UniProtKB - Q05343 (RXRA_RAT)
Retinoic acid receptor RXR-alpha
Rxra
Functioni
Receptor for retinoic acid that acts as a transcription factor (By similarity).
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 (By similarity).
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 (By similarity).
The high affinity ligand for retinoid X receptors (RXRs) is 9-cis retinoic acid (By similarity).
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 (By similarity).
On ligand binding, the corepressors dissociate from the receptors and coactivators are recruited leading to transcriptional activation (By similarity).
Serves as a common heterodimeric partner for a number of nuclear receptors, such as RARA, RARB and PPARA (By similarity).
The RXRA/RARB heterodimer can act as a transcriptional repressor or transcriptional activator, depending on the RARE DNA element context (By similarity).
The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes (PubMed:8381967).
Together with RARA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells (By similarity).
Acts as an enhancer of RARA binding to RARE DNA element (By similarity).
May facilitate the nuclear import of heterodimerization partners such as VDR and NR4A1 (By similarity).
Promotes myelin debris phagocytosis and remyelination by macrophages (By similarity).
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 (By similarity).
Involved in the regulation of calcium signaling by repressing ITPR2 gene expression, thereby controlling cellular senescence (By similarity).
By similarity1 PublicationSites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 140 | Zinc 1By similarity | 1 | |
Metal bindingi | 143 | Zinc 1By similarity | 1 | |
Metal bindingi | 157 | Zinc 1By similarity | 1 | |
Metal bindingi | 160 | Zinc 1By similarity | 1 | |
Metal bindingi | 176 | Zinc 2By similarity | 1 | |
Metal bindingi | 182 | Zinc 2By similarity | 1 | |
Metal bindingi | 192 | Zinc 2By similarity | 1 | |
Metal bindingi | 195 | Zinc 2By similarity | 1 | |
Binding sitei | 321 | 9-cis retinoic acidBy similarity | 1 | |
Binding sitei | 332 | 9-cis retinoic acid; via amide nitrogenBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 140 – 205 | Nuclear receptorPROSITE-ProRule annotationAdd BLAST | 66 | |
Zinc fingeri | 140 – 160 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 21 | |
Zinc fingeri | 176 – 200 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 25 |
GO - Molecular functioni
- chromatin DNA binding Source: RGD
- DNA binding Source: RGD
- DNA binding domain binding Source: RGD
- DNA-binding transcription factor activity Source: RGD
- double-stranded DNA binding Source: RGD
- enzyme binding Source: RGD
- identical protein binding Source: RGD
- LBD domain binding Source: RGD
- nuclear receptor activity Source: RGD
- nuclear receptor binding Source: RGD
- peptide binding Source: RGD
- protein-containing complex binding Source: RGD
- protein domain specific binding Source: RGD
- retinoic acid binding Source: RGD
- retinoic acid receptor binding Source: RGD
- retinoic acid-responsive element binding Source: RGD
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: RGD
- RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding Source: RGD
- RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: RGD
- sequence-specific DNA binding Source: RGD
- sequence-specific double-stranded DNA binding Source: RGD
- steroid hormone receptor activity Source: RGD
- transcription cis-regulatory region binding Source: RGD
- vitamin D receptor binding Source: RGD
- zinc ion binding Source: RGD
GO - Biological processi
- aging Source: RGD
- anatomical structure development Source: GO_Central
- axon regeneration Source: RGD
- camera-type eye development Source: RGD
- cardiac muscle cell proliferation Source: RGD
- cell differentiation Source: GO_Central
- cellular response to insulin stimulus Source: RGD
- embryo implantation Source: RGD
- female pregnancy Source: RGD
- heart development Source: RGD
- inflammatory response Source: RGD
- in utero embryonic development Source: RGD
- liver development Source: RGD
- maternal placenta development Source: RGD
- midgut development Source: RGD
- negative regulation of cell population proliferation Source: RGD
- negative regulation of transcription by RNA polymerase II Source: RGD
- peroxisome proliferator activated receptor signaling pathway Source: RGD
- placenta development Source: RGD
- positive regulation of apoptotic process Source: RGD
- positive regulation of transcription, DNA-templated Source: RGD
- positive regulation of transcription by RNA polymerase II Source: RGD
- positive regulation of translational initiation by iron Source: RGD
