Nrg1
Domain
The cytoplasmic domain may be involved in the regulation of trafficking and proteolytic processing. Regulation of the proteolytic processing involves initial intracellular domain dimerization.
ERBB receptor binding is elicited entirely by the EGF-like domain.
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. Binds to ERBB4 and ERBB3. 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 (By similarity). Induces the phosphorylation and activation of MAPK3/ERK1, MAPK1/ERK2 and AKT1, and ligand-dependent ERBB4 endocytosis is essential for the NRG1-mediated activation of these kinases in neurons (PubMed:17250808).
Post-translational modifications
Proteolytic cleavage close to the plasma membrane on the external face leads to the release of the soluble growth factor form.
N- and O-glycosylated (By similarity). Extensive glycosylation precedes the proteolytic cleavage.
Sequence Similarities
Belongs to the neuregulin family.
Tissue Specificity
Widely expressed. Most tissues contain isoform alpha2A and isoform alpha2B. Isoform Alpha2 and isoform beta2 are the predominant forms in mesenchymal and non-neuronal organs. Isoform Beta1 is enriched in brain and spinal cord, but not in muscle and heart. Isoform Alpha2C is highly expressed in spinal cord, moderately in lung, brain, ovary, and stomach, in low amounts in the kidney, skin and heart and not detected in the liver, spleen, and placenta.
Cellular localization
- Pro-neuregulin-1, membrane-bound isoform
- Cell membrane
- Single-pass type I membrane protein
- Does not seem to be active.
- Neuregulin-1
- Secreted
Alternative names
Ndf, Nrg1, Pro-NRG1