Tyrosine Kinase Erbb-3 (ErbB3) Human Active Protein

This gene encodes a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. This membrane-bound protein has a neuregulin binding domain but not an active kinase domain. It therefore can bind this ligand but not convey the signal into the cell through protein phosphorylation. However, it does form heterodimers with other EGF receptor family members which do have kinase activity. Heterodimerization leads to the activation of pathways which lead to cell proliferation or differentiation. Amplification of this gene and/or overexpression of its protein have been reported in numerous cancers, including prostate, bladder, and breast tumors. Alternate transcriptional splice variants encoding different isoforms have been characterized. One isoform lacks the intermembrane region and is secreted outside the cell. This form acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported, but they have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

HER3: a receptor tyrosine kinase of the EGFR family. Binds and is activated by neuregulins and NTAK. Can form homodimers or ErbB-2/ErbB-3 heterodimers. Kinase domain lacks activity but heterodimerizes with other EGFRs to transduce growth signals. May be required for HER2 activity. Elevated expression in breast and other tumors is indicative of poor outcome. A secreted form is expressed in metastatic prostate cancer Two alternatively spliced isoforms have been described.

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

Chromosomal Location of Human Ortholog: 12q13

Cellular Component: extracellular space; integral to plasma membrane; basolateral plasma membrane; apical plasma membrane; plasma membrane; lateral plasma membrane; receptor complex

Molecular Function: identical protein binding; protein binding; transmembrane receptor activity; protein homodimerization activity; protein heterodimerization activity; protein-tyrosine kinase activity; growth factor binding; protein tyrosine kinase activator activity; ATP binding

Biological Process: epidermal growth factor receptor signaling pathway; phosphoinositide 3-kinase cascade; fibroblast growth factor receptor signaling pathway; phosphoinositide-mediated signaling; wound healing; nerve growth factor receptor signaling pathway; heart development; cranial nerve development; negative regulation of cell adhesion; signal transduction; protein amino acid phosphorylation; peripheral nervous system development; regulation of cell proliferation; negative regulation of signal transduction; positive regulation of phosphoinositide 3-kinase cascade; Schwann cell differentiation; neuron apoptosis; innate immune response; negative regulation of secretion; negative regulation of neuron apoptosis; transmembrane receptor protein tyrosine kinase signaling pathway

Disease: Lethal Congenital Contracture Syndrome 2