Reactome | UniProt:P19793 RXRA

Schema > ReferenceGeneProduct > Entries

UniProt:P19793 RXRA Show undefined attributes

chain	chain:1-462
checksum	7F952B580AD84C42
comment	FUNCTION Receptor for retinoic acid that acts as a transcription factor (PubMed:10874028, PubMed:11162439, PubMed:11915042, PubMed:37478846). 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:16107141, PubMed:17761950, PubMed:18800767, PubMed:19167885, PubMed:28167758, PubMed:37478846). 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:37478846, 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).SUBUNIT Homodimer (PubMed:10669605, PubMed:17761950). Heterodimer (via C-terminus) with RARA; required for ligand-dependent retinoic acid receptor transcriptional activity; association with RARA is enhanced by pulsatile shear stress (PubMed:10698945, PubMed:15509776, PubMed:28167758). Heterodimer with PPARA (via the leucine-like zipper in the LBD); the interaction is required for PPARA transcriptional activity (PubMed:10195690, PubMed:11698662, PubMed:11915042). Heterodimerizes with PPARG (PubMed:10882139, PubMed:11698662). Heterodimerizes (via NR LBD) with RARB (PubMed:29021580). Heterodimerizes with NR1H4; the heterodimerization enhances the binding affinity for LXXLL motifs from coactivators (PubMed:30275017). Interacts with NCOA3 and NCOA6 coactivators (PubMed:10567404, PubMed:9267036). Interacts with coactivator FAM120B (By similarity). Interacts with coactivator PELP1, SENP6, SFPQ, DNTTIP2 and RNF8 (PubMed:11259580, PubMed:14981089, PubMed:15047147, PubMed:16574651, PubMed:16912044). Interacts with PRMT2 (PubMed:12039952). Interacts with ASXL1 (By similarity). Interacts with BHLHE40/DEC1, BHLHE41/DEC2, NCOR1 and NCOR2 (PubMed:19786558). Interacts in a ligand-dependent fashion with MED1 and NCOA1 (PubMed:10882139, PubMed:11698662, PubMed:19786558). Interacts with VDR (PubMed:28698609). Interacts with EP300; the interaction is decreased by 9-cis retinoic acid (PubMed:17761950). Heterodimer (via C-terminus) with NR4A1 (via DNA-binding domain); DNA-binding of the heterodimer is enhanced by 9-cis retinoic acid (PubMed:15509776, PubMed:17761950). NR4A1 competes with EP300 for interaction with RXRA and thereby attenuates EP300 mediated acetylation of RXRA (PubMed:17761950). In the absence of hormonal ligand, interacts with TACC1 (PubMed:20078863). Interacts ith IGFBP3 (PubMed:10874028).SUBUNIT (Microbial infection) Interacts (via the DNA binding domain) with HCV core protein; the interaction enhances the transcriptional activities of the RXRA/RARA and the RXRA/PPARA heterodimers.INTERACTION 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:15509776, PubMed:17761950). Increased nuclear localization upon pulsatile shear stress (PubMed:28167758).ALTERNATIVE PRODUCTS Expressed in lung fibroblasts (at protein level) (PubMed:30216632). Expressed in monocytes (PubMed:26463675). Highly expressed in liver, also found in kidney and brain (PubMed:14702039, PubMed:2159111, PubMed:24275569).INDUCTION Down-regulated by aging (PubMed:26463675). Induced by pulsatile shear stress (PubMed:28167758).DOMAIN Composed of three domains: a modulating N-terminal domain (AF1 domain), a DNA-binding domain and a C-terminal ligand-binding domain (AF2 domain).PTM Acetylated by EP300; acetylation enhances DNA binding and transcriptional activity.