Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Retinoic acid receptor RXR-alpha

Gene

Rxra

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid. RXRA serves as a common heterodimeric partner for a number of nuclear receptors. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes.3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi140 – 205Nuclear receptorPROSITE-ProRule annotationAdd BLAST66
Zinc fingeri140 – 160NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri176 – 200NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

  • 9-cis retinoic acid receptor activity Source: MGI
  • chromatin DNA binding Source: MGI
  • DNA binding Source: MGI
  • enzyme binding Source: MGI
  • protein heterodimerization activity Source: MGI
  • retinoic acid-responsive element binding Source: MGI
  • RNA polymerase II regulatory region sequence-specific DNA binding Source: MGI
  • RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding Source: MGI
  • sequence-specific DNA binding Source: MGI
  • steroid hormone receptor activity Source: InterPro
  • transcription factor activity, sequence-specific DNA binding Source: MGI
  • transcription factor binding Source: UniProtKB
  • vitamin D receptor binding Source: MGI
  • vitamin D response element binding Source: Ensembl
  • zinc ion binding Source: InterPro

GO - Biological processi

  • angiogenesis involved in coronary vascular morphogenesis Source: DFLAT
  • camera-type eye development Source: MGI
  • cardiac muscle cell differentiation Source: DFLAT
  • cardiac muscle cell proliferation Source: DFLAT
  • embryo implantation Source: MGI
  • heart development Source: DFLAT
  • heart morphogenesis Source: DFLAT
  • in utero embryonic development Source: MGI
  • maternal placenta development Source: MGI
  • mesenchyme development Source: DFLAT
  • modulation by virus of host morphology or physiology Source: MGI
  • negative regulation of gene expression Source: DFLAT
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • peroxisome proliferator activated receptor signaling pathway Source: MGI
  • placenta development Source: MGI
  • positive regulation of transcription, DNA-templated Source: DFLAT
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus Source: MGI
  • positive regulation of translational initiation by iron Source: MGI
  • protein homotetramerization Source: MGI
  • regulation of branching involved in prostate gland morphogenesis Source: MGI
  • regulation of transcription, DNA-templated Source: MGI
  • regulation of transcription from RNA polymerase II promoter Source: MGI
  • response to retinoic acid Source: MGI
  • retinoic acid receptor signaling pathway Source: MGI
  • secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development Source: MGI
  • transcription, DNA-templated Source: UniProtKB-KW
  • ventricular cardiac muscle cell differentiation Source: MGI
  • ventricular cardiac muscle tissue morphogenesis Source: MGI
  • visceral serous pericardium development Source: DFLAT
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-159418. Recycling of bile acids and salts.
R-MMU-192105. Synthesis of bile acids and bile salts.
R-MMU-193368. Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
R-MMU-193807. Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
R-MMU-200425. Import of palmitoyl-CoA into the mitochondrial matrix.
R-MMU-204174. Regulation of pyruvate dehydrogenase (PDH) complex.
R-MMU-211976. Endogenous sterols.
R-MMU-381340. Transcriptional regulation of white adipocyte differentiation.
R-MMU-383280. Nuclear Receptor transcription pathway.
R-MMU-400206. Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha).
R-MMU-442533. Transcriptional Regulation of Adipocyte Differentiation in 3T3-L1 Pre-adipocytes.
R-MMU-5362517. Signaling by Retinoic Acid.
R-MMU-5617472. Activation of anterior HOX genes in hindbrain development during early embryogenesis.

Names & Taxonomyi

Protein namesi
Recommended name:
Retinoic acid receptor RXR-alpha
Alternative name(s):
Nuclear receptor subfamily 2 group B member 1
Retinoid X receptor alpha
Gene namesi
Name:Rxra
Synonyms:Nr2b1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:98214. Rxra.

Subcellular locationi

GO - Cellular componenti

  • nuclear chromatin Source: MGI
  • nucleoplasm Source: Reactome
  • nucleus Source: MGI
  • receptor complex Source: MGI
  • RNA polymerase II transcription factor complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi22S → A: Loss of constituitive phosphorylation. No effect on RXRA transcriptional activity. 2 Publications1
Mutagenesisi44S → A: No effect on constituitive phosphorylation. 1 Publication1
Mutagenesisi48S → A: No effect on constituitive phosphorylation. 1 Publication1
Mutagenesisi54S → A: No effect on constituitive phosphorylation. 1 Publication1
Mutagenesisi61S → A: No effect on constituitive phosphorylation, decreased stress-induced phosphorylation but no effect on RXRA transcriptional activity. Abolishes stress-induced phosphorylation but no effect on RXRA transcriptional activity; when associated with A-75 and A-87. No effect on RXRA transcriptional activity. 1 Publication1
Mutagenesisi75S → A: No effect on constituitive phosphorylation, decreased stress-induced phosphorylation but no effect on RXRA transcriptional activity. Abolishes stress-induced phosphorylation but no effect on RXRA transcriptional activity; when associated with A-61 and A-87. 1 Publication1
Mutagenesisi87T → A: No effect on constituitive phosphorylation, decreased stress-induced phosphorylation but no effect on RXRA transcriptional activity. Abolishes stress-induced phosphorylation but no effect on RXRA transcriptional activity; when associated with A-61 and A-75. phosphorylation. No effect on RXRA transcriptional activity. 1 Publication1
Mutagenesisi96S → A: No effect on constituitive phosphorylation. 1 Publication1
Mutagenesisi101S → A: No effect on constituitive phosphorylation. 1 Publication1
Mutagenesisi265S → A: No effect on constiuitive phosphorylation but loss of stress-induced phosphorylation. No effect on RXRA transcriptional activity. 1 Publication1
Mutagenesisi455 – 456FL → AA: Abolishes interaction with ASXL1 and NCOA1. 1 Publication2
Mutagenesisi459 – 460ML → AA: Abolishes interaction with ASXL1 and NCOA1. 1 Publication2

