EGFR Antibody – Mouse Monoclonal

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]

Function: Cell surface receptor for EGF, but also for other members of the EGF family, such as TGF-alpha, BTC/betacellulin, AREGAREGB/amphiregulin, HBEGF, GP30 and vaccinia virus growth factor. Ligand binding triggers a conformation change, leading to activation of the kinase and subsequent phosphorylation of down-stream protein kinases. Is involved in the control of cell growth, proliferation and differentiation. Phosphorylates MUC1 in breast cancer cells and increases the interaction of MUC1 with SRC and CTNNB1/beta-catenin. Ref.33 Ref.54 Ref.55 Ref.56 Ref.60 Ref.63 Ref.65Isoform 2 may act as an antagonist of EGF action. Ref.33 Ref.54 Ref.55 Ref.56 Ref.60 Ref.63 Ref.65

Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.56 Ref.59 Ref.60 Ref.61 Ref.62 Ref.63

Subunit structure: EGF binding triggers dimerization of the receptor and promotes autophosphorylation. The activate receptor dimer binds one EGF molecule. Heterodimer with ERBB2. Interacts with ERRFI1. Interaction with ERRFI1 inhibits dimerization of the kinase domain and autophosphorylation. Binds RIPK1. Interacts (via autophosphorylated C-terminal tail) with CBL. Part of a complex with ERBB2 and either PIK3C2A or PIK3C2B. Interacts (autophosphorylated form) with PIK3C2B; the interaction may be indirect. Interacts with PELP1. Binds MUC1. Interacts with AP2M1. Interacts with GAB2. Interacts with COPG, upon EGF treatment; interaction is 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. Ref.26 Ref.28 Ref.31 Ref.32 Ref.33 Ref.37 Ref.41 Ref.44 Ref.52 Ref.54 Ref.55 Ref.60 Ref.62 Ref.63 Ref.64 Ref.65

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. Note: In response to EGF, translocated from the cell membrane to the nucleus via Golgi and ER. Co-localizes with TNK2 on the endosomes. Ref.41 Ref.52 Ref.54 Ref.63Isoform 2: Secreted Ref.41 Ref.52 Ref.54 Ref.63.

Tissue specificity: Ubiquitously expressed. Isoform 2 is also expressed in ovarian cancers. Ref.40

Post-translational modification: Phosphorylation of Ser-695 is partial and occurs only if Thr-693 is phosphorylated. Ref.17 Ref.25 Ref.30 Ref.34 Ref.35 Ref.36 Ref.38 Ref.39 Ref.42 Ref.43 Ref.45 Ref.46 Ref.47 Ref.48 Ref.50 Ref.51 Ref.59 Ref.60 Ref.62 Ref.63Monoubiquitinated and polyubiquitinated upon EGF stimulation; which does not affect tyrosine kinase activity or signaling capacity but may play a role in lysosomal targeting. Polyubiquitin linkage is mainly through 'Lys-63', but linkage through 'Lys-48', 'Lys-11' and 'Lys-29' also occur.

Involvement in disease: Defects in EGFR are associated with lung cancer (LNCR) [

MIM:211980].

Miscellaneous: Binding of EGF to the receptor leads to dimerization, internalization of the EGF-receptor complex, induction of the tyrosine kinase activity, stimulation of cell DNA synthesis, and cell proliferation.

Sequence similarities: Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.Contains 1 protein kinase domain.