Homo sapiens Protein: EGFR
InnateDB Protein IDBP-16935.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol EGFR
Protein Name epidermal growth factor receptor
Synonyms ERBB; ERBB1; HER1; mENA; PIG61;
Species Homo sapiens
Ensembl Protein ENSP00000275493
InnateDB Gene IDBG-16933 (EGFR)
Protein Structure
UniProt Annotation
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.Isoform 2 may act as an antagonist of EGF action.
Subcellular Localization 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. Nucleus. Note=In response to EGF, translocated from the cell membrane to the nucleus via Golgi and ER. Endocytosed upon activation by ligand. Colocalized with GPER1 in the nucleus of estrogen agonist-induced cancer-associated fibroblasts (CAF).Isoform 2: Secreted.
Disease Associations Lung cancer (LNCR) [MIM:211980]: 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. {ECO:0000269PubMed:15118125, ECO:0000269PubMed:16533793, ECO:0000269PubMed:16672372}. Note=The gene represented in this entry is involved in disease pathogenesis.
Tissue Specificity Ubiquitously expressed. Isoform 2 is also expressed in ovarian cancers. {ECO:0000269PubMed:17671655}.
Number of Interactions This gene and/or its encoded proteins are associated with 800 experimentally validated interaction(s) in this database.
They are also associated with 21 interaction(s) predicted by orthology.
Experimentally validated
Total 800 [view]
Protein-Protein 790 [view]
Protein-DNA 9 [view]
Protein-RNA 0
DNA-DNA 1 [view]
Predicted by orthology
Total 21 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0001948 glycoprotein binding
GO:0003682 chromatin binding
GO:0003690 double-stranded DNA binding
GO:0004672 protein kinase activity
GO:0004709 MAP kinase kinase kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0004714 transmembrane receptor protein tyrosine kinase activity
GO:0004716 receptor signaling protein tyrosine kinase activity
GO:0004871 signal transducer activity
GO:0004888 transmembrane signaling receptor activity
GO:0005006 epidermal growth factor-activated receptor activity
GO:0005102 receptor binding
GO:0005178 integrin binding
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016772 transferase activity, transferring phosphorus-containing groups
GO:0019899 enzyme binding
GO:0019901 protein kinase binding
GO:0019903 protein phosphatase binding
GO:0030235 nitric-oxide synthase regulator activity
GO:0042802 identical protein binding
GO:0046982 protein heterodimerization activity
GO:0048408 epidermal growth factor binding
GO:0051015 actin filament binding
Biological Process
GO:0000165 MAPK cascade
GO:0000186 activation of MAPKK activity
GO:0000902 cell morphogenesis
GO:0001503 ossification
GO:0001889 liver development
GO:0001892 embryonic placenta development
GO:0001934 positive regulation of protein phosphorylation
GO:0001942 hair follicle development
GO:0006412 translation
GO:0006468 protein phosphorylation
GO:0006950 response to stress
GO:0006970 response to osmotic stress
GO:0006979 response to oxidative stress
GO:0007165 signal transduction
GO:0007166 cell surface receptor signaling pathway
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway
GO:0007173 epidermal growth factor receptor signaling pathway
GO:0007202 activation of phospholipase C activity
GO:0007411 axon guidance
GO:0007435 salivary gland morphogenesis
GO:0007611 learning or memory
GO:0007623 circadian rhythm
GO:0008283 cell proliferation
GO:0008284 positive regulation of cell proliferation
GO:0008543 fibroblast growth factor receptor signaling pathway
GO:0008544 epidermis development
GO:0010960 magnesium ion homeostasis
GO:0014070 response to organic cyclic compound
GO:0016101 diterpenoid metabolic process
GO:0016337 single organismal cell-cell adhesion
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0019694 alkanesulfonate metabolic process
GO:0021795 cerebral cortex cell migration
GO:0023014 signal transduction by phosphorylation
GO:0030324 lung development
GO:0030335 positive regulation of cell migration
GO:0031659 positive regulation of cyclin-dependent protein kinase activity involved in G1/S
GO:0032355 response to estradiol
GO:0032930 positive regulation of superoxide anion generation
GO:0033590 response to cobalamin
GO:0033594 response to hydroxyisoflavone
