RXRA_MOUSE
ID RXRA_MOUSE Reviewed; 467 AA.
AC P28700;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 03-AUG-2022, entry version 215.
DE RecName: Full=Retinoic acid receptor RXR-alpha;
DE AltName: Full=Nuclear receptor subfamily 2 group B member 1;
DE AltName: Full=Retinoid X receptor alpha;
GN Name=Rxra; Synonyms=Nr2b1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], HETERODIMERIZATION WITH RARA, AND FUNCTION.
RX PubMed=1310259; DOI=10.1016/0092-8674(92)90478-u;
RA Leid M., Kastner P., Lyons R., Nakshatri H., Saunders M., Zacharewsi T.,
RA Chen J.Y., Staub A., Garnier J.-M., Mader S., Chambon P.;
RT "Purification, cloning, and RXR identity of the HeLa cell factor with which
RT RAR or TR heterodimerizes to bind target sequences efficiently.";
RL Cell 68:377-395(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND IDENTIFICATION OF LIGAND.
RX PubMed=1312497; DOI=10.1101/gad.6.3.329;
RA Mangelsdorf D.J., Borgmeyer U., Heyman R.A., Zhou J.Y., Ong E.S., Oro A.E.,
RA Kakizuka A., Evans R.M.;
RT "Characterization of three RXR genes that mediate the action of 9-cis
RT retinoic acid.";
RL Genes Dev. 6:329-344(1992).
RN [3]
RP PROTEIN SEQUENCE OF 5-16; 27-46; 291-307 AND 446-465, AND SUBUNIT.
RC TISSUE=Adipose tissue;
RX PubMed=7838715; DOI=10.1093/nar/22.25.5628;
RA Tontonoz P., Graves R.A., Budavari A.I., Erdjument-Bromage H., Lui M.,
RA Hu E., Tempst P., Spiegelman B.M.;
RT "Adipocyte-specific transcription factor ARF6 is a heterodimeric complex of
RT two nuclear hormone receptors, PPAR gamma and RXR alpha.";
RL Nucleic Acids Res. 22:5628-5634(1994).
RN [4]
RP FUNCTION, PHOSPHORYLATION AT SER-22; SER-61; SER-75; THR-87 AND SER-265,
RP AND MUTAGENESIS OF SER-22; SER-44; SER-48; SER-54; SER-61; SER-75; THR-87;
RP SER-96; SER-101 AND SER-265.
RX PubMed=10383391; DOI=10.1074/jbc.274.27.18932;
RA Adam-Stitah S., Penna L., Chambon P., Rochette-Egly C.;
RT "Hyperphosphorylation of the retinoid X receptor alpha by activated c-Jun
RT NH2-terminal kinases.";
RL J. Biol. Chem. 274:18932-18941(1999).
RN [5]
RP INTERACTION WITH NCOA6.
RX PubMed=10788465; DOI=10.1074/jbc.275.18.13510;
RA Zhu Y.-J., Kan L., Qi C., Kanwar Y.S., Yeldandi A.V., Rao M.S., Reddy J.K.;
RT "Isolation and characterization of peroxisome proliferator-activated
RT receptor (PPAR) interacting protein (PRIP) as a coactivator for PPAR.";
RL J. Biol. Chem. 275:13510-13516(2000).
RN [6]
RP FUNCTION, PHOSPHORYLATION AT SER-22, AND MUTAGENESIS OF SER-22.
RX PubMed=12032153; DOI=10.1074/jbc.m203623200;
RA Bastien J., Adam-Stitah S., Plassat J.L., Chambon P., Rochette-Egly C.;
RT "The phosphorylation site located in the A region of retinoic X receptor
RT alpha is required for the antiproliferative effect of retinoic acid (RA)
RT and the activation of RA target genes in F9 cells.";
RL J. Biol. Chem. 277:28683-28689(2002).
RN [7]
RP INTERACTION WITH ASXL1 AND NCOA1, AND MUTAGENESIS OF 455-PHE-LEU-456 AND
RP 459-MET-LEU-460.
RX PubMed=16606617; DOI=10.1074/jbc.m512616200;
RA Cho Y.S., Kim E.J., Park U.H., Sin H.S., Um S.J.;
RT "Additional sex comb-like 1 (ASXL1), in cooperation with SRC-1, acts as a
RT ligand-dependent coactivator for retinoic acid receptor.";
RL J. Biol. Chem. 281:17588-17598(2006).
