| IED ID | IndEnz0002008124 |
| Enzyme Type ID | protease008124 |
| Protein Name |
Retinoic acid receptor RXR-alpha Nuclear receptor subfamily 2 group B member 1 Retinoid X receptor alpha |
| Gene Name | RXRA NR2B1 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MDTKHFLPLDFSTQVNSSLTSPTGRGSMAAPSLHPSLGPGIGSPGQLHSPISTLSSPINGMGPPFSVISSPMGPHSMSVPTTPTLGFSTGSPQLSSPMNPVSSSEDIKPPLGLNGVLKVPAHPSGNMASFTKHICAICGDRSSGKHYGVYSCEGCKGFFKRTVRKDLTYTCRDNKDCLIDKRQRNRCQYCRYQKCLAMGMKREAVQEERQRGKDRNENEVESTSSANEDMPVERILEAELAVEPKTETYVEANMGLNPSSPNDPVTNICQAADKQLFTLVEWAKRIPHFSELPLDDQVILLRAGWNELLIASFSHRSIAVKDGILLATGLHVHRNSAHSAGVGAIFDRVLTELVSKMRDMQMDKTELGCLRAIVLFNPDSKGLSNPAEVEALREKVYASLEAYCKHKYPEQPGRFAKLLLRLPALRSIGLKCLEHLFFFKLIGDTPIDTFLMEMLEAPHQMT |
| Enzyme Length | 462 |
| Uniprot Accession Number | P19793 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | BINDING 316; /note="9-cis retinoic acid"; /evidence="ECO:0000269|PubMed:16107141, ECO:0000269|PubMed:18800767, ECO:0000269|PubMed:19167885, ECO:0007744|PDB:2ACL, ECO:0007744|PDB:3FAL, ECO:0007744|PDB:3FC6"; BINDING 327; /note="9-cis retinoic acid; via amide nitrogen"; /evidence="ECO:0000269|PubMed:16107141, ECO:0000269|PubMed:18800767, ECO:0000269|PubMed:19167885, ECO:0007744|PDB:2ACL, ECO:0007744|PDB:3FAL, ECO:0007744|PDB:3FC6" |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | DNA_BIND 135..200; /note=Nuclear receptor; /evidence=ECO:0000255|PROSITE-ProRule:PRU00407 |
| EC Number | |
| Enzyme Function | FUNCTION: Receptor for retinoic acid that acts as a transcription factor (PubMed:11162439, PubMed:11915042). Forms homo- or heterodimers with retinoic acid receptors (RARs) and binds to target response elements in response to their ligands, all-trans or 9-cis retinoic acid, to regulate gene expression in various biological processes (PubMed:10195690, PubMed:11162439, PubMed:11915042, PubMed:28167758, PubMed:17761950, PubMed:16107141, PubMed:18800767, PubMed:19167885). The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 to regulate transcription (PubMed:10195690, PubMed:11162439, PubMed:11915042, PubMed:17761950, PubMed:28167758). The high affinity ligand for retinoid X receptors (RXRs) is 9-cis retinoic acid (PubMed:1310260). In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression (PubMed:20215566). On ligand binding, the corepressors dissociate from the receptors and coactivators are recruited leading to transcriptional activation (PubMed:20215566, PubMed:9267036). Serves as a common heterodimeric partner for a number of nuclear receptors, such as RARA, RARB and PPARA (PubMed:10195690, PubMed:11915042, PubMed:28167758, PubMed:29021580). The RXRA/RARB heterodimer can act as a transcriptional repressor or transcriptional activator, depending on the RARE DNA element context (PubMed:29021580). The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes (PubMed:10195690). Together with RARA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells (PubMed:28167758). Acts as an enhancer of RARA binding to RARE DNA element (PubMed:28167758). May facilitate the nuclear import of heterodimerization partners such as VDR and NR4A1 (PubMed:12145331, PubMed:15509776). Promotes myelin debris phagocytosis and remyelination by macrophages (PubMed:26463675). Plays a role in the attenuation of the innate immune system in response to viral infections, possibly by negatively regulating the transcription of antiviral genes such as type I IFN genes (PubMed:25417649). Involved in the regulation of calcium signaling by repressing ITPR2 gene expression, thereby controlling cellular