EGFR

As a member of the epidermal growth factor receptor (EGFR) family, EGFR protein is type I transmembrane glycoprotein that binds a subset of EGF family ligands including EGF, amphiregulin, TGF-α, betacellulin, etc. EGFR protein plays a crucial role in signaling pathway in the regulation of cell proliferation, survival and differentiation. Binding of a ligand induces EGFR protein homo- or heterodimerization, the subsequent tyrosine autophosphorylation and initiates various down stream pathways (MAPK, PI3K/PKB and STAT). In addition, EGFR signaling also has been shown to exert action on carcinogenesis and disease progression, and thus EGFR protein is proposed as a target for cancer therapy currently.

EGFR Related Areas

Enzyme>>Protein Kinase>>Receptor Tyrosine Kinase>>EGFR/ErbB/HER1

Signal Transduction>>Protein Kinase>>Receptor Tyrosine Kinase>>EGFR/ErbB/HER1

Cancer>>Cancer Stem Cell (CSC)>>EGFR/ErbB/HER1

Cancer>>Cancer Biomarkers>>EGFR/ErbB/HER1

Cancer>>Growth Factor & Receptor>>EGF Family & Receptor>>EGFR/ErbB/HER1

Cancer>>Growth Factor & Receptor>>Receptor Tyrosine Kinase>>EGFR/ErbB/HER1

Cancer>>Growth Factor & Receptor>>Receptor Tyrosine Kinase>>EGFR/ErbB/HER1

EGFR Related Pathways

• EGFR Signaling Pathway

EGFR Alternative Names

EGFR, ERBB, ERBB1, HER1, PIG61, mENA [Homo sapiens]
Egfr, Erbb, RP23-295E4.1, 9030024J15Rik, AI552599, Errp, Wa5, wa-2, wa2 [Mus musculus]
Egfr, ERBB1, ErbB-1, Errp [Rattus norvegicus]

Summaries for EGFR

The protein encoded by this gene is a transmembrane glycoprotein that is a member of the protein kinase superfamily. This protein is a receptor for members of the epidermal growth factor family. EGFR is a cell surface protein that binds to epidermal growth factor. Binding of the protein to a ligand induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation. Mutations in this gene are associated with lung cancer. Multiple alternatively spliced transcript variants that encode different protein isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

 

EGFR and its ligands are cell signaling molecules involved in diverse cellular functions, including cell proliferation, differentiation, motility, and survival, and in tissue development (Wang et al., 2004).

 

The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is the cell-surface receptor for members of the epidermal growth factor family (EGF-family) of extracellular protein ligands.[2] The epidermal growth factor receptor is a member of the ErbB family of receptors, a subfamily of four closely related receptor tyrosine kinases: EGFR (ErbB-1), HER2/c-neu (ErbB-2), Her 3 (ErbB-3) and Her 4 (ErbB-4). Mutations affecting EGFR expression or activity could result in cancer.[3] Epidermal Growth Factor was discovered by Stanley Cohen of Vanderbilt University along with Rita Levi-Montalcini for which both received the Nobel prize in Physiology or Medicine in 1986.

 

Human EGFR Protein General Information

 

• Protein names: Recommended name: Epidermal growth factor receptor
  Short Name: EGFR
• Sequence length: 1210 AA
• Domain: Repeat.Signal Transmembrane.Transmembrane.helix
• Sequence similarities: Belongs to the protein kinase superfamily. Tyr protein kinase family. EGFR receptor subfamily. Contains 1 protein kinase domain.
• Post-translational modification: Phosphorylated. Phosphorylation of Ser-695 is partial and occurs only if Thr-693 is phosphorylated. 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.
• Subunit structure: 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 COPG; 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.
• 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 EGFR, translocated from the cell membrane to the nucleus via Golgi and ER. Endocytosed upon activation by ligand.
• Tissue specificity: Ubiquitously expressed. Isoform 2 is also expressed in ovarian cancers.
• Involvement in disease: Defects in EGFR are associated with lung cancer (LNCR) [MIM:211980].

General information above from UniProt

Function for EGFR Protein

UniProtKB:

EGFR (epidermal growth factor receptor) exists on the cell surface and is activated by binding of its specific ligands, including epidermal growth factor and transforming growth factor α (TGFα) (note, a full list of the ligands able to activate EGFR and other members of the ErbB family is given in the ErbB article). ErbB2 has no known direct activating ligand, and may be in an activated state constitutively or become active upon heterodimerization with other family members such as EGFR. Upon activation by its growth factor ligands, EGFR undergoes a transition from an inactive monomeric form to an active homodimer[4] - although there is some evidence that preformed inactive dimers may also exist before ligand binding[citation needed]. In addition to forming homodimers after ligand binding, EGFR may pair with another member of the ErbB receptor family, such as ErbB2/Her2/neu, to create an activated heterodimer. There is also evidence to suggest that clusters of activated EGFRs form, although it remains unclear whether this clustering is important for activation itself or occurs subsequent to activation of individual dimers[citation needed].

Genatlas:

• EGFR acting as a receptor for EGF, but also for other members of the EGF family, as TGF-alpha, amphiregulin, betacellulin, heparin-binding EGF-like growth factor, GP30 and vaccinia virus growth factor
• EGFR is involved in the control of cell growth and differentiation
• EGFR is involved in early craniofacial development and palate closure and in keratinocyte differentiation
• EGFRactivating phosphatidylinositol and Ras pathways
• mediating the activities of both myelin inhibitors and chondroitin sulfate proteoglycans in inhibiting neurite outgrowth
• EGFR is involved in the pathogenesis and progression of different carcinoma types
• EGFR signaling is negatively regulated by CPEB3 in neurons (Pubmed 20639532)

Homology for human EGFR

• ortholog to murine Egfr
• homolog to drosophila Egfr
• homolog to zebrafish egfr

Phenotype Information for EGFR

• Gene/Locus: ERBB1 HER1 SPECIES ANTIGEN 7
• Phenotype: Adenocarcinoma of lung, response to tyrosine kinase inhibitor in Nonsmall cell lung cancer, response to tyrosine kinase inhibitor in {Nonsmall cell lung cancer, susceptibility to}

Phenotype Information for EGFR from OMIM (Online Mendelian Inheritance in Man)

Drugs for EGFR

Target	Drug Name	Disease	Drug Status
EGFR	Cetuximab DAP000394	Colorectal Cancer	Approved
EGFR	Lapatinib DAP000853	Breast cancer	Approved
EGFR	Panitumumab DAP001009	Colorectal Cancer	Approved
EGFR	Erlotinib DAP001010	Non-small cell lung cancer	Launched
EGFR	Tyverb/Tykerb DAP001451	Refractory breast cancer	Approved
EGFR	DWP-401 DAP001472	Diabetic foot ulcers	Launched
EGFR	HEGF DAP001482	Diabetic foot ulcers	Launched

Drugs for EGFR from TTD (Therapeutic Targets Database)