RN [8]
RP INTERACTION WITH FAM120B.
RX PubMed=17595322; DOI=10.1210/me.2006-0520;
RA Li D., Kang Q., Wang D.-M.;
RT "Constitutive coactivator of peroxisome proliferator-activated receptor
RT (PPARgamma), a novel coactivator of PPARgamma that promotes adipogenesis.";
RL Mol. Endocrinol. 21:2320-2333(2007).
RN [9]
RP INTERACTION WITH TACC1.
RX PubMed=20078863; DOI=10.1186/1471-2199-11-3;
RA Guyot R., Vincent S., Bertin J., Samarut J., Ravel-Chapuis P.;
RT "The transforming acidic coiled coil (TACC1) protein modulates the
RT transcriptional activity of the nuclear receptors TR and RAR.";
RL BMC Mol. Biol. 11:3-3(2010).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 230-462 OF MUTANT ALA-318 IN
RP COMPLEX WITH H.SAPIENS RARA.
RX PubMed=10882070; DOI=10.1016/s1097-2765(00)80424-4;
RA Bourguet W., Vivat V., Wurtz J.M., Chambon P., Gronemeyer H., Moras D.;
RT "Crystal structure of a heterodimeric complex of RAR and RXR ligand-binding
RT domains.";
RL Mol. Cell 5:289-298(2000).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 230-467 IN COMPLEX WITH RARB AND
RP MED1.
RX PubMed=15528208; DOI=10.1074/jbc.m409302200;
RA Pogenberg V., Guichou J.F., Vivat-Hannah V., Kammerer S., Perez E.,
RA Germain P., de Lera A.R., Gronemeyer H., Royer C.A., Bourguet W.;
RT "Characterization of the interaction between retinoic acid
RT receptor/retinoid X receptor (RAR/RXR) heterodimers and transcriptional
RT coactivators through structural and fluorescence anisotropy studies.";
RL J. Biol. Chem. 280:1625-1633(2005).
RN [13]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION BY VIRAL INFECTION.
RX PubMed=25417649; DOI=10.1038/ncomms6494;
RA Ma F., Liu S.Y., Razani B., Arora N., Li B., Kagechika H., Tontonoz P.,
RA Nunez V., Ricote M., Cheng G.;
RT "Retinoid X receptor alpha attenuates host antiviral response by
RT suppressing type I interferon.";
RL Nat. Commun. 5:5494-5494(2014).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, REPRESSION BY AGING,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=26463675; DOI=10.1093/brain/awv289;
RA Natrajan M.S., de la Fuente A.G., Crawford A.H., Linehan E., Nunez V.,
RA Johnson K.R., Wu T., Fitzgerald D.C., Ricote M., Bielekova B.,
RA Franklin R.J.;
RT "Retinoid X receptor activation reverses age-related deficiencies in myelin
RT debris phagocytosis and remyelination.";
RL Brain 138:3581-3597(2015).
CC -!- FUNCTION: Receptor for retinoic acid that acts as a transcription
CC factor (PubMed:10383391, PubMed:12032153, PubMed:25417649). Forms
CC homo- or heterodimers with retinoic acid receptors (RARs) and binds to
CC target response elements in response to their ligands, all-trans or 9-
CC cis retinoic acid, to regulate gene expression in various biological
CC processes (PubMed:1310259, PubMed:10383391). The RAR/RXR heterodimers
CC bind to the retinoic acid response elements (RARE) composed of tandem
CC 5'-AGGTCA-3' sites known as DR1-DR5 to regulate transcription
CC (PubMed:1310259). The high affinity ligand for retinoid X receptors
CC (RXRs) is 9-cis retinoic acid (PubMed:10383391, PubMed:25417649). In
CC the absence of ligand, the RXR-RAR heterodimers associate with a
CC multiprotein complex containing transcription corepressors that induce
CC histone deacetylation, chromatin condensation and transcriptional
CC suppression (By similarity). On ligand binding, the corepressors
CC dissociate from the receptors and coactivators are recruited leading to
CC transcriptional activation (By similarity). Serves as a common
CC heterodimeric partner for a number of nuclear receptors, such as RARA,
CC RARB and PPARA (PubMed:1310259). The RXRA/RARB heterodimer can act as a
CC transcriptional repressor or transcriptional activator, depending on
CC the RARE DNA element context (By similarity). The RXRA/PPARA
CC heterodimer is required for PPARA transcriptional activity on fatty
CC acid oxidation genes such as ACOX1 and the P450 system genes (By
CC similarity). Together with RARA, positively regulates microRNA-10a
CC expression, thereby inhibiting the GATA6/VCAM1 signaling response to
CC pulsatile shear stress in vascular endothelial cells (By similarity).
