RXRA (retinoid X receptor alpha)

Gene

• Entrez ID: 6256
• Gene name: Retinoid X receptor alpha
• Gene symbol: RXRA
• Synonyms: NR2B1
• Chromosome: 9
• Chromosome location: 9q34.2
• Summary: Retinoid X receptors (RXRs) and retinoic acid receptors (RARs) are nuclear receptors that mediate the biological effects of retinoids by their involvement in retinoic acid-mediated gene activation. These receptors function as transcription factors by binding as homodimers or heterodimers to specific sequences in the promoters of target genes. The protein encoded by this gene is a member of the steroid and thyroid hormone receptor superfamily of transcriptional regulators. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2014]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1057519958	C>A,T	Likely-pathogenic	Coding sequence variant, missense variant
rs1588299621	G>A	Likely-pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT042547	hsa-miR-423-3p	CLASH	23622248
MIRT054229	hsa-miR-128-3p	Luciferase reporter assay, Microarray, qRT-PCR, Western blot	23990020
MIRT054351	hsa-miR-574-3p	Luciferase reporter assay, Microarray, qRT-PCR, Western blot	23626837
MIRT486418	hsa-miR-486-3p	PAR-CLIP	23592263
MIRT486419	hsa-miR-7106-5p	PAR-CLIP	23592263
MIRT486420	hsa-miR-4734	PAR-CLIP	23592263
MIRT486421	hsa-miR-4532	PAR-CLIP	23592263
MIRT486422	hsa-miR-596	PAR-CLIP	23592263
MIRT486423	hsa-miR-3940-3p	PAR-CLIP	23592263
MIRT543477	hsa-miR-3692-3p	PAR-CLIP	21572407
MIRT543477	hsa-miR-3692-3p	PAR-CLIP	20371350
MIRT543478	hsa-miR-6817-5p	PAR-CLIP	21572407
MIRT543478	hsa-miR-6817-5p	PAR-CLIP	20371350
MIRT543479	hsa-miR-4769-3p	PAR-CLIP	21572407
MIRT543479	hsa-miR-4769-3p	PAR-CLIP	20371350
MIRT543480	hsa-miR-1976	PAR-CLIP	21572407
MIRT543480	hsa-miR-1976	PAR-CLIP	20371350
MIRT543481	hsa-miR-6747-3p	PAR-CLIP	21572407
MIRT543481	hsa-miR-6747-3p	PAR-CLIP	20371350
MIRT543482	hsa-miR-4722-3p	PAR-CLIP	21572407
MIRT543482	hsa-miR-4722-3p	PAR-CLIP	20371350
MIRT543483	hsa-miR-6727-3p	PAR-CLIP	21572407
MIRT543483	hsa-miR-6727-3p	PAR-CLIP	20371350
MIRT543484	hsa-miR-660-3p	PAR-CLIP	21572407
MIRT543485	hsa-miR-4667-3p	PAR-CLIP	21572407
MIRT543486	hsa-miR-4258	PAR-CLIP	21572407
MIRT543486	hsa-miR-4258	PAR-CLIP	20371350
MIRT617631	hsa-miR-2681-5p	HITS-CLIP	23824327
MIRT617632	hsa-miR-3180-5p	HITS-CLIP	23824327
MIRT617633	hsa-miR-7702	HITS-CLIP	23824327
MIRT617634	hsa-miR-525-5p	HITS-CLIP	23824327
MIRT617635	hsa-miR-520a-5p	HITS-CLIP	23824327
MIRT617636	hsa-miR-4724-3p	HITS-CLIP	23824327
MIRT617637	hsa-miR-488-5p	HITS-CLIP	23824327
MIRT617638	hsa-miR-6782-3p	HITS-CLIP	23824327
MIRT733218	hsa-miR-27a-3p	Luciferase reporter assay, Microarray, qRT-PCR	25915942

