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 24-JAN-2024, entry version 223. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7PDQ; X-ray; 1.58 A; A=227-467. DR PDB; 7PDT; X-ray; 3.30 A; A/B=227-467. DR PDB; 7QAA; X-ray; 2.76 A; A=230-462. DR PDBsum; 1DKF; -. DR PDBsum; 1XDK; -. DR PDBsum; 3A9E; -. DR PDBsum; 7AOS; -. DR PDBsum; 7PDQ; -. DR PDBsum; 7PDT; -. DR PDBsum; 7QAA; -. 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 GlyGen; P28700; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P28700; -. DR PhosphoSitePlus; P28700; -. DR MaxQB; P28700; -. DR PaxDb; 10090-ENSMUSP00000076491; -. DR ProteomicsDB; 260961; -. DR Pumba; P28700; -. DR Antibodypedia; 3881; 545 antibodies from 41 providers. DR DNASU; 20181; -. DR Ensembl; ENSMUST00000077257.12; ENSMUSP00000076491.6; ENSMUSG00000015846.17. DR GeneID; 20181; -. DR KEGG; mmu:20181; -. DR UCSC; uc008ixs.1; mouse. DR AGR; MGI:98214; -. 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; 5400963at2759; -. 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; 4 hits in 83 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 262 other cell types or tissues. DR ExpressionAtlas; P28700; baseline and differential. 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:0043167; F:ion 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:0046966; F:nuclear thyroid hormone receptor binding; ISO:MGI. 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: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; NAS:ComplexPortal. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IGI:MGI. 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: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:0006355; P:regulation of DNA-templated transcription; IDA: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: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 CDD; cd06956; NR_DBD_RXR; 1. DR CDD; cd06943; NR_LBD_RXR_like; 1. DR Gene3D; 3.30.50.10; Erythroid Transcription Factor GATA-1, subunit A; 1. DR Gene3D; 1.10.565.10; Retinoid X Receptor; 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 PANTHER; PTHR24083; NUCLEAR HORMONE RECEPTOR; 1. DR PANTHER; PTHR24083:SF39; RETINOIC ACID RECEPTOR RXR-ALPHA; 1. 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; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 1. DR SUPFAM; SSF48508; Nuclear receptor ligand-binding domain; 1. DR PROSITE; PS51843; NR_LBD; 1. DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1. DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1. DR Genevisible; P28700; MM. 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..245 FT /evidence="ECO:0007829|PDB:7PDQ" FT HELIX 269..290 FT /evidence="ECO:0007829|PDB:7PDQ" FT HELIX 294..296 FT /evidence="ECO:0007829|PDB:7PDQ" FT HELIX 299..321 FT /evidence="ECO:0007829|PDB:7PDQ" FT TURN 322..324 FT /evidence="ECO:0007829|PDB:7PDQ" FT STRAND 325..330 FT /evidence="ECO:0007829|PDB:7PDQ" FT STRAND 336..338 FT /evidence="ECO:0007829|PDB:7PDQ" FT HELIX 339..344 FT /evidence="ECO:0007829|PDB:7PDQ" FT HELIX 348..357 FT /evidence="ECO:0007829|PDB:7PDQ" FT HELIX 359..365 FT /evidence="ECO:0007829|PDB:7PDQ" FT HELIX 369..380 FT /evidence="ECO:0007829|PDB:7PDQ" FT HELIX 391..412 FT /evidence="ECO:0007829|PDB:7PDQ" FT HELIX 419..424 FT /evidence="ECO:0007829|PDB:7PDQ" FT HELIX 427..447 FT /evidence="ECO:0007829|PDB:7PDQ" FT HELIX 451..453 FT /evidence="ECO:0007829|PDB:3A9E" FT HELIX 454..459 FT /evidence="ECO:0007829|PDB:7PDQ" 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 //