CC Acts as an enhancer of RARA binding to RARE DNA element (By
CC similarity). May facilitate the nuclear import of heterodimerization
CC partners such as VDR and NR4A1 (By similarity). Promotes myelin debris
CC phagocytosis and remyelination by macrophages (PubMed:26463675). Plays
CC a role in the attenuation of the innate immune system in response to
CC viral infections, possibly by negatively regulating the transcription
CC of antiviral genes such as type I IFN genes (PubMed:25417649). Involved
CC in the regulation of calcium signaling by repressing ITPR2 gene
CC expression, thereby controlling cellular senescence (By similarity).
CC {ECO:0000250|UniProtKB:P19793, ECO:0000269|PubMed:10383391,
CC ECO:0000269|PubMed:12032153, ECO:0000269|PubMed:1310259,
CC ECO:0000269|PubMed:25417649, ECO:0000269|PubMed:26463675}.
CC -!- SUBUNIT: Homodimer (By similarity). Heterodimer with RARA; required for
CC ligand-dependent retinoic acid receptor transcriptional activity
CC (PubMed:10882070). Heterodimer with PPARA (via the leucine-like zipper
CC in the LBD); the interaction is required for PPARA transcriptional
CC activity (By similarity). Heterodimerizes with PPARG (PubMed:7838715).
CC Heterodimerizes (via NR LBD) with RARB (By similarity). Heterodimerizes
CC with NR1H4; the heterodimerization enhances the binding affinity for
CC LXXLL motifs from coactivators (By similarity). Interacts with
CC coactivator NCO6 (PubMed:10788465). Interacts with coactivator NCO3 (By
CC similarity). Interacts with coactivator FAM120B (PubMed:17595322).
CC Interacts with coactivator PELP1, SENP6, SFPQ, DNTTIP2 and RNF8 (By
CC similarity). Interacts with PRMT2 (By similarity). Interacts with ASXL1
CC (PubMed:16606617). Interacts with BHLHE40/DEC1, BHLHE41/DEC2, NCOR1 and
CC NCOR2 (By similarity). Interacts in a ligand-dependent fashion with
CC MED1 and NCOA1 (PubMed:15528208, PubMed:16606617). Interacts with VDR
CC (By similarity). Interacts with EP300; the interaction is decreased by
CC 9-cis retinoic acid (By similarity). Heterodimer (via C-terminus) with
CC NR4A1 (via DNA-binding domain); the interaction is enhanced by 9-cis
CC retinoic acid (By similarity). NR4A1 competes with EP300 for
CC interaction with RXRA and thereby attenuates EP300 mediated acetylation
CC of RXRA (By similarity). In the absence of hormonal ligand, interacts
CC with TACC1 (PubMed:20078863). {ECO:0000250|UniProtKB:P19793,
CC ECO:0000269|PubMed:10788465, ECO:0000269|PubMed:10882070,
CC ECO:0000269|PubMed:15528208, ECO:0000269|PubMed:16606617,
CC ECO:0000269|PubMed:17595322, ECO:0000269|PubMed:20078863,
CC ECO:0000269|PubMed:7838715}.
