NR4A3
Description
The NR4A3 (nuclear receptor subfamily 4 group A member 3) is a protein-coding gene located on chromosome 9.
The nuclear receptor 4A3 (NR4A3) (nuclear receptor subfamily 4, group A, member 3) also known as neuron-derived orphan receptor 1 (NOR1) is a protein that in humans is encoded by the NR4A3 gene. NR4A3 is a member of the nuclear receptor family of intracellular transcription factors. NR4A3 plays a central regulatory role in cell proliferation, differentiation, mitochondrial respiration, metabolism and apoptosis. NR4A3 has been shown to interact with SIX3.
NR4A3 is a transcriptional activator that binds to regulatory elements in promoter regions in a cell- and response element (target)-specific manner. It induces gene expression by binding as monomers to the NR4A1 response element (NBRE) 5'-AAAAGGTCA-3' site and as homodimers to the Nur response element (NurRE) site in the promoter of their regulated target genes. NR4A3 plays a role in the regulation of proliferation, survival and differentiation of many different cell types and also in metabolism and inflammation. NR4A3 mediates proliferation of vascular smooth muscle, myeloid progenitor cell and type B pancreatic cells. It promotes mitogen-induced vascular smooth muscle cell proliferation through transactivation of SKP2 promoter by binding a NBRE site. Upon PDGF stimulation, NR4A3 stimulates vascular smooth muscle cell proliferation by regulating CCND1 and CCND2 expression. In islets, NR4A3 induces type B pancreatic cell proliferation through up-regulation of genes that activate cell cycle, as well as genes that cause degradation of the CDKN1A. NR4A3 negatively regulates myeloid progenitor cell proliferation by repressing RUNX1 in a NBRE site-independent manner. During inner ear development, NR4A3 plays a role as a key mediator of the proliferative growth phase of semicircular canal development. NR4A3 mediates also survival of neuron and smooth muscle cells. It mediates CREB-induced neuronal survival, and during hippocampus development, plays a critical role in pyramidal cell survival and axonal guidance. NR4A3 is required for S phase entry of the cell cycle and survival of smooth muscle cells by inducing CCND1, resulting in RB1 phosphorylation. NR4A3 binds to NBRE motif in CCND1 promoter, resulting in the activation of the promoter and CCND1 transcription. NR4A3 also plays a role in inflammation. Upon TNF stimulation, NR4A3 mediates monocyte adhesion by inducing the expression of VCAM1 and ICAM1 by binding to the NBRE consensus site. In mast cells activated by Fc-epsilon receptor cross-linking, NR4A3 promotes the synthesis and release of cytokines but impairs events leading to degranulation. NR4A3 also plays a role in metabolism by modulating feeding behavior. It plays a role in energy balance by inhibiting the glucocorticoid-induced orexigenic neuropeptides AGRP expression, at least in part by forming a complex with activated NR3C1 on the AGRP- glucocorticoid response element (GRE), and thus weakening the DNA binding activity of NR3C1. Upon catecholamines stimulation, NR4A3 regulates gene expression that controls oxidative metabolism in skeletal muscle. NR4A3 plays a role in glucose transport by regulating translocation of the SLC2A4 glucose transporter to the cell surface. Finally, during gastrulation NR4A3 plays a crucial role in the formation of anterior mesoderm by controlling cell migration. NR4A3 inhibits adipogenesis. It also participates in cardiac hypertrophy by activating PARP1.
NR4A3 is also known as CHN, CSMF, MINOR, NOR1.
