Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol NR4A3 contributors: mct - updated : 19-12-2013
HGNC name nuclear receptor subfamily 4, group A, member 3
HGNC id 7982
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
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