CC -!- INTERACTION:
CC P28700; P59598: Asxl1; NbExp=2; IntAct=EBI-346715, EBI-5743705;
CC P28700; Q64337: Sqstm1; NbExp=3; IntAct=EBI-346715, EBI-645025;
CC P28700; Q8IXJ9: ASXL1; Xeno; NbExp=2; IntAct=EBI-346715, EBI-1646500;
CC P28700; Q71SY5: MED25; Xeno; NbExp=3; IntAct=EBI-346715, EBI-394558;
CC P28700; P23246-1: SFPQ; Xeno; NbExp=3; IntAct=EBI-346715, EBI-355463;
CC P28700; Q13501: SQSTM1; Xeno; NbExp=3; IntAct=EBI-346715, EBI-307104;
CC P28700; P11473: VDR; Xeno; NbExp=3; IntAct=EBI-346715, EBI-286357;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26463675}. Cytoplasm
CC {ECO:0000250|UniProtKB:P19793}. Mitochondrion
CC {ECO:0000250|UniProtKB:P19793}. Note=Localization to the nucleus is
CC enhanced by vitamin D3 (By similarity). Nuclear localization may be
CC enhanced by the interaction with heterodimerization partner VDR (By
CC similarity). Translocation to the mitochondrion upon interaction with
CC NR4A1 (By similarity). Increased nuclear localization upon pulsatile
CC shear stress (By similarity). {ECO:0000250|UniProtKB:P19793}.
CC -!- TISSUE SPECIFICITY: Expressed in macrophages (at protein level).
CC {ECO:0000269|PubMed:25417649, ECO:0000269|PubMed:26463675}.
CC -!- INDUCTION: Down-regulated by infection with viruses, such as VSV, HSV-1
CC and MHV68 (PubMed:25417649). Down-regulated by aging (PubMed:26463675).
CC {ECO:0000269|PubMed:25417649, ECO:0000269|PubMed:26463675}.
CC -!- DOMAIN: Composed of three domains: a modulating N-terminal or AF1
CC domain, a DNA-binding domain and a C-terminal ligand-binding or AF2
CC domain.
CC -!- PTM: Acetylated by EP300; acetylation enhances DNA binding and
CC transcriptional activity. {ECO:0000250|UniProtKB:P19793}.
CC -!- PTM: Phosphorylated on serine and threonine residues mainly in the N-
CC terminal modulating domain (PubMed:10383391, PubMed:12032153).
CC Constitutively phosphorylated on Ser-22 in the presence or absence of
CC ligand (PubMed:10383391, PubMed:12032153). Under stress conditions,
CC hyperphosphorylated by activated JNK on Ser-61, Ser-75, Thr-87 and Ser-
CC 265 (PubMed:10383391). Phosphorylated on Ser-28, in vitro, by PKA (By
CC similarity). This phosphorylation is required for repression of cAMP-
CC mediated transcriptional activity of RARA (By similarity).
CC {ECO:0000250, ECO:0000250|UniProtKB:P19793,
CC ECO:0000269|PubMed:10383391, ECO:0000269|PubMed:12032153}.
CC -!- PTM: Sumoylation negatively regulates transcriptional activity.
CC Desumoylated specifically by SENP6. {ECO:0000250|UniProtKB:P19793}.
CC -!- DISRUPTION PHENOTYPE: Reduced myelin debris uptake by bone marrow-
CC derived macrophages (PubMed:26463675). Conditional knockout in myeloid
CC cells results in reduced myelin debris clearing by macrophages, delayed
CC oligodendrocyte progenitor cell differentiation and slowern
CC remyelination after induced focal demyelination (PubMed:26463675).
CC {ECO:0000269|PubMed:26463675}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR2
CC subfamily. {ECO:0000305}.
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DR EMBL; M84817; AAA40080.1; -; mRNA.
DR EMBL; X66223; CAA46962.1; -; mRNA.
DR CCDS; CCDS15830.1; -.
DR PIR; S26668; S26668.
DR RefSeq; NP_035435.1; NM_011305.3.
DR PDB; 1DKF; X-ray; 2.50 A; A=230-462.
DR PDB; 1XDK; X-ray; 2.90 A; A/E=230-467.
DR PDB; 3A9E; X-ray; 2.75 A; A=228-467.
DR PDB; 7AOS; X-ray; 2.55 A; A=230-467.
DR PDBsum; 1DKF; -.
DR PDBsum; 1XDK; -.
DR PDBsum; 3A9E; -.
DR PDBsum; 7AOS; -.
DR AlphaFoldDB; P28700; -.
DR BMRB; P28700; -.
DR SASBDB; P28700; -.
DR SMR; P28700; -.
DR BioGRID; 203038; 24.