- regulation of branching involved in prostate gland morphogenesis Source: RGD
- regulation of myelination Source: RGD
- regulation of transcription, DNA-templated Source: RGD
- regulation of transcription by RNA polymerase II Source: RGD
- response to ethanol Source: RGD
- response to glucocorticoid Source: RGD
- response to nutrient Source: RGD
- response to organic cyclic compound Source: RGD
- response to retinoic acid Source: RGD
- response to selenium ion Source: RGD
- response to vitamin A Source: RGD
- response to vitamin D Source: RGD
- retinoic acid receptor signaling pathway Source: RGD
- secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development Source: RGD
- ventricular cardiac muscle cell differentiation Source: RGD
- ventricular cardiac muscle tissue morphogenesis Source: RGD
Keywordsi
Molecular function | DNA-binding, Receptor |
Biological process | Transcription, Transcription regulation |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
Reactomei | R-RNO-159418, Recycling of bile acids and salts R-RNO-192105, Synthesis of bile acids and bile salts R-RNO-193368, Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol R-RNO-193807, Synthesis of bile acids and bile salts via 27-hydroxycholesterol R-RNO-200425, Carnitine metabolism R-RNO-204174, Regulation of pyruvate dehydrogenase (PDH) complex R-RNO-211976, Endogenous sterols R-RNO-381340, Transcriptional regulation of white adipocyte differentiation R-RNO-383280, Nuclear Receptor transcription pathway R-RNO-400206, Regulation of lipid metabolism by PPARalpha R-RNO-4090294, SUMOylation of intracellular receptors R-RNO-5362517, Signaling by Retinoic Acid R-RNO-9029569, NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux R-RNO-9616222, Transcriptional regulation of granulopoiesis R-RNO-9623433, NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis R-RNO-9707564, Cytoprotection by HMOX1 |
Names & Taxonomyi
Protein namesi | Recommended name: Retinoic acid receptor RXR-alphaAlternative name(s): Nuclear receptor subfamily 2 group B member 1 Retinoid X receptor alpha |
Gene namesi | Name:Rxra Synonyms:Nr2b1 |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 3610, Rxra |
Subcellular locationi
Nucleus
- Nucleus PROSITE-ProRule annotation2 Publications
Mitochondrion
- Mitochondrion By similarity
Cytoplasm and Cytosol
- Cytoplasm By similarity
Note: Localization to the nucleus is enhanced by vitamin D3 (By similarity). Nuclear localization may be enhanced by the interaction with heterodimerization partner VDR (By similarity). Translocation to the mitochondrion upon interaction with NR4A1 (By similarity). Increased nuclear localization upon pulsatile shear stress (By similarity).By similarity
Mitochondrion
- mitochondrion Source: UniProtKB-SubCell
Nucleus
- nucleus Source: RGD
- RNA polymerase II transcription regulator complex Source: RGD
Other locations
- axon Source: RGD
- chromatin Source: RGD
- receptor complex Source: RGD
Keywords - Cellular componenti
Cytoplasm, Mitochondrion, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000053568 | 1 – 467 | Retinoic acid receptor RXR-alphaAdd BLAST | 467 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Cross-linki | 4 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Modified residuei | 22 | PhosphoserineBy similarity | 1 | |
Modified residuei | 28 | PhosphoserineBy similarity | 1 | |
Modified residuei | 61 | Phosphoserine; by MAPK8 and MAPK9By similarity | 1 | |
Modified residuei | 75 | Phosphoserine; by MAPK8 and MAPK9By similarity | 1 | |
Modified residuei | 87 | Phosphothreonine; by MAPK8 and MAPK9By similarity | 1 | |
Cross-linki | 113 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity | ||
Modified residuei | 134 | PhosphoserineBy similarity | 1 | |
Modified residuei | 150 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 264 | PhosphoserineBy similarity | 1 | |
Modified residuei | 265 | Phosphoserine; by MAPK8 and MAPK9By similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
PaxDbi | Q05343 |
PTM databases
iPTMneti | Q05343 |
PhosphoSitePlusi | Q05343 |
Expressioni
Tissue specificityi
Interactioni
Subunit structurei
Homodimer (By similarity). Heterodimer (via C-terminus) with RARA; required for ligand-dependent retinoic acid receptor transcriptional activity; association with RARA is enhanced by pulsatile shear stress (By similarity). Heterodimer with PPARA (via the leucine-like zipper in the LBD); the interaction is required for PPARA transcriptional activity (By similarity). Heterodimerizes with PPARG (By similarity). Heterodimerizes (via NR LBD) with RARB (By similarity). Heterodimerizes with NR1H4; the heterodimerization enhances the binding affinity for LXXLL motifs from coactivators (By similarity).
