Receptor tyrosine-protein kinase erbB-4 (ErbB4), also known as Her4, is a single-pass type I transmembrane glycoprotein that is a member of the ErbB family of tyrosine kinase receptors. ErbB family members serve as receptors for the epidermal growth factor (EGF) family of growth factors. ErbB4 is expressed in normal skeletal muscle, heart, pituitary, brain and several breast carcinomas. ERBB4 contains multiple furin-like cysteine rich domains, 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-2 and -3, heparin-binding EGF-like growth factor and betacellulin. Ligand binding 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. ErbB4 appears to play important roles in neuronal development, development of the heart and cancer. ERBB4 has been shown to interact with: DLG4, NRG1, STAT5A, and YAP1. Mutations in this gene have been associated with cancer. Other single-nucleotide polymorphisms and a risk haplotype have been linked to schizophrenia.
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