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FLASH GENE
Symbol NR4A3 contributors: mct - updated : 19-12-2013
HGNC name nuclear receptor subfamily 4, group A, member 3
HGNC id 7982
Location 9q31.1      Physical location : 102.584.136 - 102.629.173
Synonym name
  • neuron-derived orphan receptor 1
  • nuclear hormone receptor NOR-1
  • mitogen-induced nuclear orphan receptor
  • chondrosarcoma, extraskeletal myxoid, fused to EWS
  • translocated in extraskeletal chondrosarcoma
  • Synonym symbol(s) CHN, TEC, CSMF, MINOR, NOR1, TFG
    DNA
    TYPE functioning gene
    STRUCTURE 45.04 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map see FANCC FANCC
    Physical map
    ANP32B 9q22.32 acidic (leucine-rich) nuclear phosphoprotein 32 family, member B NANS 9p24.1-p23 N-acetylneuraminic acid synthase (sialic acid synthase) TRIM14 9q22.32 tripartite motif-containing 14 CORO2A 9q22.3 coronin, actin binding protein, 2A TBC1D2 9q22.33 TBC1 domain family, member 2 GPR51 9q22.1 G protein-coupled receptor 51 SAMD6 9q31.1 sterile alpha motif domain containing 6 GALNT12 9q22.33 UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 12 (GalNAc-T12) LOC392372 9 similar to Nucleoside diphosphate kinase B (NDK B) (NDP kinase B) (P18) COL15A1 9q22.32-q22.33 collagen, type XV, alpha 1 TGFBR1 9q22 transforming growth factor, beta receptor I (activin A receptor type II-like kinase, 53kDa) ALG2 9q31.1 asparagine-linked glycosylation 2 homolog (yeast, alpha-1,3-mannosyltransferase) SEC61B 9q22.32-q31.3 asparagine-linked glycosylation 2 homolog (yeast, alpha-1,3-mannosyltransferase) LOC347265 9q31.1 similar to bA13B9.3 (novel protein similar to KRT8) LOC389778 9 LOC389778 NR4A3 9q22.32-q22.33 nuclear receptor subfamily 4, group A, member 3 STX17 9q31.1 syntaxin 17 INVS 9q31 inversin FLJ20287 9q31.1 hypothetical protein FLJ20287 MGC17337 9q31.1 similar to RIKEN cDNA 5730528L13 gene TMEFF1 9q31 transmembrane protein with EGF-like and two follistatin-like domains 1 LOC347273 9q31.1 similar to RIKEN cDNA 2310039E09 LOC392373 9 similar to ACTB protein LOC392374 9 similar to uracil DNA glycosylase FLJ20300 LOC347275 9q31.1 similar to RIKEN cDNA C730036D15 BAAT 9q22.3 bile acid Coenzyme A: amino acid N-acyltransferase (glycine N-choloyltransferase) MRPL50 9q31.1 mitochondrial ribosomal protein L50 ZNF189 9q22-q31 zinc finger protein 189 ALDOB 9q21.3-q22.2 aldolase B, fructose-bisphosphate MGC12992 9q31.1 hypothetical protein MGC12992 RNF20 9q22 ring finger protein 20
    RNA
    TRANSCRIPTS type messenger
    text with alternatively spliced variants
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 5635 - 626 . detected in human fetus brain . distributed in cytoplasm 2011 2186837
    isoform a, variant 1
    7 - 5707 - 637 - 2008 18325999
    isoform b, variant 3
    5 - 2588 - 443 - 2008 18325999
    isoform c, variant4
    7 splicing - - - . detected in human fetus brain, sole isoform in other tissues but brain . distributed in cytoplasm 2011 2186837
  • lacking of exon 2
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineadrenal gland   highly
    Hearing/Equilibriumear   highly
    Nervousnerve   highly
    Reproductivemale systemtestis  highly Homo sapiensNR4A3 mRNA
    Skin/Tegumentskin    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    physiological period fetal
    Text
  • moderate expression in human fetus nasopharynx, trachea, brain, and kidney tissues, and weak or undetectable in other tissues (PMIUD: 21873782)
  • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal modulator domain
  • a central bipartite (class II) zinc finger DNA binding domain
  • a C terminal ligand domain
  • HOMOLOGY
    interspecies homolog to rattus neuron derived orphan receptor 1
    Homologene
    FAMILY
  • nuclear hormone receptor family
  • subfamily 4, group A
  • NR4A subfamily of the nuclear receptor superfamily
  • CATEGORY receptor nuclear
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • may be acting as a transcriptional activator
  • modulating vascular smooth muscle cell proliferation
  • playing a role in spontaneous and accelerated atherosclerosis