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).PTM Ubiquitinated by UBR5, leading to its degradation: UBR5 specifically recognizes and binds ligand-bound RXRA when it is not associated with coactivators (NCOAs) (PubMed:37478846). In presence of NCOAs, the UBR5-degron is not accessible, preventing its ubiquitination and degradation (PubMed:37478846).PTM Sumoylation negatively regulates transcriptional activity. Desumoylated specifically by SENP6.SIMILARITY Belongs to the nuclear hormone receptor family. NR2 subfamily.ONLINE INFORMATION Retinoid X receptor entry
crossReference	[DatabaseIdentifier:11849405] HPA:ENSG00000186350-RXRA [DatabaseIdentifier:12818080] ZINC - World Drugs:RXRA_HUMAN [DatabaseIdentifier:12817135] ZINC target:P19793 [DatabaseIdentifier:12813711] ZINC - Substances:RXRA_HUMAN [DatabaseIdentifier:12809983] ZINC - Predictions - Purchasable:RXRA_HUMAN [DatabaseIdentifier:12807838] ZINC - Metabolites:RXRA_HUMAN [DatabaseIdentifier:12806583] ZINC - Investigational:RXRA_HUMAN [DatabaseIdentifier:12805522] ZINC - FDA approved:RXRA_HUMAN [DatabaseIdentifier:12804353] ZINC - Biogenic:RXRA_HUMAN [DatabaseIdentifier:12348607] RefSeq:NP_002948.1 [DatabaseIdentifier:12348608] RefSeq:NP_001278850.1 [DatabaseIdentifier:12294267] Pharos - Targets:P19793 [DatabaseIdentifier:12256633] PRO:P19793 [DatabaseIdentifier:12213880] PDB:4POJ [DatabaseIdentifier:12213912] PDB:1MVC [DatabaseIdentifier:12172927] PDB:1FM6 [DatabaseIdentifier:12213869] PDB:2ZY0 [DatabaseIdentifier:12233112] PDB:4CN3 [DatabaseIdentifier:12233115] PDB:5MMW [DatabaseIdentifier:12213856] PDB:6SJM [DatabaseIdentifier:12213882] PDB:2ZXZ [DatabaseIdentifier:12147416] PDB:1XVP [DatabaseIdentifier:12213879] PDB:3R5M [DatabaseIdentifier:12233113] PDB:1G5Y [DatabaseIdentifier:12213846] PDB:3OZJ [DatabaseIdentifier:12172937] PDB:1K74 [DatabaseIdentifier:12214004] PDB:2ACL [DatabaseIdentifier:12233108] PDB:5TBP [DatabaseIdentifier:12213876] PDB:4PP3 [DatabaseIdentifier:12213903] PDB:1MV9 [DatabaseIdentifier:12214002] PDB:3FAL [DatabaseIdentifier:12213833] PDB:7NKE [DatabaseIdentifier:12213884] PDB:4K4J [DatabaseIdentifier:12233114] PDB:4CN5 [DatabaseIdentifier:12213852] PDB:8PP0 [DatabaseIdentifier:12233116] PDB:9RMR [DatabaseIdentifier:12204264] PDB:2NLL [DatabaseIdentifier:12203083] PDB:4J5X [DatabaseIdentifier:12213902] PDB:3PCU [DatabaseIdentifier:12233111] PDB:4CN2 [DatabaseIdentifier:12213843] PDB:4RME [DatabaseIdentifier:12172945] PDB:1FM9 [DatabaseIdentifier:12141944] PDB:6A60 [DatabaseIdentifier:12213898] PDB:4K6I [DatabaseIdentifier:12213875] PDB:4ZSH [DatabaseIdentifier:12233109] PDB:1FBY [DatabaseIdentifier:12203225] PDB:1DSZ [DatabaseIdentifier:12233123] PDB:1G1U [DatabaseIdentifier:12141933] PDB:6A5Z [DatabaseIdentifier:12233124] PDB:5MJ5 [DatabaseIdentifier:12173155] PDB:3E00 [DatabaseIdentifier:12204278] PDB:4ZO1 [DatabaseIdentifier:12141913] PDB:5Z12 [DatabaseIdentifier:12213886] PDB:7B9O [DatabaseIdentifier:12213892] PDB:6LB5 [DatabaseIdentifier:12203081] PDB:4J5W [DatabaseIdentifier:12232647] PDB:6JNR [DatabaseIdentifier:12213840] PDB:4RMC [DatabaseIdentifier:12213895] PDB:4PP5 [DatabaseIdentifier:12213900] PDB:3OAP [DatabaseIdentifier:12233118] PDB:7CFO [DatabaseIdentifier:12173071] PDB:3DZU [DatabaseIdentifier:12173061] PDB:3DZY [DatabaseIdentifier:12204238] PDB:5UAN [DatabaseIdentifier:12213893] PDB:6LB4 [DatabaseIdentifier:12141942] PDB:6A5Y [DatabaseIdentifier:12172922] PDB:5JI0 [DatabaseIdentifier:12233110] PDB:4CN7 [DatabaseIdentifier:12233121] PDB:6HN6 [DatabaseIdentifier:12213877] PDB:4POH [DatabaseIdentifier:12233120] PDB:4N5G [DatabaseIdentifier:12213878] PDB:7BK4 [DatabaseIdentifier:12213831] PDB:1MZN [DatabaseIdentifier:12233125] PDB:1BY4 [DatabaseIdentifier:12213842] PDB:4RMD [DatabaseIdentifier:12213894] PDB:6LB6 [DatabaseIdentifier:12213825] PDB:3FUG [DatabaseIdentifier:12213889] PDB:4M8E [DatabaseIdentifier:12233119] PDB:5ZQU [DatabaseIdentifier:12213881] PDB:4M8H [DatabaseIdentifier:12233122] PDB:1RXR [DatabaseIdentifier:12172939] PDB:1RDT [DatabaseIdentifier:12145132] PDB:3UVV [DatabaseIdentifier:12213870] PDB:7A77 [DatabaseIdentifier:12173047] PDB:3H0A [DatabaseIdentifier:12213907] PDB:4RFW [DatabaseIdentifier:12233117] PDB:6JNO [DatabaseIdentifier:12146287] PDB:3R2A [DatabaseIdentifier:12233104] PDB:6XWH [DatabaseIdentifier:12213866] PDB:2P1T [DatabaseIdentifier:12233107] PDB:5MKU [DatabaseIdentifier:12213865] PDB:2P1U [DatabaseIdentifier:12182162] PDB:1R0N [DatabaseIdentifier:12162733] PDB:1XLS [DatabaseIdentifier:12213862] PDB:5EC9 [DatabaseIdentifier:12213819] PDB:4OC7 [DatabaseIdentifier:12233102] PDB:9QX6 [DatabaseIdentifier:12147417] PDB:1XV9 [DatabaseIdentifier:12233103] PDB:5MKJ [DatabaseIdentifier:12213808] PDB:6STI [DatabaseIdentifier:12233100] PDB:3NSQ [DatabaseIdentifier:12233106] PDB:6FBR [DatabaseIdentifier:12213863] PDB:7B88 [DatabaseIdentifier:12194984] PDB:1YNW [DatabaseIdentifier:12232634] PDB:6L6K [DatabaseIdentifier:12213811] PDB:7UW4 [DatabaseIdentifier:12146291] PDB:3R29 [DatabaseIdentifier:12214003] PDB:3FC6 [DatabaseIdentifier:12213868] PDB:3KWY [DatabaseIdentifier:12213860] PDB:3E94 [DatabaseIdentifier:12233105] PDB:4N8R [DatabaseIdentifier:12213864] PDB:2P1V [DatabaseIdentifier:12213818] PDB:4NQA [DatabaseIdentifier:12233101] PDB:6FBQ [DatabaseIdentifier:12233099] PDB:3NSP [DatabaseIdentifier:12203223] PDB:6XWG [DatabaseIdentifier:12213812] PDB:7UW2 [DatabaseIdentifier:12213810] PDB:5MK4 [DatabaseIdentifier:12213809] PDB:5LYQ [DatabaseIdentifier:12141918] PDB:8HBM [DatabaseIdentifier:12134102] OpenTargets:ENSG00000186350 [DatabaseIdentifier:11463887] ENSEMBL:ENSG00000186350 [DatabaseIdentifier:11558614] ENSEMBL:ENSP00000419692 [DatabaseIdentifier:11681313] ENSEMBL:ENST00000481739 [DatabaseIdentifier:11780409] Guide to Pharmacology - Targets:610 [DatabaseIdentifier:11796437] GeneCards:RXRA [DatabaseIdentifier:11812203] GlyGen:P19793 [DatabaseIdentifier:11833637] HMDB Protein:HMDBP01926
