Neuregulin-1/Heregulin Alpha (NRG1 A) Human Active Protein

The protein encoded by this gene is a membrane glycoprotein that that mediates cell-cell signaling and plays a critical role in the growth and development of multiple organ systems. An extraordinary variety of different isoforms are produced from this gene through alternative promoter usage and splicing. These isoforms are expressed in a tissue-specific manner and differ significantly in their structure, and are classified as types I, II, III, IV, V and VI. Dysregulation of this gene has been linked to diseases such as cancer, schizophrenia, and bipolar disorder (BPD). [provided by RefSeq, Jun 2014]

NRG1: Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. The multiple isoforms perform diverse functions such as inducing growth and differentiation of epithelial, glial, neuronal, and skeletal muscle cells; inducing expression of acetylcholine receptor in synaptic vesicles during the formation of the neuromuscular junction; stimulating lobuloalveolar budding and milk production in the mammary gland and inducing differentiation of mammary tumor cells; stimulating Schwann cell proliferation; implication in the development of the myocardium such as trabeculation of the developing heart. Isoform 10 may play a role in motor and sensory neuron development. The cytoplasmic domain interacts with the LIM domain region of LIMK1. Interacts with ERBB3 and ERBB4. Type I isoforms are the predominant forms expressed in the endocardium. Isoform alpha is expressed in breast, ovary, testis, prostate, heart, skeletal muscle, lung, placenta liver, kidney, salivary gland, small intestine and brain, but not in uterus, stomach, pancreas, and spleen. Isoform 3 is the predominant form in mesenchymal cells and in non-neuronal organs, whereas isoform 6 is the major neuronal form. Isoform 8 is expressed in spinal cord and brain. Isoform 9 is the major form in skeletal muscle cells; in the nervous system it is expressed in spinal cord and brain. Also detected in adult heart, placenta, lung, liver, kidney, and pancreas. Isoform 10 is expressed in nervous system: spinal cord motor neurons, dorsal root ganglion neurons, and brain. Predominant isoform expressed in sensory and motor neurons. Not detected in adult heart, placenta, lung, liver, skeletal muscle, kidney, and pancreas. Not expressed in fetal lung, liver and kidney. Type IV isoforms are brain-specific. Belongs to the neuregulin family. 10 isoforms of the human protein are produced by alternative splicing.

Protein type: Motility/polarity/chemotaxis; Cytokine; Cell development/differentiation; Ligand, receptor tyrosine kinase; Membrane protein, integral

Chromosomal Location of Human Ortholog: 8p12

Cellular Component: extracellular space; membrane; integral to plasma membrane; axon; apical plasma membrane; cytoplasm; extracellular region; nucleus; neuromuscular junction

Molecular Function: ErbB-2 class receptor binding; transmembrane receptor protein tyrosine kinase activator activity; protein binding; ErbB-3 class receptor binding; growth factor activity; cytokine activity; transcription cofactor activity; protein tyrosine kinase activator activity; receptor tyrosine kinase binding; receptor binding

Biological Process: regulation of protein heterodimerization activity; positive regulation of cell adhesion; transmembrane receptor protein tyrosine kinase activation (dimerization); nerve growth factor receptor signaling pathway; neural crest cell development; cellular protein complex disassembly; wound healing; ventricular cardiac muscle cell differentiation; cell morphogenesis; locomotory behavior; positive regulation of striated muscle cell differentiation; cardiac muscle cell differentiation; synaptogenesis; mammary gland development; cell communication; positive regulation of cardiac muscle cell proliferation; epidermal growth factor receptor signaling pathway; nervous system development; cell migration; phosphoinositide-mediated signaling; fibroblast growth factor receptor signaling pathway; neurotransmitter receptor metabolic process; regulation of protein homodimerization activity; MAPKKK cascade; neuron fate commitment; positive regulation of cell growth; peripheral nervous system development; positive regulation of protein kinase B signaling cascade; cell proliferation; embryonic development; glial cell fate commitment; innate immune response; negative regulation of secretion; positive regulation of Ras protein signal transduction; negative regulation of transcription, DNA-dependent; negative regulation of protein catabolic process; transmembrane receptor protein tyrosine kinase signaling pathway

Disease: Schizophrenia 6