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: Protein kinase, TK; Kinase, protein; Protein kinase, tyrosine (receptor); Membrane protein, integral; EC 2.7.10.1; TK group; EGFR family
Chromosomal Location of Human Ortholog: 2q33.3-q34
Cellular Component: basolateral plasma membrane; cytosol; extracellular region; mitochondrial matrix; mitochondrion; nucleoplasm; nucleus; plasma membrane; receptor complex
Molecular Function: epidermal growth factor receptor binding; phosphatidylinositol-4,5-bisphosphate 3-kinase activity; protein binding; protein homodimerization activity; protein-tyrosine kinase activity; Ras guanyl-nucleotide exchange factor activity; transmembrane receptor protein tyrosine kinase activity
Biological Process: cell migration; cell proliferation; central nervous system morphogenesis; embryonic pattern specification; heart development; lactation; MAPKKK cascade; mitochondrial fragmentation during apoptosis; negative regulation of cell proliferation; nervous system development; neural crest cell migration; olfactory bulb interneuron differentiation; peptidyl-tyrosine phosphorylation; phosphoinositide-mediated signaling; positive regulation of cardiac muscle cell proliferation; positive regulation of cell proliferation; positive regulation of protein amino acid phosphorylation; positive regulation of transcription, DNA-dependent; positive regulation of tyrosine phosphorylation of Stat5 protein; protein amino acid autophosphorylation; regulation of cell migration; regulation of phosphoinositide 3-kinase cascade; signal transduction; transmembrane receptor protein tyrosine kinase signaling pathway
Disease: Amyotrophic Lateral Sclerosis 19
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