DR ComplexPortal; CPX-505; RXRalpha-PXR nuclear receptor complex.
DR ComplexPortal; CPX-5343; RXRalpha-NCOA1 activated retinoic acid receptor complex.
DR ComplexPortal; CPX-584; RXRalpha-RARalpha retinoic acid receptor complex.
DR ComplexPortal; CPX-643; RXRalpha-NCOA2 activated retinoic acid receptor complex.
DR ComplexPortal; CPX-672; RXRalpha-RXRalpha retinoic acid receptor complex.
DR ComplexPortal; CPX-673; RXRalpha-VDR nuclear hormone receptor complex.
DR ComplexPortal; CPX-679; RXRalpha-LXRbeta nuclear hormone receptor complex.
DR ComplexPortal; CPX-708; RXRalpha-LXRalpha nuclear hormone receptor complex.
DR ComplexPortal; CPX-710; RXRalpha-TRbeta nuclear hormone receptor complex.
DR ComplexPortal; CPX-713; RXRalpha-TRalpha nuclear hormone receptor complex.
DR ComplexPortal; CPX-818; RXRalpha-RARalpha-NCOA2 retinoic acid receptor complex.
DR IntAct; P28700; 22.
DR MINT; P28700; -.
DR STRING; 10090.ENSMUSP00000076491; -.
DR BindingDB; P28700; -.
DR ChEMBL; CHEMBL3084; -.
DR DrugCentral; P28700; -.
DR GuidetoPHARMACOLOGY; 610; -.
DR iPTMnet; P28700; -.
DR PhosphoSitePlus; P28700; -.
DR MaxQB; P28700; -.
DR PaxDb; P28700; -.
DR PRIDE; P28700; -.
DR ProteomicsDB; 260961; -.
DR Antibodypedia; 3881; 430 antibodies from 41 providers.
DR DNASU; 20181; -.
DR Ensembl; ENSMUST00000077257; ENSMUSP00000076491; ENSMUSG00000015846.
DR Ensembl; ENSMUST00000166775; ENSMUSP00000133044; ENSMUSG00000015846.
DR GeneID; 20181; -.
DR KEGG; mmu:20181; -.
DR UCSC; uc008ixs.1; mouse.
DR CTD; 6256; -.
DR MGI; MGI:98214; Rxra.
DR VEuPathDB; HostDB:ENSMUSG00000015846; -.
DR eggNOG; KOG3575; Eukaryota.
DR GeneTree; ENSGT00940000159789; -.
DR InParanoid; P28700; -.
DR OMA; NAVSHIC; -.
DR OrthoDB; 912470at2759; -.
DR PhylomeDB; P28700; -.
DR TreeFam; TF352097; -.
DR Reactome; R-MMU-159418; Recycling of bile acids and salts.
DR Reactome; R-MMU-192105; Synthesis of bile acids and bile salts.
DR Reactome; R-MMU-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR Reactome; R-MMU-193807; Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
DR Reactome; R-MMU-200425; Carnitine metabolism.
DR Reactome; R-MMU-204174; Regulation of pyruvate dehydrogenase (PDH) complex.
DR Reactome; R-MMU-211976; Endogenous sterols.
DR Reactome; R-MMU-381340; Transcriptional regulation of white adipocyte differentiation.
DR Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
DR Reactome; R-MMU-400206; Regulation of lipid metabolism by PPARalpha.
DR Reactome; R-MMU-4090294; SUMOylation of intracellular receptors.
DR Reactome; R-MMU-5362517; Signaling by Retinoic Acid.
DR Reactome; R-MMU-9029569; NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux.
DR Reactome; R-MMU-9616222; Transcriptional regulation of granulopoiesis.
DR Reactome; R-MMU-9623433; NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis.
DR Reactome; R-MMU-9707564; Cytoprotection by HMOX1.
DR BioGRID-ORCS; 20181; 3 hits in 78 CRISPR screens.
DR ChiTaRS; Rxra; mouse.
DR EvolutionaryTrace; P28700; -.
DR PRO; PR:P28700; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P28700; protein.
DR Bgee; ENSMUSG00000015846; Expressed in lip and 259 other tissues.
DR ExpressionAtlas; P28700; baseline and differential.