GO:0033993 response to lipid
GO:0035413 positive regulation of catenin import into nucleus
GO:0035556 intracellular signal transduction
GO:0035690 cellular response to drug
GO:0038095 Fc-epsilon receptor signaling pathway
GO:0042059 negative regulation of epidermal growth factor receptor signaling pathway
GO:0042127 regulation of cell proliferation
GO:0042177 negative regulation of protein catabolic process
GO:0042327 positive regulation of phosphorylation
GO:0042698 ovulation cycle
GO:0042743 hydrogen peroxide metabolic process
GO:0043006 activation of phospholipase A2 activity by calcium-mediated signaling
GO:0043066 negative regulation of apoptotic process
GO:0043406 positive regulation of MAP kinase activity
GO:0043586 tongue development
GO:0045087 innate immune response (InnateDB)
GO:0045429 positive regulation of nitric oxide biosynthetic process
GO:0045739 positive regulation of DNA repair
GO:0045740 positive regulation of DNA replication
GO:0045907 positive regulation of vasoconstriction
GO:0045909 positive regulation of vasodilation
GO:0045930 negative regulation of mitotic cell cycle
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0046777 protein autophosphorylation
GO:0048011 neurotrophin TRK receptor signaling pathway
GO:0048015 phosphatidylinositol-mediated signaling
GO:0048143 astrocyte activation
GO:0048146 positive regulation of fibroblast proliferation
GO:0048546 digestive tract morphogenesis
GO:0048661 positive regulation of smooth muscle cell proliferation
GO:0048812 neuron projection morphogenesis
GO:0050679 positive regulation of epithelial cell proliferation
GO:0050729 positive regulation of inflammatory response
GO:0050730 regulation of peptidyl-tyrosine phosphorylation
GO:0050999 regulation of nitric-oxide synthase activity
GO:0051205 protein insertion into membrane
GO:0051592 response to calcium ion
GO:0051897 positive regulation of protein kinase B signaling
GO:0051968 positive regulation of synaptic transmission, glutamatergic
GO:0060571 morphogenesis of an epithelial fold
GO:0070141 response to UV-A
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0071230 cellular response to amino acid stimulus
GO:0071260 cellular response to mechanical stimulus
GO:0071363 cellular response to growth factor stimulus
GO:0071364 cellular response to epidermal growth factor stimulus
GO:0071392 cellular response to estradiol stimulus
GO:0071549 cellular response to dexamethasone stimulus
Cellular Component
GO:0000139 Golgi membrane
GO:0005615 extracellular space
GO:0005622 intracellular
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005768 endosome
GO:0005789 endoplasmic reticulum membrane
GO:0005886 plasma membrane
GO:0009986 cell surface
GO:0010008 endosome membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0016323 basolateral plasma membrane
GO:0016324 apical plasma membrane
GO:0030122 AP-2 adaptor complex
GO:0030139 endocytic vesicle
GO:0031965 nuclear membrane
GO:0043235 receptor complex
GO:0045121 membrane raft
GO:0048471 perinuclear region of cytoplasm
GO:0070435 Shc-EGFR complex
Protein Structure and Domains
InterPro IPR000494 EGF receptor, L domain
IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR006211 Furin-like cysteine-rich domain
IPR006212 Furin-like repeat
IPR009030 Insulin-like growth factor binding protein, N-terminal
IPR011009 Protein kinase-like domain
IPR016245 Tyrosine protein kinase, EGF/ERB/XmrK receptor
IPR020635 Tyrosine-protein kinase, catalytic domain
PFAM PF01030
Post-translational Modifications
SwissProt P00533
PhosphoSite PhosphoSite-P00533
UniProt Splice Variant
Entrez Gene 1956
UniGene Hs.731652
RefSeq NP_005219
OMIM 131550
HPRD 00579
EMBL AB360855 AB686642 AC006977 AC073324 AF125253 AF125538 AF125539 AF277897 AF288738 AY588246 AY698024 HQ999997 JQ739160 JQ739162 JQ739163 JQ739164 JQ739165 JQ739166 JQ739167 M11234 M38425 U48722 U48723 U48724 U48725 U48726 U48727 U48728 U48729 U95089 X00588 X00663 X06370
GenPept AAA52370 AAA63171 AAB53063 AAC50796 AAC50797 AAC50798 AAC50799 AAC50800 AAC50801 AAC50802 AAC50804 AAG35786 AAG35787 AAG35788 AAG35789 AAG35790 AAG43240 AAG43243 AAK01080 AAS07524 AAS83109 AAT97979 ADY76965 AFK93471 AFK93473 AFK93474 AFK93475 AFK93476 AFK93477 AFK93478 BAF80003 BAL41217 CAA25240 CAA25282 CAA29668