Interacts with NCOA3 and NCOA6 coactivators (By similarity).
Interacts with FAM120B (By similarity).
Interacts with coactivator PELP1, SENP6, SFPQ, DNTTIP2 and RNF8 (By similarity).
Interacts with PRMT2 (By similarity).
Interacts with ASXL1 (By similarity).
Interacts with BHLHE40/DEC1, BHLHE41/DEC2, MED1, NCOR1 and NCOR2 (By similarity).
Interacts in a ligand-dependent fashion with MED1 and NCOA1 (By similarity).
Interacts with VDR (By similarity).
Interacts with EP300; the interaction is decreased by 9-cis retinoic acid (By similarity). Heterodimer (via C-terminus) with NR4A1 (DNA-binding domain); the interaction is enhanced by 9-cis retinoic acid (By similarity). NR4A1 competes with EP300 for interaction with RXRA and thereby attenuates EP300 mediated acetylation of RXRA (By similarity). In the absence of hormonal ligand, interacts with TACC1 (By similarity).
By similarityGO - Molecular functioni
- DNA binding domain binding Source: RGD
- enzyme binding Source: RGD
- identical protein binding Source: RGD
- LBD domain binding Source: RGD
- nuclear receptor binding Source: RGD
- protein domain specific binding Source: RGD
- retinoic acid receptor binding Source: RGD
- vitamin D receptor binding Source: RGD
Protein-protein interaction databases
STRINGi | 10116.ENSRNOP00000012892 |
Chemistry databases
BindingDBi | Q05343 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 232 – 463 | NR LBDPROSITE-ProRule annotationAdd BLAST | 232 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 139 | ModulatingBy similarityAdd BLAST | 139 | |
Regioni | 1 – 61 | DisorderedSequence analysisAdd BLAST | 61 | |
Regioni | 79 – 109 | DisorderedSequence analysisAdd BLAST | 31 | |
Regioni | 165 – 170 | Nuclear localization signalBy similarity | 6 | |
Regioni | 206 – 229 | HingeBy similarityAdd BLAST | 24 | |
Regioni | 211 – 233 | DisorderedSequence analysisAdd BLAST | 23 | |
Regioni | 353 – 373 | Required for nuclear exportBy similarityAdd BLAST | 21 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 9 – 28 | Polar residuesSequence analysisAdd BLAST | 20 | |
Compositional biasi | 79 – 108 | Polar residuesSequence analysisAdd BLAST | 30 | |
Compositional biasi | 211 – 227 | Basic and acidic residuesSequence analysisAdd BLAST | 17 |
Domaini
Sequence similaritiesi
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 140 – 160 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 21 | |
Zinc fingeri | 176 – 200 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 25 |
Keywords - Domaini
Zinc-fingerPhylogenomic databases
eggNOGi | KOG3575, Eukaryota |
InParanoidi | Q05343 |
PhylomeDBi | Q05343 |
Family and domain databases
Gene3Di | 1.10.565.10, 1 hit 3.30.50.10, 1 hit |
InterProi | View protein in InterPro IPR035500, NHR-like_dom_sf IPR021780, Nuc_recep-AF1 IPR000536, Nucl_hrmn_rcpt_lig-bd IPR001723, Nuclear_hrmn_rcpt IPR000003, Retinoid-X_rcpt/HNF4 IPR001628, Znf_hrmn_rcpt IPR013088, Znf_NHR/GATA |
Pfami | View protein in Pfam PF00104, Hormone_recep, 1 hit PF11825, Nuc_recep-AF1, 1 hit PF00105, zf-C4, 1 hit |
PRINTSi | PR00545, RETINOIDXR PR00398, STRDHORMONER PR00047, STROIDFINGER |
SMARTi | View protein in SMART SM00430, HOLI, 1 hit SM00399, ZnF_C4, 1 hit |
SUPFAMi | SSF48508, SSF48508, 1 hit |
PROSITEi | View protein in PROSITE PS51843, NR_LBD, 1 hit PS00031, NUCLEAR_REC_DBD_1, 1 hit PS51030, NUCLEAR_REC_DBD_2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
10 20 30 40 50
MDTKHFLPLD FSTQVNSSSL SSPTGRGSMA APSLHPSLGP GLGSPLGSPG
60 70 80 90 100
QLHSPISTLS SPINGMGPPF SVISSPMGPH SMSVPTTPTL GFETGSPQLN