DR Genevisible; P28700; MM.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IDA:BHF-UCL.
DR GO; GO:0005667; C:transcription regulator complex; IPI:ComplexPortal.
DR GO; GO:0031490; F:chromatin DNA binding; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0050692; F:DNA binding domain binding; ISO:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IGI:MGI.
DR GO; GO:0003690; F:double-stranded DNA binding; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0050693; F:LBD domain binding; ISO:MGI.
DR GO; GO:0004879; F:nuclear receptor activity; IDA:MGI.
DR GO; GO:0016922; F:nuclear receptor binding; ISO:MGI.
DR GO; GO:0042974; F:nuclear retinoic acid receptor binding; ISO:MGI.
DR GO; GO:0003707; F:nuclear steroid receptor activity; IEA:InterPro.
DR GO; GO:0042809; F:nuclear vitamin D receptor binding; ISO:MGI.
DR GO; GO:0042277; F:peptide binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0001972; F:retinoic acid binding; ISO:MGI.
DR GO; GO:0044323; F:retinoic acid-responsive element binding; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0001162; F:RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; IGI:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
DR GO; GO:0001223; F:transcription coactivator binding; IPI:UniProtKB.
DR GO; GO:0001221; F:transcription coregulator binding; ISO:MGI.
DR GO; GO:0070644; F:vitamin D response element binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; ISO:MGI.
DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR GO; GO:0060978; P:angiogenesis involved in coronary vascular morphogenesis; TAS:DFLAT.
DR GO; GO:0043010; P:camera-type eye development; IGI:MGI.
DR GO; GO:0055007; P:cardiac muscle cell differentiation; TAS:DFLAT.
DR GO; GO:0060038; P:cardiac muscle cell proliferation; IMP:MGI.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0007566; P:embryo implantation; IGI:MGI.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0003007; P:heart morphogenesis; TAS:DFLAT.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; ISO:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IGI:MGI.
DR GO; GO:0001893; P:maternal placenta development; IGI:MGI.
DR GO; GO:0060485; P:mesenchyme development; TAS:DFLAT.
DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; IDA:ComplexPortal.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; TAS:DFLAT.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0035357; P:peroxisome proliferator activated receptor signaling pathway; ISO:MGI.
DR GO; GO:0001890; P:placenta development; IMP:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0030501; P:positive regulation of bone mineralization; IC:ComplexPortal.
DR GO; GO:0002157; P:positive regulation of thyroid hormone mediated signaling pathway; IDA:ComplexPortal.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IGI:MGI.
DR GO; GO:0045994; P:positive regulation of translational initiation by iron; IGI:MGI.
DR GO; GO:0070564; P:positive regulation of vitamin D receptor signaling pathway; ISO:MGI.
DR GO; GO:0060687; P:regulation of branching involved in prostate gland morphogenesis; IMP:MGI.
DR GO; GO:0031641; P:regulation of myelination; ISO:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0051384; P:response to glucocorticoid; ISO:MGI.
DR GO; GO:0032526; P:response to retinoic acid; ISO:MGI.
DR GO; GO:0048384; P:retinoic acid receptor signaling pathway; IDA:ComplexPortal.
DR GO; GO:0060528; P:secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development; IMP:MGI.
DR GO; GO:0055012; P:ventricular cardiac muscle cell differentiation; IMP:MGI.
DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; IMP:MGI.
DR GO; GO:0061032; P:visceral serous pericardium development; TAS:DFLAT.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR021780; Nuc_recep-AF1.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR InterPro; IPR000003; Retinoid-X_rcpt/HNF4.
DR InterPro; IPR001628; Znf_hrmn_rcpt.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF11825; Nuc_recep-AF1; 1.
DR Pfam; PF00105; zf-C4; 1.
DR PRINTS; PR00545; RETINOIDXR.
DR PRINTS; PR00398; STRDHORMONER.
DR PRINTS; PR00047; STROIDFINGER.
DR SMART; SM00430; HOLI; 1.
DR SMART; SM00399; ZnF_C4; 1.
DR SUPFAM; SSF48508; SSF48508; 1.
