Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536, PubMed:2790960, PubMed:35538033). Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF (PubMed:12297049, PubMed:15611079, PubMed:17909029, PubMed:20837704, PubMed:27153536, PubMed:2790960, PubMed:7679104, PubMed:8144591, PubMed:9419975). 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). 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 (PubMed:20462955).
Plays a role in enhancing learning and memory performance (By similarity). Plays a role in mammalian pain signaling (long-lasting hypersensitivity) (By similarity)
Binding of the ligand triggers homo- and/or heterodimerization of the receptor triggering its autophosphorylation. Heterodimer with ERBB2 (PubMed:10805725). Forms a complex with CCDC88A/GIV (via SH2-like regions) and GNAI3 which leads to enhanced EGFR signaling and triggering of cell migration; binding to CCDC88A requires autophosphorylation of the EGFR C-terminal region, and ligand stimulation is required for recruitment of GNAI3 to the complex (PubMed:20462955, PubMed:25187647).
Interacts with ERRFI1; inhibits dimerization of the kinase domain and autophosphorylation (PubMed:18046415). Part of a complex with ERBB2 and either PIK3C2A or PIK3C2B (PubMed:10805725). 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, CBLB and CBLC; involved in EGFR ubiquitination and regulation; interaction with CBL is reduced in the presence of tensin TNS4 (PubMed:23774213). Interacts with SOCS5; regulates EGFR degradation through ELOC- and ELOB-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 (PubMed:17115032). 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 (PubMed:10026169). Interacts with ATXN2. Interacts with GAREM1.
Interacts (ubiquitinated) with ANKRD13A/B/D; the interaction is direct and may regulate EGFR internalization after EGF stimulation. Interacts with GPER1; the interaction occurs in an estrogen-dependent manner. Interacts (via C-terminal cytoplasmic kinase domain) with ZPR1 (via zinc fingers).
Interacts with RNF115 and RNF126 (PubMed:23418353). Interacts with GPRC5A (via its transmembrane domain) (PubMed:25311788). Interacts with FAM83B; positively regulates EGFR inducing its autophosphorylation in absence of stimulation by EGF (PubMed:23912460).
Interacts with LAPTM4B; positively correlates with EGFR activation (PubMed:28479384). Interacts with STX19 (PubMed:16420529). Interacts with CD44 (PubMed:23589287).
Interacts with PGRMC1; the interaction requires PGRMC1 homodimerization (PubMed:26988023). Interacts with PIKFYVE (PubMed:17909029). Interacts with NEU3.
Interacts with TRAF4 (PubMed:30352854). Interacts with the ant venom OMEGA-myrmeciitoxin(02)-Mg1a (By similarity). Interacts with CD82; this interaction facilitates ligand-induced endocytosis of the receptor and its subsequent desensitization (PubMed:35538033).
Interacts with SNX32; the interaction is required for endolysosomal EGFR trafficking (PubMed:39073202)
Ubiquitously expressed. Isoform 2 is also expressed in ovarian cancers
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.
An autosomal recessive disorder characterized by intrauterine growth retardation, premature birth, fragile skin, recurrent skin infections and sepsis, failure to thrive, nephrocalcinosis, and nephromegaly with tubular dysfunction. Some patients have chronic diarrhea, and necrotizing enterocolitis.
Click a pathway to open the interactive Reactome viewer.
Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to EGFR, aggregated across our SSL data sources. Click any partner node to view that gene’s page.
Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.
Total Trials Found: 2420
| NCT ID | Condition | Brief Title | Phase | Status |
|---|---|---|---|---|
| NCT02229435 | Chronic Kidney Disease (CKD) | Urologic-nephrological Care of Chronic Kidney Disease in Saxony-Anhalt/Magdeburg. | N/A | COMPLETED |
| NCT07074418 | Chronic Kidney Diseases | Effect of Empagliflozin in Patients With eGFR Between 10 and 20 ml/Min/1.73m2 | PHASE4 | NOT_YET_RECRUITING |
| NCT05132413 | Advanced or Metastatic Non-squamous Non-small-cell Lung Cancer | A Study of SHR-1701 Plus Bevacizumab and Chemotherapy in Non-Small-Cell-Lung-Cancer | PHASE3 | UNKNOWN |
| NCT07545213 | Non-small Cell Lung Cancer, EGFR Mutant Advanced Non-small Cell Lung Cancer | Efficacy and Safety of SKB264 Plus Anlotinib in EGFR-TKI-Resistant Advanced NSCLC With Liver Metastasis | PHASE2 | NOT_YET_RECRUITING |
| NCT05360368 | Solid Tumor | HLX07(Anti-EGFR mAb) in Patients With Advanced or Metastatic Solid Tumors | PHASE1 | UNKNOWN |
| NCT03766490 | Non-Small-Cell Lung | Anlotinib Hydrochloride Combined With EGFR TKIs in Advanced Non-small Cell Lung Cancer | NA | UNKNOWN |
| NCT03239340 | EGFR Mutation Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer | A Molecular Profiling Study of Patients With EGFR Mutation-positive Locally Advanced or Metastatic NSCLC Treated With Osimertinib | PHASE2 | COMPLETED |
| NCT04222335 | Lung Cancer, Nonsmall Cell | Understanding and Overcoming the Early Adaptive Resistance to EGFR Tyrosine-kinase Inhibitors in Lung Cancer Patients | NA | ACTIVE_NOT_RECRUITING |
| NCT03424759 | Non Small Cell Lung Cancer | Uncommon EGFR AZD9291 | PHASE2 | UNKNOWN |
| NCT02113813 | Non-Small-Cell Lung Cancer (NSCLC), Epidermal Growth Factor Receptor Mutations | A Dose Escalation Study of ASP8273 in Subjects With Non-Small-Cell Lung Cancer (NSCLC) Who Have Epidermal Growth Factor Receptor (EGFR) Mutations | PHASE1 | COMPLETED |