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  3. NR4A3

NR4A3 (Nuclear receptor subfamily 4 group A member 3)

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The Function of NR4A3

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.

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Protein names

Recommended name:

Nuclear receptor subfamily 4 group A member 3

Alternative name(s):

Mitogen-induced nuclear orphan receptor
Neuron-derived orphan receptor 1
Nuclear hormone receptor NOR-1

Top Gene-Substance Interactions

NR4A3 Interacts with These Diseases

Disease Score

Substances That Increase NR4A3

Substances Interaction Organism Category

Substances That Decrease NR4A3

Substances Interaction Organism Category

Conditions with Increased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Conditions with Decreased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Technical

The following transcription factors affect gene expression:

  • ER-alpha
  • CREB
  • Max
  • deltaCREB
  • PPAR-alpha
  • Sp1
  • AML1a
  • Pax-2

Tissue specificity:

Isoform alpha is highly expressed in skeletal muscle. Isoform beta is highly expressed in skeletal muscle and low expressed in fetal brain and placenta.

Gene Pathways:

  • Gene Expression

Induction:

Induced by inflammatory stimuli in endothelial cells through an NF-kappa-B-dependent transactivation of the NR4A3 Promoter.

Molecular Function:

  • Core Promoter Sequence-Specific Dna Binding
  • Dna Binding
  • Protein Homodimerization Activity
  • Protein Kinase Binding
  • Rna Polymerase Ii Core Promoter Proximal Region Sequence-Specific Dna Binding
  • Steroid Hormone Receptor Activity
  • Thyroid Hormone Receptor Activity
  • Transcriptional Activator Activity, Rna Polymerase Ii Core Promoter Proximal Region Sequence-Specific Binding
  • Zinc Ion Binding

Biological Processes:

  • Adult Behavior
  • Animal Organ Regeneration
  • Axon Guidance
  • Cellular Respiration
  • Cellular Response To Catecholamine Stimulus
  • Cellular Response To Corticotropin-Releasing Hormone Stimulus
  • Cellular Response To Leptin Stimulus
  • Common Myeloid Progenitor Cell Proliferation
  • Energy Homeostasis
  • Fat Cell Differentiation
  • Gastrulation
  • Hippocampus Development
  • Mast Cell Degranulation
  • Mesoderm Formation
  • Negative Regulation Of Hydrogen Peroxide-Induced Neuron Death
  • Negative Regulation Of Neuron Apoptotic Process
  • Negative Regulation Of Transcription From Rna Polymerase Ii Promoter
  • Neuromuscular Process Controlling Balance
  • Positive Regulation Of Cardiac Muscle Hypertrophy
  • Positive Regulation Of Cell Cycle
  • Positive Regulation Of Epithelial Cell Proliferation
  • Positive Regulation Of Fatty Acid Oxidation
  • Positive Regulation Of Feeding Behavior
  • Positive Regulation Of Glucose Transport
  • Positive Regulation Of Leukocyte Apoptotic Process
  • Positive Regulation Of Mast Cell Activation By Fc-Epsilon Receptor Signaling Pathway
  • Positive Regulation Of Mast Cell Cytokine Production
  • Positive Regulation Of Monocyte Aggregation
  • Positive Regulation Of Smooth Muscle Cell Proliferation
  • Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
  • Pyruvate Oxidation
  • Regulation Of Energy Homeostasis
  • Regulation Of Smooth Muscle Cell Proliferation
  • Regulation Of Type B Pancreatic Cell Proliferation
  • Response To Hydrogen Peroxide
  • Semicircular Canal Morphogenesis
  • Transcription Initiation From Rna Polymerase Ii Promoter
  • Vestibular Reflex
*synonyms

Synonyms/Aliases/Alternative Names of the Gene:

hypothetical protein| tec| nuclear receptor subfamily 4, group A, member 2| AS27_15908| AS28_02250| CB1_000794018| CHN| chondrosarcoma, extraskeletal myxoid, fused to EWS| CSMF| I79_013437| M91_20265| M959_13561| MDA_GLEAN10021531| minor| mitogen-induced nuclear orphan receptor| N300_10501| N301_04531| N302_10360| N305_02148| N306_00830| N307_15458| N308_09086| N309_06798| N320_10753| N321_04769| N322_00101| N324_02234| N325_02509| N326_08443| N330_02095| N331_00750| N332_02359| N336_11345| N339_11889| neural orphan nuclear receptor NOR1| neural orphan receptor 1| neuron-derived nuclear orphan receptor| neuron-derived orphan receptor 1| neuron-derived orphan receptor 1/2| neuron-derived orphan receptor-1 alfa| NOR1| NOR-1| NOR-2| NR4A2| nuclear hormone receptor NOR-1| nuclear hormone receptor NOR-1/NOR-2| nuclear receptor subfamily 4, group A, member 3| orphan nuclear receptor TEC| PAL_GLEAN10008003| translocated in extraskeletal chondrosarcoma| TREES_T100017349| UY3_08942| Y1Q_004492| Y956_00758| Z169_15953| nr4a3

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