
MIMi131550 gene
neXtProtiNX_P00533

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini25 – 645ExtracellularSequence analysisAdd BLAST621
Transmembranei646 – 668HelicalSequence analysisAdd BLAST23
Topological domaini669 – 1210CytoplasmicSequence analysisAdd BLAST542

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Endosome, Golgi apparatus, Membrane, Nucleus, Secreted

Pathology & Biotechi

Involvement in diseasei

Lung cancer (LNCR)3 Publications
The gene represented in this entry is involved in disease pathogenesis.
Disease descriptionA 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.
See also OMIM:211980
Inflammatory skin and bowel disease, neonatal, 2 (NISBD2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:616069
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_072435428G → D in NISBD2; loss of function; the mutant does not localize to the cell membrane; has diffuse cytoplasmic localization. 1 PublicationCorresponds to variant dbSNP:rs606231253EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi275Y → A: Strongly reduced autophosphorylation and activation of downstream kinases; when associated with A-309. 1 Publication1
Mutagenesisi287F → A: Strongly reduced autophosphorylation and activation of downstream kinases; when associated with A-309. 1 Publication1
Mutagenesisi309R → S: Strongly reduced autophosphorylation and activation of downstream kinases; when associated with A-275. Strongly reduced autophosphorylation and activation of downstream kinases; when associated with A-287. 1 Publication1
Mutagenesisi429R → E: Abolishes autophosphorylation and activation of downstream kinases. 1 Publication1
Mutagenesisi587 – 590DGPH → AGPA: Decreases intramolecular interactions and facilitates EGF binding. 1 Publication4
Mutagenesisi609K → A: Decreases intramolecular interactions and facilitates EGF binding. 1 Publication1
Mutagenesisi688L → A: Strongly reduced phosphorylation. 2 Publications1
Mutagenesisi689V → A: Reduced autophosphorylation. 1 Publication1
Mutagenesisi689V → M: Constitutively activated kinase. 1 Publication1
Mutagenesisi690E → A: Reduced phosphorylation. 2 Publications1
Mutagenesisi692L → A or P: Strongly reduced phosphorylation. 2 Publications1
Mutagenesisi693T → A: Increased phosphorylation. 1 Publication1
Mutagenesisi693T → D: Strongly reduced phosphorylation. 1 Publication1
Mutagenesisi694P → A: Strongly reduced phosphorylation. 1 Publication1
Mutagenesisi699P → A: Reduced phosphorylation. 1 Publication1
Mutagenesisi700N → A: Abolishes phosphorylation. 1 Publication1
Mutagenesisi704L → A: Abolishes phosphorylation. 1 Publication1
Mutagenesisi705R → A: Abolishes phosphorylation. 1 Publication1
Mutagenesisi706I → A: Abolishes phosphorylation. 1 Publication1
Mutagenesisi745K → A or M: Abolishes kinase activity. 1 Publication1
Mutagenesisi974D → A: Strongly reduced phosphorylation. 1
Mutagenesisi977R → A: Reduced phosphorylation. 1 Publication1
Mutagenesisi1005 – 1006ED → RK: Constitutively activated kinase. 1 Publication2
Mutagenesisi1016Y → F: 50% decrease in interaction with PIK3C2B. 65% decrease in interaction with PIK3C2B; when associated with F-1197. Abolishes interaction with PIK3C2B; when associated with F-1197 and F-1092. 1 Publication1
Mutagenesisi1048 – 1210Missing : Abolishes palmitoylation. 1 PublicationAdd BLAST163
Mutagenesisi1049C → A: Decreased palmitoylation. 1 Publication1
Mutagenesisi1067Q → G: No effect on interaction with CBLC. 1 Publication1
Mutagenesisi1068R → G: Strongly decreases interaction with CBLC. 1 Publication1
Mutagenesisi1069Y → F: Abolishes interaction with CBLC. 1 Publication1
Mutagenesisi1092Y → F: No change in interaction with PIK3C2B. Abolishes interaction with PIK3C2B; when associated with F-1197 and F-1016. 1 Publication1
Mutagenesisi1110Y → F: No change in interaction with PIK3C2B. 1 Publication1
Mutagenesisi1146C → A: Decreased palmitoylation. 1 Publication1
Mutagenesisi1172Y → F: No change in interaction with PIK3C2B. 1 Publication1
Mutagenesisi1197Y → F: No change in interaction with PIK3C2B. 65% decrease in interaction with PIK3C2B; when associated with F-1016. Abolishes interaction with PIK3C2B; when associated with F-1092 and F-1016. 1 Publication1

Keywords - Diseasei

Disease mutation, Proto-oncogene

Organism-specific databases

DisGeNETi1956
MalaCardsiEGFR
MIMi211980 phenotype
616069 phenotype
OpenTargetsiENSG00000146648
Orphaneti251579 Giant cell glioblastoma
251576 Gliosarcoma
294023 Neonatal inflammatory skin and bowel disease
357191 Selection of therapeutic option in non-small cell lung carcinoma
PharmGKBiPA7360

