Pro-neuregulin-1, membrane-bound isoform (Q02297)

Uniprot ID	Q02297
Protein Name	Pro-neuregulin-1, membrane-bound isoform
Gene Name	NRG1
Species	Homo sapiens (Human)

Signal peptide^(a)	N	Secretome P^(b)	0.047
Function	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. Binds to ERBB4 (PubMed:10867024, PubMed:7902537). Binds to ERBB3 (PubMed:20682778). Acts as a ligand for integrins and binds (via EGF domain) to integrins ITGAV:ITGB3 or ITGA6:ITGB4. Its binding to integrins and subsequent ternary complex formation with integrins and ERRB3 are essential for NRG1-ERBB signaling. Induces the phosphorylation and activation of MAPK3/ERK1, MAPK1/ERK2 and AKT1 (PubMed:20682778). Ligand-dependent ERBB4 endocytosis is essential for the NRG1-mediated activation of these kinases in neurons (By similarity). .
GO - Molecular function	chemorepellent activity : IEA:Ensembl cytokine activity : TAS:BHF-UCL ErbB-2 class receptor binding : IEA:Ensembl ErbB-3 class receptor binding : IDA:BHF-UCL growth factor activity : IDA:BHF-UCL integrin binding : IDA:UniProtKB protein tyrosine kinase activator activity : IDA:BHF-UCL receptor tyrosine kinase binding : NAS:UniProtKB signaling receptor binding : IPI:BHF-UCL transcription coregulator activity : IDA:MGI transmembrane receptor protein tyrosine kinase activator activity : NAS:UniProtKB
GO - Biological process	activation of MAPK activity : IMP:UniProtKB activation of protein kinase B activity : IMP:UniProtKB activation of transmembrane receptor protein tyrosine kinase activity : IDA:BHF-UCL cardiac conduction system development : IEA:Ensembl cardiac muscle cell differentiation : ISS:BHF-UCL cardiac muscle cell myoblast differentiation : IDA:BHF-UCL cell communication : TAS:BHF-UCL cell morphogenesis : IEA:Ensembl cell population proliferation : IDA:BHF-UCL cellular protein complex disassembly : IGI:MGI chemorepulsion involved in interneuron migration from the subpallium to the cortex : IEA:Ensembl endocardial cell differentiation : IDA:BHF-UCL ERBB signaling pathway : IDA:BHF-UCL ERBB2 signaling pathway : TAS:Reactome ERBB3 signaling pathway : IDA:CAFA ERBB4 signaling pathway : IDA:UniProtKB glial cell fate commitment : IEA:Ensembl intracellular signal transduction : IBA:GO_Central locomotory behavior : IEA:Ensembl mammary gland development : TAS:BHF-UCL MAPK cascade : TAS:Reactome myelination in peripheral nervous system : IEA:Ensembl negative regulation of cardiac muscle cell apoptotic process : IDA:BHF-UCL negative regulation of extrinsic apoptotic signaling pathway in absence of ligand : IDA:BHF-UCL negative regulation of neuron migration : IEA:Ensembl negative regulation of protein catabolic process : IEA:Ensembl negative regulation of secretion : IDA:BHF-UCL negative regulation of transcription, DNA-templated : IDA:MGI nervous system development : IBA:GO_Central neural crest cell development : TAS:BHF-UCL neuron fate commitment : IEA:Ensembl neurotransmitter receptor metabolic process : IEA:Ensembl oligodendrocyte differentiation : IEA:Ensembl positive regulation of calcineurin-NFAT signaling cascade : IEA:Ensembl positive regulation of cardiac muscle cell differentiation : IEA:Ensembl positive regulation of cardiac muscle cell proliferation : IDA:BHF-UCL positive regulation of cell adhesion : IDA:BHF-UCL positive regulation of cell growth : IDA:BHF-UCL positive regulation of cell population proliferation : IMP:UniProtKB positive regulation of gene expression : IEA:Ensembl positive regulation of peptidyl-tyrosine autophosphorylation : IDA:UniProtKB positive regulation of protein kinase B signaling : TAS:Reactome positive regulation of Ras protein signal transduction : IEA:Ensembl positive regulation of striated muscle cell differentiation : ISS:BHF-UCL postsynapse to nucleus signaling pathway : IEA:Ensembl regulation of cell motility : TAS:Reactome regulation of postsynaptic neurotransmitter receptor internalization : IDA:SynGO regulation of protein heterodimerization activity : IDA:BHF-UCL regulation of protein homodimerization activity : TAS:BHF-UCL synapse assembly : IEA:Ensembl synaptic membrane adhesion : IDA:SynGO transmembrane receptor protein tyrosine kinase signaling pathway : IDA:BHF-UCL ventricular cardiac muscle cell differentiation : IDA:BHF-UCL ventricular trabecula myocardium morphogenesis : IDA:BHF-UCL wound healing : IDA:BHF-UCL

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^{(a) The Signal peptide D-score cutoff for "YES"(having signal peptide) is 0.45.}
^{(b) Non-classically secreted proteins should obtain an NN-score(Neural Networks score) exceeding the normal threshold of 0.5, but not at the same time be predicted to contain a signal peptide.}