Retinoic acid receptor RXR-alpha
Also known as: NR2B1, RXRA
Function
Receptor for retinoic acid that acts as a transcription factor. 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. 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. The high affinity ligand for retinoid X receptors (RXRs) is 9-cis retinoic acid. 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. On ligand binding, the corepressors dissociate from the receptors and coactivators are recruited leading to transcriptional activation. Serves as a common heterodimeric partner for a number of nuclear receptors, such as RARA, RARB and PPARA. The RXRA/RARB heterodimer can act as a transcriptional repressor or transcriptional activator, depending on the RARE DNA element context. The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes. Together with RARA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells. Acts as an enhancer of RARA binding to RARE DNA element. May facilitate the nuclear import of heterodimerization partners such as VDR and NR4A1. Promotes myelin debris phagocytosis and remyelination by macrophages. 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. Involved in the regulation of calcium signaling by repressing ITPR2 gene expression, thereby controlling cellular senescence.
Classification
- Family (Pfam)
- PF00104 Hormone_recep, PF11825 Nuc_recep-AF1, PF00105 zf-C4
- InterPro
- NHR-like_dom_sf, Nuc_recep-AF1, Nucl_hrmn_rcpt_lig-bd, Nuclear_hormone_rcpt_NR2, Nuclear_hrmn_rcpt, Retinoid-X_rcpt/HNF4, Znf_hrmn_rcpt, Znf_NHR/GATA
- Functional cluster
- Homeobox & Zinc-Finger Transcription Factors
Experimental structures · PDB · 109
- 1BY4 X-ray 2.10A
- 1DSZ X-ray 1.70A
- 1FBY X-ray 2.25A
- 1FM6 X-ray 2.10A
- 1FM9 X-ray 2.10A
- 1G1U X-ray 2.50A
- 1G5Y X-ray 2.00A
- 1K74 X-ray 2.30A
- 1MV9 X-ray 1.90A
- 1MVC X-ray 1.90A
- 1MZN X-ray 1.90A
- 1R0N X-ray 2.60A
- … and 97 more
A predicted model is available from AlphaFold.
Gene Ontology · 49
- GO:0000785 chromatin
- GO:0005829 cytosol
- GO:0005739 mitochondrion
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:0043235 receptor complex
- GO:0090575 RNA polymerase II transcription regulator complex
- GO:0050692 DNA binding domain binding
- GO:0003700 DNA-binding transcription factor activity
- GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
- GO:0003690 double-stranded DNA binding
- GO:0019899 enzyme binding
- GO:0042802 identical protein binding
- GO:0050693 LBD domain binding
- GO:0004879 nuclear receptor activity
- GO:0003707 nuclear steroid receptor activity
- GO:0042809 nuclear vitamin D receptor binding
- GO:0042277 peptide binding
- GO:0001972 retinoic acid binding
- GO:0044323 retinoic acid-responsive element binding
- GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
- GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding
- GO:0043565 sequence-specific DNA binding
- GO:1990837 sequence-specific double-stranded DNA binding
- GO:0000976 transcription cis-regulatory region binding
- GO:0003712 transcription coregulator activity
- GO:0001221 transcription coregulator binding
- GO:0008270 zinc ion binding
- GO:0015721 bile acid and bile salt transport
- GO:0030154 cell differentiation
- GO:0048469 cell maturation
- GO:0071404 cellular response to low-density lipoprotein particle stimulus
- GO:0009755 hormone-mediated signaling pathway
- GO:0030224 monocyte differentiation
- GO:0042789 mRNA transcription by RNA polymerase II
- GO:0000122 negative regulation of transcription by RNA polymerase II
- GO:0007399 nervous system development
- GO:0035357 peroxisome proliferator activated receptor signaling pathway
- GO:0030501 positive regulation of bone mineralization
- GO:0010875 positive regulation of cholesterol efflux
- GO:0045893 positive regulation of DNA-templated transcription
- GO:0045834 positive regulation of lipid metabolic process
- GO:0140077 positive regulation of lipoprotein transport
- GO:0002157 positive regulation of thyroid hormone receptor signaling pathway
- GO:0045944 positive regulation of transcription by RNA polymerase II
- GO:0070564 positive regulation of vitamin D receptor signaling pathway
- GO:0019216 regulation of lipid metabolic process
- GO:0032526 response to retinoic acid
- GO:0048384 retinoic acid receptor signaling pathway
Drugs targeting this protein · 8
- BEXAROTENE agonist
- ACITRETIN agonist
- MOFAROTENE modulator
- SDX-101 modulator
- ETRETINATE agonist
- DANTHRON antagonist
- ALITRETINOIN agonist
- IRX-4204 agonist
Related proteins · sequence + function similarity
- Retinoic acid receptor RXR-alpha 1.00
- Retinoic acid receptor RXR-alpha 0.99
- Retinoic acid receptor RXR-alpha-A 0.99
- Retinoic acid receptor RXR-alpha 0.98
- Retinoic acid receptor RXR-gamma 0.97
- Retinoic acid receptor RXR-gamma 0.97
- Retinoic acid receptor RXR-gamma 0.97
- Retinoic acid receptor RXR-gamma 0.97
- Retinoic acid receptor RXR-gamma 0.97
- Retinoic acid receptor RXR-gamma-B 0.97
- Retinoic acid receptor RXR-gamma-A 0.96
- Retinoic acid receptor RXR-gamma 0.96
Co-cited proteins · studied together in the literature
- Oxysterols receptor LXR-alpha 3 shared papers
- Retinoic acid receptor alpha 10 shared papers
- Peroxisome proliferator-activated receptor alpha 5 shared papers
- Retinoic acid receptor beta 2 shared papers
- Vitamin D3 receptor 4 shared papers
- Nuclear receptor subfamily 1 group I member 3 1 shared papers
- Retinoic acid receptor RXR-alpha 3 shared papers
- Peroxisome proliferator-activated receptor gamma 5 shared papers
- Thyroid hormone receptor beta 3 shared papers
- Thyroid hormone receptor alpha 1 shared papers
- Insulin-like growth factor-binding protein 3 1 shared papers
- Nuclear receptor subfamily 4immunitygroup A member 1 2 shared papers
Literature · 52 cited papers
- UBR5 forms ligand-dependent complexes on chromatin to regulate nuclear hormone receptor stability. Mol. Cell · 2023
- Ligand binding and heterodimerization with retinoid X receptor alpha (RXRalpha) induce farnesoid X receptor (FXR) conformational changes affecting coactivator binding. J. Biol. Chem. · 2018
- The nuclear receptor RXRA controls cellular senescence by regulating calcium signaling. Aging Cell · 2018
- The quaternary architecture of RARbeta-RXRalpha heterodimer facilitates domain-domain signal transmission. Nat. Commun. · 2017
- Functional analyses of a novel missense and other mutations of the vitamin D receptor in association with alopecia. Sci. Rep. · 2017
- MicroRNA-10a is crucial for endothelial response to different flow patterns via interaction of retinoid acid receptors and histone deacetylases. Proc. Natl. Acad. Sci. U.S.A. · 2017
- Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
- Retinoid X receptor activation reverses age-related deficiencies in myelin debris phagocytosis and remyelination. Brain · 2015
- Retinoid X receptor alpha attenuates host antiviral response by suppressing type I interferon. Nat. Commun. · 2014
- An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
- Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
- Activity of retinoic acid receptor-alpha is directly regulated at its protein kinase A sites in response to follicle-stimulating hormone signaling. Endocrinology · 2010
- … and 40 more in the literature graph