Chemistry databases

ChEMBLiCHEMBL3084.
GuidetoPHARMACOLOGYi610.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000535671 – 467Retinoic acid receptor RXR-alphaAdd BLAST467

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei22PhosphoserineCombined sources2 Publications1
Modified residuei28PhosphoserineBy similarity1
Modified residuei61Phosphoserine; by MAPK8 and MAPK91 Publication1
Modified residuei75Phosphoserine; by MAPK8 and MAPK91 Publication1
Modified residuei87Phosphothreonine; by MAPK8 and MAPK91 Publication1
Cross-linki113Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei134PhosphoserineBy similarity1
Modified residuei264PhosphoserineBy similarity1
Modified residuei265Phosphoserine; by MAPK8 and MAPK91 Publication1

Post-translational modificationi

Phosphorylated on serine and threonine residues mainly in the N-terminal modulating domain. Phosphorylated on Ser-28, in vitro, by PKA. This phosphorylation is required for repression of cAMP-mediated transcriptional activity of RARA (By similarity). Constiutively phosphorylated on Ser-22 in the presence or absence of ligand. Under stress conditions, hyperphosphorylated by activated JNK on Ser-61, Ser-75, Thr-87 and Ser-265.By similarity2 Publications
Sumoylation negatively regulates transcriptional activity. Desumoylated specifically by SENP6 (By similarity).By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP28700.
PaxDbiP28700.
PRIDEiP28700.

PTM databases

iPTMnetiP28700.
PhosphoSitePlusiP28700.

Expressioni

Gene expression databases

BgeeiENSMUSG00000015846.
CleanExiMM_RXRA.
ExpressionAtlasiP28700. baseline and differential.
GenevisibleiP28700. MM.

Interactioni

Subunit structurei

Homodimer (By similarity). Heterodimer with RARA; required for ligand-dependent retinoic acid receptor transcriptional activity. Heterodimer with PPARA (via the leucine-like zipper in the LBD); the interaction is required for PPARA transcriptional activity. Also heterodimerizes with PPARG (By similarity). Interacts with coactivator NCOA3, PELP1, SENP6, SFPQ, DNTTIP2 and RNF8. Interacts with PRMT2. Interacts with BHLHE40/DEC1, BHLHE41/DEC2, NCOR1 and NCOR2. Interacts in a ligand-dependent fashion with MED1 (By similarity). Interacts with coactivator NCOA6, and FAM120B. Interacts with ASXL1. Interacts in a ligand-dependent fashion with NCOA1.By similarity6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ASXL1Q8IXJ92EBI-346715,EBI-1646500From a different organism.
Asxl1P595982EBI-346715,EBI-5743705
MED25Q71SY53EBI-346715,EBI-394558From a different organism.
SFPQP23246-13EBI-346715,EBI-355463From a different organism.

GO - Molecular functioni

  • enzyme binding Source: MGI
  • protein heterodimerization activity Source: MGI
  • transcription factor binding Source: UniProtKB
  • vitamin D receptor binding Source: MGI

Protein-protein interaction databases

BioGridi203038. 16 interactors.
IntActiP28700. 14 interactors.
MINTiMINT-2775018.
STRINGi10090.ENSMUSP00000076491.

Chemistry databases

BindingDBiP28700.

Structurei

Secondary structure

1467
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi231 – 234Combined sources4
Helixi237 – 246Combined sources10
Helixi269 – 282Combined sources14
Helixi284 – 289Combined sources6
Turni292 – 296Combined sources5
Helixi299 – 321Combined sources23
Beta strandi323 – 330Combined sources8
Beta strandi336 – 338Combined sources3
Helixi339 – 344Combined sources6
Helixi348 – 357Combined sources10
Helixi359 – 364Combined sources6
Helixi369 – 380Combined sources12
Helixi391 – 412Combined sources22
Helixi419 – 424Combined sources6
Helixi426 – 438Combined sources13
Turni439 – 443Combined sources5
Helixi447 – 449Combined sources3
Helixi452 – 461Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DKFX-ray2.50A230-462[»]
1XDKX-ray2.90A/E230-467[»]
3A9EX-ray2.75A228-467[»]
ProteinModelPortaliP28700.
SMRiP28700.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP28700.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 139Modulating domainBy similarityAdd BLAST139
Regioni206 – 229HingeAdd BLAST24
Regioni230 – 467Ligand-binding domainAdd BLAST238

Domaini

Composed of three domains: a modulating N-terminal or AF1 domain, a DNA-binding domain and a C-terminal ligand-binding or AF2 domain.

