Erbb4/HER4 (ERBB4) Active Protein

This gene is a member of the Tyr protein kinase family and the epidermal growth factor receptor subfamily. It encodes a single-pass type I membrane protein with multiple cysteine rich domains, a transmembrane domain, a tyrosine kinase domain, a phosphotidylinositol-3 kinase binding site and a PDZ domain binding motif. The protein binds to and is activated by neuregulins and other factors and induces a variety of cellular responses including mitogenesis and differentiation. Multiple proteolytic events allow for the release of a cytoplasmic fragment and an extracellular fragment. Mutations in this gene have been associated with cancer. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

HER4: a receptor tyrosine kinase of the EGFR family. Specifically binds and is activated by neuregulins, NRG- 2, NRG-3, heparin-binding EGF-like growth factor, betacellulin and NTAK. Heterodimerizes and signals with other EGF receptors. Interaction with these factors induces cell differentiation. Not activated by EGF, TGF-A, and amphiregulin. Interacts with PDZ domains of DLG2, DLG3, DLG4 and the syntrophin SNTB2. Interacts with WWOX. May act as a tumor suppressor: overexpressed in head and neck cancer , but downregulated in renal cancer, papillary carcinoma, high-grade gliomas and invasive breast cancer. 3 alternatively-spliced isoforms of the human protein have been reported.

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

Chromosomal Location of Human Ortholog: 2q33.3-q34

Cellular Component: nucleoplasm; mitochondrion; basolateral plasma membrane; mitochondrial matrix; plasma membrane; extracellular region; integral to membrane; cytosol; nucleus; receptor complex

Molecular Function: protein binding; protein homodimerization activity; protein-tyrosine kinase activity; transmembrane receptor protein tyrosine kinase activity; receptor signaling protein tyrosine kinase activity; ATP binding; epidermal growth factor receptor binding

Biological Process: lactation; peptidyl-tyrosine phosphorylation; nerve growth factor receptor signaling pathway; protein amino acid autophosphorylation; heart development; positive regulation of transcription, DNA-dependent; signal transduction; embryonic pattern specification; regulation of cell migration; olfactory bulb interneuron differentiation; negative regulation of cell proliferation; positive regulation of cell proliferation; neural crest cell migration; positive regulation of cardiac muscle cell proliferation; epidermal growth factor receptor signaling pathway; nervous system development; cell migration; cell fate commitment; fibroblast growth factor receptor signaling pathway; phosphoinositide-mediated signaling; transcription, DNA-dependent; positive regulation of phosphoinositide 3-kinase activity; cell proliferation; central nervous system morphogenesis; positive regulation of tyrosine phosphorylation of Stat5 protein; innate immune response; mitochondrial fragmentation during apoptosis; positive regulation of protein amino acid phosphorylation; transmembrane receptor protein tyrosine kinase signaling pathway; negative regulation of apoptosis

Disease: Amyotrophic Lateral Sclerosis 19