NRG1
Description
The NRG1 (neuregulin 1) is a protein-coding gene located on chromosome 8.
Neuregulin 1, or NRG1, is a gene belonging to the epidermal growth factor family that is encoded by the NRG1 gene in humans. NRG1 is one of four proteins in the neuregulin family that interact with the EGFR family of receptors. NRG1 is produced in numerous isoforms through alternative splicing, enabling it to perform a wide range of functions. It is crucial for the normal development of the nervous system and the heart.
== Structure == Neuregulin 1 (NRG1) was initially identified as a 44-kD glycoprotein that interacts with the NEU/ERBB2 receptor tyrosine kinase to enhance its phosphorylation on tyrosine residues. The NRG1 gene produces an exceptional variety of different isoforms through alternative splicing. These isoforms include heregulins (HRGs), glial growth factors (GGFs), and sensory and motor neuron-derived factor (SMDF). They exhibit tissue specificity and significant structural differences. All HRG isoforms contain immunoglobulin (Ig) and epidermal growth factor-like (EGF-like) domains. GGF and GGF2 isoforms include a kringle-like sequence in addition to Ig and EGF-like domains; the SMDF isoform shares only the EGF-like domain with other isoforms.
Neuregulin 1 (NRG1) is a direct ligand for the ERBB3 and ERBB4 tyrosine kinase receptors, also recruiting ERBB1 and ERBB2 coreceptors, leading to ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. NRG1's diverse isoforms have various functions, including inducing growth and differentiation of epithelial, glial, neuronal, and skeletal muscle cells; stimulating acetylcholine receptor expression during neuromuscular junction formation; promoting lobuloalveolar budding and milk production in the mammary gland, as well as differentiation of mammary tumor cells; stimulating Schwann cell proliferation; and contributing to myocardium development, specifically trabeculation of the developing heart. Isoform 10 potentially plays a role in motor and sensory neuron development. NRG1 binds to ERBB4 (PubMed:10867024, PubMed:7902537) and ERBB3 (PubMed:20682778), acting as a ligand for integrins by binding (through its EGF domain) to ITGAV:ITGB3 or ITGA6:ITGB4 integrins. This interaction and subsequent ternary complex formation with integrins and ERRB3 are essential for NRG1-ERBB signaling. NRG1 induces phosphorylation and activation of MAPK3/ERK1, MAPK1/ERK2, and AKT1 (PubMed:20682778). Ligand-dependent ERBB4 endocytosis is crucial for NRG1-mediated activation of these kinases in neurons (By similarity). The cytoplasmic domain interacts with the LIM domain region of LIMK1 (By similarity). NRG1 forms a ternary complex with ERBB3 and ITGAV:ITGB3 or ITGA6:ITGB4 (PubMed:20682778). It interacts with NRDC and BACE1 (By similarity).
NRG1 is also known as ARIA, GGF, GGF2, HGL, HRG, HRG1, HRGA, MST131, MSTP131, NDF, NRG1-IT2, SMDF.