senescence (PubMed:30216632). {ECO:0000269|PubMed:10195690, ECO:0000269|PubMed:11162439, ECO:0000269|PubMed:11915042, ECO:0000269|PubMed:12145331, ECO:0000269|PubMed:1310260, ECO:0000269|PubMed:15509776, ECO:0000269|PubMed:16107141, ECO:0000269|PubMed:17761950, ECO:0000269|PubMed:18800767, ECO:0000269|PubMed:19167885, ECO:0000269|PubMed:20215566, ECO:0000269|PubMed:25417649, ECO:0000269|PubMed:26463675, ECO:0000269|PubMed:28167758, ECO:0000269|PubMed:29021580, ECO:0000269|PubMed:30216632, ECO:0000269|PubMed:9267036}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (1); Beta strand (9); Binding site (2); Chain (1); Compositional bias (4); Cross-link (2); DNA binding (1); Domain (1); Helix (19); Metal binding (8); Modified residue (9); Mutagenesis (11); Natural variant (4); Region (6); Turn (5); Zinc finger (2) |
| Keywords | 3D-structure;Acetylation;Alternative splicing;Cytoplasm;DNA-binding;Host-virus interaction;Isopeptide bond;Metal-binding;Mitochondrion;Nucleus;Phosphoprotein;Receptor;Reference proteome;Transcription;Transcription regulation;Ubl conjugation;Zinc;Zinc-finger |
| Interact With | O14503; P35637; Q15648; Q71SY5; Q15788; Q15596; P55055; P55055-1; Q13133; P27986; P37231-1; P10276; P42224; P11473; P97792-1; Q9JLI4; P04625; Q03463 |
| Induction | INDUCTION: Down-regulated by aging (PubMed:26463675). Induced by pulsatile shear stress (PubMed:28167758). {ECO:0000269|PubMed:26463675, ECO:0000269|PubMed:28167758}. |
| Subcellular Location | SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407, ECO:0000269|PubMed:11915042, ECO:0000269|PubMed:12145331, ECO:0000269|PubMed:15509776, ECO:0000269|PubMed:17761950, ECO:0000269|PubMed:28167758}. Cytoplasm {ECO:0000269|PubMed:12145331, ECO:0000269|PubMed:15509776}. Mitochondrion {ECO:0000269|PubMed:17761950}. Note=Localization to the nucleus is enhanced by vitamin D3 (PubMed:15509776). Nuclear localization may be enhanced by the interaction with heterodimerization partner VDR (PubMed:12145331). Translocation to the mitochondrion upon interaction with NR4A1 (PubMed:17761950, PubMed:15509776). Increased nuclear localization upon pulsatile shear stress (PubMed:28167758). {ECO:0000269|PubMed:12145331, ECO:0000269|PubMed:15509776, ECO:0000269|PubMed:17761950, ECO:0000269|PubMed:28167758}. |
| Modified Residue | MOD_RES 21; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P28700; MOD_RES 27; /note=Phosphoserine; /evidence=ECO:0000269|PubMed:11162439; MOD_RES 56; /note=Phosphoserine; by MAPK8 and MAPK9; /evidence=ECO:0000250|UniProtKB:P28700; MOD_RES 70; /note=Phosphoserine; by MAPK8 and MAPK9; /evidence=ECO:0000250|UniProtKB:P28700; MOD_RES 82; /note=Phosphothreonine; by MAPK8 and MAPK9; /evidence=ECO:0000250|UniProtKB:P28700; MOD_RES 129; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163; MOD_RES 145; /note=N6-acetyllysine; by EP300; /evidence=ECO:0000269|PubMed:17761950; MOD_RES 259; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:24275569; MOD_RES 260; /note=Phosphoserine; by MAPK8 and MAPK9; /evidence=ECO:0000250|UniProtKB:P28700 |
| Post Translational Modification | PTM: Acetylated by EP300; acetylation enhances DNA binding and transcriptional activity. {ECO:0000269|PubMed:17761950}.; PTM: Phosphorylated on serine and threonine residues mainly in the N-terminal modulating domain (By similarity). Constitutively phosphorylated on Ser-21 in the presence or absence of ligand (By similarity). Under stress conditions, hyperphosphorylated by activated JNK on Ser-56, Ser-70, Thr-82 and Ser-260 (By similarity). Phosphorylated on Ser-27, in vitro, by PKA (PubMed:11162439). This phosphorylation is required for repression of cAMP-mediated transcriptional activity of RARA (PubMed:11162439). {ECO:0000250|UniProtKB:P28700, ECO:0000269|PubMed:11162439}.; PTM: Sumoylation negatively regulates transcriptional activity. Desumoylated specifically by SENP6. {ECO:0000269|PubMed:16912044}. |
