EGFR

GeneName

EGFR

Summary

EGFR, also known as the epidermal growth factor receptor or Cer, is a 134kDa transmembrane protein that is primarily expressed in epithelial tissues. It is localised to various cellular compartments including the plasma membrane, endosomes, and the cytoplasm. EGFR is a receptor tyrosine kinase that plays a crucial role in cell surface receptor signalling pathways, particularly in response to epidermal growth factor (EGF). It is involved in diverse biological processes such as cell proliferation, differentiation, and survival, and mediates signal transduction through pathways like the MAPK cascade and PI3K/AKT signalling. EGFR also participates in cell-cell adhesion and is important for morphogenetic processes during development.

Importance

EGFR is relevant to: - Cancer research, particularly in the context of non-small cell lung cancer and other malignancies where EGFR mutations or overexpression are common. - Targeted therapies, including monoclonal antibodies and tyrosine kinase inhibitors that aim to block EGFR signalling in tumours. - Understanding developmental biology, as it is crucial for processes such as embryonic development and tissue regeneration. - Investigating mechanisms of resistance to cancer therapies, as alterations in EGFR signalling can contribute to treatment failure.

Top Products

For researchers investigating EGFR, we highly recommend two primary antibodies that stand out for their performance and validation. The first is the well-cited Anti-EGFR antibody [EP38Y] (ab52894), a monoclonal antibody that has garnered 450 citations, reflecting its reliability in the field. This antibody is validated for a wide range of applications, including Western blotting (WB), immunohistochemistry (IHC), immunocytochemistry (ICC), flow cytometry (FC), immunoprecipitation (IP), and ELISA, making it an excellent choice for various experimental needs. Importantly, it has also been validated in knockout models, ensuring its effectiveness in specific research contexts.Additionally, we offer the recombinant Anti-EGFR antibody [E235] (ab32077), which is also validated in knockout models and suitable for applications such as WB, IHC, ICC, FC, and IP. With 49 citations, this recombinant antibody provides the batch-to-batch consistency that many researchers seek. Together, these antibodies provide robust options for studying EGFR with confidence. The Human soluble EGFR ELISA Kit (ab269558) is a reliable option for researchers looking to measure soluble EGFR levels in their samples.

Abcam Product Citation Summary

The data indicates a significant focus on the use of Abcam antibodies targeting EGFR in various human cell lines, particularly in cancer research contexts such as breast cancer, neuroblastoma, and non-small cell lung cancer (NSCLC). The applications primarily involve Western blotting and immunohistochemistry, highlighting the importance of EGFR in studies related to cell adhesion, tumor growth, and receptor activation. Additionally, there are mentions of studies involving mouse models, suggesting a broader investigation into the role of EGFR in different biological systems.

Abcam Product Citation Table

Function

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).

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.

Involvement in disease

Lung cancer

LNCR

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.

None

The gene represented in this entry is involved in disease pathogenesis.

Neonatal nephrocutaneous inflammatory syndrome

NNCIS

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Phosphorylated on Tyr residues in response to EGF (PubMed:20462955, 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.

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). Ubiquitinated by ZNRF1 or CBL at different lysines in response to EGF stimulation; leading to recruitment of the ESCRT machinery and subsequent degradation in the lysosomes (PubMed:33996800). Deubiquitinated by UCHL1 leading to the inhibition of its degradation (By similarity).

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.

Methylated. Methylation at Arg-1199 by PRMT5 stimulates phosphorylation at Tyr-1197.

Sequence Similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.

Tissue Specificity

Ubiquitously expressed. Isoform 2 is also expressed in ovarian cancers.

Cellular 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
• In response to EGF, translocated from the cell membrane to the nucleus via Golgi and ER (PubMed:17909029, PubMed:20674546). Endocytosed upon activation by ligand (PubMed:17182860, PubMed:17909029, PubMed:27153536, PubMed:2790960). Colocalized with GPER1 in the nucleus of estrogen agonist-induced cancer-associated fibroblasts (CAF) (PubMed:20551055).
• Isoform 2
• Secreted

Alternative names

ERBB, ERBB1, HER1, EGFR, Epidermal growth factor receptor, Proto-oncogene c-ErbB-1, Receptor tyrosine-protein kinase erbB-1

Database links

swissprot:P00533 entrezGene:1956 omim:131550

Other research areas

• Immuno-oncology