Transcription factors

Transcription factor	Regulation	Reference
NR1I2	Unknown	21295138

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IBA	21873635
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IDA	17426122
GO:0000785	Component	Chromatin	IDA	18511497, 25592151
GO:0000785	Component	Chromatin	ISA
GO:0000976	Function	Transcription regulatory region sequence-specific DNA binding	IDA	18511497
GO:0000977	Function	RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA	7831303
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA	21873635
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA	12037571
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001972	Function	Retinoic acid binding	IDA	19043829
GO:0003690	Function	Double-stranded DNA binding	IMP	19043829
GO:0003700	Function	DNA-binding transcription factor activity	IDA	12037571, 17426122
GO:0003707	Function	Steroid hormone receptor activity	IEA
GO:0004879	Function	Nuclear receptor activity	IBA	21873635
GO:0004879	Function	Nuclear receptor activity	IDA	1651173, 7990953, 20219900, 25592151
GO:0004879	Function	Nuclear receptor activity	TAS	19374686
GO:0005515	Function	Protein binding	IPI	9653119, 10428834, 10866662, 11915042, 12040021, 14701856, 15722453, 16769902, 17363140, 17426122, 17641689, 17673910, 17947383, 19047629, 19345331, 19786558, 19917671, 20219900, 20541701, 20682316, 21220114, 21478865, 21988832, 22179700, 22474364, 23602807, 24561505, 25241761, 2530
GO:0005634	Component	Nucleus	IDA	7990953, 19917671
GO:0005654	Component	Nucleoplasm	TAS
GO:0005739	Component	Mitochondrion	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA	21873635
GO:0006367	Process	Transcription initiation from RNA polymerase II promoter	TAS
GO:0008203	Process	Cholesterol metabolic process	TAS	19374686
GO:0008270	Function	Zinc ion binding	IDA	19043829
GO:0015721	Process	Bile acid and bile salt transport	TAS
GO:0016922	Function	Nuclear receptor binding	IPI	19043829
GO:0019048	Process	Modulation by virus of host process	IDA	11915042
GO:0019216	Process	Regulation of lipid metabolic process	TAS
GO:0019899	Function	Enzyme binding	IPI	12039952
GO:0030154	Process	Cell differentiation	IBA	21873635
GO:0032526	Process	Response to retinoic acid	IBA	21873635
GO:0032526	Process	Response to retinoic acid	IMP	17538076
GO:0035357	Process	Peroxisome proliferator activated receptor signaling pathway	IDA	10195690
GO:0042277	Function	Peptide binding	IDA	19043829
GO:0042802	Function	Identical protein binding	IPI	7831303
GO:0042809	Function	Vitamin D receptor binding	IPI	17426122
GO:0043235	Component	Receptor complex	IDA	17426122, 19043829
GO:0043401	Process	Steroid hormone mediated signaling pathway	IEA
GO:0043565	Function	Sequence-specific DNA binding	IDA	11915042
GO:0044323	Function	Retinoic acid-responsive element binding	IBA	21873635
GO:0044323	Function	Retinoic acid-responsive element binding	IDA	19917671, 25592151
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IDA	1651173
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IBA	21873635
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	12037571, 20219900, 25592151
GO:0048384	Process	Retinoic acid receptor signaling pathway	IBA	21873635
GO:0048384	Process	Retinoic acid receptor signaling pathway	IMP	17538076
GO:0048856	Process	Anatomical structure development	IBA	21873635
GO:0050692	Function	DNA binding domain binding	IDA	19043829
GO:0050693	Function	LBD domain binding	IDA	19043829
GO:0070644	Function	Vitamin D response element binding	IDA	17426122
GO:0090575	Component	RNA polymerase II transcription regulator complex	IBA	21873635
GO:0090575	Component	RNA polymerase II transcription regulator complex	IDA	17426122, 18511497
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536

