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Database: UniProt
Entry: P28700
LinkDB: P28700
Original site: P28700 
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   07-APR-2021, entry version 210.
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   PDBsum; 1DKF; -.
DR   PDBsum; 1XDK; -.
DR   PDBsum; 3A9E; -.
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; 19.
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; 416 antibodies.
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   eggNOG; KOG3575; Eukaryota.
DR   GeneTree; ENSGT00940000159789; -.
DR   InParanoid; P28700; -.
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   BioGRID-ORCS; 20181; 2 hits in 52 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 liver and 312 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: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: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:0042974; F:retinoic acid receptor 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:0003707; F:steroid hormone receptor activity; IEA:InterPro.
DR   GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB.
DR   GO; GO:0000976; F:transcription regulatory region sequence-specific DNA binding; ISO:MGI.
DR   GO; GO:0042809; F:vitamin D receptor 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:0007507; P:heart development; IMP:MGI.
DR   GO; GO:0003007; P:heart morphogenesis; TAS:DFLAT.
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:0019048; P:modulation by virus of host process; ISO:MGI.
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:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR   GO; GO:1901522; P:positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus; IDA:MGI.
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: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:MGI.
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          165..170
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250|UniProtKB:P19793"
FT   REGION          206..229
FT                   /note="Hinge"
FT   REGION          353..373
FT                   /note="Required for nuclear export"
FT                   /evidence="ECO:0000250|UniProtKB:P19793"
FT   METAL           140
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000250|UniProtKB:P19793"
FT   METAL           143
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000250|UniProtKB:P19793"
FT   METAL           157
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000250|UniProtKB:P19793"
FT   METAL           160
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000250|UniProtKB:P19793"
FT   METAL           176
FT                   /note="Zinc 2"
FT                   /evidence="ECO:0000250|UniProtKB:P19793"
FT   METAL           182
FT                   /note="Zinc 2"
FT                   /evidence="ECO:0000250|UniProtKB:P19793"
FT   METAL           192
FT                   /note="Zinc 2"
FT                   /evidence="ECO:0000250|UniProtKB:P19793"
FT   METAL           195
FT                   /note="Zinc 2"
FT                   /evidence="ECO:0000250|UniProtKB:P19793"
FT   BINDING         321
FT                   /note="9-cis retinoic acid"
FT                   /evidence="ECO:0000250|UniProtKB:P19793"
FT   BINDING         332
FT                   /note="9-cis retinoic acid; via amide nitrogen"
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:0007744|PDB:1DKF"
FT   HELIX           237..246
FT                   /evidence="ECO:0007744|PDB:1DKF"
FT   HELIX           269..282
FT                   /evidence="ECO:0007744|PDB:1DKF"
FT   HELIX           284..289
FT                   /evidence="ECO:0007744|PDB:1DKF"
FT   TURN            292..296
FT                   /evidence="ECO:0007744|PDB:1DKF"
FT   HELIX           299..321
FT                   /evidence="ECO:0007744|PDB:1DKF"
FT   STRAND          323..330
FT                   /evidence="ECO:0007744|PDB:1DKF"
FT   STRAND          336..338
FT                   /evidence="ECO:0007744|PDB:1DKF"
FT   HELIX           339..344
FT                   /evidence="ECO:0007744|PDB:1DKF"
FT   HELIX           348..357
FT                   /evidence="ECO:0007744|PDB:1DKF"
FT   HELIX           359..364
FT                   /evidence="ECO:0007744|PDB:1DKF"
FT   HELIX           369..380
FT                   /evidence="ECO:0007744|PDB:1DKF"
FT   HELIX           391..412
FT                   /evidence="ECO:0007744|PDB:1DKF"
FT   HELIX           419..424
FT                   /evidence="ECO:0007744|PDB:1DKF"
FT   HELIX           426..438
FT                   /evidence="ECO:0007744|PDB:1DKF"
FT   TURN            439..443
FT                   /evidence="ECO:0007744|PDB:1DKF"
FT   HELIX           447..449
FT                   /evidence="ECO:0007744|PDB:1DKF"
FT   HELIX           452..461
FT                   /evidence="ECO:0007744|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
//
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