View source for Retinoid X receptor

{{Short description|Genes on human chromosome 9}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox protein
| Name = [[retinoid X receptor alpha]]
| caption = 
| image = 
| width = 
| HGNCid = 10477
| Symbol = RXRA
| AltSymbols = 
| EntrezGene = 6256
| OMIM = 180245
| RefSeq = NM_002957
| UniProt = P19793
| PDB = 
| ECnumber = 
| Chromosome = 9
| Arm = q
| Band = 34
| LocusSupplementaryData = 
}}
{{Infobox protein
| Name = [[retinoid X receptor beta]]
| caption = 
| image = 
| width = 
| HGNCid = 10478
| Symbol = RXRB
| AltSymbols = 
| EntrezGene = 6257
| OMIM = 180246
| RefSeq = NM_021976
| UniProt = P28702
| PDB = 
| ECnumber = 
| Chromosome = 6
| Arm = p
| Band = 21.3
| LocusSupplementaryData = 
}}
{{Infobox protein
| Name = [[retinoid X receptor gamma]]
| caption = 
| image = 
| width = 
| HGNCid = 10479
| Symbol = [[retinoid X receptor gamma|RXRG]]
| AltSymbols = 
| EntrezGene = 6258
| OMIM = 180247
| RefSeq = NM_006917
| UniProt = P48443
| PDB = 
| ECnumber = 
| Chromosome = 1
| Arm = q
| Band = 22
| LocusSupplementaryData = -q23}}

The '''retinoid X receptor''' ('''RXR''')<ref name="Germain_2006b">{{cite journal | vauthors = Germain P, Chambon P, Eichele G, Evans RM, Lazar MA, Leid M, De Lera AR, Lotan R, Mangelsdorf DJ, Gronemeyer H | title = International Union of Pharmacology. LXIII. Retinoid X receptors | journal = Pharmacological Reviews | volume = 58 | issue = 4 | pages = 760–772 | date = December 2006 | pmid = 17132853 | doi = 10.1124/pr.58.4.7 | s2cid = 1476000 }}</ref> is a type of [[nuclear receptor]] that is activated by [[9-cis retinoic acid]], which is discussed controversially to be of endogenous relevance,<ref name="De Lera et al. 2016">{{cite journal | vauthors = de Lera ÁR, Krezel W, Rühl R | title = An Endogenous Mammalian Retinoid X Receptor Ligand, At Last! | journal = ChemMedChem | volume = 11 | issue = 10 | pages = 1027–1037 | date = May 2016 | pmid = 27151148 | doi = 10.1002/cmdc.201600105 | s2cid = 269196 }}</ref><ref name="Allenby_1993">{{cite journal | vauthors = Allenby G, Bocquel MT, Saunders M, Kazmer S, Speck J, Rosenberger M, Lovey A, Kastner P, Grippo JF, Chambon P | title = Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 1 | pages = 30–34 | date = January 1993 | pmid = 8380496 | pmc = 45593 | doi = 10.1073/pnas.90.1.30 | doi-access = free | bibcode = 1993PNAS...90...30A }}</ref> and 9-''cis''-13,14-dihydroretinoic acid, which may be an endogenous mammalian RXR-selective agonist.<ref name="Rühl et al._2015">{{cite journal | vauthors = Rühl R, Krzyżosiak A, Niewiadomska-Cimicka A, Rochel N, Szeles L, Vaz B, Wietrzych-Schindler M, Álvarez S, Szklenar M, Nagy L, de Lera AR, Krężel W | title = 9-cis-13,14-Dihydroretinoic Acid Is an Endogenous Retinoid Acting as RXR Ligand in Mice | journal = PLOS Genetics | volume = 11 | issue = 6 | pages = e1005213 | date = June 2015 | pmid = 26030625 | pmc = 4451509 | doi = 10.1371/journal.pgen.1005213 | doi-access = free }}</ref> [[Bexarotene]] is the only specific activator of the RXRs which does not activate the [[Retinoic acid receptor|Retinoic Acid Receptors]].<ref>{{cite journal | vauthors = Panchal MR, Scarisbrick JJ | title = The utility of bexarotene in mycosis fungoides and Sézary syndrome | journal = OncoTargets and Therapy | volume = 8 | pages = 367–373 | date = 2015-02-03 | pmid = 25678803 | pmc = 4322887 | doi = 10.2147/OTT.S61308 | doi-access = free }}</ref>

There are three retinoic X receptors (RXR): [[retinoid X receptor alpha|RXR-alpha]], [[retinoid X receptor beta|RXR-beta]], and [[retinoid X receptor gamma|RXR-gamma]], encoded by the {{gene|RXRA}}, {{gene|RXRB}}, {{gene|RXRG}} genes, respectively.