Other IDs

• MIM: 180245
• HGNC: 10477
• e!Ensembl: ENSG00000186350

Protein

• UniProt ID: P19793
• Protein name: Retinoic acid receptor RXR-alpha (Nuclear receptor subfamily 2 group B member 1) (Retinoid X receptor alpha)
• Protein function: Receptor for retinoic acid that acts as a transcription factor (PubMed:11162439, PubMed:11915042). Forms homo- or heterodimers with retinoic acid receptors (RARs) and binds to target response elements in response to their ligands, all-trans or 9-cis retinoic acid, to regulate gene expression in various biological processes (PubMed:10195690, PubMed:11162439, PubMed:11915042, PubMed:28167758, PubMed:17761950, PubMed:16107141, PubMed:18800767, PubMed:19167885). The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 to regulate transcription (PubMed:10195690, PubMed:11162439, PubMed:11915042, PubMed:17761950, PubMed:28167758). The high affinity ligand for retinoid X receptors (RXRs) is 9-cis retinoic acid (PubMed:1310260). In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression (PubMed:20215566). On ligand binding, the corepressors dissociate from the receptors and coactivators are recruited leading to transcriptional activation (PubMed:20215566, PubMed:9267036). Serves as a common heterodimeric partner for a number of nuclear receptors, such as RARA, RARB and PPARA (PubMed:10195690, PubMed:11915042, PubMed:28167758, PubMed:29021580). The RXRA/RARB heterodimer can act as a transcriptional repressor or transcriptional activator, depending on the RARE DNA element context (PubMed:29021580). The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes (PubMed:10195690). Together with RARA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells (PubMed:28167758). Acts as an enhancer of RARA binding to RARE DNA element (PubMed:28167758). May facilitate the nuclear import of heterodimerization partners such as VDR and NR4A1 (PubMed:12145331, PubMed:15509776). Promotes myelin debris phagocytosis and remyelination by macrophages (PubMed:26463675). Plays a role in the attenuation of the innate immune system in response to viral infections, possibly by negatively regulating the transcription of antiviral genes such as type I IFN genes (PubMed:25417649). Involved in the regulation of calcium signaling by repressing ITPR2 gene expression, thereby controlling cellular senescence (PubMed:30216632).
• PDB: 1BY4, 1DSZ, 1FBY, 1FM6, 1FM9, 1G1U, 1G5Y, 1K74, 1MV9, 1MVC, 1MZN, 1R0N, 1RDT, 1RXR, 1XLS, 1XV9, 1XVP, 1YNW, 2ACL, 2NLL, 2P1T, 2P1U, 2P1V, 2ZXZ, 2ZY0, 3DZU, 3DZY, 3E00, 3E94, 3FAL, 3FC6, 3FUG, 3H0A, 3KWY, 3NSP, 3NSQ, 3OAP, 3OZJ, 3PCU, 3R29, 3R2A, 3R5M, 3UVV, 4CN2, 4CN3, 4CN5, 4CN7, 4J5W, 4J5X, 4K4J, 4K6I
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF11825	Nuc_recep-AF1	17 → 127	Nuclear/hormone receptor activator site AF-1	Family
  PF00105	zf-C4	133 → 202	Zinc finger, C4 type (two domains)	Domain
  PF00104	Hormone_recep	257 → 442	Ligand-binding domain of nuclear hormone receptor	Domain

• Sequence:

  MDTKHFLPLDFSTQVNSSLTSPTGRGSMAAPSLHPSLGPGIGSPGQLHSPISTLSSPING
  MGPPFSVISSPMGPHSMSVPTTPTLGFSTGSPQLSSPMNPVSSSEDIKPPLGLNGVLKVP
  AHPSGNMASFTKHICAICGDRSSGKHYGVYSCEGCKGFFKRTVRKDLTYTCRDNKDCLID
  KRQRNRCQYCRYQKCLAMGMKREAVQEERQRGKDRNENEVESTSSANEDMPVERILEAEL
  AVEPKTETYVEANMGLNPSSPNDPVTNICQAADKQLFTLVEWAKRIPHFSELPLDDQVIL
  LRAGWNELLIASFSHRSIAVKDGILLATGLHVHRNSAHSAGVGAIFDRVLTELVSKMRDM
  QMDKTELGCLRAIVLFNPDSKGLSNPAEVEALREKVYASLEAYCKHKYPEQPGRFAKLLL
  RLPALRSIGLKCLEHLFFFKLIGDTPIDTFLMEMLEAPHQMT

• Sequence length: 462