databaseName	UniProt
dbId	63882
description	recommendedName: Retinoic acid receptor RXR-alpha alternativeName: Nuclear receptor subfamily 2 group B member 1 alternativeName: Retinoid X receptor alpha
displayName	UniProt:P19793 RXRA
geneName	RXRA NR2B1
identifier	P19793
isSequenceChanged	false
keyword	3D-structure Acetylation Alternative splicing Cytoplasm DNA-binding Host-virus interaction Isopeptide bond Metal-binding Mitochondrion Nucleus Phosphoprotein Proteomics identification Receptor Reference proteome Transcription Transcription regulation Ubl conjugation Zinc Zinc-finger
modified	[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
moleculeType	Protein
name	RXRA
otherIdentifier	11742843_a_at 11742844_a_at 17090917 17090936 202426_PM_s_at 202426_s_at 202449_PM_s_at 202449_s_at 3193367 3193368 3193370 3193371 3193372 3193382 3193383 3193384 3193389 3193390 3193391 3193392 3193393 3193396 3193399 3193400 3193408 3193410 3193412 3193413 3193414 3193415 3193416 3193418 32800_at 405_at 6256 8159127 A_14_P100547 A_14_P104460 A_23_P219176 A_23_P423197 A_24_P930985 GE568327 GE61154 GO:0000122 GO:0000785 GO:0000976 GO:0000977 GO:0000978 GO:0000981 GO:0001221 GO:0001972 GO:0002157 GO:0003677 GO:0003690 GO:0003700 GO:0003707 GO:0004879 GO:0005515 GO:0005634 GO:0005654 GO:0005667 GO:0005737 GO:0005739 GO:0005829 GO:0006351 GO:0006355 GO:0007399 GO:0008270 GO:0008289 GO:0009755 GO:0010875 GO:0016071 GO:0019899 GO:0030154 GO:0030163 GO:0030224 GO:0030501 GO:0030518 GO:0032526 GO:0035357 GO:0042277 GO:0042789 GO:0042802 GO:0042809 GO:0043235 GO:0043565 GO:0044323 GO:0045834 GO:0045893 GO:0045944 GO:0046872 GO:0048384 GO:0048469 GO:0048856 GO:0050692 GO:0050693 GO:0070564 GO:0070644 GO:0071404 GO:0071630 GO:0090575 GO:0140077 GO:1990837 HMNXSV003002266 HMNXSV003021752 Hs.20084.0.S1_3p_a_at ILMN_1687315 PH_hs_0001748 TC09000782.hg TC09000783.hg X52773_at g10862707_3p_a_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-381319] RXRA [nucleoplasm] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-4341130] monoSUMO1-K108-RXRA [nucleoplasm] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5334811] p-S21-RXRA [nucleoplasm] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9619757] RXRA [cytosol] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000186350] ENSEMBL:ENSG00000186350 RXRA [ReferenceDNASequence:12680243] UCSC:P19793 RXRA [ReferenceDNASequence:12118296] OMIM:180245 RXRA [ReferenceDNASequence:12042092] NCBI Gene:6256 RXRA [ReferenceDNASequence:11957999] Monarch:6256 RXRA [ReferenceDNASequence:11870392] KEGG:hsa:6256 RXRA [ReferenceDNASequence:11328210] BioGPS Gene:6256 RXRA [ReferenceDNASequence:11392245] COSMIC - genes:RXRA RXRA [ReferenceDNASequence:11425667] CTD Gene:6256 RXRA [ReferenceDNASequence:11428010] dbSNP Gene:6256 RXRA [ReferenceDNASequence:11828146] HGNC:10477 RXRA