  • required for T-cells receptor mediated apoptosis of immature thymocytes
  • playing a necessary role for oxidative metabolism in skeletal muscle
  • its up-regulation plays a key role in thrombin-induced endothelial cell growth
  • mediating vascular smooth muscle cell proliferation
  • is involved in the regulation of the survival response of endothelial cells to hypoxia via the upregulation of CIAP2
  • downstream effector of HIF-1 signaling
  • essential mediator of neuroprotection after exposure to neuropathological stress
  • key downstream mediator of CREB1-induced neuroprotection
  • mediates monocyte adhesion by inducing VCAM1 and intercellular adhesion molecule-1 expression in endothelial cells
  • induction of NR4A1, NR4A2, NR4A3 in activated mast cells and NR4A family nuclear receptors are implicated in the regulation of mast cell function
  • is a novel positive transcriptional regulator of SKP2 expression and downstream CDKN1B degradation in vascular smooth muscle cells
  • specific requirement of NR4A3 for SKP2 expression during neointima formation in response to vascular injury
  • NR4A1, NR4A2, NR4A3 have key roles in determining CD4(+) T cell fates in the thymus and thus contribute to immune homeostasis
  • NR4A1, NR4A2, NR4A3 are regulated by different physiological and pathophysiological settings known to be associated with marked alterations in glucose metabolism and energy status
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS development , nervous system
    text neural development processes
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • direct target of RUNX1 and restoration of NR4A3 expression in acute myelogenous leukemia partially reduced the clonogenic potential of patient progenitors
  • SKP2 is a direct transcriptional target for NR4A1
  • PIN1 is a novel binding partner of NR4A1, NR4A2, NR4A3
  • mutual antagonism between NR4A3 and NR3C1 to be a key rheostat for peripheral metabolic signals to centrally control energy balance
  • NKX6-1 induces expression of NR4A1 and NR4A3 orphan nuclear receptors, and these factors are both necessary and sufficient for NKX6-1-mediated beta-cell proliferation
  • cell & other
    REGULATION
    activated by thrombin in umbilical vein endothelial cells (HUVEC)
    induced by the cAMP axis in response to glucagon
    platelet-derived growth factor
    CREB1 in neurons exposed to stressful insults and function as mediator of CREB1-induced neuronal survival
    Other upregulated by hypoxia
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   translocation    
    in extraskeletal and skeletal myxoid chondrosarcoma EMC with t(9;22)(q22;q12) see EWS, EWSR, or t(9;17)(q22;q11),(see TAF2N)
    constitutional     --over  
    in coronary atherosclerosis, and in atherosclerotic plaques
    tumoral fusion      
    fused to TFG in myxoid chondrosarcoma
    tumoral     --other  
    aberrant coexpression with SIX3 is a potential alternative mechanism underlying the development of extraskeletal myxoid chondrosarcomas
    constitutional     --over  
    in human endothelial cells increased the expression of vascular cell adhesion molecule VCAM1 and intercellular adhesion molecule-1
    tumoral     --low  
    of NR4A1 and NR4A3 was a common feature in leukemic blasts from human acute myeloid leukemia patients
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • pathognomic rearrangement of NR4A3 is a useful diagnostic feature in identifying cellular extraskeletal myxoid chondrosarcoma
  • Therapy target
    SystemTypeDisorderPubmed
    cardiovascular  
    blockage of NR4A3 could be useful to prevent vascular effects triggered by thrombin
    cancer  
    identification of pro-apoptotic agents inducing NR4A expression or acting as agonists suggests that these members could serve as potential targets for cancer therapy
    ANIMAL & CELL MODELS
  • expression increased in diabetic mice that exhibit elevated gluconeogenesis
  • Nor1 deficiency reduces hypercholesterolemia-induced atherosclerosis formation in apoE(-/-) mice by decreasing the macrophage content of the lesion