DR PROSITE; PS51843; NR_LBD; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Direct protein sequencing;
KW DNA-binding; Isopeptide bond; Metal-binding; Mitochondrion; Nucleus;
KW Phosphoprotein; Receptor; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..467
FT /note="Retinoic acid receptor RXR-alpha"
FT /id="PRO_0000053567"
FT DOMAIN 232..463
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 140..205
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 140..160
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 176..200
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..139
FT /note="Modulating domain"
FT /evidence="ECO:0000250"
FT REGION 1..112
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 165..170
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P19793"
FT REGION 206..229
FT /note="Hinge"
FT REGION 211..233
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 353..373
FT /note="Required for nuclear export"
FT /evidence="ECO:0000250|UniProtKB:P19793"
FT COMPBIAS 9..28
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 50..68
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 76..108
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 211..227
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 140
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19793"
FT BINDING 143
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19793"
FT BINDING 157
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19793"
FT BINDING 160
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19793"
FT BINDING 176
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19793"
FT BINDING 182
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19793"
FT BINDING 192
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19793"
FT BINDING 195
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19793"
FT BINDING 321
FT /ligand="9-cis-retinoate"
FT /ligand_id="ChEBI:CHEBI:78630"
FT /evidence="ECO:0000250|UniProtKB:P19793"
FT BINDING 321
FT /ligand="all-trans-retinoate"
FT /ligand_id="ChEBI:CHEBI:35291"
FT /evidence="ECO:0000250|UniProtKB:P19793"
FT BINDING 332
FT /ligand="9-cis-retinoate"
FT /ligand_id="ChEBI:CHEBI:78630"
FT /evidence="ECO:0000250|UniProtKB:P19793"
FT BINDING 332
FT /ligand="all-trans-retinoate"
FT /ligand_id="ChEBI:CHEBI:35291"
FT /evidence="ECO:0000250|UniProtKB:P19793"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:10383391,
FT ECO:0000269|PubMed:12032153, ECO:0007744|PubMed:21183079"
FT MOD_RES 28
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19793"
FT MOD_RES 61
FT /note="Phosphoserine; by MAPK8 and MAPK9"
FT /evidence="ECO:0000269|PubMed:10383391"
FT MOD_RES 75
FT /note="Phosphoserine; by MAPK8 and MAPK9"
FT /evidence="ECO:0000269|PubMed:10383391"
FT MOD_RES 87
FT /note="Phosphothreonine; by MAPK8 and MAPK9"
FT /evidence="ECO:0000269|PubMed:10383391"
FT MOD_RES 134
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19793"
FT MOD_RES 150
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P19793"
FT MOD_RES 264
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19793"
FT MOD_RES 265
FT /note="Phosphoserine; by MAPK8 and MAPK9"
FT /evidence="ECO:0000269|PubMed:10383391"
FT CROSSLNK 4
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P19793"
FT CROSSLNK 113
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT MUTAGEN 22
FT /note="S->A: Loss of constituitive phosphorylation. No
FT effect on RXRA transcriptional activity."
FT /evidence="ECO:0000269|PubMed:10383391,
FT ECO:0000269|PubMed:12032153"
FT MUTAGEN 44
FT /note="S->A: No effect on constituitive phosphorylation."
FT /evidence="ECO:0000269|PubMed:10383391"
FT MUTAGEN 48
FT /note="S->A: No effect on constituitive phosphorylation."
FT /evidence="ECO:0000269|PubMed:10383391"
FT MUTAGEN 54
FT /note="S->A: No effect on constituitive phosphorylation."
FT /evidence="ECO:0000269|PubMed:10383391"
FT MUTAGEN 61
FT /note="S->A: No effect on constituitive phosphorylation,
FT decreased stress-induced phosphorylation but no effect on
FT RXRA transcriptional activity. Abolishes stress-induced
FT phosphorylation but no effect on RXRA transcriptional
FT activity; when associated with A-75 and A-87. No effect on
FT RXRA transcriptional activity."
FT /evidence="ECO:0000269|PubMed:10383391"
FT MUTAGEN 75
FT /note="S->A: No effect on constituitive phosphorylation,
FT decreased stress-induced phosphorylation but no effect on
FT RXRA transcriptional activity. Abolishes stress-induced
FT phosphorylation but no effect on RXRA transcriptional
FT activity; when associated with A-61 and A-87."