| Signal Peptide | |
| Structure 3D | NMR spectroscopy (1); X-ray crystallography (99) |
| Cross Reference PDB | 1BY4; 1DSZ; 1FBY; 1FM6; 1FM9; 1G1U; 1G5Y; 1K74; 1MV9; 1MVC; 1MZN; 1R0N; 1RDT; 1RXR; 1XLS; 1XV9; 1XVP; 1YNW; 2ACL; 2NLL; 2P1T; 2P1U; 2P1V; 2ZXZ; 2ZY0; 3DZU; 3DZY; 3E00; 3E94; 3FAL; 3FC6; 3FUG; 3H0A; 3KWY; 3NSP; 3NSQ; 3OAP; 3OZJ; 3PCU; 3R29; 3R2A; 3R5M; 3UVV; 4CN2; 4CN3; 4CN5; 4CN7; 4J5W; 4J5X; 4K4J; 4K6I; 4M8E; 4M8H; 4N5G; 4N8R; 4NQA; 4OC7; 4POH; 4POJ; 4PP3; 4PP5; 4RFW; 4RMC; 4RMD; 4RME; 4ZO1; 4ZSH; 5EC9; 5JI0; 5LYQ; 5MJ5; 5MK4; 5MKJ; 5MKU; 5MMW; 5TBP; 5UAN; 5Z12; 5ZQU; 6A5Y; 6A5Z; 6A60; 6FBQ; 6FBR; 6HN6; 6JNO; 6JNR; 6L6K; 6LB4; 6LB5; 6LB6; 6SJM; 6STI; 6XWG; 6XWH; 7A77; 7B88; 7B9O; 7BK4; 7CFO; |
| Mapped Pubmed ID | 10075656; 10233885; 10235266; 10330422; 10334992; 10334993; 10373014; 10377179; 10425206; 10529898; 10542397; 10558993; 10579975; 10588945; 10654609; 10679930; 10777502; 10777541; 10858438; 10866662; 10938283; 10940626; 11027271; 11042264; 11121228; 11139380; 11149950; 11226238; 11267664; 11278854; 11287605; 11330046; 11356169; 11387316; 11414710; 11485553; 11486000; 11493525; 11500512; 11574675; 11604492; 11606411; 11790787; 11790793; 11826406; 11839661; 11855864; 11865025; 11870371; 11875109; 11891985; 11929748; 11929766; 11972046; 11981034; 12032151; 12036869; 12037571; 12040021; 12048211; 12077340; 12097375; 12118000; 12150943; 12177166; 12213831; 12235159; 12297106; 12385756; 12393611; 12454263; 12485829; 12486725; 12505311; 12514092; 12518032; 12529369; 12576329; 12582161; 12591602; 12612088; 12663868; 12736215; 12771132; 12815072; 12815623; 12829629; 12914524; 12969790; 1360810; 14517221; 14572640; 14592980; 14636573; 14636649; 14651853; 14671211; 14699511; 14703507; 14705796; 14711372; 14738865; 14764426; 14980219; 15006913; 15056000; 15067378; 15073272; 15082790; 15130092; 15147902; 15171703; 15175151; 15199055; 15225774; 15231748; 15255287; 15273253; 15285879; 15340071; 15494375; 15500444; 15544927; 15608692; 15610735; 15634700; 15635043; 15635645; 15654074; 15691842; 15850785; 15896744; 15919796; 15933212; 16166636; 16169070; 16184197; 16380219; 16407282; 16476485; 16494845; 16503871; 16517099; 16541101; 16549775; 16551633; 16606617; 1673098; 16751179; 16757478; 16778766; 16806672; 1682218; 16871576; 16908160; 1693558; 16972786; 17007889; 17008383; 17010333; 17011499; 17018855; 17038419; 17060461; 17170071; 17185360; 17186944; 17272513; 17272748; 17306620; 17341859; 17433303; 17451432; 17476214; 17525233; 17562868; 17641689; 17663992; 17673910; 17684114; 17687072; 17713478; 17761849; 17851529; 17875646; 17900311; 17905826; 17947383; 17980149; 18003614; 18039840; 18162523; 18217139; 18234786; 18239067; 18288277; 18292238; 18362166; 18375961; 1840554; 18540824; 18542081; 18607089; 18634911; 18660489; 18676680; 18719978; 18761406; 18776924; 18782758; 18787068; 18840407; 18848529; 18931025; 18957410; 19043829; 19070893; 19088433; 19115207; 19115252; 19144697; 19170196; 19172745; 19211732; 19232136; 19255064; 19258929; 19270714; 19279199; 19282365; 19289416; 19345331; 19374686; 19408900; 19442374; 19453261; 19464171; 19481530; 19496083; 19520913; 19575673; 19625176; 19692168; 19703992; 19710929; 1975088; 19753122; 19782034; 19850744; 19888660; 19902255; 