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FLASH GENE

Symbol

RXRA

contributors: mct/npt - updated : 04-04-2019

HGNC name	retinoid X receptor, alpha
HGNC id	10477

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	9q34.2      Physical location : 137.218.315 - 137.332.431
Synonym name	nuclear receptor subfamily 2 group B member 1
Synonym symbol(s)	NR2B1, FLJ00280, FLJ00318, FLJ16020, FLJ16733, MGC102720

DNA

TYPE	functioning gene
STRUCTURE	114.12 kb     10 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence
text structure	GC rich region in the 5'UTR

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002957 10 - 5547 NP_002948 - 462 - 1992 1314167 also known as RXR alpha1 NM_001291920 10 - 6202 NP_001278849 - 435 - 1992 1314167 also known as RXR alpha2 transcriptional activity and a dose response curve against the agonist LG100268 similar to RXR alpha 1 in reporter assay for the RXR alpha homodimer or that for the heterodimer with PPAR gamma 2 NM_001291921 9 - 5993 NP_001278850 - 365 in brain, spleen and prostate 1992 1314167 also known as RXR alpha3 transcriptional activity and a dose response curve against the agonist LG100268 similar to RXR alpha 1 in reporter assay for the RXR alpha homodimer or that for the heterodimer with PPAR gamma 2

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Nervous brain       highly Reproductive female system uterus         male system prostate     highly Respiratory lung           respiratory tract larynx     highly Urinary bladder           kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     highly Connective bone     highly

cell lineage
cell lines
fluid/secretion	blood

at STAGE

physiological period

pregnancy

Text

placenta

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed miscelleaneous senescence   as a potential therapeutic target for treating the age-related diseases immunology infectious   represents a potential target for immunotherapy of sepsis cancer digestive oesophagus may serve as a potential targeted therapeutic marker in the treatment of EC neurosensorial visual   RXR agonists might provide potential pharmacological tools for treating retina degenerative diseases cancer skin   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