HER2/neu Antibody – Rat Monoclonal

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

Chromosomal Location of Human Ortholog: 17q12

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

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

Biological Process: myelination; axon guidance; phosphoinositide 3-kinase cascade; positive regulation of cell adhesion; peptidyl-tyrosine phosphorylation; positive regulation of translation; wound healing; nerve growth factor receptor signaling pathway; protein amino acid autophosphorylation; heart development; motor axon guidance; signal transduction; protein amino acid phosphorylation; enzyme linked receptor protein signaling pathway; 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; fibroblast growth factor receptor signaling pathway; phosphoinositide-mediated signaling; transcription, DNA-dependent; positive regulation of cell growth; regulation of angiogenesis; peripheral nervous system development; cell proliferation; innate immune response; positive regulation of transcription from RNA polymerase III promoter; 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