110 120 130 140 150
SPMNPVSSSE DIKPPLGLNG VLKVPAHPSG NMSSFTKHIC AICGDRSSGK
160 170 180 190 200
HYGVYSCEGC KGFFKRTVRK DLTYTCRDNK DCLIDKRQRN RCQYCRYQKC
210 220 230 240 250
LAMGMKREAV QEERQRGKDR NENEVESTSS ANEDMPVEKI LEAELAVEPK
260 270 280 290 300
TETYVEANMG LNPSSPNDPV TNICQAADKQ LFTLVEWAKR IPHFSELPLD
310 320 330 340 350
DQVILLRAGW NELLIASFSH RSIAVKDGIL LATGLHVHRN SAHSAGVGAI
360 370 380 390 400
FDRVLTELVS KMRDMQMDKT ELGCLRAIVL FNPDSKGLSN PAEVEALREK
410 420 430 440 450
VYASLEAYCK HKYPEQPGRF AKLLLRLPAL RSIGLKCLEH LFFFKLIGDT
460
PIDTFLMEML EAPHQTT
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketQ0VJ96 | Q0VJ96_RAT | Retinoic acid receptor RXR-alpha | Rxra rCG_45555 | 467 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L06482 mRNA Translation: AAA42093.1 |
PIRi | A47278 I67427 |
Genome annotation databases
UCSCi | RGD:3610, rat |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L06482 mRNA Translation: AAA42093.1 |
PIRi | A47278 I67427 |
3D structure databases
BMRBi | Q05343 |
SMRi | Q05343 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 10116.ENSRNOP00000012892 |
Chemistry databases
BindingDBi | Q05343 |
ChEMBLi | CHEMBL4431 |
DrugCentrali | Q05343 |
PTM databases
iPTMneti | Q05343 |
PhosphoSitePlusi | Q05343 |
Proteomic databases
PaxDbi | Q05343 |
Genome annotation databases
UCSCi | RGD:3610, rat |
Organism-specific databases
RGDi | 3610, Rxra |
Phylogenomic databases
eggNOGi | KOG3575, Eukaryota |
InParanoidi | Q05343 |
PhylomeDBi | Q05343 |
Enzyme and pathway databases
Reactomei | R-RNO-159418, Recycling of bile acids and salts R-RNO-192105, Synthesis of bile acids and bile salts R-RNO-193368, Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol R-RNO-193807, Synthesis of bile acids and bile salts via 27-hydroxycholesterol R-RNO-200425, Carnitine metabolism R-RNO-204174, Regulation of pyruvate dehydrogenase (PDH) complex R-RNO-211976, Endogenous sterols R-RNO-381340, Transcriptional regulation of white adipocyte differentiation R-RNO-383280, Nuclear Receptor transcription pathway R-RNO-400206, Regulation of lipid metabolism by PPARalpha R-RNO-4090294, SUMOylation of intracellular receptors R-RNO-5362517, Signaling by Retinoic Acid R-RNO-9029569, NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux R-RNO-9616222, Transcriptional regulation of granulopoiesis R-RNO-9623433, NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis R-RNO-9707564, Cytoprotection by HMOX1 |
Miscellaneous databases
PROi | PR:Q05343 |
Family and domain databases
Gene3Di | 1.10.565.10, 1 hit 3.30.50.10, 1 hit |
InterProi | View protein in InterPro IPR035500, NHR-like_dom_sf IPR021780, Nuc_recep-AF1 IPR000536, Nucl_hrmn_rcpt_lig-bd IPR001723, Nuclear_hrmn_rcpt IPR000003, Retinoid-X_rcpt/HNF4 IPR001628, Znf_hrmn_rcpt IPR013088, Znf_NHR/GATA |
Pfami | View protein in Pfam PF00104, Hormone_recep, 1 hit PF11825, Nuc_recep-AF1, 1 hit PF00105, zf-C4, 1 hit |
PRINTSi | PR00545, RETINOIDXR PR00398, STRDHORMONER PR00047, STROIDFINGER |
SMARTi | View protein in SMART SM00430, HOLI, 1 hit SM00399, ZnF_C4, 1 hit |
SUPFAMi | SSF48508, SSF48508, 1 hit |
PROSITEi | View protein in PROSITE PS51843, NR_LBD, 1 hit PS00031, NUCLEAR_REC_DBD_1, 1 hit PS51030, NUCLEAR_REC_DBD_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | RXRA_RAT | |
Accessioni | Q05343Primary (citable) accession number: Q05343 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1994 |
Last sequence update: | February 1, 1994 | |
Last modified: | February 23, 2022 | |
This is version 175 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families