DegronMD - Q92570(NR4A3)

FUNCTION: Transcriptional activator that binds to regulatory elements in promoter regions in a cell- and response element (target)-specific manner. 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 (By similarity). Plays a role in the regulation of proliferation, survival and differentiation of many different cell types and also in metabolism and inflammation. Mediates proliferation of vascular smooth muscle, myeloid progenitor cell and type B pancreatic cells; promotes mitogen-induced vascular smooth muscle cell proliferation through transactivation of SKP2 promoter by binding a NBRE site (By similarity). Upon PDGF stimulation, stimulates vascular smooth muscle cell proliferation by regulating CCND1 and CCND2 expression. In islets, 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 (By similarity). Negatively regulates myeloid progenitor cell proliferation by repressing RUNX1 in a NBRE site-independent manner. During inner ear, plays a role as a key mediator of the proliferative growth phase of semicircular canal development (By similarity). Mediates also survival of neuron and smooth muscle cells; mediates CREB-induced neuronal survival, and during hippocampus development, plays a critical role in pyramidal cell survival and axonal guidance. Is required for S phase entry of the cell cycle and survival of smooth muscle cells by inducing CCND1, resulting in RB1 phosphorylation. Binds to NBRE motif in CCND1 promoter, resulting in the activation of the promoter and CCND1 transcription (By similarity). Plays also a role in inflammation; upon TNF stimulation, mediates monocyte adhesion by inducing the expression of VCAM1 and ICAM1 by binding to the NBRE consensus site (By similarity) (PubMed:20558821). In mast cells activated by Fc-epsilon receptor cross-linking, promotes the synthesis and release of cytokines but impairs events leading to degranulation (By similarity). Plays also a role in metabolism; by modulating feeding behavior; and by playing 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, regulates gene expression that controls oxidative metabolism in skeletal muscle (By similarity). Plays a role in glucose transport by regulating translocation of the SLC2A4 glucose transporter to the cell surface (PubMed:24022864). Finally, during gastrulation plays a crucial role in the formation of anterior mesoderm by controlling cell migration. Inhibits adipogenesis (By similarity). Also participates in cardiac hypertrophy by activating PARP1 (By similarity). {ECO:0000250|UniProtKB:P51179, ECO:0000250|UniProtKB:Q9QZB6, ECO:0000269|PubMed:20558821, ECO:0000269|PubMed:24022864}. View more >>

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GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.S296L	TCGA-EB-A5UN	SKCM	TCGA	SSSSGE	DEG_Kelch_Keap1_1	284:289	Mutation rewiring degron network	0.1389
p.D297Y	DO50090	COAD	ICGC	SSSSGE	DEG_Kelch_Keap1_1	284:289	Mutation rewiring degron network	0.1111
p.T262A	DO227802	COCA	ICGC	LGLTPSPT	DEG_SCF_FBW7_1	259:266	Mutation altering degron motif	0.7139
p.S279L	DO234227	ESAD	ICGC	SSSSGE	DEG_Kelch_Keap1_1	284:289	Mutation rewiring degron network	0.1944
p.S279L	DO229462	SKCA	ICGC	SSSSGE	DEG_Kelch_Keap1_1	284:289	Mutation rewiring degron network	0.1944
p.E289Q	DO233671	GACA	ICGC	SSSSGE	DEG_Kelch_Keap1_1	284:289	Mutation altering degron motif	0.6744
p.V294M	DO233737	GACA	ICGC	SSSSGE	DEG_Kelch_Keap1_1	284:289	Mutation rewiring degron network	0.1944
p.A251V	DO233903	GACA	ICGC	LGLTPSPT	DEG_SCF_FBW7_1	259:266	Mutation rewiring degron network	0.1111
p.S285L	DO47267	SKCM	ICGC	SSSSGE	DEG_Kelch_Keap1_1	284:289	Mutation altering degron motif	0.6556
p.P275S	DO37432	SKCM	ICGC	SSSSGE	DEG_Kelch_Keap1_1	284:289	Mutation rewiring degron network	0.0833
p.P275S	DO37432	SKCM	ICGC	LGLTPSPT	DEG_SCF_FBW7_1	259:266	Mutation rewiring degron network	0.0833
p.A299T	DO47849	STAD	ICGC	SSSSGE	DEG_Kelch_Keap1_1	284:289	Mutation rewiring degron network	0.0556
p.C295R	DO229121	THCA	ICGC	SSSSGE	DEG_Kelch_Keap1_1	284:289	Mutation rewiring degron network	0.1667
p.P280Q	ACH-000712	Lung Cancer	CCLE	SSSSGE	DEG_Kelch_Keap1_1	284:289	Mutation rewiring degron network	0.2222

DegronMD: protein-targeted degradation, mutation and drug response to degrons

NR4A3

UniProt ID: Q92570

Entrez ID: 8013

Protein name: Nuclear receptor subfamily 4 group A member 3 (Mitogen-induced nuclear orphan receptor) (Neuron-derived orphan receptor 1) (Nuclear hormone receptor NOR-1)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for NR4A3 in