FT /evidence="ECO:0000269|PubMed:10383391"
FT MUTAGEN 87
FT /note="T->A: No effect on constituitive phosphorylation,
FT decreased stress-induced phosphorylation but no effect on
FT RXRA transcriptional activity. Abolishes stress-induced
FT phosphorylation but no effect on RXRA transcriptional
FT activity; when associated with A-61 and A-75.
FT phosphorylation. No effect on RXRA transcriptional
FT activity."
FT /evidence="ECO:0000269|PubMed:10383391"
FT MUTAGEN 96
FT /note="S->A: No effect on constituitive phosphorylation."
FT /evidence="ECO:0000269|PubMed:10383391"
FT MUTAGEN 101
FT /note="S->A: No effect on constituitive phosphorylation."
FT /evidence="ECO:0000269|PubMed:10383391"
FT MUTAGEN 265
FT /note="S->A: No effect on constiuitive phosphorylation but
FT loss of stress-induced phosphorylation. No effect on RXRA
FT transcriptional activity."
FT /evidence="ECO:0000269|PubMed:10383391"
FT MUTAGEN 455..456
FT /note="FL->AA: Abolishes interaction with ASXL1 and NCOA1."
FT /evidence="ECO:0000269|PubMed:16606617"
FT MUTAGEN 459..460
FT /note="ML->AA: Abolishes interaction with ASXL1 and NCOA1."
FT /evidence="ECO:0000269|PubMed:16606617"
FT HELIX 231..234
FT /evidence="ECO:0007829|PDB:1DKF"
FT HELIX 237..246
FT /evidence="ECO:0007829|PDB:1DKF"
FT HELIX 269..282
FT /evidence="ECO:0007829|PDB:1DKF"
FT HELIX 284..289
FT /evidence="ECO:0007829|PDB:1DKF"
FT TURN 292..296
FT /evidence="ECO:0007829|PDB:1DKF"
FT HELIX 299..321
FT /evidence="ECO:0007829|PDB:1DKF"
FT STRAND 323..330
FT /evidence="ECO:0007829|PDB:1DKF"
FT STRAND 336..338
FT /evidence="ECO:0007829|PDB:1DKF"
FT HELIX 339..344
FT /evidence="ECO:0007829|PDB:1DKF"
FT HELIX 348..357
FT /evidence="ECO:0007829|PDB:1DKF"
FT HELIX 359..364
FT /evidence="ECO:0007829|PDB:1DKF"
FT HELIX 369..380
FT /evidence="ECO:0007829|PDB:1DKF"
FT HELIX 391..412
FT /evidence="ECO:0007829|PDB:1DKF"
FT HELIX 419..424
FT /evidence="ECO:0007829|PDB:1DKF"
FT HELIX 426..438
FT /evidence="ECO:0007829|PDB:1DKF"
FT TURN 439..443
FT /evidence="ECO:0007829|PDB:1DKF"
FT HELIX 447..449
FT /evidence="ECO:0007829|PDB:1DKF"
FT HELIX 452..461
FT /evidence="ECO:0007829|PDB:1DKF"
SQ SEQUENCE 467 AA; 51217 MW; 0AF62396BCDC87DB CRC64;
MDTKHFLPLD FSTQVNSSSL NSPTGRGSMA VPSLHPSLGP GIGSPLGSPG QLHSPISTLS
SPINGMGPPF SVISSPMGPH SMSVPTTPTL GFGTGSPQLN SPMNPVSSTE DIKPPLGLNG
VLKVPAHPSG NMASFTKHIC AICGDRSSGK HYGVYSCEGC KGFFKRTVRK DLTYTCRDNK
DCLIDKRQRN RCQYCRYQKC LAMGMKREAV QEERQRGKDR NENEVESTSS ANEDMPVEKI
LEAELAVEPK TETYVEANMG LNPSSPNDPV TNICQAADKQ LFTLVEWAKR IPHFSELPLD
DQVILLRAGW NELLIASFSH RSIAVKDGIL LATGLHVHRN SAHSAGVGAI FDRVLTELVS
KMRDMQMDKT ELGCLRAIVL FNPDSKGLSN PAEVEALREK VYASLEAYCK HKYPEQPGRF
AKLLLRLPAL RSIGLKCLEH LFFFKLIGDT PIDTFLMEML EAPHQAT