19913121; 19915048; 19934321; 19965660; 20042001; 20063036; 20070029; 20101261; 20110263; 20133701; 20133893; 20145122; 20159610; 20171203; 20176747; 20194623; 20231276; 20306291; 20307661; 20354914; 20364085; 20379614; 20398753; 20478996; 20494359; 20541701; 20558521; 20602615; 20628086; 20661648; 20682316; 20817722; 20819778; 20836077; 20855565; 20861222; 20947021; 21030586; 21049972; 21053424; 21084305; 21087926; 21135166; 21187453; 21262235; 21284483; 21310195; 21320481; 21355951; 21359593; 21402532; 21451113; 21478865; 21497760; 21507939; 21561764; 21613212; 21618588; 21670079; 21673049; 21707843; 21709632; 21900206; 21937108; 21949683; 21988832; 21998312; 22022577; 22066143; 22130024; 22140563; 22179700; 22210720; 22384078; 22474364; 22475777; 22541735; 22542077; 22569366; 22573555; 22710246; 22871568; 22872084; 22872755; 22879880; 22936343; 22949521; 23056264; 23079705; 23180655; 23389291; 23392891; 23413886; 23534758; 23602807; 23612120; 23630040; 23638021; 23639973; 23690070; 23714182; 23723417; 23775127; 23790976; 23826131; 2384150; 23955559; 23990020; 23991366; 24080207; 24174538; 24187139; 24196956; 24232815; 24312487; 24321096; 24359708; 24379003; 24513686; 24561505; 24586203; 24604522; 24606918; 24704507; 24752325; 24801499; 24821627; 24821725; 24824382; 24832862; 24972164; 25013807; 25053412; 25101834; 25135475; 25205379; 25241761; 25303530; 25609649; 25645674; 2570724; 2571087; 2571936; 25738607; 25762635; 25944918; 25954810; 26030625; 26116533; 26289479; 26310932; 26331194; 26355550; 26443578; 26447153; 26610845; 26644513; 26727233; 26820900; 26883505; 26898458; 26984517; 27071062; 27357804; 27636996; 27852823; 28076928; 28079136; 28082258; 28129653; 28407400; 28611266; 28691794; 28714476; 28740126; 28774779; 28842423; 28869506; 2891503; 28923935; 2898782; 29143738; 29228308; 29305749; 29431622; 29437960; 29661715; 29748541; 29934308; 30088172; 30093910; 30413149; 30476562; 30518934; 30535437; 30565665; 30713160; 30931933; 31210298; 31483660; 31531208; 31694317; 31874245; 31929206; 32064346; 32513869; 32579962; 32819587; 32862196; 32878625; 32969715; 32974652; 32990725; 33187070; 33321102; 33356247; 33647291; 33684567; 33793232; 34081964; 34239022; 34312718; 34830351; 7488013; 7499431; 7531665; 7566114; 7685352; 7743939; 7831296; 7831297; 7838715; 7892212; 7901228; 7908827; 7914354; 7916164; 7981125; 8001151; 8093325; 8100763; 8325954; 8386511; 8402897; 8643605; 8647822; 8674428; 8703472; 8706692; 8759021; 8770873; 8798399; 8830050; 8970730; 8999919; 9012850; 9053316; 9065481; 9106661; 9154799; 9171241; 9177240; 9218805; 9242684; 9272954; 9344464; 9347914; 9360992; 9405293; 9463349; 9463359; 9482740; 9501100; 9570764; 9653119; 9691089; 9697850; 9748239; 9789037; |
| Motif | |
| Gene Encoded By | |
| Mass | 50,811 |
| Kinetics | |
| Metal Binding | METAL 135; /note="Zinc 1"; /evidence="ECO:0000269|PubMed:10669605, ECO:0007744|PDB:1BY4"; METAL 138; /note="Zinc 1"; /evidence="ECO:0000269|PubMed:10669605, ECO:0007744|PDB:1BY4"; METAL 152; /note="Zinc 1"; /evidence="ECO:0000269|PubMed:10669605, ECO:0007744|PDB:1BY4"; METAL 155; /note="Zinc 1"; /evidence="ECO:0000269|PubMed:10669605, ECO:0007744|PDB:1BY4"; METAL 171; /note="Zinc 2"; /evidence="ECO:0000269|PubMed:10669605, ECO:0007744|PDB:1BY4"; METAL 177; /note="Zinc 2"; /evidence="ECO:0000269|PubMed:10669605, ECO:0007744|PDB:1BY4"; METAL 187; /note="Zinc 2"; /evidence="ECO:0000269|PubMed:10669605, ECO:0007744|PDB:1BY4"; METAL 190; /note="Zinc 2"; /evidence="ECO:0000269|PubMed:10669605, ECO:0007744|PDB:1BY4" |
| Rhea ID | |
| Cross Reference Brenda |