RXRA

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]

Retinoid X Receptor Alpha

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).

Biological Process anatomical structure developmentManual Assertion Based On ExperimentIBA:GO_Central
Biological Process cell differentiationManual Assertion Based On ExperimentIBA:GO_Central
Biological Process hormone-mediated signaling pathwayManual Assertion Based On ExperimentIDA:ComplexPortal
Biological Process mRNA transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:ComplexPortal
Biological Process negative regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process peroxisome proliferator activated receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of bone mineralization1 PublicationIC:ComplexPortal
Biological Process positive regulation of cholesterol effluxManual Assertion Based On ExperimentTAS:BHF-UCL
Biological Process positive regulation of DNA-templated transcriptionManual Assertion Based On ExperimentIDA:GO_Central
Biological Process positive regulation of thyroid hormone mediated signaling pathwayManual Assertion Based On ExperimentIDA:ComplexPortal
Biological Process positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of transporter activityManual Assertion Based On ExperimentTAS:BHF-UCL
Biological Process positive regulation of vitamin D receptor signaling pathwayManual Assertion Based On ExperimentIDA:ComplexPortal
Biological Process regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIBA:GO_Central
Biological Process response to retinoic acidManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process retinoic acid receptor signaling pathwayManual Assertion Based On ExperimentIDA:ComplexPortal

Nucleus
Cytoplasm
Mitochondrion
Localization to the nucleus is enhanced by vitamin D3 (PubMed:15509776).
Nuclear localization may be enhanced by the interaction with heterodimerization partner VDR (PubMed:12145331).
Translocation to the mitochondrion upon interaction with NR4A1 (PubMed:17761950, PubMed:15509776).
Increased nuclear localization upon pulsatile shear stress (PubMed:28167758).

Acetylated by EP300; acetylation enhances DNA binding and transcriptional activity.
Phosphorylated on serine and threonine residues mainly in the N-terminal modulating domain (By similarity).
Constitutively phosphorylated on Ser-21 in the presence or absence of ligand (By similarity).
Under stress conditions, hyperphosphorylated by activated JNK on Ser-56, Ser-70, Thr-82 and Ser-260 (By similarity).
Phosphorylated on Ser-27, in vitro, by PKA (PubMed:11162439).
This phosphorylation is required for repression of cAMP-mediated transcriptional activity of RARA (PubMed:11162439).
Sumoylation negatively regulates transcriptional activity. Desumoylated specifically by SENP6.