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); Kinase, protein; EC 2.7.10.1; Protein kinase, TK; Membrane protein, integral; Oncoprotein; TK group; EGFR family
Chromosomal Location of Human Ortholog: 17q12
Cellular Component: perinuclear region of cytoplasm; basolateral plasma membrane; cytoplasm; apical plasma membrane; integral to membrane; plasma membrane; endosome membrane; cytoplasmic vesicle; nucleus; receptor complex
Molecular Function: protein dimerization activity; protein C-terminus binding; identical protein binding; protein binding; transmembrane receptor activity; ErbB-3 class receptor binding; protein heterodimerization activity; protein-tyrosine kinase activity; growth factor binding; transmembrane receptor protein tyrosine kinase activity; receptor signaling protein tyrosine kinase activity; protein phosphatase binding; ATP binding
Biological Process: myelination; axon guidance; phosphoinositide 3-kinase cascade; peptidyl-tyrosine phosphorylation; positive regulation of cell adhesion; wound healing; nerve growth factor receptor signaling pathway; positive regulation of translation; heart development; protein amino acid autophosphorylation; motor axon guidance; signal transduction; enzyme linked receptor protein signaling pathway; protein amino acid phosphorylation; positive regulation of transcription from RNA polymerase I promoter; positive regulation of MAP kinase activity; cell surface receptor linked signal transduction; oligodendrocyte differentiation; neuromuscular junction development; epidermal growth factor receptor signaling pathway; negative regulation of immature T cell proliferation in the thymus; regulation of microtubule-based process; phosphoinositide-mediated signaling; fibroblast growth factor receptor signaling pathway; transcription, DNA-dependent; regulation of angiogenesis; positive regulation of cell growth; peripheral nervous system development; cell proliferation; positive regulation of transcription from RNA polymerase III promoter; innate immune response; positive regulation of protein amino acid phosphorylation; positive regulation of epithelial cell proliferation; transmembrane receptor protein tyrosine kinase signaling pathway
Disease: Gastric Cancer; Lung Cancer; Glioma Susceptibility 1
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