referenceTranscript	[ReferenceRNASequence:12530461] RefSeq:NM_001291921.2 RXRA [ReferenceRNASequence:12530462] RefSeq:NM_002957.6 RXRA
schemaClass	ReferenceGeneProduct
secondaryIdentifier	RXRA_HUMAN B3KY83 Q2NL52 Q2V504
sequenceLength	462
species	[Species:48887] Homo sapiens
stId	uniprot:P19793
url	http://purl.uniprot.org/uniprot/P19793

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-381319] RXRA [nucleoplasm] [EntityWithAccessionedSequence:R-HSA-4341130] monoSUMO1-K108-RXRA [nucleoplasm] [EntityWithAccessionedSequence:R-HSA-5334811] p-S21-RXRA [nucleoplasm] [EntityWithAccessionedSequence:R-HSA-9619757] RXRA [cytosol]
(referenceSequence)	[GroupModifiedResidue:4341060] sumoylated lysine (monoSUMO1 [nucleoplasm]) at 108 [ModifiedResidue:5334799] O-phospho-L-serine at 21
(interactor)	[UndirectedInteraction:11166125] UniProt:P11473 <-> UniProt:P19793 (IntAct) [UndirectedInteraction:11182287] UniProt:P37231 <-> UniProt:P19793 (IntAct) [UndirectedInteraction:11182401] UniProt:P27986 <-> UniProt:P19793 (IntAct) [UndirectedInteraction:11207159] UniProt:Q15788 <-> UniProt:P19793 (IntAct) [UndirectedInteraction:11219997] UniProt:P04625 <-> UniProt:P19793 (IntAct) [UndirectedInteraction:11255429] UniProt:P37231-1 <-> UniProt:P19793 (IntAct) [UndirectedInteraction:11258555] UniProt:Q15648 <-> UniProt:P19793 (IntAct) [UndirectedInteraction:11266177] UniProt:Q13133 <-> UniProt:P19793 (IntAct) [UndirectedInteraction:11273387] UniProt:P42224 <-> UniProt:P19793 (IntAct) [UndirectedInteraction:11282943] UniProt:P10276 <-> UniProt:P19793 (IntAct) [UndirectedInteraction:11291429] UniProt:O14503 <-> UniProt:P19793 (IntAct) [UndirectedInteraction:11293727] UniProt:Q15596 <-> UniProt:P19793 (IntAct) [UndirectedInteraction:11297371] UniProt:P19793 <-> UniProt:Q71SY5 (IntAct) [UndirectedInteraction:11297375] UniProt:P19793 <-> ChEBI:9352 (IntAct) [UndirectedInteraction:11297377] UniProt:P19793 <-> UniProt:P55055 (IntAct) [UndirectedInteraction:11297379] UniProt:P19793 <-> UniProt:P35637 (IntAct) [UndirectedInteraction:11297383] UniProt:P19793 <-> IntAct:EBI-15743714 (IntAct) [UndirectedInteraction:11297387] UniProt:P19793 <-> UniProt:P97792-1 (IntAct) [UndirectedInteraction:11297389] UniProt:P19793 <-> UniProt:P48443 (IntAct) [UndirectedInteraction:11297393] UniProt:P19793 <-> IntAct:EBI-11173918 (IntAct) [UndirectedInteraction:11297397] UniProt:P19793 <-> UniProt:Q03463-PRO_0000278730 (IntAct) [UndirectedInteraction:11297401] UniProt:P19793 <-> IntAct:EBI-11173879 (IntAct) [UndirectedInteraction:11297405] UniProt:P19793 <-> IntAct:EBI-11173957 (IntAct) [UndirectedInteraction:11297409] UniProt:P19793 <-> IntAct:EBI-11173936 (IntAct) [UndirectedInteraction:11297411] UniProt:P19793 <-> UniProt:Q9JLI4 (IntAct) [UndirectedInteraction:11297415] UniProt:P19793 <-> IntAct:EBI-10055402 (IntAct) [UndirectedInteraction:11297419] UniProt:P19793 <-> IntAct:EBI-10055663 (IntAct) [UndirectedInteraction:11297423] UniProt:P19793 <-> IntAct:EBI-10055654 (IntAct)