Sequence similaritiesi

Contains 1 nuclear receptor DNA-binding domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri140 – 160NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri176 – 200NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
GeneTreeiENSGT00760000118948.
HOGENOMiHOG000260821.
HOVERGENiHBG005606.
InParanoidiP28700.
KOiK08524.
OMAiMDTKHFL.
OrthoDBiEOG091G0YX6.
PhylomeDBiP28700.
TreeFamiTF352097.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR021780. 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.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF11825. Nuc_recep-AF1. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR00545. RETINOIDXR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P28700-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDTKHFLPLD FSTQVNSSSL NSPTGRGSMA VPSLHPSLGP GIGSPLGSPG
60 70 80 90 100
QLHSPISTLS SPINGMGPPF SVISSPMGPH SMSVPTTPTL GFGTGSPQLN
110 120 130 140 150
SPMNPVSSTE DIKPPLGLNG VLKVPAHPSG NMASFTKHIC 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 EAPHQAT
Length:467
Mass (Da):51,217
Last modified:December 1, 1992 - v1
Checksum:i0AF62396BCDC87DB
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M84817 mRNA. Translation: AAA40080.1.
X66223 mRNA. Translation: CAA46962.1.
CCDSiCCDS15830.1.
PIRiS26668.
RefSeqiNP_035435.1. NM_011305.3.
UniGeneiMm.24624.

Genome annotation databases

EnsembliENSMUST00000077257; ENSMUSP00000076491; ENSMUSG00000015846.
ENSMUST00000166775; ENSMUSP00000133044; ENSMUSG00000015846.
GeneIDi20181.
KEGGimmu:20181.
UCSCiuc008ixs.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M84817 mRNA. Translation: AAA40080.1.
X66223 mRNA. Translation: CAA46962.1.
CCDSiCCDS15830.1.
PIRiS26668.
RefSeqiNP_035435.1. NM_011305.3.
UniGeneiMm.24624.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DKFX-ray2.50A230-462[»]
1XDKX-ray2.90A/E230-467[»]
3A9EX-ray2.75A228-467[»]
ProteinModelPortaliP28700.
SMRiP28700.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi203038. 16 interactors.
IntActiP28700. 14 interactors.
MINTiMINT-2775018.
STRINGi10090.ENSMUSP00000076491.

Chemistry databases

BindingDBiP28700.
ChEMBLiCHEMBL3084.
GuidetoPHARMACOLOGYi610.

PTM databases

iPTMnetiP28700.
PhosphoSitePlusiP28700.

Proteomic databases

MaxQBiP28700.
PaxDbiP28700.
PRIDEiP28700.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000077257; ENSMUSP00000076491; ENSMUSG00000015846.
ENSMUST00000166775; ENSMUSP00000133044; ENSMUSG00000015846.
GeneIDi20181.
KEGGimmu:20181.
UCSCiuc008ixs.1. mouse.

Organism-specific databases

CTDi6256.
MGIiMGI:98214. Rxra.

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
GeneTreeiENSGT00760000118948.
HOGENOMiHOG000260821.
HOVERGENiHBG005606.
InParanoidiP28700.
KOiK08524.
OMAiMDTKHFL.
OrthoDBiEOG091G0YX6.
PhylomeDBiP28700.
TreeFamiTF352097.

Enzyme and pathway databases

ReactomeiR-MMU-159418. Recycling of bile acids and salts.
R-MMU-192105. Synthesis of bile acids and bile salts.
R-MMU-193368. Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
R-MMU-193807. Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
R-MMU-200425. Import of palmitoyl-CoA into the mitochondrial matrix.
R-MMU-204174. Regulation of pyruvate dehydrogenase (PDH) complex.
R-MMU-211976. Endogenous sterols.
R-MMU-381340. Transcriptional regulation of white adipocyte differentiation.
R-MMU-383280. Nuclear Receptor transcription pathway.
R-MMU-400206. Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha).
R-MMU-442533. Transcriptional Regulation of Adipocyte Differentiation in 3T3-L1 Pre-adipocytes.
R-MMU-5362517. Signaling by Retinoic Acid.
R-MMU-5617472. Activation of anterior HOX genes in hindbrain development during early embryogenesis.

Miscellaneous databases

ChiTaRSiRxra. mouse.
EvolutionaryTraceiP28700.
PROiP28700.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000015846.
CleanExiMM_RXRA.
ExpressionAtlasiP28700. baseline and differential.
GenevisibleiP28700. MM.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR021780. 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.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF11825. Nuc_recep-AF1. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR00545. RETINOIDXR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRXRA_MOUSE
AccessioniPrimary (citable) accession number: P28700
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: December 1, 1992
Last modified: November 2, 2016
This is version 173 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.