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FLASH GENE
Symbol RXRA contributors: mct/npt - updated : 04-04-2019
HGNC name retinoid X receptor, alpha
HGNC id 10477
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminal modulator domain
  • a central bipartite (class II) zinc finger DNA binding domain
  • a C terminal ligand domain, DNA-binding domain (C-domain) that bound IGFBP3 (Schedlich 2007)
  • AF-1 and AF-2 domains involved in the processes of transactivation and degradation
    • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies homolog to murine rxra
    Homologene
    FAMILY
  • steroid/thyroid/retinoic receptor superfamily
  • NR2 subfamily
    • CATEGORY transcription factor , receptor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • involved in retinoic acid response pathway
  • regulating cardiac morphogenesis
  • dimerization partner for the RARs, T3Rs and VD3R having important implications as to the function of these receptors and their ligands in development, homeostasis and neoplasia (Bugge 1992)
  • not required for the nuclear translocation of IGFBP3 and IGFBP3 can induce apoptosis in human prostate cancer cells without binding RXRA (Zappala 2008)
  • inhibition of its expression is essential for neutrophil development from granulocyte/monocyte progenitors (Taschner 2007)
  • plays a central role in the regulation of many intracellular receptor signaling pathways and can mediate ligand-dependent transcription by forming homodimers or heterodimers with other nuclear receptors
  • functions as an allosteric activator of NCOA1–NR1H3 interaction
  • combinatorial effects of SUMOylation may regulate RXRA-directed signalling in a gene-specific fashion
    • CELLULAR PROCESS cell life
    nucleotide, transcription
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism vitamin
    signaling signal transduction
  • PPARG/RXRA signaling in human totrophoblast (CT) and a disturbed PPARG/RXRA pathway could contribute to pathological human pregnancies
    • a component
  • with PML, RARA and TIF1 of a transcription complex, retinoic acid dependent, obligate member of heterodimeric nuclear receptor
  • LXR/RXR heterodimer
  • NR1I2 and RXRA form a heterotetramer unprecedented in the nuclear receptor family of ligand-regulated transcription factors
  • RARG/RXRA heterodimers
    • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • ion Zn2+
    • protein
  • LXR to regulating ABCA1 and cholesterol efflux process
  • cooperating with RAR gamma 2 through its AF-2 domain and its phosphorylated AF-1 domain in both the transcription activity and the degradation of the RAR gamma 2/RXR alpha heterodimers
  • binding to IGFBP3 may be required for inhibition, and raise the possibility that the induction of IGFBP3 by hypoxia and TNF may contribute to their ability to inhibit adiponectin transcription and promote insulin resistance (Zappala 2009)
  • F3-dependent liver injury causes release of retinoid receptors (RXRA and RARA) as lipid droplets
  • P1 and P2 of PLAC1 are activated by RXRA in conjunction with LXRA or LXRB
  • HSPA9 was required for RARA/RXRA-mediated transcriptional regulation and was shown to reduce the proteasome-mediated degradation of RARA/RXRA in a RA-dependent manner
  • TGIF1 is an RXRA transcriptional co-repressor and represses RXRA-dependent transcriptional responses
  • RXRA interacts physically with NFE2L2 in cancer cells (RXRA diminishes cytoprotection by NFE2L2 by binding directly to the newly defined Neh7 domain in NFE2L2)
  • unexpected function of the corepressor CTBP2 as a coactivator for RAR/RXRA in RA signaling
  • RXRA mediates the sex-dependent influence of GH on CYP3A expression as an important signalling molecule
  • RXRG as well as RXRA increased SREBF1 promoter activity in hepatocytes
  • NR4A1 nuclear export requires RXRA as a carrier
  • RXRA is a protein that exhibited MAPK9-promoted phosphorylation
    • cell & other
    REGULATION
    activated by 9-cis-retinoic acid (only 9-cisRA)
    all-trans retinoic acid
    Other inhibition of RXRA nuclear export reduced neuronal apoptosis
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    mediates the elevation of PTGS2 expression and PGE2 production in senescent macrophages
    constitutional     --low  
    in senescent macrophages and partially accounts for higher risk of atherosclerosis in aged population
    tumoral     --over  
    in Esophageal carcinoma (EC) correlated with unfavorable prognosis
    Susceptibility to chronic glomerulonephritis
    Variant & Polymorphism SNP
  • rs10776909 allele T is specifically involved in the pathogenesis of chronic glomerulonephritis
    • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneoussenescence 
    as a potential therapeutic target for treating the age-related diseases
    immunologyinfectious 
    represents a potential target for immunotherapy of sepsis
    cancerdigestiveoesophagus
    may serve as a potential targeted therapeutic marker in the treatment of EC
    neurosensorialvisual 
    RXR agonists might provide potential pharmacological tools for treating retina degenerative diseases
    cancerskin 
    RXRA, RXRB are potential targets for therapy against UV induced melanoma (PMID: 24810760)
    ANIMAL & CELL MODELS
  • activation of Rxrs protects rat photoreceptor neurons from oxidative stress-induced apoptosis