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RXRA - retinoid X receptor alpha
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).
Uniprot BrowserEntrez ID | EnsEMBL ID | Preferred Name | Uniprot ID |
---|---|---|---|
6256 | ENSG00000186350 | RXRA | P19793 |
Causal Flows
are statistically significant links between putative causal events (somatic mutations, copy number variations, chromosomal translocations, etc.) and the activity levels of regulators and regulons. In the causal flow, a mutation
may causally activate or deactivate a downstream regulator
which then might up- down-regulates a regulon
that contains genes with similar expression profiles and binding sites.
Causal Mechanistic Flows with ENSG00000186350 as Regulator
ID | Mutation | Role | Regulator | Role | Regulon | # downstream regulons | # diffexp regulons | Drugs |
---|---|---|---|---|---|---|---|---|
CMF-09252 | RP1 | down-regulates | RXRA | activates | R-3219 | 13 | 3 | Drugs (5) |
CMF-09254 | RP1 | down-regulates | RXRA | activates | R-3213 | 13 | 3 | Drugs (12) Regulator Drugs (2)Regulon Drugs (10)SULTHIAME, CILENGITIDE, SENICAPOC, DKN-01, CG250 177LU, GIRENTUXIMAB, CG250 111IN, INTETUMUMAB, BHQ-880, ABITUZUMAB |
CMF-15046 | PTEN | up-regulates | RXRA | activates | R-3213 | 13 | 1 | Drugs (12) Regulator Drugs (2)Regulon Drugs (10)SULTHIAME, CILENGITIDE, SENICAPOC, DKN-01, CG250 177LU, GIRENTUXIMAB, CG250 111IN, INTETUMUMAB, BHQ-880, ABITUZUMAB |
CMF-17131 | CDH18 | up-regulates | RXRA | activates | R-3213 | 13 | 1 | Drugs (12) Regulator Drugs (2)Regulon Drugs (10)SULTHIAME, CILENGITIDE, SENICAPOC, DKN-01, CG250 177LU, GIRENTUXIMAB, CG250 111IN, INTETUMUMAB, BHQ-880, ABITUZUMAB |
CMF-24284 | SMCHD1 | up-regulates | RXRA | activates | R-3213 | 13 | 1 | Drugs (12) Regulator Drugs (2)Regulon Drugs (10)SULTHIAME, CILENGITIDE, SENICAPOC, DKN-01, CG250 177LU, GIRENTUXIMAB, CG250 111IN, INTETUMUMAB, BHQ-880, ABITUZUMAB |
CMF-25400 | CENPF | up-regulates | RXRA | activates | R-3213 | 13 | 2 | Drugs (12) Regulator Drugs (2)Regulon Drugs (10)SULTHIAME, CILENGITIDE, SENICAPOC, DKN-01, CG250 177LU, GIRENTUXIMAB, CG250 111IN, INTETUMUMAB, BHQ-880, ABITUZUMAB |