RXR [[Protein dimer|heterodimerizes]] with multiple nuclear receptors including [[constitutive androstane receptor|CAR]], [[farnesoid X receptor|FXR]], [[liver X receptor|LXR]], [[peroxisome proliferator-activated receptor|PPAR]],<ref name="pmid21493923">{{cite journal | vauthors = Plutzky J | title = The PPAR-RXR transcriptional complex in the vasculature: energy in the balance | journal = Circulation Research | volume = 108 | issue = 8 | pages = 1002–1016 | date = April 2011 | pmid = 21493923 | doi = 10.1161/CIRCRESAHA.110.226860 | doi-access = free }}</ref> [[pregnane X receptor|PXR]], [[retinoic acid receptor|RAR]], [[thyroid hormone receptor|TR]], [[Estrogen receptor|ER]] and [[vitamin D receptor|VDR]]. RXRs are permissive co-receptors as only one of six alleles is needed for normal development and health.<ref>{{cite journal | vauthors = Krezel W, Dupé V, Mark M, Dierich A, Kastner P, Chambon P | title = RXR gamma null mice are apparently normal and compound RXR alpha +/-/RXR beta -/-/RXR gamma -/- mutant mice are viable | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 17 | pages = 9010–9014 | date = August 1996 | pmid = 8799145 | pmc = 38586 | doi = 10.1073/pnas.93.17.9010 | doi-access = free }}</ref> Given this, it is difficult to extrapolate whether the RXR pathway has its own endogenous activity driven by 9-cis retinoic acid species or whether it merely participates in other pathways, predominantly the retinoic nuclear receptor pathway. Genomic knockout of the RXRs results in obesity resistance<ref>{{cite journal | vauthors = Haugen BR, Jensen DR, Sharma V, Pulawa LK, Hays WR, Krezel W, Chambon P, Eckel RH | title = Retinoid X receptor gamma-deficient mice have increased skeletal muscle lipoprotein lipase activity and less weight gain when fed a high-fat diet | journal = Endocrinology | volume = 145 | issue = 8 | pages = 3679–3685 | date = August 2004 | pmid = 15087432 | doi = 10.1210/en.2003-1401 }}</ref> while [[bexarotene]] treatment causes severe [[hypothyroidism]],<ref>{{cite journal | vauthors = Esposito M, Amory JK, Kang Y | title = The pathogenic role of retinoid nuclear receptor signaling in cancer and metabolic syndromes | journal = The Journal of Experimental Medicine | volume = 221 | issue = 9 | date = September 2024 | pmid = 39133222 | doi = 10.1084/jem.20240519 | doi-access = free | pmc = 11318670 }}</ref> suggesting that the RXR pathway functions at least to regulate the [[Thyroid|Thyroid Receptor]] pathway.

As with other [[Nuclear receptor#Type II|type II]] nuclear receptors, the RXR heterodimer in the absence of ligand is bound to hormone response elements complexed with [[corepressor (genetics)|corepressor]] protein.  Binding of agonist [[ligand]]s to RXR results in dissociation of corepressor and recruitment of [[coactivator (genetics)|coactivator]] protein, which, in turn, promotes [[gene transcription|transcription]] of the downstream target [[gene]] into [[mRNA]] and eventually [[protein]].

== See also ==
* [[Retinoic acid receptor]]
* [[RXRA|Retinoid X receptor alpha]]
* [[RXRB|Retinoid X receptor beta]]
* [[RXRG|Retinoid X receptor gamma]]

== References ==
{{Reflist|2}}

== External links ==
* {{MeshName|Retinoid+X+Receptors}}

{{Transcription factors|g2}}
{{Retinoid receptor modulators}}

[[Category:Intracellular receptors]]
[[Category:Transcription factors]]

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