Chemistry databases

ChEMBLiCHEMBL203
DrugBankiDB08916 Afatinib
DB00002 Cetuximab
DB05424 CI-1033
DB00530 Erlotinib
DB03496 Flavopiridol
DB00317 Gefitinib
DB05324 HuMax-EGFr
DB11737 Icotinib
DB04988 IGN311
DB05774 IMC-11F8
DB05900 INSM-18
DB01259 Lapatinib
DB00281 Lidocaine
DB05101 Matuzumab
DB07662 N-[4-(3-BROMO-PHENYLAMINO)-QUINAZOLIN-6-YL]-ACRYLAMIDE
DB09559 Necitumumab
DB13164 Olmutinib
DB09330 Osimertinib
DB01269 Panitumumab
DB05374 Rindopepimut
DB07602 S-{3-[(4-ANILINOQUINAZOLIN-6-YL)AMINO]-3-OXOPROPYL}-L-CYSTEINE
DB00072 Trastuzumab
DB05294 Vandetanib
GuidetoPHARMACOLOGYi1797

Polymorphism and mutation databases

BioMutaiEGFR
DMDMi2811086

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 243 PublicationsAdd BLAST24
ChainiPRO_000001666525 – 1210Epidermal growth factor receptorAdd BLAST1186

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi31 ↔ 58Combined sources3 Publications
GlycosylationiCAR_00022756N-linked (GlcNAc...) (complex) asparagine; atypical; partialCombined sources6 Publications1
Glycosylationi73N-linked (GlcNAc...) asparagine; atypicalCombined sources1 Publication1
Glycosylationi128N-linked (GlcNAc...) asparagine3 Publications1
Disulfide bondi157 ↔ 187Combined sources5 Publications
Glycosylationi175N-linked (GlcNAc...) asparagineCombined sources5 Publications1
Disulfide bondi190 ↔ 199Combined sources5 Publications
Disulfide bondi194 ↔ 207Combined sources5 Publications
Glycosylationi196N-linked (GlcNAc...) asparagineCombined sources5 Publications1
Disulfide bondi215 ↔ 223Combined sources5 Publications
Disulfide bondi219 ↔ 231Combined sources5 Publications
Modified residuei229Phosphoserine1 Publication1
Disulfide bondi232 ↔ 240Combined sources5 Publications
Disulfide bondi236 ↔ 248Combined sources5 Publications
Disulfide bondi251 ↔ 260Combined sources5 Publications
Disulfide bondi264 ↔ 291Combined sources5 Publications
Disulfide bondi295 ↔ 307Combined sources
Disulfide bondi311 ↔ 326Combined sources5 Publications
Disulfide bondi329 ↔ 333Combined sources
Disulfide bondi337 ↔ 362Combined sources5 Publications
Glycosylationi352N-linked (GlcNAc...) asparagineCombined sources8 Publications1
Glycosylationi361N-linked (GlcNAc...) asparagineCombined sources6 Publications1
Glycosylationi413N-linked (GlcNAc...) asparagineCombined sources4 Publications1
Glycosylationi444N-linked (GlcNAc...) asparagineCombined sources6 Publications1
Disulfide bondi470 ↔ 499Combined sources
Disulfide bondi506 ↔ 515Combined sources5 Publications
Disulfide bondi510 ↔ 523Combined sources5 Publications
Disulfide bondi526 ↔ 535Combined sources4 Publications
Glycosylationi528N-linked (GlcNAc...) asparagineCombined sources5 Publications1
Disulfide bondi539 ↔ 555Combined sources3 Publications
Disulfide bondi558 ↔ 571Combined sources3 Publications
Disulfide bondi562 ↔ 579Combined sources3 Publications
Glycosylationi568N-linked (GlcNAc...) asparagine; partialCombined sources5 Publications1
Disulfide bondi582 ↔ 591Combined sources3 Publications
Disulfide bondi595 ↔ 617Combined sources3 Publications
Glycosylationi603N-linked (GlcNAc...) asparagine; partialCombined sources4 Publications1
Disulfide bondi620 ↔ 628Combined sources3 Publications
Glycosylationi623N-linked (GlcNAc...) (high mannose) asparagine1 Publication1
Disulfide bondi624 ↔ 636Combined sources3 Publications
Modified residuei678Phosphothreonine; by PKC and PKD/PRKD11 Publication1
Modified residuei693Phosphothreonine; by PKD/PRKD1Combined sources3 Publications1
Modified residuei695PhosphoserineCombined sources1 Publication1
Cross-linki716Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki737Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki754Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki867Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki929Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki970Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei991PhosphoserineCombined sources1 Publication1
Modified residuei995PhosphoserineCombined sources1
Modified residuei998Phosphotyrosine; by autocatalysisCombined sources1 Publication1
Modified residuei1016Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei1026PhosphoserineCombined sources1 Publication1
Modified residuei1039PhosphoserineCombined sources1
Modified residuei1041PhosphothreonineCombined sources1
Modified residuei1042PhosphoserineCombined sources1
Lipidationi1049S-palmitoyl cysteine1 Publication1
Modified residuei1064PhosphoserineCombined sources1
Modified residuei1069Phosphotyrosine1 Publication1
Modified residuei1070Phosphoserine1 Publication1
Modified residuei1071Phosphoserine1 Publication1
Modified residuei1081PhosphoserineCombined sources1
Modified residuei1092Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei1110Phosphotyrosine; by autocatalysis2 Publications1
Lipidationi1146S-palmitoyl cysteine1 Publication1
Modified residuei1166PhosphoserineCombined sources1
Modified residuei1172Phosphotyrosine; by autocatalysisCombined sources1 Publication1
Modified residuei1197Phosphotyrosine; by autocatalysisCombined sources3 Publications1
Modified residuei1199Omega-N-methylarginine1 Publication1

Post-translational modificationi

Phosphorylated on Tyr residues in response to EGF (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 PTPN2.9 Publications
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).By similarity4 Publications
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.1 Publication