Receptor Tyrosine-Protein Kinase Erbb-2 (ERBB2) Human Active Protein

This gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. This protein has no ligand binding domain of its own and therefore cannot bind growth factors. However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase. Allelic variations at amino acid positions 654 and 655 of isoform a (positions 624 and 625 of isoform b) have been reported, with the most common allele, Ile654/Ile655, shown here. Amplification and/or overexpression of this gene has been reported in numerous cancers, including breast and ovarian tumors. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized. [provided by RefSeq, Jul 2008]

HER2: a proto-oncogenic receptor tyrosine kinase of the EGFR family. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. Not activated by EGF, TGF- alpha and amphiregulin. Amplified in breast cancer. Overexpression induces constitutive activity, and the gene is amplified or overexpressed in up to 30% of breast cancers, correlating with poor survival. The antibody Herceptin is approved for treatment of metastatic breast cancer with HER2 amplification/overexpression. Somatic mutations seen in 4% of lung cancers and also in breast, gastric, ovarian cancer and glioblastoma. One SNP shows predisposition to breast and gastric cancer. Inhibitors: Herceptin, lapatinib, PKI-166, EKB-569, CI-1033.

Protein type: Protein kinase, tyrosine (receptor); Protein kinase, TK; Kinase, protein; Membrane protein, integral; EC 2.7.10.1; Oncoprotein; TK group; EGFR family

Chromosomal Location of Human Ortholog: 17q12

Cellular Component: apical plasma membrane; basolateral plasma membrane; cytoplasm; cytoplasmic vesicle; endosome membrane; integral to membrane; myelin sheath; nucleus; perinuclear region of cytoplasm; plasma membrane; receptor complex

Molecular Function: ATP binding; ErbB-3 class receptor binding; growth factor binding; identical protein binding; protein binding; protein C-terminus binding; protein dimerization activity; protein heterodimerization activity; protein phosphatase binding; protein-tyrosine kinase activity; receptor signaling protein tyrosine kinase activity; transmembrane receptor activity; transmembrane receptor protein tyrosine kinase activity

Biological Process: activation of MAPKK activity; axon guidance; cell proliferation; cell surface receptor linked signal transduction; enzyme linked receptor protein signaling pathway; epidermal growth factor receptor signaling pathway; fibroblast growth factor receptor signaling pathway; heart development; innate immune response; insulin receptor signaling pathway; MAPKKK cascade; motor axon guidance; myelination; negative regulation of immature T cell proliferation in the thymus; nerve growth factor receptor signaling pathway; neuromuscular junction development; oligodendrocyte differentiation; peptidyl-tyrosine phosphorylation; peripheral nervous system development; phosphoinositide 3-kinase cascade; phosphoinositide-mediated signaling; positive regulation of cell adhesion; positive regulation of cell growth; positive regulation of epithelial cell proliferation; positive regulation of GTPase activity; positive regulation of MAP kinase activity; positive regulation of protein amino acid phosphorylation; positive regulation of transcription from RNA polymerase I promoter; positive regulation of transcription from RNA polymerase III promoter; positive regulation of translation; protein amino acid autophosphorylation; protein amino acid phosphorylation; Ras protein signal transduction; regulation of angiogenesis; regulation of microtubule-based process; signal transduction; small GTPase mediated signal transduction; transcription, DNA-dependent; transmembrane receptor protein tyrosine kinase signaling pathway; vascular endothelial growth factor receptor signaling pathway; wound healing

Disease: Gastric Cancer; Glioma Susceptibility 1; Lung Cancer